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RISS 인기검색어
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- 저자 : Hiroshi Asano (검색결과 5 건)
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Hiroshi Asano,Katsutoshi Oda,Kosuke Yoshihara,Yoichi M Ito,Noriomi Matsumura,Muneaki Shimada,Hidemichi Watari,Takayuki Enomoto 대한부인종양학회 2022 Journal of Gynecologic Oncology Vol.33 No.4
Background: Poly (adenosine diphosphate)-ribose polymerase (PARP) inhibitors for tumors with homologous recombination deficiency (HRD), including pathogenic mutationsin , have been developed. Genomic analysis revealed that about 20% of uterine leiomyosarcoma (uLMS) have HRD, including 7.5%–10% of alterations and 4%–6% of carcinomas of the uterine corpus, and 2.5%–4% of the uterine cervix have alterations of. Preclinical and clinical case reports suggest that PARP inhibitors may be effective against those targets. The Japanese Gynecologic Oncology Group (JGOG) is now planning to conduct a new investigator-initiated clinical trial, JGOG2052. Methods: JGOG2052 is a single-arm, open-label, multi-center, phase 2 clinical trial to evaluate the efficacy and safety of niraparib monotherapy for a recurrent or persistent rare fraction of gynecologic malignancies with mutations except for ovarian cancers. We will independently consider the effect of niraparib for uLMS or other gynecologic malignancies with mutations (cohort A, C) and HRD positive uLMS without mutations (cohort B). Participants must have 1–3 lines of previous chemotherapy and at least one measurable lesion according to RECIST (v.1.1). Niraparib will be orally administered once a day until lesion exacerbation or unacceptable adverse events occur. Efficacy will be evaluated by imaging through an additional computed tomography scan every 8 weeks. Safety will be measured weekly in cycle 1 and every 4 weeks after cycle 2 by blood tests and physical examinations. The sample size is 16–20 in each of cohort A and B, and 31 in cohort C. Primary endpoint is the objective response rate.
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Lymphadenectomy issues in endometrial cancer
Yosuke Konno,Hiroshi Asano,Ayumi Shikama,Daisuke Aoki,Michihiro Tanikawa,Akinori Oki,Koji Horie,Akira Mitsuhashi,Akira Kikuchi,Hideki Tokunaga,Yasuhisa Terao,Toyomi Satoh,Kimio Ushijima,Mitsuya Ishika 대한부인종양학회 2021 Journal of Gynecologic Oncology Vol.32 No.2
Objectives: This review aims to introduce preoperative scoring systems to predict lymphnode metastasis (LNM) and ongoing clinical trials to investigate the therapeutic role oflymphadenectomy for endometrial cancer. Methods: We summarized previous reports on the preoperative prediction models forLNM and evaluated their validity to omit lymphadenectomy in our recent cohorts. Next, wecompared characteristics of two ongoing lymphadenectomy trials (JCOG1412, ECLAT) toexamine the survival benefit of lymphadenectomy in endometrial cancer, and described thedetails of JCOG1412. Results: Lymphadenectomy has been omitted for 64 endometrial cancer patients who met low risk criteria to omit lymphadenectomy using our scoring system (LNM score) and no lymphaticfailure has been observed. Other two models also produced comparable results. Two randomizedphase III trials to evaluate survival benefit of lymphadenectomy are ongoing for endometrialcancer. JCOG1412 compares pelvic lymphadenectomy alone with pelvic and para-aorticlymphadenectomy to evaluate the therapeutic role of para-aortic lymphadenectomy for patients atrisk of LNM. For quality assurance of lymphadenectomy, we defined several regulations, includinglower limit of the number of resected nodes, and submission of photos of dissected area toevaluate thoroughness of lymphadenectomy in the protocol. The latest monitoring report showedthat the quality of lymphadenectomy has been well-controlled in JCOG1412. Conclusion: Our strategy seems reasonable to omit lymphadenectomy and could begeneralized in clinical practice. JCOG1412 is a high-quality lymphadenectomy trial in terms ofthe quality of surgical procedures, which would draw the bona-fide conclusions regarding thetherapeutic role of lymphadenectomy for endometrial cancer.
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Mineko Murakami,Takamitsu Fujimaki,Shuichiro Asano,Hiroshi Nakaguchi,Shoko M. Yamada,Katsumi Hoya,Kazuto Yamazaki,Yasuo Ishida,Akira Matsuno 연세대학교의과대학 2011 Yonsei medical journal Vol.52 No.6
High-dose methotrexate-based chemotherapy has extended survival in patients with primary central nervous system lymphoma (PCNSL). However, although salvage treatment is necessary in recurrent and refractory PCNSL, this has not been standardized. We herein describe the efficacy of a combination of rituximab and temozolomide (TMZ) in two consecutive patients with recurrent and refractory PCNSL. Based on the immunohistochemical study, case 1 had a non-germinal center B-cell-like (non-GCB) subtype, was positive for bcl-2 and negative for O6-methylguanine-DNA methyltransferase (MGMT). Case 2 was GCB subtype, bcl-2-, and MGMT+. Because of the positive expression of MGMT, interferon-beta was additionally given in case 2. Complete responses and partial responses were obtained after the third and fourth cycles of combination therapy, respectively. This was maintained for 12 months, with acceptable toxicity. The combination of rituximab and TMZ was effective in tumors with different immunohistochemical profiles. This combination therapy warrants further study in a larger population.
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Masako Tada,Ayaka Hayashi,Yumi Asano,Musashi Kubiura-Ichimaru,Takamasa Ito,Miho Yoshii,Hiroshi Kimura,Yoichi Matsuda,Mitsuo Oshimura 한국유전학회 2021 Genes & Genomics Vol.43 No.3
Background DNA methylation is a signifcant epigenetic modifcation that is evolutionarily conserved in various species and often serves as a repressive mark for transcription. DNA methylation levels and patterns are regulated by a balance of opposing enzyme functions, DNA methyltransferases, DNMT1/3A/3B and methylcytosine dioxygenases, TET1/2/3. In mice, the TET enzyme converts DNA cytosine methylation (5mC) to 5-hydroxymethylcytosine (5hmC) at the beginning of fertilisation and gastrulation and initiates a global loss of 5mC, while the 5mC level is increased on the onset of cell differentiation during early embryonic development. Objective Global loss and gain of DNA methylation may be diferently regulated in diverged species. Methods Chicken B-cell lymphoma DT40 cells were used as an avian model to compare diferences in the overall regulation of DNA modifcation with mammals. Results We found that DNA methylation is maintained at high levels in DT40 cells through compact chromatin formation, which inhibits TET-mediated demethylation. Human and mouse chromosomes introduced into DT40 cells by cell fusion lost the majority of 5mC, except for human subtelomeric repeats. Conclusion Our attempt to elucidate the diferences in the epigenetic regulatory mechanisms between birds and mammals explored the evidence that they share a common chromatin-based regulation of TET–DNA access, while chicken DNMT1 is involved in diferent target sequence recognition systems, suggesting that factors inducing DNMT–DNA association have already diverged.
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