- Gastrointestinal cancer
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A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer
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Keun-Wook Lee, Sae-Won Han, Tae Won Kim, Joong Bae Ahn, Ji Yeon Baek, Sang Hee Cho, Howard Lee, Jin Won Kim, Ji-Won Kim, Tae-You Kim, Yong Sang Hong, Seung-Hoon Beom, Yongjun Cha, Yoonjung Choi, Seonhui Kim, Yung-Jue Bang
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Cancer Res Treat. 2024;56(2):590-601. Published online December 7, 2023
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DOI: https://doi.org/10.4143/crt.2023.1117
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a).
Materials and Methods
Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study.
Results
RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0).
Conclusion
GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.
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- Drug combinations of camptothecin derivatives promote the antitumor properties
Zhen Liu, Yajie Yuan, Ning Wang, Peng Yu, Yuou Teng European Journal of Medicinal Chemistry.2024; 279: 116872. CrossRef
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- General
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Increased Radiosensitivity of Solid Tumors Harboring ATM and BRCA1/2 Mutations
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Kyung Hwan Kim, Han Sang Kim, Seung-seob Kim, Hyo Sup Shim, Andrew Jihoon Yang, Jason Joon Bock Lee, Hong In Yoon, Joong Bae Ahn, Jee Suk Chang
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Cancer Res Treat. 2022;54(1):54-64. Published online June 4, 2021
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DOI: https://doi.org/10.4143/crt.2020.1247
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
Preclinical data indicate that response to radiotherapy (RT) depends on DNA damage repair. In this study, we investigated the role of mutations in genes related to DNA damage repair in treatment outcome after RT.
Materials and Methods
Patients with solid tumor who participated in next generation sequencing panel screening using biopsied tumor tissue between October 2013 and February 2019 were reviewed and 97 patients that received RT were included in this study. Best response to RT and the cumulative local recurrence rate (LRR) were compared according to absence or presence of missense, nonsense, and frameshift mutations in ATM and/or BRCA1/2.
Results
Of the 97 patients, five patients harbored mutation only in ATM, 22 in only BRCA1/2, and six in both ATM and BRCA1/2 (ATMmtBRCAmt). Propensity score matching was performed to select the control group without mutations (ATMwtBRCAwt, n=33). In total, 90 RT-treated target lesions were evaluated in 66 patients. Highest objective response rate of 80% was observed in ATMmtBRCAmt lesions (p=0.007), which was mostly durable. Furthermore, the cumulative 1-year LRR was the lowest in ATMmtBRCAmt lesions and the highest in ATMwtBRCAwt lesions (0% vs. 47.9%, p=0.008). RT-associated toxicities were observed in 10 treatments with no significant difference among the subgroups (p=0.680).
Conclusion
Tumors with ATM and BRCA1/2 mutations exhibited superior tumor response and local control after RT compared to tumors without these mutations. The results are hypothesis generating and suggest the need for integrating the tumor mutation profile of DNA repair genes during treatment planning.
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- Effects of Ataxia-Telangiectasia Mutated Variants on Radionecrosis and Local Control After Stereotactic Radiation Surgery for Non-Small Cell Lung Cancer Brain Metastases
Warren Floyd, David Carpenter, Eugene Vaios, Rachel Shenker, Peter Hendrickson, Justus D. Adamson, William M. Giles, Chunhao Wang, Karen Allen, Trey Mullikin, Scott R. Floyd, John P. Kirkpatrick, Michelle Green, Zachary J. Reitman Advances in Radiation Oncology.2024; 9(1): 101320. CrossRef - Long-term survival after systemic chemotherapy, chemoradiotherapy, and maintenance therapy for an older adult patient with recurrent pancreatic acinar cell carcinoma
Makiko Urabe, Kenji Ikezawa, Kazuhiro Kozumi, Yugo Kai, Ryoji Takada, Kaori Mukai, Tasuku Nakabori, Hiroyuki Uehara, Hirofumi Akita, Kazuyoshi Ohkawa Clinical Journal of Gastroenterology.2024; 17(4): 771. CrossRef - Robustness of carbon‐ion radiotherapy against DNA damage repair associated radiosensitivity variation based on a biophysical model
Hans Liew, Thomas Tessonnier, Stewart Mein, Giuseppe Magro, Lars Glimelius, Elias Coniavitis, Thomas Held, Thomas Haberer, Amir Abdollahi, Jürgen Debus, Ivana Dokic, Andrea Mairani Medical Physics.2024; 51(5): 3782. CrossRef - Use of Radiation Therapy for Ataxia-Telangiectasia Mutated (ATM)-Mutation Metastatic Renal Cell Carcinoma: A Case Report
Steven N Seyedin, Garrett Harada, Eleen Garemanian, Desiree Rafizadeh, Dalia Kaakour, Sami Dwabe, Michael Daneshvar, Nataliya Mar Cureus.2024;[Epub] CrossRef - Star wars against leukemia: attacking the clones
Monika M. Toma, Tomasz Skorski Leukemia.2024;[Epub] CrossRef - Predicting tumour radiosensitivity to deliver precision radiotherapy
James M. Price, Asmithaa Prabhakaran, Catharine M. L. West Nature Reviews Clinical Oncology.2023; 20(2): 83. CrossRef - Locoregional Chemoradiation for a Patient with BRCA1 Stage IV Pancreatic Adenocarcinoma
Pranit Singh, Jacob Adams, Sylvia Choo, Matthew Adams, Jordan McDonald, Laura Barton, Richard Levine, Dae Won Kim, Russell Palm, Jessica Frakes, Sarah Hoffe Applied Radiation Oncology.2023;[Epub] CrossRef - A genomic score to predict local control among patients with brain metastases managed with radiation
Nayan Lamba, Daniel N Cagney, Paul J Catalano, Dewey Kim, Hesham Elhalawani, Daphne A Haas-Kogan, Patrick Y Wen, Nikhil Wagle, Ayal A Aizer Neuro-Oncology.2023; 25(10): 1815. CrossRef - Lineage plasticity and treatment resistance in prostate cancer: the intersection of genetics, epigenetics, and evolution
Jarrell Imamura, Shinjini Ganguly, Andrew Muskara, Ross S. Liao, Jane K. Nguyen, Christopher Weight, Christopher E. Wee, Shilpa Gupta, Omar Y. Mian Frontiers in Endocrinology.2023;[Epub] CrossRef - Ex Vivo Chromosomal Radiosensitivity Testing in Patients with Pathological Germline Variants in Breast Cancer High-Susceptibility Genes BReast CAncer 1 and BReast CAncer 2
Tara Zuhair Kassem, Marius Wunderle, Lukas Kuhlmann, Matthias Ruebner, Hanna Huebner, Juliane Hoyer, André Reis, Peter A. Fasching, Matthias W. Beckmann, Carolin C. Hack, Rainer Fietkau, Luitpold Distel Current Issues in Molecular Biology.2023; 45(8): 6618. CrossRef - Moving the Needle Forward in Genomically-Guided Precision Radiation Treatment
Andrew Tam, Benjamin D. Mercier, Reeny M. Thomas, Eemon Tizpa, Irene G. Wong, Juncong Shi, Rishabh Garg, Heather Hampel, Stacy W. Gray, Terence Williams, Jose G. Bazan, Yun R. Li Cancers.2023; 15(22): 5314. CrossRef - Case Report: MR-Guided Adaptive Radiotherapy, Some Room to Maneuver
Winnie Li, Jeff Winter, Jerusha Padayachee, Jennifer Dang, Vickie Kong, Peter Chung Frontiers in Oncology.2022;[Epub] CrossRef - Dramatic response to local radiotherapy in a refractory metastatic mediastinal yolk sac tumor patient harboring a germline BRCA2 frameshift mutation: a case report
Xi Cheng, Haiming Yu, Jinying Li, Xiaona Han, Erhong Meng, Houqing Zhou, Dongliang Wang, Beifang Niu, Xiaotao Zhang Cancer Biology & Therapy.2022; 23(1): 393. CrossRef - Ovarian Cancer Radiosensitivity: What Have We Understood So Far?
Amelia Barcellini, Alexandra Charalampopoulou, Loris De Cecco, Andrei Fodor, Emanuela Rabaiotti, Giorgio Candotti, Simona Secondino, Angelica Facoetti, Laura Deborah Locati, Sandro Pignata, Ester Orlandi, Giorgia Mangili Life.2022; 13(1): 6. CrossRef
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- Gastrointestinal cancer
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A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair–Deficient/Microsatellite Instability–High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer
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Jwa Hoon Kim, Sun Young Kim, Ji Yeon Baek, Yong Jun Cha, Joong Bae Ahn, Han Sang Kim, Keun-Wook Lee, Ji-Won Kim, Tae-You Kim, Won Jin Chang, Joon Oh Park, Jihun Kim, Jeong Eun Kim, Yong Sang Hong, Yeul Hong Kim, Tae Won Kim
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Cancer Res Treat. 2020;52(4):1135-1144. Published online April 24, 2020
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DOI: https://doi.org/10.4143/crt.2020.218
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Abstract
PDFSupplementary MaterialPubReaderePub
- Purpose
We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations.
Materials and Methods
In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1.
Results
The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in 4 and 2 patients, respectively, with no treatment-related deaths.
Conclusion
Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.
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A Single Arm, Phase II Study of Simvastatin Plus XELOX and Bevacizumab as First-Line Chemotherapy in Metastatic Colorectal Cancer Patients
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Youjin Kim, Tae Won Kim, Sae Won Han, Joong Bae Ahn, Seung Tae Kim, Jeeyun Lee, Joon Oh Park, Young Suk Park, Ho Yeong Lim, Won Ki Kang
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Cancer Res Treat. 2019;51(3):1128-1134. Published online November 21, 2018
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DOI: https://doi.org/10.4143/crt.2018.379
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Abstract
PDFPubReaderePub
- Purpose
Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, apoptosis, and anti-angiogenesis. This phase II trial evaluated the efficacy and toxicity profile of conventional XELOX and bevacizumab chemotherapy plus simvastatin in metastatic colorectal cancer patients (MCRC).
Materials and Methods
Patients with MCRC received first-line XELOX in 3-week treatment cycles of intravenous oxaliplatin 130 mg/m2 plus bevacizumab 7.5 mg/kg (day 1), followed by oral capecitabine 1,000 mg/m2 twice daily (day 1-14). Simvastatin 80 mg tablets were taken orally once daily every day during the period of chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, duration of response, overall survival (OS), time to progression, and toxicity.
Results
From January 2014 to April 2015, 60 patients were enrolled and 55 patients were evaluable for tumor response. The median follow-up duration was 30.1 months (range, 28.5 to 31.7 months). The median PFS was 10.4 months (95% confidence interval [CI], 9.6 to 11.1). The median OS of all patients was 19.0 months (95% CI, 11.9 to 26.0). The disease-control rate and overall response rate were 88.3% (95% CI, 74 to 96) and 58.3% (95% CI, 44 to 77), respectively, by intent-to-treat protocol analysis. There was one complete response and 34 partial responses. One patient experienced grade 3 creatine kinase elevation and liver enzyme elevation.
Conclusion
Based on the current study, the addition of 80 mg simvastatin to XELOX and bevacizumab showed comparable clinical efficacy in patients with MCRC as first-line chemotherapy and did not increase toxicity.
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Citations
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- Therapeutic Effects of Statins: Promising Drug for Topical and
Transdermal Administration
Fatemeh Zahedipour, Seyede Atefe Hosseini, Željko Reiner, Eugenia Tedeschi-Reiner, Tannaz Jamialahmadi, Amirhossein Sahebkar Current Medicinal Chemistry.2024; 31(21): 3149. CrossRef - Are statins onco- suppressive agents for every type of tumor? A systematic review of literature
Luca Filaferro, Fabiana Zaccarelli, Giovanni Francesco Niccolini, Andrea Colizza, Federica Zoccali, Michele Grasso, Massimo Fusconi Expert Review of Anticancer Therapy.2024; 24(6): 435. CrossRef - Cholesterol synthesis is essential for the growth of liver metastasis‐prone colorectal cancer cells
Kumiko Taniguchi, Kei Sugihara, Takashi Miura, Daisuke Hoshi, Susumu Kohno, Chiaki Takahashi, Eishu Hirata, Etsuko Kiyokawa Cancer Science.2024;[Epub] CrossRef - Statins in Mitigating Anticancer Treatment-Related Cardiovascular Disease
Rong Jiang, Lian Lou, Wen Shi, Yuxiao Chen, Zhaoming Fu, Shuo Liu, Thida Sok, Zhihang Li, Xuan Zhang, Jian Yang International Journal of Molecular Sciences.2024; 25(18): 10177. CrossRef - Assessment in vitro of interactions between anti-cancer drugs and noncancer drugs commonly used by cancer patients
Claes R. Andersson, Jiawei Ye, Kristin Blom, Mårten Fryknäs, Rolf Larsson, Peter Nygren Anti-Cancer Drugs.2023; 34(1): 92. CrossRef - A phase 1 study of simvastatin in combination with topotecan and cyclophosphamide in pediatric patients with relapsed and/or refractory solid and CNS tumors
Thomas Cash, Hunter C. Jonus, Maya Tsvetkova, Jan H. Beumer, Arhanti Sadanand, Jasmine Y. Lee, Curtis J. Henry, Dolly Aguilera, R. Donald Harvey, Kelly C. Goldsmith Pediatric Blood & Cancer.2023;[Epub] CrossRef - New insights into the therapeutic potentials of statins in cancer
Chengyu Liu, Hong Chen, Bicheng Hu, Jiajian Shi, Yuchen Chen, Kun Huang Frontiers in Pharmacology.2023;[Epub] CrossRef - The Association of Metformin, Other Antidiabetic Medications, and Statins With the Prognosis of Colon Cancer in Patients With Type 2 Diabetes: A Retrospective Cohort Study
Sami Erkinantti, Ari Hautakoski, Reijo Sund, Martti Arffman, Elina Urpilainen, Ulla Puistola, Arja Jukkola, Karihtala Peeter, Esa Läärä Cancer Control.2022;[Epub] CrossRef - Performance of capecitabine in novel combination therapies in colorectal cancer
Fahima Danesh Pouya, Yousef Rasmi, Irem Yalim Camci, Yusuf Tutar, Mohadeseh Nemati Journal of Chemotherapy.2021; 33(6): 375. CrossRef - The potential use of simvastatin for cancer treatment: A review
Jaqueline Aparecida Duarte, Andre Luis Branco de Barros, Elaine Amaral Leite Biomedicine & Pharmacotherapy.2021; 141: 111858. CrossRef - Cholesterol-Lowering Drugs on Akt Signaling for Prevention of Tumorigenesis
Navneet Kumar, Chandi C. Mandal Frontiers in Genetics.2021;[Epub] CrossRef - Targeting Inflammatory Signaling in Prostate Cancer Castration Resistance
Shangwei Zhong, Changhao Huang, Zhikang Chen, Zihua Chen, Jun-Li Luo Journal of Clinical Medicine.2021; 10(21): 5000. CrossRef - Osteolytic metastasis in breast cancer: effective prevention strategies
Chandi C Mandal Expert Review of Anticancer Therapy.2020; 20(9): 797. CrossRef
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Clinical Practices and Outcomes on Chemotherapy-Induced Nausea and Vomiting Management in South Korea: Comparison with Asia-Pacific Data of the Pan Australasian Chemotherapy Induced Emesis Burden of Illness Study
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Myung Ah Lee, Eun Kyung Cho, Sung Yong Oh, Joong Bae Ahn, Ji Yun Lee, Burke Thomas, Hun Jung, Jong Gwang Kim
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Cancer Res Treat. 2016;48(4):1420-1428. Published online February 12, 2016
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DOI: https://doi.org/10.4143/crt.2015.309
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Abstract
PDFPubReaderePub
- Purpose
This study reported patient outcomes of chemotherapy-induced nausea and vomiting (CINV) prophylaxis for highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) regimens and evaluated its adherence to acute-phase CINV prophylaxis in the Korean population subset of the Pan Australasian Chemotherapy Induced Emesis burden of illness (PrACTICE) study. Materials and Methods This subgroup analysis evaluated 158 Korean patients receiving HEC or MEC and compared the data (wherever possible) with that of 648 patients from the Asia-Pacific (AP) region. Study endpoints included evaluation of primary CINV prophylaxis and adherence to acutephase CINV prophylaxis in cycle 1 (American Society of Clinical Oncology [ASCO] Quality Oncology Practice Initiative [QOPI]).
Results In South Korea and the AP, a 5-hydroxytryptamine-3 receptor antagonist (5HT3-RA) prophylaxis for the acute phase was administered to 79/80 patients (98.8%) for HEC and 70/71 patients (98.6%) for MEC regimens (QOPI-1). Triple regimen (corticosteroid–5HT3-RA–neurokinin 1-RA) was initiated in 46/80 patients (57.5%) for prophylaxis of acute CINV in cycle 1 of HEC (QOPI-3). Double regimen (corticosteroid–5HT3-RA, with or within NK1-RA) was initiated in 61/71 patients (83.1%) for control of acute CINV in cycle 1 of MEC a(QOPI-2). Conclusion Active management of CINV is necessary in cycle 1 of HEC in South Korea, despite higher rates than the AP region. Adherence to the international guidelines for CINV prophylaxis requires attention in the acute phase in cycle 1 of the HEC regimen.
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- Adherence to antiemetic guidelines in solid cancer patients receiving highly emetogenic chemotherapy in Korea
Ryugyoung Lee, Minhee Ku, Nam Kyung Je Supportive Care in Cancer.2024;[Epub] CrossRef - Chemotherapy-Associated Nausea and Vomiting
Kelvin Mogesa Manyega, Benjamin Nasara Joseph, Okunlola Charity Rotkangmwa, Maxwell P. Dapar Annals of African Medicine.2022; 21(2): 124. CrossRef - Expert Consensus on Effective Management of Chemotherapy-Induced Nausea and Vomiting: An Indian Perspective
Ashok K. Vaid, Sudeep Gupta, Dinesh C. Doval, Shyam Agarwal, Shona Nag, Poonam Patil, Chanchal Goswami, Vikas Ostwal, Sagar Bhagat, Saiprasad Patil, Hanmant Barkate Frontiers in Oncology.2020;[Epub] CrossRef - Construção e avaliação de bundle frente ao extravasamento de antineoplásicos: estudo metodológico
João Marcos Alves Melo, Patrícia Peres de Oliveira, Andrea Bezerra Rodrigues, Raíssa Silva Souza, Deborah Franscielle da Fonseca, Thaís Fonseca Gontijo, Edilene Aparecida Araújo da Silveira Acta Paulista de Enfermagem.2020;[Epub] CrossRef - A cost-utility analysis of risk model-guided versus physician’s choice antiemetic prophylaxis in patients receiving chemotherapy for early-stage breast cancer: a net benefit regression approach
Kednapa Thavorn, Doug Coyle, Jeffrey S. Hoch, Lisa Vandermeer, Sasha Mazzarello, Zhou Wang, George Dranitsaris, Dean Fergusson, Mark Clemons Supportive Care in Cancer.2017; 25(8): 2505. CrossRef
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Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Surrogate Biomarker for Bevacizumab in Colorectal Cancer Liver Metastasis: A Single-Arm, Exploratory Trial
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Yeo-Eun Kim, Bio Joo, Mi-Suk Park, Sang Joon Shin, Joong Bae Ahn, Myeong-Jin Kim
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Cancer Res Treat. 2016;48(4):1210-1221. Published online March 17, 2016
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DOI: https://doi.org/10.4143/crt.2015.374
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Abstract
PDFPubReaderePub
- Purpose
The purpose of this study is to investigate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and plasma cytokines and angiogenic factors (CAFs) as pharmacodynamic and prognostic biomarkers of bevacizumab monotherapy in colorectal cancer with liver metastasis (CRCLM). Materials and Methods From July 2011 to March 2012, 28 patients with histologically confirmed CRCLM received bevacizumab monotherapy followed by combined FOLFOX therapy. The mean age of the patients was 57 years (range, 30 to 77 years). DCE-MRI (Ktransand IAUC60) was performed at baseline, first follow-up (3 days after bevacizumab monotherapy), and second follow-up (3 days after combined therapy). CAF levels (vascular endothelial growth factor [VEGF], placental growth factor [PlGF], and interleukin-8) were assessed on the same days. Progression-free survival (PFS) time distributions were summarized using the Kaplan-Meier method and compared using log-rank tests.
Results The median PFS period was 11.2 months. Ktrans, IAUC60, VEGF, and PlGF values on the first follow-up day were significantly different compared with baseline values. No differences were observed on the second follow-up day. A > 40% decrease in Ktrans from baseline to first follow-up was associated with a longer PFS (hazard ratio, 0.349; 95% confidence interval, 0.133 to 0.912; p=0.032). Changes in CAFs did not show correlation with PFS time. Conclusion DCE-MRI parameters and CAFs are pharmacodynamic biomarkers of bevacizumab for CRCLM. In our study, change in Ktrans at 3 days after bevacizumab monotherapy was a favorable prognostic factor; however, the value of CAFs as a prognostic biomarker was not found.
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Martina Caruso, Arnaldo Stanzione, Anna Prinster, Laura Micol Pizzuti, Arturo Brunetti, Simone Maurea, Pier Paolo Mainenti World Journal of Gastroenterology.2023; 29(3): 521. CrossRef - Dynamic Contrast-Enhanced Magnetic Resonance Imaging for the Prediction of Monoclonal Antibody Tumor Disposition
Brandon M. Bordeau, Joseph Ryan Polli, Ferdinand Schweser, Hans Peter Grimm, Wolfgang F. Richter, Joseph P. Balthasar International Journal of Molecular Sciences.2022; 23(2): 679. CrossRef - The cancer angiogenesis co-culture assay: In vitro quantification of the angiogenic potential of tumoroids
Sarah Line Bring Truelsen, Nabi Mousavi, Haoche Wei, Lucy Harvey, Rikke Stausholm, Erik Spillum, Grith Hagel, Klaus Qvortrup, Ole Thastrup, Henrik Harling, Harry Mellor, Jacob Thastrup, Christina L. Addison PLOS ONE.2021; 16(7): e0253258. CrossRef - [18F]Fluciclatide PET as a biomarker of response to combination therapy of pazopanib and paclitaxel in platinum-resistant/refractory ovarian cancer
Rohini Sharma, Pablo Oriol Valls, Marianna Inglese, Suraiya Dubash, Michelle Chen, Hani Gabra, Ana Montes, Amarnath Challapalli, Mubarik Arshad, George Tharakan, Ed Chambers, Tom Cole, Jingky P. Lozano-Kuehne, Tara D. Barwick, Eric O. Aboagye European Journal of Nuclear Medicine and Molecular Imaging.2020; 47(5): 1239. CrossRef - Combination of DCE-MRI and DWI in Predicting the Treatment Effect of Concurrent Chemoradiotherapy in Esophageal Carcinoma
Changmin Liu, Roger Sun, Jing Wang, Fangling Ning, Zhenbo Wang, Judong Luo, Shaoshui Chen, Shuanghu Yuan BioMed Research International.2020; 2020: 1. CrossRef - Colorectal cancer: Parametric evaluation of morphological, functional and molecular tomographic imaging
Pier Paolo Mainenti, Arnaldo Stanzione, Salvatore Guarino, Valeria Romeo, Lorenzo Ugga, Federica Romano, Giovanni Storto, Simone Maurea, Arturo Brunetti World Journal of Gastroenterology.2019; 25(35): 5233. CrossRef - Pharmacodynamic and Pharmacokinetic Markers For Anti-angiogenic Cancer Therapy: Implications for Dosing and Selection of Patients
Matteo Morotti, Prashanth Hari Dass, Adrian L. Harris, Simon Lord European Journal of Drug Metabolism and Pharmacokinetics.2018; 43(2): 137. CrossRef - Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial
Loïc Lebellec, François Bertucci, Emmanuelle Tresch-Bruneel, Isabelle Ray-Coquard, Axel Le Cesne, Emmanuelle Bompas, Jean-Yves Blay, Antoine Italiano, Olivier Mir, Thomas Ryckewaert, Yves Toiron, Luc Camoin, Anthony Goncalves, Nicolas Penel, Marie-Cécile BMC Cancer.2018;[Epub] CrossRef - Functional Parameters Derived from Magnetic Resonance Imaging Reflect Vascular Morphology in Preclinical Tumors and in Human Liver Metastases
Pavitra Kannan, Warren W. Kretzschmar, Helen Winter, Daniel Warren, Russell Bates, Philip D. Allen, Nigar Syed, Benjamin Irving, Bartlomiej W. Papiez, Jakob Kaeppler, Bosjtan Markelc, Paul Kinchesh, Stuart Gilchrist, Sean Smart, Julia A. Schnabel, Tim Mau Clinical Cancer Research.2018; 24(19): 4694. CrossRef - Dynamic Contrast-Enhanced Ultrasound of Colorectal Liver Metastases as an Imaging Modality for Early Response Prediction to Chemotherapy
Marie Mogensen, Martin Hansen, Birthe Henriksen, Thomas Axelsen, Ben Vainer, Kell Osterlind, Michael Nielsen Diagnostics.2017; 7(2): 35. CrossRef - Nano-sized and other improved reporters for magnetic resonance imaging of angiogenesis
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p16 Hypermethylation and KRAS Mutation Are Independent Predictors of Cetuximab Plus FOLFIRI Chemotherapy in Patients with Metastatic Colorectal Cancer
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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
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Cancer Res Treat. 2016;48(1):208-215. Published online April 24, 2015
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DOI: https://doi.org/10.4143/crt.2014.314
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Abstract
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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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?
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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
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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
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Amana Saadallah-Kallel, Rania Abdelmaksoud-Dammak, Mouna Triki, Slim Charfi, Abdelmajid Khabir, Tahia Sallemi-Boudawara, Raja Mokdad-Gargouri Medical Oncology.2017;[Epub] CrossRef - DNA methylation of CMTM3 , SSTR2 , and MDFI genes in colorectal cancer
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Results of a Phase II Study to Evaluate the Efficacy of Docetaxel and Carboplatin in Metastatic Malignant Melanoma Patients Who Failed First-Line Therapy Containing Dacarbazine
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Choong-kun Lee, Minkyu Jung, Hye Jin Choi, Hye Ryun Kim, Hyo Song Kim, Mi Ryung Roh, Joong Bae Ahn, Hyun Cheol Chung, Su Jin Heo, Sun Young Rha, Sang Joon Shin
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Cancer Res Treat. 2015;47(4):781-789. Published online February 16, 2015
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DOI: https://doi.org/10.4143/crt.2014.261
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Abstract
PDFPubReaderePub
- Purpose
There is no standard second-line regimen for malignant melanoma patients with disease progression after first-line chemotherapy, and platinum-alkylating agents combined with paclitaxel have shown modest efficacy. Materials and Methods We conducted a phase II, open-label, single-arm study to test the efficacy of docetaxel combined with carboplatin for malignant melanoma patients who failed previous treatment with dacarbazine. Intravenous docetaxel (35 mg/m2 on days 1 and 8 of each cycle) and carboplatin (area under the curve 3 on days 1 and 8 of each cycle) was administered every 21 days. Primary end point was objective response rate (ORR).
Results Thirty patients were enrolled in the study, and the median follow-up duration was 19.8 months. Among 25 per-protocol patients, there were three responders (1 with complete response and 2 with partial response) and 17 stable disease patients (ORR, 12.0%). Among the per-protocol population, the median progression-free survival (PFS) was 4.3 months and the median overall survival (OS) was 9.6 months. Uveal melanoma patients (n=9) showed the best prognosis compared to other subtypes (median PFS, 7.6 months; OS, 9.9 months). The most common grade 3 or 4 adverse event was neutropenia (n=15, 50.0%). Conclusion Docetaxel combined with carboplatin showed association with an acceptable safety profile and overall efficacy for patients with malignant melanoma who had progressed on chemotherapy containing dacarbazine.
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Courtney R. Croley, Joshua Pumarol, Blake E. Delgadillo, Andrew C. Cook, Faith Day, Tea Kaceli, Caroline C. Ward, Imran Husain, Ali Husain, Sabyasachi Banerjee, Anupam Bishayee Pharmacology & Therapeutics.2023; 248: 108479. CrossRef - A Phase 1 study of ADI‐PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1‐negative metastatic uveal melanoma
Pui Ying Chan, Melissa M. Phillips, Stephen Ellis, Amanda Johnston, Xiaoxing Feng, Amit Arora, Gordon Hay, Victoria M. L. Cohen, Mandeep S. Sagoo, John S. Bomalaski, Michael T. Sheaff, Peter W. Szlosarek Pigment Cell & Melanoma Research.2022; 35(4): 461. CrossRef - iUMRG: multi-layered network-guided propagation modeling for the inference of susceptibility genes and potential drugs against uveal melanoma
Yueping Ren, Congcong Yan, Lili Wu, Jingting Zhao, Mingwei Chen, Meng Zhou, Xiaoyan Wang, Tonghua Liu, Quanyong Yi, Jie Sun npj Systems Biology and Applications.2022;[Epub] CrossRef - Systemic and Liver-Directed Therapies in Metastatic Uveal Melanoma: State-of-the-Art and Novel Perspectives
Francesca Comito, Paola Valeria Marchese, Angela Dalia Ricci, Nastassja Tober, Chiara Peterle, Francesca Sperandi, Barbara Melotti Future Oncology.2021; 17(33): 4583. CrossRef - New Therapeutic Perspectives in the Treatment of Uveal Melanoma: A Systematic Review
Mario Damiano Toro, Lucia Gozzo, Luciano Tracia, Marco Cicciù, Filippo Drago, Claudio Bucolo, Teresio Avitabile, Robert Rejdak, Katarzyna Nowomiejska, Sandrine Zweifel, Yacoub A. Yousef, Rashed Nazzal, Giovanni Luca Romano Biomedicines.2021; 9(10): 1311. CrossRef - Interferon-α versus interleukin-2 in Chinese patients with malignant melanoma
Shenglong Li, Xixi Wu, Peng Chen, Yi Pei, Ke Zheng, Wei Wang, Enduo Qiu, Xiaojing Zhang Anti-Cancer Drugs.2019; 30(4): 402. CrossRef - Mechanism of HN‑3 cell apoptosis induced by carboplatin: Combination of mitochondrial pathway associated with Ca2+ and the nucleus pathways
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Mohamed Hassan World Journal of Experimental Medicine.2015; 5(4): 206. CrossRef
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Novel Methods for Clinical Risk Stratification in Patients with Colorectal Liver Metastases
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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
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Cancer Res Treat. 2015;47(2):242-250. Published online September 11, 2014
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DOI: https://doi.org/10.4143/crt.2014.066
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Abstract
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
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Incidence and Survival of Pediatric Soft Tissue Sarcomas: Comparison between Adults and Children
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Sun Min Lim, Cheol Joo Yoo, Jung Woo Han, Yong Jin Cho, Soo Hee Kim, Joong Bae Ahn, Sun Young Rha, Sang Joon Shin, Hyun Cheol Chung, Woo Ick Yang, Kyoo-Ho Shin, Jae Kyung Rho, Hyo Song Kim
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Cancer Res Treat. 2015;47(1):9-17. Published online August 21, 2014
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DOI: https://doi.org/10.4143/crt.2013.157
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Abstract
PDFPubReaderePub
- Purpose
Pediatric-type sarcomas such as rhabdomyosarcoma (RMS), Ewing sarcoma (EWS), primitive neuroectodermal tumor (PNET), and desmoplastic small round-cell tumor (DSRCT) are rare in adults, with limited studies on their prognosis and optimal treatment strategies. We aimed to examine the outcome of children and adult patients with RMS, EWS, PNET, and DSRCT and relevant prognostic factors. Materials and Methods We retrospectively reviewed 220 pediatric-type sarcoma patients at a single institution between 1985 and 2011. Comparisons were made in order to examine differences in demographics, disease characteristics, and survival. Survival analyses were performed using the Kaplan-Meier method with log-rank tests and Cox proportional hazards models. Results A total of 220 consecutive patients were identified at our institute. Median age was 15.6 years (range, 0 to 81 years) and there were 108 children (49%) and 112 adult patients (51%). According to histological classification, 106 patients (48.2%) had RMS, 60 (27.3%) had EWS, 50 (22.7%) had PNET, and 4 (1.8%) had DSRCT. With a median follow-up period of 6.6 years, the estimated median overall survival (OS) of all patients was 75 months (95% confidence interval [CI], 27.2 to 122.8 months) and median event-free survival (EFS) for all patients was 11 months (95% CI, 8.8 to 13.2 months). No significant difference in OS and EFS was observed between adults and children. In multivariate analysis, distant metastasis (hazard ratio [HR], 1.617; 95% CI, 1.022 to 2.557; p=0.040) and no debulking surgery (HR, 1.443; 95% CI, 1.104 to 1.812; p=0.012) showed independent association with worse OS. Conclusion Metastatic disease and no surgical treatment are poor prognostic factors for OS among pediatric-type sarcomas for both adults and children.
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Grace Guzman, Megan R. Reed, Kevin Bielamowicz, Brian Koss, Analiz Rodriguez Current Oncology Reports.2023; 25(5): 479. CrossRef - Clinicopathological and treatment response characteristics of updated rhabdomyosarcoma histomolecular subtypes: An Asian population‐based study
Guo Yuan How, Chik Hong Kuick, Min Hwee Yong, Shui Yen Soh, Esther XY Hee, Meng Kang Wong, Richard Quek, Mohd Farid Harunal, Sathiyamoorthy Selvarajan, Kesavan Sittampalam, Chetan Anil Dhamne, Victor Lee, Kenneth TE Chang, Amos HP Loh Asia-Pacific Journal of Clinical Oncology.2023;[Epub] CrossRef - Pediatric sarcoma survivorship: A call for a developmental cascades approach
Peter M. Fantozzi, Gina Sprint, Anna Marie Medina Development and Psychopathology.2022; 34(4): 1221. CrossRef - Clinical Perspectives for 18F-FDG PET Imaging in Pediatric Oncology: Μetabolic Tumor Volume and Radiomics
Vassiliki Lyra, Sofia Chatziioannou, Maria Kallergi Metabolites.2022; 12(3): 217. CrossRef - Desmoplastic Small Round Cell Tumors With EWS-WT1 Transcript Expression: Should We Consider Children and Adult Patients Differently?
Laura Olivier-Gougenheim, Daniel Orbach, Vincent Atallah, Perrine Marec-Berard, Amandine Bertrand Journal of Pediatric Hematology/Oncology.2022; 44(3): e637. CrossRef - Next-Generation Sequencing Identifies Potential Actionable Targets in Paediatric Sarcomas
Antonio Juan Ribelles, Pablo Gargallo, Pablo Berlanga, Vanessa Segura, Yania Yáñez, Bárbara Juan, Marta Salom, Margarita Llavador, Jaime Font de Mora, Victoria Castel, Adela Cañete Journal of Personalized Medicine.2021; 11(4): 268. CrossRef - Ewing Sarcoma
Hee Young Ju Clinical Pediatric Hematology-Oncology.2019; 26(1): 27. CrossRef - Emerging trends in immunotherapy for pediatric sarcomas
Kyle A. Dyson, Brian D. Stover, Adam Grippin, Hector R. Mendez-Gomez, Joanne Lagmay, Duane A. Mitchell, Elias J. Sayour Journal of Hematology & Oncology.2019;[Epub] CrossRef
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Clinicopathologic Features of Metachronous or Synchronous Gastric Cancer Patients with Three or More Primary Sites
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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
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Cancer Res Treat. 2010;42(4):217-224. Published online December 31, 2010
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DOI: https://doi.org/10.4143/crt.2010.42.4.217
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Abstract
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 MethodsBetween 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. ResultsPatients 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). ConclusionMultiplicity of primary malignancies itself does not seem to indicate a poor prognosis. The early detection of additional primary malignancies will enable proper management with curative intent.
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A Locally Advanced Breast Cancer with Difficult Differential Diagnosis of Carcinosarcoma and Atypical Medullary Carcinoma, which had Poor Response to Adriamycin- and Taxane-based Neoadjuvant Chemotherapy: A Case Report
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Se Hyun Kim, Hyun Cheol Chung, Jaeheon Jeong, Ji Hoon Kim, Sun Young Rha, Joong Bae Ahn, Nam Hoon Cho, Hei-Cheul Jeung
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Cancer Res Treat. 2007;39(3):134-137. Published online September 30, 2007
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DOI: https://doi.org/10.4143/crt.2007.39.3.134
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Abstract
PDFPubReaderePub
Atypical medullary carcinomas and carcinosarcoma have unique histopathological features. Here we present a case with a breast malignancy that had pathological characteristics of both. A 54-year old patient with a malignant breast mass received 6 cycles of adriamycin-based chemotherapy, followed by 3 cycles of paclitaxel monotherapy, and had a poor clinical response to treatment. A modified radical mastectomy was performed. The pathological diagnosis was complicated by an inability to distinguish between atypical medullary carcinoma and carcinosarcoma. The findings included a tumor that was well-circumscribed, high grade and a syncytial growth pattern as well as biphasic sarcomatous and carcinomatous characteristics. In conclusion, atypical medullary carcinoma and carcinosarcoma of the breast have entirely different prognoses and should be managed differently. Both should be treated by surgical resection, and additional therapy should be considered based on the cancer with the poorer prognosis.
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- A Rare Case of Primary Carcinosarcoma of the Breast
Maria Kiakou, Maria Tolia, Nektarios Koufopoulos, Konstantinos Tsapakidis, Eleni Arvanitou, Gkikas Konstantinos, Nikolaos Charalambakis, Michalis Nikolaou, Dimitrios Matthaios, Nikolaos Tsoukalas Forum of Clinical Oncology.2022; 13(1): 48. CrossRef - Carcinosarcoma (Metaplastic Carcinoma) Breast: A Rare and Aggressive Primary – Report of Two Cases with Review of Literature
Gunjesh Kumar Singh, Pragya Singh, KT Bhowmik Indian Journal of Medical and Paediatric Oncology.2018; 39(03): 400. CrossRef - Carcinosarcoma of the Breast: An Aggressive Subtype of Metaplastic Cancer. Report of a Rare Case in a Young BRCA-1 Mutated Woman
Matteo Ghilli, Donatella M. Mariniello, Giovanni Fanelli, Francesca Cascione, Andrea Fontana, Agostino Cristaudo, Anna Cilotti, Adelaide M. Caligo, Giampiero Manca, Livio Colizzi, Antonio G. Naccarato, Manuela Roncella Clinical Breast Cancer.2017; 17(1): e31. CrossRef
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Long-term Survival after Surgical Resection for Liver Metastasis from Gastric Cancer: Two Case Reports
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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
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Cancer Res Treat. 2006;38(3):184-188. Published online June 30, 2006
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DOI: https://doi.org/10.4143/crt.2006.38.3.184
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Abstract
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
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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
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Cancer Res Treat. 2004;36(4):228-234. Published online August 31, 2004
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DOI: https://doi.org/10.4143/crt.2004.36.4.228
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Abstract
PDFPubReaderePub
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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 Methods130 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. ResultsWith 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). ConclusionAn 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.
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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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Phase II Study of Gemcitabine and Vinorelbine as Second-Line Chemotherapy in Non-Small Cell Lung Cancer
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Yoon Jae Kim, Joo Hyuk Sohn, Chul Kim, Yong Tai Kim, Hai Jin Kim, Joong Bae Ahn, Se Kyu Kim, Joon Chang, Nae Choon Yoo, Joo Hang Kim, Jae Yong Cho
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Cancer Res Treat. 2003;35(4):294-298. Published online August 31, 2003
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DOI: https://doi.org/10.4143/crt.2003.35.4.294
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With the increased use of chemotherapy for non small cell lung cancer (NSCLC), a growing group of patients can now be considered for second-line chemotherapy. However, guidelines for the second line treatment remain to be developed. The objective of this study was to evaluate the efficacy and safety of the gemcitabine and vinorelbine combination therapy in patients with advanced NSCLC, pretreated with taxane and platinum based regimens.
Gemcitabine has already demonstrated activity in this patient group, with the combination therapy having been reported to be well tolerated in previous phase I/II studies. MATERIALS AND METHODS Forty two patients with advanced NSCLC (stages III/IV), having received prior taxane and platinum based chemotherapy, with an ECOG performance status (PS) 0~2, and unimpaired hematopoietic and organ function, were treated with vinorelbine, 20 mg/m2, followed by gemcitabine, 1, 000 mg/m2, both administered on days 1, 8 and 15, every 4 weeks. RESULTS Out of the 42 patients enrolled, 41 were evaluable for their response, and all 42 for their toxicity. The patient's characteristics were as follows; median age=60 years (42~73), median PS=1 (range 0~2), a gender ratio 31: 11 males/females, with stages IIIA, IIIB and IV in 3, 14 and 25 cases. The objective responses included a partial response (PR) 8/41 (19.5%), a stable disease 15/41 (36.6%) and a progressive disease 18/41 (43.9%). The median time-to progression (TTP) and survival were 4 months, ranging from 2 to 14 months, and 8 months, ranging from 2 to 17+ months, respectively. Grade 3 neutropenia was seen in 19% of the patient, and there was no grade 4 neutropenia or episodes of febrile neutropenia. No grade 4 thrombocytopenia or other grade 3/4 non-hematological toxicities were observed. CONCLUSION The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC having failed prior taxane/platinum therapy.
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The Efficacy and Safety of Docetaxel in Patients with Anthracychne pretreated Metastatic Breast Cancer: A Multicenter Phase II Study
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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
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J Korean Cancer Assoc. 2000;32(2):235-243.
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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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Tumor - specific Virus Replication and Cytotoxicity of E1B 55 kD - deleted Adenovirus
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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
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J Korean Cancer Assoc. 2000;32(1):200-209.
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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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Prognostic Value of PCNA , c-erbB-2 , c-fos in Patients with Non-small Cell Lung Cancer
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Yi Hyeong Lee, Joong Bae Ahn, Dong Hwang Shin, Soon Won Hong, Jeong Yeon Shim, Kyung Young Jung, Se Kyu Kim, Joon Chang, Joo Hang Kim, Won Youn Lee, Byung Soo Kim, Sung Kyu Kim
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J Korean Cancer Assoc. 1999;31(4):678-685.
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Abstract
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Oncogenes, tumor suppressor genes, and growth variables of tumors are important in the assessment of prognosis in lung cancer. The expression of PCNA, c-erbB-2 (HER-2/neu), and c-fos oncoprotein and their prognostic implications in surgically resected patients with non-small cell lung cancer were evaluated. MATERIALS AND METHODS Seventy patients with non-small cell lung cancer were included and PCNA, c-erbB-2 and c-fos overexpression were evaluated by immunohistochemical stain using paraffin-embedded tissue. RESULTS The mean proportion of PCNA positive cells was 18.6%, and there was no significant difference according to cell type and stage. The median survival time was significantly shorter in the group with high PCNA expression (>10%) as compared with the group with low PCNA expression (<10%) (37 months vs 16 months). Four (6.3%) of 64 cases demonstrated c-erbB-2 positivity. These were all adenocarcinoma cases. c-fos protein was only rarely overexpressed (1/51). CONCLUSION PCNA expression was shown to be a useful prognostic parameter in resected non-small cell lung cancer while c-erbB-2 and c-fos oncoprotein were infrequently expressed.
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Efficacy of Gemcitabine Chemotherpy in Advanced Non-small cell Lung Cancer ( NSCLC ): A Phase 2 Study
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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
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J Korean Cancer Assoc. 1999;31(3):523-532.
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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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The Efficacy of Pre - operative Chamotherapy with Intra-arterial Cisplatin and Intravenous Adriamycin for High Grade Osteosarcoma
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Sun Young Rha, Soo Jung Gong, Hee Cheol Chung, Kwang Yong Shim, Joong Bae Ahn, Nae Choon Yoo, Hyn Cheol Chung, Joo Hang Kim, Hae Kyung Roh, Jin Sik Min, Byung Soo Kim, Kyu Ho Shin, Woo Ick Yang, Chong In Lee
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J Korean Cancer Assoc. 1999;31(1):134-143.
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Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment [pre-operative chemotherapy + surgery (limb salvage or amputation) + adjuvant chemotherapy] had improved the overall survival and quality of life. To improve the local control rate, we introduced pre-operative chemotherapy combined with intra-arterial (IA) cisplatin and continuous intravenous infusion (CI) of adriamycin. We evaluated the efficacy and feasibility, such as limb salvage rate, recurrence pattern and the survival impact, based on the histologic response of pre-operative chemotherapy. MATERIALS AND METHODS Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1996.
Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72hrs CI, was administered for 3 cycles with 3 week interval, followed by surgery. Post-operative chemotherapy was applied by the tumor necrosis rate. If the tumor necrosis of the specimen was more than 90%, the same regimen af the preoperative one was administered for 3 cycles. A salvage regimen (Ifosfamide 7.5 gm/m2/5d IV + high dose MTX 10 gm/m2 IV VP-16 360 mg/m2/3d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%. RESULTS Of 41 patients, 37 were evaluable for efficacy and toxicities, because 4 refused further chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 female, with the median age of 16 years (8-41). The tumor locations were as follows: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (10 with grade III, 27.8%; 17 with grade IV, 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lungs. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive care. CONCLUSION Pre-operative chemotherapy combined with IA cisplatin and CI adriamycin induced higher good response rate without survival benefits. To improve the survival rate, the design of good salvage chemotherapy with a non-cross resistant regimen should be considered.
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Microsatellite Instability Correlate with a Prognosis in Breast Cancer
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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
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J Korean Cancer Assoc. 1998;30(5):914-920.
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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
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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
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J Korean Cancer Assoc. 1998;30(5):935-942.
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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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Effects of Herpes Simplex Virus - Thymidine Kinase Gene Transduction into the Hepatocellular Carcinoma Cell Lines Using the Retrovirus on Ganciclovir Cytoxicity
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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
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J Korean Cancer Assoc. 1998;30(5):1034-1043.
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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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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
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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
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J Korean Cancer Assoc. 1998;30(4):683-691.
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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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Effect on Malignant Phenotype of Gastric Cancer Cell Line after p53 Gene Transduction
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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
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J Korean Cancer Assoc. 1998;30(3):508-520.
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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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Brain Metastasis and Leptomeningeal Carcinomatosis in Breast Cancer
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Yoon Soo Chang, Jeong Hun Seo, Ruth Lee, Joong Bae Ahn, Kwang Yong Shim, Soo Jung Gong, Hwa Young Lee, Sun Young Rha, Nae Choon Yoo, Chang Ok Suh, Joo Hang Kim, Jae Kyung Rho, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung
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J Korean Cancer Assoc. 1998;30(3):464-474.
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Brain metastasis is estimated to occur in 20 to 40% of cancer patients, and meningeal involvement has been reported in 5% to 8% of cancer patients. Even if the prognosis is grave, standard treatment modality of brain metastasis or leptomeningeal carcinomatosis has not been established. We evaluated the prognosis and the clinical features of the brain and leptomeningeal metastasis of the breast cancer. MATERIALS AND METHODS The 43 patients who was diagnosed as brain parenchymal metastasis or leptomeningeal carcinomatosis clinically, radiologically and/or cytologically were included in this study. The median age was 44(range: 27-61) years. RESULTS The median duration from brain metastasis to death was 181 days(range: 8~1599), and the median duration from leptomeningeal carcinomatosis to death was 39 days(range: 25~152). Age(p=0.7174) and number of brain metastatic lesion(p=0.4097) did not influence the survival, but the presence of other systemic metastatic lesion affected the survival(p 0.0224). When we compared the survival rates of patients according to treatment modality, the patients with systemic chemotherapy versus patients without systemic chemotherapy showed differences(p= 0.0009). Patients treated with whole brain radiation only versus patients with whole brain radiation and other systemic management also showed different survival rate(p=0.0009). But intrathecal chemotherapy had no effect on survival. Well differentiated, solitary lesions were treated by operation and/or gamma-knife surgery, and their effects were good. CONCLUSION Prolongation of survival was suggested with whole brain radiotherapy combined with systemic treatment in brain or leptomeningeal metastasis. Further study is expected to confirm this finding.
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Expression and Clinical Relevance of c-erbB-3 in Rectal Cancer
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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
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J Korean Cancer Assoc. 1996;28(1):50-63.
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- 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
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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
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J Korean Cancer Assoc. 1995;27(6):897-907.
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- 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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Detection of Soluble c-erbB-2 Oncoproteins in the Serum of Gastric Cnacer patients as a Tumor Marker
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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
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J Korean Cancer Assoc. 1995;27(2):175-184.
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- 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
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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
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J Korean Cancer Assoc. 1995;27(2):265-275.
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- 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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