Cancer Research and Treatment

Sun Young Rha

78 Articles

Gastrointestinal cancer

Varlitinib and Paclitaxel for EGFR/HER2 Co-expressing Advanced Gastric Cancer: A Multicenter Phase Ib/II Study (K-MASTER-13): Dong-Hoe Koo, Minkyu Jung, Yeul Hong Kim, Hei-Cheul Jeung, Dae Young Zang, Woo Kyun Bae, Hyunki Kim, Hyo Song Kim, Choong-kun Lee, Woo Sun Kwon, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2024;56(4):1136-1145. Published online April 29, 2024; DOI: https://doi.org/10.4143/crt.2023.1324

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Purpose
Varlitinib is a pan-human epidermal growth factor receptor (HER) inhibitor targeting epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4. We present a phase Ib/II study of a combination of varlitinib and weekly paclitaxel as a second-line treatment for patients with EGFR/HER2 co-expressing advanced gastric cancer (AGC).
Materials and Methods
Patients whose tumors with EGFR and HER2 overexpression by immunohistochemistry (≥ 1+) were enrolled. Varlitinib and paclitaxel were investigated every 4 weeks. After determining the recommended phase II dose (RP2D) in phase Ib, a phase II study was conducted to evaluate the antitumor activity.
Results
RP2D was treated with a combination of varlitinib (300 mg twice daily) and paclitaxel. Among 27 patients treated with RP2D, the median progression-free survival and overall survival (OS) were 3.3 months (95% confidence interval [CI], 1.7 to 4.9) and 7.9 months (95% CI, 5.0 to 10.8), respectively, with a median follow-up of 15.7 months. Among 16 patients with measurable disease, the objective response rate (ORR) and disease control rate were 31% and 88%, respectively. Patients with strong HER2 expression (n=8) had a higher ORR and longer OS, whereas those with strong EGFR expression (n=3) had poorer outcomes. The most common adverse events (AEs) of any grade were neutropenia (52%), diarrhea (27%), aspartate aminotransferase/alanine transaminase elevation (22%), and nausea (19%). No treatment-related deaths or unexpected AEs resulting from treatment cessation were observed in patients with RP2D.
Conclusion
A combination of varlitinib and paclitaxel displayed manageable toxicity and modest antitumor activity in patients with EGFR/HER2 co-expressing AGC who progressed after first-line chemotherapy.

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Unraveling the future: Innovative design strategies and emerging challenges in HER2-targeted tyrosine kinase inhibitors for cancer therapy
Sixiang Zheng, Ruixian Chen, Lele Zhang, Lun Tan, Lintao Li, Fangyi Long, Ting Wang
European Journal of Medicinal Chemistry.2024; 276: 116702. CrossRef

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First-in-Human Phase 1 Study of a B Cell– and Monocyte-Based Immunotherapeutic Vaccine against HER2-Positive Advanced Gastric Cancer: Minkyu Jung, Jii Bum Lee, Hyo Song Kim, Woo Sun Kwon, Hyun Ok Kim, Sinyoung Kim, Myunghwan Park, Wuhyun Kim, Ki-Young Choi, Taegwon Oh, Chang-Yuil Kang, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2024;56(1):208-218. Published online June 28, 2023; DOI: https://doi.org/10.4143/crt.2022.1328

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Purpose
BVAC-B is an autologous B cell– and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer.
Materials and Methods
Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×10⁷ cells/dose), medium (5.0×10⁷ cells/dose), or high dose (1.0×10⁸ cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses.
Results
Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients.
Conclusion
BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy.

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HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments
Magdalena K. Scheck, Ralf D. Hofheinz, Sylvie Lorenzen
Cancers.2024; 16(7): 1336. CrossRef

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General

Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study: Yae Jee Baek, Youn-Jung Lee, So Ra Park, Kyoo Hyun Kim, Seung-Hoon Beom, Choong-kun Lee, Sang Joon Shin, Sun Young Rha, Sinyoung Kim, Kyoung Hwa Lee, Jung Ho Kim, Su Jin Jeong, Nam Su Ku, Jun Yong Choi, Joon-Sup Yeom, Minkyu Jung, Jin Young Ahn; Cancer Res Treat. 2023;55(3):746-757. Published online February 9, 2023; DOI: https://doi.org/10.4143/crt.2022.1541

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Purpose
We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs).
Materials and Methods
Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer.
Results
Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs.
Conclusion
CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

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Safety, immunogenicity and protective effect of sequential vaccination with inactivated and recombinant protein COVID-19 vaccine in the elderly: a prospective longitudinal study
Hong-Hong Liu, Yunbo Xie, Bao-Peng Yang, Huan-Yue Wen, Peng-Hui Yang, Jin-E Lu, Yan Liu, Xi Chen, Meng-Meng Qu, Yang Zhang, Wei-Guo Hong, Yong-Gang Li, Junliang Fu, Fu-Sheng Wang
Signal Transduction and Targeted Therapy.2024;[Epub] CrossRef
Immune response of COVID-19 vaccines in solid cancer patients: A meta-analysis
Tiantian Hua, Ru Fan, Yang Fan, Feng Chen
Human Vaccines & Immunotherapeutics.2024;[Epub] CrossRef
A Three-Dose mRNA COVID-19 Vaccine Regime Produces Both Suitable Immunogenicity and Satisfactory Efficacy in Patients with Solid Cancers
Urska Janzic, Urska Bidovec-Stojkovic, Peter Korosec, Katja Mohorcic, Loredana Mrak, Marina Caks, Maja Ravnik, Erik Skof, Matija Rijavec
Vaccines.2023; 11(6): 1017. CrossRef
Neutralizing Antibody Response following a Third Dose of the mRNA-1273 Vaccine among Cancer Patients
Christopher W. Dukes, Marine Potez, Jeffrey Lancet, Barbara J. Kuter, Junmin Whiting, Qianxing Mo, Brett Leav, Haixing Wang, Julie S. Vanas, Christopher L. Cubitt, Kimberly Isaacs-Soriano, Kayoko Kennedy, Julie Rathwell, Julian Diaz Cobo, Wesley O’Nan, Br
Vaccines.2023; 12(1): 13. CrossRef

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Status of Using Complementary and Alternative Medicine among Patients with Cancer in Korea: an Online Survey of Online Cancer Support Groups (KCSG PC21-20): Jung Sun Kim, Jung Hye Kwon, Sun Young Rha, Sang-Cheol Lee, Yoon Jung Chang, In-Sun Kwon, Kyung Han You, Ho Young Yoon; Cancer Res Treat. 2023;55(2):442-451.; DOI: https://doi.org/10.4143/crt.2022.1483

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Purpose
An increasing number of patients with cancers are interested in complementary and alternative medicine (CAM), which lacks scientific evidence. This study aimed to determine how CAM was used and how media affected patients in online cancer support groups (OCSG).
Materials and Methods
Between August 18 and September 12, 2021, an online survey was conducted among the members of OCSG. The survey consisted of five parts: baseline characteristics, attitudes toward and experience with CAM, source of information and reliabilities, experience with anthelmintics, and online health information literacy and usage.
Results
Among the 644 responders, a total of 221 patients with cancer completed the survey, and 78.2% (173/221) used CAM. The users’ median age was 52 years; 46.8% were males, and 43.9% had metastatic disease. Fifty-three CAM users (30.6%) discussed their physicians about CAM. In addition, 16.2% (28/173) of CAM users had the experience of anthelmintics. The use of anthelmintics in patients with cancers was associated with younger age (odds ratio [OR], 0.89; 95% confidence interval [CI], 0.84 to 0.95), metastatic disease (OR, 10.88; 95% CI, 3.39 to 34.86), previous exposure to CAM information (OR, 5.57; 95% CI, 1.01 to 30.72), experience with more types of CAM (OR, 1.98; 95% CI, 1.29 to 3.05), and side effects (OR, 5.10; 95% CI 1.46 to 17.75).
Conclusion
Use of anthelmintics, a CAM of which information is widespread online, is affected by several factors. This study will provide essential information for developing a CAM management strategy in this digital age.

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Uso de medicina alternativa en pacientes oncológicos en la ciudad de Neiva (Colombia)
Nicolás Martínez-Ramos, Carolina Mariño, Laura Camila Olaya-SanMiguel, Raúl Murillo
Universitas Médica.2024; 65: 1. CrossRef
Factors associated with nursing practice for cancer patients using complementary and alternative medicine
Junko Kusunoki, Sumie Ikezaki, Tomoko Majima
Collegian.2023; 30(5): 668. CrossRef

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Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea: Jii Bum Lee, Minkyu Jung, June Hyuk Kim, Bo Hyun Kim, Yeol Kim, Young Seok Kim, Byung Chang Kim, Jin Kim, Sung Ho Moon, Keon-Uk Park, Meerim Park, Hyeon Jin Park, Sung Hoon Sim, Hong Man Yoon, Soo Jung Lee, Eunyoung Lee, June Young Chun, Youn Kyung Chung, So-Youn Jung, Jinsoo Chung, Eun Sook Lee, Hyun Cheol Chung, Tak Yun, Sun Young Rha; Cancer Res Treat. 2021;53(2):323-329. Published online March 15, 2021; DOI: https://doi.org/10.4143/crt.2020.1256

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At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.

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Preoperative COVID-19 and Postoperative Mortality in Cancer Surgery: A South Korean Nationwide Study
Jae-Woo Ju, Soo-Hyuk Yoon, Tak Kyu Oh, Ho-Jin Lee
Annals of Surgical Oncology.2024; 31(10): 6394. CrossRef
Impact of the COVID-19 Pandemic on Esophagogastroduodenoscopy and Gastric Cancer Claims in South Korea: A Nationwide, Population-Based Study
Min Ah Suh, Su Bee Park, Min Seob Kwak, Jin Young Yoon, Jae Myung Cha
Yonsei Medical Journal.2023; 64(9): 549. CrossRef
The elderly population are more vulnerable for the management of colorectal cancer during the COVID-19 pandemic: a nationwide, population-based study
Hong Sun Kang, Seung Hoon Jeon, Su Bee Park, Jin Young Youn, Min Seob Kwak, Jae Myung Cha
Intestinal Research.2023; 21(4): 500. CrossRef
Impact of Coronavirus Disease 2019 on Gastric Cancer Diagnosis and Stage: A Single-Institute Study in South Korea
Moonki Hong, Mingee Choi, JiHyun Lee, Kyoo Hyun Kim, Hyunwook Kim, Choong-Kun Lee, Hyo Song Kim, Sun Young Rha, Gyu Young Pih, Yoon Jin Choi, Da Hyun Jung, Jun Chul Park, Sung Kwan Shin, Sang Kil Lee, Yong Chan Lee, Minah Cho, Yoo Min Kim, Hyoung-Il Kim,
Journal of Gastric Cancer.2023; 23(4): 574. CrossRef
Health-Seeking Behavior Returning to Normalcy Overcoming COVID-19 Threat in Breast Cancer
Eun-Gyeong Lee, Yireh Han, Dong-Eun Lee, Hyeong-Gon Moon, Hyoung Won Koh, Eun-Kyu Kim, So-Youn Jung
Cancer Research and Treatment.2023; 55(4): 1222. CrossRef
Adherence to Physical Distancing and Health Beliefs About COVID-19 Among Patients With Cancer
Sajida Fawaz Hammoudi, Oli Ahmed, Hoyoung An, Youjin Hong, Myung Hee Ahn, Seockhoon Chung
Journal of Korean Medical Science.2023;[Epub] CrossRef
To overcome medical gap in screening and surveillance of colorectal cancer during the COVID-19 pandemic
Yoo Min Han
Intestinal Research.2023; 21(4): 418. CrossRef
COVID-19 pandemic: a new cause of unplanned interruption of radiotherapy in breast cancer patients
Shiho Lee, Jaesung Heo
Medical Oncology.2022;[Epub] CrossRef
Impact of the COVID-19 Pandemic on Breast Cancer Management in Portugal: A Cross-Sectional Survey-Based Study of Medical Oncologists
Diogo Alpuim Costa, José Guilherme Gonçalves Nobre, João Paulo Fernandes, Marta Vaz Batista, Ana Simas, Carolina Sales, Helena Gouveia, Leonor Abreu Ribeiro, Andreia Coelho, Margarida Brito, Mariana Inácio, André Cruz, Mónica Mariano, Joana Savva-Bordalo,
Oncology and Therapy.2022; 10(1): 225. CrossRef
Organisation of cancer care in troubling times: A scoping review of expert guidelines and their implementation during the COVID-19 pandemic
Brenda Bogaert, Victoria Buisson, Zizis Kozlakidis, Pierre Saintigny
Critical Reviews in Oncology/Hematology.2022; 173: 103656. CrossRef
Surgical safety in the COVID-19 era: present and future considerations
Young Il Kim, In Ja Park
Annals of Surgical Treatment and Research.2022; 102(6): 295. CrossRef
Effect of Cancer-Related Dysfunctional Beliefs About Sleep on Fear of Cancer Progression in the Coronavirus Pandemic
Harin Kim, Inn-Kyu Cho, Dongin Lee, Kyumin Kim, Joohee Lee, Eulah Cho, C. Hyung Keun Park, Seockhoon Chung
Journal of Korean Medical Science.2022;[Epub] CrossRef
Impact of the COVID-19 Pandemic on Gastric Cancer Screening in South Korea: Results From the Korean National Cancer Screening Survey (2017–2021)
Kyeongmin Lee, Mina Suh, Jae Kwan Jun, Kui Son Choi
Journal of Gastric Cancer.2022; 22(4): 297. CrossRef
Changes in cancer screening before and during COVID‐19: findings from the Korean National Cancer Screening Survey 2019 and 2020
Thao Thi Kim Trinh, Yun Yeong Lee, Mina Suh, Jae Kwan Jun, Kui Son Choi
Epidemiology and Health.2022; 44: e2022051. CrossRef
Treatment decision for cancer patients with fever during the coronavirus disease 2019 (COVID-19) pandemic
In Hee Lee, Sung Ae Koh, Soo Jung Lee, Sun Ah Lee, Yoon Young Cho, Ji Yeon Lee, Jin Young Kim
Yeungnam University Journal of Medicine.2021; 38(4): 344. CrossRef

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Characteristics and Treatment Patterns of Patients with Advanced Soft Tissue Sarcoma in Korea: Hyo Song Kim, Chung Mo Nam, Suk-Yong Jang, Sun Kyu Choi, Minkyung Han, Seonmin Kim, Maria Victoria Moneta, Sae Young Lee, Jae Min Cho, Diego Novick, Sun Young Rha; Cancer Res Treat. 2019;51(4):1380-1391. Published online February 18, 2019; DOI: https://doi.org/10.4143/crt.2018.476

Abstract PDF Supplementary Material PubReader ePub

Purpose
A soft tissue sarcoma (STS) is a rare type of cancer, accounting for 1% of adult solid cancers. The aim of the present study is to determine the incidence of localized and advanced STS in Korean patients, their treatment patterns, and the survival of patients by disease status.
Materials and Methods
The STS patient cohort was defined using National Health Insurance Service medical data from 2002 to 2015. Incidence, distribution, anatomical location of tumors, survival rates (Kaplan-Meyer survival function) and treatment patterns were analyzed by applying different algorithms to the STS cohort containing localized and advanced STS cases.
Results
A total of 7,813 patients were diagnosed with STS from 2007 to 2014, 4,307 were localized STS and 3,506 advanced STS cases. The total incidence of STS was 2.49 per 100,000 person- years: 1.37 per 100,000 person-years for localized STS and 1.12 per 100,000 person-years for advanced STS. The 5-year survival rate after diagnosis was 56.4% for all STS, 82.4% for localized, and 27.2% for advanced STS. Half of the advanced STS patients (49.98%) received anthracycline-containing chemotherapy as initial treatment after diagnosis.
Conclusion
This study provides insights into localized and advanced STS epidemiology, treatment patterns and outcomes in Korea, which could be used as fundamental data in improving clinical outcomes of STS patients in the future.

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Factors predictive of second‐line chemotherapy in soft tissue sarcoma: An analysis of the National Genomic Profiling Database
Takao Mochizuki, Masachika Ikegami, Toru Akiyama
Cancer Science.2024; 115(2): 575. CrossRef
Comparative Evaluation of Second-Line Chemotherapy Agents for Advanced Soft Tissue Sarcoma: Gemcitabine/Docetaxel, Pazopanib, and Alternatives
Tae Hun Kim, Ki Hyuk Sung, So Hak Chung
Journal of the Korean Orthopaedic Association.2024; 59(1): 22. CrossRef
Secondary hematological malignancies in patients with sarcoma: A single‑center retrospective study
Yoon Jang, Hong Jeong, Chang-Bae Kong, Won Song, Wan Cho, Dae Jeon, Heyjin Kim, Sung Yang, Im Na, Hyo-Rak Lee, Hye Kang
Oncology Letters.2024;[Epub] CrossRef
Necroptosis-related lncRNA-based novel signature to predict the prognosis and immune landscape in soft tissue sarcomas
Qiuzhong Long, Zhengtian Li, Wenkang Yang, Ke Huang, Gang Du
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
First-Line Anlotinib Treatment for Soft-Tissue Sarcoma in Chemotherapy-Ineligible Patients: An Open-Label, Single-Arm, Phase 2 Clinical Trial
Tao Li, Ying Dong, Yongzhong Wei, Shoufeng Wang, Yunxia Liu, Jia Chen, Wenhua Xiong, Nong Lin, Xin Huang, Meng Liu, Xiaobo Yan, Zhaoming Ye, Binghao Li
Clinical Cancer Research.2024; 30(19): 4310. CrossRef
Mortality patterns of soft-tissue sarcomas worldwide up to 2018, with predictions for 2025
Margherita Pizzato, Giulia Collatuzzo, Claudia Santucci, Matteo Malvezzi, Paolo Boffetta, Alessandro Comandone, Fabio Levi, Carlo La Vecchia, Paola Bertuccio, Eva Negri
European Journal of Cancer Prevention.2023; 32(1): 71. CrossRef
Chemotherapeutic drugs for soft tissue sarcomas: a review
Zhichao Tian, Weitao Yao
Frontiers in Pharmacology.2023;[Epub] CrossRef
Identification of m5C-related molecular subtypes and prediction models in the prognosis and tumor microenvironment infiltration of soft tissue sarcoma
Xianfeng Wang, Yicheng Mao, Hanlu Xu, Jiyang Chen, Xiao chen
Heliyon.2023; 9(9): e19680. CrossRef
Incidence, Treatment and Outcome of Patients with Retroperitoneal Soft‐Tissue Sarcoma in Switzerland 2005–2015: A Population‐Based Analysis
Johanna C. F. Willburger, Marco von Strauss, Caspar J. Peterson, Tracy R. Glass, Christoph Kettelhack
World Journal of Surgery.2022; 46(2): 461. CrossRef
A Necroptosis-Related lncRNA Signature Predicts Prognosis and Indicates the Immune Microenvironment in Soft Tissue Sarcomas
Binfeng Liu, Zhongyue Liu, Chengyao Feng, Chao Tu
Frontiers in Genetics.2022;[Epub] CrossRef
A novel inflammatory signature for evaluating immune microenvironment status in soft tissue sarcoma
Zhehong Li, Honghong Zheng, Lirui Liu, Zhen Fen, Haiying Cao, Jilong Yang, Junqiang Wei
Frontiers in Oncology.2022;[Epub] CrossRef
Issues of diagnostic search of soft tissue sarcoma
A. N. Sergeev, D. A. Maksimov, A. M. Morozov, M. A. Belyak, E. V. Penyaz', M. O. Popova
Bulletin of the Medical Institute "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH).2022;[Epub] CrossRef
Issues of diagnostic search of soft tissue sarcoma
A. N. Sergeev, D. A. Maksimov, A. M. Morozov, M. A. Belyak, E. V. Penyaz', M. O. Popova
Bulletin of the Medical Institute "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH).2022; 12(6): 15. CrossRef
Development and validation of an immune gene-set based prognostic signature for soft tissue sarcoma
Rui Shen, Bo Liu, Xuesen Li, Tengbo Yu, Kuishuai Xu, Jinfeng Ma
BMC Cancer.2021;[Epub] CrossRef
Identification of Novel Prognostic Risk Signatures of Soft Tissue Sarcoma Based on Ferroptosis-Related Genes
Wenjing Huang, Yuhe Duan, Xiuwei Yang, Cong Shang, Xin Chen, Huanyu Zhang, Fujiang Li
Frontiers in Oncology.2021;[Epub] CrossRef
Pulmonary metastasectomy in bone and soft tissue sarcoma with metastasis to the lung
Charles A Gusho, Christopher W Seder, Nicolas Lopez-Hisijos, Alan T Blank, Marta Batus
Interactive CardioVascular and Thoracic Surgery.2021; 33(6): 879. CrossRef
Construction of a Novel Signature and Prediction of the Immune Landscape in Soft Tissue Sarcomas Based on N6-Methylandenosine-Related LncRNAs
Li Zhang, Xianzhe Tang, Jia Wan, Xianghong Zhang, Tao Zheng, Zhengjun Lin, Tang Liu
Frontiers in Molecular Biosciences.2021;[Epub] CrossRef
Identification and Validation of Pyroptosis-Related lncRNA Signature and Its Correlation with Immune Landscape in Soft Tissue Sarcomas
Zhengjun Lin, Yiting Xu, Xianghong Zhang, Jia Wan, Tao Zheng, Hongxuan Chen, Shijie Chen, Tang Liu
International Journal of General Medicine.2021; Volume 14: 8263. CrossRef
Demographics, Changes in Treatment Patterns, and Outcomes of Bone and Soft Tissue Sarcomas in Korea—A Sarcoma-Specific, Institutional Registry-Based Analysis
Hyehyun Jeong, Hyeon-Su Im, Wanlim Kim, Jong-Seok Lee, Si Yeol Song, Joon Seon Song, Kyung-Ja Cho, Hye Won Chung, Min Hee Lee, Jeong Eun Kim, Jin-Hee Ahn
Cancer Management and Research.2021; Volume 13: 8795. CrossRef
Characterization of Immune-Related Long Non-coding RNAs to Construct a Novel Signature and Predict the Prognosis and Immune Landscape of Soft Tissue Sarcoma
Zhengjun Lin, Ke Pang, Hongli Li, Xianghong Zhang, Jia Wan, Tao Zheng, Tang Liu, Weijun Peng
Frontiers in Cell and Developmental Biology.2021;[Epub] CrossRef
Real-World Outcomes of Pazopanib Treatment in Korean Patients with Advanced Soft Tissue Sarcoma: A Multicenter Retrospective Cohort Study
Chung Ryul Oh, Jung Yong Hong, Jee Hung Kim, Ji Sung Lee, Hyo Song Kim, Tae Won Kim, Jin-Hee Ahn, Jeong Eun Kim
Targeted Oncology.2020; 15(4): 485. CrossRef
Comprehensive profiling of immune-related genes in soft tissue sarcoma patients
Chuan Hu, Bo Chen, Zhangheng Huang, Chuan Liu, Lin Ye, Cailin Wang, Yuexin Tong, Jiaxin Yang, Chengliang Zhao
Journal of Translational Medicine.2020;[Epub] CrossRef

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Temsirolimus in Asian Metastatic/Recurrent Non-clear Cell Renal Carcinoma: Jii Bum Lee, Hyung Soon Park, Sejung Park, Hyo Jin Lee, Kyung A Kwon, Young Jin Choi, Yu Jung Kim, Chung Mo Nam, Nam Hoon Cho, Beodeul Kang, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2019;51(4):1578-1588. Published online April 16, 2019; DOI: https://doi.org/10.4143/crt.2018.671

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Purpose
Temsirolimus is effective in the treatment for metastatic non-clear cell renal cell carcinoma (nccRCC) with poor prognosis. We aim to investigate the efficacy and tolerability of temsirolimus in treatment of naïve Asian patients with metastatic/recurrent nccRCC.
Materials and Methods
From January 2008 to July 2017, data of treatment-naïve, metastatic/recurrent nccRCC patients, who were treated with temsirolimus according to the standard protocol, were collected. The primary end-point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), and tolerability of temsirolimus.
Results
Forty-four metastatic/recurrent nccRCC patients, 10 from prospective and 34 from retrospective groups, were enrolled; 24 patients (54%) were papillary type, and other histology subtypes included 11 chromophobes (25%), two collecting ducts (5%), one Xp11.2 translocation (2%), and six others (14%). The median PFS and OS were 7.6 months and 17.6 months, res-pectively. ORR was 11% and disease control rate was 83%. Patients with prior nephrectomy had longer PFS (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.06 to 0.42; p < 0.001) and OS (HR, 0.15; 95% CI, 0.05 to 0.45; p < 0.001). Compared to favorable/intermediate prognosis group, poor prognosis group had shorter median PFS (4.7 months vs. 7.6 months [HR, 2.91; 95% CI, 1.39 to 6.12; p=0.005]) and median OS (9.2 months vs. 17.6 months [HR, 2.84; 95% CI, 1.23 to 6.56; p=0.015]).
Conclusion
Temsirolimus not only benefits poor-risk nccRCC patients, but it is also effective in favorable or intermediate-risk group in Asians. Temsirolimus was well-tolerated with manageable adverse events.

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Advances in non‐clear cell renal cell carcinoma management: From heterogeneous biology to treatment options
Nathaniel R. Wilson, Yusuf Acikgoz, Elshad Hasanov
International Journal of Cancer.2024; 154(6): 947. CrossRef
Cancer stem cells and angiogenesis
Yanru Yang, Jingyu Guo, Mingyang Li, Guangxin Chu, Hai Jin, Jing Ma, Qingge Jia
Pathology - Research and Practice.2024; 253: 155064. CrossRef
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Aimin Jiang, Jinxin Li, Ziwei He, Ying Liu, Kun Qiao, Yu Fang, Le Qu, Peng Luo, Anqi Lin, Linhui Wang
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Cost-effectiveness analysis of anlotinib versus sunitinib as first-line treatment for metastatic renal cell carcinoma in China
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PLOS ONE.2023; 18(2): e0281402. CrossRef
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Kidney Cancer.2023; 7(1): 123. CrossRef

7,988 View
184 Download
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Behaviors and Attitudes toward the Use of Complementary and Alternative Medicine among Korean Cancer Patients: Jung Hye Kwon, Sang-Cheol Lee, Myung Ah Lee, Yu Jung Kim, Jung Hun Kang, Jin Young Kim, Hyo Jin Lee, Woo Kyun Bae, Mi-Jung Kim, Eui Kyu Chie, Jin Kim, Yeul Hong Kim, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2019;51(3):851-860. Published online June 7, 2019; DOI: https://doi.org/10.4143/crt.2019.137

Abstract PDF Supplementary Material PubReader ePub

Purpose
A cross-sectional survey was conducted to explore the current awareness and use of complementary and alternative medicine (CAM), as well as attitudes toward CAM, in patients with cancer and their family members in South Korea.
Materials and Methods
Between September 21 and October 31, 2017, a 25-item questionnaire regarding CAM experiences among cancer patients and their family members was conducted in 10 oncology clinics in South Korea after institutional review board approval at each institution.
Results
In total, 283/310 patients were analyzed. The median age was 60 years, and 60% were male. Most of the patients were actively receiving anticancer treatment at the time of the survey. A total of 106 patients (37%) had experienced a median of two types (interquartile range, 1 to 3) of CAM. Belief in CAM (odds ratio [OR], 3.015; 95% confidence interval [CI], 1.611 to 5.640) and duration of disease (OR, 1.012; 95% CI, 1.004 to 1.020) were independent factors for using CAM in multivariable analysis. Belief in CAM was significantly associated with current use of CAM (OR, 3.633; 95% CI, 1.567 to 8.424). Lay referral was the most common reason for deciding to use CAM, and only 25% of patients (72/283) discussed CAM with their physicians.
Conclusion
Patient attitudes toward and confidence in CAM modalities were strongly associated with their CAM experiences, and only a small number of patients had an open discussion about CAM with their physicians. A patient education program for CAM is needed.

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Immunohistochemistry Biomarkers Predict Survival in Stage II/III Gastric Cancer Patients: From a Prospective Clinical Trial: Min Hwan Kim, Xianglan Zhang, Minkyu Jung, Inkyung Jung, Hyung Soon Park, Seung-Hoon Beom, Hyo Song Kim, Sun Young Rha, Hyunki Kim, Yoon Young Choi, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Hyun Cheol Chung; Cancer Res Treat. 2019;51(2):819-831. Published online September 27, 2018; DOI: https://doi.org/10.4143/crt.2018.331

Abstract PDF Supplementary Material PubReader ePub

Purpose
Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection.
Materials and Methods
This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomy with or without adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values.
Results
Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis.
Conclusion
This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.

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Hirofumi Tazawa, Takahisa Suzuki, Akihisa Saito, Akira Ishikawa, Toshiaki Komo, Haruki Sada, Norimitsu Shimada, Naoto Hadano, Takashi Onoe, Takeshi Sudo, Yosuke Shimizu, Kazuya Kuraoka, Hirotaka Tashiro
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Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis
van den Ende, ter Veer, Mali, van Berge Henegouwen, Hulshof, van Oijen, van Laarhoven
Cancers.2019; 11(4): 530. CrossRef

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S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial: Choong-kun Lee, Minkyu Jung, Hyo Song Kim, Inkyung Jung, Dong Bok Shin, Seok Yun Kang, Dae Young Zang, Ki Hyang Kim, Moon Hee Lee, Bong-Seog Kim, Kyung Hee Lee, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2019;51(1):1-11. Published online February 5, 2018; DOI: https://doi.org/10.4143/crt.2018.028

Abstract PDF Supplementary Material PubReader ePub

Purpose
We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients.
Materials and Methods
Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m² /day on days 1-14 plus docetaxel 35 mg/m² on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m² /day on days 1-14 plus cisplatin 60 mg/m² on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate.
Results
Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment.
Conclusion
Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.

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Efficacy and safety of docetaxel plus S-1-based therapy in gastric cancer: a quantitative evidence synthesis of randomized controlled trials
Hui-Fen Lv, Li-Feng Qin, Rui-Zhi Ran, Xue-Ping Jiang, Fang-Yu Zhao, Bo Li
Frontiers in Pharmacology.2024;[Epub] CrossRef
A novel method of bedside hyperthermic intraperitoneal chemotherapy as adjuvant therapy for stage-III gastric cancer
Lili Liu, Li Sun, Ning Zhang, Cheng-gong Liao, Haichuan Su, Jie Min, Yang Song, Xue Yang, Xiaofeng Huang, Dongxu Chen, Yu Chen, Hong-wei Zhang, Helong Zhang
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Ina Valeria Zurlo, Michele Basso, Antonia Strippoli, Maria Alessandra Calegari, Armando Orlandi, Alessandra Cassano, Mariantonietta Di Salvatore, Giovanna Garufi, Emilio Bria, Giampaolo Tortora, Carlo Barone, Carmelo Pozzo
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Long Ge, Liangying Hou, Qingxia Yang, Yiting Wu, Xiue Shi, Jiang Li, Kehu Yang
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Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis
Tom van den Ende, Emil ter Veer, Rosa M. A. Mali, Mark I. van Berge Henegouwen, Maarten C. C. M. Hulshof, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven
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Tom van den Ende, Frank A. Abe Nijenhuis, Héctor G. van den Boorn, Emil ter Veer, Maarten C. C. M. Hulshof, Suzanne S. Gisbertz, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven
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Landscape of Actionable Genetic Alterations Profiled from 1,071 Tumor Samples in Korean Cancer Patients: Se-Hoon Lee, Boram Lee, Joon Ho Shim, Kwang Woo Lee, Jae Won Yun, Sook-Young Kim, Tae-You Kim, Yeul Hong Kim, Young Hyeh Ko, Hyun Cheol Chung, Chang Sik Yu, Jeeyun Lee, Sun Young Rha, Tae Won Kim, Kyung Hae Jung, Seock-Ah Im, Hyeong-Gon Moon, Sukki Cho, Jin Hyoung Kang, Jihun Kim, Sang Kyum Kim, Han Suk Ryu, Sang Yun Ha, Jong Il Kim, Yeun-Jun Chung, Cheolmin Kim, Hyung-Lae Kim, Woong-Yang Park, Dong-Young Noh, Keunchil Park; Cancer Res Treat. 2019;51(1):211-222. Published online April 23, 2018; DOI: https://doi.org/10.4143/crt.2018.132

Abstract PDF Supplementary Material PubReader ePub

Purpose
With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data.
Materials and Methods
To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared.
Results
We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration.
Conclusion
In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

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Genetic Alterations among Korean Melanoma Patients Showing Tumor Heterogeneity: A Comparison between Primary Tumors and Corresponding Metastatic Lesions: Si-Hyung Lee, Jee Eun Kim, Hong Sun Jang, Kyu Hyun Park, Byung Ho Oh, Sang Joon Shin, Kee Yang Chung, Mi Ryung Roh, Sun Young Rha; Cancer Res Treat. 2018;50(4):1378-1387. Published online January 22, 2018; DOI: https://doi.org/10.4143/crt.2017.535

Abstract PDF Supplementary Material PubReader ePub

Purpose
Melanoma is a highly heterogeneous neoplasm, composed of subpopulations of tumor cells with distinct molecular and biological phenotypes and genotypes. In this study, to determine the genetic heterogeneity between primary and metastatic melanoma in Korean melanoma patients, we evaluated several well-known genetic alterations of melanoma. In addition, to elucidate the clinical relevance of each genetic alteration and heterogeneity between primary and metastatic lesions, clinical features and patient outcome were collected.
Materials and Methods
In addition to clinical data, BRAF, NRAS, GNAQ/11 mutation and KIT amplification data was acquired from an archived primary Korean melanoma cohort (KMC) of 188 patients. Among these patients, 43 patients were included for investigation of tumor heterogeneity between primary melanoma and its corresponding metastatic lesions.
Results
Overall incidence of genetic aberrations of the primary melanomas in KMC was 17.6% of BRAF V600, 12.6% of NRAS mutation, and 28.6% of KIT amplification. GNAQ/11 mutation was seen in 66.6% of the uveal melanoma patients. Patients with BRAF mutation were associated with advanced stage and correlated to poor prognosis (p < 0.01). Among 43 patients, 55.8% showed heterogeneity between primary and metastatic lesion. The frequency of BRAF mutation and KIT amplification significantly increased in the metastatic lesions compared to primary melanomas. Conclusion
Our data demonstrated heterogeneity between primary melanomas and corresponding metastatic lesions for BRAF, NRAS mutation and KIT amplification. However, GNAQ/11 mutation was genetically homogeneous between primary and metastatic melanoma lesions in uveal melanoma.

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N. N. Mazurenko, I. V. Tsyganova, V. V. Nazarova, I. A. Utyashev, K. V. Orlova, D. A. Ponkratova, D. V. Martinkov, L. V. Demidov
Advances in molecular oncology.2018; 5(3): 51. CrossRef

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Pazopanib for the Treatment of Non-clear Cell Renal Cell Carcinoma: A Single-Arm, Open-Label, Multicenter, Phase II Study: Ki Sun Jung, Su Jin Lee, Se Hoon Park, Jae-Lyun Lee, Se-Hoon Lee, Jae Yun Lim, Jung Hun Kang, Suee Lee, Sun Young Rha, Kyung Hee Lee, Ho Young Kim, Ho Yeong Lim; Cancer Res Treat. 2018;50(2):488-494. Published online May 22, 2017; DOI: https://doi.org/10.4143/crt.2016.584

Abstract PDF Supplementary Material PubReader ePub

Purpose
The optimal treatment strategy for patients with metastatic non-clear cell type renal cell carcinoma (nccRCC) remains unclear. Although several inhibitors of vascular endothelial growth factor have recently shown efficacy against nccRCC, the clinical benefit of pazopanib in nccRCC has not been analyzed. We therefore designed a single-arm, open-label, phase II study to determine the efficacy and safety of pazopanib in patients with nccRCC.
Materials and Methods
Patientswith locally advanced or metastatic nccRCC, exceptfor collecting duct or sarcomatoid type, received 800 mg/day of pazopanib daily until progression of disease or intolerable toxicity. One cyclewas defined as 4weeks and tumorresponsewas evaluated every two cycles. The primary objective was overall response rate (ORR).
Results
A total of 29 eligible patients were enrolled at nine centers in Korea from December 2012 and September 2014. The median age of the patients was 58 years (range, 27 to 76 years) and 21 patients (72%) were male. Regarding histology type, 19 patients had papillary, three had chromophobe, two had unclassified and five had unknown non-clear cell type. Of 28 evaluable patients, eight achieved a confirmed partial response with ORR of 28%. The median progression-free survival was 16.5 months (95% confidence interval, 10.9 to 22.1) and median overall survival was not reached. Sixteen patients (55%) experienced treatment-related toxicity of grade 3 or more, but most adverse events were overcome through dose reduction and delay.
Conclusion
In this prospective phase II study, pazopanib demonstrated promising activity and tolerable safety profile in patients with metastatic nccRCC.

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Efficacy and Toxicity of Mammalian Target Rapamycin Inhibitors in Patients with Metastatic Renal Cell Carcinoma with Renal Insufficiency: The Korean Cancer Study Group GU 14-08: Ki Hyang Kim, Joo Hoon Kim, Ji Young Lee, Hyo Song Kim, Su Jin Heo, Ji Hyung Kim, Ho Young Kim, Sun Young Rha; Cancer Res Treat. 2016;48(4):1286-1292. Published online February 12, 2016; DOI: https://doi.org/10.4143/crt.2016.018

Abstract PDF PubReader ePub

Purpose
We evaluated the efficacy and toxicity of mammalian target rapamycin inhibitors in Korean patients with metastatic renal cell carcinoma (mRCC) with chronic renal insufficiency not requiring dialysis. Materials and Methods Korean patients with mRCC and chronic renal insufficiency not requiring dialysis treated with everolimus or temsirolimus between January 2008 and December 2014 were included. Patient characteristics, clinical outcomes, and toxicities were evaluated. Overall survival (OS) and progression-free survival (PFS) durations were evaluated according to the degree of renal impairment.
Results
Eighteen patients were considered eligible for the study (median age, 59 years). The median glomerular filtration rate was 51.5 mL/min/1.73 m2. The best response was partial response in six patients and stable disease in 11 patients. The median PFS and OS durations were 8 months (95% confidence interval [CI], 0 to 20.4) and 32 months (95% CI, 27.5 to 36.5), respectively. The most common non-hematologic and grade 3/4 adverse events included stomatitis, fatigue, flu-like symptoms, and anorexia as well as elevated creatinine level. Conclusion Mammalian target rapamycin inhibitors were efficacious and did not increase toxicity in Korean patients with mRCC and chronic renal insufficiency not requiring dialysis.

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Prevalence of acute oral mucosal damage secondary to the use of systemic antineoplastics: A systematic review and meta-analysis
Manuel Eros Rodríguez-Fuentes, Mario Pérez-Sayáns, Carmen Martín Carreras-Presas, Xabier Marichalar-Mendia, Leticia Bagán-Debón, Rafael López-López
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.2023; 135(3): 385. CrossRef
Renal toxicity of targeted therapies for renal cell carcinoma in patients with normal and impaired kidney function
Łukasz Mielczarek, Anna Brodziak, Paweł Sobczuk, Maciej Kawecki, Agnieszka Cudnoch-Jędrzejewska, Anna M. Czarnecka
Cancer Chemotherapy and Pharmacology.2021; 87(6): 723. CrossRef
Safety and Efficacy of Pazopanib in First-Line Metastatic Renal-Cell Carcinoma With or Without Renal Failure: CORE-URO-01 Study
Cristina Masini, Maria Giuseppa Vitale, Marco Maruzzo, Giuseppe Procopio, Ugo de Giorgi, Sebastiano Buti, Sabrina Rossetti, Roberto Iacovelli, Francesco Atzori, Laura Cosmai, Francesca Vignani, Giuseppe Prati, Sarah Scagliarini, Annalisa Guida, Annalisa B
Clinical Genitourinary Cancer.2019; 17(1): e150. CrossRef
Renal toxicity with mammalian target of rapamycin inhibitors: A meta-analysis of randomized clinical trials
Ravi K. Paluri, Guru Sonpavde, Charity Morgan, Jacob Rojymon, Anastasia Hartzes Mar, Radhika Gangaraju
Oncology Reviews.2019;[Epub] CrossRef

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PTEN Methylation Dependent Sinonasal Mucosal Melanoma: Sang Hee Lee, Mi Ryung Roh, Beodeul Kang, Kyu Hyun Park, Soo Hee Kim, Sang Eun Lee, Sun Young Rha; Cancer Res Treat. 2016;48(2):853-858. Published online March 18, 2015; DOI: https://doi.org/10.4143/crt.2014.356

Abstract PDF PubReader ePub

Sinonasal mucosal melanoma (SMM) is an aggressive and rare type of melanoma. Although the classic RAS-RAF-MEK pathway is thought to be the main pathway involved in melanoma pathogenesis, genetic alterations in the phosphatidylinositol 3-kinase–AKT pathway, including PTEN-regulated signaling, are also thought to contribute. So far, data regarding altered PTEN expression and epigenetic mechanism of PTEN silencing in development of SMM is extremely limited. Herein we report on a case of SMM with liver and bone metastases with an epigenetic alteration of PTEN. Results of mutation analysis for BRAF, NRAS, HRAS, KRAS, PIK3CA, c-Kit, and PTEN were negative; however, methylation of PTEN CpG islands was observed. Our case not only supports PTEN as a major tumor suppressor involved in melanoma tumorigenesis, but also a potential epigenetic mechanism of PTEN silencing in development of SMM.

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Mucosal Melanoma: Epidemiology, Clinical Features, and Treatment
Maria Chiara Sergi, Elisabetta Filoni, Giacomo Triggiano, Gerardo Cazzato, Valeria Internò, Camillo Porta, Marco Tucci
Current Oncology Reports.2023; 25(11): 1247. CrossRef
Mucosal melanomas of different anatomic sites share a common global DNA methylation profile with cutaneous melanoma but show location‐dependent patterns of genetic and epigenetic alterations
Philipp Jurmeister, Niklas Wrede, Inga Hoffmann, Claudia Vollbrecht, Daniel Heim, Michael Hummel, Peggy Wolkenstein, Ines Koch, Verena Heynol, Wolfgang Daniel Schmitt, Anne Thieme, Daniel Teichmann, Christine Sers, Andreas von Deimling, Julia Cara Thierau
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Actionable Mutation Profile of Sun-Protected Melanomas in South America
Ricardo Hsieh, Marcello M. S. Nico, Cláudia M. C. Camillo, Kátia K. Oliveira, Dirce M. Carraro, Martin Sangueza, Silvia V. Lourenço
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A Retrospective Analysis for Patients with HER2-Positive Gastric Cancer Who Were Treated with Trastuzumab-Based Chemotherapy: In the Perspectives of Ethnicity and Histology: Jun Ho Yi, Jung Hun Kang, In Gyu Hwang, Hee Kyung Ahn, Hyun Jin Baek, Soon Il Lee, Do Hyoung Lim, Young-Woong Won, Jun Ho Ji, Hyo Song Kim, Sun Young Rha, Sung Yong Oh, Kyung Eun Lee, Taekyu Lim, Chi Hoon Maeng, Moon Jin Kim, Seung Tae Kim, Jeeyun Lee, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang, Se Hoon Park; Cancer Res Treat. 2016;48(2):553-560. Published online August 10, 2015; DOI: https://doi.org/10.4143/crt.2015.155

Abstract PDF PubReader ePub

Purpose
While the Trastuzumab for Gastric Cancer (ToGA) trial demonstrated the efficacy and safety of trastuzumab-based chemotherapy in HER2-positive metastatic gastric cancer, the overall survival (OS) benefit was not found in Asian and diffuse-type cancer patients. The aim of the study is to investigate predictive markers for trastuzumab-based chemotherapy.
Materials and Methods
Data of patients with HER2-positive gastric cancer treated with trastuzumab-based chemotherapy were analyzed retrospectively.
Results
A total of 168 Asian patients were included. The median age was 60 years (range, 27 to 85 years) and the male:female ratio was 118 (70.2%):50 (29.8%). Fourteen (8.3%), 63 (37.5%), 75 (44.6%), and 11 (6.5%) patients had well, moderately, poorly-differentiated tubular adenocarcinoma and signet ring cell carcinoma, respectively. With 14 complete responses and 73 partial responses, the response rate was 50.6%. The median progression-free survival (PFS) was 10.2 months (95% confidence interval [CI], 8.7 to 11.7), and the median OS was 18.5 months (95% CI, 16.4 to 50.6). Next, we investigated the effect of poorly-differentiated histology (PDH, poorly-differentiated tubular adenocarcinoma+signet ring cell carcinoma) on clinical outcomes. The median PFS (8.9 months vs. 11.5 months, p=0.16) was slightly inferior in PDH patients, and the median OS was significantly shorter in PDH patients (14.6 months vs. 19.0 months, p=0.025).
Conclusion
While subset analysis of the ToGA trial demonstrated that trastuzumab-based chemotherapy may not be beneficial for Asians and patients with PDH, our data may suggest that even in Asian patients and patients with PDH, trastuzumab-based chemotherapy could be associated with improved clinical outcomes in patients with HER2-positive gastric cancer.

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p16 Hypermethylation and KRAS Mutation Are Independent Predictors of Cetuximab Plus FOLFIRI Chemotherapy in Patients with Metastatic Colorectal Cancer: Se Hyun Kim, Kyu Hyun Park, Sang Joon Shin, Kang Young Lee, Tae Il Kim, Nam Kyu Kim, Sun Young Rha, Jae Kyung Roh, Joong Bae Ahn; Cancer Res Treat. 2016;48(1):208-215. Published online April 24, 2015; DOI: https://doi.org/10.4143/crt.2014.314

Abstract PDF PubReader ePub

Purpose
Hypermethylation of the CpG island of p16INK4a occurs in a significant proportion of colorectal cancer (CRC). We aimed to investigate its predictive role in CRC patients treated with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), and cetuximab.
Materials and Methods
Pyrosequencing was used to identify KRASmutation and hypermethylation of 6 CpG island loci (p16, p14, MINT1, MINT2, MINT31, and hMLH1) in DNA extracted from formalin-fixed paraffin-embedded specimens. Logistic regression and Cox regression were performed for analysis of the relation between methylation status of CpG island methylator phenotype (CIMP) markers including p16 and clinical outcome.
Results
Hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) and showed significant association with KRASmutation (Fisher exact, p=0.01) and CIMP positivity (Fisher exact, p=0.002). Patients with p16-unmethylated tumors had significantly longer time to progression (TTP; median, 9.0 months vs. 3.5 months; log-rank, p=0.001) and overall survival (median, 44.9 months vs. 16.4 months; log-rank, p=0.008) than those with p16-methylated tumors. Patients with both KRAS and p16 aberrancy (n=6) had markedly shortened TTP (median, 2.8 months) compared to those with either KRAS or p16 aberrancy (n=11; median, 8.6 months; p=0.021) or those with neither (n=32; median, 9.0 months; p < 0.0001). In multivariate analysis, KRAS mutation and p16 methylation showed independent association with shorter TTP (KRAS mutation: hazard ratio [HR], 3.21; p=0.017; p16 methylation: HR, 2.97; p=0.027).
Conclusion
Hypermethylation of p16 was predictive of clinical outcome in metastatic CRC patients treated with cetuximab and FOLFIRI, irrespective of KRAS mutation.

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Can Kong, Tao Fu
Oncology Reports.2021;[Epub] CrossRef
Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma
Maja T. Tomicic, Mona Dawood, Thomas Efferth
Cancers.2021; 13(16): 4072. CrossRef
Multiple gene promoter methylation and clinical stage in adjacent normal tissues: Effect on prognosis of colorectal cancer in Taiwan
Chih-Hsiung Hsu, Cheng-Wen Hsiao, Chien-An Sun, Wen-Chih Wu, Tsan Yang, Je-Ming Hu, Yu-Chan Liao, Chi-Hua Huang, Chao-Yang Chen, Fu-Huang Lin, Yu-Ching Chou
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Klara Cervena, Anna Siskova, Tomas Buchler, Pavel Vodicka, Veronika Vymetalkova
Cells.2020; 9(6): 1540. CrossRef
CpG Island Methylator Phenotype and Methylation of Wnt Pathway Genes Together Predict Survival in Patients with Colorectal Cancer
Se Hyun Kim, Kyu Hyun Park, Sang Joon Shin, Kang Young Lee, Tae Il Kim, Nam Kyu Kim, Sun Young Rha, Joong Bae Ahn
Yonsei Medical Journal.2018; 59(5): 588. CrossRef
Recent advances in understanding colorectal cancer
Sebastian Stintzing
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Amana Saadallah-Kallel, Rania Abdelmaksoud-Dammak, Mouna Triki, Slim Charfi, Abdelmajid Khabir, Tahia Sallemi-Boudawara, Raja Mokdad-Gargouri
Medical Oncology.2017;[Epub] CrossRef
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Jinyun Li, Cheng Chen, Xuer Bi, Chongchang Zhou, Tao Huang, Chao Ni, Ping Yang, Si Chen, Meng Ye, Shiwei Duan
Gene.2017; 630: 1. CrossRef

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Results of a Phase II Study to Evaluate the Efficacy of Docetaxel and Carboplatin in Metastatic Malignant Melanoma Patients Who Failed First-Line Therapy Containing Dacarbazine: Choong-kun Lee, Minkyu Jung, Hye Jin Choi, Hye Ryun Kim, Hyo Song Kim, Mi Ryung Roh, Joong Bae Ahn, Hyun Cheol Chung, Su Jin Heo, Sun Young Rha, Sang Joon Shin; Cancer Res Treat. 2015;47(4):781-789. Published online February 16, 2015; DOI: https://doi.org/10.4143/crt.2014.261

Abstract PDF PubReader ePub

Purpose
There is no standard second-line regimen for malignant melanoma patients with disease progression after first-line chemotherapy, and platinum-alkylating agents combined with paclitaxel have shown modest efficacy. Materials and Methods We conducted a phase II, open-label, single-arm study to test the efficacy of docetaxel combined with carboplatin for malignant melanoma patients who failed previous treatment with dacarbazine. Intravenous docetaxel (35 mg/m2 on days 1 and 8 of each cycle) and carboplatin (area under the curve 3 on days 1 and 8 of each cycle) was administered every 21 days. Primary end point was objective response rate (ORR).
Results
Thirty patients were enrolled in the study, and the median follow-up duration was 19.8 months. Among 25 per-protocol patients, there were three responders (1 with complete response and 2 with partial response) and 17 stable disease patients (ORR, 12.0%). Among the per-protocol population, the median progression-free survival (PFS) was 4.3 months and the median overall survival (OS) was 9.6 months. Uveal melanoma patients (n=9) showed the best prognosis compared to other subtypes (median PFS, 7.6 months; OS, 9.9 months). The most common grade 3 or 4 adverse event was neutropenia (n=15, 50.0%). Conclusion Docetaxel combined with carboplatin showed association with an acceptable safety profile and overall efficacy for patients with malignant melanoma who had progressed on chemotherapy containing dacarbazine.

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Signaling pathways driving ocular malignancies and their targeting by bioactive phytochemicals
Courtney R. Croley, Joshua Pumarol, Blake E. Delgadillo, Andrew C. Cook, Faith Day, Tea Kaceli, Caroline C. Ward, Imran Husain, Ali Husain, Sabyasachi Banerjee, Anupam Bishayee
Pharmacology & Therapeutics.2023; 248: 108479. CrossRef
A Phase 1 study of ADI‐PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1‐negative metastatic uveal melanoma
Pui Ying Chan, Melissa M. Phillips, Stephen Ellis, Amanda Johnston, Xiaoxing Feng, Amit Arora, Gordon Hay, Victoria M. L. Cohen, Mandeep S. Sagoo, John S. Bomalaski, Michael T. Sheaff, Peter W. Szlosarek
Pigment Cell & Melanoma Research.2022; 35(4): 461. CrossRef
iUMRG: multi-layered network-guided propagation modeling for the inference of susceptibility genes and potential drugs against uveal melanoma
Yueping Ren, Congcong Yan, Lili Wu, Jingting Zhao, Mingwei Chen, Meng Zhou, Xiaoyan Wang, Tonghua Liu, Quanyong Yi, Jie Sun
npj Systems Biology and Applications.2022;[Epub] CrossRef
Systemic and Liver-Directed Therapies in Metastatic Uveal Melanoma: State-of-the-Art and Novel Perspectives
Francesca Comito, Paola Valeria Marchese, Angela Dalia Ricci, Nastassja Tober, Chiara Peterle, Francesca Sperandi, Barbara Melotti
Future Oncology.2021; 17(33): 4583. CrossRef
New Therapeutic Perspectives in the Treatment of Uveal Melanoma: A Systematic Review
Mario Damiano Toro, Lucia Gozzo, Luciano Tracia, Marco Cicciù, Filippo Drago, Claudio Bucolo, Teresio Avitabile, Robert Rejdak, Katarzyna Nowomiejska, Sandrine Zweifel, Yacoub A. Yousef, Rashed Nazzal, Giovanni Luca Romano
Biomedicines.2021; 9(10): 1311. CrossRef
Interferon-α versus interleukin-2 in Chinese patients with malignant melanoma
Shenglong Li, Xixi Wu, Peng Chen, Yi Pei, Ke Zheng, Wei Wang, Enduo Qiu, Xiaojing Zhang
Anti-Cancer Drugs.2019; 30(4): 402. CrossRef
Mechanism of HN‑3 cell apoptosis induced by carboplatin: Combination of mitochondrial pathway associated with Ca2+ and the nucleus pathways
Bo Shen, Wenjing Mao, Jin‑Chul Ahn, Phil‑Sang Chung, Peijie He
Molecular Medicine Reports.2018;[Epub] CrossRef
Endoplasmic reticulum stress-mediated pathways to both apoptosis and autophagy: Significance for melanoma treatment
Mohamed Hassan
World Journal of Experimental Medicine.2015; 5(4): 206. CrossRef

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Incidence and Survival of Pediatric Soft Tissue Sarcomas: Comparison between Adults and Children: Sun Min Lim, Cheol Joo Yoo, Jung Woo Han, Yong Jin Cho, Soo Hee Kim, Joong Bae Ahn, Sun Young Rha, Sang Joon Shin, Hyun Cheol Chung, Woo Ick Yang, Kyoo-Ho Shin, Jae Kyung Rho, Hyo Song Kim; Cancer Res Treat. 2015;47(1):9-17. Published online August 21, 2014; DOI: https://doi.org/10.4143/crt.2013.157

Abstract PDF PubReader ePub

Purpose
Pediatric-type sarcomas such as rhabdomyosarcoma (RMS), Ewing sarcoma (EWS), primitive neuroectodermal tumor (PNET), and desmoplastic small round-cell tumor (DSRCT) are rare in adults, with limited studies on their prognosis and optimal treatment strategies. We aimed to examine the outcome of children and adult patients with RMS, EWS, PNET, and DSRCT and relevant prognostic factors. Materials and Methods We retrospectively reviewed 220 pediatric-type sarcoma patients at a single institution between 1985 and 2011. Comparisons were made in order to examine differences in demographics, disease characteristics, and survival. Survival analyses were performed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards models. Results A total of 220 consecutive patients were identified at our institute. Median age was 15.6 years (range, 0 to 81 years) and there were 108 children (49%) and 112 adult patients (51%). According to histological classification, 106 patients (48.2%) had RMS, 60 (27.3%) had EWS, 50 (22.7%) had PNET, and 4 (1.8%) had DSRCT. With a median follow-up period of 6.6 years, the estimated median overall survival (OS) of all patients was 75 months (95% confidence interval [CI], 27.2 to 122.8 months) and median event-free survival (EFS) for all patients was 11 months (95% CI, 8.8 to 13.2 months). No significant difference in OS and EFS was observed between adults and children. In multivariate analysis, distant metastasis (hazard ratio [HR], 1.617; 95% CI, 1.022 to 2.557; p=0.040) and no debulking surgery (HR, 1.443; 95% CI, 1.104 to 1.812; p=0.012) showed independent association with worse OS. Conclusion Metastatic disease and no surgical treatment are poor prognostic factors for OS among pediatric-type sarcomas for both adults and children.

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Grace Guzman, Megan R. Reed, Kevin Bielamowicz, Brian Koss, Analiz Rodriguez
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Clinicopathological and treatment response characteristics of updated rhabdomyosarcoma histomolecular subtypes: An Asian population‐based study
Guo Yuan How, Chik Hong Kuick, Min Hwee Yong, Shui Yen Soh, Esther XY Hee, Meng Kang Wong, Richard Quek, Mohd Farid Harunal, Sathiyamoorthy Selvarajan, Kesavan Sittampalam, Chetan Anil Dhamne, Victor Lee, Kenneth TE Chang, Amos HP Loh
Asia-Pacific Journal of Clinical Oncology.2023;[Epub] CrossRef
Pediatric sarcoma survivorship: A call for a developmental cascades approach
Peter M. Fantozzi, Gina Sprint, Anna Marie Medina
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Vassiliki Lyra, Sofia Chatziioannou, Maria Kallergi
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Desmoplastic Small Round Cell Tumors With EWS-WT1 Transcript Expression: Should We Consider Children and Adult Patients Differently?
Laura Olivier-Gougenheim, Daniel Orbach, Vincent Atallah, Perrine Marec-Berard, Amandine Bertrand
Journal of Pediatric Hematology/Oncology.2022; 44(3): e637. CrossRef
Next-Generation Sequencing Identifies Potential Actionable Targets in Paediatric Sarcomas
Antonio Juan Ribelles, Pablo Gargallo, Pablo Berlanga, Vanessa Segura, Yania Yáñez, Bárbara Juan, Marta Salom, Margarita Llavador, Jaime Font de Mora, Victoria Castel, Adela Cañete
Journal of Personalized Medicine.2021; 11(4): 268. CrossRef
Ewing Sarcoma
Hee Young Ju
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Emerging trends in immunotherapy for pediatric sarcomas
Kyle A. Dyson, Brian D. Stover, Adam Grippin, Hector R. Mendez-Gomez, Joanne Lagmay, Duane A. Mitchell, Elias J. Sayour
Journal of Hematology & Oncology.2019;[Epub] CrossRef

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Clinical Features and Treatment of Collecting Duct Carcinoma of the Kidney from the Korean Cancer Study Group Genitourinary and Gynecology Cancer Committee: Kyung A Kwon, Sung Yong Oh, Ho Young Kim, Hyo Song Kim, Ha Young Lee, Tae Min Kim, Ho Yeong Lim, Na-Ri Lee, Hyo Jin Lee, Sook Hee Hong, Sun Young Rha; Cancer Res Treat. 2014;46(2):141-147. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.141

Abstract PDF PubReader ePub

Purpose

Collecting duct carcinoma (CDC) of the kidney is an aggressive disease with a poor prognosis, accountings for less than 1% of all renal cancers. To date, no standard therapy for CDC has been established. The aim of this study is an investigation of clinicopathologic findings of CDC and correlation of the disease status with a prognosis.

Materials and Methods

From 1996 to 2009, 35 patients with CDC were treated at eight medical centers. The diagnosis of CDC was made based on nephrectomy in 27 cases and renal biopsy in eight cases.

Results

Median PFS and OS for all patients were 5.8 months (95% CI 3.5 to 9.2) and 54.4 months (95% CI 0 to 109.2), respectively. The OS of patients with Stages I-III was 69.9 months (95% CI 54.0 to 85.8), while that of patients with Stage IV was 8.6 months (95% CI 0 to 23.3), which showed a statistically significant difference (p=0.01). In addition, among patients with Stage IV, the OS of patients who received a palliative treatment (immunotherapy, chemotherapy, or targeted therapy) was 18.4 months, which was higher than the OS of patients without treatment of 4.5 months.

Conclusion

CDC is a highly aggressive form of renal cell carcinoma. Despite most of the treatments, PFS and OS were short, however, there were some long-term survivors, therefore, conduct of additional research on the predictive markers of the several clinical, pathological differences and their treatments will be necessary.

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Urothelial Carcinoma of the Renal Pelvis with Synchronous Ipsilateral Collecting Duct Carcinoma: Two Case Reports
Sang Bin Bae, Seong Kuk Yoon, Seo-hee Rha
Journal of the Korean Society of Radiology.2024; 85(1): 222. CrossRef
A curious case: Concurrent collecting duct renal cell carcinoma and upper tract urothelial carcinoma
Adib Rahman, Daniel Matheson, Joanna Perry-Keene, Devang Desai
Urology Case Reports.2024; 54: 102698. CrossRef
Cancer subtype identification by multi-omics clustering based on interpretable feature and latent subspace learning
Tianyi Shi, Xiucai Ye, Dong Huang, Tetsuya Sakurai
Methods.2024; 231: 144. CrossRef
Tumeurs de Bellini et carcinomes médullaires rénaux à l’ère des nouvelles thérapies
Zoé Guillaume, Yves Allory, Edouard Auclin, Claire Gervais, Marie Auvray, Adrien Rochand, Arnaud Mejean, François Audenet, Yann-Alexandre Vano, Stéphane Oudard, Constance Thibault
Bulletin du Cancer.2023; 110(4): 450. CrossRef
Metastatic Renal Medullary and Collecting Duct Carcinoma in the Era of Antiangiogenic and Immune Checkpoint Inhibitors: A Multicentric Retrospective Study
Zoé Guillaume, Emeline Colomba, Jonathan Thouvenin, Carolina Saldana, Luca Campedel, Clément Dumont, Brigitte Laguerre, Denis Maillet, Cécile Vicier, Frédéric Rolland, Delphine Borchiellini, Philippe Barthelemy, Laurence Albiges, Edouard Auclin, Matthieu
Cancers.2022; 14(7): 1678. CrossRef
Uncommon malignant renal tumors and atypical presentation of common ones: a guide for radiologists
Benjamin Laguna, Antonio C. Westphalen, C. T. Guimarães, Zhen Whang, Jeff Simko, Ronald Zagoria
Abdominal Radiology.2019; 44(4): 1430. CrossRef
Collecting Duct Carcinoma of the Kidney: Analysis of Our Experience at the SPANISH ‘Grupo Centro’ of Genitourinary Tumors
A. Pinto, M. Garrido, C. Aguado, T. Alonso, P. Gajate, C. Maximiano, I. García-Carbonero, A. Martín, I. Gallegos, J.A. Arranz, J. Puente, E. Grande
Kidney Cancer.2019; 3(3): 177. CrossRef
Non-Clear Cell Renal Cell Carcinoma: Current Management and Best Practice
Meghan Salgia, Jacob Adashek, Paulo Bergerot, Sumanta K. Pal
Kidney Cancer.2017; 1(2): 99. CrossRef
Unique Transcriptomic Profile of Collecting Duct Carcinomas Relative to Upper Tract Urothelial Carcinomas and other Kidney Carcinomas
Gabriel G. Malouf, Eva Compérat, Hui Yao, Roger Mouawad, Veronique Lindner, Nathalie Rioux-leclercq, Virginie Verkarre, Xavier Leroy, Linda Dainese, Marion Classe, Jean-Luc Descotes, Philippe Barthelemy, Mokrane Yacoub, Morgan Rouprêt, Jean-Christophe Ber
Scientific Reports.2016;[Epub] CrossRef
Clinical and computed tomography imaging features of renal medullary carcinoma: A report of six cases
ZHENSHAN SHI, QIAN ZHUANG, RUIXIONG YOU, YUEMING LI, JIAN LI, DAIRONG CAO
Oncology Letters.2016; 11(1): 261. CrossRef
Collecting duct carcinoma of the kidney is associated withCDKN2Adeletion andSLCfamily gene up-regulation
Jianmin Wang, Antonios Papanicolau-Sengos, Sreenivasulu Chintala, Lei Wei, Biao Liu, Qiang Hu, Kiersten Marie Miles, Jeffrey M. Conroy, Sean T. Glenn, Manuela Costantini, Cristina Magi-Galluzzi, Sabina Signoretti, Toni Choueiri, Michele Gallucci, Steno Se
Oncotarget.2016; 7(21): 29901. CrossRef

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Weekly Gemcitabine and Docetaxel in Refractory Soft Tissue Sarcoma: A Retrospective Analysis: Ha-young Lee, Sang Joon Shin, Hyo Song Kim, Soo Jung Hong, Jung Woo Han, Seung Taek Lim, Jae Kyung Roh, Sun Young Rha; Cancer Res Treat. 2012;44(1):43-49. Published online March 31, 2012; DOI: https://doi.org/10.4143/crt.2012.44.1.43

Abstract PDF PubReader ePub

PURPOSE
The combination of gemcitabine and docetaxel (GD) is used to effectively treat patients with soft tissue sarcoma (STS). It is widely considered that the conventional doses used are too high for long term use and many patients must discontinue GD treatment due to its toxicity. Therefore, to determine the appropriate dose meeting acceptable efficacy results, while minimizing toxic side effects, we treated patients with a weekly infusion of GD (weekly GD).
MATERIALS AND METHODS
A total of 22 patients presenting a variety of STSs were treated at Yonsei Cancer Center. All patients had metastatic or recurrent cancer and had previously received doxorubicin and ifosfamide combination chemotherapy. In all cases, gemcitabine (1,000 mg/m2) and docetaxel (35 mg/m2) were administered intravenously on days 1 and 8 of a 21-day cycle. We retrospectively reviewed the medical records of these patients.
RESULTS
The response rate was 4.5%, with one patient diagnosed with leiomyosarcoma having a partial response, and the disease control rate was 40.9%. The median progression-free survival (PFS) duration was 2.7 months and the PFS was correlated with the treatment response to a weekly GD. The median overall survival (OS) duration was 7.8 months and the OS was correlated with histology. There was no significant difference in OS between patients who received weekly GD as a 2nd line chemotherapy and those who received 3rd line or more. Treatment was generally well tolerated.
CONCLUSION
Weekly GD was well tolerated and showed moderate efficacy, indicating that this could be a reasonable option as a salvage treatment for metastatic STS.

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Comparative Evaluation of Second-Line Chemotherapy Agents for Advanced Soft Tissue Sarcoma: Gemcitabine/Docetaxel, Pazopanib, and Alternatives
Tae Hun Kim, Ki Hyuk Sung, So Hak Chung
Journal of the Korean Orthopaedic Association.2024; 59(1): 22. CrossRef
当科における再発・進行骨軟部肉腫に対するゲムシタビン＋ドセタキセル療法の使用経験
悠太久保田, 正典河野, 達也岩﨑, 一朗糸永, 信広加来, 弘津村, 和宏田仲
Orthopedics & Traumatology.2024; 73(2): 292. CrossRef
Primary pleomorphic leiomyosarcoma of descending mesocolon
Suhaildeen Kajamohideen, Balasubramanian Venkitaraman, Sathyanarayanan M Shivkumaran, Prithviraj Premkumar
Formosan Journal of Surgery.2021; 54(5): 196. CrossRef
Surgical resection of leiomyosarcoma of the inferior vena cava: A case series and literature review
Maggie Zhou, Christopher Javadi, Greg W. Charville, Nam Q. Bui, E John Harris, George A. Poultsides, Jeffrey A. Norton, Brendan Visser, Byrne Lee, Monica M. Dua, Kristen N. Ganjoo
Surgical Oncology.2021; 39: 101670. CrossRef
Stabilization of Metastatic Uterine Leiomyosarcoma Using Pembrolizumab
Katherine Cotangco, Mary Meram, M. Patrick Lowe
Journal of the National Comprehensive Cancer Network.2020; 18(8): 1012. CrossRef
Gemcitabine and docetaxel combination chemotherapy for advanced bone and soft tissue sarcomas: protocol for an open-label, non-randomised, Phase 2 study
Hitomi Hara, Teruya Kawamoto, Naomasa Fukase, Yohei Kawakami, Toshiyuki Takemori, Shuichi Fujiwara, Kazumichi Kitayama, Kotaro Nishida, Ryosuke Kuroda, Toshihiro Akisue
BMC Cancer.2019;[Epub] CrossRef
Gemcitabine and Docetaxel Combination for Advanced Soft Tissue Sarcoma: A Nationwide Retrospective Study
Yunjung Choi, Mi Sun Yun, Sang Hee Lim, Jeeyun Lee, Jin-Hee Ahn, Yu Jung Kim, Kyong Hwa Park, Young Suk Park, Ho Yeong Lim, Hyonggin An, Dong-Churl Suh, Yeul Hong Kim
Cancer Research and Treatment.2018; 50(1): 175. CrossRef
Establishment and characterization of a canine soft tissue sarcoma patient‐derived xenograft model
J. P. Frazier, E. Beirne, S. H. Ditzler, I. Tretyak, J. R. Casalini, D. J. Thirstrup, S. Knoblaugh, J. G. Ward, C. D. Tripp, R. A. Klinghoffer
Veterinary and Comparative Oncology.2017; 15(3): 754. CrossRef
Feasibility and efficacy of gemcitabine and docetaxel combination chemotherapy for bone and soft tissue sarcomas: multi-institutional retrospective analysis of 134 patients
Kazuhiro Tanaka, Susumu Joyama, Hirokazu Chuman, Hiroaki Hiraga, Hideo Morioka, Hideki Yoshikawa, Masami Hosaka, Mitsuru Takahashi, Tadahiko Kubo, Hiroshi Hatano, Mitsunori Kaya, Junya Toguchida, Yoshihiro Nishida, Akihito Nagano, Hiroshi Tsumura, Yukihid
World Journal of Surgical Oncology.2016;[Epub] CrossRef
A Phase II Study of Gemcitabine, Vincristine, and Cisplatin (Gvp) As Second-Line Treatment for Patients with Advanced Soft Tissue Sarcoma
Zhiguo Luo, Xiaowei Zhang, Wei Peng, Xianghua Wu, Huijie Wang, Hui Yu, Jialei Wang, Jianhua Chang, Xiaonan Hong
Medicine.2015; 94(43): e1777. CrossRef
Emerging therapies for adult soft tissue sarcoma
Stefano Radaelli, Sivia Stacchiotti, Paolo G Casali, Alessandro Gronchi
Expert Review of Anticancer Therapy.2014; 14(6): 689. CrossRef
A Randomized Phase II/III Trial of Perioperative Chemotherapy with Adriamycin Plus Ifosfamide Versus Gemcitabine Plus Docetaxel for High-grade Soft Tissue Sarcoma: Japan Clinical Oncology Group Study JCOG1306
K. Kataoka, K. Tanaka, J. Mizusawa, A. Kimura, H. Hiraga, A. Kawai, T. Matsunobu, A. Matsumine, N. Araki, Y. Oda, H. Fukuda, Y. Iwamoto
Japanese Journal of Clinical Oncology.2014; 44(8): 765. CrossRef
Docetaxel-associated palmar-plantar erythrodysesthesia: A case report and review of the literature
Christy S Harris, Dorothy Wang, Alison Carulli
Journal of Oncology Pharmacy Practice.2014; 20(1): 73. CrossRef
Gemcitabine and Docetaxel for Metastatic Soft Tissue Sarcoma - a Single Center Experience
Thomas Schmitt, Florentina Kosely, Patrick Wuchter, Johann-Wilhelm Schmier, Anthony D. Ho, Gerlinde Egerer
Oncology Research and Treatment.2013; 36(7-8): 415. CrossRef

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Clinicopathologic Features of Metachronous or Synchronous Gastric Cancer Patients with Three or More Primary Sites: Joo Hoon Kim, Sun Young Rha, Chan Kim, Gun Min Kim, Sang Hyun Yoon, Ki Hyang Kim, Min Jae Kim, Joong Bae Ahn, Hyun Cheol Chung, Jae Kyung Roh, Hyo Song Kim; Cancer Res Treat. 2010;42(4):217-224. Published online December 31, 2010; DOI: https://doi.org/10.4143/crt.2010.42.4.217

Abstract PDF PubReader ePub

Purpose

We investigated the clinicopathologic information of patients with gastric cancer with multiple primary cancers (GC-MPC) of three or more sites.

Materials and Methods

Between 1995 and 2009, 105,908 patients were diagnosed with malignancy at Severance Hospital, Yonsei University Health System. Of these, 113 (0.1%) patients with MPC of three or more sites were registered, and 41 (36.3%) of these were GC-MPC. We retrospectively reviewed the clinical data and overall survival using the medical records of these 41 GC-MPC patients. We defined synchronous cancers as those occurring within 6 months of the first primary cancer, while metachronous cancers were defined as those occurring more than 6 months later.

Results

Patients with metachronous GC-MPC were more likely to be female (p=0.003) and young than patients with synchronous GC-MPC (p=0.013). The most common cancer sites for metachronous GC-MPC patients were the colorectum, thyroid, lung, kidney and breast, while those for synchronous GC-MPC were the head and neck, esophagus, lung, and kidney. Metachronous GC-MPC demonstrated significantly better overall survival than synchronous GC-MPC, with median overall survival durations of 4.7 and 14.8 years, respectively, and 10-year overall survival rates of 48.2% and 80.7%, respectively (p<0.001).

Conclusion

Multiplicity of primary malignancies itself does not seem to indicate a poor prognosis. The early detection of additional primary malignancies will enable proper management with curative intent.

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Alexios-Fotios A. Mentis, Efthimios Dardiotis
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Multiple primary malignancies involving lung cancer
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European Archives of Oto-Rhino-Laryngology.2013; 270(2): 727. CrossRef

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Novel Sunitinib Strategy in Metastatic Renal Cell Carcinoma on Hemodialysis: Intermittent Dose of Sunitinib after Hemodialysis: Sang Hyun Yoon, Ki Hyang Kim, Junjeong Choi, Gun Min Kim, Joo Hoon Kim, Hyo Song Kim, Young Nyun Park, Sun Young Rha; Cancer Res Treat. 2010;42(3):180-184. Published online September 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.3.180

Abstract PDF PubReader ePub

The proper dose and schedule of sunitinib have yet to be established for patients with metastatic renal cell carcinoma (RCC) on hemodialysis. We reviewed two patients with metastatic RCC on hemodialysis who had been treated with sunitinib in Yonsei Cancer Center, Yonsei University College of Medicine. Fifty milligrams of sunitinib was administered intermittently after each hemodialysis session (3 or 4 times a week). Overall responses were partial response in both cases. Progression-free survivals were 16 and 6 months, respectively, at the time of reporting (April 2010). Both subjects tolerated the treatment.

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Targeted and immune therapies among patients with metastatic renal carcinoma undergoing hemodialysis: A systemic review
Elodie Klajer, Louis Garnier, Morgan Goujon, Friederike Schlurmann-Constans, Benoite Mery, Thierry Nguyen Tan Hon, Guillaume Mouillet, Fabien Calcagno, Antoine Thiery-Vuillemin
Seminars in Oncology.2020; 47(2-3): 103. CrossRef
Targeted Agents in Patients with Metastatic Renal Cell Carcinoma on Dialysis: Myths and Reality
Annalisa Guida, Laura Cosmai, Fabio Gelsomino, Cristina Masini, Roberto Sabbatini, Camillo Porta
EMJ Nephrology.2016; : 66. CrossRef
Recent Aspects of Sunitinib Therapy in Patients with Metastatic Clear-Cell Renal Cell Carcinoma: a Systematic Review of the Literature
Daniele Minardi, Luigi Quaresima, Matteo Santoni, Maristella Bianconi, Mario Scartozzi, Stefano Cascinu, Giovanni Muzzonigro
Current Urology Reports.2015;[Epub] CrossRef
Feasibility, Efficacy and Safety of Tyrosine Kinase Inhibitor Treatment in Hemodialyzed Patients with Renal Cell Cancer: 10 Years of Experience
Anna M Czarnecka, Maciej Kawecki, Fei Lian, Jan Korniluk, Cezary Szczylik
Future Oncology.2015; 11(16): 2267. CrossRef
Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with renal insufficiency
Ki Hyang Kim, Ho Young Kim, Hye Ryun Kim, Jong-Mu Sun, Ho Yeong Lim, Hyo Jin Lee, Suee Lee, Woo Kyun Bae, Sun Young Rha
European Journal of Cancer.2014; 50(4): 746. CrossRef
Intolerance to Sunitinib Treatment in Hemodialysis Patients With Metastatic Renal Cell Carcinoma
Ibrahim Yildiz, Fatma Sen, Leyla Kilic, Rumeysa Ciftci, Mert Basaran
Korean Journal of Urology.2014; 55(1): 74. CrossRef
A contemporary update on rates and management of toxicities of targeted therapies for metastatic renal cell carcinoma
Ahmed Alasker, Malek Meskawi, Maxine Sun, Salima Ismail, Nawar Hanna, Jens Hansen, Zhe Tian, Marco Bianchi, Paul Perrotte, Pierre I. Karakiewicz
Cancer Treatment Reviews.2013; 39(4): 388. CrossRef
Use of tyrosine kinase inhibitors in patients with metastatic kidney cancer receiving haemodialysis: a retrospective Italian survey
Cristina Masini, Roberto Sabbatini, Camillo Porta, Giuseppe Procopio, Giuseppe Di Lorenzo, Azzurra Onofri, Sebastiano Buti, Roberto Iacovelli, Roberta Invernizzi, Luca Moscetti, Maria Giuseppina Aste, Maria Pagano, Federica Grosso, Anna Lucia Manenti, Cin
BJU International.2012; 110(5): 692. CrossRef

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Wernicke's Encephalopathy in Advanced Gastric Cancer: Eun Suk Jung, Obin Kwon, Soo Hyun Lee, Ki Byung Lee, Joo Hoon Kim, Sang Hyun Yoon, Gun Min Kim, Hei-Cheul Jeung, Sun Young Rha; Cancer Res Treat. 2010;42(2):77-81. Published online June 30, 2010; DOI: https://doi.org/10.4143/crt.2010.42.2.77

Abstract PDF PubReader ePub

Purpose

With their prolonged survival and malnutrition, cancer patients, and especially gastrointestinal (GI) tract cancer patients, can develop Wernicke's encephalopathy (WE). The aim of this study is to remind physicians of the importance of WE and prompt management in patients with GI tract cancer.

Materials and Methods

This study is a retrospective review of 2 cases of WE in advanced gastric cancer (AGC) patients, and we review the literature for cases of GI tract cancer related to WE.

Results

A 48-year-old female with AGC presented dizziness and diplopia for 5 days and a 20 kg weight loss. Neurologic exam showed nystagmus and gaze disturbance. Her symptoms improved after daily parenteral injection of thiamine 100 mg for 17 days. A 58-year-old female with AGC presented with sudden disorientation, confusion and 15 kg weight loss. Neurologic exam showed gaze limitation and mild ataxia. Despite daily parenteral injection of thiamine 100 mg for 4 days, she died 5 days after the onset of neurologic symptoms. Combining the cases noted in the literature review with our 2 cases, the 7 gastric cancer cases and 2 colorectal cancer cases related to WE showed similar clinical characteristics; 1) a history of long-period malnutrition and weight loss, 2) relatively typical neurologic signs and symptoms and 3) specific magnetic resonance image findings. Except for 2 patients who had irreversible neurologic symptoms, the other 7 patients were improved with prompt thiamine treatment.

Conclusion

It is important to consider WE in GI tract cancer patients with acute neurologic symptoms and who are in a state of malnutrition. Thiamine should be given as soon as possible when WE is suspected.

Citations

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Duodenal Adenocarcinoma in the Setting of Bariatric Surgery: A Perfect Storm for Wernicke’s Encephalopathy
Aliza Gross, Allen T Yu, Jacques Lara-Reyna, Koji Park, Eugenius J Harvey
Cureus.2023;[Epub] CrossRef
Thiamine deficiency in pregnancy and lactation: implications and present perspectives
Ozaifa Kareem, Sobia Nisar, Masood Tanvir, Umar Muzaffer, G. N. Bader
Frontiers in Nutrition.2023;[Epub] CrossRef
Beware of lethal Wernicke's encephalopathy after cytoreductive surgery with HIPEC for peritoneal pseudomyxoma: Case report of morbidity and mortality review
Oumayma Lahnaoui, Nezha EL Bahaoui, Sara El Atiq, Laila Amrani, Mohammed Anass Majbar, Amine Benkabbou, Raouf Mohsine, Amine Souadka
International Journal of Surgery Case Reports.2022; 98: 107500. CrossRef
Thiamine deficiency unrelated to alcohol consumption in high‐income countries: a literature review
Filomena Gomes, Gilles Bergeron, Megan W. Bourassa, Philip R. Fischer
Annals of the New York Academy of Sciences.2021; 1498(1): 46. CrossRef
WERNICKE ENCEPHALOPATHY IN A PATIENT WITH GASTRIC CANCER RECURRENCE AFTER UPPER GASTROINTESTINAL SURGERY: A CASE REPORT AND REVIEW OF THE LITERATURE
Zining Liu, Xin Ye, Jiejin Yang, Zeyang Chen
Gastroenterology Nursing.2020; 43(6): 463. CrossRef
Wernicke's encephalopathy in a subject with enter-colic fistula
Daniele Canova, Paola Scalon, Fabio Monica, Stefano A. Grassi, Anna Giacomin, Tiziana Tumelero, Gaetano Mastropaolo, Francesco Malfa
Gazzetta Medica Italiana Archivio per le Scienze Mediche.2019;[Epub] CrossRef
Wernicke's encephalopathy in a patient with non-Hodgkin's lymphoma post-Autologous HSCT
João Paulo de Vasconcelos Leitão, Romélia Pinheiro Gonçalves Lemes, Maritza Cavalcante Barbosa, Beatriz Stela Gomes de Souza Pitombeira Araújo, Karine Sampaio Nunes Barroso, Jacques Kaufman, Talyta Ellen de Jesus dos Santos, Anna Thawanny Gadelha Moura, A
Revista da Associação Médica Brasileira.2018; 64(10): 882. CrossRef
Wernicke encephalopathy as initial presentation of lymphoma
Ju Hyun Seo, Ju Hee Kim, Der Sheng Sun, Hye Sung Won, Jeong Wook Park, Yoon Ho Ko
The Korean Journal of Internal Medicine.2017; 32(6): 1112. CrossRef
The Role of Thiamine and Effects of Deficiency in Dogs and Cats
Georgia Kritikos, Jacqueline Parr, Adronie Verbrugghe
Veterinary Sciences.2017; 4(4): 59. CrossRef
Association between malignancy and non-alcoholic Wernicke's encephalopathy: a case report and literature review
Evan Y. Choi, William A. Gomes, Missak Haigentz, Jerome J. Graber
Neuro-Oncology Practice.2016; 3(3): 196. CrossRef
Wernicke encephalopathy as rare complication of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
Antonio Macrì, Francesco Fleres, Antonio Ieni, Maurizio Rossitto, Tommaso Mandolfino, Salvatore Micalizzi, Francesco Iaropoli, Carmelo Mazzeo, Massimo Trovato, Eugenio Cucinotta, Edoardo Saladino
International Journal of Surgery Case Reports.2015; 16: 29. CrossRef
Two Cases of Wernicke's Encephalopathy That Developed during Total Parenteral Nutrition in Colon Cancer Patients Treated with 5-Fluorouracil-based Chemotherapy
Kyung Pyo Cho, Jae Sung Lee, Ji Seok Seong, Yong Moon Woo, Young Jun Cho, Beom Jin Jeong, Jee Hoon Sohn, Su-Jung Kim
The Korean Journal of Gastroenterology.2014; 64(3): 158. CrossRef
Wernicke's encephalopathy in a patient with gastric carcinoma: a diagnosis not to miss
Chandrashekar Udyavara Kudru, Shivashankara Kaniyoor Nagiri, Sandeep Rao
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Wernicke-Korsakoff Syndrome in Primary Peritoneal Cancer
Ki Hyang Kim
Case Reports in Oncology.2013; 6(3): 593. CrossRef

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Docetaxel versus Paclitaxel Combined with 5-FU and Leucovorin in Advanced Gastric Cancer: Combined Analysis of Two Phase II Trials: Hong Jae Chon, Sun Young Rha, Chong Kun Im, Chan Kim, Min Hee Hong, Hye Ryun Kim, Jung Ryun An, Sung Hoon Noh, Hyun Cheol Chung, Hei-Cheul Jeung; Cancer Res Treat. 2009;41(4):196-204. Published online December 31, 2009; DOI: https://doi.org/10.4143/crt.2009.41.4.196

Abstract PDF PubReader ePub

Purpose

This is an ad hoc analysis of two phase II studies which compared the efficacy and safety of two taxanes (paclitaxel and docetaxel) combined with 5-fluorouracil (5-FU) and leucovorin (LV) in advanced gastric cancer.

Materials and Methods

Patients with advanced gastric adenocarcinoma who were untreated or had only received first-line chemotherapy, were treated with either paclitaxel (PFL; 175 mg/m²) or docetaxel (DFL; 75 mg/m²) on day 1, followed by a bolus of LV (20 mg/m² days 1~3) and a 24-hour infusion of 5-FU (1,000 mg/m² days 1~3) every 3 weeks. The primary endpoint was overall response rate (ORR) and the secondary endpoint included survival and toxicity.

Results

Sixty-six patients received DFL (first-line [n=38]; and second-line [n=28]) and 60 patients received PFL (first-line [n=37]; and second-line [n=23]). The ORRs were not significantly different between the 2 groups (DFL, 26%; PFL, 38%). With a median follow-up of 9.5 months, the progression free survival was 5.2 months (95% confidence interval [CI], 4.2~6.5 months) for DFL and 3.3 months (95% CI, 1.3~5.5 months) for PFL (p=0.17). The overall survival was also comparable between the patients who received DFL and PFL (10.0 months [95% CI, 7.2~12.5 months] and 13.9 months [95% CI, 10.9~19.2 months], respectively; p=0.37). The most frequent grade 3~4 adverse event was neutropenia (DFL, 71%; PFL, 62%). DFL and PFL had different non-hematologic toxicities; specifically, grade ≥3 mucositis (5%) and diarrhea (3%) were common in DFL, while nausea/vomiting (15%) and peripheral neuropathy (5%) were common in PFL.

Conclusion

Thus, the two taxanes had similar efficacy in the treatment of advanced gastric cancer, but different toxicity profiles. Prospective comparative studies are required to further clarify the role of taxanes in the treatment of advanced gastric cancer.

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Diala Merheb, Georgette Dib, Maroun Bou Zerdan, Clara El Nakib, Saada Alame, Hazem I. Assi
Current Cancer Drug Targets.2022; 22(1): 49. CrossRef
Treatment Outcome and Safety of the TCX Regimen for Advanced Gastric Cancer: A Prospective Cohort Study
Hieu Trong Nguyen, Kien Hung Do, Nguyen Ba Le, Thang Tran
Cancer Management and Research.2022; Volume 14: 2825. CrossRef
Role for Drug Transporters in Chemotherapy‐Induced Peripheral Neuropathy
Tore B. Stage, Shuiying Hu, Alex Sparreboom, Deanna L. Kroetz
Clinical and Translational Science.2021; 14(2): 460. CrossRef
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Daniel V.T. Catenacci, Stephanie Moya, Samantha Lomnicki, Leah M. Chase, Bryan F. Peterson, Natalie Reizine, Lindsay Alpert, Namrata Setia, Shu-Yuan Xiao, John Hart, Uzma D. Siddiqui, D. Kyle Hogarth, Oliver S. Eng, Kiran Turaga, Kevin Roggin, Mitchell C.
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Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy
Giulia Fumagalli, Laura Monza, Guido Cavaletti, Roberta Rigolio, Cristina Meregalli
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Nathan P. Staff, Jill C. Fehrenbacher, Martial Caillaud, M. Imad Damaj, Rosalind A. Segal, Sandra Rieger
Experimental Neurology.2020; 324: 113121. CrossRef
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Yoko Tomita, Max Moldovan, Rachael Chang Lee, Amy HC Hsieh, Amanda Townsend, Timothy Price
Cochrane Database of Systematic Reviews.2020;[Epub] CrossRef
Paclitaxel, 5-fluorouracil, and leucovorin combination chemotherapy as first-line treatment in patients with advanced gastric cancer
Wan-Cai Que, Yan-Fang Huang, Xiao-Yan Lin, Yan-Qin Lan, Xin-Yan Gao, Xin-Li Wang, Ri-Ping Wu, Bin Du, Xiao-Bin Huang, Hong-qiang Qiu, Dong-Ta Zhong
Anti-Cancer Drugs.2019; 30(3): 302. CrossRef
Randomised phase II trial comparing four front-line doublets in Asian patients with metastatic gastric cancer
Chan Kim, Hong Jae Chon, Joo Hoon Kim, Minkyu Jung, Chung Mo Nam, Hyo Song Kim, Beodeul Kang, Hyun Cheol Chung, Sun Young Rha
European Journal of Cancer.2019; 112: 20. CrossRef
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Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy
Hana Starobova, Irina Vetter
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Identifying therapeutic targets in gastric cancer: the current status and future direction
Beiqin Yu, Jingwu Xie
Acta Biochimica et Biophysica Sinica.2016; 48(1): 90. CrossRef
Role of Transient Receptor Potential Channels in Paclitaxel- and Oxaliplatin-induced Peripheral Neuropathy
Kyoji Taguchi
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Chunmei Shi, Qiang Chen, Songfei Shen, Riping Wu, Baoyu Yang, Qing Liu, Qian Xu
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HYUN SU LEE, JUN BEOM PARK, MYUNG SUN LEE, EUN YOUNG CHA, JI YEON KIM, JI YOUNG SUL
Molecular Medicine Reports.2015; 12(3): 4782. CrossRef
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Zengqing Guo, Xiaojie Wang, Rongbo Lin, Ling Chen, Nanfeng Fan, Yu Chen, Jinyuan Lin, Jiami Yu
Journal of Chemotherapy.2015; 27(2): 94. CrossRef
A phase 2 study of fluorouracil/leucovorin in combination with paclitaxel and oxaliplatin as a salvage treatment in patients with refractory or relapsed advanced gastric cancer
Rongbo Lin, Nanfeng Fan, Guangfeng Wu, Ying Chen, Zengqing Guo, Xiaojie Wang, Feng Jin, Ling Chen, Jie Liu
Journal of Chemotherapy.2015; 27(1): 52. CrossRef
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MEIQIN YUAN, YUNSHAN YANG, WANGXIA LV, ZHENGBO SONG, HAIJUN ZHONG
Oncology Letters.2014; 8(1): 351. CrossRef
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Andreas A. Argyriou, Jordi Bruna, Paola Marmiroli, Guido Cavaletti
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W. Grisold, G. Cavaletti, A. J. Windebank
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Clinical Value of Ezrin Expression in Primary Osteosarcoma: Chan Kim, Eunah Shin, Soojung Hong, Hong Jae Chon, Hye Ryun Kim, Jung Ryun Ahn, Min Hee Hong, Woo Ick Yang, Jae Kyung Roh, Sun Young Rha; Cancer Res Treat. 2009;41(3):138-144. Published online September 28, 2009; DOI: https://doi.org/10.4143/crt.2009.41.3.138

Abstract PDF PubReader ePub

Purpose

Ezrin is a membrane cytoskeletal linker protein and it is known to be associated with metastasis of primary osteosarcoma. The aim of this study is to determine the relationship between an ezrin expression and several key clinical parameters and to elucidate its potential prognostic value for patients with osteosarcoma.

Materials and Methods

Seventy patients with histologically confirmed osteosarcoma and who had no distant metastasis were enrolled between 1995 and 2005 at Yonsei Cancer Center, Severance Hospital, Korea. The clinical parameters were retrospectively reviewed and immunohistochemical staining (IHC) for ezrin was performed using the surgically resected specimens.

Results

Of the 70 tumor specimens, 39 (55.7%) revealed an ezrin expression. More of an osteoblastic histology and an elevated initial ALP level were observed in the ezrin positive patients than in the ezrin negative patients (p=0.008 and 0.001, respectively). The proportion of patients who favorably responded to neoadjuvant chemotherapy (≥90% necrosis) was significantly higher in the group of ezrin positive patients than that in the group of ezrin negative patient (72.2% vs 45.2%, respectively, p=0.024). The ezrin positive patients showed more frequent recurrence than did the ezrin negative patients (64.1% vs 35.5%, respectively, p=0.017). The patients with an ezrin expression also demonstrated poorer survival than did those patients without ezrin expression (5-year EFS: 31.7% vs 61.3%, respectively, p=0.023, 5-year OS: 53.4% vs 71.0%, respectively, p=0.022). When comparing EFS according to both an ezrin expression and chemoresponsiveness, there were trends that the ezrin negative/chemoresponsive group showed the best 5-year EFS (71.4%), followed by the ezrin negative/chemoresistant group (52.9%), the ezrin positive/chemoresponsive group (38.1%) and the ezrin positive/chemoresistant group (13.6%). These trends were statistically significant (p=0.036).

Conclusion

The expression of ezrin by IHC staining was found in 55.7% of the patients with metastasis-free osteosarcoma. Immunoreactivity to ezrin is a negative prognostic factor for survival for the patients suffering with osteosarcoma. Identifying an ezrin expression might offer a valuable piece of information when treating patients with primary osteosarcoma.

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Bulent Cetin, Ipek Isik Gonul, Ozge Gumusay, Baris Afsar, Irem Bilgetekin, Ahmet Ozet, Aytug Uner
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Rongju Zhang, Shaohui Zhang, Rongge Xing, Qin Zhang
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Feng Wang, Tao Yu, Chengbin Ma, Haifei Zhang, Zhiyu Zhang
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J. McGuire, T.J. Utset-Ward, D.R. Reed, C.C. Lynch
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Thomas Cash, Hong Yin, Courtney McCracken, Zhi Geng, Steven G. DuBois, Bahig M. Shehata, Thomas A. Olson, Howard M. Katzenstein, Cynthia Wetmore
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Treatment Outcomes of Sunitinib Treatment in Advanced Renal Cell Carcinoma Patients: A Single Cancer Center Experience in Korea: Min Hee Hong, Hyo Song Kim, Chan Kim, Jung Ryun Ahn, Hong Jae Chon, Sang-Joon Shin, Joong-Bae Ahn, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2009;41(2):67-72. Published online June 30, 2009; DOI: https://doi.org/10.4143/crt.2009.41.2.67

Abstract PDF PubReader ePub

Purpose

The retrospective study was performed to assess the efficacy and toxicity profiles of sunitinib in Korean patients with metastatic renal cell carcinoma (RCC).

Materials and Methods

Between January 2005 and December 2008, 76 Korean patients with recurrent/metastatic RCC who received sunitinib were retrospectively reviewed. The primary end point was progression-free survival and the secondary end points were overall survival and response rate. We also assessed the toxicities associated with sunitinib treatment.

Results

Of the 76 patients, 69 (90.1%) were diagnosed with clear cell RCC. The median progression-free survival and overall survival were 7.2 and 22.8 months, respectively in overall patients. Sixty-two patients (81.6%) received 50 mg 4 week and 2 week off schedule, and 14 patients (18.4%) received 37.5 mg daily on a daily continuous schedule. The objective response rate and disease control rate were 27.6% and 84.2%, respectively. A dose reduction or reduction in dose due to adverse events occurred in 76% of the patients, whereas 11% of the patients had discontinued treatment. Other common laboratory abnormalities were increased serum creatinine (75.6%), elevated alanine aminotransferase (71.0%), neutropenia (61.8%), anemia (69.7%), and increased aspartate aminotrasferase (53.3%). Grade 3/4 toxicities occurred as follows: thrombocytopenia (38.2%), fatigue (10.5%), stomatitis (10.5%), and hand-foot syndrome (9.2%).

Conclusion

Our results indicate that sunitinib treatment is effective and tolerable for ecurrent/metastatic RCC patients in Korea. Further studies with prognostic or biochemical factors are needed to clarify the different toxicity profiles of this study.

Citations

Citations to this article as recorded by

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Prognosis of pN3 Stage Gastric Cancer: Jung Ryun Ahn, Minkyu Jung, Chan Kim, Min Hee Hong, Hong Jae Chon, Hye Ryun Kim, Hei-Cheul Jeung, Woo Jin Hyung, Sung Sook Lee, Hyun Cheol Chung, Sung Hoon Noh, Sun Young Rha; Cancer Res Treat. 2009;41(2):73-79. Published online June 30, 2009; DOI: https://doi.org/10.4143/crt.2009.41.2.73

Abstract PDF PubReader ePub

Purpose

The aim of this study was to determine the prognosis of pN3 stage gastric cancer patients after they have undergone curative resection, and we also wanted to identify the prognostic factors according to the clinico-pathologic features.

Materials and Methods

Between January 2000 and December 2004, we retrospectively reviewed the medical records of the patients with histologically confirmed pN3 stage gastric cancer. They underwent both gastrectomy and lymphadenectomy with a curative aim. We categorized the pN3 stage patients into 2 groups; one with pN3 only (pN3M0) and the other with pN3 combined with M1 stage (pN3M1) that included peritoneal seeding, hepatic metastasis or para-aortic LN metastasis.

Results

Out of 467 patients with stage IV gastric adenocarcinoma who received surgery, 260 patients underwent curative resection and they were pathologically staged as N3. Among these 260 patients, 78 patients were classified as the pN3/M1 stage. For all the patients, the median follow-up period was 19 months (range: 1~108 months) and the median overall survival time was 16.2 months (95% CI, 14.1~18.3%). The 5-year survival rate of the pN3/M0 group was significantly higher than that of the pN3/M1 group (12.6% vs. 2.6%, respectively, p<0.0001). The identified predictor for a worse prognosis was an advanced T4 stage (HR: 3.38, 95% CI, 1.4~8.3, p=0.008) for the pN3 patients.

Conclusion

The survival for the pN3 gastric cancer patients after curative gastrectomy was significantly longer in the pN3/M0 group as compared to that of the pN3/M1 group. An advanced T stage was a predictor for a poor prognosis for the pN3 patients. Therefore, diverse treatment strategies for these heterogeneous pN3 gastric cancer patients are needed for improving their survival.

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GSK461364A suppresses proliferation of gastric cancer cells and induces apoptosis
Dilara Ataseven, Şeyma Taştemur, Fatih Yulak, Sebahattin Karabulut, Mustafa Ergul
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HDAC4 promotes the growth and metastasis of gastric cancer via autophagic degradation of MEKK3
Wei-Jie Zang, Yi-Lin Hu, Chen-Yu Qian, Ying Feng, Jia-Zhou Liu, Jun-Ling Yang, Hua Huang, Yi-Zhun Zhu, Wan-Jiang Xue
British Journal of Cancer.2022; 127(2): 237. CrossRef
Tumor purity as a prognosis and immunotherapy relevant feature in gastric cancer
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S100A10 Accelerates Aerobic Glycolysis and Malignant Growth by Activating mTOR-Signaling Pathway in Gastric Cancer
Yan Li, Xiao-Yu Li, Li-Xiang Li, Ru-Chen Zhou, Yinhe Sikong, Xiang Gu, Bi-Ying Jin, Bing Li, Yan-Qing Li, Xiu-Li Zuo
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Is it worthy of adding dissection of the superior mesenteric vein lymph node (14v) to standard D2 gastrectomy for distal gastric cancers with No. 6 lymph node metastasis?
J. Zhang, S. Zou, R. Luo, Z. Zhu, Z. Wang, H. Xu, B. Huang
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Reduced expression of Rap1GAP as a prognostic biomarker for primary gastric cancer patients
Jingjing Zhao, Cong Mai, Desheng Weng, Changlong Chen, Ziqi Zhou, Yuan Liu, Zhiwei Zhou, Peng Wang
Cancer Biomarkers.2018; 22(3): 375. CrossRef
Prognostic Discrepancy of the 6th and 7th UICC N Classification for Lymph Node Staging in Gastric Cancer Patients after Curative Resection
Sung Jin Oh, Byoung Jo Suh, Jong Kwon Park, Sung Don Oh, Hang Jong Yu
Case Reports in Oncology.2017; 10(1): 57. CrossRef
Gastric biomarkers: a global review
Nick Baniak, Jenna-Lynn Senger, Shahid Ahmed, S. C. Kanthan, Rani Kanthan
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MiR 21‐5p as a predictor of recurrence in young gastric cancer patients
Soo‐Kyung Park, Young Soo Park, Ji Yong Ahn, Eun‐Ju Do, Dongho Kim, Jee Eun Kim, kyoungwon Jung, Jeong‐Sik Byeon, Byong Duk Ye, Dong Hoon Yang, Sang Hyoung Park, Sung Wook Hwang, Hwoon‐Yong Jung, Seung‐Jae Myung
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Functional polymorphisms in apoptosis pathway genes and survival in patients with gastric cancer
Dongying Gu, Mulong Du, Cuiju Tang, Haiyan Chu, Zhi Xu, Xinyin Huo, Weida Gong, Yongfei Tang, Jianwei Zhou, Na Tong, Yong Xu, Zhengdong Zhang, Meilin Wang, Jinfei Chen
Environmental and Molecular Mutagenesis.2014; 55(5): 421. CrossRef
Improved survival after adding dissection of the superior mesenteric vein lymph node (14v) to standard D2 gastrectomy for advanced distal gastric cancer
Bang Wool Eom, Jungnam Joo, Young-Woo Kim, Daniel Reim, Ji Yeon Park, Hong Man Yoon, Keun Won Ryu, Jong Yeul Lee, Myeong-Cherl Kook
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Comprehensive genomic meta-analysis identifies intra-tumoural stroma as a predictor of survival in patients with gastric cancer
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Validity and Necessity of Sub-classification of N3 in the 7thUICC TNM Stage of Gastric Cancer
Fang-Xuan Li, Ru-Peng Zhang, Han Liang, Ji-Chuan Quan, Hui Liu, Hui Zhang
Asian Pacific Journal of Cancer Prevention.2013; 14(3): 2091. CrossRef
Is the New Seventh AJCC/UICC Staging System Appropriate for Patients with Gastric Cancer?
Hong Man Yoon, Keun Won Ryu, Byung Ho Nam, Soo Jeong Cho, Sook Ryun Park, Jong Yeul Lee, Jun Ho Lee, Myeong-Cherl Kook, Il Ju Choi, Young-Woo Kim
Journal of the American College of Surgeons.2012; 214(1): 88. CrossRef
Comparison of the 6th and 7th Editions of the UICC TNM Staging System for Gastric Cancer: Results of a Chinese Single-Institution Study of 1,503 Patients
Wei Wang, Xiao-wei Sun, Chao-feng Li, Lin Lv, Yuan-fang Li, Ying-bo Chen, Da-zhi Xu, Rajiv Kesari, Chun-yu Huang, Wei Li, You-qing Zhan, Zhi-wei Zhou
Annals of Surgical Oncology.2011; 18(4): 1060. CrossRef

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A Locally Advanced Breast Cancer with Difficult Differential Diagnosis of Carcinosarcoma and Atypical Medullary Carcinoma, which had Poor Response to Adriamycin- and Taxane-based Neoadjuvant Chemotherapy: A Case Report: Se Hyun Kim, Hyun Cheol Chung, Jaeheon Jeong, Ji Hoon Kim, Sun Young Rha, Joong Bae Ahn, Nam Hoon Cho, Hei-Cheul Jeung; Cancer Res Treat. 2007;39(3):134-137. Published online September 30, 2007; DOI: https://doi.org/10.4143/crt.2007.39.3.134

Abstract PDF PubReader ePub

Atypical medullary carcinomas and carcinosarcoma have unique histopathological features. Here we present a case with a breast malignancy that had pathological characteristics of both. A 54-year old patient with a malignant breast mass received 6 cycles of adriamycin-based chemotherapy, followed by 3 cycles of paclitaxel monotherapy, and had a poor clinical response to treatment. A modified radical mastectomy was performed. The pathological diagnosis was complicated by an inability to distinguish between atypical medullary carcinoma and carcinosarcoma. The findings included a tumor that was well-circumscribed, high grade and a syncytial growth pattern as well as biphasic sarcomatous and carcinomatous characteristics. In conclusion, atypical medullary carcinoma and carcinosarcoma of the breast have entirely different prognoses and should be managed differently. Both should be treated by surgical resection, and additional therapy should be considered based on the cancer with the poorer prognosis.

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Carcinosarcoma of the breast: Facing the challenge of a rare nosologic entity
Aikaterini Mastoraki, Maria Tsamopoulou, Foivos-Konstantinos Stamatis, Alexios Strimpakos, Ero Mouchtouri, Christiana Panagi, Evgenia Mela, Sotiria Mastoraki, Aristotelis Kechagias, Dimitrios Schizas
World Journal of Clinical Cases.2025;[Epub] CrossRef
A Rare Case of Primary Carcinosarcoma of the Breast
Maria Kiakou, Maria Tolia, Nektarios Koufopoulos, Konstantinos Tsapakidis, Eleni Arvanitou, Gkikas Konstantinos, Nikolaos Charalambakis, Michalis Nikolaou, Dimitrios Matthaios, Nikolaos Tsoukalas
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Carcinosarcoma (Metaplastic Carcinoma) Breast: A Rare and Aggressive Primary – Report of Two Cases with Review of Literature
Gunjesh Kumar Singh, Pragya Singh, KT Bhowmik
Indian Journal of Medical and Paediatric Oncology.2018; 39(03): 400. CrossRef
Carcinosarcoma of the Breast: An Aggressive Subtype of Metaplastic Cancer. Report of a Rare Case in a Young BRCA-1 Mutated Woman
Matteo Ghilli, Donatella M. Mariniello, Giovanni Fanelli, Francesca Cascione, Andrea Fontana, Agostino Cristaudo, Anna Cilotti, Adelaide M. Caligo, Giampiero Manca, Livio Colizzi, Antonio G. Naccarato, Manuela Roncella
Clinical Breast Cancer.2017; 17(1): e31. CrossRef

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An Attempt for Combining Microarray Data Sets by Adjusting Gene Expressions: Ki-Yeol Kim, Se Hyun Kim, Dong Hyuk Ki, Jaeheon Jeong, Ha Jin Jeong, Hei-Cheul Jeung, Hyun Cheol Chung, Sun Young Rha; Cancer Res Treat. 2007;39(2):74-81. Published online June 30, 2007; DOI: https://doi.org/10.4143/crt.2007.39.2.74

Abstract PDF PubReader ePub

Purpose

The diverse experimental environments in microarray technology, such as the different platforms or different RNA sources, can cause biases in the analysis of multiple microarrays. These systematic effects present a substantial obstacle for the analysis of microarray data, and the resulting information may be inconsistent and unreliable. Therefore, we introduced a simple integration method for combining microaray data sets that are derived from different experimental conditions, and we expected that more reliable information can be detected from the combined data set rather than from the separated data sets.

Materials and Methods

This method is based on the distributions of the gene expression ratios among the different microarray data sets and it transforms, gene by gene, the gene expression ratios into the form of the reference data set. The efficiency of the proposed integration method was evaluated using two microarray data sets, which were derived from different RNA sources, and a newly defined measure, the mixture score.

Results

The proposed integration method intermixed the two data sets that were obtained from different RNA sources, which in turn reduced the experimental bias between the two data sets, and the mixture score increased by 24.2%. A data set combined by the proposed method preserved the inter-group relationship of the separated data sets.

Conclusion

The proposed method worked well in adjusting systematic biases, including the source effect. The ability to use an effectively integrated microarray data set yields more reliable results due to the larger sample size and this also decreases the chance of false negatives.

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spatiAlign: an unsupervised contrastive learning model for data integration of spatially resolved transcriptomics
Chao Zhang, Lin Liu, Ying Zhang, Mei Li, Shuangsang Fang, Qiang Kang, Ao Chen, Xun Xu, Yong Zhang, Yuxiang Li
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AMDBNorm: an approach based on distribution adjustment to eliminate batch effects of gene expression data
Xu Zhang, Zhiqiang Ye, Jing Chen, Feng Qiao
Briefings in Bioinformatics.2022;[Epub] CrossRef
reComBat: batch-effect removal in large-scale multi-source gene-expression data integration
Michael F Adamer, Sarah C Brüningk, Alejandro Tejada-Arranz, Fabienne Estermann, Marek Basler, Karsten Borgwardt, Thomas Lengauer
Bioinformatics Advances.2022;[Epub] CrossRef
Harmonization strategies for multicenter radiomics investigations
R Da-Ano, D Visvikis, M Hatt
Physics in Medicine & Biology.2020; 65(24): 24TR02. CrossRef
A Novel Statistical Method to Diagnose, Quantify and Correct Batch Effects in Genomic Studies
Gift Nyamundanda, Pawan Poudel, Yatish Patil, Anguraj Sadanandam
Scientific Reports.2017;[Epub] CrossRef
Batch effect removal methods for microarray gene expression data integration: a survey
C. Lazar, S. Meganck, J. Taminau, D. Steenhoff, A. Coletta, C. Molter, D. Y. Weiss-Solis, R. Duque, H. Bersini, A. Nowe
Briefings in Bioinformatics.2013; 14(4): 469. CrossRef
Identification of genes related to a synergistic effect of taxane and suberoylanilide hydroxamic acid combination treatment in gastric cancer cells
Hyun Chang, Sun Young Rha, Hei-Cheul Jeung, Jae-Jun Jung, Tae Soo Kim, Ho Jeong Kwon, Byung Soo Kim, Hyun Cheol Chung
Journal of Cancer Research and Clinical Oncology.2010; 136(12): 1901. CrossRef

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Long-term Survival after Surgical Resection for Liver Metastasis from Gastric Cancer: Two Case Reports: Jong Keun Lim, Joong Bae Ahn, Sung Ha Cheon, Hyun Chang, Jong Yul Jung, Sun Young Rha, Jae Kyung Roh, Sung Hoon Noh, Ho Geun Kim, Hyun Cheol Chung, Hei-Cheul Jeung; Cancer Res Treat. 2006;38(3):184-188. Published online June 30, 2006; DOI: https://doi.org/10.4143/crt.2006.38.3.184

Abstract PDF PubReader ePub

Surgical resection of colorectal cancer metastasis to the liver results in a 5-year survival rate of around 40%. Liver metastasis from other cancers such as neuroendocrine carcinoma and genitourinary tumors are also treated effectively with combined liver resection. However, hepatic metastasectomy for liver tumor from gastric cancer hasn't been considered as a standard treatment, and the benefit for this treatment has not been established. We report here on two cases of gastrectomy and combined liver resection for synchronous liver metastasis without any evidence of other metastatic lesions, and these two patients have survived for more than 7 years without evidence of disease recurrence. In conclusion, for patients with hepatic metastasis from gastric cancer, combined surgical resection of the liver metastasis should be considered as a treatment option when metastasis to other sites can be excluded.

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Radical gastrectomy with hepatoarterial catheter implantation for late-stage gastric cancer
Guo-Liang Yao
World Journal of Gastroenterology.2015; 21(9): 2754. CrossRef

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cDNA Microarray Experiment: Design Issues in Early Stage and the Need of Normalization: Byung Soo Kim, Sunho Lee, Sun Young Rha, Hyun Cheol Chung; Cancer Res Treat. 2003;35(6):533-540. Published online December 31, 2003; DOI: https://doi.org/10.4143/crt.2003.35.6.533

Abstract PDF

PURPOSE
The cDNA microarray has become a useful tool for observing the expression of thousands of genes simultaneously. However, obtaining good quality microarray data is not easy due to the inherent noise at various stages of the experiment. Therefore, it is essential to understand the source of the variation in the microarray experiment and its size as an initial step of the data analyses. MATERIALS AND METHODS: The total RNA extracted from HT-1080 fibrosarcoma and normal rat tissues were hybridized to the cDNA microarrays with 0.5 K human and 5 K rat genes, respectively. A homotypic reaction and dye swap experiments were used to identify the sources of the variation. RESULTS: The relative fluorescent intensities of the microarray, if unnormalized, have a large variation, particularly in the lower intensity region. The distribution of the log intensity ratios also exhibit some departure from a band around zero, which is the distribution pattern expected when the majority of genes in the microarray are not regulated. Normalization of the log ratios is usually required as a means of preprocessing the data. We claim that a within-print tip group, an intensity-dependent normalization through a loess fit adjustment will be useful for this purpose, particularly in the initial stages of the microarray experiment. CONCLUSION: For proper data analysis, an understanding the source of the variation and preprocessing of data with a suitable normalization method will be important. It is important to have an interactive cooperation between a researcher and a statistician from the early stages of the study design and to the final stages of data analysis.

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Whole genome analysis for liver metastasis gene signatures in colorectal cancer
Dong Hyuk Ki, Hei‐Cheul Jeung, Chan Hee Park, Seung Hee Kang, Gui Youn Lee, Won Suk Lee, Nam Kyu Kim, Hyun Chul Chung, Sun Young Rha
International Journal of Cancer.2007; 121(9): 2005. CrossRef

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Paclitaxel and Cisplatin Combination Chemotherapy in Pretreated Breast Cancer: Joo Hyuk Sohn, Yong Tai Kim, Sun Young Rha, Nae Choon Yoo, Jae Kyung Roh, Byung Soo Kim, Chang Ok Suh, Gwi Eon Kim, Woo Ick Jang, Hyun Cheol Chung; Cancer Res Treat. 2003;35(3):267-273. Published online June 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.3.267

Abstract PDF

PURPOSE
A single institute trial of combination chemotherapy, with paclitaxel and cisplatin, in patients with metastatic breast cancer, having failed previous combination chemotherapy, was performed. MATERIALS AND METHODS: Patients were only eligible for this study if there disease had progressed, following treatment with previous chemotherapy, in either an adjuvant or a metastatic setting. Paclitaxel 175 mg/m2 was administered as a 3-hour continuous infusion on day 1, and cisplatin 80 mg/m2 was administered for 2 hours on day 2, with adequate hydration. This was repeated every 3 weeks, and continued until one of the following events occurred: disease progression, unacceptable adverse effect or treatment refusal by the patient. Intercurrent palliative radiotherapy, or concurrent hormonal therapy, was permitted, depending on each patient's status. All the endpoints were evaluated under the principle of intention to treat analysis. RESULTS: A total of 24 patients entered the study, and 18 had at least one measurable lesion, but 6 did not. The objective response rate of the 18 patients was 50%(9/18). Two were complete responses and seven showed partial responses. The median response duration, progression free and overall survival were 5.3 months (range, 4~18), 6 months (95% CI, 5~7) and 12 months (95% CI, 7~17), respectively. 67% of the planned dose was administered. Out of a total 135 cycles administered, about 20% of cycles showed grade 3 or 4 leukopenia and 7% showed grade 3 thrombocytopenia. Two patients suffered from pneumonia, and one experienced neutropenic fever. Mucositis, greater than grade 3, existed in three cases. No treatment related deaths were reported. CONCLUSION: The combination chemotherapy, with paclitaxel and cisplatin, was active in the treatment of metastatic breast cancer patients having failed previous chemotherapy.

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Aleksandra Zoń, Ilona Bednarek
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Shiva Mehran, Afshin Taravati, Esfandiar Baljani, Yousef Rasmi, Zafar Gholinejad
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Salvador Harguindey, Khalid Alfarouk, Julián Polo Orozco, Kévin Hardonnière, Daniel Stanciu, Stefano Fais, Jesús Devesa
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Salvador Harguindey, Khalid Alfarouk, Julián Polo Orozco, Stefano Fais, Jesús Devesa
International Journal of Molecular Sciences.2020; 21(20): 7475. CrossRef

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Infusional 5-Fluorouracil, Leucovorin and Docetaxel in Advanced Gastric Cancer: Yong Tai Kim, Joo Hyuk Sohn, So Hun Kim, Sun Young Rha, Chul Kim, Jae Kyung Roh, Byung Soo Kim, Woo Ick Jang, Hyun Cheol Chung; Cancer Res Treat. 2003;35(2):123-129. Published online April 30, 2003; DOI: https://doi.org/10.4143/crt.2003.35.2.123

Abstract PDF

PURPOSE
This study was performed to estimate the response rate and toxicity of a combination chemotherapy, which included infusional 5-Fluorouracil, Leucovorin and Docetaxel in the treatment of patients with an advanced gastric carcinoma. MATERIALS AND METHODS: Twenty two advanced gastric cancer patients, with a bidimensionally measurable or an evaluable disease, were enrolled in this study. The patients received a 5-fluorouracil 1, 000 mg/m2 intravenous (IV) 24 hour infusion (Day 1~3), leucovorin 20 mg/m2 (Day 1~3) and docetaxel 75 mg/m2 intravenously (Day 2) every 3 weeks. RESULTS: The overall response rate was 45.0%. The median duration of response was 10.0 weeks (range: 4~24), the median time to response was 8 weeks (range: 8~20) the median time to progression was 30.0 weeks (95% CI: 16.3~43.2) and the median overall survival duration was 36.0 weeks (95% CI: 1.7~70.2). The median cumulative dose of 5-fluorouracil were 316.2 mg/m2/week and docetaxel was 23.9 mg/m2/week. WHO grade III, IV neutropenia, thromocytopenia and anemia occurred in 50.0%, 4.5% and 4.5% of patients, respectively. There were no occurrence of WHO grade III and IV nausea, vomiting, mucositis, conspitation, diarrhea, or neurotoxicity. CONCLUSION: This chemotherapy regimen, including infusional 5-fluorouracil, leucovorin and docetaxel was an active agent against advanced gastric cancer patients, especially for previous chemotherapy naive patients.

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The Efficacy of Docetaxel and Cisplatin Combination Chemotherapy for the Treatment of Advanced Gastric Cancer after Failing to 5-Fluorouracil Based Chemotherapy
Sang-Joon Shin, Min-Kyoung Kim, Kyung-Hee Lee, Myung-Soo Hyun, Sang Woon Kim, Sun Kyo Song, Sung-Hwa Bae, Hun-Mo Ryoo
Cancer Research and Treatment.2004; 36(6): 367. CrossRef

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A Phase II Study of Gemcitabine Monotherapy in Breast Cancer Patients Refractory to Anthracycline and Taxane: Jun Yong Park, Chul Kim, Joo Hyuk Sohn, Yong Tae Kim, Sun Young Rha, Woo Ick Jang, Gwi Eon Kim, Hyun Cheol Chung; Cancer Res Treat. 2002;34(4):274-279. Published online August 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.4.274

Abstract PDF

We performed a phase II trial to evaluate the efficacy and the safety of gemcitabine monotherapy, a pyrimidine antimetabolite, in patients, who had previously failed anthracycline and taxane-based chemotherapy for the treatment of metastatic breast cancer.
MATERIALS AND METHODS
Twenty-one patients with metastatic breast cancer, which was unresponsive to previous chemotherapy, were entered into this study. Gemcitabine was administered at 850 mg/m2, as a 60- minute intravenous infusion on days 1, 8 and 15. This regimen was repeated every 28 days with G-CSF support, but without dose reduction.
RESULTS
Objective responses were seen in 6 of the 20 patients who were able to be evaluated (1 complete response and 5 partial responses), with an objective response rate of 30%. The median time to progression was 5 (1~20) months, and the median overall survival duration was 11 (2~21) months. The actual dose intensity was 566.7 mg/m2/wk (range; 340~637.5 mg/m2/wk) and the relative dose intensity was 0.89 (range; 0.40~1.00). Toxicity was mainly hematological. Toxicities included: grade 3 neutropenia in 20% and anemia in 5%. Grades 3 and 4 thrombocytopenia occurred in 15% of the patients.
CONCLUSION
Gemcitabine monotherapy is an effective and safe treatment for refractory breast cancer patients heavily treated with the anthracycline and taxane- based regimen.

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Clinton Yam, Rashmi K. Murthy, Vicente Valero, Janio Szklaruk, Girish S. Shroff, Carol J. Stalzer, Aman U. Buzdar, James L. Murray, Wei Yang, Gabriel N. Hortobagyi, Stacy L. Moulder, Banu Arun
Investigational New Drugs.2018; 36(2): 299. CrossRef
Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines
Woo Sun Kwon, Sun Young Rha, Yeon Ho Choi, Jung Ok Lee, Kyu Hyun Park, Jae Joon Jung, Tae Soo Kim, Hei-Cheul Jeung, Hyun Cheol Chung
Pharmacogenetics and Genomics.2006; 16(6): 429. CrossRef
Gemcitabine Single or Combination Chemotherapy in Post Anthracycline and Taxane Salvage Treatment of Metastatic Breast Cancer: Retrospective Analysis of 124 Patients
Min Kyoung Kim, Sung-Bae Kim, Jin Hee Ahn, Soon Im Lee, Sei-Hyun Ahn, Byung Ho Son, Gyungyub Gong, Hak-Hee Kim, Jung-Shin Lee, Yoon-Koo Kang, Woo Kun Kim
Cancer Research and Treatment.2006; 38(4): 206. CrossRef
Gemcitabine monotherapy as salvage chemotherapy in heavily pretreated metastatic breast cancer
Sun Young Rha, Yong Hwa Moon, Hei Chul Jeung, Yong Tae Kim, Joo Hyuk Sohn, Woo Ick Yang, Chang Ok Suh, Gwi Eon Kim, Jae Kyung Roh, Hyun Cheol Chung
Breast Cancer Research and Treatment.2005; 90(3): 215. CrossRef

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Changes of Telomerase Activity and Proliferation by Inhibition of Reverse Transcriptase Activity in Human Cancer Cell: Hyun Jung Ji, Kyu Hyun Park, Tae Soo Kim, Sun Young Rha, Nae Choon Yoo, Jun Myung Kim, Jun Suk Kim, Jae Kyoung Roh, Woo Ick Jang, Hyun Cheol Chung; Cancer Res Treat. 2002;34(3):223-233. Published online June 30, 2002; DOI: https://doi.org/10.4143/crt.2002.34.3.223

Abstract PDF: PURPOSE
Activation of telomerase is proposed to be an essential step in cancer cell immortalization and cancer progression. 3'-azido-2',3'-dideoxythymidine (AZT), a reverse transcriptase inhibitor, was reported to be incorporated in telomeric sequences of immortalized cells in culture and to suppress the activity of telomerase and the cell proliferation. In this study, after induction of cancer cell senescence with long-term treatment of AZT, we investigated the dynamics of telomerase subunits (hTERT, hTR, TEP), transcription factors (c-Myc, Mad1), telomerase activity, and finally, telomere length in a human breast cancer cell line. MATERIALS AND METGODS: Human breast cancer cell (MDA-MB-231) was treated with AZT. Senescence was measured by senescence-associated beta-gal staining and apoptosis was counted by dTd enzyme assay. Telomerase activity (by TRAP assay), expression of telomerase subunit genes (by RT-PCR and real-time PCR) and telomere length (by Southern blot analysis) were measured after the AZT treatment.
RESULTS
We found evidences of senescence, apoptosis and growth delay after AZT treatment. In addition, AZT- treated cancer cells showed inhibition of telomerase activity and shortening of telomere length in a dose- and duration-dependent way. Among the telomerase subunits, hTERT and c-Myc were the first factors to change after AZT treatment, subsequently, followed by the changes of hTR, Mad1 and TEP.
CONCLUSION
The suppression of hTERT and c-Myc by AZT treatment was the initial genetic phenomenon, subsequently followed by the changes of hTR, Mad1 and TEP.

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Efficacy of Pre- and Postoperative Chemotherapy in Patients with Osteosarcoma of the Extremities: Joo Hyuk Sohn, Sun Young Rha, Hei Cheul Jeung, Hyun Joon Shin, Young Suck Goo, Hyun Cheol Chung, Woo Ick Yang, Soo Bong Hahn, Kyu Ho Shin, Jin Sik Min, Byung Soo Kim, Jae Kyung Roh, Woo Ick Jang; Cancer Res Treat. 2001;33(6):520-526. Published online December 31, 2001; DOI: https://doi.org/10.4143/crt.2001.33.6.520

Abstract PDF

PURPOSE
We evaluated the treatment efficacy including survival and recurrence, and factors associated with recurrence in osteosarcoma patients treated with preoperative chemotherapy, surgery, and adjuvant chemotherapy.
MATERIALS AND METHODS
Forty nine patients with osteosarcoma were treated with preoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion for 3 cycles, followed by surgery. According to the pathologic response, if tumor was necrotized more than 90%, the same adjuvant chemotherapy was reintroduced for 3 cycles, and if the response was not enough, then the salvage regimen was introduced. Plain chest film and chest CT scan were taken monthly and every 3 months, respectively. When tumor recurred, the metastasectomy was performed whenever possible.
RESULTS
Forty three patients were evaluable with amedian follow up of 53 months. Five-year disease-free and overallsurvival rate was 47.0% and 66.9%, respectively. The recurrence was observed in 22 patients (51.2%) with median time of 12.5 months. Baseline alkaline phosphatase (ALP) was the only significant factor for recurrence (p=0.03) and the patients with the possibility of metastasectomy recurrence showed higher post-relapse survival compared to other treatment modalities (26 momths vs 5~12 months).
CONCLUSION
These results indicates that pre- and postoperative chemotherapy with intra-arterial cisplatin and adriamycin infusion showed comparable treatment efficacy and acceptable toxicities.

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Jie Zhang, Ping Ye, Lizheng Zhang, Hongliu Wu, Tianxi Chi, Zhaohua Chang
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The multidisciplinary treatment of osteosarcoma of the proximal tibia: a retrospective study
Junqi Huang, Wenzhi Bi, Gang Han, Jinpeng Jia, Meng Xu, Wei Wang
BMC Musculoskeletal Disorders.2018;[Epub] CrossRef
Expression change of ezrin as a prognostic factor in primary osteosarcoma
Yao Fei Wang, Jing Nan Shen, Xian Biao Xie, Jin Wang, Gang Huang
Medical Oncology.2011; 28(S1): 636. CrossRef
Comparison of Long-Term Outcome between Doublet and Triplet Neoadjuvant Chemotherapy in Non-Metastatic Osteosarcoma of the Extremity
Soojung Hong, Sang Joon Shin, Minkyu Jung, Jaeheon Jeong, Young Joo Lee, Kyoo-Ho Shin, Jae Kyung Roh, Sun Young Rha
Oncology.2011; 80(1-2): 107. CrossRef
Clinical Value of Ezrin Expression in Primary Osteosarcoma
Chan Kim, Eunah Shin, Soojung Hong, Hong Jae Chon, Hye Ryun Kim, Jung Ryun Ahn, Min Hee Hong, Woo Ick Yang, Jae Kyung Roh, Sun Young Rha
Cancer Research and Treatment.2009; 41(3): 138. CrossRef
Carboxypeptidase-G2 Rescue in a Patient with High Dose Methotrexate-induced Nephrotoxicity
Eun Sil Park, Kyung Hee Han, Hyoung Soo Choi, Hee Young Shin, Hyo Seop Ahn
Cancer Research and Treatment.2005; 37(2): 133. CrossRef

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Clinical Significance of Urokinase - type Plasminogen Activator Receptor ( uPAR ) Expression in Breast Cancer Tissues: Soo Jung Gong, Sun Young Rha, Hei Chul Jung, Joon Oh Park, Nae Choon Yoo, Jae Kyung Roh, Woo Ick Yang, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 2000;32(1):53-59.

Abstract PDF: PURPOSE
Cancer invasion is induced by several proteolytic enzyme systems associated with the destruction of basement membrane and extracellular matrix. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have been reported as prognostic factors in breast cancer patients and plasminogen activation is regulated by various factor such as uPAR and growth factor. So we examined the tissue levels of urokinase-type plasminogen activator receptor (uPAR) in breast cancer patients.
MATERIALS AND METHODS
Tissue uPAR levels were measured by ELISA assay in 268 breast cancer patients.
RESULTS
The median and mean values of tissue uPAR level in breast cancer were 3.5 ng/mg and 4.8+-3.6 ng/mg cytosol protein, respectively. Tissue uPAR level was the highest in T1 stage, but there was no statistical significance between T stage (p >0.05). In nodal stage, there was also no difference in the value of uPAR according to progression. And the value of uPAR expression was not associated with estrogen and progesteron receptor status, number of involved node and percent of node involvement. In TNM stage, tissue uPAR levels were higher in patients with stage I-II than in patients with stage III-IV (p=0.027). In univariate analysis, nodal factor (p=0.0023) and TNM stage (p=0.0004) were significantly associated with overall survival. But, multivariate analysis showed that TNM stage was the only significant prognostic factor (p=0.0002). CONCLUSION: These results suggest that uPAR is mainly associated with initial tumor invasion and other factors might be involved in later stages of cancer progression.

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Application of Gabexate Mesylate IC against MMP - 9 Using ex vivo Model in Gastric Cancer: Prognostic Factor and Selection Criteria for Anti - MMP Treatment: Yong Wha Moon, Hoon Yang, Hei Chul Jung, Sun Young Rha, Tae Soo Kim, Nae Choon Yoo, Sung Hoon Noh, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 2000;32(1):7-18.

Abstract PDF: PURPOSE
Among the many biological characteristics of cancer, matrix metalloproteinases(MMPs) are essential for tumor invasion and metastasis. The correction of the imbalance between MMPs and tissue inhibitors of matrix metalloproteinase (TIMP) has been suggested as a possible goal for the control of invasive phenotype of the cancer. To test the possible inhibition of MMP-9 in ex vivo model and the selection of the patients who are sensitive to MMP inhibitory (MMPI) treatment, we evaluated IC50 of the gabexate mesylate (Foy) against MMP-9 and compared them to the clinical parameters and patients survivals. MATERIALS AND METHODS: Thirty-four paired normal and gastric cancer tissues were tested for the IC50 of the gabexate mesylate. MMP-9 activity was measured by zymography.
RESULTS
MMP-9 expression (percent of sample band density to control band) (p=0.04) and IC50 (p=0.02) of cancer tissues were significantly higher than those of normal tissues. Cancer tissue IC50 was higher than that of normal tissues in cases when the tumor mass diameter was longer than 5 cm (p=0.03) as well as in higher T-stage (p=0.04), lymph node metastasis (p=0.04) and in advanced stages (p=0.04). There was a tendency of increased IC50 of diffuse and mixed type than that of intestinal type (diffuse & mixed: 11.0+-20.8 mg/ml, intestinal: 2.7+-3.9 mg/ml; p 0.07), in spite of no difference in MMP-9 expression (diffuse & mixed: 40.3+49.2%, intestinal: 51.0+-58.0%). In early gastric cancer (EGC), there was no difference in IC50 between normal and cancer tissues whereas cancer tissue IC50 was higher than that of normal tissue in advanced gastric cancer (p 0.02). There was a tendency of increment of ICo in cancer tissues of advanced gastric cancer than that of EGC whereas no difference was found in MMP-9 expression between these types of cancers. Poor prognosis was found in high IC50 patients in curatively resected patients (p=0.04). In multivariate analysis, high IC50 was suggested as a possible independent prognostic factor.
CONCLUSION
We could differentiate the high risk patients using IC50 of gabexate mesylate in ex vivo model. This model can be applied in detecting patients with poor prognosis and patients who can have a possible benefit with MMPI treatment.

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Efficacy of Gemcitabine Chemotherpy in Advanced Non-small cell Lung Cancer ( NSCLC ): A Phase 2 Study: Hyuk Jae Chang, Joong Bae Ahn, Jun Gu Lee, Kwang Yong Shim, Sun Young Rha, Sae Kyu Kim, Jun Chang, Sung Kyu Kim, Won Young Lee, Nae Chun Yoo, Hyun Cheol Chung, Jae Kyung Roh, Byung Soo Kim, Sung Jun Choi, Tae Won Kim, Chul Won Suh, Joo Hang Kim; J Korean Cancer Assoc. 1999;31(3):523-532.

Abstract PDF: PURPOSE
To evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite against advanced non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
Forty patients with unresectable stage IIIb to IV, pathologacally documented NSCLC were evaluated. Patients received gemcitabine 1000 mg/m, as a 30 to 60-min, intravenous infusion on days 1, 8 and 15, which was repeated every 28 days. Responses were assessed every two courses. Twenty-five to fifty percent dose reduction was permitted, ptovided that overall toxicity was severe according to World Health Organization (WHO) toxicity criteria.
RESULTS
Of all 40 patients (32 men, 8 women; age range 37 to 73 years; median 63 years), 3S patients were assessable for response. 15 patients had stage IIIb disease and 25 had stage IV. Nineteen patients were histologically classified as adenocarcinoma (47.5%), 17 as squamous cell carcinoma (42.5%), 1 as large cell carcinoma (2.5%), 1 as mixed carcinoma (2.5%) and 2 as undifferentiated carcinoma (5.0%). The overall response rate was 20%. None of the patients showed complete response while 7 showed partial response (20%), 5 had stable diseases (23%) and 23 had progressive diseases (57%). During a total of 119 courses, hematologic toxicity was negligible. Granulo- cytopenia worse than WHO grade 3 occured in 11.8%, anemia in O.S% and thrombocytopenia in 0.8%, respectively. Non-hematologic toxicity was minor and easily controlled. There was no case of febrile neutropenia or treatment-related death.
CONCLUSION
The single agent efficacy of gemcitabine is comparable to other agents commonly used to treat NSCLC. Gemcitabine has unusually mild side effect profile for such an active agent. This significant activity in conjunction with a very favorable toxicity profile supports further investigation in combination with other agents in patients with inoperable NSCLC.

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Midkine Expression in Cell Lines and tumor Tissues of Glioblastoma Multiforme: Jin Woo Chang, Sun Young Rha, Sang Sup Chung, Frank Czubayko, Hyun Cheol Chung; J Korean Cancer Assoc. 1999;31(3):617-626.

Abstract PDF: PURPOSE
We measured the expression of midkine (MK) gene and biophenotypes in brain tumor cell lines and tumor tissues.
MATERIALS AND METHODS
We used the cell lines purchased from ATCC: two glioblastoma cell lines (T98G, U87MG), rat bladder tumor cell line (NBT-II), NIH/3T3, and two endothelial cell lines [(human umbilical vein endothelial cell (HUVEC) and fetal bovine heart endothelial cell (FBHE)]. RNA was taken from 4 cancer tissues of glioblastoma multiforme. Tissue cytosol was obtained from 5 cancer patients and 2 tissues of epilepsy patients. Pentosanpolysulfate(PPS) was used as a competitive inhibitor of heparin-binding growth factor (HBGF). MK and pleiotrophin (PTN) mRNA expression was tested by Northem hybridization, uPA and PAI-1 levels were measured by ELISA (Monozyme, Netherlands). Cross-feeding assay was done to measure the activity of endothelial cell growth stimulation induced by cancer cell lines.
RESULTS
T98G cell line expressed both MK and PTN while U87MG expressed only PTN. In cross-feeding assay, endothelial cell growth increased in proportion to the number of administered feeding tumor cells, T98G and U87MG. This phenomenon was found in HUVEC, but not in FBHE. Conditioned media of T98G and U87MG showed similar stimulatory effect on the growth of NIH/3T3 cells. T98G cell showed higher excretion rate of uPA into conditioned media while U87MG showed higher excretion rate of PAI-1 into conditioned media. 20% of growth inhibition was induced on T98G cell with 100 pg/ml PPS, while 40% of growth inhibition was induced with 10 pg/ml PPS on U87MG cell. In four cancer tissues, thee expressed MK. In cancer tissue cytosol, uPA and PAI-1 expressions varied in individuals. No PAI-1 was found in non-tumor tissues.
CONCLUSION
MK expression was found in brain tumor cell lines and tumor tissues. Modulation of biophenotypes (angiogenic activity and growth) by PPS in tumor cells with MK expression suggested a possible biotherapy in brain tumor targeting growth factor.

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Clinical Relevance of Urokinase-type Plasminogen Activator ( uPA ) , uPA Receptor , Plasminogen Activator Inhibitor-1 Co-expression from Tissue and Serum of Breast Cancer as Targets of Biotherapy: Sun Young Rha, Joon Oh Park, Soo Jung Gong, Se Ho Park, Nae Choon Yoo, Woo Ick Yang, Jae Kyung Roh, Jin Sik Min, Kyong Sik Lee, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1999;31(2):256-266.

Abstract PDF: PURPOSE
We measured and compared the uPA, plasminogen activator inhibitor-1 (PAI-1) and uPA receptor (uPAR) levels in breast cancer tissues and blood of the patients to evaluate their clinical relevance for biotherapy.
MATERIALS AND METHODS
uPA, PAI-1 (Monozyme, Netherland), uPAR (American Diagnostics, USA) levels were measured by ELISA assay in 192 breast cancer tissues, in 18 normal breast tissues and in 163 blood from breast cancer patients. RESULTS: There was a tendency of uPA increment from ductal carcinoma in situ while increment of PAI-1 and uPAR occurred from Ti. With the progression of cancer, uPA, PAI-1, uPAR tended to decrease; however, the uPA/uPAR, uPA/PAI-1 ratios remained unchanged. There was a correlation of uPA expression between normal and cancer tissues ( r(2)= 0.49). Correlation of uPA and PAI-1 was found in normal tissue and stage I cancer tissue while correlation of uPAR and PAI-1 was found with cancer progression. Between cancer tissue and blood significant correlations were found in uPA, PAI-1, uPAR levels.
CONCLUSION
uPA, PAI-1, uPAR levels in cancer tissue elevated from the early stage maintaining correlative expressions with cancer progression. A positive correlation between cancer tissue and blood level suggested the applicability of the levels of uPA, PAI-1 or uPAR for detecting patients for biotherapy.

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The Efficacy of Pre - operative Chamotherapy with Intra-arterial Cisplatin and Intravenous Adriamycin for High Grade Osteosarcoma: Sun Young Rha, Soo Jung Gong, Hee Cheol Chung, Kwang Yong Shim, Joong Bae Ahn, Nae Choon Yoo, Hyn Cheol Chung, Joo Hang Kim, Hae Kyung Roh, Jin Sik Min, Byung Soo Kim, Kyu Ho Shin, Woo Ick Yang, Chong In Lee; J Korean Cancer Assoc. 1999;31(1):134-143.

Abstract PDF: PURPOSE
Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment [pre-operative chemotherapy + surgery (limb salvage or amputation) + adjuvant chemotherapy] had improved the overall survival and quality of life. To improve the local control rate, we introduced pre-operative chemotherapy combined with intra-arterial (IA) cisplatin and continuous intravenous infusion (CI) of adriamycin. We evaluated the efficacy and feasibility, such as limb salvage rate, recurrence pattern and the survival impact, based on the histologic response of pre-operative chemotherapy.
MATERIALS AND METHODS
Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1996. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72hrs CI, was administered for 3 cycles with 3 week interval, followed by surgery. Post-operative chemotherapy was applied by the tumor necrosis rate. If the tumor necrosis of the specimen was more than 90%, the same regimen af the preoperative one was administered for 3 cycles. A salvage regimen (Ifosfamide 7.5 gm/m2/5d IV + high dose MTX 10 gm/m2 IV VP-16 360 mg/m2/3d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%.
RESULTS
Of 41 patients, 37 were evaluable for efficacy and toxicities, because 4 refused further chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 female, with the median age of 16 years (8-41). The tumor locations were as follows: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (10 with grade III, 27.8%; 17 with grade IV, 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lungs. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive care.
CONCLUSION
Pre-operative chemotherapy combined with IA cisplatin and CI adriamycin induced higher good response rate without survival benefits. To improve the survival rate, the design of good salvage chemotherapy with a non-cross resistant regimen should be considered.

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Microsatellite Instability Correlate with a Prognosis in Breast Cancer: Hwa Young Lee, Chengshi Quan, Soo Jung Gong, Joon Oh Park, Joong Bae Ahn, Kwang Yong Shim, Sun Young Rha, Nae Choon Yoo, Woo Ick Yang, Joo Hang Kim, Jae Kyung Roh, Kyong Sik Lee, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(5):914-920.

Abstract PDF: PURPOSE
Microsatellite instability in patients with defects in the mismatch repair system resulting in RER has a high risk of accumulating mutations in oncogene and tumor suppressor gene. In this study, we evaluated the incidence of microsatellite instability in breast cancer by comparing PCR-amplified sequences from frozen samples of normal and tumor tissue fram affected patients. We also investigated whether RER was associated with TGF-beta RII mutation.
MATERIALS AND METHODS
Fifty surgically resected breast cancer specimens from Jan. 1996 to June, 1997 were used for study. Microsatellite instability(referred to as replication error, RER) at three loci with BAT 26, BAT 40, TA10 was analyzed by polymerase chain reaction and the results were compared with clinicopathologic characteristics.
RESULTS
Of the 50 breast cancer patients, 14(28%) were RER(+) at one or more microsatellite loci, and 4(8%) showed TGF-beta RII mutation. Microsatellite instability was significantly correlated with lymph node involvement(especially in case of 4 or more lymph nodes involvement). But we could not find any correlation between RER and other prognostic factors including tumor size, tumor grade, hormone receptor status and pathology. One of fourteen tumors with RER(+) showed TGF-beta RII mutstion. There was no signiticant correlation between RER(+) and TGF-beta type II receptor gene mutation.
CONCLUSION
The findings suggest that microsatellite instability would be useful prognostic factor in unilateral breast cancer patients, and the role of targeting to gene mutation will be explored in future studies.

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Restoration of Wild - type p53 Induces Chemo-sensitization in the Gastric Cancer Cell Line with Mutant p53: Ho Young Maeng, Sun Young Rha, Byung Soh Min, Yong Bae Kim, Hyun Joo Kwak, Tae Soo Kim, Kyu Hyun Park, Nae Choon Yoo, Ho Young Lim, Jin Hyuk Choi, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):497-507.

Abstract PDF: PURPOSE
It has been theorized that p53 may be involved in the sensitivity to chemotherapeutic agents. We evaluated the chemosensitivity of wild p53 after transduction into gastric cancer cell lines with mutant p53.
MATERIALS AND METHODS
YCC-3(parent cell line with mutant p53), YCC-3v(parent cell line transduced with vector alone) and YCC-3C3(clone with wild p53) cell lines were used in this study. p53 protein expression was measured by ELISA assay. Tumorigenicity and drug sensitivity were evaluated by soft agar and proliferation assay, respectively. Cell cycle analysis was performed by flowcytometry. Telomerase activity was measured by TRAP assay and terminal restriction fragment(TRF) length was measured after Southern blot analysis.
RESULTS
Even though p53 production from the YCC-3C3 cell line was three times higher than those of YCC-3 and YCC-3v cell lines, the cell cycle was the same in these three cell lines. In the YCC-3C3 cell line, drug sensitivity to etoposide and cisplatin was increased when we compared it to those of the YCC-3v cell line(etoposide, 50% versus 83%; cisplatin, 67% versus 83%). However, there was no chemo-sensitization effect with vincristine, vinblastine and carboplatin. After exposure to cisplatin, a G0/G1 check-point effect was found in the YCC-3C3 cell line, but not in the YCC-3v cell line. No differences were found in telomerase activity, TRFs length or DNA fragmentation between the YCC-3v and YCC-3C3 cell lines after cisplatin treatment.
CONCLUSION
Wild-type p53 gene transduction in the gastric cancer cell line induced sensitization to the cytotoxicity of etoposide and cisplatin. This suggests the possible application of combined chemo-gene therapy with an EP regimen and wild-type p53 in gastric cancer patients with p53 mutation.

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Brain Metastasis and Leptomeningeal Carcinomatosis in Breast Cancer: Yoon Soo Chang, Jeong Hun Seo, Ruth Lee, Joong Bae Ahn, Kwang Yong Shim, Soo Jung Gong, Hwa Young Lee, Sun Young Rha, Nae Choon Yoo, Chang Ok Suh, Joo Hang Kim, Jae Kyung Rho, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):464-474.

Abstract PDF: PURPOSE
Brain metastasis is estimated to occur in 20 to 40% of cancer patients, and meningeal involvement has been reported in 5% to 8% of cancer patients. Even if the prognosis is grave, standard treatment modality of brain metastasis or leptomeningeal carcinomatosis has not been established. We evaluated the prognosis and the clinical features of the brain and leptomeningeal metastasis of the breast cancer.
MATERIALS AND METHODS
The 43 patients who was diagnosed as brain parenchymal metastasis or leptomeningeal carcinomatosis clinically, radiologically and/or cytologically were included in this study. The median age was 44(range: 27-61) years.
RESULTS
The median duration from brain metastasis to death was 181 days(range: 8~1599), and the median duration from leptomeningeal carcinomatosis to death was 39 days(range: 25~152). Age(p=0.7174) and number of brain metastatic lesion(p=0.4097) did not influence the survival, but the presence of other systemic metastatic lesion affected the survival(p 0.0224). When we compared the survival rates of patients according to treatment modality, the patients with systemic chemotherapy versus patients without systemic chemotherapy showed differences(p= 0.0009). Patients treated with whole brain radiation only versus patients with whole brain radiation and other systemic management also showed different survival rate(p=0.0009). But intrathecal chemotherapy had no effect on survival. Well differentiated, solitary lesions were treated by operation and/or gamma-knife surgery, and their effects were good.
CONCLUSION
Prolongation of survival was suggested with whole brain radiotherapy combined with systemic treatment in brain or leptomeningeal metastasis. Further study is expected to confirm this finding.

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Effect on Malignant Phenotype of Gastric Cancer Cell Line after p53 Gene Transduction: Sun Young Rha, Tae Soo Kim, Sook Jung Jeong, Joong Bae Ahn, kwang Yong Shim, Soo Jung Kong, Hwa Young Lee, Nae Choon Yoo, Jin Hyuk Choi, Ho Young Lim, Joo Young Lim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(3):508-520.

Abstract PDF: PURPOSE
To evaluate the effect of wild type p53 gene transduction on the malignant phenotypes for metastasis in gastric cancer, we compared the biological phenpotypes of gastric cancer cell lines based on p53 gene status. Then, after retrovirus-mediated wild-type p53 gene transduction, we compared those phenotypes among parent YCC-3 cell line, vector transduced YCC-3v cell line and a clone of YCC-3C3. MATERIAL AND METHODS: Four human gastric cancer celi lines were used; YCC-l(mutant), YCC-2(wild), YCC-3(mutant) and AGS(wild). DNAs of the cell lines were analyzed to evaluate the mobility shift with PCR-SSCP. Tumorigenecity and proliferation were evaluated by soft agar assay and proliferation assay. Migratory capacity was measured by adhesion assay and Boyden chamber assay. p53 protein expression was measured by Western blot analysis and VEGF, WAF-1 were measured by ELISA assay. Angiogenic activity was measured by cross-feeding assay and cell cycle analysis was performed by flowcytometry. In vivo tumorigenicity was measured by xenograft in nude mice.
RESULTS
YCC-3 cell line with mutant p53 gene expressed all the phenotypes for the metastasis such as tumorigenicity, migration and angiogenesis. In a stable clone of YCC-3C3, no differences were found in proliferation, cell cycle and WAP-1 expression when compared to those of the control YCC-3v and parent YCC-3 cell line, even if increased p53 protein production was found by Western blot analysis. However, both in vitro and in vivo tumorigenicity were decreased in a stably transduced YCC-3C3 clone. The adhesive capacity was also decreased in YCC-3C3 clone whereas the endothelial cell growth stimulatory effect and VEGF production showed no difference compared to those of the YCC-3v cell line.
CONCLUSION
Wild-type p53 gene transduction in gastric cancer cell line decreased tumorigenicity which resulted from decreased colony forming activity and adhesive capacity but not formed changes of angiogenic activity. This suggested the possible application of anti- metastasis strategy with p53 gene therapy in gastric cancer.

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Semi - quantitative Comparison of Terminal Restriction Fragment Length and Telomerase in Breast Cancer for Biotherapy: Sun Young Rha, Kyu Hyun Park, Tae Soo Kim, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Kyung Shik Lee, Byung Soo Kim, Hyun Cheol Chung; J Korean Cancer Assoc. 1998;30(2):231-241.

Abstract PDF: PURPOSE
We determined the clinical significance of telomerase activity and telomere length in breast cancer patients and also developed the measuring system of telomerase activity change with RNAse A pre-treatment.
MATERIALS AND METHODS
We measured the telomerase activity in 71 breast cancer tissues and paired normal tissues with TRAP (Telomeric Repeat Amplification Protocol) assay. Telomerase activity was calculated by computer-assisted densitometry compared to telomerase activity of the 293 control cell line. To develop the measuring system of telomerase activity modulation, we measured the telomerase activity after the treatment with RNAse A, 150microgram/ml, which inhibited 70% of telomerase activity compared to control in the 293 control cell line. In 59 paired tissues with telomerase activity, terminal restriction fragment (TRFs) length were measured using Southern blotting.
RESULTS
Sixty-three out of 71 cancer tissues showed telomerase activity (88.7%), while no telomerase activity was detected in their paired normal tissues. Telomerase activity was correlated to the node metastasis (p=0.02) and stage (p=0.005), but not to the tumor size or the hormonal receptor status. TRFs were neither specific to tumor tissues nor related to any of the clinical parameters. However, changes of TRFs of the tumor tissues from their paired normal tissues were correlated to the telomerase activities. Also the patients with different TRFs between cancer and normal tissues were in more advanced stage. After pre-treatment with the 150microgram/ml of RNAse A, telomerase activity in the tumor tissues showed variable inhibition. Relative inhibition, the ratio of inhibited telomerase activity in each tumor tissue compared to the inhibition of 293 control cell line, was proportional to the telomerase activity.
CONCLUSION
In breast cancer, telomerase activity was specific to the tumor tissues and correlated to tumor progression. A combination of telomerase activity and TRFs changes can be used as a guidline in detecting a better candidate for telomerase inhibition. Semi-quantitative assay with RI system can be used in evaluating the changes of telomerase activity after treatment with a new telomerase inhibitor with TRAP assay.

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Gene Transfer Effects of Thymidine Kinase Gene of Herpes Simplex Type 1 on Ganciclovir Cytotoxicity in Gastric Cancer Cell Line: Jae Kyung Roh, Soo Jung Gong, Joo Hang Kim, Hyo Dong Um, Nae Chun Yoo, Jin Hyuk Choi, Jae Jin Song, Sun Young Rha, Hyun Cheol Chung, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1998;30(1):20-30.

Abstract PDF: PURPOSE
Gastric cancer is the most common malignancy in Korea. Although treatment such as surgery, chemotherapy, and immunotherapy has greatly improved, the mortality rate of gastic cancer is still high, A new therapeutic trial is necessary to improve the cure rate of gastric cancer. Therefore we investigated the pre-clinical significance of HSV-tk gene therapy using retroviral vector for gastric cancer cell lines.
MATERIALS AND METHODS
LNC/HSV-tk retroviral vector and PA317/LNC/HSV-tk producer cell line were constructed. HSV-tk gene transduction and expression were detected by PCR. An in vitro ganciclovir(GCV) sensitivity test was performed by MTT assay. To evaluate in vivo GCV sensitivity, GCV was intraperitoneally injected after tumor formation in the nude mice. Bystander effect was observed in vitro MTT assay using YCC- S-2 cell line and in vivo using N87 and YCC-S-2 cell lines.
RESULTS
The in vitro GCV sensitivity test showed that the growth inhibition was 30~32% with 0.5 uM GCV and 52~77% with 500 uM GCV in the HSV-tk transduced cell line in comparison with 0- 5% with 0.5 and 500 uM GCV in the parent cell line. The in vivo GCV administration showed that the tumors induced by HSV-tk transduced N87 cell line and YCC-S-2 cell line decreased completely, while the tumors with the parent cell lines continued to grow in nude mice. We observed no tumor cells in tissue specimen of the tumor induced by the N87/HSV-tk cell line after. GCV administration. In vitro and in vivo bystander effects were observed in HSV-tk/GCV system due to the resultant cell death exceeding the proportion of HSV-tk transduced cells in the mixtures of HSV-tk transduced and parent cells.
CONCLUSION
HSV-tk transduced gastric cancer cell lines showed sensitivity to GCV and a bystander effect was observed. These results suggested that HSV-tk/GCV system should be evaluated in the clinical settings.

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Increment of Telomerase Activity with Breast Cancer Progression: Kyu Hyun Park, Sun Young Rha, Tae Soo Kim, Byung Chan Lee, Sei Ho Park, Hyun Cheol Chung, Won Young Lee, Joo Hang Kim, Jae Kyung Roh, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(6):1032-1040.

Abstract PDF: PURPOSE
We studied the telomerase activity in normal and cancer tissues of the breast and then compared it to the clinical parameters.
MATERIALS AND METHODS
36 paired normal and cancerous breast tissues were assayed for telomerase activity by PCR-based TRAP assay (telomeric repeat amplification protocol). In 17 cancer tissues, flow cytometric analysis for S-phase fraction was done.
RESULTS
None of the normal breast tissue expressed telomerase activity while 23 out of 26 breast cancer tissue expressed telomerase activity (92%). Clinical parameters such as T-factor, tumor grade, hormone receptor expression, mitosis, S-phase fraction did not correlate with telomerase expression. However, telomerase acitvity increased with cancer progression such as; in a state of lymph node metastasis and in an advanced pathological stage.
CONCLUSION
Telomerase activity was expressed only from cancer tissues. And this expression increased with cancer progression suggesting a possible therapeutic target in breast cancer.

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A Report of Hepatocellular Carcinoma with Renal Metastasis: Seung Hyuk Choi, Seung Won Choi, Young Nyun Park, Ho Guun Na, Sun Young Rha, Hyun Cheol Chung, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(5):914-914.

Abstract PDF: Hepatocellular carcinoma is a fatal disease with median survival less than 6 months. About 50% of hepatocellular carcinoma patients showed distant metastasis at earlier stage. Common metastatic sites are lung, intraabdominal lymph nodes, adrenal gland or bone, in order of frequency. Renal metastasis from hepatocellular carcinoma is rare with the incidence of 1.2-4.3% at autopsy. Lack of clinical symptoms and signs make it difficult to diagnose metastatic renal cancer before dying of. Common primary sites of metastatic renal cancer are malignant lymphoma, lung, stomach or breast. We report a case of hepatocellular carcinoma with renal metastasis. A 54 female patient was found to have coincidental right hepatic and right renal tumors on abdominal ultrasonographic and computed tomographic examinations. After the percutaneous needle biopsy on the right hepatic tumor and right renal tumor, histopathologic and immunohistochemical studies ultimately confirmed the diagnosis of hepatocellular cracinoma with renal metastasis. Intraarterial chemotherapy with cisplatin for primary hepatocellular carcinoma and intraarterial embolization for renal metastatic lesion were performed.

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A Phase I/II Trial of DA3030 in Chemotherapy Induced Neutropenia: Hyun Cheol Chung, Sun Young Rha, Soo Jung Gong, Hwa Young Lee, Hei Cheol Chung, Churl Woo Ahn, Wook Jin Chung, Rutha Lee, Bo Young Choung, Seung Keun Lee, Yoon Soo Chang, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Bum Soo Park, Mi Young Bahng; J Korean Cancer Assoc. 1997;29(5):886-898.

Abstract PDF: PURPOSE
We planned to evaluate the toxicity and efficacy of DA-3030 to determine the recommended dose for phase III clinical trial based on the biologically active doses from phase I/II clinical trial.
MATERIALS AND METHODS
Open non-randomized phase I/II study was carried out in 64 cancer patients with chemotheray-induced myelosuppression. After 1 cycle of control period (chemotherapy without DA-3030), DA-3030 was started 24 hours after the second cycle of chemotherapy to 4 groups of patients with the doses of 50 microgram/m2/day (step I), 100 microgram/m2/day (step II), 150 microgram/m2/day (step III), 200microgram/m2/day (step IV) by once-a-day subcutaneous administration for 10 days.
RESULTS
Of the 64 enrolled patients, 46 patients were evaluable. Tmax reached after 2 hours of injection in step I and 4 hours in step II-IV. Terminal half life was 1.8 hours in step I and 3.2 hours in step II, 3.3 hours in step III, 3.0 hours in step IV. Area under the curve (AUC) and AUMC increased dose dependently from step I through step IV. Total clearance rate decreased in a dose dependent manner but the volume of distribution showed no differences between the steps.The mean nadir count of total WBC and neutrophil increased in all 4 steps of DA-3030 administration. Also the duration of leukopenia, equal to or less than 2,000/uL or neutropenia and the recovery time of WBC or neutrophil from nadir decreased with DA-3030 administration in all 4 steps. But no differece of DA-3030 effect was found among 4 steps. When we compared the clinical efficacy of DA-3030 with total WBC and neutrophil criteria, it was 58.3% and 58.3% in step I, 90.0% and 80.0% in step II, 91.7% and 91.7% in step III, 75.0% and 70.0% in step IV. Although the duration of antibiotics administration showed no difference between control and DA-3030 administration period in step I, it decreased with DA-3030 administration in step II-IV. Infection was found only in step I. Life-threatening side effect was not found in all steps. Only mild myalgia was found without any dose relationship.
CONCLUSION
When we considered the efficacy, toxicity and pharmacokinetic parameters, we suggest that 100microgram/m2 is an appropriate dosage for the phase III clinical trial.

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Clinical Significance of Urokinase-type Plasminogen Activator (uPA) Expression from Serum and Tissue of Gastric Cancer Patients: Hyun Cheol Chung, Joon Oh Park, Hyun Ja Kwon, Tae Soo Kim, Hei Cheol Chung, Soo Jung Gong, Hwa Young Lee, Sun Young Rha, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Sung Hoon Noh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(5):765-773.

Abstract PDF: PURPOSE
We measured the gastric cancer tissue uPA and plasminogen activator inhibitor-1 (PAI-1) levels and compared them to those of the peripheral and portal blood levels to evaluate the correlation.
MATERIALS AND METHODS
Tissue uPA and PAI-1 levels were measured by ELISA assay (Monozyme, Netherland) in paired 85 normal and cancer tissues resected from gastric cancer patients. In 50 patients, blood uPA and PAI-1 levels were measured from pre- operative peripheral and portal blood, post-operative portal blood.
RESULTS
Gastric cancer tissue uPA and PAI-1 levels increased from the early stage. The elevated cancer-to-normal ratios of the uPA and PAI-1 were constant from stage I to IV. There were correlations of uPA between normal and cancer tissues (r2=0.38) and between peripheral and pre-resection portal blood level (r2=0.64). There were no correlations between tissue PAI-1 level and blood PAI-1 levels. However, there were correlations in PAI- 1/uPA ratio between cancer tissue and peripheral blood (r2=0.25), peripheral blood and pre- resection portal blood (r2=0.60).
CONCLUSION
Even if the cancer tissue levels of uPA and PAI-1 increased from the early stage of gastric cancer, only blood uPA level correlated with tissue uPA level. A modest correlation found in PAI-1/uPA ratio between cancer tissue and blood suggests applicability of blood PAI-1/uPA ratio in predicting tissue uPA, PAI-1 expression.

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A Study of Retrovirus-mediated p53 Gene Transduction Into Human Gastric Cancer Cell Lines: Joo Hang Kim, Yoo Sun Moon, Dong Hwan Shin, Jae Jin Song, Soo Jung Gong, Sun Young Rha, Soo Kyoung Kim, Sook Jung Jeong, Hyun Cheol Chung, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(5):754-764.

Abstract PDF: PURPOSE
The development of new therapeutic modalities such as gene therapy, which still requires further investigation, is clearly important to improve the prognosis of gastric cancer. This study was conducted to evaluate the effect on the growth and the tumorigenicity of retrovirus-mediated p53 gene transduction into gastric cancer cells.
MATERIALS AND METHODS
Human gastric cancer cell lines were cultured and their DNAs were analyzed to evaluate the p53 status with PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) and DNA sequencing. Retroviral supernatants were obtained from each producer cell line, PA317/LNCX and PA317/LNC/p53, after construction of retroviral vector LNC/p53 containing human p53 cDNA and producer cell line PA 317/ LNC/p53. To investigate the effect of retrovirus-mediated p53 gene transduction in human gastric cancer cell lines, the in vitro growth rates and in vivo tumorigenicities of the N-87 cell line having mutant p53 and the YCC-S-2 cell line having wild-type p53 were compared before and after infection with LNC/p53 retrovirus. RESULTS: The following results were obtained: 1) The growth inhibition of N-87 cells after p53 transduction was signficant when compared to that of the parent N-87 cells. The growth of the p53 transduced YCC-S-2 cells and the parent YCC-S-2 cells was not different. 2) In nude mice, the growth of tumors formed by N-87 cells was modestly inhibited after retrovirus-mediated wild-type p53 gene transduction. However, the growth of tumors formed by YCC-S-2 cells was not inhibited by retrovirus-mediated p53 gene transduction. 3) The expression rate of p53 protein after p53-containing retroviral infection in the KATO-III cell lines, which have no p53 gene, was dose-dependent on the m.o.i. of retrovirus, although it was not more than 15% with the m.o.i. of 100 upon immunohistochemical analysis.
CONCLUSION
The growth inhibition by retrovirus-mediated p53 transduction in human gastric cancer cells was significant in a gastric cancer cell line having mutant p53 in vitro, and the growth of tumor masses formed by a gastric cancer cell line having mutant p53 was modestly inhibited after p53 transduction using retroviral vector in nude mice, although it was not statistically significant. Only modest inhibition of tumor growth using retrovirus-mediated p53 gene transduction in vivo is most likely to be due to low transduction efficiency.

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Effects of Interleukin-2 Transduction into the Human Hepatoma Cell Lines Using Retroviral Vector: Soo Jung Gong, Nae Chun Yoo, Joo Hang Kim, Dong Hwan Shin, Hyo Dong Uhm, Sook Jung Jeong, Jae Yong Cho, Sun Young Rha, Yeon Soo Kim, Hyun Cheol Chung, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(4):555-564.

Abstract PDF: PURPOSE
We compared the differences between parent hepatoma cell lines and interleukin-2 (IL-2) transduced hepatoma cell lines using N2A/IL-2 and LNC/IL-2 retrovirus with regards to in vitro sensitivity to peripheral blood monocytes and in vivo tumorigenic activity.
MATERIALS AND METHODS
Retroviral vector and producer cell line were constructed and IL-2 gene was transduced into the human hepatoma cell lines (SK-Hep1, Hep-G2, Hep-3B). IL-2 secretion after IL-2 transduction was measured by ELISA. MTT assay for in vitro sensitivity to peripheral blood monocytes was performed and the tumorigenic activity was observed in BALB/c mice and nude mice.
RESULTS
IL-2 secretion was 186 pg/10 degrees C cells/24 hrs in SK-Hep1 cell line and was 147 pg/10 (6) cells/24 hrs in Hep-3B cell line with N2A/IL-2 retroviral vector and was 55,000 pg/10 (6) cells/24 hrs with LNC/IL-2 retroviral vector. In vitro sensitivity to peripheral blood monocytes was increased by 163.8~254% in IL-2 transduced hepatoma cell lines (Hep -3B/N2A/IL-2, Hep-G2/N2A/IL-2) compared to those of the parent cell lines. The tumorigenicity was observed in 1 of 3 BALB/c mice and all 3 nude mice. Simultaneous injection of 1 X 10 (7) cells of the parent cell line (Hep-3B) into the right flank and IL-2 transduced cell line (Hep-3B/LNC/IL-2) into the left flank of the three BALB/c mice and of 5 X 10 (5) cells for the three nude mice resulted in a complete regression of the IL-2 modified tumor cell line (Hep-3B/LNC/IL-2) in 3 weeks and the parent cell line (Hep-3B) in 5 weeks. But, after the injection of 1.5 X 10 (7) cells for other five nude mice, the tumor of the IL-2 transduced hepatoma cell line (Hep-3B/LNC/IL-2) was gradually disappeared, and the tumor of the parent hepatoma cell line (Hep-3B) was initially decreased and then gradually regrew 20 days later.
CONCLUSION
IL-2 transduced hepatoma cell lines secreting IL-2 became more sensitive to peripheral blood monocytes and resulted in the increased antigenicity to the tumors formed by IL-2 transduced hepatoma cell line and parent cell line, and finally resulted in the regression of the tumors in experimental animals.

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A Case of Cryptococcal Meningitis in a Brest Cancer Patient with Liver Metastasis, Suffering from Herpes Zoster: Chul Woo Ahn, Wook Jin Chung, Beom Seok Kim, Se Hang Cho, Sun Young Rha, Hyun Cheol Chung, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim, Hee Jung Kim, Kwang Gil Lee; J Korean Cancer Assoc. 1997;29(3):540-540.

Abstract PDF: Cryptococcosis is a relatively common mycosis of human caused by a worldwide Cryptococcus neoformans. Cryptococcosis occurs more frequently in immuno-compromised hosts such as patients with lymphoma, AIDS, leukemia and other debilitating diseases which manifest a condition of altered cell mediated immunity. Also cancer patients with anticancer chemotherapy are at high risk. Cryptococcosis is primarily a pulmonary disease that remains asymptomatic and unrecognised in most cases. Meningitic and meningoencephalitc forms are more frequently diagnosed because of their striking clinical symptoms.Meningoencephalitis is an uncommon form of cryptoccocosis that often leads to coma and death within a short time, if it is not quickly diagnosed and treated properly. The treatment of choice for the cryptococcosis consists of intravenous amphotericin B and 5-fluorocytocine. We report a case of cryptococcal meningitis in 47-year-old female breast cancer patient with liver metastasis after systemic chemotherapy. She complained headach, fever and diagnosed as cryptococcal meningitis after the India ink smear and culture of CSF. After treated with amphotericin B, her conditions were improved.

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Anti-tumor Effects of Growth Factor Inhibitors and Anti-metastatic Agents in Human Gastric Cancer Cell Lines: Sun Young Rha, Hee Cheol Chung, Soo Jung Gong, Hyun Cheol Chung, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(3):391-403.

Abstract PDF: PURPOSE
For tumor growth, invasion and metastasis, a cascade of linked sequential biological events is essential; overproduction of growth factors, activation of proteolytic enzymes, induction of tumor angiogenesis, and enhanced tumor cell motility and attachment. We tried to test whether the biological therapy against the biological targets can modulate the specific biological characteristics, and furthermore increased anti-tumor effects can be induced when the biological therapy and cytotoxic chemotherapy were combined.
MATERIALS AND METHODS
YCC-1, 2, 3, 7, and AGS human gastric cancer cell lines were used in these studies. Pentosan polysulfate (PPS) as a heparin-binding growth factor (HBGF) inhibitor, Tranexamic acid as a plasmin inhibitor, Adriamycin as a chemotherapeutic agent, were selected. The methods were Northern blot analysis for the detection of Midkine (MK) expression, soft agar assay for autocrine tumorigenicity. The expression of uPA, PAI-1 was determined by ELISA, while the MMPs activities were evaluated by zymography. The effects of each drug on tumorigenicity and tumor cell proliferation were evaluated by soft agar assay and cell proliferation assay, respectively.
RESULTS
YCC-3, 7, AGS cell lines expressed MK mRNA, whereas YCC-1, 2 did not. YCC-2 cell line showed increased expression of uPA and MMP activities. Only MK expressing YCC-3 and 7 cell lines showed the tumorigenicity. PPS suppressed the colony forming activities as much as Adriamycin did (PPS; 8~24%, Adriamycin; 12~40%), but it showed only cytostatic effects in cell proliferation assay (PPS; 60~103%, Adriamycin; 22~97%). When PPS was combined with Adriamycin on the Adriamycin resistant, MK expressing YCC-7 cell line, the growth inhibition rate increased up to 84%, while that of PPS or Adriamycin single treatment was 40%, 22%, respectively (p=0.001).
CONCLUSION
The modulation of specific biological targets can induce the anti-tumor effects. This suggests the possible clinical application of biological therapy in gastric cancer.

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Midkine Gene Expression in Gastric Cancer Tissues: Hyun Joo Kwak, Yong Bae Kim, Byung Soh Min, Ho Young Maeng, Sung Hoon Song, Hye Weon Chung, Tae Soo Kim, Hei Cheol Chung, Sun Young Rha, Hyun Cheol Chung, Sung Hoon Noh, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(2):204-211.

Abstract PDF: PURPOSE
We evaluated the clinical significance of the tumor growth factor, midkine (MK), in paired gastric cancer and normal tissues.
MATERIALS AND METHODS
Twenty paired normal and cancer tissues were tested for MK mRNA expression by Northern blot analysis. Vessel staining was done by immunohistochemical staining using CD-31 monoclonal antibody (Dako).
RESULTS
MK mRNA was mainly expressed in cancer tissues (11 versus 1). Lymph node metastasis, pathological stage and tumor differentiation did not correlate with MK expression. However, MK expression rate increased with increment in tumor size (p=0.05). Microvascular density did not correlate with tumor invasion, lymph node metastasis, and pathological stages. However, there was a tendency of vascular density increment with MK expression in T1-T2 stage.
CONCLUSION
MK was mainly expressed in larger gastric cancer tissues suggesting its role in cancer growth in vivo. But no definite correlation between MK expression and tumor microvascular density was found.

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Synchronous Expression of Circulating Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) During Gastric Cancer Progression: Hei Cheol Chung, Joon Oh Park, Sun Young Rha, Hyun Cheol Chung, Soo Jung Gong, Choong Bae Kim, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Sung Hoon Noh; J Korean Cancer Assoc. 1997;29(1):81-92.

Abstract PDF: PURPOSE
The circulating forms of ICAM-1 (cICAM-1) and VCAM-1 (cVCAM-1) has been reported from supernatant of cytokine activated endothelial cells, cancer cells and from cancer patient serum even though the biological significance of the cCAMs are not fully elucidated.
MATERIALS AND METHODS
To evaluate the correlation of the expression of cICAM-1 and cVCAM-1 and prognosis in gastric cancer, we measured cICAM-1 and cVCAM-1 levels in 20 healthy volunteers and 142 gastric cancer patients' sera by ELISA assay. Also we compared cCAMs levels with vascular endothelial growth factor (sVEGF) and FP. Ninety-five patients were operable and 47 patients were advanced or relapsed state at the time of the study. In 28 operable patients, we simultaneously sampled portal and peripheral vein and measured the cCAMs.
RESULTS
The cCAMs level and positive rate in serum increased with cancer progression from healthy control, operable to advanced or relapsed gastric cancer. In advanced cancer, cICAM-1 level increased with liver metastasis. The cICAM-1 level in portal blood was correlated modestly with that in peripheral blood. And in cVCAM-1 positive subgroup, cCAM-1 level correlated with cVCAM-1 level. The peripheral cICAM-1 level decreased in 6% compared to that of portal cICAM-1 level while peripheral cVCAM-1 level increased in 1% compared to that of portal level. Synchronous expression of both cCAMs was found in 58.3% of the patients with liver metastasis and 22.9% of the patients without liver metastasis (p=0.03). But, there were no correlation between cCAMs and FP expression regardless of liver metastasis. The sVEGF level correlated with neither cICAM-1 nor cVCAM-1 level regardless of liver metastasis. The median disease-free and overall survival of patients with synchronous cICAM-1 and cVCAM-1 expression was 8 months and 9 months, while in patients without co-expression it was more than 24 months and 23 months respectively.
CONCLUSION
We suggest that synchronous cICAM-1 and cVCAM-1 elevation may be a useful monitor of tumor burden and progression in gastric cancer, especially in liver metastasis.

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Evaluation of Biologic Phenotype by Midkine Gene Expression in Gastric Cancer as a Target for Biotherapy: Hyun Cheol Chung, Sun Young Rha, Hei Cheol Chung, Hyun Joo Kwak, Jae Yong Cho, Soo Jung Gong, Sung Hoon Noh, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1997;29(1):69-80.

Abstract PDF: PURPOSE
We studied biological phenotypes of gastric cancer cell lines based on a novel heparin-binding growth/differentiation factor, midkine (MK) expression.
MATERIALS AND METHODS
Nine gastric cancer cell lines and 25 gastric cancer tissues were tested for MK expression by Northern blot analysis. Soft agar assay for in vitro tumorigenesis, cross- feeding assay for paracrine angiogenic activity, ELISA for uPA and PAI-1 measurement were performed.
RESULTS
MK expression was found in 67% (6/9) of the gastric cancer cell lines, and 56% (14/25) of the primary gastric cancer tissues. Gastric cancer cell lines with MK expression were more tumorigenic in soft agar assay and endothelial cell growth stimulatory in cross-feeding assay than cells which did not express MK. However, urokinase-type plasminogen activator (uPA) expression did not correlate with MK expression. Growth of MK expressing cells was inhibited by a heparin-binding blocking agent, pentosan polysulfate (PPS). In cancer tissues, MK expression correlated with tumor size, suggesting in vivo autocrine and paracrine activity.
CONCLUSION
Gastric cancer cells with increased MK gene expression showed increased tumorigenic and angiogenic activity. Therefore, this proliferation promoting activity of MK can be targeted by an anti-heparin binding agent as a biotherapy model in gastric cancer treatment.

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A Phase 1 Clinical Trial and Pharmacokinetic Evaluation of DA-125 ( A Novel Anthracycline Derivative ) in Advanced Carcer Patients: Jae Kyung Roh, Sun Young Rha, Jong In Lee, Kyung Hee Lee, Joon Oh Park, Jae Yong Cho, Nae Chun Yoo, Hyun Cheol chung, Joo Hang Kim, Jin Sik Min, Byung Soo Kim, Myung Geol Lee, Won Bae Kim, Joong Ik Y; J Korean Cancer Assoc. 1996;28(6):961-973.

Abstract PDF: Background
DA-125 {(7-0-12.6-dioxy-2-fluoro-2-L-talopyranosyl)- adriamycinone-14-b-alaninate HC1}, is a novel water soluble derivative of fluorinated doxorubicin. Our previous studies showed that DA-125 is more stable and effective than doxorubicin, especially to doxorubicin resistant tumor cell lines in vitro and in vivo. We initiated phase I clinical trial to evaluate the toxicities and the pharmacokinetics of DA-l25 in advanced cancer patients. Method: Advanced cancer patients who were refractory to the standard treatment with normal hepatic and renal functions were eligible after informed consent. Drug was administered intravenously for 5 minutes with initial starting dose of 20 mg/§³(10% of murine LD10). For each dose level, 3 patients were enrolled and the next increased dose was administered if there were no toxicities greater than WHO grade III. Blood, urine and bile (if possible) were collected for the pharmacokinetic evaluation. Result: Twenty three patients were enrolled with 22 evaluable patients (3 at 20 mg/§³, 3 at 40 mg/§³, 3 at 60 mg/§³, 6 at 80 mg/§³ and 7 at 100 mg/§³ of DA-125). All treated patients did not suffer from life-threatening side effects. Hematologic alterations especially neutropenia were major toxicities. Up to 60 mg/§³ dose, toxicities greater than WHO grade II were not observed. At 80 mg/§³ dose, one heavily pretreated patient developed grade III neutropenia. At 100 mg/§³ dose, one patient developed grade IV thrombocytopenia without evidence of clinical bleeding and 2 patients showed grade III neutropenia Grade I and II nausea and vomiting were observed at 80 mg/§³ and 100 mg/§³ dose level. Cardiac toxicities did not occur in any patient. DA-125 was rapidly hydralized to Ml(active metabolite), after IV administration. The plasma half life of M1 was 1.1~2.6 hours and that of M2 was 7.8~9.4 hours. The AUC of both metabolites were dose dependent(Ml: 0.154~0.638ug.hr/ml, M2: 0.684~3.07 ug.hr;ml). Urinary excretion of Ml wss less than 1% of administered dose until 96 hours and that of M2 was 10~22%. In one patient with periampullary cancer, 52.3% of the metabolites were excreted through bile. Conclusion: The results of the present study demonstrated that DA-125 was well tolerable to the advanced cancer patients and 100 mg/§³ was considered as maximally tolerated dose. We are planning the phase II trial on the basis of these results.

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Effect of Combined Modality Treatment and Clinical Significance of P-Glycoprotein Overexpression in Patients with Osteosarcoma: Yong Seok Yun, Jae Kyung Roh, Hyun Cheol Chung, Jae Yong Cho, Kyoo Ho Shin, Soo Bong Han, Beom Seok Kim, Joon Oh Park, Soo Jung Gong, Sun Young Rha, Nae Choon Yoo, Joo Hang Kim, Jin Sik Min, Byung So; J Korean Cancer Assoc. 1996;28(6):1104-1117.

Abstract PDF: Osteosarcoma is a highly malignant bone tumor and usually encountered in the first three decades of life. The Prognosis of osteasarcoma treated with surgery alone had been poor, with 20% of the patients surviving 5 years. The addition of adjuvant chemotherapy after surgery has siginificantly improved the outcome of osteosarcoma. The new concept of pre-operative chemotherapy has permitted histological assessment of treatment effect and limb salvage procedures. As the role of chemotherapy has been raised, the resistance of tumors to multiple drugs, such as p-glycoprotein overexpression, has become a major problem in the treatment of osteosarcoma. We retrospectively reviewed the clinical records of 53 patients with stage IIB osteosarcoma who were treated at Yonsei Medical Center and Yonsei Cancer Center between March 1, 1986 and June 30, 1996. The purpose of this study was to assess the efficacy and toxicity of cisplatin(IA)-adriamycin(IV) combination pre-operative chemotherapy and the clinical significance of p-glycoprotein status and histologic response as prognostic factors. Among 53 patients, 33 were male and 20 were female with a median age of 21 years(range: 5~61). The tumor locations were as follows: distal femur 24(45.3%), proximal tibia 17(32.1%), humerus 7(13.2%), proximal femur 3(5.4%), fibular 1(1.9%), radius 1(1.9%). Histologic subclassifications were as follows: osteoblastic type 42(78.2%), telangiectatic type 4(7.5%), chondrablastic type 3(5.7%), fibroblastic type 2(3.8%) and undetermined 2(2.8%). The three year overall survival and disease-free survival rates were 66.1% and 61.9% respectively in all patients. Thirty-two patients were treated by pre-operative cisplatin(IA)-adriamycin(IV) combination chemotherapy and 21 patients were taken only post-operative adjuvant chemotherapy. No significant difference was found between the two groups in probability of survival and recurrence rates. The histological response ta pre-operative chemotherapy was scored by degree of tumor necrosis. Twenty-two patients had a good response [grade IV, 13(40.6%);grade III, 8(25.0%)] and 11 patients had a poor response [grade II, 6(18.8%);grade I, 5(15.6%)]. The histological response was not significantly related to the probability of the survival rate. However, the recurrence rate was higher in the poor-response group(p=0.04). Overexpression of p-glycoprotein was found in tumors from 11 of l8 patients(61.1%) who were given only post-operative adjuvant chemotherapy. No relation was found between the p-glycoprotein expression and survival rate. The degree of tumor necrosis after pre-operative chemotherapy and initial serum alkaline-phosphatase level were considered as prognositic factors. Other clinicopathologic features including age, gender, anatomical site, histological subclassification,operation types,tumor size.p-glycoprotein expression were not associate with patient outcome. Treatment-related side effects were relatively tolerable and reversible by conservative treatment. Pre-operative cisplatin(IA)-adriamycin(IV) combination chemotherapy in our study did not show improved survival than conventional post-operative chemotherapy with limited follow-up duration. The degree of histologic response after chemotherapy and the initial alkaline phosphatase level were found to be the major predictor for tumor recurrences, while p-glycoprotein overexpression did not alter the clinical outcome. Further studies are warranted to improve the efficacy of adjuvant chemotherapy and to evaluate the significance of multiple resistance gene overexpression in osteosarcoma.

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Expression of Urokinase - type Plasminogen Activator a New Biologic Marker of the Invasion and Metastasis in Gastric Cancer: Sung Hoon Noh, Jae Yong Cho, Sun Young Rha, Hyun Cheol Chung, Joon Oh Park, Chong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Jin Sup Choi, Jin Sik Min, Byung Soo Kim; J Korean Cancer Assoc. 1996;28(2):198-207.

Abstract PDF: Mortality in gastric cancer is related to invasion and metastasis. Evidence has accumulated that invasion and rnetastasis in solid tumors require the action of tumor associated proteases, which promotes the dissolution of the surrounding tumor matrix and the basement membrane. The serine protease urokinase-type plasminogen activator(uPA), which is elevated in solid tumors, appears to play a key role in these processes. We used enzymelinked immunoabsorbent assays(ELISA) to test uPA antigen expression in tissue extracts of normal and cancer tissue of 160 gastric cancer patients. uPA level was significantly higher in cancerous tissue than normal gastric tissue(9.4 vs 5.3 ng/mg protein cytosol: p<0.001). When the uPA level was correlated to other prognostic parameters, uPA positivity is associated with grade of anaplasia(p=0.005). Univariate analysis showed that a uPA positivity is significantly associated with short. disease-free survival(p=0.005). Multivariate analysis with known prognostic parameters revealed that the uPA positivity was an independent prognostic parameter for short disease-free survival. These data indicate that uPA is a potentially important prognostic factor in gastric cancer. Consequently, we suggest that modulation of uPA is needed to prevent invasion and metastasis in gastric cancer patients.

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Expression of Matrix-metalloproteinase- 9 ( MMP- 9 ) in Breast Cancer: Sun Young Rha, Se Joong Kim, Hyun Cheol Chung, Joo Hang Kim, Jae Kyung Roh, Kyung Shik Lee, Byung Soo Kim; J Korean Cancer Assoc. 1996;28(2):247-253.

Abstract PDF: The degradation of the basement membrane by matrix-metalloproteinase(MMP) and serine protease is a critical point in tumor invasion and metastasis. We measured the activity of MMP-9 from 28 normal, 12 benign, and 126 breast cancer tissues using gelatin zymography with an image analysis system. Inactive MMP-9 was expressed in 17.5% of the cancer patients compared to 2.5% in 40 non-cancerous tissues(p=0.008). The active form of MMP-9(82kD) was expressed only in T2-T4 stages. During the early phase of breast cancer (DCIS and Tl stage) progression, only the production of inactive MMP-9 was increased. However, as the cancer grew or invaded skin(T2-T4), or with lymphovascular permeation, both production and activation of MMP-9 were increased. In conclusion, MMP-9 productian was the main cause of increased MMP-9 activity during the ear1y phase, while both production and activation were increased in the late phase of breast cancer.

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Expression and Clinical Relevance of c-erbB-3 in Rectal Cancer: Chong In Lee, Sun Young Rha, Jin Oh Park, Hyun Cheol Chung, Jae Yong Cho, Joong Bae Ahn, Nae Choon Yoon, Tae Soo Kim, Joo Hang Kim, Jae Kyung Roh, Jin Sup Choi, Jin Sik Min, Byung Soo Kim, Woo Ick Ja; J Korean Cancer Assoc. 1996;28(1):50-63.

Abstract PDF: Recently, there is an increasing tendency of colorectal cancer in Korea, probably due to changes of diet pattern to western style. In rectal cancer, as the local recurrence is a common and major problem despite of radical resection, it is recommended to use 5-fluorouracil(5-FU)- based chemotherapy in combination with pelvic radiation after radical operation in MAC B,-C, cancers. But until now, there are many controversies about the effective chemotherapeutic agent, radiation dose, route, and chemoradiation schedule. There is increasing evidence that genes involved in normal cell growth and differentiation(oncogenes) or genes that encode for growth factor are important in determining the development and biologic aggressiveness of various cancers. Among many oncogenes thought to be related with cancer, c-erbB-2 is a relatively well known protein to be associated with cancers, especially in breast and colorectal cancers. In addition to c-erbB-2 and Epidermal Growth Factor Receptor(EGFR), c-erbB-3 belongs to Type -I Growth Factor Receptor Family(EGFR-related Family) and is the most recently identified protein in EGFR-related Family. There have been a few reports about the prognostic value of c-erbB-3 in breast and prostate cancers. In this study we performed immunohistochemical staining of 114 surgically resected specimens of rectal cancers to investigate the expression rate and clinical relevance of c-erbB-3 as a prognostic factor and drug selection marker. c-erbB-3 expression rate was 46% in 114 rectal cancers and there were significant differences in recurrence rate and survival rate between c- erbB-3 positive and negative group. Twenty-one cases(40%) recurred in 52 c-erbB-3 positive cases and 10 cases(16%) recurred in 62 c-erbB-3 negative cases(p=0.004). The difference in recurrence rate between c-erbB-3 positive and negative group was significant exclusively in MAC stage C(p=0.0126), but not in MAC stage B(p=0.4357). In c-erbB-3 positive and negative group, 2-year disease free survival rate was 66% and 87%, respectively(p=0.0052), and 2-year overall survival rate was 84% and 95%, respectively(p=0.005). Again, the difference in 2-year disease free survival rate between the two groups was significant only in MAC stage C(p=0. 0137), not in stage B(p=0.4182). There were no significant differences in recurrence rate and 2- year disease free survival rate in chemo-radiation group regardless of c-erbB-3 expression and stage. But in adjuvant radiotherapy alone group, increased recurrence rate and decreased survival rate were found in c-erbB-3 positive group. This finding suggested c-erbB-3 as a possible relative radioresistance marker, in whom a higher radiotherapy dose is needed. In conclusion, c-erbB-3 may be regared as a prognostic marker and as a possible indicator of radioresistance in the treatment of rectal cancer.

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Expression in Matrix - Metalloproteinases ( MMP-2 , MMP-9 ) in Gastric Cancer as new Targets for Biotherapy: Hyun Cheol Chung, Jae Yong cho, Sun Young Rha, Joon Oh Park, Joong Bae Ahn, Choong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Sung Hoon Noh, Jin Sik Min, Byung Soo Kim, Ho Yeong Lim, Jin Hyu Choi; J Korean Cancer Assoc. 1995;27(6):897-907.

Abstract PDF: The proteolytic processes are thought to be the critical point in tumor invasion and metastasis, mainly by matrix-metalloproteinases (MMPs) and serine proteases. We measured the activities of MMP-9 and MMP-2 in the 120 normal and cancer tissue samples from the same patients using gelatin zymography. Inactive MMP-9(92 kD) was expressed in 73.3% of the normal and 87.5% of the cancer tissues, respectively (p=0.009), while active MMP-9(82 kD) was expressed in 24.2% and 53.3%, respectively (p=0.0001). Inactive MMP-2 (72kD) was expressed in 33.3% of the normal and 55.0% of the cancer tissues, respectively (p=0.001), while active MMP-2(62kD) was expressed in 4.2% and 31.7%, respectively (p=0.0001). In Tl state, only frequency of expression and enzymatic activity of the active MMP-2(62kD) were increased, while from T2 stage, the expression and the activation of the both MMP-9 and MMP-2 were increased as the cancer progressed. The expression frequency of the MMP-9 was more common than of the MMP-2. The co-expression rate of the active forms (82 kD, 62 kD), activites of 82 kD and 62 kD, and the activation rates of the both MMPs were increased as the cancer invades and metastasizes to distant lymph node areas. In conclusion, MMP-2 activation was the main causes of the increased MMPs activity during the Tl phase of the gastric cancer, while production and activation of the both MMP-9 and MMP-2 were increased as the cancer progressed. Therefore, we suggest that the different expression and activation of the MMPs in the gastric cancer progression can be a potential therapeutic target in gastric cancer biotherapy.

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A Comparative Study of Intravenous granistron Versus Intravenous / Oral Ondansetron in the Prevention of Nausea and Vomiting Associated with Moderately: Joon Oh Park, Hyun Cheol Chung, Yong Seok Yoon, Woong Chol Kang, Sang Hak Lee, Heui Cheul Chung, Jae Yong Cho, Sun Young Rha, Chong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, By; J Korean Cancer Assoc. 1995;27(6):1048-1061.

Abstract PDF: Nausea and vomiting are common and the most distressing side effects of cancer chemotherapy. As these symtoms can cause emotional instability and malnutrion from poor oral intake, which further lead to decrease the effect of chemotherapy, it is important to prevent emesis adequately and effectively. Ondansetron is a selective 5-HT, receptor antagonist and is reported to be effective in preventing cisplatin-induced emesis, Granisetron is a potent and the most selective 5-HT, receptor antagonist currently available. We conducted a prospective, randomized, open, single center, parallel group study to compare the antiemetic effect and safety of granisetron versus ondansetron in patients receiving moderately emetogenic chemotherapy. Form December l994 to May 1995, 65 consecutive patients who planned to receive moderately emetogenic chemotherapy(80 to 100 mg/§³ of cisplatin or 40 mg/§³of doxorubicin) were enrolled in this study. Granisetron was administered intravenously prior to chemotherapy at a dose of 3mg, and up to two doses of granisetron could be administered as rescue therapy within the first 24 hour period. Ondansetron 8 mg was given intravenously prior to chemotherapy followed by 2 more doses at 8 and 16 hours after chemotherapy. Finally, we evaluated 63 patients(32 receiving granisetron and 31 receiving ondansetron). In the first 24 hours after chemotherapy, complete and major response were achieved in 78.1 % of patients receiving granisetron and 74.2 % of patients receiving ondansetron(P=0.7163). There were also no differences in the control of delayed nausea and vomiting between two groups(56.3% vs 45.2%, P=0.3826). There were no differences in percentages of patients who received rescue therapy across the treatment groups: 3I.5% for granisetron vs. 45.2% for ondansetron during the study(P=0.3803). During the first 24 hours following chemotherapy, there were no differences in time to first episodes of nausea(granisetron 14 hours 20 minutes vs ondansetron 13 hours) and vomiting(granisetron 20 hours vs ondansetron 19 hours 20 minutes) between two groups. There were no significant adverse effects or toxicities with these antiemetics. We concluded that single dose granisetron was as effective in prophylaxis of emesis induced by moderatly emetogenic chemotherapy as triple doses of ondansetron and oral maintainence combination. For the non-responders to granisetron, combination of granisetron with other antiemetics of different action mechanism or maintainence granisetron trials are warranted.

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A Phase 3 Clinical Trial of Recombinant Human Granulocyte - Macrophage Colony Stimulating: Kyung Hee Lee, Sun Young Rha, Jae Kyung Roh, Jong In Lee, Hae Ran Lee, Jun Oh Park, Jae Woong Cho, Hyun Cheol Chung, Joo Hang Kim, Jee Sook Hahn, Yun Woong Ko, Byung Soo Kim, Ho Young Lim, Jin Hyuk Choi; J Korean Cancer Assoc. 1995;27(5):804-816.

Abstract PDF: Background
Recombinant human granulocyte-macrophage colony stimulating factor(rhGM- CSF, LBD-005) may reduce chemotherapy induced myelosuppression, and thus reduce the incidence of neutropenic fever and infection after the dose intensive chemotherapy. In previous phase I and II studies, clinical efficacies and side effects of rhGM-CSF were evaluated, and the dose of 250ug/m(2)/day for 10 consecutive days subcutaneous administration was recommended for the further clinical triaL Methods: In this phase III trial, we evaluated the efficacy and safety of rhGM-CSF in 35 advanced cancer pstients after combination chemotherapy. Every eligible patients received at least 2 cycles of chemotherapy with the same dose and schedule. At the first cycle, control period, scheduled chemotherapy was given without rhGM-CSF, and at the second cycle, treatment period, rhGM-CSF was administered for 10 consecutive days subcutaneously with the dose of 250u/m(2)/day after the same chemotherapy given previously. During observation and treatment period, clinical and pathoiogical effects were monitered. Resnlta: All enrolled 35 patients were evaluable, and 14 patients(40%) had stomach cancer. The hematologic parameters were compared between two periods; mean nadir of WBC(neutrophil) counts during the control period and treatment period were 1,154+-485/mm(3)(241/mm(3)+ 242) and 2,486+1,554/mm(3)(912+-1,186/mm(3)) respectively(P<0.0001). Also the recovery time of neutropenia was shortened(P<0.0001). Incidence of infection and the necessities of antibiotics administration were decreased(days of antibiotics adminiatration: 7 days during control period and 10 days during treatment period). Most petients showed mild, talerable toxicities like chest tightness and general malaise, except 2 patients with the reduced dose of 150 ug/m(2)/day due to grade II toxicities of chest tightness and abdominal pain. Conclnsion: Above results suggested that the administration of rhGM-CSF after chemotherapy can reduce the degree of neutropenia and the side effects of rhGM-CSF were acceptable.

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Expression and Significance of c-erbB-2 in Radically Resected Colorectal Cancer: Hyun Cheol Chung, Sun Young Rha, Joon Oh Park, Seung Hun Song, Jae Yong Cho, Jung Bae Aha, Hye Ran Lee, Chong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Jin Sil Seong, Gwi Eon Kim, Jin Sik M; J Korean Cancer Assoc. 1995;27(3):389-403.

Abstract PDF: Overexpression of c-erbB-2 oncoprotein has been shown to correlate with poor prognosis and drug-resistance to the conventional chemotherapy with 5-fluorouracil in breast and gastric cancers. To evaluate the clinical significance of c-erbB-2 overexpreseion in colorectal cancer, immunohistochemical staining was performed with the paraffin-embedded tiasues of 141 colorectal cancer patients with curative surgery. The follow-up duration ranged from 7 to 61 months(median 30 months). Two-year disease- free and overall survival rate of the total patients were 77%, 91%, respectively. The c-erbB-2 positive rate was 24.8%, Even if patients with c-erbB-2 overexpression showed a tendency of poor prognosis than c-erbB-2 negative patients, T-factor and the TNM stage were independent prognostic factors in multivariate analysis. In subset analysis with c-erbB-2 negative patienta, there were no differences in recurrence rate and 2-year disease-free survival rate between pa- tients with chemotherapy and without chemotherapy(20.0% versus 26.1%)(80.0% versus 82.0%). However, in c-erbB-2 positive patients, those subgroup with chemotherapy showed tendencies toward advantages in relapse rate and 2-year disease-free survival rate than those of subgroup without chemotherapy(21.0% versus 50.0%; p=0.09)(76.0% versus 50.0%: p=0.06). Also, there was a tendency of increased time to relapse in patients with chemotherapy comparing to that of the patients without chemotherapy(7.5 months versus l7.0 months; p = 0.09). In stage III, patients with c-erbB-2 overexpression showed increased 2-year disease-free survival rate with chemotherapy as comparing to that of patients without chemotherapy(81.0% versus 29.0%; p= 0.003). Again, this survival benefit was not found in c-erbB-2 negative stage III patients regard- less of chemotherapy. In conclusion, c-erbB-2 overexyression might be a marker of relative drug resistance to 5-FU which will be converted with the high dose treatment of modulation with leucovorin. A prospective randomized trial is warrented to confirm this suggestion and for the clinical applica- tion of c-erbB-2 overexpression.

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A Phase 2 Clinical Trial of Recombinant Human Granulocyte Macrophage Colony Stimulatin: Sun Young Rha, Jae Kyung Roh, Kyung Hee Lee, Hyun Cheol Chung, Jong Inn Lee, Jin Hyuk Choi, Hye Ran Lee, Nae Chun Yoo, Joo Hang Kim, Dae Seog Heo, Jin Hyuk Choi, Ho Yeong Lim, Jee Sook Hahn, Byung So; J Korean Cancer Assoc. 1995;27(3):490-504.

Abstract PDF: Background
; Rh GM-CSF is known to stimulate the growth of granulocyte-macrophage pre- cursors and can prevent the neutropenia and infection after high dose chemotherapy. We planned to evaluate the efficacy and toxicities of rh GM-CSF and to determine the clinically recommended dose of yeast-derived rh GM-CSF(LBD-005), based on the biologicaily active doses from phase I clinical triaL Methods; Open non-randomized phase II study was carried out in 40 cancer patients with chemotherapy induced myelosuppression. After the control period(chemotherapy without rh GM-CSF), rh GM-CSF was started 24 hours after the second chemotherapy to 3 groups of patients with the doses of 150, 250, 350 ug/m(2)/d by once-daily subcutaneous admlnistration for 10 days. Resnlts; Of the 40 enrolled patients, two patients refused to be followed and. one patient couldn't finish the study due to the disease progression. So 37 patients were evaluable and the number of patients at the dose of 150, 250, 350 pg/m/d were 12, 12 and 13 petients, respectively. They were consisted of 12 with stomach cancers, 10 with breast cancers, 5 with osteosarcoma and 10 patients with other malignancies, and received chemotherapeutic agents like VP-16, cisplatinum, adriamycin. When we compared the hematologic parameters between the control and treatment periods, the mean nadir of WBC counts(/mm(3)) at the dose of 150ug/m(2)/d were 1480, 2085, each, l280, l997 at the dose of 250 ug/m/d, and 1091, 1788 at the dose of 350 ug/m(2)/d respectively. Also the recovery days of WBC counts from nadir to 4000/m(3) were improved from 8 days in control period to 4.7 days in treatment period at the dose of 150 ug/m(2)/d. There were the same results at the dose of 250 and 350 ug/m(2)/d, such as from 7.4 days to 4.4 days and from 8.5 days to 5.2 days, respectively. In view of neutrophils, we could find the same results(p<0.05). There are trends that the recovery from nadir at the dose of 250 ug/m(2)/d or more is rapid, rather than l50ug/m(2)/d. Two patients with 350ug/m(2)/d complained of severe (WHO toxicity grade III) skin reaction and chest tightness, but they tolerated well after reduction to 250 ug/m(2) /d dose. Conclasion; This study suggested the effects of yeast-derived rh GM-CSF with the dose of 1SO, 250, 350ug/m(2)/d, S.Q. for 10 days to prvent the chemotherapy induced neutropenia. And when we considered the efficacy and tolerability, 250 ug/m(2)/d is appropriate for phase III clinical triaL

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A Retrospective Comparison of Infusional 5-Fluorouracil , Doxorubicin , Mitomycin - C ( Modified FAM ) Combination Chemotherapy Versus Palliative Therapy in: Joon Oh Park, Jae Kyung Roh, Hyun Cheol Chung, Hyun Jin Noh, Jae Yong Cho, Sun Young Rha, Chong In Lee, Cheol Woo Kim, Joo Hang Kim, Choong Bai Kim, Sung Hoon Noh, Kyong Sik Lee, Jin Sik Min, Byung S; J Korean Cancer Assoc. 1995;27(2):165-175.

Abstract PDF: In Korea, gastric cancer is the most common cancer and the leading cause of cancer death. About one-third of the patients with gastric cancer is unresectable at the time of diagnosis. Their median survival is less than 6 months with very poor prognosis. Accordingly, various regimens of chemotherapy have been proposed as intensive treatment for unresectable patients. After MacDonald et aL reported 42% response rate and 9 months response duration using combination of 5-Fluorouracil, Doxorubicin and Mitomycin-CFAM), it became the most widely used regimen in the treatment of advanced gastric cancer. However, despite of high initial response rate, there was no survival benefit in randomised comparative trials. To increase the drug effect, we modified the standard FAM regimen by continuously infusing the 5- Fluorouracil instead of bolus injection(modified FAM). We retrospectively reviewed the clinical recoreds of 409 patients with histologically proven advanced gastric cancer in Yonsei University Medical Center and Yonsei Cencer Center between Jan. 1, 1991 and Dec. 31, 1993. The purpose of this study is to assess the efficacy of infusional FAM combination chemotherapy compared with other palliative therapy in advanced gastric cancer. Among 409 patients, 266 were male and 143 were female with a median age of 57-year(range: 15~75). There were 202 patients in mFAM-treated group and 207 patients in control group. In mFAM-treated group, 140 patients had no surgery, 30 patients underwent a palliative bypass and 32 patients underwent a palliative resection. In control group, 151 patients had no surgery, 33 patients underwent a palliative bypass and 23 patients underwent a palliative resection. In preoperative staging, 257 patients had locally advanced disease, 48 had carcinomatosis and 104 had distant metastasis. There was no difference of distribution in age, sex, perfomance status, preoperative stege and treatment modalities between mFAM-treated and control group. 1) Among 154 of evaluable patients, no CRs were observed. PR were seen in 17.5% of patients in mFAM-treated group. The median response duration was 30 weeks and progression free survival was 23 weeks. 2) Higher 1-year survival rate was demonstrated in mFAM-treated group comparing to control group(34.1% vs 22.5)(p=0.0135). 3) Median survival was longer in mFAM-treated group than that of control group(40 week vs 28 week). 4) The toxicities were relatively tolerable and reversible. This results proposed that the infusional FAM combination chemotherapy showed a probalbility of survival pralongation, especially combined with palliative surgery in advanced gastric cancer. Further prospective randomized study will be warranted.

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Detection of Soluble c-erbB-2 Oncoproteins in the Serum of Gastric Cnacer patients as a Tumor Marker: Hyung Cheol Chung, Joong Bae Ahn, Joon Oh Park, Jae Yong Cho, Sun Young Rha, Chong In Lee, Hye Ran Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Sung Hoon Noh, Jin Sik Min, Byung Soo Kim, Ho Yeon; J Korean Cancer Assoc. 1995;27(2):175-184.

Abstract PDF: A soluble fragment of the c-erbB-2 oncoprotein become detectable in the serum of the breast cancer petients by enzyme-linked immunosorbent assay(ELISA). To evaluate the clinical sig- nificance of soluble c-erbB-2 in gastric cancer, we measured the serum levels in 45 normal healthy persons and in 86 gastric cancer patients. Fifty-five patients were underwent surgery(47 curative surgery, 8 palliative surgery) and thirty-one patients were inoperable(18 advanced, 8 relapsed, 6 progressed after palliative surgery). The c-erbB-2 serum levels were below 14 U/ml in normal persons. Three of 86(3.5%) sam- ples from gastric cancer patients had elevated serum c-erbB-2 leveL In 55 operated patients, all serum samples were negative for c-erbB-2. Elevated serum levels were predominantly found in patients with initially advanced cancers(3/18: 16.7%). In 22 operated cases, immunohisto- chemical staining showed 36.4% c-erbB-2 positive ratio(8/22) in tissues. Comparing the results from sera and tissues studies, the sensitivity of serum ELISA assay was too low even if the specificity was high. Our data suggest that the soluble c-erbB-2 oncoprotein can be a tumor marker only in advanced stage of gastric cancer. Further studies are warrented to elucidate the discrepancy between the serum and tissue results in oprable early stage gastric cancer.

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Prognostic Factors in Node - Negative Breast Cancer: Kyung Hee Lee, Hyun Cheol Chung, Jae Yong Cho, Sun Young Rha, Joong Bae Ahn, Chong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim, Kyung Sik Lee, Kyl Beom Lee, Ho Yeong Lim, Jin Hy; J Korean Cancer Assoc. 1995;27(2):265-275.

Abstract PDF: Breast cancer is the third most common malignant neoplasm in Korean women. The effect of postoperative adjuvant systemic therapy in the treatment of primary breast cancer with pathologic involvement of the axillary lymph nodes has been well established. But, 20 30% of node-negative breast cancer patients will develop recurrent disease and risk death within 10 years after initial local therapy without adjuvant treatment. Therfore, it is reasonable to identify those node-negative breast cancer patients at significant risk for recurrence and who could be treated with adjuvant therapies. A clinical study was perofrmed in 184 cases of primary node-negative breast cancers from January 198l to December 1991 to study the natural course of the diaease and to find-out the prognostic factors. The following results were obtained; l) During 73 monthe(9-143) of follow-up duration, 5-year and 10-year relapse free survival rates were 88%, 77% respectively, and overall survival rates were 89%, 88%, respectively. 10 year recurrence rate was 19%. 2) Median disease-free and survival durations were 80 month, 17 months, respectively, in tumor size<2 cm group and 68.5 months, 62 months respectively in tumor size 2-5 cm group. 3) Median disease-free and overall survival durations were 73 months, 61 months, respectively, in premenopause patients and 74 months, 73 months in postmenopause patients. 4) No differences were found in disease-free and survival duration based on types of operation. 5) With adjuvant treatment, there was a decreasing tendency of systemic relapse. In conclusion, continuous relapse was found in node-negative breast cancer even after 5 years of operation. Even if decreasing tendency of systemic relapse was induced with adjuvant treatment, no clinically useful prognostic factors were found from surgical and pathologic factors until now. Further study of biological factors in node-negative breast cancer is warrented.

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Phase 1b Clinical Trial and Pharmacokinetic Evaluation of Recombinant Human Granulocyte - Macrophage Colony: Jae Kyung Roh, Jin Hyuk Choi, Hyung Keun Roh, Sun Young Rha, Kyung Hee Lee, Hye Ran Lee, Jee Sook Hahn, Pum Soo Kim, Byung Soo Kim; J Korean Cancer Assoc. 1994;26(3):495-510.

Abstract PDF: To define the clinical safeties and hematologic effects of subcutaneously administered yeast- derived recombinant human granulocyte-macrophage colony stimulatina factor(rh GM-CSF, LBD-005h and to determine the maximally tolerated dose(MTD) and the pharmacokinetics. Sngle arm open non-randomized phase Ib study was carried in 15 cancer patients#(14 patients evaluable) with chemotherapy induced bone marrow depression. Rh GM-CSF by once-daily subcutaneous administration to groups of 3-6 patients at doses of 50, 100, 150, 250, 350, 500, 700 ug/m/d for 10 consecutive days was escalated unless greater than WHO grade III toxicites were observed. Intrapatient dose escalation was permitted. Clinical safeties and toxicities were observed with frequent hematologic monitering. Blood and urine were collected on day 1, and 8 of rh GM-CSF administration to evaluate the parmacokinetic parameters. Of the 15 enrolled patients, 14 patients were evaluable. Male to female ratio was 8: 6 with median age 32 y-o(10~70 y-o). Seven patients had osteosarcoma, 2 malignant lymphoma, 2 gastric carcinoma, 2 lung cancer and 1 had uterine leiomyosarcoma. The total administered cycles of rh GM-CSF were 24. At each dose step, 3 patients were treated with exception of 6 patients at 500 ug/m/d dose. At all the doses administered, fever and flue-like syndrome were common side effects. Grade I fever and flue-like syndrome 50~150 pg/m dose, and grade II fever flue- like syndrome were observed at the dose of grater than 250 u/m(2)/d dose. Even at the 700 ug/m(2)/ d dose, no greater than grade III toxicities were observed. Leucocytosis were dose dependent with 120-480% increment of baseline. Pharmacokinetic parameters are as follows; Cmax were dose dependent(0.42-11.7 ng/ml) with 2-4 hours of Tmax. AUC were also dose dependent(3.93~87.9ng.hr/ml) with sustained serum levels(0.2-2ng/ml) up to 12 hours after rh GM-CSF administration. Urinary excretion(0-24 hours) after GM-CSF was less than 1% of administered dose. Yeast-derived rh GM-CSF induces leucocytosis in the dose range of 150~500ug/m(2)/d with tolerable side effects. Subcutaneously administered rh GM-CSF has sustained serum levels up to 12 hours after administration. The doses of 150-500 ug/m/d would be appropriated for the further trials.

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Induction Chemotherapy and Surgery in Locally Advanced Stomach Cancer Showing Pancreas Involvement: Kyung Hee Lee, Jin Hyuk Choi, Sun Young Rha, Hye Ran Lee, Nae Chun Yoo, Ho Yeong Lim, Hyun Cheol Chung, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim; J Korean Cancer Assoc. 1994;26(3):377-385.

Abstract PDF: Gastric cancer is the most common malignancy in Korea. Cure for patients with gastric carcinoma can be achieved only by radical surgery. From August 1988 to May 1992, 25 patients with locally advanced unresectable gastric cancer received 5-FU(Fiuorouracil) + adriamydn + mitomycin-c or 5-FU + cisplatin based induction chemotherapy before surgem. The partial response rate after me- dian 3 cycles of induction cemotherapy was 52%, stable disease 12%, progressive disease 36%. Gastric resection was performed in 18 patients(72%); 13 patients(52%) underwent radical surgery and 5 patients(20%) underwent palliative surgery. Median survival of the patients who underwent cura- tive and palliative surgery was 24. 2 and 27 months, respectively. However, median survival of the patient who didnt undergo any surgery was only 6.5 months. The difference of median survival between curative surgery and none surgery group were significant statistically(P<0.03). Side effects of induction chemotherapy were acceptable and there were no life threatening toxicities In this study, half of the patients can undergo curative surgery after induction chemotherapy. We observe the long term survival in some patients after induction chemotherapy and surgery in loco-regionally advanced gsstric cancer. This therapeutic approch for the locally advanced stomach cancer seems to be feasible. But, prospective tandomized clinical trial is warranted in the future.

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Predictive Value of the nProfiler 1 Assay for the Efficacy of Adjuvant S-1-Based Doublet Chemotherapy in Stage III Gastric Cancer: A Post-Hoc Analysis of a Randomized Phase III Trial: Dong Ki Lee, Choong-kun Lee, Hyo Song Kim, Sun Jin Sym, Dae Young Zang, Ki Hyang Kim, Joo Han Lim, Hae Su Kim, Kyung Hee Lee, Heon Yung Gee, Sun Young Rha, Hyunki Kim, Minkyu Jung; Received July 25, 2024 Accepted November 9, 2024 Published online November 12, 2024; DOI: https://doi.org/10.4143/crt.2024.705 [Accepted]

Abstract PDF: Purpose
The nProfiler 1 Stomach Cancer Assay (nProfiler1), designed to predict responses to fluorouracil-based adjuvant chemotherapy, measures the expression of four gastric cancer target genes (GZMB, WARS, SFRP4, and CDX1). The randomized phase III POST trial aimed to compare the efficacies of two adjuvant S-1-based doublet chemotherapies: S-1 plus cisplatin (SP) and S-1 plus docetaxel (DS). This study aimed to validate the nProfiler1 assay using a distinct cohort from the POST trial.
Materials and Methods
The nProfiler1 assay stratifies patients into three groups (low-risk, intermediate-risk, and high-risk) using the prognostic single-patient classifier and two groups (chemotherapy-benefit and no-benefit) using the predictive single-patient classifier. The nProfiler1 assay was applied to formalin-fixed paraffin-embedded slides obtained from the POST trial. Disease-free survival (DFS) and overall survival (OS), including 5-year survival rates, were calculated for the enrolled patients.
Results
Of the 153 patients in the POST trial, 118 were included in the post-hoc analysis. With a median follow-up of 57.9 months, no significant difference in DFS or OS was observed between the SP and DS groups. The prognostic single-patient classifier predicted the OS in the SP group (p=0.0425) but not in the DS group (p=0.5940). The chemotherapy-benefit group exhibited numerically longer DFS than the no-benefit group in the SP and DS groups.
Conclusion
The nProfiler1 assay offers valuable insights into the prognosis and efficacy of adjuvant chemotherapy based on fluorouracil plus platinum doublet regimens but not docetaxel-containing regimens. Further validation with larger patient cohorts and different regimens is warranted.

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Psychometric Validation of Sheffield Profile for Assessment and Referral to Care (SPARC) in Korean Cancer Patients: Hong Jun Kim, Eun Hee Jung, Jung Hye Kwon, Yu Jung Kim, Su-Jin Koh, Myung Ah Lee, Jung Hun Kang, Sun Young Rha, Eun Mi Nam, Sun Kyung Baek, Ha Yeon Lee, Hun Ho Song, Young-Woong Won, Hanbyul Lee; Received July 26, 2024 Accepted December 4, 2024 Published online December 5, 2024; DOI: https://doi.org/10.4143/crt.2024.706 [Accepted]

Abstract PDF: Purpose
Identifying the palliative care needs of patients with advanced cancer is important for maintaining quality of life and timely transition to palliative care. We aimed to validate the Korean Sheffield Profile for Assessment and Referral for Care (K-SPARC) in such patients and establish its psychometric properties, including reliability, validity, and responsiveness to change.
Materials and Methods
We used the forward-back translated version of SPARC, which was verified through a pilot study, to assess the palliative care needs of patients with advanced cancer. Reliability was evaluated by internal consistency using Cronbach's alpha coefficients and test-retest reliability. Criterion validity was analyzed against other questionnaires, including the Korean versions of the Functional Assessment of Cancer Therapy-General (FACT-G Korean) and Korean versions of the Edmonton Symptom Assessment System (K-ESAS). Factor analysis was used to assess construct validity.
Results
Two hundred fifty-nine patients were included from 2019 to 2022. Forty-nine percent of all patients were women, and the median age was 63 years. Cronbach’s alpha coefficient (range, 0.642–0.903) and test-retest reliability (range, 0.574–0.749) indicated acceptable reliability. The correlation coefficients between K-SPARC and FACT-G Korean suggested significant criterion validity. The correlation coefficients for the physical, social, emotional, and functional domains were 0.701, 0.249, 0.718, and 0.511, respectively (p-value <0.001, all). Factor analysis demonstrated satisfactory construct validity of the tool.
Conclusion
This study demonstrated the utility of K-SPARC as an evaluation tool for providing palliative care to patients with advanced cancer through psychometric validation; the tool had good internal consistency, reliability, and acceptable validity.

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Identifying Trends in Oncology Research through a Bibliographic Analysis of Cancer Research and Treatment: Choong-kun Lee, Jeong Min Choo, Yong Chan Ahn, Jin Kim, Sun Young Rha, Chai Hong Rim, On behalf of the 50th anniversary of the Korean Cancer Association Committing Board; Received July 22, 2024 Accepted December 4, 2024 Published online December 5, 2024; DOI: https://doi.org/10.4143/crt.2024.688 [Accepted]

Abstract PDF: During the celebration of the 50th anniversary of the founding of the Korean Cancer Association, articles published in Cancer Research and Treatment from 2004 to 2023 were assessed based on the subject and design of each study. Based on this analysis, trends in domestic cancer research were inferred and directions were suggested for the future development of Cancer Research and Treatment.

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