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1.
Shinichi Tsuruta Kenichi Kohashi Yuichi Yamada Minako Fujiwara Yutaka Koga Eikichi Ihara Yoshihiro Ogawa Eiji Oki Masafumi Nakamura Yoshinao Oda 《Cancer science》2020,111(3):1008-1019
ARID1A, one of the subunits in SWI/SNF chromatin remodeling complex, is frequently mutated in gastric cancers with microsatellite instability (MSI). The most frequent MSI in solid‐type poorly differentiated adenocarcinoma (PDA) has been reported, but the SWI/SNF complex status in solid‐type PDA is still largely unknown. We retrospectively analyzed 54 cases of solid‐type PDA for the expressions of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), SWI/SNF complex subunits (ARID1A, INI1, BRG1, BRM, BAF155, and BAF170) and EBER, and mutations in KRAS and BRAF. We analyzed 40 cases of another histological type of gastric cancer as a control group. The solid‐type PDAs showed coexisting glandular components (76%), MMR deficiency (39%), and complete/partial loss of ARID1A (31%/7%), INI1 (4%/4%), BRG1 (48%/30%), BRM (33%/33%), BAF155 (13%/41%), and BAF170 (6%/2%), EBER positivity (4%), KRAS mutation (2%), and BRAF mutation (2%). Compared to the control group, MMR deficiency and losses of ARID1A, BRG1, BRM, and BAF155 were significantly frequent in solid‐type PDAs. Mismatch repair deficiency was associated with the losses of ARID1A, BRG1, and BAF155 in solid‐type PDAs. In the MMR‐deficient group, solid components showed significantly more frequent losses of ARID1A, BRG1, BRM, and BAF155 compared to glandular components (P = .0268, P = .0181, P = .0224, and P = .0071, respectively). In the MMR‐proficient group, solid components showed significantly more frequent loss of BRG1 compared to glandular components (P = .012). In conclusion, solid‐type PDAs showed frequent losses of MMR proteins and the SWI/SNF complex. We suggest that loss of the SWI/SNF complex could induce a morphological shift from differentiated‐type adenocarcinoma to solid‐type PDA. 相似文献
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Takeshi Nagashima Ken Yamaguchi Kenichi Urakami Yuji Shimoda Sumiko Ohnami Keiichi Ohshima Tomoe Tanabe Akane Naruoka Fukumi Kamada Masakuni Serizawa Keiichi Hatakeyama Kenya Matsumura Shumpei Ohnami Koji Maruyama Tohru Mochizuki Masatoshi Kusuhara Akio Shiomi Yasuhisa Ohde Masanori Terashima Katsuhiko Uesaka Tetsuro Onitsuka Seiichiro Nishimura Yasuyuki Hirashima Nakamasa Hayashi Yoshio Kiyohara Yasuhiro Tsubosa Hirohisa Katagiri Masashi Niwakawa Kaoru Takahashi Hiroya Kashiwagi Masahiro Nakagawa Yuji Ishida Takashi Sugino Mitsuru Takahashi Yasuto Akiyama 《Cancer science》2020,111(2):687-699
This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single‐center study called “High‐tech Omics‐based Patient Evaluation” or “Project HOPE” conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole‐exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed “Shizuoka Multi‐omics Analysis Protocol” developed in‐house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non–cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients. 相似文献
3.
Megumi Oshima Meg J. Jardine Rajiv Agarwal George Bakris Christopher P. Cannon David M. Charytan Dick de Zeeuw Robert Edwards Tom Greene Adeera Levin Soo Kun Lim Kenneth W. Mahaffey Bruce Neal Carol Pollock Norman Rosenthal David C. Wheeler Hong Zhang Bernard Zinman Hiddo J.L. Heerspink 《Kidney international》2021,99(4):999-1009
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Tada Kazuhiro Iwashita Yukio Shiraiwa Ken Uchida Hiroki Oshima Yusuke Sato Yuhki Nakanuma Hiroaki Hirashita Teijiro Masuda Takashi Endo Yuichi Takeuchi Yu Ohta Masayuki Itoh Hiroki Inomata Masafumi 《Cancer chemotherapy and pharmacology》2020,85(2):345-352
Cancer Chemotherapy and Pharmacology - Chemotherapy after hepatectomy for colorectal liver metastasis has not been established, due to the toxic side effects, which are likely related to impaired... 相似文献
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Tomotaka Shingaki Kentaro Taki Momoha Koyanagi Soshi Nagaoka Kenichi Yoshizawa Norika Oki 《Current medical research and opinion》2020,36(6):947-958
AbstractObjective: To evaluate the long-term safety and effectiveness of biosimilar insulin glargine (GLY) in real-world clinical practice.Methods: This prospective, non-interventional, multicenter, observational, post-marketing safety study (PMSS) enrolled Japanese patients with type 1 or 2 diabetes mellitus (T1DM or T2DM) starting GLY therapy, and was required by Japanese Pharmaceutical Affairs Law mandating post-marketing safety surveillance to acquire safety and effectiveness data of biosimilar products. Data collected from the 12-month observation included patient characteristics, adverse events, and blood glucose control.Results: The study enrolled 141 patients with T1DM and 1104 patients with T2DM. Pre-study insulin was used by 94.1% of patients with T1DM and 75.0% with T2DM. 65.4% of patients with T1DM and 64.3% with T2DM switched from the reference product (GLY-switched), while 25.0% with T2DM were insulin-naive. Adverse events were reported by 5.7% and 8.5% in T1DM and T2DM, respectively. Similar incidences were reported in GLY-switched. Adverse events were reported by 10.7% in insulin-naive T2DM. Baseline mean hypoglycemic events/month were 1.8 and 0.1 in T1DM and T2DM, respectively: the mean change from baseline (CFB) was –1.2 (p?=?.066) and 0.0 (p?=?.915), respectively. Baseline mean HbA1c was 8.4% and 8.7% in T1DM and T2DM, respectively; the mean CFB was –0.5% (p?<?.001) and –0.9% (p?<?.001), respectively, and –1.5% (p?<?.001) in insulin-naive T2DM.Conclusions: This first long-term Japanese PMSS of GLY demonstrated adverse events, hypoglycemia, and glycemic control consistent with the known GLY profile for T1DM and T2DM patients, in routine clinical practice. 相似文献
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