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- 저자 : Ikuko Sakamoto (검색결과 2 건)
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Ikuko Sakamoto,Yosuke Hirotsu,Kenji Amemiya,Takahiro Nozaki,Hitoshi Mochizuki,Masao Omata 대한부인종양학회 2023 Journal of Gynecologic Oncology Vol.34 No.1
Objective: Elucidation of clonal origin of synchronous endometrial and ovarian cancers (SEOs). Methods: We reviewed 852 patients who diagnosed endometrial and/or ovarian cancer. Forty-five (5.3%) patients were diagnosed as SEOs. We evaluated blood and tissue samples from 17 patients. We analyzed the clonal origins of 41 samples from 17 patients by gene sequencing, mismatch microsatellite instability (MSI) polymerase chain reaction assay and immunohistochemical (IHC) staining of 4 repair genes. Results: Sixteen of 17 patients had at least 2 or more trunk mutations shared between endometrial and ovarian cancer suggesting the identical clonal origins. The shared trunk mutation are frequently found in endometrial cancer of the uterus, suggesting the uterine primary. Four out of 17 (24%) SEOs had mismatch repair (MMR) protein deficiency and MSI-high (MSI-H) states. One case was an endometrial carcinoma with local loss of MSH6 protein expression by IHC staining, and the result of MSI analysis using the whole formalin-fixed, paraffin-embedded specimen was microsatellite stable. In contrast, ovarian tissue was deficient MMR and MSI-H in the whole specimen. This indicated that MMR protein deficiency could occur during the progression of disease. Conclusion: Most SEOs are likely to be a single tumor with metastasis instead of double primaries, and their origin could be endometrium. In addition, SEOs have a high frequency of MMR gene abnormalities. These findings not only can support the notion of uterine primary, but also can help to expect the benefit for patients with SEOs by immuno-oncology treatment.
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Clinical and molecular biomarkers predicting response to PARP inhibitors in ovarian cancer
Takahiro Nozaki,Ikuko Sakamoto,Keiko Kagami,Kenji Amemiya,Yosuke Hirotsu,Hitoshi Mochizuki,Masao Omata 대한부인종양학회 2024 Journal of Gynecologic Oncology Vol.35 No.4
Objective: To determine the useful biomarker for predicting the effects of poly-(ADP ribose)-polymerase (PARP) inhibitors in Japanese patients with ovarian cancer. Methods: We collected clinical information and performed molecular biological analysis on42 patients with ovarian, fallopian tube, and primar y peritoneal carcinomas who receivedPARP inhibitors. Results: Among the analyzed patients with ovarian cancer, 23.8% had germline BRCAmutation (gBRCAm), 42.9% had homologous recombination repair-related gene mutation(HRRm), and 61.1% had a genomic instability score (GIS) of ≥42. Patients with HRRm hada significantly longer progression-free sur vival (PFS) than those without HRRm (medianPFS 35.6 vs. 7.9 months; p=0.009), with a particularly marked increase in PFS in patientswith gBRCAm (median PFS 42.3 months). Similarly, among patients with recurrent ovariancancer, those with HRRm had a longer PFS than those without HRRm (median PFS 42.3 vs. 7.7 months; p=0.040). Multivariate Cox proportional hazards regression analysis found thatperformance status and gBRCAm status were independent factors associated with prolongedPFS with PARP inhibitors. In recurrent ovarian cancer, multivariate regression analysisidentified platinum-free inter val (PFI) in addition to performance status as a significantpredictor of PFS. On the contrar y, no significant association was obser ved between PFS and aGIS of ≥42 used in clinical practice. Conclusion: We found that HRRm can be a useful biomarker for predicting the effects ofPARP inhibitors in treating ovarian cancer and that the PFI can also be useful in recurrentovarian cancer.
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