Cancer Research and Treatment

Sung Hoon Noh

32 Articles

Gastrointestinal cancer

A Multi-cohort Study of the Prognostic Significance of Microsatellite Instability or Mismatch Repair Status after Recurrence of Resectable Gastric Cancer: Ji Yeong An, Yoon Young Choi, Jeeyun Lee, Woo Jin Hyung, Kyoung-Mee Kim, Sung Hoon Noh, Min-Gew Choi, Jae-Ho Cheong; Cancer Res Treat. 2020;52(4):1153-1161. Published online May 4, 2020; DOI: https://doi.org/10.4143/crt.2020.173

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Purpose
High microsatellite instability (MSI) is related to good prognosis in gastric cancer. We aimed to identify the prognostic factors of patients with recurrent gastric cancer and investigate the role of MSI as a prognostic and predictive biomarker of survival after tumor recurrence.
Materials and Methods
This retrospective cohort study enrolled patients treated for stage II/III gastric cancer who developed tumor recurrence and in whom the MSI status or mismatch repair (MMR) status of the tumor was known. MSI status and the expression of MMR proteins were evaluated using polymerase chain reaction and immunohistochemical analysis, respectively.
Results
Of the 790 patients included, 64 (8.1%) had high MSI status or MMR deficiency. The tumor-node-metastasis stage, type of recurrence, Lauren classification, chemotherapy after recurrence, and interval to recurrence were independently associated with survival after tumor recurrence. The MSI/MMR status and receiving adjuvant chemotherapy were not associated with survival after recurrence. In a subgroup analysis of patients with high MSI or MMR-deficient gastric cancer, those who did not receive adjuvant chemotherapy had better treatment response to chemotherapy after recurrence than those who received adjuvant chemotherapy.
Conclusion
Patients with high MSI/MMR-deficient gastric cancer should be spared from adjuvant chemotherapy after surgery, but aggressive chemotherapy after recurrence should be considered. Higher tumor-node-metastasis stage, Lauren classification, interval to recurrence, and type of recurrence are associated with survival after tumor recurrence and should thus be considered when establishing a treatment plan and designing clinical trials targeting recurrent gastric cancer.

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HIGD1B, as a novel prognostic biomarker, is involved in regulating the tumor microenvironment and immune cell infiltration; its overexpression leads to poor prognosis in gastric cancer patients
Shibo Wang, Siyi Zhang, Xiaoxuan Li, Xiangxue Li, Shufen Zhao, Jing Guo, Shasha Wang, Rui Wang, Mengqi Zhang, Wensheng Qiu
Frontiers in Immunology.2024;[Epub] CrossRef
Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis
Li-Hua Zhang, Hui-Qin Zhuo, Jing-Jing Hou, Yang Zhou, Jia Cheng, Jian-Chun Cai
World Journal of Gastrointestinal Oncology.2022; 14(11): 2097. CrossRef
The distinct clinical trajectory, metastatic sites, and immunobiology of microsatellite-instability-high cancers
Shuting Han, Aik Yong Chok, Daniel Yang Yao Peh, Joshua Zhi-Ming Ho, Emile Kwong Wei Tan, Si-Lin Koo, Iain Bee-Huat Tan, Johnny Chin-Ann Ong
Frontiers in Genetics.2022;[Epub] CrossRef
Mismatch Repair Status Characterization in Oncologic Pathology: Taking Stock of the Real-World Possibilities
Roberto Piciotti, Konstantinos Venetis, Elham Sajjadi, Nicola Fusco
Journal of Molecular Pathology.2021; 2(2): 93. CrossRef
The Impact of Mismatch Repair Status on Prognosis of Patients With Gastric Cancer: A Multicenter Analysis
Wen-Long Guan, Yue Ma, Yue-Hong Cui, Tian-Shu Liu, Yan-Qiao Zhang, Zhi-Wei Zhou, Jian-Ying Xu, Li-Qiong Yang, Jia-Yu Li, Yu-Ting Sun, Rui-Hua Xu, Feng-Hua Wang, Miao-Zhen Qiu
Frontiers in Oncology.2021;[Epub] CrossRef
Establishment of a 5-gene risk model related to regulatory T cells for predicting gastric cancer prognosis
Gang Hu, Ningjie Sun, Jiansong Jiang, Xiansheng Chen
Cancer Cell International.2020;[Epub] CrossRef
Mismatch Repair System Genomic Scars in Gastroesophageal Cancers: Biology and Clinical Testing
Gianluca Lopez, Konstantinos Venetis, Elham Sajjadi, Nicola Fusco
Gastrointestinal Disorders.2020; 2(4): 341. CrossRef

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

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

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Utility of TMPRSS4 as a Prognostic Biomarker and Potential Therapeutic Target in Patients with Gastric Cancer
Hirofumi Tazawa, Takahisa Suzuki, Akihisa Saito, Akira Ishikawa, Toshiaki Komo, Haruki Sada, Norimitsu Shimada, Naoto Hadano, Takashi Onoe, Takeshi Sudo, Yosuke Shimizu, Kazuya Kuraoka, Hirotaka Tashiro
Journal of Gastrointestinal Surgery.2022; 26(2): 305. CrossRef
Scoring systems for PD-L1 expression and their prognostic impact in patients with resectable gastric cancer
Marina Alessandra Pereira, Marcus Fernando Kodama Pertille Ramos, André Roncon Dias, Renan Ribeiro, Leonardo Cardili, Bruno Zilberstein, Ivan Cecconello, Ulysses Ribeiro, Evandro Sobroza de Mello, Tiago Biachi de Castria
Virchows Archiv.2021; 478(6): 1039. CrossRef
Epstein–Barr Virus Positive Gastric Cancer: A Distinct Subtype Candidate for Immunotherapy
Marina Alessandra Pereira, Daniel Amadeus Molon Batista, Marcus Fernando Kodama Pertille Ramos, Leonardo Cardili, Renan Ribeiro e Ribeiro, Andre Roncon Dias, Bruno Zilberstein, Ulysses Ribeiro Jr, Ivan Cecconello, Venâncio Avancini Ferreira Alves, Evandro
Journal of Surgical Research.2021; 261: 130. CrossRef
Cytotoxic T‐lymphocyte‐associated protein 4 in gastric cancer: Prognosis and association with PD‐L1 expression
Marina Alessandra Pereira, Tiago Biachi de Castria, Marcus Fernando Kodama Pertille Ramos, André Roncon Dias, Leonardo Cardili, Rafael Dyer Rodrigues de Moraes, Bruno Zilberstein, Sergio Carlos Nahas, Ulysses Ribeiro, Evandro Sobroza de Mello
Journal of Surgical Oncology.2021; 124(7): 1040. CrossRef
Remnant gastric cancer: a neglected group with high potential for immunotherapy
Marcus Fernando Kodama Pertille Ramos, Marina Alessandra Pereira, Tiago Biachi de Castria, Renan Ribeiro e Ribeiro, Leonardo Cardili, Evandro Sobroza de Mello, Bruno Zilberstein, Ulysses Ribeiro-Júnior, Ivan Cecconello
Journal of Cancer Research and Clinical Oncology.2020; 146(12): 3373. CrossRef
Molecular Bases of Mechanisms Accounting for Drug Resistance in Gastric Adenocarcinoma
Jose J. G. Marin, Laura Perez-Silva, Rocio I. R. Macias, Maitane Asensio, Ana Peleteiro-Vigil, Anabel Sanchez-Martin, Candela Cives-Losada, Paula Sanchon-Sanchez, Beatriz Sanchez De Blas, Elisa Herraez, Oscar Briz, Elisa Lozano
Cancers.2020; 12(8): 2116. CrossRef
Clinical Significance of CLDN18.2 Expression in Metastatic Diffuse-Type Gastric Cancer
Seo Ree Kim, Kabsoo Shin, Jae Myung Park, Han Hong Lee, Kyo Yong Song, Sung Hak Lee, Bohyun Kim, Sang-Yeob Kim, Junyoung Seo, Jeong-Oh Kim, Sang-Young Roh, In-Ho Kim
Journal of Gastric Cancer.2020; 20(4): 408. CrossRef
Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis
van den Ende, ter Veer, Mali, van Berge Henegouwen, Hulshof, van Oijen, van Laarhoven
Cancers.2019; 11(4): 530. CrossRef

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

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

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Efficacy and safety of docetaxel plus S-1-based therapy in gastric cancer: a quantitative evidence synthesis of randomized controlled trials
Hui-Fen Lv, Li-Feng Qin, Rui-Zhi Ran, Xue-Ping Jiang, Fang-Yu Zhao, Bo Li
Frontiers in Pharmacology.2024;[Epub] CrossRef
A novel method of bedside hyperthermic intraperitoneal chemotherapy as adjuvant therapy for stage-III gastric cancer
Lili Liu, Li Sun, Ning Zhang, Cheng-gong Liao, Haichuan Su, Jie Min, Yang Song, Xue Yang, Xiaofeng Huang, Dongxu Chen, Yu Chen, Hong-wei Zhang, Helong Zhang
International Journal of Hyperthermia.2022; 39(1): 239. CrossRef
Comment on “post-discharge oral nutritional supplements with dietary advice in patients at nutritional risk after surgery for gastric cancer: A randomized clinical trial”
Qiang Hu, Yuanshui Sun
Clinical Nutrition.2021; 40(3): 1438. CrossRef
THE ROLE OF ADJUVANT CHEMOTHERAPY IN THE TREATMENT OF LOCALLY ADVANCED GASTRIC CANCER
A. A. Bobryshev, M. M. Davudov, M. N. Narimanov, S. B. Polycarpova, V. Y. Kirsanov, V. N. Blindar
Siberian journal of oncology.2021; 20(1): 133. CrossRef
Multidisciplinary treatment strategy for locally advanced gastric cancer: A systematic review
Kotaro Sugawara, Yoshikuni Kawaguchi, Yasuyuki Seto, Jean-Nicolas Vauthey
Surgical Oncology.2021; 38: 101599. CrossRef
Surgery alone, adjuvant tegafur/gimeracil/octeracil (S-1), or platinum-based chemotherapies for resectable gastric cancer: real-world experience and a propensity score matching analysis
Chih-Chieh Yen, Yan-Shen Shan, Ying-Jui Chao, Ting-Kai Liao, I-Shu Chen, Hsuan-Yi Huang, I-Ting Liu, Chia-Jui Yen
BMC Cancer.2021;[Epub] CrossRef
Treatment of Locally Advanced Gastric Cancer (LAGC): Back to Lauren’s Classification in Pan–Cancer Analysis Era?
Ina Valeria Zurlo, Michele Basso, Antonia Strippoli, Maria Alessandra Calegari, Armando Orlandi, Alessandra Cassano, Mariantonietta Di Salvatore, Giovanna Garufi, Emilio Bria, Giampaolo Tortora, Carlo Barone, Carmelo Pozzo
Cancers.2020; 12(7): 1749. CrossRef
A systematic review and network meta-analysis protocol of adjuvant chemotherapy regimens for resected gastric cancer
Long Ge, Liangying Hou, Qingxia Yang, Yiting Wu, Xiue Shi, Jiang Li, Kehu Yang
Medicine.2019; 98(7): e14478. CrossRef
Prognostic and Predictive Factors for the Curative Treatment of Esophageal and Gastric Cancer in Randomized Controlled Trials: A Systematic Review and Meta-Analysis
Tom van den Ende, Emil ter Veer, Rosa M. A. Mali, Mark I. van Berge Henegouwen, Maarten C. C. M. Hulshof, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven
Cancers.2019; 11(4): 530. CrossRef
COMplot, A Graphical Presentation of Complication Profiles and Adverse Effects for the Curative Treatment of Gastric Cancer: A Systematic Review and Meta-Analysis
Tom van den Ende, Frank A. Abe Nijenhuis, Héctor G. van den Boorn, Emil ter Veer, Maarten C. C. M. Hulshof, Suzanne S. Gisbertz, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven
Frontiers in Oncology.2019;[Epub] CrossRef
Cutting-edge evidence of adjuvant treatments for gastric cancer
Dai Shimizu, Mitsuro Kanda, Yasuhiro Kodera, Junichi Sakamoto
Expert Review of Gastroenterology & Hepatology.2018; 12(11): 1109. CrossRef

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

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Purpose

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

Materials and Methods

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

Results

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

Conclusion

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

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Drug-Induced Peripheral Neuropathy: Diagnosis and Management
Diala Merheb, Georgette Dib, Maroun Bou Zerdan, Clara El Nakib, Saada Alame, Hazem I. Assi
Current Cancer Drug Targets.2022; 22(1): 49. CrossRef
Treatment Outcome and Safety of the TCX Regimen for Advanced Gastric Cancer: A Prospective Cohort Study
Hieu Trong Nguyen, Kien Hung Do, Nguyen Ba Le, Thang Tran
Cancer Management and Research.2022; Volume 14: 2825. CrossRef
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Tore B. Stage, Shuiying Hu, Alex Sparreboom, Deanna L. Kroetz
Clinical and Translational Science.2021; 14(2): 460. CrossRef
Personalized Antibodies for Gastroesophageal Adenocarcinoma (PANGEA): A Phase II Study Evaluating an Individualized Treatment Strategy for Metastatic Disease
Daniel V.T. Catenacci, Stephanie Moya, Samantha Lomnicki, Leah M. Chase, Bryan F. Peterson, Natalie Reizine, Lindsay Alpert, Namrata Setia, Shu-Yuan Xiao, John Hart, Uzma D. Siddiqui, D. Kyle Hogarth, Oliver S. Eng, Kiran Turaga, Kevin Roggin, Mitchell C.
Cancer Discovery.2021; 11(2): 308. CrossRef
Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy
Giulia Fumagalli, Laura Monza, Guido Cavaletti, Roberta Rigolio, Cristina Meregalli
Frontiers in Immunology.2021;[Epub] CrossRef
Pathogenesis of paclitaxel-induced peripheral neuropathy: A current review of in vitro and in vivo findings using rodent and human model systems
Nathan P. Staff, Jill C. Fehrenbacher, Martial Caillaud, M. Imad Damaj, Rosalind A. Segal, Sandra Rieger
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Yoko Tomita, Max Moldovan, Rachael Chang Lee, Amy HC Hsieh, Amanda Townsend, Timothy Price
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Prognosis of pN3 Stage Gastric Cancer: Jung Ryun Ahn, Minkyu Jung, Chan Kim, Min Hee Hong, Hong Jae Chon, Hye Ryun Kim, Hei-Cheul Jeung, Woo Jin Hyung, Sung Sook Lee, Hyun Cheol Chung, Sung Hoon Noh, Sun Young Rha; Cancer Res Treat. 2009;41(2):73-79. Published online June 30, 2009; DOI: https://doi.org/10.4143/crt.2009.41.2.73

Abstract PDF PubReader ePub

Purpose

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

Materials and Methods

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

Results

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

Conclusion

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

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Nick Baniak, Jenna-Lynn Senger, Shahid Ahmed, S. C. Kanthan, Rani Kanthan
World Journal of Surgical Oncology.2016;[Epub] CrossRef
MiR 21‐5p as a predictor of recurrence in young gastric cancer patients
Soo‐Kyung Park, Young Soo Park, Ji Yong Ahn, Eun‐Ju Do, Dongho Kim, Jee Eun Kim, kyoungwon Jung, Jeong‐Sik Byeon, Byong Duk Ye, Dong Hoon Yang, Sang Hyoung Park, Sung Wook Hwang, Hwoon‐Yong Jung, Seung‐Jae Myung
Journal of Gastroenterology and Hepatology.2016; 31(8): 1429. CrossRef
Functional polymorphisms in apoptosis pathway genes and survival in patients with gastric cancer
Dongying Gu, Mulong Du, Cuiju Tang, Haiyan Chu, Zhi Xu, Xinyin Huo, Weida Gong, Yongfei Tang, Jianwei Zhou, Na Tong, Yong Xu, Zhengdong Zhang, Meilin Wang, Jinfei Chen
Environmental and Molecular Mutagenesis.2014; 55(5): 421. CrossRef
Improved survival after adding dissection of the superior mesenteric vein lymph node (14v) to standard D2 gastrectomy for advanced distal gastric cancer
Bang Wool Eom, Jungnam Joo, Young-Woo Kim, Daniel Reim, Ji Yeon Park, Hong Man Yoon, Keun Won Ryu, Jong Yeul Lee, Myeong-Cherl Kook
Surgery.2014; 155(3): 408. CrossRef
Comprehensive genomic meta-analysis identifies intra-tumoural stroma as a predictor of survival in patients with gastric cancer
Yonghui Wu, Heike Grabsch, Tatiana Ivanova, Iain Beehuat Tan, Jacinta Murray, Chia Huey Ooi, Alexander Ian Wright, Nicholas P West, Gordon G A Hutchins, Jeanie Wu, Minghui Lee, Julian Lee, Jun Hao Koo, Khay Guan Yeoh, Nicole van Grieken, Bauke Ylstra, Sun
Gut.2013; 62(8): 1100. CrossRef
Validity and Necessity of Sub-classification of N3 in the 7thUICC TNM Stage of Gastric Cancer
Fang-Xuan Li, Ru-Peng Zhang, Han Liang, Ji-Chuan Quan, Hui Liu, Hui Zhang
Asian Pacific Journal of Cancer Prevention.2013; 14(3): 2091. CrossRef
Is the New Seventh AJCC/UICC Staging System Appropriate for Patients with Gastric Cancer?
Hong Man Yoon, Keun Won Ryu, Byung Ho Nam, Soo Jeong Cho, Sook Ryun Park, Jong Yeul Lee, Jun Ho Lee, Myeong-Cherl Kook, Il Ju Choi, Young-Woo Kim
Journal of the American College of Surgeons.2012; 214(1): 88. CrossRef
Comparison of the 6th and 7th Editions of the UICC TNM Staging System for Gastric Cancer: Results of a Chinese Single-Institution Study of 1,503 Patients
Wei Wang, Xiao-wei Sun, Chao-feng Li, Lin Lv, Yuan-fang Li, Ying-bo Chen, Da-zhi Xu, Rajiv Kesari, Chun-yu Huang, Wei Li, You-qing Zhan, Zhi-wei Zhou
Annals of Surgical Oncology.2011; 18(4): 1060. CrossRef

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

Abstract PDF PubReader ePub

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

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

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The Serum Assay of Soluble CD44 Standard, CD44 Variant 5, and CD44 Variant 6 in Patients with Gastric Cancer: Chang Hak Yoo, Sung Hoon Noh; Cancer Res Treat. 2003;35(1):3-8. Published online February 28, 2003; DOI: https://doi.org/10.4143/crt.2003.35.1.3

Abstract PDF

PURPOSE
Alternative splicing of CD44 and aberrant levels of soluble CD44 (sCD44) protein in the serum of cancer patients has been correlated to tumor progression and metastasis. The purpose of this study was to evaluate the concentrations, and the prognostic potential of sCD44s, sCD44v5 and sCD44v6, in patients with gastric cancer. MATERIALS AND METHODS: The serum levels of sCD44s, sCD44v5 and sCD44v6 were determined quantitatively using an enzyme-linked immunosorbent assay. Serum samples were obtained from 116 patients with gastric cancer, both before and after surgery, and from 30 healthy controls. RESULTS: The serum sCD44v6 levels were significantly higher in patients with gastric cancer than in the healthy controls, whereas those of sCD44s and sCD44v5 were no different. The surgical resection of the tumor resulted in a significant reduction in all the sCD44 proteins, whereas if a surgical resection was not performed the concentrations of the sCD44v5 and sCD44v6 were not reduced prior to surgery. The serum sCD44v6 levels correlated with the venous or lymphatic invasion of the tumor and lymph node metastasis. In addition, a high preoperative serum sCD44v6 level was significantly associated with poor prognosis in patients with gastric cancer. CONCLUSION: The preoperative serum level of sCD44v6 in patients with gastric cancer was significantly higher than that in the healthy controls, and correlated with the venous or lymphatic invasion of the tumor and lymph node metastasis. In addition, a high preoperative serum sCD44v6 level was significantly associated with poor prognosis in patients with gastric cancer. These results suggest that an elevation of the serum sCD44v6 level might be used as a new predictor of tumor invasiveness, and poor prognosis, in patients with gastric cancer.

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Identification of novel biomarkers, MUC5AC, MUC1, KRT7, GAPDH, CD44 for gastric cancer
Jie Yang
Medical Oncology.2020;[Epub] CrossRef
Breast Cancer Cell–Derived Soluble CD44 Promotes Tumor Progression by Triggering Macrophage IL1β Production
Jeong-Hoon Jang, Do-Hee Kim, Jae Min Lim, Joon Won Lee, Su Jin Jeong, Kwang Pyo Kim, Young-Joon Surh
Cancer Research.2020; 80(6): 1342. CrossRef
BRCA1 and BRCA2 germline mutations in Korean ovarian cancer patients
Myong Cheol Lim, Sokbom Kang, Sang-Soo Seo, Sun-Young Kong, Bo-Yon Lee, Seon-Kyung Lee, Sang-Yoon Park
Journal of Cancer Research and Clinical Oncology.2009; 135(11): 1593. CrossRef
Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance
Kamran Ghaffarzadehgan, Mostafa Jafarzadeh, Hamid Reza Raziee, Hamid Reza Sima, Ehsan Esmaili-Shandiz, Hanieh Hosseinnezhad, Ali Taghizadeh-Kermani, Omeed Moaven, Maryam Bahrani
World Journal of Gastroenterology.2008; 14(41): 6376. CrossRef

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Suppression of Peritoneal Metastases by Expression of Murine Endostatin cDNA: Seung Ho Choi, Jae Hoon Lee, Sung Hee Hong, Woo Jin Hyung, Sung Hoon Noh, Hyun Cheol Chung, Jae Kyung Roh, Jin Sik Min; Cancer Res Treat. 2002;34(4):302-307. Published online August 31, 2002; DOI: https://doi.org/10.4143/crt.2002.34.4.302

Abstract PDF

Peritoneal seeding is one of problems to be solved in gastrointestinal and ovarian cancers. Angiogenesis is the critical step for a dormancy tumor cluster to be an overt metastatic nodule. However, whether an anti-angiogenesis strategy is effective in the control of peritoneal metastases is still obscure. In this study, we evaluated whether endostatin, an endogenous angiogenesis inhibitor, suppresses peritoneal metastases.
MATERIALS AND METHODS
We transduced a human gastric cancer cell line, AGS and a murine renal cancer cell line, Renca, with the plasmid pEndoSTHB, which encodes a secretable form of murine endostatin. Endostatin expression was tested with western blotting, and the biological activity of the secreted endostatin was confirmed with in vitro endothelial cell growth inhibition. In the animal experiments, stable transfectants were injected intraperitoneally.
RESULTS
We demonstrated secretion of endostatin from two cell lines transduced with the plasmid pEndoSTHB. Conditioned media secreted from pEndoSTSB-transduced mammalian cells were shown to potently inhibit endothelial cell growth in vitro. We selected stable transfectants with similar in vitro growth rates of their parental cell lines. Significant tumor growth inhibition was observed in the endostatin-expressing Renca cells intraperitoneal injection group at days of 28, compared to the null transfectants intraperitoneal injection control group.
CONCLUSION
These results support that peritoneal seeding is angiogenesis-dependant and an anti-angiogenesis strategy is a good way to control peritoneal metastases.

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The kringle domain of tissue-type plasminogen activator inhibits in vivo tumor growth
Byoung-Shik Shim, Byoung-Hak Kang, Yong-Kil Hong, Hyun-Kyung Kim, Il-Ha Lee, Soo-Young Lee, Young-Joon Lee, Suk-Keun Lee, Young Ae Joe
Biochemical and Biophysical Research Communications.2005; 327(4): 1155. CrossRef

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

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

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Prognostic Significance of p53, c-erbB-2, nm23 and Ki-67 Expression in Patients with Advanced Gastric Carcinoma: Sung Hoon Noh, Chang Hak Yoo, Ho Gune Kim, Young Ha Oh, Jin Sik Min; J Korean Cancer Assoc. 1999;31(4):699-709.

Abstract PDF: PURPOSE
We investigated the prognostic impacts of p53, c-erbB-2, nm23 and Ki-67 expression in patients with stage II and IIIA gastric carcinoma who underwent curative (RO) resections.
MATERIALS AND METHODS
261 paraffin-embedded gastric carcinoma tissues (stage II, 121; stage IIIA, 135) were stained with the monoclonal antibodies, p53, c-erbB-2, nm23 and Ki-67 using the labelled streptovidin biotin method. The positivity was determined by two pathologists who were kept blind for the patients outcome.
RESULTS
The overexpression was seen in 51.7% for p53, 11.9% for c-erbB-2, and 70.1% for nm23. The mean Ki-67 labelling index was 25.5+ 16.7. The rates of overexpression between the stage II and stage IIIA were not significantly different in all these molecules. Overexpression of p53 was more likely to be associated with old age and lymph node metastasis. Overexpression of c-erbB-2 was more likely to be associated with Borrmann type I, II and well-differentiated tumor. However, nm23 was more frequently expressed in patients with older age and well-differentiated tumor. In survival analysis, the overexpressions of p53 and Ki-67 were significantly associated with poor prognosis of the patients (p<0.01), but c-erbB-2 and nm23 were not related to the patients outcome. In a multivariate analysis of prognostic factors, only. the lymph node metastasis was an independent prognostic factor.
CONCLUSION
Although the values did not reach statistical significance in a multivariate analysis, the overexpression of p53 and Ki-67 tended to have adverse effects an the prognosis of patients with gastric cancer.

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Gastric Adenosquamous Carcinoma: Jae Ho Cheong, Dong Woo Shin, Sung Hoon Noh, Jin Sik Min; J Korean Cancer Assoc. 1999;31(4):710-715.

Abstract PDF: PURPOSE
Adenosquamous carcinoma, a rare malignant tumor of the stomach, is characterized by two different cell components, one adenomatous and the other squamous component. Its clinicopathologic feature and prognosis are quite different from the ordinary adenocarcinomas. We report our experience of 9 such cases.
MATERIALS AND METHODS
Clinical and pathologic features were reviewed for the 9 patients who undenwent gastrectomies and were confirmed as adenosquamous carcinoma by pathologists during the 10-year period of from 1987 to 1998. Postoperative adjuvant therapy and prognosis were also reviewed.
RESULTS
The ages of 6 male and 3 female patients ranged from 30 to 59, with the median age of 48. Total gastrectomy was done in 4 cases, while other underwent subtotal gastrectomy. Curative resection was done in four cases. Fourteeen additional organs were resected concomitantly due to suspicious tumor invasion and among them 9 organs were histologically confirmed for tumor invasion. The mean tumor size was 7.4 cm (2.5-27 cm) and all cases were pathologically advanced. One case showed peritoneal seeding and 3 cases showed hepatic metastases. There were 7 cases of stage IV disease by the UICC TNM classification (5th ed.) and the other two were stage II and stage IIlb respectively. Eight cases received postoperative adjuvant chemotherapy comprising S-FU, DDP, adriamycin, picibanil or VP-16. Of 9 patients, 6 died and the overall 5-year survival rate was 15.3%.
CONCLUSION
Adenosquamous cancer of stomach is regarded as a disease of unfavorable prognosis, which was confirmed by this study. The treatments were not quite different from those for other stomach cancers. Although more cases and further investigations are essential for complete understanding of the clinical prognosis and proper treatment of the gastric adenosquamous cancer, early diagnosis, curative resection and close postoperative follow-ups are currently available options for better outcome of this disease.

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Combined Resection in Advanced Gastric Cancer: Dong Woo Shin, Chang Hak Yoo, Sung Hoon Noh, Jin Sik Min; J Korean Cancer Assoc. 1999;31(3):448-457.

Abstract PDF: PURPOSE
Prognosis of primary gastric cancer invading neighboring organs is very poor. However, with en bloc resection, a relatively favorable prognosis can be expected even in patients with such advanced cancer. But there has been controversy on the effectiveness of gastrectomy combined with en bloc resection of the invaded organs, and we conducted this study to evaluate the prognostic effects as well as the outcome of the combined resection.
MATERIALS AND METHODS
Among 2,603 who underwent gastrectomy due to gastric carcinoma from January 1987 to December 1994 at the Department of Surgery, Yonsei University College of Medicine, 157 patients (6.0%) in whom curative combined resections of grossly invaded adjacent organs (cT4) were perfonned entered this study. Any case with distant metastasis was excluded. Comparisons and multivariate analysis between the invasion (pT3) group and the non-invasion (pT4) group were made for age, sex, tumor size, location, Borrmann type, depth of invasion, lymph node metastasis, histologic type and 5-year survival rate.
RESULTS
One-organ combined resection was done in 60 (38.2%) patients; Two-organ, in 80 (51.0%) patients; and three-organ, in 17 (10.8%) patients. Most commonly combined organ was distal pancreas and transverse colon was the next. Histologic confirmation of invasion was made in 40.9%. 157 patients with T4 were divided into pT3 or pT4. Significant differences were found in type of operation, location of tumor, and TNM staging. Postoperative complications of combined resection were observed in 48 cases (30.6%) and the wound infection was the most frequent one. There were only 2 cases (1.3%) of immediate postoperative mortality in the combined group, and the causes of death were pulmonary complication and acute renal failure. Five-year survival rate (5-YSR) of pT3 group was 43.0% and that of pT4 was 26.2%. In comparison of 5-YSR according to TNM stages, no significant difference was found between pT3 and pT4 (45.0% vs. 66.7% in IIIa; 25.4% vs. 18.4% in IV). No difference of 5-YSR was observed in the groups categorized according to the number of resected organs. The comparison of 5-YSR between the 157 curatively-combined cases and the 63 palliatively-combined cases showed a significant difference (35.6% vs. 4.2%, p=0.000). Multivariate analysis showed that lymph node metastasis and microscopic tumor invasion served as significant parametets.
CONCLUSION
En bloc combined resection of adjacent invaded organs along with systematic lymph node dissection would be beneficial to gastric cancer patients with neighboring organ invasion.

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Clinicopathologic Significance of Lymphatic Vessel Invasion and Blood Vessel Invasion in Gastric Cancer: Sang Wook Kim, Ki Hyeok Lah, Chang Hak Yoo, Yong Il Kim, Sung Hoon Noh, Jin Sik Min; J Korean Cancer Assoc. 1999;31(1):16-23.

Abstract PDF: PURPOSE
The vessel invasion by cancer cells can be easily detected with the photomicroscope, but still there is an arguement on the value as a prognostic factor. The following study was conducted to evaluate the clinicopathologic significance of blood vessel invasion (BVI) and lymphatic vessel invasion (LVI) as a potential prognostic factor in gastric cancer treatment.
MATERIALS AND METHODS
618 patients who had undergone gastrectomies for gastric cancer at the Department of Surgery, Yonsei University College of Medicine, from August, 1993 to December, 1994, were retrospectively reviewed. Patients, based on the presence of BVI and/or LVI by HE stain, were arranged into three groups: Group 1 (n=338) consisted of patients with no evidence of BVI and LVI; group 2 (n=224), with evidence of either BVI or LVI; group 3 (n=56), with evidence of both BVI and LVI. The clinicopathologic features were analyzed and the survival rates of BVI, LVI and the three groups were studied.
RESULTS
BVI-positive patients were seen in 10.5% of all patients, and LVI-positive, in 43.9%. Certain factors such as tumor size, gross type, depth of invasion, lymph node metastasis, distant metastasis, and TNM staging showed significant differences among the three groups by univariate analyses. Survival rates between the BVI-positive (48.1%) and the BVI-negative (73.9%) and between the LVI-positive (55.4%) and the LVI-negative (82.6%) showed significant differences. 3-year survival rates of group 1, 2, and 3 were 82.5%, 59.7%, and 42.0%, respectively, with significant differences. But multivariate analysis demonstrated that distant metastasis, lymph node metastasis, depth of invasion, age, and gross type served as significant prognostic parameters while BVI and LVI did not.
CONCLUSION
Patients with BVI and/or LVI were associated with larger tumor size, infiltrative type tumor, deeper gastric wall invasion, more lymph node metastases, and advanced stages of tumor. BVI and LVI also played significantly adverse influence in the survival time in univariate analysis. With further studies on their roles in clinicopathologic features, lymphovascular invasion would be a useful prognostic factor in gastric cancer.

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Primary Intestinal Lymphoma Treatment Results and prognostic Factors in 52 Cases: In Chul Hong, Chang Hak Yoo, Sung Hoon Noh, Chang Hwan Cho, Kyung Shik Lee; J Korean Cancer Assoc. 1998;30(1):158-168.

Abstract PDF: PURPOSE
In spite of many published reports about the primary gastrointcstinal lymphoma in Korea, the majority of them unfortunately involved a small number of patients with diverse results conceming treatment, patient survival, and prognostic factors. There also were few reports mainly focusing on primary intestinal lymphoma alone. Therefore we studied the patient-survival and prognostic factors in 52 cases of intestinal lymphomas.
MATERIALS AND METHODS
We reviewed fifty two patients who received treatment due to primary intestinal lymphoma at Severance hospital, from January 1980 to June 1995.
RESULTS
The intestinal lymphomas were located in descending order of frequency at the terminal ileum, i1eocecal region, right colon, and the jejunum. The most common histologic type was diffuse large cell type and the majority showed an intermediate grade of differentiation. The average survival time was 40.7 months with a 5 year survival rate of 41.4%. The overall and complete remission rate of the intestinal lymphoma were 76.2%, 64.3%, respectively. Additional chemotherapy or radiotherapy to surgery improved remission rate. The overall 5 year survival rates were 50.4%, 47.3%, 33.3%, and 25.0% in stage I, II1, II2 and III~IV, respectively. The 5 year survival rate after curative resection was 57.0% and 16.6% after incomplete resection. The significant prognostic factors were residual tumor, site of the lesion, multiplicity, and adjacent organ invasion. However, the site of the lesion alone (worst in the jejunum) was the sole independent variable on multivariate analysis.
CONCLUSION
We concluded that early diagnosis and curative resection were important to improve survival rates in the primary intestinal lymphoma. More number of such cases are needed for further comparison of various treatment methods and results.

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Characteristics and Prognosis in Gastric Cancer with Liver Metastasis: Seung Ki Kim, Sung Hoon Noh, Chang Hak Yoo, Yong Il Kim, Jin Sik Min, Kyong Sik Lee; J Korean Cancer Assoc. 1997;29(6):1085-1093.

Abstract PDF: PURPOSE
Until several years ago, gastric or hepatic resection was seldom indicated for metastatic gastric cancer because of the expected dismal prognosis. Recently, some studies have reported benefits from gastric or hepatic resection for metastatic gastric cancer. We performed this retrospective study to see the prognosis after aggressive surgery in gastric cancer patients with hepatic metastasis.
MATERIALS AND METHODS
A total of 112 gastric cancer patients were confirmed to have liver metastasis at the time of initial surgery or preoperative evaluation during the 8-year period from January, 1987 to December, 1994 at the Department of Surgery, Yonsei University, College of Medicine. Thirty eight cases (33.9%) underwent gastrectomy (total gastrectomy: 15, subtotal gastrectomy: 23). Of these 38 cases, 12 underwent a combined resection of metastatic hepatic tumors (segmentectomy: 7, wedge resection: 3, lobectomy: 1 and enucleation: 1).
RESULTS
The locations of primary lesion were most common in the lower 1/3 of the stomach in all of the nonresected, the gastrectomy only, and the gastrectomy & hepatectomy group. Most of the cancers belonged to Borrmann type III and IV. Histologically, dedifferentiated cancer (poorly differentiated cancer, signet ring cell cancer, mucinous cancer) was more frequent in the nonresected group (67.4%) while differentiated cancer (papillary cancer, well differentiated cancer, moderately differentiated cancer) was more frequent in the resected group (60.9%). The number of metastatic hepatic nodules were less than two in the resected group and the location of metastatic lesions tended to be limited to one lobe. Concerning the prognosis, the mean survival of the resected group was better than the nonresected group (nonresected group: 8.4 months, gastrectomy only group: 18.4 months, gastrectomy & hepatectomy group: 35.5 months). The mean score of QOL (quality of life) according to Spitzer index was better in the resected group (nonresected group: 5.1, gastrectomy only group: 6.0, gastrectomy & hepatectomy group: 7.5).
CONCLUSION
Resection of both the primary gastric lesion and the metastatic hepatic lesion should be considered in selected cases to improve the survival and the quality of life in patients with hepatic metastasis.

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

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

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

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

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

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

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

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

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Cininicopathological Study of Esophageal Invading Carcinoma of the Upper Third Part of the Stomach: Sung Hoon Noh, Chang Hak Yoo, Yong Il Kim, Coong Bai Kim, Jin Sik Min, Kyung Shik Lee; J Korean Cancer Assoc. 1996;28(5):852-860.

Abstract PDF: To evaluate clinicopathological characteristics and prognostic factors of esophageal invading cancer of the upper third of the stomach, we analyzed retrospectively 198 patients who underwent total gastrectomy for adenocarcinoma arising from the upper third of the stomach during 1987 to 1993 at Deparment of Surgery, Yonsei University, College of Medicine and divided into two groups as esophageal invading group(n=39) and non-invading group(n=159). Esophageal invading group had larger tumor size and higher rates of serosal invasion, lymph node metastasis, liver and peritoneal metastasis than non-invading group. Therefore more advanced stage and palliative resection were observed in esophageal invading group. The 5-year survival rate of esophageal invading group(37.6%) was significantly lower than that of non-invading group(60.8%). The significant prognostic factors of esophageal invading group using Cox's proportional hazard method were lymph node metastasis and curability of gastric resection. In conclusion, esophageal invading gastric cancer had more aggressive behavior than that of non-invading group and frozen section of proximal resection margin during operation should be performed for curative resection. For some of patients with far advanced upper third gastric cancer, neoadjuvant chemotherapy, early postoperative intraperitoneal chemotherapy(EPIC) or intraperitoneal hyperthermic chemotherapy(IPHC) may provide better qualiity of life and survival benefit.

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What is the Proper Management for Stage 4 Gastric Cancer ?: Chang Hak Yoo, Sung Hoon Noh, Yong Il Kim, Jin Sik Min, Kyung Shik Lee; J Korean Cancer Assoc. 1996;28(5):860-868.

Abstract PDF: Among 2118 patients with gastric cancer who had undergone gastric resection in the Department of Sursery, Yonsei University College of Medicine over the 7 years period from January 1987 to December 1993, there were 214(10.l%) with stage IV gastric cancer, designated as a lesion with factors such as direct invasion of adjacent organs(T factor), tertiary or quaternary nodal involvement(N factor), peritoneal metastasis(P factor) or hepatic metastasis(H factor). The overall 5-year survival rate in patients with stage IV gastric cancer after gastric resection was 11.3%. The 5-year survival rate in patients without distant metastasis(n=122) was 17.5%, being significantly higher than the 4.4% in cases with distant metastasis(n=92). Patients with tertiary nodal involvement or directly invaded organs alone survived at a rate of 23.8% and 10.2% in the 5-year follow-up, respectively. Signifi cant difference in 5-year survival rates were also noted in curability(curative resection:22.3 %, palliative resection: 5.1%) and type of operation(subtotal: 15.6%, total: 6.0%). But the mean survival time was less than 10months in patients with more than 2 factors in combination. In conclusion, there appear to be 2 subgroups in whom the rates of survival differ in stage IV gastric cancer according to distant metastasis. Therefore radical procedures such as extended lymphadenectomy and combined resection of invaded organ should be performed in M0 cases. On the other hand, in Ml cases, consideration and adaptation of new therapeutic approach except gastric resection will improve the survival and quality of life.

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

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

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Analysis of High Risk Factors for Lymph Node Metastasis in Early Gastric Cancer: Sung Hoon Noh, Wan Soo Kim, Ki Hyeok Lah, Yong Il Kim, Seung Ho Choi, Coong Bai Kim, Jin Sik Min, Kyung Shik Lee; J Korean Cancer Assoc. 1996;28(1):27-35.

Abstract PDF: The prognosis of early gastric cancer (EGC) is generally excellent, and the proportion of EGC cases to advanced gastric cancer cases is steadily increasing nowadays. The presence or absence of lymph node metastasis in EGC is important prognostic factor, in other words, the survival rate or recurrence rate of node negative EGC is known to be much better than that of node positive ones. Retrospective analysis was performed for 682 EGC cases which underwent more than D2 resection in Yonsei medical center between 1986 Jan. to 1993 Dec, in order to investigate the clinicopathological factors to predict the possibility of lymph node metastasis. In this study, several factors such as age, sex, tumor location, tumor size, multiplicity, depth of invasion, macroscopic and histologic type were evaluated to determine the significance. In the analysis of these eight factors, sex, tumor size, depth of invasion and macroscopic type were statistically correlated with lymph node metastasis. We consider these factors to be possible high risk factors for lymph node metastasis in early gastric cancer.

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Prognosis and Quality of Life of Non - resectable Gastric Cancer: Kang Young Lee, Yong Il Kim, Sung Hoon Noh, Jin Sik Min; J Korean Cancer Assoc. 1996;28(1):35-43.

Abstract PDF: The records of 217 patients with proven non-resectable gastric cancer were studied at Yonsei University Hospital over the 4 years period from January 1990, to December 1993 to clarify Quality of life of gastric cancer patients who could not be resected. The mean survival time of total patients was 10.5 months.(Male: 10.6, Female; 10.4) The survival time was affected by gross type and histologic type. Survivals according to the Borrmann type were as follows; Borrmann type I: 11.5 months, II: 11.3 months, III: 10.2 months, IV; 8.2 months. Survivals according to the histological type were as follows; well differentiated: 20.3 months, moderately differentiated: ll.5 months, poorly differentiated: 9.2 months, signet ring cell carcinoma: 7.9 months. The age, sex and cause of non-resectability did not affect the survival. The mean score of QOL(quality of life) according to Spitzer index was 4.8. The QOL was affected by histological type and type of operation. QOL index scores according to histo logic type were as follows; well differentiated: 6.4, moderately differentiated: 5.5, poorly differentiated: 4.7 and signet ring cell type: 3.5. QOL index scores according to type of operation were as follows; by pass procedure: 5.6, Explo-lapa & closure: 4.0. In conclusion, we could confirm the bad limited survival and quality of life of non-resectable gastric cancer patients. We suggest a new therapeutic approach to improve the survival and QOL of non-resectable gastric cancer patients.

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

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

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

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

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

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

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Natural Killer ( NK ) Cell cytotoxicity According to the Expression of c-erbB-2 Protein in Human Gastric Cancer Cells: Byeong Woo Park, Kang Sup Shim, Sung Hoon Noh, Coong Bai Kim, Kyung Shik Lee; J Korean Cancer Assoc. 1995;27(1):1-8.

Abstract PDF: Although there is still controversy to the relationship between c-erbB-2 protein expression and prognosis of the gastric carcinoma, there were many reports about the poor prognosis with the expression of c-erbB-2 in gastric carcinoma. The mechanisms underlying this phenomenon are not known. However several possibilities such as acquired resistance to 5-Fluorouracil(5-FU) and resistance to the host immune system were suggested. So we performed this study to evaluate whether c-erbB-2 expression can alter the natural killeriNK) cell cytotoxic activity. Using single cell suspensions from primary gastric cancer tissues and malignant ascites due to stomach cancer, the immunohistochemical reactivity to c-cerB-2 protein was examined and we performed the tests for NK cell cytotoxic activity. The c-erbB-2(+) cancer cells were significantly more resistant to NK cell cytotoxic activity than c-erbB-2( ) cancer cells. However there was no significant difference in the resiatance to NK cell cytotoxic activity according to their immunohistochemical staining intensities. These results suggest that the resistance to the NK cel1 cytotoxicity may be one of the possi- ble mechanisms of the poorer prognosis of the c-erbB-2(+ ) gastric cancers.

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Gastric carcinoid tumor: Wan Soo Kim, Seung Ho Choi, Sung Hoon Noh, Jin Sik Min, Ho Geun Kim, Won Ho Kim; J Korean Cancer Assoc. 1991;23(3):596-605.

Abstract PDF: No abstract available.

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Remnant stomach cancer: Sung Hoon Noh, Dong Sup Yoon, Seung Ho Choi, Jin Sik Min, Jae Kyung Roh, Byung Soo Kim; J Korean Cancer Assoc. 1991;23(3):578-585.

Abstract PDF: No abstract available.

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Gastroduodenal artery-duodenal fistula complicated during intraartrial chemotherapy for metastatic hepatic tumor: Sung Hoon Noh, Kwang Wook Suh, Jin Sik Min, Hae Kyung Noh; J Korean Cancer Assoc. 1991;23(2):451-457.

Abstract PDF: No abstract available.

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Splenic metastasis of gastric cancer: Myo Kyung Lee, Sung Hoon Noh, Woo Ik Yong; J Korean Cancer Assoc. 1991;23(1):157-160.

Abstract PDF: No abstract available.

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