2010 Fiscal Year Final Research Report
A quantitative evaluation of the determinant proteins for drug responsiveness assists in patient selection to chemotherapy in advanced gastrointestinal cancer
Project/Area Number |
20591631
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Digestive surgery
|
Research Institution | Saga University |
Principal Investigator |
KOHJI Miyazaki Saga University, 医学部, 教授 (30159173)
|
Co-Investigator(Renkei-kenkyūsha) |
KOYA Naohiko 佐賀大学, 医学部, 助教 (70404150)
|
Project Period (FY) |
2008 – 2010
|
Keywords | 定量的蛍光二重免疫染色法 / プロテオミックス解析 / 胃癌 / 術前化学療法 / 個別化治療 |
Research Abstract |
The present study analyzed the expression of 5-fluorouracil related enzymes, TS, DPD and OPRT in 47 gastric cancer biopsy specimens using quantitative double-fluorescence immunohistochemistry (qDFIHC), which is a newly developed system to quantify protein expression. The study first determined whether the cancer heterogeneity within the sample influences evaluationby qDFIHC system. Thereafter, the expression values of the TS, DPD, OPRT and OPRT/TS, OPRT/DPD, OPRT/(TS+DPD) ratios were retrospectively correlated with the clinical or pathological response in the patients. The expression values of TS, DPD and OPRT at a single field were significantly correlated with mean of the values evaluated at three fields. Among the 6 candidate factors analyzed, OPRT, OPRT/TS, OPRT/DPD and OPRT/(TS+DPD) showed significant correlations with the clinical response in 47 patients. Cut-off values to differentiate the clinical response were determined in the four factors. OPRT/TS showed the strongest correlation with the clinical response. qDFIHC was able to quantify the TS, DPD and OPRT expressions in cancer biopsy specimens without being affected by the heterogeneity. Effective therapy using tailored S-1 NAC accordingto the OPRT/TS ratio is therefore expected in advanced gastric cancer patients.
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[Journal Article] Gallbladder carcinoma with a large monolocular cystic cancerous component.2010
Author(s)
Hiraki M, Yakushiji H, Hashiguchi K, Harada S, Kohya N, Kai K, Yamaguchi K, Mori D, Irie K, Tokunaga O, Noshiro H, Miyazaki K.
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Journal Title
Oncol Lett 1
Pages: 995-998
Peer Reviewed
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[Journal Article] Evaluation of acoustic radiation force impulse elastography for fibrosis staging of chronic liver diseases : a pilot study.2010
Author(s)
Takahashi H, Ono N, Eguchi Y, Kitajima Y, Kawaguchi Y, Nakashita S, Ozaki I, Mizuta T, Toda S, Kudo S, Miyoshi A, Miyazaki K, Fujimoto K
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Journal Title
Liver Int 30
Pages: 538-545
Peer Reviewed
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[Presentation]2009
Author(s)
Hiraki M, Kitajima Y, Mitsuno M, Nakamura J, Hashiguchi K, Sato S, Miyazaki K.
Organizer
The significance of aderrant methylation in lymph node of gastric cancer AACR 100th Annual Meeting 2009
Place of Presentation
Denver, Colorado
Year and Date
20090418-20090422
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[Presentation]2008
Author(s)
Kai K, Kitajima Y, Hashiguchi K, Tokunaga O, Miyazaki K.
Organizer
Protein ratio of OPRT/TS or OPRT/(TS+DPD) evaluated by quantiative double fluorescence immunohistochemistry is a useful tool to predict drug efficacy of S-1 for gastric cancer. AACR annual meeting 2008.
Place of Presentation
Proceedings 49 36 San Diego ,CA
Year and Date
20080412-20080416
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[Presentation]2008
Author(s)
Ohtsuka T, Mitsuno M, Ide T, Kitajima Y, Miyazaki K.
Organizer
AACR annual meeting 2008 Possible mechanism of chemo-resistance under hypoxia and the effect of expressed ASC on hypoxia-mediated cell death in pancreatic cancer.
Place of Presentation
San Diego, CA
Year and Date
20080412-20080416
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[Presentation]2008
Author(s)
Kitajima Y, Mitsuno M, Hashiguchi K, Nakamnura J, Hiraki M, Miyazaki K.
Organizer
AACR annual meeting 2008 Tranilast increased the drug effect of gemcitabine via protain degradation of RRM1 in pancreatic cancer cells.
Place of Presentation
San Diego, CA
Year and Date
20080412-20080416