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Jae Kyung Roh 91 Articles
Symposium: “Oncology Leadership in Asia”
Dong-Young Noh, Jae Kyung Roh, Yeul Hong Kim, Kazuhiro Yoshida, Hideo Baba, Marie Cherry Lynn Samson-Fernando, Sanjeev Misra, Zeba Aziz, Rainy Umbas, Yogendra P. Singh, Tony Shu Kam Mok, Han-Kwang Yang, Hideyuki Akaza
Cancer Res Treat. 2017;49(2):283-291.   Published online March 9, 2017
DOI: https://doi.org/10.4143/crt.2017.090
AbstractAbstract PDFPubReaderePub
The symposium on “Oncology Leadership in Asia” was held as part of the official program of the 42nd Annual Meeting of the Korean Cancer Association with International Cancer Conference. Given the increasing incidence of cancer in all countries and regions of Asia, regardless of developmental stage, and also in light of the recognized need for Asian countries to enhance collaboration in cancer prevention, research, treatment and follow-up, the symposium was held with the aim of bringing together oncology specialists from eight countries and regions in Asia to present the status in their own national context and discuss the key challenges and requirements in order to establish a greater Asian presence in the area of cancer control and research. The task of bringing together diverse countries and regions is made all the more urgent in that while Asia now accounts for more than half of all new cancer cases globally, clinical guidelines are based predominantly on practices adopted in Western countries, which may not be optimized for unique ethnic, pharmacogenomic and cultural characteristics in Asia. Recognizing the need for Asia to better gather information and data for the compilation of Asia-specific clinical guidelines, the participants discussed the current status in Asia in the national and regional contexts and identified future steps towards integrated and collaborative initiatives in Asia. A key outcome of the symposium was a proposal to combine and integrate the activities of existing pan-Asian societies, including the Asian Pacific Federation of Organizations for Cancer Research and Control (APFOCC) and Asian Clinical Oncology Society (ACOS). Further proposals included the expansion of pan-Asian society membership to include individuals and the essential need to encourage the participation of young researchers in order to ensure self-sustainability of cancer control efforts in the future.

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Citations to this article as recorded by  
  • The levels, prevalence and related factors of compassion fatigue among oncology nurses: a systematic review and meta‐analysis
    Wanqing Xie, Jialin Wang, Yonggang Zhang, Min Zuo, Hua Kang, Ping Tang, Li Zeng, Man Jin, Wanying Ni, Chun Ma
    Journal of Clinical Nursing.2021; 30(5-6): 615.     CrossRef
  • A Novel Prediction Model for Bloodstream Infections in Hepatobiliary–Pancreatic Surgery Patients
    Po‐Sheng Yang, Chang‐Pan Liu, Yi‐Chiung Hsu, Chuen‐Fei Chen, Chi‐Chan Lee, Shih‐Ping Cheng
    World Journal of Surgery.2019; 43(5): 1294.     CrossRef
  • Global Survey of Clinical Oncology Workforce
    Aju Mathew
    Journal of Global Oncology.2018; (4): 1.     CrossRef
  • 8,580 View
  • 173 Download
  • 3 Web of Science
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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
AbstractAbstract PDFPubReaderePub
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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  • Prediction of Response to Anti-Angiogenic Treatment for Advanced Colorectal Cancer Patients: From Biological Factors to Functional Imaging
    Giuseppe Corrias, Eleonora Lai, Pina Ziranu, Stefano Mariani, Clelia Donisi, Nicole Liscia, Giorgio Saba, Andrea Pretta, Mara Persano, Daniela Fanni, Dario Spanu, Francesca Balconi, Francesco Loi, Simona Deidda, Angelo Restivo, Valeria Pusceddu, Marco Puz
    Cancers.2024; 16(7): 1364.     CrossRef
  • Alteration in DNA methylation patterns: Epigenetic signatures in gastrointestinal cancers
    Zahra Heydari, Farideh Moeinvaziri, Seyed Mohammad Ali Mirazimi, Fatemeh Dashti, Olga Smirnova, Anastasia Shpichka, Hamed Mirzaei, Peter Timashev, Massoud Vosough
    European Journal of Pharmacology.2024; 973: 176563.     CrossRef
  • Chromatin factors: Ready to roll as biomarkers in metastatic colorectal cancer?
    Cristina Moreta-Moraleda, Cristina Queralt, Carla Vendrell-Ayats, Sonia Forcales, Eva Martínez-Balibrea
    Pharmacological Research.2023; 196: 106924.     CrossRef
  • A 10-gene-methylation-based signature for prognosis prediction of colorectal cancer
    Dong-hai Li, Xiao-hui Du, Ming Liu, Rui Zhang
    Cancer Genetics.2021; 252-253: 80.     CrossRef
  • Value of methylation markers in colorectal cancer (Review)
    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
    Scientific Reports.2020;[Epub]     CrossRef
  • Methylation-Based Therapies for Colorectal Cancer
    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
    F1000Research.2018; 7: 1528.     CrossRef
  • Clinical and prognosis value of the CIMP status combined with MLH1 or p16 INK4a methylation in colorectal cancer
    Amana Saadallah-Kallel, Rania Abdelmaksoud-Dammak, Mouna Triki, Slim Charfi, Abdelmajid Khabir, Tahia Sallemi-Boudawara, Raja Mokdad-Gargouri
    Medical Oncology.2017;[Epub]     CrossRef
  • DNA methylation of CMTM3 , SSTR2 , and MDFI genes in colorectal cancer
    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
  • 12,467 View
  • 110 Download
  • 12 Web of Science
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Novel Methods for Clinical Risk Stratification in Patients with Colorectal Liver Metastases
Ki-Yeol Kim, Nam Kyu Kim, In-Ho Cha, Joong Bae Ahn, Jin Sub Choi, Gi-Hong Choi, Joon Suk Lim, Kang Young Lee, Seung Hyuk Baik, Byung Soh Min, Hyuk Hur, Jae Kyung Roh, Sang Joon Shin
Cancer Res Treat. 2015;47(2):242-250.   Published online September 11, 2014
DOI: https://doi.org/10.4143/crt.2014.066
AbstractAbstract PDFPubReaderePub
Purpose
Colorectal cancer patients with liver-confined metastases are classified as stage IV, but their prognoses can differ from metastases at other sites. In this study, we suggest a novel method for risk stratification using clinically effective factors. Materials and Methods Data on 566 consecutive patients with colorectal liver metastasis (CLM) between 1989 and 2010 were analyzed. This analysis was based on principal component analysis (PCA). Results The survival rate was affected by carcinoembryonic antigen (CEA) level (p < 0.001; risk ratio, 1.90), distribution of liver metastasis (p=0.014; risk ratio, 1.46), and disease-free interval (DFI; p < 0.001; risk ratio, 1.98). When patients were divided into three groups according to PCA score using significantly affected factors, they showed significantly different survival patterns (p < 0.001). Conclusion The PCA scoring system based on CEA level, distribution of liver metastasis, and DFI may be useful for preoperatively determining prognoses in order to assist in clinical decisionmaking and designing future clinical trials for CLM treatment.

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  • Differential Perspectives by Specialty on Oligometastatic Colorectal Cancer: A Korean Oligometastasis Working Group’s Comparative Survey Study
    Won Kyung Cho, Gyu Sang Yoo, Chai Hong Rim, Jae-Uk Jeong, Eui Kyu Chie, Yong Chan Ahn, Hyeon-Min Cho, Jun Won Um, Yang-Gun Suh, Ah Ram Chang, Jong Hoon Lee
    Cancer Research and Treatment.2023; 55(4): 1281.     CrossRef
  • Long disease-free interval diminishes the prognostic value of primary tumor stage for patients with colorectal cancer liver metastases
    Jia-Ming Liu, Yan-Yan Wang, Wei Liu, Da Xu, Kun Wang, Bao-Cai Xing
    HPB.2022; 24(5): 737.     CrossRef
  • A Randomized Phase II Study of Perioperative Chemotherapy Plus Bevacizumab Versus Postoperative Chemotherapy Plus Bevacizumab in Patients With Upfront Resectable Hepatic Colorectal Metastases
    You Jin Chun, Seong-Geun Kim, Keun-Wook Lee, Sang Hee Cho, Tae Won Kim, Ji Yeon Baek, Young Suk Park, Soojung Hong, Chong Woo Chu, Seung-Hoon Beom, Minkyu Jung, Sang Joon Shin, Joong Bae Ahn
    Clinical Colorectal Cancer.2020; 19(3): e140.     CrossRef
  • Preclinical Efficacy of [V4 Q5 ]dDAVP, a Second Generation Vasopressin Analog, on Metastatic Spread and Tumor-Associated Angiogenesis in Colorectal Cancer
    Juan Garona, Natasha T. Sobol, Marina Pifano, Valeria I. Segatori, Daniel E. Gomez, Giselle V. Ripoll, Daniel F. Alonso
    Cancer Research and Treatment.2019; 51(2): 438.     CrossRef
  • A multi-gene expression profile panel for predicting liver metastasis: An algorithmic approach
    Kanisha Shah, Shanaya Patel, Sheefa Mirza, Rakesh M. Rawal, Kapil Mehta
    PLOS ONE.2018; 13(11): e0206400.     CrossRef
  • A combined prognostic factor for improved risk stratification of patients with oral cancer
    K‐Y Kim, X Zhang, S‐M Kim, B‐D Lee, I‐H Cha
    Oral Diseases.2017; 23(1): 91.     CrossRef
  • 11,188 View
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  • 7 Web of Science
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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
AbstractAbstract PDFPubReaderePub
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.

Citations

Citations to this article as recorded by  
  • 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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  • 68 Download
  • 14 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
AbstractAbstract PDFPubReaderePub
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.

Citations

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  • Metachronous or Synchronous Presentation of Acute Myeloid Leukemia and Lung Cancer: A Single Center Experience
    Başak Ünver Koluman, Atike Gökçen Demiray, Gulsum Akgun Cagliyan, Sibel Hacıoğlu, Nil Güler, Taner Durak, Yeliz Karakaya, Ferda Bir
    Akdeniz Medical Journal.2024;[Epub]     CrossRef
  • A Disguising Fast-Growing Metachronous Melanoma and COVID-19
    Alina Avram, Lucian G Scurtu, Mariana Costache, Olga Simionescu
    Cureus.2023;[Epub]     CrossRef
  • Solitary solutions to a metastasis model represented by two systems of coupled Riccati equations
    I. Timofejeva, T. Telksnys, Z. Navickas, R. Marcinkevicius, R. Mickevicius, M. Ragulskis
    Journal of King Saud University - Science.2023; 35(5): 102682.     CrossRef
  • Triple synchronous malignancies of the stomach, bladder and thyroid in a previously treated prostate cancer patient: A Case Report
    Oliver Oey, Siaw Sze Tiong, Sze Ling Wong, Suresh Navadgi, Yasir Khan
    Folia Medica.2023; 65(4): 693.     CrossRef
  • Features of synchronous and metachronous dual primary gastric and colorectal cancer
    Yi-Jia Lin, Hua-Xian Chen, Feng-Xiang Zhang, Xian-Sheng Hu, Hai-Juan Huang, Jian-Hua Lu, Ye-Zi Cheng, Jun-Sheng Peng, Lei Lian
    World Journal of Gastrointestinal Oncology.2023; 15(11): 1864.     CrossRef
  • Definitions and treatment of oligometastatic oesophagogastric cancer according to multidisciplinary tumour boards in Europe
    Tiuri E. Kroese, Richard van Hillegersberg, Sebastian Schoppmann, Pieter R.A.J. Deseyne, Philippe Nafteux, Radka Obermannova, Marianne Nordsmark, Per Pfeiffer, Maria A. Hawkins, Elizabeth Smyth, Sheraz Markar, George B. Hanna, Edward Cheong, Asif Chaudry,
    European Journal of Cancer.2022; 164: 18.     CrossRef
  • Stereotactic radiotherapy or metastasectomy for oligometastatic esophagogastric cancer: A nationwide population-based cohort study
    Tiuri E. Kroese, Nikita K.N. Jorritsma, Hanneke W.M. van Laarhoven, Rob H.A. Verhoeven, Stella Mook, Nadia Haj Mohammad, Jelle P. Ruurda, Peter S.N. van Rossum, Richard van Hillegersberg
    Clinical and Translational Radiation Oncology.2022; 37: 109.     CrossRef
  • Simultaneous triple primary malignancies, including bladder cancer, lymphoma, and lung cancer, in an elderly male: A case report
    Risheng Huang, Zhijia Li, Shanshan Weng, Shenghao Wu
    Open Life Sciences.2022; 17(1): 1263.     CrossRef
  • A Case Report of Mesothelioma Response to Endocrine Therapy in Synchronous Breast Cancer and Pleural Epithelioid Mesothelioma: A Double Exemestane Effect
    Marta Pina, Rute Fernandes, Diogo Fonseca, Cristina Oliveira, Ana Rodrigues
    Cureus.2022;[Epub]     CrossRef
  • Management of patients with synchronous head-and-neck and lung cancers
    Nicolas Paleiron, Radj Gervais, Gaelle Rousseau-Bussac, Laurence Bigay Game, Anne Marie Chiappa, Regine Lamy, Florian Guisier, Hervé Le Caer, Gilles Robinet, Acya Bizieux, Christos Chouaïd
    Journal of Cancer Research and Therapeutics.2022; 18(Suppl 2): S160.     CrossRef
  • Multiple primary malignancies involving lung cancer: a single-center experience
    Luigi Ventura, Paolo Carbognani, Letizia Gnetti, Maurizio Rossi, Marcello Tiseo, Enrico Maria Silini, Nicola Sverzellati, Mario Silva, Marcello Succi, Cesare Braggio, Sara Cattadori, Giovanni Bocchialini, Valeria Balestra, Michele Rusca, Luca Ampollini
    Tumori Journal.2021; 107(3): 196.     CrossRef
  • A Case Series of Multiple Primary Malignancies Among Patients With Advanced Melanoma
    Matthew I Ebia, Stephen Capone, Charité Ricker, Jacob S Thomas, Varsha Tulpule, Irene Kang, Anishka D'Souza, David R Freyer, Kimberly Miller, Gino K In
    Cureus.2021;[Epub]     CrossRef
  • A Rare Case of Synchronous Esophageal and Pancreatic Malignancy
    Ali Khalifa, Arkady Broder
    Cureus.2021;[Epub]     CrossRef
  • Efficacy and Safety of Local Radiotherapy to All Oligometastatic Sites in Elderly Patients with Metachronous Oligometastatic Cancers After Initial Treatment for the Primary Tumor
    Xiaolong Hu, Hongqi Li, Xiaoli Kang, Xuan Wang, Haifeng Pang, Chen Liu, Jianchun Zhang, Yingjie Wang
    Cancer Management and Research.2021; Volume 13: 9247.     CrossRef
  • Synergistic Effect of Lymphatic Invasion and Venous Invasion on the Risk of Lymph Node Metastasis in Patients with Non-Curative Endoscopic Resection of Early Gastric Cancer
    Hye Jin Kang, Hyunsoo Chung, Sang Gyun Kim, Jung Kim, Jue Lie Kim, Eunwoo Lee, Hyun Chae Jung
    Journal of Gastrointestinal Surgery.2020; 24(7): 1499.     CrossRef
  • Clear cell renal carcinoma synchronous with dedifferentiated liposarcoma: a case report and review of the literature
    Estefania Beltran, Juan Esteban Garcia-Robledo, Lisa X. Rodríguez-Rojas, Martin Rengifo, Bladimir Perez, Harry Pachajoa, Angela R. Zambrano
    Journal of Medical Case Reports.2020;[Epub]     CrossRef
  • Characterisation and classification of oligometastatic disease: a European Society for Radiotherapy and Oncology and European Organisation for Research and Treatment of Cancer consensus recommendation
    Matthias Guckenberger, Yolande Lievens, Angelique B Bouma, Laurence Collette, Andre Dekker, Nandita M deSouza, Anne-Marie C Dingemans, Beatrice Fournier, Coen Hurkmans, Frédéric E Lecouvet, Icro Meattini, Alejandra Méndez Romero, Umberto Ricardi, Nicola S
    The Lancet Oncology.2020; 21(1): e18.     CrossRef
  • Rare heterochronous liver and pancreatic multiple primary cancers: a case report and literature review
    Wangjun Zhang, Fan Xiao, Jie Li, Xiaoyu Guo, Zhitao Lin, Zijian Huang, Ning Mao, Bei Sun, Gang Wang
    Zeitschrift für Gastroenterologie.2020; 58(11): 1094.     CrossRef
  • Gastric carcinoma and renal cell carcinoma as an atypical presentation of multiple primary malignancies: a case report and review of the literature
    J. A. Martín-Pérez, C. Torres-Silva, R. Tenorio-Arguelles, D. A. García-Corona, S. Silva-González, J. A. Dominguez-Rodriguez, I. De Alba-Cruz, J. F. Nagore-Ancona, J. A. González-Luna, K. A. López-Bochm
    Journal of Medical Case Reports.2020;[Epub]     CrossRef
  • Helicobacter pylori Eradication for Metachronous Gastric Cancer: An Unsuitable Methodology Impeding Broader Clinical Usage
    Alexios-Fotios A. Mentis, Efthimios Dardiotis
    Frontiers in Oncology.2019;[Epub]     CrossRef
  • A case report of cholangiocarcinoma combined with moderately differentiated gastric adenocarcinoma
    Yan-Hui Yang, Qing Deng, Tian-Bao Yang, Yang Gui, Yu-xiang Zhang, Jiang-Bo Liu, Qian Deng, Wei-Feng Liu, Jun-Jun Sun
    Medicine.2019; 98(30): e16332.     CrossRef
  • Management and Follow-up of Patients with a Bronchial Neuroendocrine Tumor in the Last Twenty Years in Ireland: Expected Inconsistencies and Unexpected Discoveries
    Asta Agasarova, Clare Harnett, Niall Mulligan, Muhammad Shakeel Majeed, Alberto Caimo, Gianluca Tamagno
    International Journal of Endocrinology.2018; 2018: 1.     CrossRef
  • Clinicopathologic characteristics and survival rate in patients with synchronous or metachronous double primary colorectal and gastric cancer
    Ji-Hyeon Park, Jeong-Heum Baek, Jun-Young Yang, Won-Suk Lee, Woon-Kee Lee
    Korean Journal of Clinical Oncology.2018; 14(2): 83.     CrossRef
  • Synchronous primary of periampullary and lung cancer: A case report and review of literature
    Vikas Talreja, Vanita Noronha, Amit Joshi, Vijay Patil, Kumar Prabhash
    Cancer Research, Statistics, and Treatment.2018; 1(2): 173.     CrossRef
  • Synchronous occurrence of hereditary gastric adenocarcinoma, gastrointestinal stromal tumor, and esophageal small cell and squamous carcinoma in situ: an extremely rare case report
    Huijie Fan, Pei Lu, Li Xu, Yanru Qin, Jing Li
    BMC Cancer.2017;[Epub]     CrossRef
  • Multiple primary malignancies involving lung cancer
    Feng Li, Wen-Zhao Zhong, Fei-Yu Niu, Ning Zhao, Jin-Ji Yang, Hong-Hong Yan, Yi-Long Wu
    BMC Cancer.2015;[Epub]     CrossRef
  • Limitations of PET and PET/CT in detecting upper gastrointestinal synchronous cancer in patients with head and neck carcinoma
    Kenichiro Yabuki, Akira Kubota, Choichi Horiuchi, Takahide Taguchi, Goshi Nishimura, Masahiko Inamori
    European Archives of Oto-Rhino-Laryngology.2013; 270(2): 727.     CrossRef
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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
AbstractAbstract PDFPubReaderePub
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.

Citations

Citations to this article as recorded by  
  • Osteosarcoma-Specific Genes as a Diagnostic Tool and Clinical Predictor of Tumor Progression
    Pattaralawan Sittiju, Parunya Chaiyawat, Dumnoensun Pruksakorn, Jeerawan Klangjorhor, Weerinrada Wongrin, Phichayut Phinyo, Rawikant Kamolphiwong, Areerak Phanphaisarn, Pimpisa Teeyakasem, Prachya Kongtawelert, Peraphan Pothacharoen
    Biology.2022; 11(5): 698.     CrossRef
  • Ezrin gone rogue in cancer progression and metastasis: An enticing therapeutic target
    Ganesh Kumar Barik, Osheen Sahay, Debasish Paul, Manas Kumar Santra
    Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2022; 1877(4): 188753.     CrossRef
  • Mass Spectrometric-Based Proteomics for Biomarker Discovery in Osteosarcoma: Current Status and Future Direction
    Nutnicha Sirikaew, Dumnoensun Pruksakorn, Parunya Chaiyawat, Somchai Chutipongtanate
    International Journal of Molecular Sciences.2022; 23(17): 9741.     CrossRef
  • Ezrin is a prognostic biomarker in patients with clear cell metastatic renal cell carcinoma receiving sunitinib
    Bulent Cetin, Ipek Isik Gonul, Ozge Gumusay, Baris Afsar, Irem Bilgetekin, Ahmet Ozet, Aytug Uner
    Journal of Cancer Research and Therapeutics.2021; 17(2): 408.     CrossRef
  • High expression of EZR (ezrin) gene is correlated with the poor overall survival of breast cancer patients
    Rongju Zhang, Shaohui Zhang, Rongge Xing, Qin Zhang
    Thoracic Cancer.2019; 10(10): 1953.     CrossRef
  • The clinical prognostic significance of ezrin in patients with bone and soft tissue sarcomas: a meta‐analysis
    Feng Wang, Tao Yu, Chengbin Ma, Haifei Zhang, Zhiyu Zhang
    FEBS Open Bio.2019; 9(10): 1744.     CrossRef
  • Re-calculating! Navigating through the osteosarcoma treatment roadblock
    J. McGuire, T.J. Utset-Ward, D.R. Reed, C.C. Lynch
    Pharmacological Research.2017; 117: 54.     CrossRef
  • Correlation of Ezrin Expression Pattern and Clinical Outcomes in Ewing Sarcoma
    Thomas Cash, Hong Yin, Courtney McCracken, Zhi Geng, Steven G. DuBois, Bahig M. Shehata, Thomas A. Olson, Howard M. Katzenstein, Cynthia Wetmore
    Sarcoma.2017; 2017: 1.     CrossRef
  • Differentially activated Src kinase in chemo‐naïve human primary osteosarcoma cells and effects of a Src kinase inhibitor
    Marcella Laschi, Giulia Bernardini, Michela Geminiani, Fabrizio Manetti, Mattia Mori, Adriano Spreafico, Domenico Campanacci, Rodolfo Capanna, Silvia Schenone, Maurizio Botta, Annalisa Santucci
    BioFactors.2017; 43(6): 801.     CrossRef
  • The Prognostic Role of Ezrin and HER2/neu Expression in Osteosarcoma
    Asmaa G. Abdou, Mona Kandil, Nancy Y. Asaad, Marwa M. Dawoud, Ahmed A. Shahin, Amal F. Abd Eldayem
    Applied Immunohistochemistry & Molecular Morphology.2016; 24(5): 355.     CrossRef
  • Establishment of Four New Human Primary Cell Cultures from Chemo‐Naïve Italian Osteosarcoma Patients
    Marcella Laschi, Giulia Bernardini, Michela Geminiani, Lorenzo Ghezzi, Loredana Amato, Daniela Braconi, Lia Millucci, Bruno Frediani, Adriano Spreafico, Alessandro Franchi, Domenico Campanacci, Rodolfo Capanna, Annalisa Santucci
    Journal of Cellular Physiology.2015; 230(11): 2718.     CrossRef
  • Prognostic Significance of Serum Alkaline Phosphatase Level in Osteosarcoma: A Meta-Analysis of Published Data
    Hai-Yong Ren, Ling-Ling Sun, Heng-Yuan Li, Zhao-Ming Ye
    BioMed Research International.2015; 2015: 1.     CrossRef
  • Prognostic Value of Ezrin in Various Cancers: A Systematic Review and Updated Meta-analysis
    Jianwei Li, Kuanhai Wei, Hailang Yu, Dan Jin, Gang Wang, Bin Yu
    Scientific Reports.2015;[Epub]     CrossRef
  • Alteration of WWOX in human cancer, a clinical view
    Izabela Baryła, Ewa Styczeń-Binkowska, Andrzej K Bednarek
    Experimental Biology and Medicine.2015; 240(3): 305.     CrossRef
  • The prognostic value of elevated ezrin in patients with osteosarcoma
    Deng-Xing Lun, Yong-Cheng Hu, Zhao-Wan Xu, Li-Na Xu, Bin-Wu Wang
    Tumor Biology.2014; 35(2): 1263.     CrossRef
  • Prognostic role of cytovillin expression in patients with osteosarcoma: a meta-analysis
    Shibing Guo, Rui Bai, Wei Zhao, Yuxin Wang, Zhenqun Zhao, Wei Feng
    Tumor Biology.2014; 35(1): 469.     CrossRef
  • CD99 suppresses osteosarcoma cell migration through inhibition of ROCK2 activity
    C Zucchini, M C Manara, R S Pinca, P De Sanctis, C Guerzoni, M Sciandra, P-L Lollini, G Cenacchi, P Picci, L Valvassori, K Scotlandi
    Oncogene.2014; 33(15): 1912.     CrossRef
  • Correlations of Ezrin Expression with Pathological Characteristics and Prognosis of Osteosarcoma: A Meta-Analysis
    Da-Hang Zhao, Jiang Zhu, Wen-Bo Wang, Feng Dong, Qiao Zhang, Hong-Wu Fan, Jing-Zhe Zhang, Yong-Ming Wang
    The Scientific World Journal.2014; 2014: 1.     CrossRef
  • Expression of HMGA1 and Ezrin in laryngeal squamous cell carcinoma
    De-Sheng Wang, Chun-Chen Pan, Hai-Chun Lai, Jian-Min Huang
    Acta Oto-Laryngologica.2013; 133(6): 626.     CrossRef
  • The β5/focal adhesion kinase/glycogen synthase kinase 3β integrin pathway in high-grade osteosarcoma: a protein expression profile predictive of response to neoadjuvant chemotherapy
    Sophie Le Guellec, Elizabeth Cohen-Jonathan Moyal, Thomas Filleron, Marie-Bernadette Delisle, Christine Chevreau, Hervé Rubie, Marie-Pierre Castex, Jerome Sales de Gauzy, Paul Bonnevialle, Anne Gomez-Brouchet
    Human Pathology.2013; 44(10): 2149.     CrossRef
  • Meta-analysis of Associations of the Ezrin Gene with Human Osteosarcoma Response to Chemotherapy and Prognosis
    Zhe Wang, Mao-Lin He, Jin-Min Zhao, Hai-Hui Qing, Yang Wu
    Asian Pacific Journal of Cancer Prevention.2013; 14(5): 2753.     CrossRef
  • The Prognostic Role of Ezrin Immunoexpression in Osteosarcoma: A Meta-Analysis of Published Data
    Hongtao Li, Daliu Min, Hui Zhao, Zhiyu Wang, Weixiang Qi, Shuier Zheng, Lina Tang, Aina He, Yuanjue Sun, Yang Yao, Zan Shen, David Loeb
    PLoS ONE.2013; 8(6): e64513.     CrossRef
  • Effects of siRNA-mediated Cdc2 silencing on MG63 cell proliferation and apoptosis
    XIANG-YONG QUE, YI LI, YU HAN, XIN-ZHI LI
    Molecular Medicine Reports.2013; 7(2): 466.     CrossRef
  • Clinicopathologic Implication of Ezrin Expression in Non-small Cell Lung Cancer
    Ho Won Lee, Eui Han Kim, Mee-Hye Oh
    Korean Journal of Pathology.2012; 46(5): 470.     CrossRef
  • Effects of transplantation sites on tumour growth, pulmonary metastasis and ezrin expression of canine osteosarcoma cell lines in nude mice
    T. Jaroensong, Y. Endo, S.‐J. Lee, A. Kamida, M. Mochizuki, R. Nishimura, N. Sasaki, T. Nakagawa
    Veterinary and Comparative Oncology.2012; 10(4): 274.     CrossRef
  • Prognostic implication of ezrin expression in esophageal squamous cell carcinoma
    Jian‐Jun Xie, Li‐Yan Xu, Zhi‐Yong Wu, Qing Zhao, Xiu‐E Xu, Jian‐Yi Wu, Qiao Huang, En‐Min Li
    Journal of Surgical Oncology.2011; 104(5): 538.     CrossRef
  • Identification of the VIL2 enhancer in human embryonic kidney cells
    Shu‐Ying Gao, Yan‐Peng Dai, Xia Long, Fang‐Ting Zhang, Jie Yu
    Cell Biology International.2011; 35(10): 967.     CrossRef
  • Rôle du pathologiste dans la prise en charge des tumeurs osseuses primitives malignes : ostéosarcomes et tumeurs de la famille Ewing après traitement néoadjuvant
    Anne Gomez-Brouchet, Corinne Bouvier, Anne-Valérie Decouvelaere, Frédérique Larousserie, Sébastien Aubert, Xavier Leroy, Jean-Marc Guinebretière, Aurore Coulomb, Elisabeth Cassagnau, Anne de Muret, Virginie Audard, Béatrice Marie, Gonzague de Pinieux
    Annales de Pathologie.2011; 31(6): 455.     CrossRef
  • Potential transcriptional regulatory regions exist upstream of the human ezrin gene promoter in esophageal carcinoma cells
    S. Gao, Y. Dai, M. Yin, J. Ye, G. Li, J. Yu
    Acta Biochimica et Biophysica Sinica.2011; 43(6): 455.     CrossRef
  • YY1 overexpression is associated with poor prognosis and metastasis-free survival in patients suffering osteosarcoma
    Filomena de Nigris, Licciana Zanella, Francesco Cacciatore, Anna De Chiara, Flavio Fazioli, Gennaro Chiappetta, Gaetano Apice, Teresa Infante, Mario Monaco, Raffaele Rossiello, Gaetano De Rosa, Marco Alberghini, Claudio Napoli
    BMC Cancer.2011;[Epub]     CrossRef
  • 17β-Estradiol Enhances Breast Cancer Cell Motility and Invasion via Extra-Nuclear Activation of Actin-Binding Protein Ezrin
    Shuhui Zheng, Jinghe Huang, Kewen Zhou, Chengxi Zhang, Qiuling Xiang, Zhi Tan, Tinghuai Wang, Xiaodong Fu, Jean-Marc Vanacker
    PLoS ONE.2011; 6(7): e22439.     CrossRef
  • Ezrin expression predicts local recurrence and development of metastases in soft tissue sarcomas
    Ana Carneiro, Pär-Ola Bendahl, Måns Åkerman, Henryk A Domanski, Anders Rydholm, Jacob Engellau, Mef Nilbert
    Journal of Clinical Pathology.2011; 64(8): 689.     CrossRef
  • Immunoexpression of Ezrin and CD44 in Patients With Osteosarcoma
    Erica Boldrini, Stela Verzinhasse Peres, Sandra Morini, Beatriz de Camargo
    Journal of Pediatric Hematology/Oncology.2010; 32(6): e213.     CrossRef
  • Prognostic and predictive biomarkers of canine osteosarcoma
    Gayathri Thevi Selvarajah, Jolle Kirpensteijn
    The Veterinary Journal.2010; 185(1): 28.     CrossRef
  • 11,145 View
  • 78 Download
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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
AbstractAbstract PDFPubReaderePub

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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Efficacy of Postoperative Concurrent Chemoradiation for Resectable Rectal Cancer: A Single Institute Experience
Joong Bae Ahn, Hee Chul Chung, Nae Choon Yoo, Jae Kyung Roh, Nam Kyu Kim, Chang Ok Suh, Gwi Eon Kim, Jin Sil Seong, Woong Ho Shim, Hyun Cheol Chung
Cancer Res Treat. 2004;36(4):228-234.   Published online August 31, 2004
DOI: https://doi.org/10.4143/crt.2004.36.4.228
AbstractAbstract PDFPubReaderePub
Purpose

For patients with Dukes' stage B and C rectal cancer, surgery followed by adjuvant chemoradiotherapy is considered to be the standard treatment. However, the drugs used in combination with 5-fluorouracil (5-FU), the method of administration, duration of adjuvant therapy and the frequencies of administration presently remain controversial topics. We investigated (1) the efficacy and safety of adjuvant radiotherapy and 5-FU/leucovorin (LV) chemotherapy for patients who had undergone curative resection and (2) the effect of dose related factors of 5-FU on survival.

Materials and Methods

130 rectal cancer patients with Dukes' B or C stage disease who were treated with curative resection were evaluated. The adjuvant therapy consisted of two cycles of 5-FU/LV chemotherapy followed by pelvic radiotherapy with chemotherapy, and then 4~10 more cycles of the same chemotherapy regimen were delivered based on the disease stage. The cumulative dose of 5-FU per body square meter (BSA), actual dose intensity and relative dose intensity were obtained. The patients were divided into two groups according to the median value of each factor, and the patients' survival rates were compared.

Results

With a median follow-up duration of 52 months, the 5-year disease-free survival and overall survival rates of 130 patients were 57% and 73%, respectively. Locoregional failure occurred in 17 (13%) of the 130 patients, and the distant failure rate was 27% (35/130). The chemotherapy related morbidity was minimal, and there was no mortality for these patients. The cumulative dose of 5-FU/BSA had a significant effect on the 5-year overall survival for Dukes' C rectal cancer patients (p=0.03). Multivariate analysis demonstrated that only the performance status affected the 5-year overall survival (p=0.003).

Conclusion

An adjuvant therapy of radiotherapy and 5-FU/LV chemotherapy is effective and tolerable for Dukes' B and C rectal cancer patients. A prospective, multicenter, randomized study to evaluate the effects of the cumulative dose of 5-FU/BSA on survival is required.

Citations

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  • Seven low-mass ions in pretreatment serum as potential predictive markers of the chemoradiotherapy response of rectal cancer
    Kangsan Roh, Seung-Gu Yeo, Byong Chul Yoo, Kyung-Hee Kim, Sun Young Kim, Min-Jeong Kim
    Anti-Cancer Drugs.2016; 27(8): 787.     CrossRef
  • A 19-Gene expression signature as a predictor of survival in colorectal cancer
    Nurul Ainin Abdul Aziz, Norfilza M. Mokhtar, Roslan Harun, Md Manir Hossain Mollah, Isa Mohamed Rose, Ismail Sagap, Azmi Mohd Tamil, Wan Zurinah Wan Ngah, Rahman Jamal
    BMC Medical Genomics.2016;[Epub]     CrossRef
  • Safety of Early Chemotherapy after a Laparoscopic Colorectal Cancer Resection: A Case-Control Study
    Seung Ho Shin, Sun-Il Lee, Dong-Jin Choi, Si-Uk Woo, Jin Kim, Byung-Wook Min, Hong-Young Moon, Seon Hahn Kim
    Journal of the Korean Society of Coloproctology.2009; 25(6): 429.     CrossRef
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Associations between Depression, Anxiety, Hostility and Fighting Spirit among Cancer Patients in a Cancer Center in Korea
Joohyung Kim, Jae Kyung Roh, Jeoung Soon Yoon, Suk Jeong Lee, Dong Yeon Lee
Cancer Res Treat. 2003;35(5):411-418.   Published online October 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.5.411
AbstractAbstract PDF
PURPOSE
The aim of this study was to examine the associations between depression, anxiety, hostility and fighting spirit among patients with stomach, colorectal or breast cancer. MATERIALS AND METHODS: 223 patients, diagnosed as with stomach, colorectal or breast cancer, undergoing chemotherapy or follow up care, were the subjects of the study. The study design was cross-sectional at the time of the survey. The degrees of depression, anxiety and hostility of the patients were assessed by the SCL-90-R scores, and the fighting spirit was measured by the Mental Adjustment to Cancer (MAC) scale score. RESULTS: The scores of anxiety and hostility of the patients at younger age were higher than those at older age (p<0.01). The patients with metastasis were more depressed than those without it (p<0.01). There was a negative association between depression and fighting spirit (p<0.001). CONCLUSION: The study showed the more depressed cancer patients had lower fighting spirit score, which was known to be one of the most active psychosocial contributors in adjusting to cancer and survival.

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  • Associations of diagnostic awareness with psychosocial symptoms and survival time in patients with advanced lung cancer
    Hulya Abali, Seda Tural Onur, Yusuf Baser, Dilara Demir, Asli Bicen
    The International Journal of Psychiatry in Medicine.2024;[Epub]     CrossRef
  • Association of Depression and Survival in Patients with Cancer over 10 Years
    Joohyung Kim, Suk Jeong Lee, Jae-Kyung Roh, Sang Jun Shin
    Asian Oncology Nursing.2015; 15(1): 37.     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
AbstractAbstract 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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  • Fever and breast cancer: A critical review of the literature and possible underlying mechanisms
    Shiva Mehran, Afshin Taravati, Esfandiar Baljani, Yousef Rasmi, Zafar Gholinejad
    Breast Disease.2021; 40(3): 117.     CrossRef
  • 3D Collagen Vascular Tumor-on-a-Chip Mimetics for Dynamic Combinatorial Drug Screening
    Li Wan, Jun Yin, John Skoko, Russell Schwartz, Mei Zhang, Philip R. LeDuc, Carola A. Neumann
    Molecular Cancer Therapeutics.2021; 20(6): 1210.     CrossRef
  • A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer Based upon Its Hydrogen Ion Dynamics
    Salvador Harguindey, Khalid Alfarouk, Julián Polo Orozco, Kévin Hardonnière, Daniel Stanciu, Stefano Fais, Jesús Devesa
    International Journal of Molecular Sciences.2020; 21(3): 1110.     CrossRef
  • Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era
    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
AbstractAbstract 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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Suppression of Peritoneal Metastases by Expression of Murine Endostatin cDNA
Seung Ho Choi, Jae Hoon Lee, Sung Hee Hong, Woo Jin Hyung, Sung Hoon Noh, Hyun Cheol Chung, Jae Kyung Roh, Jin Sik Min
Cancer Res Treat. 2002;34(4):302-307.   Published online August 31, 2002
DOI: https://doi.org/10.4143/crt.2002.34.4.302
AbstractAbstract PDF
Peritoneal seeding is one of problems to be solved in gastrointestinal and ovarian cancers. Angiogenesis is the critical step for a dormancy tumor cluster to be an overt metastatic nodule. However, whether an anti-angiogenesis strategy is effective in the control of peritoneal metastases is still obscure. In this study, we evaluated whether endostatin, an endogenous angiogenesis inhibitor, suppresses peritoneal metastases.
MATERIALS AND METHODS
We transduced a human gastric cancer cell line, AGS and a murine renal cancer cell line, Renca, with the plasmid pEndoSTHB, which encodes a secretable form of murine endostatin. Endostatin expression was tested with western blotting, and the biological activity of the secreted endostatin was confirmed with in vitro endothelial cell growth inhibition. In the animal experiments, stable transfectants were injected intraperitoneally.
RESULTS
We demonstrated secretion of endostatin from two cell lines transduced with the plasmid pEndoSTHB. Conditioned media secreted from pEndoSTSB-transduced mammalian cells were shown to potently inhibit endothelial cell growth in vitro. We selected stable transfectants with similar in vitro growth rates of their parental cell lines. Significant tumor growth inhibition was observed in the endostatin-expressing Renca cells intraperitoneal injection group at days of 28, compared to the null transfectants intraperitoneal injection control group.
CONCLUSION
These results support that peritoneal seeding is angiogenesis-dependant and an anti-angiogenesis strategy is a good way to control peritoneal metastases.

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  • The kringle domain of tissue-type plasminogen activator inhibits in vivo tumor growth
    Byoung-Shik Shim, Byoung-Hak Kang, Yong-Kil Hong, Hyun-Kyung Kim, Il-Ha Lee, Soo-Young Lee, Young-Joon Lee, Suk-Keun Lee, Young Ae Joe
    Biochemical and Biophysical Research Communications.2005; 327(4): 1155.     CrossRef
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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
AbstractAbstract 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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    Junqi Huang, Wenzhi Bi, Gang Han, Jinpeng Jia, Meng Xu, Wei Wang
    BMC Musculoskeletal Disorders.2018;[Epub]     CrossRef
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    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
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Leptomeningeal Carcinomatosis in Solid Tumors; Clinical Manifestation and Treatment
Joon Oh Park, Hyun Joon Shin, Hyung Jong Kim, Sang Wook Lee, Hei Cheul Jeung, Seung Min Kim, Nae Choon Yoo, Hyun Cheol Chung, Joo Hang Kim, Byung Soo Kim, Jin Sik Min, Jae Kyung Roh
J Korean Cancer Assoc. 2001;33(1):34-40.
AbstractAbstract PDF
PURPOSE
Leptomeningeal carcinomatosis occurs in about 5% of patients with solid tumor and is being diagnosed with increasing frequency as patients live longer and as neuro-imaging studies improve. In general, the most commom cancers that involved the leptomeninges are breast cancer, lung cancer, and malignant melanoma.
MATERIALS AND METHODS
We investigated 25 patients presented with multiple neurologic symptoms and signs who were diagnosed with leptomeningeal carcinomatosis at the Yonsei Cancer Center from January 1990 to December 1999.
RESULTS
The primary disease of leptomeningeal carcinomatosis were stomach cancer (10 cases), breast cancer (7 cases), lung cancer (5 cases), unknown primary cancer (2 cases) and common bile duct cancer (1 case). All patients were presented with multiple neurologic symptoms and signs involving the central nervous system (CNS), cranial nerve or spinal nerves. Twenty-one of twenty- five patients were treated with intrathecal chemotherapy, radiotherapy, or combination therapy. Fourteen of them (66.7%) experienced improvement or stabilization of neurologic symptom and sign. The median survival was 122 days (10-2190).
CONCLUSION
In conclusion, although early diagnosis and active treatment of leptomeningeal carcinomatosis may improve the quality of life in selected patients, the median survival was relatively short. Therefore, new diagnostic and therapeutic strategy for leptomeningeal carcinomatosis were needed.
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The Efficacy and Safety of Docetaxel in Patients with Anthracychne pretreated Metastatic Breast Cancer: A Multicenter Phase II Study
Joong Bae Ahn, Kwang Yong Shim, Joon Oh Park, Hei Chul Jung, Nae Choon Yoo, Hyun Cheol Chung, Joo Hang Kim, Jin Hyuk Choi, Hyun Soo Kim, Hugh Chul Kim, Woo Kun Kim, Jae Kyung Roh
J Korean Cancer Assoc. 2000;32(2):235-243.
AbstractAbstract PDF
PURPOSE
Tbis phase II study was performed to evaluate the efficacy and safety of docetaxel in patients with anthracycline-pretreated metastatic breast cancer (MBC).
MATERIALS AND METHODS
From September 1996 to January 1998, 27 patients with metastatic breast cancer from 31 to 63 years of age with a performance status of 0 to 2 were registered in the phase II trial. All patients had metastatic breast cancer which had progressed or relapsed 2 during or after treatment with an anthracycline-based regimen. Docetaxel 75 mg/m2 was ad- ministered over 1 hour every 21 days until disease progression was documented or until toxic effects precluded further therapy. All patients received dexamethasone orally at the dose of 16 mg on days -1, 0, 1 of each cycle.
RESULTS
Objective responses were seen in 9 of 25 assessable patients (two complete and seven partial responses), with an overall objective response rale of 36%. The median duration of response was 36 weeks (range 19.0~40.5). The median time to progression and survival duration were 17.5 and 69 weeks, respectively, for assessable patients. One hundred fifty cycles (median, five) of docetaxel were administered. Among 27 patients assessable for toxicity, the following side effects were reported: nadir neutropenia grade 3 (4 patients) and grade 4 (22 patients); grade 2 stomatitis (6 patients); grade 2 alopecia (5 patients); grade 2 to 3 neurosensory toxicity (4 patients); no hypersensitivity reaction; mild fluid retention (4 patients).
CONCLUSION
Docetaxel is an active agent in patients with antracycline-pretreated metastatic breast cancer. Docetaxel was associated with severe but reversible neutropenia. Dexamethasone prevented hypersensitivity reactions and appeared to ameliorate fluid retention.
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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.
AbstractAbstract 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.
AbstractAbstract 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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Tumor - specific Virus Replication and Cytotoxicity of E1B 55 kD - deleted Adenovirus
Jaesung Kim, Boyoung Lee, Jinahn Kim, Joong Bae Ahn, Joon Oh Park, Nae Chun Yoo, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Heuiran Lee
J Korean Cancer Assoc. 2000;32(1):200-209.
AbstractAbstract PDF
PURPOSE
To overcome the limitations of cancer gene therapy using replication-incom- petent adenovirus, we generated E1B 55 kD-deleted adenovirus (YKL-1) by polymerase chain reaction (PCR) and homologous recombination. We then investigated tumor-specific virus replication and cytotoxicity of YKL-1 in vitro and in vivo.
MATERIALS AND METHODS
YKL-1 was constructed by reintroducting E1A and E1B 19 kD into pTG-CMV El/E3-deficient adenoviral vector and inducing homologous recombination in E. coli. The recombinant vector pYKL-1 was transfected into 293 cells to generate YKL-1. The properties of newly constructed YKL-1 was defined by PCR and immuno- blotting analysis. Virus replication was examined by infecting human normal and cancer cells on 6-wells at multiplicity of infection (MOI) of 10 for 3 days. Virus was then recovered and titered. Cytopathic effect was analyzed by infecting human normal and cancer cells on 24-wells at MOIs of 10, 1 or 0.1 for 7 to 10 days and staining them with crystal violet solution. Inhibition of tumor growth was examined in human cancer cell xenografts in nu/nu mice by intratumoral injection of YKL-l.
RESULTS
PCR and immunoblotting analysis confirmed that YKL-1 contained E1A and E1B 19 kD but not E1B 55 kD. In human normal cells, virus replication and subsequent cytopathic effect of E1B 55 kD-deleted adenovirus YKL-1 was markedly attenuated by larger than 2 to 3 log in magnitude, compared to that of wild-type ad-XJ. In contrast, YKL-1 was capable of replicating and inducing cytotoxicity i.n most human cancer cells. C33A and Hep3B containing p53 mutation were much more sensitive, whereas HeLa and H460 with wild type p53 were relatively resistant to YKL-1. Finally, the tumor growth was dramatically retarded by intratumoral injection of YKL-1 in C33A cervical cancer xenograft and the histology showed significant necrosis by intratumoral injection of YKL-1.
CONCLUSION
The results here demonstrated the ability of preferential virus replication and cytotoxicity of ElB 55 kD-deleted adenovirus YKL-1 in human cancer cells. Therefore, these indicated a promising potential of YKL-1 as an antitumoral virus agent and a selective replication-competent virus vector.
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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.
AbstractAbstract 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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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.
AbstractAbstract 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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Effects of Herpes Simplex Virus - Thymidine Kinase Gene Transduction into the Hepatocellular Carcinoma Cell Lines Using the Retrovirus on Ganciclovir Cytoxicity
Joo Hang Kim, Jae Jin Song, Yoon Soo Chang, Eun Hee Kim, Jae Sung Kim, Heui Ran Lee, Jae Kyung Roh, Byung Soo Kim, Joong Bae Ahn, Nae Chun Yoo, Hyun Cheol Chung
J Korean Cancer Assoc. 1998;30(5):1034-1043.
AbstractAbstract PDF
PURPOSE
Hepatocellular carcinoma (HCC) is one of the most common malignancy with high mortality in Korea. A new therapeutic modality such as gene therapy is necessary to improve the prognosis of hepatoma patients. Therefore we investigated the preclinical significance of Herpes simplex virus - thymidine kinase/ganciclovir (HSV-tk/GCV) gene therapy model using the retroviral vector for HCC cell lines.
MATERIALS AND METHODS
LNC/HSV-tk retroviral vector and PA317/LNC/HSV-tk pro- ducer cell line were constructed. HSV-tk transduced HCC cells using the LNC/HSV-tk retrovirus were selected by the G418 containing media. In vitro GCV sensitivity test of the HCC cells was performed by MTT assay. To evaluate in vivo GCV sensitivity, GCV was intraperitoneally injected after subcutaneous administration of HCC cells into each flank of the nude mouse.
RESULTS
HSV-tk gene transduction and expression in HCC cells were confirmed by RT-PCR. HSV-tk transduced HCC cell lines (SK-Hepl/HSV-tk and Hep-3B/HSV-tk) showed the marked GCV sensitivity comparing with the parental cell lines (SK-Hepl and Hep-3B) by MTT assay (p<0.001). The MTT test revealed that SK-Hepl/HSV-tk cells were more sensitive to GCV compare with that of Hep-3B/H5V-tk cells, and the parent cell line showed minimal growth suppression by the GCV treatment. In 12 nude mice received tumor cell mixtures of Hep-3B and Hep-3B/HSV-tk cells which contained more than 50% of HSV-tk transduced cells, the tumor was not developed in ll mice by the intraperitoneal administration of GCV. The tumors developed in 1 of 6 mice and 5 of 6 mice when mixtures contained 30% and 10% of HSV-tk transduced cells, respectively. Five mice out of 6 mice received inoculum containing the mixtures of 70% and 50% of HSV-tk transduced cells into each flank survived more than 6 month after HSV-tk/GCV treatment. Conelusion: HSV-tk gene transduced HCC cells showed the enhanced sensitivity to GCV. In nude mice HSV-tk/GCV strategy for HCC seemed to be more effective when tumor cell inoculum contained more than 30% of HSV-tk transduced HCC cells.
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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.
AbstractAbstract 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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Plasma TGF-beta1 as a Tumor Marker in Breast Cancer Patients
Hwa Young Lee, Sun Young Rah, Soo Jung Gong, Joong Bae Ahn, Kwang Yong Shim, Joon Oh Park, Hyun Ja Kwon, Nae Choon Yoo, Sook Jung Jeong, Hyun Cheol Chung, Joo Hang Kim, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Jae Kyung Roh
J Korean Cancer Assoc. 1998;30(5):935-942.
AbstractAbstract PDF
PURPOSE
Transforming Growth Factor-beta1(TGF-beta1) is the most potent inhibitor of the progression of normal mammary epithelial cells through the cell cycle. However, advanced breast cancers are mostly refractory to TGF-beta mediated growth inhibition and produce large amounts of TGF-beta, which may enhance tumor cell invasion and metastasis by its effects on extracellular matrix. Yet, little is known about the association of TGF-beta1 with progression of malignant disease in vivo. In this study, we evaluated the preoperative and postoperative plama level of TGF- in breast cancer and analyzed the utility of plasma TGF-beta1 as possible tumor marker.
MATERIALS AND METHODS
ELISA(enzyme-linked immunosorbent assay) was used to measure plasma TGF-beta1 level in 45 newly diagnosed breast cancer patients and in 15 normal healthy people, and the results were compared with clinicopathologic characteristics.
RESULTS
The mean plasma TGF-beta1 levels were 1.73+/-0.47 ng/ml in normal people and 5.05+/-1.41 ng/ml in breast cancer patiens. In 37 operated patients, the preoperative plasma TGF-beta1 level was 6.34+/-1.34 ng/ml and decreased to 4.48+/-1.07 ng/ml in patients with follow-up after surgery and 4.74+/-0.79 ng/ml in patients with chemotherapy. However, there was no significant correlation between plasma TGF-beta1 level and known prognostic factors including tumor size, LN involvement, tumor grade, hormone receptor status, and pathology.
CONCLUSION
These findings suggest that the plasma TGF-g level can be a tumor marker in breast cancer patients and the association with progression of breast cancer will be explored in future studies.
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GEnetic Change in Transforming Growth Factor-B (TGF-B) Receptor Type I and Type II Genes with Resistance to TGF-B of Human Breast Cancer Cells
Hwa Young Lee, Sung Sil Jeon, Hyun Ja Kwon, Soo Jung Kong, Seon Young Rah, Joong Bae Ahn, Kwang Yong Sim, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Kyung Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Chul Chung
J Korean Cancer Assoc. 1998;30(4):683-691.
AbstractAbstract PDF
PURPOSE
Transforming growth factor-Bs (TGF-Bs) are prototypic multifunctional negative growth factors that inhibit the growth of many cell types. TGF-B type I and II receptors(RI, RII) are transmembrane receptors containing cytoplasmic serine/ threonine kinase domain and have been implicated in mediating TGF-B activity. Because a heteromeric complex of RI and RII is required for TGF-B signal transduction, cancer cells may reduce the expression of either RI or RII to escape from growth inhibition of TGF-B. We examined the correlation between the growth inhibitory activity of TGF-B1 and the genetic expression of RI &RII genes in human breast cancer cell lines.
MATERIALS AND METHODS
We examined the growth inhibitory activity of TGF-B1 in 5 breast cancer cell lines by incorporation of [3H] thymidine. To investigate the correlation between TGF-B1 insensitivity and genetic change of TGF-B receptor genes (RI, RII), Southem blot analysis, Northern blot analysis, and Western blot analysis were performed. We also examined whether microsatellite instability(RER) was associated with RII mutation.
RESULTS
We found that 3 breast cancer cell lines (MCF-7, YCC-B101, YCC-B151) were resistant to growth inhibitory effect of TGF-B1. MCF-7 cell line expressed no detectable RII mRNA and RII protein, but showed normal structure of RII gene and normal expression of RI gene. And we did not find any abnormal expression of mRNA, protein, and genetic structure of RI &RII in YCC-B101 and YCC-B151.
CONCLUSION
Our results suggest that aquired resistance to the growth inhibitory effect of TGF-B1> could be transcription regulation system of RII in MCF-7 cell line, and could be postreceptor signal transduction pathway in YCC-B101 and YCC-B151 cell lines.
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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.
AbstractAbstract 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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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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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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A Case of Lambert - Eaton Myasthenic Syndrome with Small Cell Lung Charcinoma
Chong Seog Park, Se Haeng Cho, Jae Min Park, Joo Hang Kim, Jae Kyung Roh, Joon Chang, Il Nam SunWoo, Sung Kyu Kim, Won Young Lee
J Korean Cancer Assoc. 1996;28(4):772-776.
AbstractAbstract PDF
The Lambert-Eaton myasthenic syndrome(LEMS) is a rare disorder of neuro-muscular transmission that is frequently associated with malignancy, particulary small cell carcinoma of the lung. We report a case of 66 year old man who complained of muscle weakness and fatigability of proximal lower limbs on the tappering af prednisolone administeredfor usual interstitial pneumonitis. He was diagnosed LEMS by electrophysiological studies and small cell lung carcinoma by cytologic examination of brochoscopicwashing. The electrophysiological studies support the clinical diagnosis of LEMS with ¨c low amplitude of evoked compound muscle potential to a single supra-maximal stimulus an nerve, ¨e significant decremental response at low rates of stimulation and ¨e marked incremental response at high rates of stimulation.
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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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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.
AbstractAbstract 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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Prognostic Significance of Proliferating Cell Nuclear Antigen ( PCNA
Ho Yeong Lim, Joo Hang Kim, Hyun Cheol Chung, Hyo Dong Um, Jin Hyuk Choi, Byung Soo Kim, Dong Hwan Shin, Jae Kyung Roh, Byung Soo Kim
J Korean Cancer Assoc. 1995;27(1):18-28.
AbstractAbstract PDF
Proliferatina cell nuclear antigen(PCNA) is known to be closely correlated with DNA synthesis and cell proliferation. Proliferative activities of tumors have recently been consid- ered as one of important prognostic factors in a variety of human cancers. A total of 195 gastric carcinomas was evaluated with immunohistochemical study, using an- tibody(PC 10) with special reference to the correlation between PCNA expression and progno- sis. PCNA expression was assessed semi-quantitatively based on the proportion of tumor cells with immunostained nuclei. There was no significant correlation between PCNA expression and clinicopathological variables such as age, sex, tumor site, size, histologic grade, tumor stage, or the presence of lymph node metastases. To analyse survival, we evaluated disease-free survival and overall survival according to the extent of PCNA expression. No significant correlations between PCNA expression and both disease-free survival and overall survival were found. In conclusion, PCNA expression assessed by semi-quantitative PCNA grading system was not a significant prognostic factor in gastric carcinoma.
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Concurrent Chemoradiotherapy of Locally Advanced Pancreatic Carcinoma and Effects of Hyperthemia
Myung Wook Kim, Kyung Hee Lee, Jae Bok Chung, Jin Sil Sung, Hye Ran Lee, Jin Hyuk Chil, Hyun Cheol Chung, Woo Cheol Kim, Ki Chang Keum, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim
J Korean Cancer Assoc. 1994;26(4):561-567.
AbstractAbstract PDF
The prognosis of pancreati cancer is still poor in spite of advance in surgical treatment and parasurgical adjuvant management. Eighteen patients with histologically confirmed locally advanced adenocarcinoma of the pancreas were received radiation(5000cGy)+5-FU. Patients were treated with 5-FU 200 mg/m IV bolus, 1 hour before irradiation each day. In some patients, within 30 minutes after radiotherapy, hyperthemia was added to above protocol two times weekly. Median survival of total patients was 9.5months. Median survival with RT+ 5-FU was 12.7months from the date of treatment. Median survival with hyperthemia added group was 7.6months, but the survival dif- ference was not significant statistically. The side effects were acceptable. There were no episodes of any life threatening toxicities.
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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.
AbstractAbstract 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.
AbstractAbstract 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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Identification of Number of Positive Axillary Nodes to Influence Prognosis in Breast Cancer after Adjuvant CMF Chemotherapy
Ho Yeong Lim, Hyo Min Yoo, Eun Hee Koh, Nae Chun Yoo, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim, Kyung Shik Lee, In Sung Cho
J Korean Cancer Assoc. 1994;26(2):236-242.
AbstractAbstract PDF
The most important prognostic indicator for patients with operable breast cancer is the histological involvement of axillary lymph nodes metastasis, and the extent of nodal metastasis is highly prognostic, larger numbers of positive nodes are associated poorer prognosis. One hundred and nine patients of resected breast cancer with nodal involvement treated at Yonsei University College of Medicine from Dec. 1980 to Dec. 19S9 weres studied to identify the number of positive axillary nodes to influence prognosis after adjuvant CMF chemotherapy. And we obtained the following results. There was no significant difference in the disease free survival and overall survival between those with 1-3 positive axillary nodes and those with 4-7 positive nodes. So, we tried to reas- sess positive nodal groupings for determining the prognosis of breast cancer and identifying high risk group according to their nodal status. The current results showed that there was a significant difference in the disease free survival and overall survival between those with 1-7 positive axillary nodes and those with >= 8 positive nodes(DFS; 73% vs. 42%, OS; 78% vs. 40%, p < 0.05). This resport emphasizes the prognostic importance of positive nodal involvement with pa- tients of breast cancer and necessity of intensive managment for those with >= 8 positive nodes.
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Mechanism of Ahtitumor Activity of DA - 125 , a New Anthracycline Antiviotics ( 1 )
Mi Won Son, Jae Kyung Roh, Won Bae Kim, JunnIck Yang, Byung Soo Kim
J Korean Cancer Assoc. 1994;26(1):127-136.
AbstractAbstract PDF
From various new anthracylines containing fluorine in their sugar moieties, 7-0-(2,6-dideoxy- 2-fluoro-e-1-talopyranosyl)-adriamycinone-l4-0-alaninate HC10A-125) has been selected for ciinicai investigation, because of its excellent antitumor acitivity and low toxicity. In this paper the mechanism whereby DA-125 exhibits good antitumor activity in viw was studied through in vitro experiments in comparison with doxorubicin(DXR). DA-125 had stronger activity than DXR in single and double strand scission in P388 cells and in inhibition of nucleic acid synthesis in L1210 cells. But DA-125 had weaker activity than DXR in binding to calf thymus DNA. DA-125 was taken up by P388 cells faster than DXR and accumulated reaching at 2. 7 fold higher leveL
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Therapeautic effect of hepatic arterial infusion of cisplatin in primary hepatocelluar carcinoma
Jae Yong Cho, Jin Hyuk Choi, Nae Choon Yoo, Ho Young Lim, Joo Hang Kim, Jae Kyung Roh, Jong Tae Lee, Byung Soo Kim
J Korean Cancer Assoc. 1993;25(6):865-872.
AbstractAbstract PDF
No abstract available.
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Four cases of primary malignant lymphoma of the breast
Jin Ahn Kim, Jin Hyuk Choi, Jae Yong Cho, Hee Yong Moon, Bum Soo Kim, Ho Young Lim, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim
J Korean Cancer Assoc. 1993;25(5):773-779.
AbstractAbstract PDF
No abstract available.
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Phase II clinical trial of recombinant human granulocyte colony-stimulating factor(fhG-CSF)(KRN8601) in advanced cancer patients with myelosuppression after chemotherapy
Jae Kyung Roh, Jin Hyuk Choi, Kyung Hee Lee, Hye Ran Lee, Nae Choon Yoo, Joo Hang Kim, Byung Soo Kim, Ho Young Lim
J Korean Cancer Assoc. 1993;25(5):725-735.
AbstractAbstract PDF
No abstract available.
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The role of combined induction chemotherapy and radical radiation therapy in the treatment of advanced nasopharyngeal cancer
Jin Hyuk Choi, Jae Kyung Roh, Ho Young Lim, Hyun Chul Jung, Nae Choon Yoo, Shin Ki Ahn, Eun Hee Koh, Joo Hang Kim, Chang Ok Seo, Kwi Un Kim, Joon Kyoo Roh, Byung Soo Kim
J Korean Cancer Assoc. 1993;25(3):403-416.
AbstractAbstract PDF
No abstract available.
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p53 gene mutation in hepatocellular carcinoma from Korean patients and in established hepatocellular carcinoma cell lines
Joo Hang Kim, Joo Bae Park, Mitsudomi Tetsuya, Jung Joo Choi, Nae Choon Yoo, Jin Hyuk Choi, Ho Young Lim, Jae Kyung Roh, Kyung Sik Lee, Byung Soo Kim
J Korean Cancer Assoc. 1993;25(3):359-367.
AbstractAbstract PDF
No abstract available.
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Efficacy of recombinant human granulocyte colony-stimulating factor(neutrogin) for chemotherapy induced neutropenia in patients with advanced lung carcinoma
Nae Choon Yoo, Joo Hang Kim, Yi Young Lee, Se Kyoo Kim, Sung Kyoo Kim, Won Young Lee, Bong Soo Cha, Jin Hyuk Choi, Ho Young Lim, Jae Kyung Roh, Byung Soo Kim
J Korean Cancer Assoc. 1993;25(2):236-246.
AbstractAbstract PDF
No abstract available.
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Effects of verapamil, tamoxifen and cyclosporin A for the modulation of multidrug resistance in human lung cancer lines
Joo Hang Kim, Byung Soo Kim, Jung Joo Choi, Kyung Mi Kim, Nae Choon Yoo, Jin Hyuk Choi, Ho Young Lim, Jae Kyung Roh, Kyung Sik Lee, Byung Soo Kim
J Korean Cancer Assoc. 1993;25(2):225-235.
AbstractAbstract PDF
No abstract available.
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Efficacy of clodronate(ostac) on bone metastases in malignancy
Joo Hang Kim, Ho Young Lim, Nae Choon Yoo, Sun Young Rah, Jin Hyuk Choi, Eun Hee Koh, Jae Kyung Roh, Byung Soo Kim
J Korean Cancer Assoc. 1993;25(1):85-91.
AbstractAbstract PDF
No abstract available.
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Esophageal squamous cell carcinoma-comparison of radiotherapy alone to chemo-radiotherapy combination with or without surgery-
Hyung Sik Lee, Won Joo Huh, Gwi Eon Kim, Chang Ok Seo, Joon Kyoo Roh, Jae Kyung Roh, Byung Soo Kim
J Korean Cancer Assoc. 1993;25(1):59-66.
AbstractAbstract PDF
No abstract available.
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The serum levels of retinoids, beta-carotene and alpha-tocopherol of cancer patients
Kyung Jin Yeum, Yang Cha Lee-Kim, Ki Yull Lee, Byung Soo Kim, Jae Kyung Roh, Kye Sook Park
J Korean Cancer Assoc. 1992;24(3):343-351.
AbstractAbstract PDF
No abstract available.
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A case report of extraocular sebaceous gland carcinoma with lung metastasis
Dong Lip Kim, Hyun Cheol Chung, Ho Young Lim, Eun Hee Koh, Joo Hang Kim, Jae Kyung Roh, Joon Chang, Jung Soo Park, Eun Kyung Han, Gwi Eon Kim, Byung Soo Kim, Jin Ju Kim
J Korean Cancer Assoc. 1992;24(1):174-179.
AbstractAbstract PDF
No abstract available.
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Intrapleural instillation of OK-432 for malignant pleural effusion
Ho Yeong Lim, Joo Hang Kim, Young Hwan Park, Hyun Cheol Chung, Joung Ju Choi, Seoung Goo Choi, Ho Geun Kim, Jin Hyuk Choi, Nae Chun Yoo, Eun Hee Koh, Joon Chang, Jae Kyung Roh
J Korean Cancer Assoc. 1992;24(1):47-55.
AbstractAbstract PDF
No abstract available.
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Efficacy of ONDANSETRON(GR38032F) for the control of cisplatin induced nausea and vomiting in patients with advanced malignancies
Jae Kyung Roh, Nae Chun Yoo, Jin Hyuk Choi, Hyun Cheol Chung, Ho Young Lim, Eun Hee Koh, Joo Hang Kim, Byung Soo Kim
J Korean Cancer Assoc. 1991;23(4):814-820.
AbstractAbstract PDF
No abstract available.
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A clinical study of leiomyosarcoma of gastrointestinal tract
Hwa Young Lee, Jae Kyung Roh, Hyun Cheol Chung, Dong Lip Kim, Ho Yeong Lim, Eun Hee Koh, Joo Hang Kim, Hoon Sang Chi, Byung Soo Kim
J Korean Cancer Assoc. 1991;23(3):606-618.
AbstractAbstract PDF
No abstract available.
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Remnant stomach cancer
Sung Hoon Noh, Dong Sup Yoon, Seung Ho Choi, Jin Sik Min, Jae Kyung Roh, Byung Soo Kim
J Korean Cancer Assoc. 1991;23(3):578-585.
AbstractAbstract PDF
No abstract available.
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5-fluorouracil and low dose leucovorin in advanced colorectal carcinoma
Ho Yeong Lim, Hyun Cheol Chung, Jin Hyuk Choi, Nae Chun Yoo, Dong Lip Kim, Eun Hee Koh, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim
J Korean Cancer Assoc. 1991;23(3):563-570.
AbstractAbstract PDF
No abstract available.
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In vitro cytotoxicity of various anticancer drugs to short-term cultured gastric adenocarcinoma cell lines
Jae Kyung Roh, Hyun Cheol Chung, Eun Hee Koh, Won Yong Lee, Jee Sook Hahn, Byung Soo Kim
J Korean Cancer Assoc. 1991;23(3):495-517.
AbstractAbstract PDF
No abstract available.
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Overexpression of P-glycoprotein in gastric cancer by immunohistochemical staining method
Hyun Cheol Chung, Ho Young Lim, Eun Hee Koh, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Joung Ju Choi, Jung Kyu Youn, Byung Soo Kim, Kyi Beom Lee
J Korean Cancer Assoc. 1991;23(3):485-494.
AbstractAbstract PDF
No abstract available.
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A phase II trial of combined sequential FP (5-FU+cisplatin) chemotheraphy and radiotherapy in locally advanced unresectable esophageal cancer
Jong Won Ha, Hyun Cheol Chung, Dong Lip Kim, Jin Hyuk Choi, Nae Choon Yoo, Eun Hee Koh, Joo Hang Kim, Jae Kyung Roh, Gwi Eon Kim, John Kyu Loh Juhn, Byung Soo Kim
J Korean Cancer Assoc. 1991;23(2):307-314.
AbstractAbstract PDF
No abstract available.
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Phase II trial of sequential VP-16, cisplatin combination chemotherapy and radiotherapy for locally advanced (stage III) non-small cell lung cancer
Hyun Cheol Chung, Jin Hyuk Choi, Yoon Seok Chung, Dong Jip Kim, Young Sik Lee, Joon Chang, Eun Hee Koh, Joo Hang Kim, Jae Kyung Roh, Sung Kyu Kim, Won Young Lee, Gwi Eon Kim
J Korean Cancer Assoc. 1991;23(1):131-139.
AbstractAbstract PDF
No abstract available.
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Expression of Carcinoembryonic Antigen by Immunohistochemical Staining Method in Primary Male Breast Cancer
Hyun Cheol Chung, Dong Lip Kim, Eun Hee Koh, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Kyung Shik Lee, Woo Ik Yang, Byung Soo Kim, Byung Soo Kim
J Korean Cancer Assoc. 1990;22(3):440-451.
AbstractAbstract PDF
Carcinoembryonic antigen (CEA) immunohistochemistry was evaluated with 12 sections of male breast cancer diagnosed at Severance Hospital during the year of 1979-1990. Ten of twelve (83.3%) primary breast masses and four of five (80%) metastatic lymph nodes were CEA positive. There was concordance of CEA positivity and CEA positivity grade between primary mass and metastatic lymph nodes. The grade of CEA positivity did not appear to be related to size, tumor depth (T) and pathological stages. It was difficult to find a relationship between nuclear grade and CEA positive grade, because there was no nuclear grade 3 patient. Tumor heterogeneity was a constant feature of CEA staining with positivity varying from region to region.
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Significance of Serum Total Lactate Dehydrogenase ( LDH ) Level and Isoenzyma Patterns in Non - Hodgkin's Lymphoma as a Prognostic Factor
Jee Sook Hahn, Hyun Cheol Chung, Joo Hang Kim, Sun Ju Lee, Eun Hee Koh, Jae Kyung Roh, Hyon Suk Kim, Yun Woong Ko, Byung Soo Kim
J Korean Cancer Assoc. 1990;22(3):476-490.
AbstractAbstract PDF
Serum total lactate dehydrogenase (LDH) and LDH isoenzyme activities were studied in 33 cases w i th non-H odgk in's lymphom a to compare the cl inical significance of serological staging with these two serological markers to anatomical staging. Serum total LDH activity correlated with tumor burden as determined by clinical stage at presentation. Initially, LDH-3 was the major fraction of increment for the reflection of increased serum total LDH activity. With the increment of tumor burden (total LDH >200 IU/L), LDH-3 with additional LDH-4 fraction increased, which resulted in LDH-1/LDH-3 flipped pattern. These changes were normalized if complete remission state was induced with treatment. A high pretreatment LDH level (total LDH> 200 IU/L) correlated significantly to a decreased survival rate IP.0.01l> Furthermore, the flip pattern of LDH-I/LDH-3 isoenzyme at diagnosis showed a decreased survival rate (p<0.05), in which 4-year survival rate of patients with non-flipped pattern was 73.8%, comparable to 25.4%; of patients with flippd pattern. The 4-year survival rate of the low risk group Itotal LDH 200 IU/L with unftipped pattern: serological stage A) was 73g while 2-year survival rate of the high risk group (total LDH>200 IU/L withflipped pattern: serological stage D) was 0%, which showed a significant difference (p<0.05). Stepwise Cox regression analysis to identify the important prognostic factors among the serum total LDH, LDH1/LDH-3 flip, serological stage, anatomical stage, B symptoms, cell type, hepatos- plemomegaly, mediastinal mass reveated that the serological stage was the only prognostic factor. In conclusion, based on results of the multivariate analysis, we propose a new prognostic classification of patients with serological staging system in non-Hodgkins lymphoma. Furthermore, the reproducibility and therapeutic stratigies will be warranted.
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Efficacy of Combined Modality , Multidisciplinary Treatment ( Neoadjuvant Chemotherapy , Difinite Local Treatment , and Adjuvant Chemotherapy ) in Locally Advanced Head and Neck Squamous Cell Carcinoma
Jae Kyung Roh, Wha Young Lee, Hyun Cheol Chung, Young Joon Park, Hyung Keun Roh, Chang Ok Suh, Gwi Eon Kim, Jun Kyu Loh, Won Pyo Hong, Cheong Soo Park, Byung Soo Kim
J Korean Cancer Assoc. 1990;22(3):518-532.
AbstractAbstract PDF
Between January, 1986 and October, 1989, 40 patients with previously untreated, locally advanced head and neck squamous cell carcinoma enrolled for combined modality treatment (CMT) with neoadjuvant chemotherapy (2 cycles of infusional 5-FU and cis-platin), definite local treatment (DLT) (surgery and/or radiotheray) and adjuvant chemotherapy (3 cycles of infusional 5-FU and cis-platin) to enhance the therpeutic efficacy. Of the 40 enrolled, all the patients were evaluable for tumor responses and treatmen#t related toxicities after neoadjuvant chemotherapy, and 35 patients finished scheduled CMT. Male to female ratio were 33:7, median age 54 year old (34-69), and median ECOG performance grade 1 (0-2). Primary sites were nasopharynx 19, oral cavity 16, larynx 3, hypopharynx 1, and maxillary sinus l. After the 2 cycles of neoadjuvnt therpay, 8/40 (20%), 23/40 (72.5%) achieved compIete remission (CR) and partial remission (PR), respectively with 92.5% over all response rates. After the DLT, 23/ 35 (67.5%) 11/35 (31.4%) achieved CR, and PR respectively with 97.1% over all response rates. Of the 35 patients who finished the DLT, 15 received the 3 cycles of adjuvnat chemotherapy with infusional 5-FU and cis-platin. The median failure-free, and overal survival duration of 35 evaluable patients were 21.7 months and 31.0 months, respectively after the CMT. The median survival duration was significantly prolonged in patients with objective respanses after the neoadjuvant chemotherapy compared to those of non-responders (p<0.05). Of the 35 patients who finished the DLT, patients who received the adjuvant chemotherapy showed trend of prolongation of survival when compared to no adjuvant chemotherapy patients Imedian overall survival duration; adjuvant group 21.7 months, no adjuvant group 17.6 month (p>0.05). This study strongly suggests that CMT can increase the median response duration and survival especially in patients with locally advanced head and neck squamous cell carcinoma who showed responses after the neoadjuvant chemotherapy with infusional 5-FU and cis-platin, but phase III randomized controlled prospective studies are warranted for the verification of this study.
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Four Cases of Primary Urachal Adenocarcinoma
Don Haeng Lee, Hyun Cheol Chung, Young Jin Kim, Sin Ki Ahn, Young Ho Kim, Dong Lip Kim, Eun Hee Koh, Joo Hang Kim, Jae Kyung Roh, Young Tae Lee, Eun Kyung Han, Hyun Joo Chung, Gui Eon Kim, Byung Soo
J Korean Cancer Assoc. 1990;22(3):579-587.
AbstractAbstract PDF
The primary adenocarcinoma of bladder is a rare cancer and it was known that the prognasis is poor. The primary adenocarcinoma of bladder is divided by its embriological orign: I) nonurachal carcinoma derived from transformation of bladder epithelium, 2) urachal carcinoma arising from urachal remnant. This report represent four cases of primary urachal adenocarcinoma at Yonsei University Medical College from 1971 to 1989. The commonest sign is a painless hematuria. The specific site of origin is evaluated by measns of cystocopy, ultrasonography and computerized tomography. The choice of treatment is wide surgical resection and the role of chemotheraphy and radiotheraphy is still controversial. Our first two cases were treated only conservatively in advanced stages. The third cases was treated by curative resection and postoperative adjuvant chemotherapy. But 10 months later, intraabdominal carcinomatosis was developed. The fouth case showed metastatic lesions in both lung fields at the time of diagnosie. So we started chemotherapy of FAM regimen and a partill response was noticed after 3 cycles of chemotherapy. But after additional 3 cycles, the metastatic resions were aggrevated.
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Role of Chemofherapy in Unresectable Stage Biliary Tract Cancer
Hyun Cheol Chung, Eun Hee Koh, Jae Kyung Roh, Jin Sik Min, Kyung Shik Lee, Byung Soo Kim
J Korean Cancer Assoc. 1990;22(1):116-125.
AbstractAbstract PDF
Twenty evaluable patients with disseminated unresectable biliary tract cancer received chemotherapy after biliary tract drainage procedures. Two cambination chemotherapy protocols were applied; FAM (5-fluorouracil 1000 mg/m 24-hour infusion, day 1-3, adriamycin 40 mg/m i.v. day 1, mitomycin 10 mg/m i.v. day 1) in 13 patients, and MDF (5-fluorouracil 1000 mg/m' 24-hour infusion day 1-3, mitomycin 10 mg/m(2) i.v, day 1, cisplatin 80 mg/m i.v. day 4) in 7 patients. Course were repeated every three weeks. Seven patients(35%) achieved partial response. The median survival was 13.5 months in responders and 8.0 months in non-responders. No difference of drug response rate was observed between two chemotherapy protocols. Comparing the survival of biliary drainage plus chemotherapy group with that of billary drainage alone group, there was a trend of survival benefit in chemotherapy group with a median follow-up duration of 10 months. Gallbladder cancer and distal bile duct cancer showed favorable response rate and median survivals with chemotherapy and bile drainage than bile drainage alone. Most serious drug toxicities were myelosuppression and infection. But no chemotherapy related death was observed. Further randomized controlled trials to evaluate the effect of chemotherapy in advanced biliary tract cancer would be warrented.
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The Treatment Results of Combination of Radiotherapy and chemotherapy in Limited Stage Small Cell Lyug Cancer
Chang Ok Suh, Jun Kyu Loh, Kyung Ran Park, Chang Ok Suh, Gwi Eon Kim, Jae Kyung Roh, Seong Kyu Kim, Byung Soo Kim
J Korean Cancer Assoc. 1990;22(1):131-144.
AbstractAbstract PDF
A total of 72 patients with limited stage small cell lung cancer treated with combination of chemotherapy and radiotherapy at Department of Radiation Oncology, Yonsei University College of Meidcine between Jan. 1975 and Dec. 1986 were retrospectively analysed. 1) Age distribution of patients was between forty and seventy-one with median age fifty-five and male to female ratio was 5:l. 2) Complete response rate by treatment modality was as follows; CV+RT was 33.3%; CAV+RT, 43.59o, MOCA+RT. 28.6% and CAV+VP+RT was 62.5%. CAV+VP+RT group showed best result and this was statistically significant to MOCA+RT group (p=0.02) but insignificant to CV+ RT or CAV+RT grouP (P>0.1). 3) Median survival and 5 year actuarial survival rate by treatment modality were as follows; CVt RT was 15 3 months and 16.2%. CAV+RT, 14months and 16.396; MOCA+RT, 7month and 09; and CAV+ VP+ RT was 24 month and 30.7% respectively. CAV+VP+ RT groulp shawed the best results and these were statistically significant to MOCA+RT group(p<0.05) but insignificant to CV+RT or CAV+RT group (p>0,05). 4l Patterns of failure in complete response group were as follows; local failure was 24%, distant failure, 52% and local and distant failure was 24%. 5) Local control rate by radiation dosage in complete response group was as follows; when total dose of 4500-4900 cGv was given, local control rate was 50%; 5000 cGy, 43% however when total dose was given between 5100-7000 cGy, local control rate was significantly improved to 100%. 6) The incidences of brain metastsis in PCI (prophylactic cranial irradiation) group and control group were 20% and 32% respectively, although this was statistically insignificant (p=0.32). 7) Statistically significant factors affecting prognosis were performance status, TNM stage, initial status of presentation of superior vena cava syndrome and pleural effusion, location of tumor, response status to treatment and whether or not maintenance chemotherapy is added.
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Malignant Fibrous Histiocytoma of the Mediastinum - Report of two cases -
Young Jin Kim, Hyun Cheol Chung, Wha Young Lee, Hyung Jung Kim, Jae Kyung Roh, Doo Yun Lee, Jong Doo Lee, Gwi Eon Kim, Jun Kyu Loh, Nam Hoon Cho, In Joon Choi, Byung Soo Kim
J Korean Cancer Assoc. 1989;21(2):440-448.
AbstractAbstract PDF
Malignant fibrus histiocytoma (MFH) is a deep seated plemorphic sarcoma of older adults, which occurs most frequently in the deep fascia and skeletal muscle of the extremities and trunk. A rare tumor initially described in 1964 by OBriend and Stout, who considered it to have a histiocytic origin, it has been increasingly recognized as a discrete entity. There are only few descriptions of the intrathoracic occurrence of the MFI-l. Here, we report two cases of MFH originated from the mediastium which is a very unusual site. Radiation appeared to be a useful adjuvant treatment to surgical therapy in one case. Clinical features of the other reported cases of the intrathoracic MFH were also reviewed.
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Two Cases of Spontaneous Pneumothorax During Chemotherapy
Hyung Keun Roh, Nae Chun Yoo, Wha Young Lee, Hyun Cheol Chung, Jae Kyung Roh, Byung Soo Kim
J Korean Cancer Assoc. 1989;21(2):448-454.
AbstractAbstract PDF
Spontaneous pneumothorax usually occurs abruptly without antecedent trauma to the chest. This diagnosis is subdivided into primary spontaneous pneumothorax, which accurs in healthy individuals without any known etiology, and secondary spontaneous pneumothorax, which is associated with underlying lung disease. There are many etiologic lung diseases producing secondary spontaneous pneumothorax, which is rare in lung cancer as a complication. Moreover, the occurrence of spantaneous pneumothorax after chemotherapy is very rare. The mechanism far development of spontaneous pneumothorax in primary or metastatic lung cancer has been described as a rupture of an emphysematous bulla in an overexpanded portion of lung partially obstructed by neoplasm, or an actual rupture of peripheral necrotic tumor into the pleural space. And effective chemotherapy may increase the risk of spontaneous pneumothorax in patients with manifest or occult lung metastases by inducing rapid lysis of the tumor tissue and by interfering with repair process. This report describes two cases of repeated spontaneous pneumothorax after chemotherapy in a patient with osteosarcoma and another patient with epithelioid sarcoma, and discusses possible pathophysiologic mechanisms.
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The Effective Use Chlorophyll Derivatives ( CpD ) in Photodynamic Therapy of Ascites Tumors in Mice
Young Joon Park, Won Young Lee, Bo Sup Hahn, Man Jeong Hahn, Jae Kyung Roh, Byung Soo Kim
J Korean Cancer Assoc. 1989;21(1):1-7.
AbstractAbstract PDF
A murine ascites tumor was treated with intraperitoneal chlorophyll derivatives (CpD), which were developed as a new photosensitizer in Korea, and light of an appropriate wavelength (670nm). Photodynamic therapy (PDT) was given 3 times at 24h, 48h, and 72h after injection of CpD intraperitoneally. When the PDT was started at 1 week after inoculation of S-180 tumor cells, 80% of the complete remission(clinical) ratewas obtained. When the PDT was started at the 14th day or at the 21st day, the complete remission (clinical) rate was 30% or 0% respectively. This suggested that the lesser the tumor burden was, the higher the complete remission rate was. Our results illustrate the effective use of CpD in photodynamic therapy for the treatment of ascites tumors and reveal the possibility for photodynamic therapy in human ascites tumors.
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Combined Hyperthermia and Radiation Therapy on Primary Hepatocellular Carcinoma
Jin Sil Seong, Yun Ku Lee, Chang Ok Suh, John Juhn Kyu Loh, Hyung Sik Yoo, Jae Kyung Roh, Byung Soo Kim, Kwang Hyub Hahn, Sang In Lee, Heung Jae Choi
J Korean Cancer Assoc. 1989;21(1):117-129.
AbstractAbstract PDF
Thirty patients with unresectable hepatocellular carcinoma due to either locally advanced lesion or association with liver cirrhosis, treated with combined hyperthermia and radiotherapy between April 1988 and July 1988, at Dept. of Radiation Oncology, Yonsei University College of Medicine, were prospectively ananlysed. External radiotherapy of a total dose of 3060 cGy/3.5 wks was given. Hyperthermia was given twice a week with a total of 6 treatment sessions using 8 MHz radiofrequency capacitive type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases hyperthermia was given within 30 minutes after radiotherapy. Temperature was measured by inserting thermocouple into the tumor mass under the ultrasonographic guidance in all patients except for those who had bleeding tendency. As a result, PR was achieved in 12 patients (40%) and symptomatic improvement was observed in 22 patients (78. 6%) among 2S patients who had suffered from abdominal pain. The most significant factor affecting tumor responae rate was the type of tumor (single massive; 10/14, 71.4%, diffuse infiltrative; 2/10, 20%, multinodular; 0/6, 0%, P< 0.005>. There were not any significant side effects relating to combined treatment. Hepatic failure was the leading cause of death (5/11, 45.5%) and distant metastases were observed in 5 patients (one to brain, four to lung). In conclusion, combined hyperthermia and radiotherapy can be considered as an effective treatment modality in management of primary hepatocellular carcinoma.
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A Report of Two Cases of Leptomeningeal Carcinomatosis on Stomach Cancer
Dong Lip Kim, Jae Kyung Roh, Jin Hyuk Choi, Hyun Cheol Chung, Yong Jun Park, Won Ho Kim, Seung Min Kim, Jin Sik Min, Kwang Hwa Park, Chang Ok Suh, Jun Kyu Loh, Byung Soo Kim
J Korean Cancer Assoc. 1989;21(1):141-150.
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Meningeal carcinomatosis is an important neurologic complication. It is increasingly being recog- nized as a cause of neurologic disability in life. But stomach cancer has rarely been reported to be a cause of meningeal carcinomatosis. We reported two cases of 46-year-old male and 56-year-oldfemale who were diagnosed gastric cancer by biopsy under fiberoptic gastroscopy. These two cases of stomach cancer with meningeal invasion revealed malignant cells in their cerebrospinal fluid by repeated lumbar puncture. After diagnosis, they were treated radiation therapy in whole brain field. And, now, we have the plan of intrathecal chemotherapy.
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Effect of Radiofrequency Hyperthermia on Hepatocellular Carcinoma - Preliminary report -
Chang Ok Suh, John J. K. Loh, Jin Sil Seong, Jae Kyung Roh, Byung Soo Kim, In Suh Park, Heung Jae Choi
J Korean Cancer Assoc. 1988;20(2):117-126.
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Effectiveness of hyperthermia in the treatment of hepatocellular carcinoma was evaluated by the restrospective analysis of 31 patients who received radiofrequency hyperthermia at Department of Radiation Oncology, Yonsei Cancer Center, Yonsei Univ. College of Medicine between May 1985 and March 198B. All patients had advanced unresectable tumors, either unsuitable or re,fractory to conventional treatment modalities. B MHz radiofrequency capacitive type of hyperthermia was used either alone (1 case) or combined with other treatment modalities; i.e. 16 cases with external radiation, 7 cases with chemotherapy, 4 cases with l-131 Lipoidol and 3 cases with external radiation+ chemotherapy. Hyperthermia was given once or twice a week, usually 30 minutes after radiotherapy or chemotherapy. External radiotherapy was given with an average dose of 2,500-3000 cGy in 3 weeks. Response rate (CR! PR+ MR) was 32.3% (10/31); CR was achieved in one patient, PRa in 2 cases, PRb in 4 cases, and MR in 3 cases. All responders except for one received external radiotherapy with hyperthermia. Response rate of the patients who received combined radiotherapy and hyperth- ermia was 47.4% (9/19). On the other hand, only one of tweleve patients who received combination of hyperthermia and chemotherapy or I-131-Lipiodol showed partial response. As a result, hyperthermia was more effective when combined with external radiation than when combining with chemotherapy or other modality. In conclusion, hyperthermia, combined with external radiotherapy, is promising treatment method in the management of unresectable hepatocelluar carcinomas.
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