Project/Area Number |
21390450
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Obstetrics and gynecology
|
Research Institution | Kanazawa University |
Principal Investigator |
INOUE Masaki 金沢大学, 医学系, 教授 (10127186)
|
Co-Investigator(Kenkyū-buntansha) |
KYO Satoru 金沢大学, 医学系, 講師 (50272969)
TAKAKURA Masahiro 金沢大学, 附属病院, 助教 (20313661)
NAKAMURA Mitsuhiro 金沢大学, 附属病院, 助教 (50377397)
|
Project Period (FY) |
2009 – 2011
|
Project Status |
Completed (Fiscal Year 2011)
|
Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2011: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2010: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2009: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
|
Keywords | テロメラーゼ / 腫瘍融解ウイルス / 難治性がん / 腫瘍可視化 / 末梢血中腫瘍細胞 / 非侵襲性癌診断 / 遺伝子診断 / 先進医療 / Circulating tumor cell / Cancer screening / Telomerase / hTERT / Tumor-lysing virus / Gynecologic Cancer / 婦人科癌 / 卵巣癌 / 遺伝子治療 / 末梢血循環腫瘍細胞 / circulating tumor cells |
Research Abstract |
Despite tremendous development in chemotherapy for refractory gynecologic cancers over the past few decades, the prognosis of the advanced cases is still unsatisfactory, and novel treatment modalities are urgent needed. We developed virotherapy for solid tumors using telomerase-specific replication-selective adenoviruses(OBP-301), in which the human telomerase reverse transcriptase(hTERT) gene promoter has been inserted to direct tumor-specific E1 gene expression. In vitro treatment of Ovarian cancer cell with OBP-301 induced significant cell death in dose-dependent manner, although normal cells showed no significant cell death. Xenograft mouse model of ovarian cancer cells showed the improved survival of mice treated with Telomelysin. These findings support the therapeutic potential of virotherapy using oncolytic virus. OBP401 in which GFP gene is driven by the CMV-promotor, selectively replicates only in telomerase-positive cells, and therefore may be a tool for cancer screening. We collected a single cell with GFP from blood samples of cervical cancer patients and detected the same HPV-genotype in both CTC and original cancer tissues. This finding suggests that CTC detecting by OBP401 is the useful non-invasive diagnostic way for cancer screening and early detection of recurrent malignant tumors.
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