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Joong Bae Ahn 30 Articles
Gastrointestinal cancer
A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer
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
Cancer Res Treat. 2024;56(2):590-601.   Published online December 7, 2023
DOI: https://doi.org/10.4143/crt.2023.1117
AbstractAbstract 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
  • 2,950 View
  • 117 Download
  • 1 Web of Science
  • 1 Crossref
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General
Increased Radiosensitivity of Solid Tumors Harboring ATM and BRCA1/2 Mutations
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
Cancer Res Treat. 2022;54(1):54-64.   Published online June 4, 2021
DOI: https://doi.org/10.4143/crt.2020.1247
AbstractAbstract 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
  • 8,781 View
  • 233 Download
  • 14 Web of Science
  • 14 Crossref
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Gastrointestinal cancer
A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair–Deficient/Microsatellite Instability–High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer
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
Cancer Res Treat. 2020;52(4):1135-1144.   Published online April 24, 2020
DOI: https://doi.org/10.4143/crt.2020.218
AbstractAbstract 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.

Citations

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    International Journal of Gynecology & Obstetrics.2024; 164(2): 436.     CrossRef
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    Expert Review of Molecular Diagnostics.2023; 23(10): 863.     CrossRef
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  • 473 Download
  • 57 Web of Science
  • 33 Crossref
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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
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
Cancer Res Treat. 2019;51(3):1128-1134.   Published online November 21, 2018
DOI: https://doi.org/10.4143/crt.2018.379
AbstractAbstract 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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  • 221 Download
  • 17 Web of Science
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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
Myung Ah Lee, Eun Kyung Cho, Sung Yong Oh, Joong Bae Ahn, Ji Yun Lee, Burke Thomas, Hun Jung, Jong Gwang Kim
Cancer Res Treat. 2016;48(4):1420-1428.   Published online February 12, 2016
DOI: https://doi.org/10.4143/crt.2015.309
AbstractAbstract 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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    Ryugyoung Lee, Minhee Ku, Nam Kyung Je
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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
Yeo-Eun Kim, Bio Joo, Mi-Suk Park, Sang Joon Shin, Joong Bae Ahn, Myeong-Jin Kim
Cancer Res Treat. 2016;48(4):1210-1221.   Published online March 17, 2016
DOI: https://doi.org/10.4143/crt.2015.374
AbstractAbstract 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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p16 Hypermethylation and KRAS Mutation Are Independent Predictors of Cetuximab Plus FOLFIRI Chemotherapy in Patients with Metastatic Colorectal Cancer
Se Hyun Kim, Kyu Hyun Park, Sang Joon Shin, Kang Young Lee, Tae Il Kim, Nam Kyu Kim, Sun Young Rha, Jae Kyung Roh, Joong Bae Ahn
Cancer Res Treat. 2016;48(1):208-215.   Published online April 24, 2015
DOI: https://doi.org/10.4143/crt.2014.314
AbstractAbstract PDFPubReaderePub
Purpose
Hypermethylation of the CpG island of p16INK4a occurs in a significant proportion of colorectal cancer (CRC). We aimed to investigate its predictive role in CRC patients treated with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), and cetuximab.
Materials and Methods
Pyrosequencing was used to identify KRASmutation and hypermethylation of 6 CpG island loci (p16, p14, MINT1, MINT2, MINT31, and hMLH1) in DNA extracted from formalin-fixed paraffin-embedded specimens. Logistic regression and Cox regression were performed for analysis of the relation between methylation status of CpG island methylator phenotype (CIMP) markers including p16 and clinical outcome.
Results
Hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) and showed significant association with KRASmutation (Fisher exact, p=0.01) and CIMP positivity (Fisher exact, p=0.002). Patients with p16-unmethylated tumors had significantly longer time to progression (TTP; median, 9.0 months vs. 3.5 months; log-rank, p=0.001) and overall survival (median, 44.9 months vs. 16.4 months; log-rank, p=0.008) than those with p16-methylated tumors. Patients with both KRAS and p16 aberrancy (n=6) had markedly shortened TTP (median, 2.8 months) compared to those with either KRAS or p16 aberrancy (n=11; median, 8.6 months; p=0.021) or those with neither (n=32; median, 9.0 months; p < 0.0001). In multivariate analysis, KRAS mutation and p16 methylation showed independent association with shorter TTP (KRAS mutation: hazard ratio [HR], 3.21; p=0.017; p16 methylation: HR, 2.97; p=0.027).
Conclusion
Hypermethylation of p16 was predictive of clinical outcome in metastatic CRC patients treated with cetuximab and FOLFIRI, irrespective of KRAS mutation.

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    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
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Results of a Phase II Study to Evaluate the Efficacy of Docetaxel and Carboplatin in Metastatic Malignant Melanoma Patients Who Failed First-Line Therapy Containing Dacarbazine
Choong-kun Lee, Minkyu Jung, Hye Jin Choi, Hye Ryun Kim, Hyo Song Kim, Mi Ryung Roh, Joong Bae Ahn, Hyun Cheol Chung, Su Jin Heo, Sun Young Rha, Sang Joon Shin
Cancer Res Treat. 2015;47(4):781-789.   Published online February 16, 2015
DOI: https://doi.org/10.4143/crt.2014.261
AbstractAbstract 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
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Novel Methods for Clinical Risk Stratification in Patients with Colorectal Liver Metastases
Ki-Yeol Kim, Nam Kyu Kim, In-Ho Cha, Joong Bae Ahn, Jin Sub Choi, Gi-Hong Choi, Joon Suk Lim, Kang Young Lee, Seung Hyuk Baik, Byung Soh Min, Hyuk Hur, Jae Kyung Roh, Sang Joon Shin
Cancer Res Treat. 2015;47(2):242-250.   Published online September 11, 2014
DOI: https://doi.org/10.4143/crt.2014.066
AbstractAbstract PDFPubReaderePub
Purpose
Colorectal cancer patients with liver-confined metastases are classified as stage IV, but their prognoses can differ from metastases at other sites. In this study, we suggest a novel method for risk stratification using clinically effective factors. Materials and Methods Data on 566 consecutive patients with colorectal liver metastasis (CLM) between 1989 and 2010 were analyzed. This analysis was based on principal component analysis (PCA). Results The survival rate was affected by carcinoembryonic antigen (CEA) level (p < 0.001; risk ratio, 1.90), distribution of liver metastasis (p=0.014; risk ratio, 1.46), and disease-free interval (DFI; p < 0.001; risk ratio, 1.98). When patients were divided into three groups according to PCA score using significantly affected factors, they showed significantly different survival patterns (p < 0.001). Conclusion The PCA scoring system based on CEA level, distribution of liver metastasis, and DFI may be useful for preoperatively determining prognoses in order to assist in clinical decisionmaking and designing future clinical trials for CLM treatment.

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Incidence and Survival of Pediatric Soft Tissue Sarcomas: Comparison between Adults and Children
Sun Min Lim, Cheol Joo Yoo, Jung Woo Han, Yong Jin Cho, Soo Hee Kim, Joong Bae Ahn, Sun Young Rha, Sang Joon Shin, Hyun Cheol Chung, Woo Ick Yang, Kyoo-Ho Shin, Jae Kyung Rho, Hyo Song Kim
Cancer Res Treat. 2015;47(1):9-17.   Published online August 21, 2014
DOI: https://doi.org/10.4143/crt.2013.157
AbstractAbstract 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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    Kyle A. Dyson, Brian D. Stover, Adam Grippin, Hector R. Mendez-Gomez, Joanne Lagmay, Duane A. Mitchell, Elias J. Sayour
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Clinicopathologic Features of Metachronous or Synchronous Gastric Cancer Patients with Three or More Primary Sites
Joo Hoon Kim, Sun Young Rha, Chan Kim, Gun Min Kim, Sang Hyun Yoon, Ki Hyang Kim, Min Jae Kim, Joong Bae Ahn, Hyun Cheol Chung, Jae Kyung Roh, Hyo Song Kim
Cancer Res Treat. 2010;42(4):217-224.   Published online December 31, 2010
DOI: https://doi.org/10.4143/crt.2010.42.4.217
AbstractAbstract PDFPubReaderePub
Purpose

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

Materials and Methods

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

Results

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

Conclusion

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

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A Locally Advanced Breast Cancer with Difficult Differential Diagnosis of Carcinosarcoma and Atypical Medullary Carcinoma, which had Poor Response to Adriamycin- and Taxane-based Neoadjuvant Chemotherapy: A Case Report
Se Hyun Kim, Hyun Cheol Chung, Jaeheon Jeong, Ji Hoon Kim, Sun Young Rha, Joong Bae Ahn, Nam Hoon Cho, Hei-Cheul Jeung
Cancer Res Treat. 2007;39(3):134-137.   Published online September 30, 2007
DOI: https://doi.org/10.4143/crt.2007.39.3.134
AbstractAbstract 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
Jong Keun Lim, Joong Bae Ahn, Sung Ha Cheon, Hyun Chang, Jong Yul Jung, Sun Young Rha, Jae Kyung Roh, Sung Hoon Noh, Ho Geun Kim, Hyun Cheol Chung, Hei-Cheul Jeung
Cancer Res Treat. 2006;38(3):184-188.   Published online June 30, 2006
DOI: https://doi.org/10.4143/crt.2006.38.3.184
AbstractAbstract PDFPubReaderePub

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

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  • Radical gastrectomy with hepatoarterial catheter implantation for late-stage gastric cancer
    Guo-Liang Yao
    World Journal of Gastroenterology.2015; 21(9): 2754.     CrossRef
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Efficacy of Postoperative Concurrent Chemoradiation for Resectable Rectal Cancer: A Single Institute Experience
Joong Bae Ahn, Hee Chul Chung, Nae Choon Yoo, Jae Kyung Roh, Nam Kyu Kim, Chang Ok Suh, Gwi Eon Kim, Jin Sil Seong, Woong Ho Shim, Hyun Cheol Chung
Cancer Res Treat. 2004;36(4):228-234.   Published online August 31, 2004
DOI: https://doi.org/10.4143/crt.2004.36.4.228
AbstractAbstract PDFPubReaderePub
Purpose

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

Materials and Methods

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

Results

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

Conclusion

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

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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
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
Cancer Res Treat. 2003;35(4):294-298.   Published online August 31, 2003
DOI: https://doi.org/10.4143/crt.2003.35.4.294
AbstractAbstract PDF
PURPOSE
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
Joong Bae Ahn, Kwang Yong Shim, Joon Oh Park, Hei Chul Jung, Nae Choon Yoo, Hyun Cheol Chung, Joo Hang Kim, Jin Hyuk Choi, Hyun Soo Kim, Hugh Chul Kim, Woo Kun Kim, Jae Kyung Roh
J Korean Cancer Assoc. 2000;32(2):235-243.
AbstractAbstract PDF
PURPOSE
Tbis phase II study was performed to evaluate the efficacy and safety of docetaxel in patients with anthracycline-pretreated metastatic breast cancer (MBC).
MATERIALS AND METHODS
From September 1996 to January 1998, 27 patients with metastatic breast cancer from 31 to 63 years of age with a performance status of 0 to 2 were registered in the phase II trial. All patients had metastatic breast cancer which had progressed or relapsed 2 during or after treatment with an anthracycline-based regimen. Docetaxel 75 mg/m2 was ad- ministered over 1 hour every 21 days until disease progression was documented or until toxic effects precluded further therapy. All patients received dexamethasone orally at the dose of 16 mg on days -1, 0, 1 of each cycle.
RESULTS
Objective responses were seen in 9 of 25 assessable patients (two complete and seven partial responses), with an overall objective response rale of 36%. The median duration of response was 36 weeks (range 19.0~40.5). The median time to progression and survival duration were 17.5 and 69 weeks, respectively, for assessable patients. One hundred fifty cycles (median, five) of docetaxel were administered. Among 27 patients assessable for toxicity, the following side effects were reported: nadir neutropenia grade 3 (4 patients) and grade 4 (22 patients); grade 2 stomatitis (6 patients); grade 2 alopecia (5 patients); grade 2 to 3 neurosensory toxicity (4 patients); no hypersensitivity reaction; mild fluid retention (4 patients).
CONCLUSION
Docetaxel is an active agent in patients with antracycline-pretreated metastatic breast cancer. Docetaxel was associated with severe but reversible neutropenia. Dexamethasone prevented hypersensitivity reactions and appeared to ameliorate fluid retention.
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Tumor - specific Virus Replication and Cytotoxicity of E1B 55 kD - deleted Adenovirus
Jaesung Kim, Boyoung Lee, Jinahn Kim, Joong Bae Ahn, Joon Oh Park, Nae Chun Yoo, Joo Hang Kim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Heuiran Lee
J Korean Cancer Assoc. 2000;32(1):200-209.
AbstractAbstract PDF
PURPOSE
To overcome the limitations of cancer gene therapy using replication-incom- petent adenovirus, we generated E1B 55 kD-deleted adenovirus (YKL-1) by polymerase chain reaction (PCR) and homologous recombination. We then investigated tumor-specific virus replication and cytotoxicity of YKL-1 in vitro and in vivo.
MATERIALS AND METHODS
YKL-1 was constructed by reintroducting E1A and E1B 19 kD into pTG-CMV El/E3-deficient adenoviral vector and inducing homologous recombination in E. coli. The recombinant vector pYKL-1 was transfected into 293 cells to generate YKL-1. The properties of newly constructed YKL-1 was defined by PCR and immuno- blotting analysis. Virus replication was examined by infecting human normal and cancer cells on 6-wells at multiplicity of infection (MOI) of 10 for 3 days. Virus was then recovered and titered. Cytopathic effect was analyzed by infecting human normal and cancer cells on 24-wells at MOIs of 10, 1 or 0.1 for 7 to 10 days and staining them with crystal violet solution. Inhibition of tumor growth was examined in human cancer cell xenografts in nu/nu mice by intratumoral injection of YKL-l.
RESULTS
PCR and immunoblotting analysis confirmed that YKL-1 contained E1A and E1B 19 kD but not E1B 55 kD. In human normal cells, virus replication and subsequent cytopathic effect of E1B 55 kD-deleted adenovirus YKL-1 was markedly attenuated by larger than 2 to 3 log in magnitude, compared to that of wild-type ad-XJ. In contrast, YKL-1 was capable of replicating and inducing cytotoxicity i.n most human cancer cells. C33A and Hep3B containing p53 mutation were much more sensitive, whereas HeLa and H460 with wild type p53 were relatively resistant to YKL-1. Finally, the tumor growth was dramatically retarded by intratumoral injection of YKL-1 in C33A cervical cancer xenograft and the histology showed significant necrosis by intratumoral injection of YKL-1.
CONCLUSION
The results here demonstrated the ability of preferential virus replication and cytotoxicity of ElB 55 kD-deleted adenovirus YKL-1 in human cancer cells. Therefore, these indicated a promising potential of YKL-1 as an antitumoral virus agent and a selective replication-competent virus vector.
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Prognostic Value of PCNA , c-erbB-2 , c-fos in Patients with Non-small Cell Lung Cancer
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
J Korean Cancer Assoc. 1999;31(4):678-685.
AbstractAbstract PDF
PURPOSE
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
Hyuk Jae Chang, Joong Bae Ahn, Jun Gu Lee, Kwang Yong Shim, Sun Young Rha, Sae Kyu Kim, Jun Chang, Sung Kyu Kim, Won Young Lee, Nae Chun Yoo, Hyun Cheol Chung, Jae Kyung Roh, Byung Soo Kim, Sung Jun Choi, Tae Won Kim, Chul Won Suh, Joo Hang Kim
J Korean Cancer Assoc. 1999;31(3):523-532.
AbstractAbstract PDF
PURPOSE
To evaluate the efficacy and safety of gemcitabine, a pyrimidine antimetabolite against advanced non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
Forty patients with unresectable stage IIIb to IV, pathologacally documented NSCLC were evaluated. Patients received gemcitabine 1000 mg/m, as a 30 to 60-min, intravenous infusion on days 1, 8 and 15, which was repeated every 28 days. Responses were assessed every two courses. Twenty-five to fifty percent dose reduction was permitted, ptovided that overall toxicity was severe according to World Health Organization (WHO) toxicity criteria.
RESULTS
Of all 40 patients (32 men, 8 women; age range 37 to 73 years; median 63 years), 3S patients were assessable for response. 15 patients had stage IIIb disease and 25 had stage IV. Nineteen patients were histologically classified as adenocarcinoma (47.5%), 17 as squamous cell carcinoma (42.5%), 1 as large cell carcinoma (2.5%), 1 as mixed carcinoma (2.5%) and 2 as undifferentiated carcinoma (5.0%). The overall response rate was 20%. None of the patients showed complete response while 7 showed partial response (20%), 5 had stable diseases (23%) and 23 had progressive diseases (57%). During a total of 119 courses, hematologic toxicity was negligible. Granulo- cytopenia worse than WHO grade 3 occured in 11.8%, anemia in O.S% and thrombocytopenia in 0.8%, respectively. Non-hematologic toxicity was minor and easily controlled. There was no case of febrile neutropenia or treatment-related death.
CONCLUSION
The single agent efficacy of gemcitabine is comparable to other agents commonly used to treat NSCLC. Gemcitabine has unusually mild side effect profile for such an active agent. This significant activity in conjunction with a very favorable toxicity profile supports further investigation in combination with other agents in patients with inoperable NSCLC.
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The Efficacy of Pre - operative Chamotherapy with Intra-arterial Cisplatin and Intravenous Adriamycin for High Grade Osteosarcoma
Sun Young Rha, Soo Jung Gong, Hee Cheol Chung, Kwang Yong Shim, Joong Bae Ahn, Nae Choon Yoo, Hyn Cheol Chung, Joo Hang Kim, Hae Kyung Roh, Jin Sik Min, Byung Soo Kim, Kyu Ho Shin, Woo Ick Yang, Chong In Lee
J Korean Cancer Assoc. 1999;31(1):134-143.
AbstractAbstract PDF
PURPOSE
Osteosarcoma is one of the most common juvenile malignant tumors in Korea. Combined modality treatment [pre-operative chemotherapy + surgery (limb salvage or amputation) + adjuvant chemotherapy] had improved the overall survival and quality of life. To improve the local control rate, we introduced pre-operative chemotherapy combined with intra-arterial (IA) cisplatin and continuous intravenous infusion (CI) of adriamycin. We evaluated the efficacy and feasibility, such as limb salvage rate, recurrence pattern and the survival impact, based on the histologic response of pre-operative chemotherapy.
MATERIALS AND METHODS
Fourty-one patients with histologically-proven high grade osteosarcoma of the extremities were enrolled from January 1990 to June 1996. Pre-operative chemotherapy, cisplatin 120 mg/m2 IA and adriamycin 75 mg/m2/72hrs CI, was administered for 3 cycles with 3 week interval, followed by surgery. Post-operative chemotherapy was applied by the tumor necrosis rate. If the tumor necrosis of the specimen was more than 90%, the same regimen af the preoperative one was administered for 3 cycles. A salvage regimen (Ifosfamide 7.5 gm/m2/5d IV + high dose MTX 10 gm/m2 IV VP-16 360 mg/m2/3d IV) was administered every 3 weeks for 6 cycles if the tumor necrosis was <90%.
RESULTS
Of 41 patients, 37 were evaluable for efficacy and toxicities, because 4 refused further chemotherapy after 1 or 2 cycles. Twenty-one patients were male and 16 female, with the median age of 16 years (8-41). The tumor locations were as follows: distal femur 20, proximal tibia 8, humerus 6, distal tibia 2 and 1 in proximal femur. All but one patient, who died of neutropenic sepsis, completed the planned pre-operative therapy. Of the 36 patients who received surgery, limb salvage surgery was possible in 30 patients (83.3%) and 27 patients (75%) showed a good response (10 with grade III, 27.8%; 17 with grade IV, 47.2%). With a median follow-up of 23 months, 3-year disease-free survival rate was 54.7% and overall survival rate was 78.3%. Of the 15 patients who recurred, the major metastatic site was the lungs. No operation-related mortality was observed. Most patients experienced grade III-IV nausea, vomiting and hematologic toxicities, which were reversible with supportive care.
CONCLUSION
Pre-operative chemotherapy combined with IA cisplatin and CI adriamycin induced higher good response rate without survival benefits. To improve the survival rate, the design of good salvage chemotherapy with a non-cross resistant regimen should be considered.
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Microsatellite Instability Correlate with a Prognosis in Breast Cancer
Hwa Young Lee, Chengshi Quan, Soo Jung Gong, Joon Oh Park, Joong Bae Ahn, Kwang Yong Shim, Sun Young Rha, Nae Choon Yoo, Woo Ick Yang, Joo Hang Kim, Jae Kyung Roh, Kyong Sik Lee, Byung Soo Kim, Hyun Cheol Chung
J Korean Cancer Assoc. 1998;30(5):914-920.
AbstractAbstract PDF
PURPOSE
Microsatellite instability in patients with defects in the mismatch repair system resulting in RER has a high risk of accumulating mutations in oncogene and tumor suppressor gene. In this study, we evaluated the incidence of microsatellite instability in breast cancer by comparing PCR-amplified sequences from frozen samples of normal and tumor tissue fram affected patients. We also investigated whether RER was associated with TGF-beta RII mutation.
MATERIALS AND METHODS
Fifty surgically resected breast cancer specimens from Jan. 1996 to June, 1997 were used for study. Microsatellite instability(referred to as replication error, RER) at three loci with BAT 26, BAT 40, TA10 was analyzed by polymerase chain reaction and the results were compared with clinicopathologic characteristics.
RESULTS
Of the 50 breast cancer patients, 14(28%) were RER(+) at one or more microsatellite loci, and 4(8%) showed TGF-beta RII mutation. Microsatellite instability was significantly correlated with lymph node involvement(especially in case of 4 or more lymph nodes involvement). But we could not find any correlation between RER and other prognostic factors including tumor size, tumor grade, hormone receptor status and pathology. One of fourteen tumors with RER(+) showed TGF-beta RII mutstion. There was no signiticant correlation between RER(+) and TGF-beta type II receptor gene mutation.
CONCLUSION
The findings suggest that microsatellite instability would be useful prognostic factor in unilateral breast cancer patients, and the role of targeting to gene mutation will be explored in future studies.
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Plasma TGF-beta1 as a Tumor Marker in Breast Cancer Patients
Hwa Young Lee, Sun Young Rah, Soo Jung Gong, Joong Bae Ahn, Kwang Yong Shim, Joon Oh Park, Hyun Ja Kwon, Nae Choon Yoo, Sook Jung Jeong, Hyun Cheol Chung, Joo Hang Kim, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Jae Kyung Roh
J Korean Cancer Assoc. 1998;30(5):935-942.
AbstractAbstract PDF
PURPOSE
Transforming Growth Factor-beta1(TGF-beta1) is the most potent inhibitor of the progression of normal mammary epithelial cells through the cell cycle. However, advanced breast cancers are mostly refractory to TGF-beta mediated growth inhibition and produce large amounts of TGF-beta, which may enhance tumor cell invasion and metastasis by its effects on extracellular matrix. Yet, little is known about the association of TGF-beta1 with progression of malignant disease in vivo. In this study, we evaluated the preoperative and postoperative plama level of TGF- in breast cancer and analyzed the utility of plasma TGF-beta1 as possible tumor marker.
MATERIALS AND METHODS
ELISA(enzyme-linked immunosorbent assay) was used to measure plasma TGF-beta1 level in 45 newly diagnosed breast cancer patients and in 15 normal healthy people, and the results were compared with clinicopathologic characteristics.
RESULTS
The mean plasma TGF-beta1 levels were 1.73+/-0.47 ng/ml in normal people and 5.05+/-1.41 ng/ml in breast cancer patiens. In 37 operated patients, the preoperative plasma TGF-beta1 level was 6.34+/-1.34 ng/ml and decreased to 4.48+/-1.07 ng/ml in patients with follow-up after surgery and 4.74+/-0.79 ng/ml in patients with chemotherapy. However, there was no significant correlation between plasma TGF-beta1 level and known prognostic factors including tumor size, LN involvement, tumor grade, hormone receptor status, and pathology.
CONCLUSION
These findings suggest that the plasma TGF-g level can be a tumor marker in breast cancer patients and the association with progression of breast cancer will be explored in future studies.
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Effects of Herpes Simplex Virus - Thymidine Kinase Gene Transduction into the Hepatocellular Carcinoma Cell Lines Using the Retrovirus on Ganciclovir Cytoxicity
Joo Hang Kim, Jae Jin Song, Yoon Soo Chang, Eun Hee Kim, Jae Sung Kim, Heui Ran Lee, Jae Kyung Roh, Byung Soo Kim, Joong Bae Ahn, Nae Chun Yoo, Hyun Cheol Chung
J Korean Cancer Assoc. 1998;30(5):1034-1043.
AbstractAbstract PDF
PURPOSE
Hepatocellular carcinoma (HCC) is one of the most common malignancy with high mortality in Korea. A new therapeutic modality such as gene therapy is necessary to improve the prognosis of hepatoma patients. Therefore we investigated the preclinical significance of Herpes simplex virus - thymidine kinase/ganciclovir (HSV-tk/GCV) gene therapy model using the retroviral vector for HCC cell lines.
MATERIALS AND METHODS
LNC/HSV-tk retroviral vector and PA317/LNC/HSV-tk pro- ducer cell line were constructed. HSV-tk transduced HCC cells using the LNC/HSV-tk retrovirus were selected by the G418 containing media. In vitro GCV sensitivity test of the HCC cells was performed by MTT assay. To evaluate in vivo GCV sensitivity, GCV was intraperitoneally injected after subcutaneous administration of HCC cells into each flank of the nude mouse.
RESULTS
HSV-tk gene transduction and expression in HCC cells were confirmed by RT-PCR. HSV-tk transduced HCC cell lines (SK-Hepl/HSV-tk and Hep-3B/HSV-tk) showed the marked GCV sensitivity comparing with the parental cell lines (SK-Hepl and Hep-3B) by MTT assay (p<0.001). The MTT test revealed that SK-Hepl/HSV-tk cells were more sensitive to GCV compare with that of Hep-3B/H5V-tk cells, and the parent cell line showed minimal growth suppression by the GCV treatment. In 12 nude mice received tumor cell mixtures of Hep-3B and Hep-3B/HSV-tk cells which contained more than 50% of HSV-tk transduced cells, the tumor was not developed in ll mice by the intraperitoneal administration of GCV. The tumors developed in 1 of 6 mice and 5 of 6 mice when mixtures contained 30% and 10% of HSV-tk transduced cells, respectively. Five mice out of 6 mice received inoculum containing the mixtures of 70% and 50% of HSV-tk transduced cells into each flank survived more than 6 month after HSV-tk/GCV treatment. Conelusion: HSV-tk gene transduced HCC cells showed the enhanced sensitivity to GCV. In nude mice HSV-tk/GCV strategy for HCC seemed to be more effective when tumor cell inoculum contained more than 30% of HSV-tk transduced HCC cells.
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GEnetic Change in Transforming Growth Factor-B (TGF-B) Receptor Type I and Type II Genes with Resistance to TGF-B of Human Breast Cancer Cells
Hwa Young Lee, Sung Sil Jeon, Hyun Ja Kwon, Soo Jung Kong, Seon Young Rah, Joong Bae Ahn, Kwang Yong Sim, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Kyung Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Chul Chung
J Korean Cancer Assoc. 1998;30(4):683-691.
AbstractAbstract PDF
PURPOSE
Transforming growth factor-Bs (TGF-Bs) are prototypic multifunctional negative growth factors that inhibit the growth of many cell types. TGF-B type I and II receptors(RI, RII) are transmembrane receptors containing cytoplasmic serine/ threonine kinase domain and have been implicated in mediating TGF-B activity. Because a heteromeric complex of RI and RII is required for TGF-B signal transduction, cancer cells may reduce the expression of either RI or RII to escape from growth inhibition of TGF-B. We examined the correlation between the growth inhibitory activity of TGF-B1 and the genetic expression of RI &RII genes in human breast cancer cell lines.
MATERIALS AND METHODS
We examined the growth inhibitory activity of TGF-B1 in 5 breast cancer cell lines by incorporation of [3H] thymidine. To investigate the correlation between TGF-B1 insensitivity and genetic change of TGF-B receptor genes (RI, RII), Southem blot analysis, Northern blot analysis, and Western blot analysis were performed. We also examined whether microsatellite instability(RER) was associated with RII mutation.
RESULTS
We found that 3 breast cancer cell lines (MCF-7, YCC-B101, YCC-B151) were resistant to growth inhibitory effect of TGF-B1. MCF-7 cell line expressed no detectable RII mRNA and RII protein, but showed normal structure of RII gene and normal expression of RI gene. And we did not find any abnormal expression of mRNA, protein, and genetic structure of RI &RII in YCC-B101 and YCC-B151.
CONCLUSION
Our results suggest that aquired resistance to the growth inhibitory effect of TGF-B1> could be transcription regulation system of RII in MCF-7 cell line, and could be postreceptor signal transduction pathway in YCC-B101 and YCC-B151 cell lines.
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Effect on Malignant Phenotype of Gastric Cancer Cell Line after p53 Gene Transduction
Sun Young Rha, Tae Soo Kim, Sook Jung Jeong, Joong Bae Ahn, kwang Yong Shim, Soo Jung Kong, Hwa Young Lee, Nae Choon Yoo, Jin Hyuk Choi, Ho Young Lim, Joo Young Lim, Jae Kyung Roh, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung
J Korean Cancer Assoc. 1998;30(3):508-520.
AbstractAbstract PDF
PURPOSE
To evaluate the effect of wild type p53 gene transduction on the malignant phenotypes for metastasis in gastric cancer, we compared the biological phenpotypes of gastric cancer cell lines based on p53 gene status. Then, after retrovirus-mediated wild-type p53 gene transduction, we compared those phenotypes among parent YCC-3 cell line, vector transduced YCC-3v cell line and a clone of YCC-3C3. MATERIAL AND METHODS: Four human gastric cancer celi lines were used; YCC-l(mutant), YCC-2(wild), YCC-3(mutant) and AGS(wild). DNAs of the cell lines were analyzed to evaluate the mobility shift with PCR-SSCP. Tumorigenecity and proliferation were evaluated by soft agar assay and proliferation assay. Migratory capacity was measured by adhesion assay and Boyden chamber assay. p53 protein expression was measured by Western blot analysis and VEGF, WAF-1 were measured by ELISA assay. Angiogenic activity was measured by cross-feeding assay and cell cycle analysis was performed by flowcytometry. In vivo tumorigenicity was measured by xenograft in nude mice.
RESULTS
YCC-3 cell line with mutant p53 gene expressed all the phenotypes for the metastasis such as tumorigenicity, migration and angiogenesis. In a stable clone of YCC-3C3, no differences were found in proliferation, cell cycle and WAP-1 expression when compared to those of the control YCC-3v and parent YCC-3 cell line, even if increased p53 protein production was found by Western blot analysis. However, both in vitro and in vivo tumorigenicity were decreased in a stably transduced YCC-3C3 clone. The adhesive capacity was also decreased in YCC-3C3 clone whereas the endothelial cell growth stimulatory effect and VEGF production showed no difference compared to those of the YCC-3v cell line.
CONCLUSION
Wild-type p53 gene transduction in gastric cancer cell line decreased tumorigenicity which resulted from decreased colony forming activity and adhesive capacity but not formed changes of angiogenic activity. This suggested the possible application of anti- metastasis strategy with p53 gene therapy in gastric cancer.
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Brain Metastasis and Leptomeningeal Carcinomatosis in Breast Cancer
Yoon Soo Chang, Jeong Hun Seo, Ruth Lee, Joong Bae Ahn, Kwang Yong Shim, Soo Jung Gong, Hwa Young Lee, Sun Young Rha, Nae Choon Yoo, Chang Ok Suh, Joo Hang Kim, Jae Kyung Rho, Kyong Sik Lee, Jin Sik Min, Byung Soo Kim, Hyun Cheol Chung
J Korean Cancer Assoc. 1998;30(3):464-474.
AbstractAbstract PDF
PURPOSE
Brain metastasis is estimated to occur in 20 to 40% of cancer patients, and meningeal involvement has been reported in 5% to 8% of cancer patients. Even if the prognosis is grave, standard treatment modality of brain metastasis or leptomeningeal carcinomatosis has not been established. We evaluated the prognosis and the clinical features of the brain and leptomeningeal metastasis of the breast cancer.
MATERIALS AND METHODS
The 43 patients who was diagnosed as brain parenchymal metastasis or leptomeningeal carcinomatosis clinically, radiologically and/or cytologically were included in this study. The median age was 44(range: 27-61) years.
RESULTS
The median duration from brain metastasis to death was 181 days(range: 8~1599), and the median duration from leptomeningeal carcinomatosis to death was 39 days(range: 25~152). Age(p=0.7174) and number of brain metastatic lesion(p=0.4097) did not influence the survival, but the presence of other systemic metastatic lesion affected the survival(p 0.0224). When we compared the survival rates of patients according to treatment modality, the patients with systemic chemotherapy versus patients without systemic chemotherapy showed differences(p= 0.0009). Patients treated with whole brain radiation only versus patients with whole brain radiation and other systemic management also showed different survival rate(p=0.0009). But intrathecal chemotherapy had no effect on survival. Well differentiated, solitary lesions were treated by operation and/or gamma-knife surgery, and their effects were good.
CONCLUSION
Prolongation of survival was suggested with whole brain radiotherapy combined with systemic treatment in brain or leptomeningeal metastasis. Further study is expected to confirm this finding.
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Expression and Clinical Relevance of c-erbB-3 in Rectal Cancer
Chong In Lee, Sun Young Rha, Jin Oh Park, Hyun Cheol Chung, Jae Yong Cho, Joong Bae Ahn, Nae Choon Yoon, Tae Soo Kim, Joo Hang Kim, Jae Kyung Roh, Jin Sup Choi, Jin Sik Min, Byung Soo Kim, Woo Ick Ja
J Korean Cancer Assoc. 1996;28(1):50-63.
AbstractAbstract PDF
Recently, there is an increasing tendency of colorectal cancer in Korea, probably due to changes of diet pattern to western style. In rectal cancer, as the local recurrence is a common and major problem despite of radical resection, it is recommended to use 5-fluorouracil(5-FU)- based chemotherapy in combination with pelvic radiation after radical operation in MAC B,-C, cancers. But until now, there are many controversies about the effective chemotherapeutic agent, radiation dose, route, and chemoradiation schedule. There is increasing evidence that genes involved in normal cell growth and differentiation(oncogenes) or genes that encode for growth factor are important in determining the development and biologic aggressiveness of various cancers. Among many oncogenes thought to be related with cancer, c-erbB-2 is a relatively well known protein to be associated with cancers, especially in breast and colorectal cancers. In addition to c-erbB-2 and Epidermal Growth Factor Receptor(EGFR), c-erbB-3 belongs to Type -I Growth Factor Receptor Family(EGFR-related Family) and is the most recently identified protein in EGFR-related Family. There have been a few reports about the prognostic value of c-erbB-3 in breast and prostate cancers. In this study we performed immunohistochemical staining of 114 surgically resected specimens of rectal cancers to investigate the expression rate and clinical relevance of c-erbB-3 as a prognostic factor and drug selection marker. c-erbB-3 expression rate was 46% in 114 rectal cancers and there were significant differences in recurrence rate and survival rate between c- erbB-3 positive and negative group. Twenty-one cases(40%) recurred in 52 c-erbB-3 positive cases and 10 cases(16%) recurred in 62 c-erbB-3 negative cases(p=0.004). The difference in recurrence rate between c-erbB-3 positive and negative group was significant exclusively in MAC stage C(p=0.0126), but not in MAC stage B(p=0.4357). In c-erbB-3 positive and negative group, 2-year disease free survival rate was 66% and 87%, respectively(p=0.0052), and 2-year overall survival rate was 84% and 95%, respectively(p=0.005). Again, the difference in 2-year disease free survival rate between the two groups was significant only in MAC stage C(p=0. 0137), not in stage B(p=0.4182). There were no significant differences in recurrence rate and 2- year disease free survival rate in chemo-radiation group regardless of c-erbB-3 expression and stage. But in adjuvant radiotherapy alone group, increased recurrence rate and decreased survival rate were found in c-erbB-3 positive group. This finding suggested c-erbB-3 as a possible relative radioresistance marker, in whom a higher radiotherapy dose is needed. In conclusion, c-erbB-3 may be regared as a prognostic marker and as a possible indicator of radioresistance in the treatment of rectal cancer.
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Expression in Matrix - Metalloproteinases ( MMP-2 , MMP-9 ) in Gastric Cancer as new Targets for Biotherapy
Hyun Cheol Chung, Jae Yong cho, Sun Young Rha, Joon Oh Park, Joong Bae Ahn, Choong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Sung Hoon Noh, Jin Sik Min, Byung Soo Kim, Ho Yeong Lim, Jin Hyu Choi
J Korean Cancer Assoc. 1995;27(6):897-907.
AbstractAbstract PDF
The proteolytic processes are thought to be the critical point in tumor invasion and metastasis, mainly by matrix-metalloproteinases (MMPs) and serine proteases. We measured the activities of MMP-9 and MMP-2 in the 120 normal and cancer tissue samples from the same patients using gelatin zymography. Inactive MMP-9(92 kD) was expressed in 73.3% of the normal and 87.5% of the cancer tissues, respectively (p=0.009), while active MMP-9(82 kD) was expressed in 24.2% and 53.3%, respectively (p=0.0001). Inactive MMP-2 (72kD) was expressed in 33.3% of the normal and 55.0% of the cancer tissues, respectively (p=0.001), while active MMP-2(62kD) was expressed in 4.2% and 31.7%, respectively (p=0.0001). In Tl state, only frequency of expression and enzymatic activity of the active MMP-2(62kD) were increased, while from T2 stage, the expression and the activation of the both MMP-9 and MMP-2 were increased as the cancer progressed. The expression frequency of the MMP-9 was more common than of the MMP-2. The co-expression rate of the active forms (82 kD, 62 kD), activites of 82 kD and 62 kD, and the activation rates of the both MMPs were increased as the cancer invades and metastasizes to distant lymph node areas. In conclusion, MMP-2 activation was the main causes of the increased MMPs activity during the Tl phase of the gastric cancer, while production and activation of the both MMP-9 and MMP-2 were increased as the cancer progressed. Therefore, we suggest that the different expression and activation of the MMPs in the gastric cancer progression can be a potential therapeutic target in gastric cancer biotherapy.
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Detection of Soluble c-erbB-2 Oncoproteins in the Serum of Gastric Cnacer patients as a Tumor Marker
Hyung Cheol Chung, Joong Bae Ahn, Joon Oh Park, Jae Yong Cho, Sun Young Rha, Chong In Lee, Hye Ran Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Sung Hoon Noh, Jin Sik Min, Byung Soo Kim, Ho Yeon
J Korean Cancer Assoc. 1995;27(2):175-184.
AbstractAbstract PDF
A soluble fragment of the c-erbB-2 oncoprotein become detectable in the serum of the breast cancer petients by enzyme-linked immunosorbent assay(ELISA). To evaluate the clinical sig- nificance of soluble c-erbB-2 in gastric cancer, we measured the serum levels in 45 normal healthy persons and in 86 gastric cancer patients. Fifty-five patients were underwent surgery(47 curative surgery, 8 palliative surgery) and thirty-one patients were inoperable(18 advanced, 8 relapsed, 6 progressed after palliative surgery). The c-erbB-2 serum levels were below 14 U/ml in normal persons. Three of 86(3.5%) sam- ples from gastric cancer patients had elevated serum c-erbB-2 leveL In 55 operated patients, all serum samples were negative for c-erbB-2. Elevated serum levels were predominantly found in patients with initially advanced cancers(3/18: 16.7%). In 22 operated cases, immunohisto- chemical staining showed 36.4% c-erbB-2 positive ratio(8/22) in tissues. Comparing the results from sera and tissues studies, the sensitivity of serum ELISA assay was too low even if the specificity was high. Our data suggest that the soluble c-erbB-2 oncoprotein can be a tumor marker only in advanced stage of gastric cancer. Further studies are warrented to elucidate the discrepancy between the serum and tissue results in oprable early stage gastric cancer.
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Prognostic Factors in Node - Negative Breast Cancer
Kyung Hee Lee, Hyun Cheol Chung, Jae Yong Cho, Sun Young Rha, Joong Bae Ahn, Chong In Lee, Nae Choon Yoo, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim, Kyung Sik Lee, Kyl Beom Lee, Ho Yeong Lim, Jin Hy
J Korean Cancer Assoc. 1995;27(2):265-275.
AbstractAbstract PDF
Breast cancer is the third most common malignant neoplasm in Korean women. The effect of postoperative adjuvant systemic therapy in the treatment of primary breast cancer with pathologic involvement of the axillary lymph nodes has been well established. But, 20 30% of node-negative breast cancer patients will develop recurrent disease and risk death within 10 years after initial local therapy without adjuvant treatment. Therfore, it is reasonable to identify those node-negative breast cancer patients at significant risk for recurrence and who could be treated with adjuvant therapies. A clinical study was perofrmed in 184 cases of primary node-negative breast cancers from January 198l to December 1991 to study the natural course of the diaease and to find-out the prognostic factors. The following results were obtained; l) During 73 monthe(9-143) of follow-up duration, 5-year and 10-year relapse free survival rates were 88%, 77% respectively, and overall survival rates were 89%, 88%, respectively. 10 year recurrence rate was 19%. 2) Median disease-free and survival durations were 80 month, 17 months, respectively, in tumor size<2 cm group and 68.5 months, 62 months respectively in tumor size 2-5 cm group. 3) Median disease-free and overall survival durations were 73 months, 61 months, respectively, in premenopause patients and 74 months, 73 months in postmenopause patients. 4) No differences were found in disease-free and survival duration based on types of operation. 5) With adjuvant treatment, there was a decreasing tendency of systemic relapse. In conclusion, continuous relapse was found in node-negative breast cancer even after 5 years of operation. Even if decreasing tendency of systemic relapse was induced with adjuvant treatment, no clinically useful prognostic factors were found from surgical and pathologic factors until now. Further study of biological factors in node-negative breast cancer is warrented.
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