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Volume 37(4); August 2005
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Original Articles
Efficacy and Safety Study of Docetaxel as Salvage Chemotherapy in Metastatic Gastric Cancer Failing Fluoropyrimidine and Platinum Combination Chemotherapy
Jae-Lyun Lee, Min-Hee Ryu, Heung Moon Chang, Tae-Won Kim, Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim, Jung Shin Lee, Yoon-Koo Kang
Cancer Res Treat. 2005;37(4):201-207.   Published online August 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.4.201
AbstractAbstract PDFPubReaderePub
Purpose

Fluoropyrimidine (F) and platinum (P) combination chemotherapy has been widely used for the first line treatment of advanced gastric cancer (AGC). Docetaxel (D) has shown promising activity in this disease. The present study retrospectively investigated the efficacy of D monotherapy as salvage chemotherapy for AGC that is failing F and P combination chemotherapy.

Materials and Methods

A total of 34 patients, fitting the eligibility criteria, were included in this study. D was administered at a dose of 75 mg/m2 IV every 3 weeks, with dexamethasone prophylaxis. Twenty-nine patients had measurable lesions. The median treatment-free interval was 38.5 days, and 91.2% of patients had progressed within 4 months of withdrawal of the first line chemotherapy.

Results

A total of 133 cycles of D were administered, with a median of 3.5 (1~8) cycles. From an intention-to-treat analysis, 6 patients achieved partial responses (PR), with a response rate of 20.7% (95% CI, 6.0~35.4). The duration of objective PRs in these six were 2.3+, 2.5+, 2.9, 3.0+, 6.2 and 6.8 months, respectively. Six patients showed a stable disease, but 15 showed progression. The median time to progression was 4.2 months (95% CI, 2.8~5.5), with a median overall survival since the start of D monotherapy of 8.4 months (95% CI, 5.5~11.3). Grade 3/4 neutropenia and febrile neutropenia occurred in 12.9% of patients and 3.1% of cycles. The incidence of grade 3 or worse non-hematological toxicities were as follows; peripheral sensory neuropathy 9.7%, asthenia 3.2% and allergic reaction 2.7%.

Conclusion

Docetaxel, 75 mg/m2, is active in AGC as second-line chemotherapy after failure of prior exposure to the F and P combination chemotherapy, with a favorable toxicity profile.

Citations

Citations to this article as recorded by  
  • Comparison of adverse events following injection of original or generic docetaxel for the treatment of breast cancer
    Nao Tagawa, Erika Sugiyama, Masataka Tajima, Yasutsuna Sasaki, Seigo Nakamura, Hiromi Okuyama, Hisanori Shimizu, Vilasinee Hirunpanich Sato, Tadanori Sasaki, Hitoshi Sato
    Cancer Chemotherapy and Pharmacology.2017; 80(4): 841.     CrossRef
  • Efficacy and Safety of Trastuzumab-based Therapy in Combination with Different Chemotherapeutic Regimens in Advanced Esophagogastric Cancer – a Single Cancer-center Experience
    Georg-Martin Haag, Leonidas Apostolidis, Dirk Jaeger
    Tumori Journal.2014; 100(3): 237.     CrossRef
  • Phase I Dose-Escalation Study of Intravenous Aflibercept in Combination with Docetaxel in Patients with Advanced Solid Tumors
    Nicolas Isambert, Gilles Freyer, Sylvie Zanetta, Benoît You, Pierre Fumoleau, Claire Falandry, Laure Favier, Sylvie Assadourian, Karen Soussan-Lazard, Samira Ziti-Ljajic, Veronique Trillet-Lenoir
    Clinical Cancer Research.2012; 18(6): 1743.     CrossRef
  • A phase II study of docetaxel as salvage chemotherapy in advanced gastric cancer after failure of fluoropyrimidine and platinum combination chemotherapy
    Jae-Lyun Lee, Min-Hee Ryu, Heung Moon Chang, Tae-Won Kim, Jeong Hwan Yook, Sung Tae Oh, Byung Sik Kim, Minsun Kim, Young Joo Chun, Jung Shin Lee, Yoon-Koo Kang
    Cancer Chemotherapy and Pharmacology.2008; 61(4): 631.     CrossRef
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A Phase II Trial of Haptaplatin/5-FU and Leucovorin for Advanced Stomach Cancer
Won Sup Lee, Gyeong-Won Lee, Hwal Woong Kim, Ok-Jae Lee, Young-Joon Lee, Gyung Hyuck Ko, Jong-Seok Lee, Joung Soon Jang, Woo Song Ha
Cancer Res Treat. 2005;37(4):208-211.   Published online August 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.4.208
AbstractAbstract PDFPubReaderePub
Purpose

Heptaplatin (SKI-2053 R) is a new platinum analogue, with a better toxicity profile than cisplatin, and has antitumor activity even in cisplatin resistant cell lines. 5-fluoruracil (5-FU) has shown synergy with platinum compounds. This phase II trial was designed to determine the efficacy and toxicities of heptaplatin/ 5-FU (5-fluorouracil) for treating stomach cancer.

Materials and Methods

Thirty-two patients with advanced, measurable gastric adenocarcinomas were enrolled in this trial. The treatment consisted of heptaplatin, 400 mg/m2/day (1 hour IV infusion), on day 1 and 5-FU, 800 mg/m2/day (12 hours IV infusion), on days 1 to 5. The cycles were repeated every 3 weeks.

Results

Of the 26 evaluable patients, 9 had partial responses and 1a complete response (overall response rate, 38%; 95% confidence interval, 19~57%). The median response duration was 23 weeks (range: 4~60 weeks). The median time to progression was 26 weeks (range: 3~68 weeks). The grades III-IV toxicities were mostly hematological toxicities: leucopenia was observed in 11 patients (35%) and thrombocytopenia 4 (13%). No definite neuropathy was observed. Grade I-II nephropathy was also noted: grade I high BUN/creatinine levels occurred in 5 patients (16%), grade II proteinuria 2 (6%), grade I proteinuria 5 (16%). Neutropenic fever developed in 5 patients (16%) and 1 died of pneumonia in a neutropenic state.

Conclusion

This study suggests that the regimen of Heptaplatin/5-FU should be effective and have a favorable toxicity profile for the patients suffering with advanced stomach cancer.

Citations

Citations to this article as recorded by  
  • Cisplatin Resistance in Cancer Therapy: Causes and Overcoming Strategies
    S. Shruthi, K. Bhasker Shenoy
    ChemistrySelect.2024;[Epub]     CrossRef
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    Dobrina Tsvetkova, Stefka Ivanova
    Molecules.2022; 27(8): 2466.     CrossRef
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    W. Xu, D. C. Wang
    Russian Journal of General Chemistry.2016; 86(4): 939.     CrossRef
  • The extract of Paris polyphylla exerts apoptotic induction and synergic antiproliferative effect with anticancer drugs in SMMC-7721 human liver cancer cells
    Jing Sun, Bao-rui Liu, Jia Wei, Xiao-ping Qian, Li-xia Yu, Ren-hua Guo, Hua Shen, Tong-shan Wang, Yong-qian Shu
    Biomedicine & Preventive Nutrition.2011; 1(3): 186.     CrossRef
  • The status of platinum anticancer drugs in the clinic and in clinical trials
    Nial J. Wheate, Shonagh Walker, Gemma E. Craig, Rabbab Oun
    Dalton Transactions.2010; 39(35): 8113.     CrossRef
  • Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer
    H.-C. Kwon, M.S. Roh, S.Y. Oh, S.-H. Kim, M.C. Kim, J.-S. Kim, H.-J. Kim
    Annals of Oncology.2007; 18(3): 504.     CrossRef
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Oxaliplatin/5-FU without Leucovorin Chemotherapy in Metastatic Colorectal Cancer
Byoung Yong Shim, Kang Moon Lee, Hyeon-Min Cho, Hyun Jin Kim, Hong Joo Cho, Jinmo Yang, Jun-Gi Kim, Hoon-Kyo Kim
Cancer Res Treat. 2005;37(4):212-215.   Published online August 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.4.212
AbstractAbstract PDFPubReaderePub
Purpose

Fluorouracil (5-FU) and leucovorin combination therapy have shown synergistic or additive effect against advanced colorectal cancer, but the frequency of mucositis and diarrhea is increased. Most previous studies have used high dose leucovorin (300~500 mg/m2). However, some studies of oxaliplatin and 5-FU with low-dose or high-dose leucovorin in Korea have shown similar response rates. Therefore, we studied the necessity of leucovorin and evaluated the objective tumor response rates and toxicities of a regimen of oxaliplatin and 5-FU without leucovorin every 2 weeks in metastatic colorectal cancer patients.

Materials and Methods

Twenty-four patients with metastatic colorectal cancer were enrolled between January 2002 and March 2003. Patients received 85 mg/m2 of oxaliplatin on day 1, a bolus 5-FU 400 mg/m2 on day 1 and a continuous 5-FU infusion at 600 mg/m2/ 22 hours days 1 and 2, every 2 weeks.

Results

Of the 24 patients treated, 17 patients received previous 5FU with leucovorin and/or other chemotherapy. Three patients could not be evaluated. Five partial responses were observed with overall response rate of 21% (n=24). Of the previous chemotherapy group (n=17), 4 partial responses were observed with response rate of 24%. Median overall survival was 18 months (range 4~32 months) and median progression free survival was 4 months (range 2~6 months). This regimen was well tolerated and only 1 grade 3 anemia was observed.

Conclusion

Oxaliplatin/5-FU combination therapy without leucovorin achieved a relatively high response rate even in patients resistant to the previous 5-FU chemotherapy, and toxicity was minimal.

Citations

Citations to this article as recorded by  
  • Clinicopathological Features and Oncological Outcomes of Early and Late Recurrence in Stage III Colorectal Cancer Patients after Adjuvant Oxaliplatin-Based Therapy
    Yu-Tang Chang, Hsiang-Lin Tsai, Yen-Cheng Chen, Ching-Chun Li, Ching-Wen Huang, Po-Jung Chen, Wei-Chih Su, Tsung-Kun Chang, Yung-Sung Yeh, Tzu-Chieh Yin, Jaw-Yuan Wang, Weiren Luo
    Journal of Oncology.2023; 2023: 1.     CrossRef
  • Targeting the SPHK1/HIF1 Pathway to Inhibit Colorectal Cancer Stem Cells Niche
    Saeideh Gholamzadeh Khoei, Hamid Sadeghi, Fateme Karimi Dermani
    Journal of Gastrointestinal Cancer.2020; 51(2): 716.     CrossRef
  • Efficacy of 5-FU or Oxaliplatin Monotherapy over Combination Therapy in Colorectal Cancer
    Maria Toloudi, Panagiotis Apostolou, Ioannis Papasotiriou
    Journal of Cancer Therapy.2015; 06(04): 345.     CrossRef
  • Gene Expression Changes in Colorectal Cancer during Metronomic Chemotherapy and High-Concentration Drug Administration
    Panagiotis Apostolou, Maria Toloudi, Irene Kalliara, Vasiliki Kipourou, Ioanna Tourna, Ioannis Papasotiriou
    Journal of Cancer Therapy.2015; 06(08): 679.     CrossRef
  • 9,779 View
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Thymidylate Synthase, Thymidine Phosphorylase, VEGF and p53 Protein Expression in Primary Colorectal Cancer for Predicting Response to 5-fluorouracil-based Chemotherapy
Myung-Ju Ahn, Jung-Hye Choi, Ho-Suk Oh, Young-Yeul Lee, In-Soon Kim, Il-Young Choi, Kang-Hong Lee, Kang-Won Song, Chan-Kum Park
Cancer Res Treat. 2005;37(4):216-222.   Published online August 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.4.216
AbstractAbstract PDFPubReaderePub
Purpose

In the treatment of advanced metastatic colorectal cancer, several new agents, such as irinotecan and oxaliplatin, have been developed, which have improved both disease free and overall survivals. Among these agents, 5-fluorouracil (5-FU) still remains one of the most active agents, and the selection of patients who can benefit from 5-FU-based chemotherapy is still important, as those unlikely to benefit could be spared the harmful side effects. The expression levels of thymidylate synthase (TS), thymidine phosphorylase (TP) and p53 have been known to be associated with the clinical response to 5-FU-based therapy as well as the prognosis, and that of vascular endothelial growth factor (VEGF) is associated with poor survival.

Materials and Methods

The relationship between the expressions of TS, TP, VEGF and p53 in primary tumors, using immunohistochemistry, and the response of 45 metastatic colorectal cancer patients (M:F=25:20, median age 59 yrs) to 5-FU-based chemotherapy were evaluated.

Results

Thirty-seven patients were treated with 5-FU/LV/irinotecan (FOLFIRI) and 8 with 5-FU/LV/oxaplatin (FOLFOX). The overall response rate was 28.9% (13/45). When immunohistochemically analyzed with monoclonal antibodies against TS, TP, VEGF and p53, 55.6% of the patients (25/45) were positive for TS, 48.9% (22/45) for TP, 82.2% (37/45) for VEGF, and 80% (36/45) for p53. There was a significant difference in the intensity of TS expression between the clinical responders and non-responders (p=0.036). In terms of the staining pattern of TS expression, diffuse staining was correlated with a poor response (p=0.012) and poor survival (p=0.045). However, there was no correlation between the expressions of TP, VEGF or P53 and the response to chemotherapy.

Conclusion

These results suggest that the expression of TS in primary colorectal cancer might be an important prognostic factor for chemotherapy response and survival, and might be a useful therapeutic marker for the response of chemotherapy.

Citations

Citations to this article as recorded by  
  • Epigenetic Approaches to Overcome Fluoropyrimidines Resistance in Solid Tumors
    Laura Grumetti, Rita Lombardi, Federica Iannelli, Biagio Pucci, Antonio Avallone, Elena Di Gennaro, Alfredo Budillon
    Cancers.2022; 14(3): 695.     CrossRef
  • Immunoexpression of TS, p53, COX2, EGFR, MSH6 and MLH1 biomarkers and its correlation with degree of differentiation, tumor staging and prognostic factors in colorectal adenocarcinoma: a retrospective longitudinal study
    Wilson Roberto Batista, Gianni Santos, Flávia Maria Ribeiro Vital, Delcio Matos
    Sao Paulo Medical Journal.2019; 137(1): 33.     CrossRef
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    Jia Che, Lun Pan, Xiangling Yang, Zhiting Liu, Lanlan Huang, Chuangyu Wen, Aihua Lin, Huanliang Liu
    Molecular and Clinical Oncology.2017;[Epub]     CrossRef
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    Hiroki Osumi, Eiji Shinozaki, Mitsukuni Suenaga, Yosuke Kumekawa, Mariko Ogura, Masato Ozaka, Satoshi Matsusaka, Keisho Chin, Noriko Yamamoto, Nobuyuki Mizunuma
    BMC Cancer.2015;[Epub]     CrossRef
  • Comparison of thymidine phosphorylase expression and prognostic factors in gallbladder and bile duct cancer
    Hye Sung Won, Myung Ah Lee, Eun-Seon Chung, Dong-Goo Kim, Young Kyoung You, Tae Ho Hong, In-Seok Lee
    BMC Cancer.2010;[Epub]     CrossRef
  • 9,017 View
  • 36 Download
  • 5 Crossref
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A Feasibility Study of Adenosine Triphosphate-based Chemotherapy Response Assay (ATP-CRA) as a Chemosensitivity Test for Lung Cancer
Shin Myung Kang, Moo Suk Park, Joon Chang, Se Kyu Kim, Haeryoung Kim, Dong-Hwan Shin, Kyung Young Chung, Dae Joon Kim, Joo Hyuk Sohn, Sung Ho Choi, Jeongmi Kim, Eun Jin Yoon, Joo-Hang Kim
Cancer Res Treat. 2005;37(4):223-227.   Published online August 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.4.223
AbstractAbstract PDFPubReaderePub
Purpose

A chemosensitivity test can reflect the differences in responses of individual cancer patients to chemotherapeutic agents. The adenosine triphosphate-based chemotherapy response assay (ATP-CRA)is an accurate method, which does not require a large amount of tissue specimen. So far, no studies have evaluated the utility of the ATP-CRA in Korea. Therefore, we investigated the clinical usefulness of the ATP-CRA in 53 patients with lung cancer.

Materials and Methods

Tumor tissues were obtained from bronchoscopic biopsies or surgical resections. The validity of ATP-CRA was assessed focusing on the success rate, experimental error level (intraassay mean coefficient of variation [CV]) and reproducibility.

Results

The overall success rate of ATP-CRA was 90.6% (48/53). Normal cells were effectively eliminated from the tumor tissues with the use of ficoll gradient centrifugation and immunomagnetic separation, which was confirmed using loss of heterozygosity analysis of the 3p deletion. The mean CV of ATP assays was 10.5±4.6%. The reproducibility of ATP assays was 94±3.8%. The results of the ATP assays were reported to physicians within 7 days of specimen collection. More than 6 anticancer drugs were tested on the tumor specimens obtained from bronchoscopic biopsies.

Conclusion

The ATP-CRA is a stable, accurate and potentially practical chemosensitivity test in patients with lung cancer.

Citations

Citations to this article as recorded by  
  • In Vitro Adenosine Triphosphate-Based Chemotherapy Response Assay as a Predictor of Clinical Response to Fluorouracil-Based Adjuvant Chemotherapy in Stage II Colorectal Cancer
    Hye Youn Kwon, Im-kyung Kim, Jeonghyun Kang, Seung-Kook Sohn, Kang Young Lee
    Cancer Research and Treatment.2016; 48(3): 970.     CrossRef
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    Joon Seong Park, Jae Keun Kim, Dong Sup Yoon
    Journal of Clinical Laboratory Analysis.2016; 30(6): 804.     CrossRef
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    Korean Journal of Clinical Oncology.2015; 11(2): 51.     CrossRef
  • Association between Chemotherapy-Response Assays and Subsets of Tumor-Infiltrating Lymphocytes in Gastric Cancer: A Pilot Study
    Jee Youn Lee, Taeil Son, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Choong-Bai Kim, Chung-Gyu Park, Hyoung-Il Kim
    Journal of Gastric Cancer.2015; 15(4): 223.     CrossRef
  • ATP-Based Chemotherapy Response Assay in Primary or Recurrent Ovarian and Peritoneal Cancer
    Maria Lee, Sang Wun Kim, Eun Ji Nam, Hanbyoul Cho, Jae Hoon Kim, Young Tae Kim, Sunghoon Kim
    Yonsei Medical Journal.2014; 55(6): 1664.     CrossRef
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    Yong Sik Yoon
    World Journal of Gastroenterology.2014; 20(44): 16398.     CrossRef
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    Yoon Pyo Choi, Hyo Sup Shim, Ming-Qing Gao, Suki Kang, Nam Hoon Cho
    Cancer Letters.2011; 307(1): 62.     CrossRef
  • Chemotherapy Response Assay Test and Prognosis for Breast Cancer Patients Who Have Undergone Anthracycline- and Taxane-Based Chemotherapy
    Anbok Lee, Woosung Lim, Byung-In Moon, Nam-Sun Paik, Suck-Hwan Koh, Jeong-Yoon Song
    Journal of Breast Cancer.2011; 14(4): 283.     CrossRef
  • Adjuvant Chemotherapy Based on the In Vitro Histoculture Drug Response Assay for Non-small Cell Lung Cancer Improves Survival
    Masayuki Tanahashi, Hiroshi Niwa, Haruhiro Yukiue, Eriko Suzuki, Hiroshi Haneda, Naoko Yoshii
    Journal of Thoracic Oncology.2010; 5(9): 1376.     CrossRef
  • In VitroAdenosine Triphosphate Based Chemotherapy Response Assay in Gastric Cancer
    Seulkee Park, Yanghee Woo, Hogeun Kim, Yong Chan Lee, Sungho Choi, Woo Jin Hyung, Sung Hoon Noh
    Journal of Gastric Cancer.2010; 10(4): 155.     CrossRef
  • Individualized Tumor Response Testing for Prediction of Response to Paclitaxel and Cisplatin Chemotherapy in Patients with Advanced Gastric Cancer
    Jee Hyun Kim, Keun-Wook Lee, Yeul Hong Kim, Kyung Hee Lee, Do Youn Oh, Joonhee Kim, Sung Hyun Yang, Seock-Ah Im, Sung Ho Choi, Yung-Jue Bang
    Journal of Korean Medical Science.2010; 25(5): 684.     CrossRef
  • In vitro chemosensitivity based on depth of invasion in advanced colorectal cancer using ATP-based chemotherapy response assay (ATP-CRA)
    Y.B. Cho, W.Y. Lee, S.Y. Song, S.H. Choi, H.J. Shin, K.-D. Ahn, J.M. Lee, H.C. Kim, S.H. Yun, H.-K. Chun
    European Journal of Surgical Oncology (EJSO).2009; 35(9): 951.     CrossRef
  • Heterogeneity of Adenosine Triphosphate-Based Chemotherapy Response Assay in Colorectal Cancer - Secondary Publication
    Jung Wook Huh, Yoon Ah Park, Kang Young Lee, Seung-Kook Sohn
    Yonsei Medical Journal.2009; 50(5): 697.     CrossRef
  • The use of an in vitro adenosine triphosphate-based chemotherapy response assay to predict chemotherapeutic response in breast cancer
    Hyun-Ah Kim, Cha-Kyong Yom, Byung-In Moon, Kuk-Jin Choe, Sun-Hee Sung, Woon-Sup Han, Hye-Young Choi, Hye-Kyoung Kim, Heung-Kyu Park, Sung-Ho Choi, Eun-Jin Yoon, Soo-Youn Oh
    The Breast.2008; 17(1): 19.     CrossRef
  • Predictive Value of Individualized Tumor Response Testing by ATP-Based Chemotherapy Response Assay in Ovarian Cancer
    Seung-Su Han, Sung Ho Choi, Yoo-Kyung Lee, Jae Weon Kim, Noh-Hyun Park, Yong-Sang Song, Hyo-Pyo Lee, Soon-Beom Kang
    Cancer Investigation.2008; 26(4): 426.     CrossRef
  • In-vitro Chemosensitivity Test for Colorectal Cancer using an Adenosine-triphosphate-based Chemotherapy Response Assay (ATP-CRA)
    Jung Wook Huh, Yoon Ah Park, Seung Kook Sohn, Sung Ho Choi
    Journal of the Korean Society of Coloproctology.2007; 23(3): 172.     CrossRef
  • Adenosine triphosphate‐based chemotherapy response assay (ATP‐CRA)‐guided platinum‐based 2‐drug chemotherapy for unresectable nonsmall‐cell lung cancer
    Yong Wha Moon, Sung Ho Choi, Yong Tai Kim, Joo Hyuk Sohn, Joon Chang, Se Kyu Kim, Moo Suk Park, Kyung Young Chung, Hyoun Ju Lee, Joo‐Hang Kim
    Cancer.2007; 109(9): 1829.     CrossRef
  • Preliminary Study of the Clinical Features of the Chemosensitivity Test in Colorectal Cancer
    Chan Sup Park, Sung Ho Choi, Hung Dai Kim
    Journal of the Korean Society of Coloproctology.2007; 23(5): 358.     CrossRef
  • Correlation between the In Vitro ATP-based Chemosensitivity Assay and HER2/neu Expression in Women with Breast Cancer
    SU Woo, JW Bae, HG Kim, SH Choi, DH Kang, JB Lee, BW Koo
    Journal of International Medical Research.2007; 35(6): 753.     CrossRef
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Expression of Maspin is associated with the Intestinal Type of Gastric Adenocarcinoma
Seong Man Kim, Seong Jin Cho, Woo Young Jang, Duck Hwan Kim, Hyung Sik Shin, Myoung Kuk Jang, Hak Yang Kim, Eun Sook Nam
Cancer Res Treat. 2005;37(4):228-232.   Published online August 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.4.228
AbstractAbstract PDFPubReaderePub
Purpose

Maspin is known as a tumor suppressor gene, but its significance has been questioned in various human cancers. The aim of this study was to investigate the expression pattern of Maspin in human gastric adenocarcinomas and its possible correlation with clinicopathological findings.

Materials and Methods

The expression of Maspin mRNA was measured by nested RT-PCR using 60 frozen adenocarcinomas of the stomach and 31 noncancerous tissues from the proximal resection margin. Immunohistochemical study for Maspin protein expression was carried out using 62 paraffin-embedded tissues, composed of both cancer and noncancerous tissues.

Results

Maspin mRNA expression was detected in 80.0% (48 of 60) of the gastric adenocarcinomas, but in only 22.6% (7 of 31) of the normal gastric mucosa (p<0.001). The positive rate of Maspin protein expression was higher in the adenocarcinomas than the normal tissues (62.9% vs. 27.4%, p<0.05). In addition, the intestinal type of tumors showed significantly higher expression levels compared to the diffuse type of tumors (81.5% vs. 48.6%, p<0.05).

Conclusion

Our results suggest that Maspin is frequently expressed in human gastric cancers, and its expression might be associated with tumorigenesis of the intestinal type of gastric cancer.

Citations

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    Muhammad Ayaz Anwar, Muhammad Haseeb, Sangdun Choi, Kwang Pyo Kim
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    Hua-Chuan Zheng, Bao-Cheng Gong
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    Thomas M. Bodenstine, Richard E. B. Seftor, Zhila Khalkhali-Ellis, Elisabeth A. Seftor, Philip A. Pemberton, Mary J. C. Hendrix
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    KE-FENG LEI, BING-YA LIU, XIAO-LONG JIN, YAN GUO, MIN YE, ZHENG-GANG ZHU
    Experimental and Therapeutic Medicine.2012; 3(6): 993.     CrossRef
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Gene Promoter Hypermethylation in Tumors and Plasma of Breast Cancer Patients
Young Kyung Bae, Young Ran Shim, Joon Hyuk Choi, Mi Jin Kim, Edward Gabrielson, Soo Jung Lee, Tae Yoon Hwang, Sei One Shin
Cancer Res Treat. 2005;37(4):233-240.   Published online August 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.4.233
AbstractAbstract PDFPubReaderePub
Purpose

To measure the hypermethylation of four genes in primary tumors and paired plasma samples to determine the feasibility of gene promoter hypermethylation markers for detecting breast cancer in the plasma.

Materials and Methods

DNA was extracted from the tumor tissues and peripheral blood plasma of 34 patients with invasive breast cancer, and the samples examined for aberrant hypermethylation in cyclin D2, retinoic acid receptor β (RARβ), twist and high in normal-1 (HIN-1) genes using methylation-specific PCR (MSP), and the results correlated with the clinicopathological parameters.

Results

Promoter hypermethylation was detected at high frequency in the primary tumors for cyclin D2 (53%), RARβ (56%), twist (41%) and HIN-1 (77%). Thirty-three of the 34 (97%) primary tumors displayed promoter hypermethylation in at least one of the genes examined. The corresponding plasma samples showed hyperme thylation of the same genes, although at lower frequencies (6% for cyclin D2, 16% for RARβ, 36% for twist, and 54% for HIN-1). Overall, 22 of the 33 (67%) primary tumors with hypermethylation of at least one of the four genes also had abnormally hypermethylated DNA in their matched plasma samples. No significant relationship was recognized between any of the clinical or pathological parameters (tumor size, axillary lymph node metastasis, stage, or Ki-67 labeling index) with the frequency of hypermethylated DNA in the primary tumor or plasma.

Conclusion

The detection of aberrant promoter hypermethylation of cancer-related genes in the plasma may be a useful tool for the detection of breast cancer.

Citations

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The Immunoexpressions and Prognostic Significance of Inhibin Alpha and Beta Human Chorionic Gonadotrophins (hCG) in Breast Carcinomas
Eundeok Chang, Eunjung Lee, Se Jeong Oh, Jeong Soo Kim, Changsuk Kang
Cancer Res Treat. 2005;37(4):241-246.   Published online August 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.4.241
AbstractAbstract PDFPubReaderePub
Purpose

Pregnancy and hCG treatments are considered essential for inhibiting breast cancer. The effect of hCG is accompanied by the synthesis of inhibin, a transforming growth factor involved in cell differentiation and proliferation. Inhibin is considered a tumor suppressor, but its role in the breast is unclear. The aim of this study was to determine the frequency and tissue distribution of the expressions of inhibin-α and β-hCG in breast cancer, and their prognostic relevance with other biological parameters.

Materials and Methods

334 of formalin-fixed, paraffin embedded tissue blocks were selected, and then immunostained for inhibin-α and β-hCG. The inhibin-α expression was compared with those of β-hCG, ER, PR and HER-2/neu, as well as the tumor characteristics and recurrences.

Results

Inhibin-α and β-hCG were expressed in 87 (26.0%) and 44 cases (13.2%), respectively. Inhibin-α was found in 25.1% of infiltrating ductal carcinomas (67/267), 26.7% of intraductal carcinomas (8/30), 33.3% of lobular tumors (3/9), 80.0% of apocrine carcinomas (4/5) and 21.7% of the other types (5/23). Inhibin-α was correlated with β-hCG (p<0.0001), PR (p=0.010) and HER-2/neu (p=0.021). HCG was focally expressed in the cytoplasm of the conventional types, but the apocrine type displayed diffusely intense cytoplasmic staining, which correlated with histological tumor types (p<0.001).

Conclusion

Inhibin was significantly correlated with the expressions of hCG, PR and HER-2/neu. Therefore, it might be a useful marker in the prevention and hormonal treatment of breast cancer, such as hCG and progesterone. HCG was expressed significantly higher in the apocrine type than the conventional types, suggesting it can be a useful adjunct in differentiating other cancer types.

Citations

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The Relationship between Expression of the Sodium/iodide Symporter Gene and the Status of Hormonal Receptors in Human Breast Cancer Tissue
Hyun Jung Oh, June-Key Chung, Joo Hyun Kang, Won Jun Kang, Dong Young Noh, In Ae Park, Jae Min Jeong, Dong Soo Lee, Myung Chul Lee
Cancer Res Treat. 2005;37(4):247-250.   Published online August 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.4.247
AbstractAbstract PDFPubReaderePub
Purpose

It has been reported that the sodium/iodide symporter (NIS) gene is expressed in several breast cancer tissues, suggesting the possibility of radionuclide imaging and therapy. However, the regulatory mechanism of NIS gene expression in breast cancer is not yet understood. To assess the relationship between the hormonal status and the NIS expression in breast cancer tissue, we investigated the NIS expression and correlated it to the expression of the thyrotropin receptor (thyroid stimulating hormone receptor, TSH-R), the estrogen receptor (ER) and the progesterone receptor (PR) in human breast cancer tissues.

Materials and Methods

Breast cancer tissues were obtained from 44 patients. Pathological examination showed 2 cases of Grade I, 17 of Grade II, 22 of Grade III, and 3 of unknown grade. We measured the expression of NIS and TSH-R genes by using RT-PCR and we measured the status of ER and PR by using immunohistochemistry.

Results

The NIS gene was expressed in 15 (34%) of the 44 breast cancer tissues. The NIS gene was expressed in 32% of the cases with TSH-R gene expression. The NIS gene was expressed in 40% of the breast cancer tissues with a positive PR and in 31% with a negative PR (p>0.05). It was positive for PR in 18% of the cases and negative for PR in 39% of the cases (p>0.05).

Conclusion

The NIS gene is expressed in approximately one-third of the human breast cancer tissues. Its expression was not related to the presence of the TSH-R gene or hormonal receptors, ER and PR.

Citations

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Characterization of RhoA-mediated Chemoresistance in Gastric Cancer Cells
Won Ki Kang, Inkyoung Lee, Chaehwa Park
Cancer Res Treat. 2005;37(4):251-256.   Published online August 31, 2005
DOI: https://doi.org/10.4143/crt.2005.37.4.251
AbstractAbstract PDFPubReaderePub
Purpose

RhoA is a critical transducer of extracellular signals, which leads to organization of actin cytoskeleton, motility, adhesion and gene regulation. The present study aimed to explore whether RhoA influences the susceptibility of gastric cancer cells to chemotherapeutic drugs.

Materials and Methods

SNU638 cells were transfected with a mock vector (pcDNA3.1), RhoA (pcDNA/RhoA), or constitutively active RhoA (pcDNA/caRhoA). MTT assay and Western blot analysis were performed to study the growth response to several chemotherapeutic drugs in the gastric cancer cell line, SNU638, with different RhoA levels.

Results

RhoA significantly enhanced the resistance to lovastatin, 5-FU, taxol and vincristine, but did not affect the sensitivity to cisplatin or etoposide in SNU638. In the Western blot analysis, RhoA decreased the PARP cleavage, which was accompanied by a concurrent reductionin cell death. The gene expression profile after a cDNA microarray analysis demonstrated that RhoA was associated with the differential expression of 19 genes, including those involved in anti-oxidant defense, glucose metabolism, anti-apoptosis and protein turnover.

Conclusion

Gastric cancer cells with a high expression of RhoA could be resistant to chemotherapeutic drugs, such as taxol or vincristine, implying that treatment strategies aimed at inactivation of RhoA might be promising for improving the efficacy of these chemotherapeutic drugs.

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