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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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Atsushi Hata Takahiro Nakajima Keisuke Matsusaka Masaki Fukuyo Junichi Morimoto Takayoshi Yamamoto Yuichi Sakairi Bahityar Rahmutulla Satoshi Ota Hironobu Wada Hidemi Suzuki Hisahiro Matsubara Ichiro Yoshino Atsushi Kaneda 《International journal of cancer. Journal international du cancer》2020,146(2):388-399
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Yusuke Satoh Hitoshi Kotani Yuichi Iida Takahito Taniura Yoshitomo Notsu Mamoru Harada 《Cancer science》2020,111(7):2248-2258
Myeloid‐derived suppressor cells (MDSCs) play a crucial role in immunosuppression in tumor‐bearing hosts. MDSCs express arginase‐I and indoleamine 2,3‐dioxygenase; they suppress T‐cell function by reducing the levels of l ‐arginine and l ‐tryptophan, respectively. We examined the anticancer effects of supplementation of these amino acids in CT26 colon carcinoma‐bearing mice. Oral supplementation of l ‐arginine or l ‐tryptophan (30 mg/mouse) did not affect tumor growth, whereas oral supplementation of d ‐arginine was lethal. Supplementation of l ‐arginine showed a tendency to augment the efficacy of cyclophosphamide (CP). CP reduced the proportions of granulocytic MDSCs and increased the proportions of monocytic MDSCs in the spleen and tumor tissues of CT26‐bearing mice. l ‐Arginine supplementation alone did not affect the MDSC subsets. CP treatment tended to reduce the plasma levels of l ‐arginine in CT26‐bearing mice and significantly increased the number of tumor‐infiltrating CD8+ T cells. In addition, l ‐arginine supplementation significantly increased the proportions of tumor peptide‐specific CD8+ T cells in draining lymph nodes. Importantly, additional supplementation of l ‐arginine significantly increased the number of cured mice that were treated with CP and anti‐PD‐1 antibody. Totally, l ‐arginine supplementation shows promise for boosting the therapeutic efficacy of chemoimmunotherapy. 相似文献
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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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Ota Yumiko Takahari Daisuke Suzuki Takeshi Osumi Hiroki Nakayama Izuma Oki Akira Wakatsuki Takeru Ichimura Takashi Ogura Mariko Shinozaki Eiji Suenaga Mitsukuni Chin Keisho Yamaguchi Kensei 《Cancer chemotherapy and pharmacology》2020,85(2):265-272
Cancer Chemotherapy and Pharmacology - In the ATTRACTION-2 trial, nivolumab significantly improved the survival of advanced gastric cancer patients. The pretreatment neutrophil-to-lymphocyte ratio... 相似文献