1998 Fiscal Year Final Research Report Summary
Comparison of pathogenesis between human uterine cervical dysplasia and carcinoma in situ
| Project/Area Number |
09671677
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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 | Osaka University |
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Principal Investigator |
AZUMA Chihiro Osaka University Medical School, Lecturer, 医学部, 講師 (20151061)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOYA Kouichiro Osaka University Medical School, Assistant Professor retire, 医学部, 助手 (40291950)
SAJI Fumitaka Osaka University Medical School, Associate Professor retire, 医学部, 助教授 (90093418)
TOKUGAWA Yosihiro Osaka University Medical School, Assistant Professor, 医学部, 助手 (70283786)
OHASHI Kazutomo Osaka University Medical School, Lecturer, 医学部, 講師 (30203897)
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| Project Period (FY) |
1997 – 1998
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| Keywords | dysplasia / CIS / PXGR gene / mol gene / telomerase / genomic lmprinting |
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| Research Abstract |
It has yet to be elucidated whether carcinoma in situ (CIS) of uterine cervix passes through cervical dysplasia or whether these two lesions of intraepithelial neoplasm belong to distinctive disease entity.In this study, the sequence of CIS and dysplasia was investigated by using restriction fragment length polymorphism (RFLP) of PXGR gene.The RFLP analysis showed that tumor cells from CIS lesion are consistently monoclonal same as the invasive uterine cancer.However, the analysis of dysplastic cells expressed diverse results of clonality.They were to be monoclonal in some cases and the others were to be polyclonal.
The immortality of cells from CIS and dysplasia was studied by comparing expression profiles of mol-1 and mol-2 genes.The conversion of expression from mol-1 protein to mol-2 protein, which is related to immortality in tumor cells, was not identified in this experiments due to unstable binding activity of the specific antibody against mol protein.The increasing of telomerase
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activity that is another index related to cell immortality was detected in tumor cells from CIS lesion.The result of the experiments in cells from dysplasia were controversial because of contamination of normal tissue surrounding dysplastic lesion of the cervix.Generally, dysplasia is recognized as very small lesion and the stratiform structure are always shifting to normal tissue, which facilities contamination of normal epithelial cells in the process of cell sampling.We are now on the road of establishing a method for obtaining pure materials of the dysplastic cells under a microscope.
Carcinogenesis of human malignancy often involves the abnormality of genome imprinting and immuno-surveillance of the host.In this study, we showed that imprinting of H-19 and SNRPN genes were lost in a malignant mixed muellerian tumor of the uterus.We also reported the clinical study in which tumor recurrence are strongly related to immunosuppression induced by allogeneic blood transfusion.These results indicate that pathogenesis of human uterine cancer is deeply related to aberration of genome imprinting and immunosuppression.Furthermore, we demonstrated that the gene therapy of suicide gene combined with herpes simplex virus and thymidine kinase was clearly effective in human uterine cancer (bistandard killing effect). Less
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