2000 Fiscal Year Annual Research Report

抗癌剤感受性増強と治療係数の上昇へ向けた遺伝子治療

Research Project

Project/Area Number	10470265
Research Institution	Osaka Medical College
Principal Investigator	谷川允彦大阪医科大学, 医学部, 教授 (00111956)
Co-Investigator(Kenkyū-buntansha)	仁木正己大阪医科大学, 医学部, 講師 (90271402) 森田眞照大阪医科大学, 医学部, 助教授 (90200419)
Keywords	遺伝子治療 / 抗癌剤感受性増強 / フッ化ピリミジン / Thymidine phosphorylase / PD-ECGF / retroviral vector / 消化器癌 / 血管新生
Research Abstract	ヒト固形癌の治療成績の向上の為に新たなアプローチが模索される状況にある。我々はかねてからThymidine phosphorylase(TP)とThymidine kinase(TK)活性と腫瘍増殖能との関連をヒト新鮮腫瘍細胞を対象に検討することにより、胃癌・大腸癌など癌組織内のTP,TK活性と5-FU感受性の相関性も明らかにしたが、そうした検討結果を踏まえてプラスミッドベクターを介した肺癌細胞PC9のstable transfectantを作成してDoxifluridineおよび5-FU感受性の増強のメカニズムと細胞接触型のby stander effectの存在を明確にしてきた。そしてこの度、本研究の遂行の間に、慈恵会医科大学微生物学1との共同によって、TP/PD-ECGF cDNAのretroviral vectorを作成することに国際的に見ても初めて成功して(unpublished data)、これを用いたフッ化ピリミジン系の抗癌剤感受性増強の機序に関する研究を展開中である。一方、TP活性は腹膜播種癌細胞やIn vitro細胞株では極端に低いことが特徴的であり、こうした事象とPD-ECGFがangiogenic peptideであることをあわせ考慮すると新規に作成したTP/PD-ECGF cDNA retroviral vectorの活用は癌の血管新生に関しても情報を提供する可能性がある。遺伝子治療研究の一方法であるこのようなvirally directed enzyme prodrug therapy研究の発展は既存の癌化学療法の効果増強法を提唱できる可能性がある。

Research Products

(8 results)

All Other

All Publications (8 results)

[Publications] T.Nohara: "Expression of cell-cycle regulator p27 is correlated to the prognosis and ER expression in breast carcinoma patients"Oncology. 60. 94-100 (2001)
[Publications] K.Nishiguchi: "Comparative evaluation of surgical stress of laparoscopic and open surgeries for colorectal carcinoma."Dis Colon Rectum. 44(2). 223-230 (2001)
[Publications] K.Tanaka: "Expression of survivn and its relationship to loss of apoptosis in breast carcinomas."Clinical Cancer Research. 6. 127-134 (2000)
[Publications] T.Tenjyo: "Prognostic significance of p27^<kip1> protein expression and spontaneous apoptosis in patients with colorectal adenocarcinomas"Oncology. 58. 45-51 (2000)
[Publications] H.Shinohara: "Intensified regression of colon cancer liver metastases in mice treated with irinotecan and the immunomodulaor JBT 3002"J.Immunotherapy. 23. 321-331 (2000)
[Publications] M.Ohtani: "Impact of the expression of cyclin-dependent kinase inhibitor p27^<kip1> and apoptosis in tumor cells on the overall survival of patients with non-early stage gastric carcinoma"Cancer. 85(8). 1711-1718 (1999)
[Publications] C-D.Lu: "Loss of p27^<kip1> expression independently predicts poor prognosis for patients with resectable pancreatic adenocarcinoma"Cancer. 85(6). 1250-1260 (1999)
[Publications] H.Kawasaki: "Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer"Cancer Research. 58. 5071-5074 (1998)

2000 Fiscal Year Annual Research Report

抗癌剤感受性増強と治療係数の上昇へ向けた遺伝子治療

Principal Investigator

谷川 允彦 大阪医科大学, 医学部, 教授 (00111956)

Research Products

[Publications] T.Nohara: "Expression of cell-cycle regulator p27 is correlated to the prognosis and ER expression in breast carcinoma patients"Oncology. 60. 94-100 (2001)

[Publications] K.Nishiguchi: "Comparative evaluation of surgical stress of laparoscopic and open surgeries for colorectal carcinoma."Dis Colon Rectum. 44(2). 223-230 (2001)

[Publications] K.Tanaka: "Expression of survivn and its relationship to loss of apoptosis in breast carcinomas."Clinical Cancer Research. 6. 127-134 (2000)

[Publications] T.Tenjyo: "Prognostic significance of p27^<kip1> protein expression and spontaneous apoptosis in patients with colorectal adenocarcinomas"Oncology. 58. 45-51 (2000)

[Publications] H.Shinohara: "Intensified regression of colon cancer liver metastases in mice treated with irinotecan and the immunomodulaor JBT 3002"J.Immunotherapy. 23. 321-331 (2000)

[Publications] M.Ohtani: "Impact of the expression of cyclin-dependent kinase inhibitor p27^<kip1> and apoptosis in tumor cells on the overall survival of patients with non-early stage gastric carcinoma"Cancer. 85(8). 1711-1718 (1999)

[Publications] C-D.Lu: "Loss of p27^<kip1> expression independently predicts poor prognosis for patients with resectable pancreatic adenocarcinoma"Cancer. 85(6). 1250-1260 (1999)

[Publications] H.Kawasaki: "Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer"Cancer Research. 58. 5071-5074 (1998)

谷川允彦大阪医科大学, 医学部, 教授 (00111956)