2001 Fiscal Year Final Research Report Summary
Genetic analyses for DNA replication error, beta-catenin gene, SKT11 etc.among the patients with gynecologic cancer
| Project/Area Number |
11671636
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
SAGAE Satoru Sapporo Medical University School of Medicine, Associate Professor, 医学部, 助教授 (00187056)
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| Co-Investigator(Kenkyū-buntansha) |
KUDO Ryuichi Sapporo Medical University School of Medicine, Professor, 医学部, 教授 (70045409)
TOKINO Takashi Sapporo Medical University School of Medicine, Professor, 医学部, 教授 (40202197)
ISHIOKA Shinichi Sapporo Medical University School of Medicine, Clinical Instructor, 医学部, 助手 (90305219)
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| Project Period (FY) |
1999 – 2001
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| Keywords | ovarian cancer / endometrial cancer / beta-catemn gene / DNA microarray / Taxol-induced apoptosis / bag-1 / hsp70 |
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| Research Abstract |
The recent studies showed that the RER abnormalities were detected in 23 % for endometrial cancer and 3 % of ovarian cancer, which genetic changes were detected in only endometrioid type of cancer. The prognosis of RER positive patients (pts) with endometrial caner tended to be worse and among them a case with MMR gene mutation (hMLH1 etc) was detected.
The mutation of beta-catenin gene were detected in 5 cases (8 %) of 61 ovarian cancer pts and 5 cases (14 %) of 35 endometrial cancer pts, and a micro metastasis of pelvic lymph node had a mutaton of beta-catenin gene,which might be useful for molecular diagnosis of lymph node metastasis.
The putative SKT11 gene, which function is Serine/Threonine Kinase, was reported as causative gene of Peutz-Jegher Syndrome. We performed the mutational analysis of STK11 gene in 30 ovarian cancer pts by SSCP-Sequence method. Only one case showed its mutation of CCG-CTG(Pro281-Leu)at exon 6 and two cases showed extra bands at exon 5.
A new anticancer drug group, Taxanes (Paclitaxel or Decetaxel) has been introduced for the treatment of ovarian cancer. However, chemosensitivities of these drugs are not determined before treatment of ovarian cancer. We tried to find out the possibilities of early detection of chemosensitivity by using genetic alteration, such as p53, BAX, Bcl-2 etc, and to analyze the mechanism of drug resistance. We showed that Paclitaxel-induced apoptosis played important roles of two different signal transductions, such as p53 independent pathway and stress-induced pathway in ovarian cancer cell lines, Blocking of these pathways and overexpression of bag-1 or hsp70 might be essential for the acquired resistance for Paclitaxel.
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