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21.
M Sakamori S Takehara M Setoguchi 《Nihon yakurigaku zasshi. Folia pharmacologica Japonica》1992,100(2):137-142
The binding of Y-25130 on serotonin 3 (5-HT3) receptors was evaluated by examining its effect on 3H-BRL 43694 (3H-granisetron) binding to rat cerebral cortex membranes in comparison with those of granisetron, ondansetron and metoclopramide. Y-25130, granisetron, ondansetron, metoclopramide, 5-HT and 2-methyl-5-HT displaced the specific binding of 3H-granisetron to the synaptosomal membranes in a concentration-dependent manner. The rank order of potency for inhibition of 3H-granisetron binding by the test compounds was Y-25130 not equal to granisetron greater than ondansetron much greater than 2-methyl-5-HT not equal to 5-HT not equal to metoclopramide. To determine the manner of interaction between Y-25130 and 5-HT3 receptors, Scatchard analysis of 3H-granisetron specific binding to the membranes of the cerebral cortex in the absence or presence of various concentrations of Y-25130 was performed. It was indicated that Y-25130 exerted a typical competitive-type inhibition of 3H-granisetron binding. The present study indicates that Y-25130 binds competitively to 5-HT3 receptors with high affinity. 相似文献
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Rie Tanioka Tomoki Michida Kentaro Shimizu Ryotaro Sakamori Eriko Satomi Keiji Yamamoto Masahiro Ikeda 《Digestive endoscopy》2004,16(3):253-256
A 32‐year‐old female was admitted to Osaka National Hospital for remarkable anemia. She had a history of food allergy for the past 6 years. Laboratory examinations revealed remarkable iron de?ciency anemia and protein‐losing gastroenteropathy. On upper gastrointestinal endoscopy, multiple nodular lesions resembling verrucous gastritis were observed in the gastric antrum and the duodenal bulb. Marked mucosal eosinophilic in?ltration was seen in the biopsy specimens. Small intestine and colon were normal by X‐ray examination and colonoscopy, respectively. She was diagnosed as eosinophilic gastritis. Her symptoms, laboratory data and endoscopic ?ndings improved by regulation of food intake and administration of steroid. Rare endoscopic appearance of eosinophilic gastritis probably has strong correlation with food allergy. 相似文献
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Impact of ribavirin dosage in chronic hepatitis C patients treated with simeprevir,pegylated interferon plus ribavirin combination therapy 下载免费PDF全文
Yuki Tahata Naoki Hiramatsu Tsugiko Oze Ayako Urabe Naoki Morishita Ryoko Yamada Takayuki Yakushijin Atsushi Hosui Masahide Oshita Akira Kaneko Hideki Hagiwara Eiji Mita Toshifumi Ito Yukinori Yamada Masami Inada Kazuhiro Katayama Shinji Tamura Yasuharu Imai Hayato Hikita Ryotaro Sakamori Yuichi Yoshida Tomohide Tatsumi Norio Hayashi Tetsuo Takehara 《Journal of medical virology》2016,88(10):1776-1784
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Tomohiro Kondo Junichi Matsubara Pham Nguyen Quy Keita Fukuyama Motoo Nomura Taro Funakoshi Keitaro Doi Yuichi Sakamori Masahiro Yoshioka Akira Yokoyama Masashi Tamaoki Tadayuki Kou Kenshiro Hirohashi Atsushi Yamada Yoshihiro Yamamoto Sachiko Minamiguchi Masakazu Nishigaki Takahiro Yamada Masashi Kanai Shigemi Matsumoto Manabu Muto 《Cancer science》2021,112(1):296-304
Comprehensive genomic profiling (CGP) testing by next‐generation sequencing has been introduced into clinical practice as part of precision cancer medicine to select effective targeted therapies. However, whether CGP testing at the time of first‐line chemotherapy could be clinically useful is not clear. We conducted this single‐center, prospective, observational study to investigate the feasibility of CGP testing for chemotherapy‐naïve patients with stage III/IV gastrointestinal cancer, rare cancer, and cancer of unknown primary, using the FoundationOne® companion diagnostic (F1CDx) assay. The primary outcome was the detection rate of at least one actionable/druggable cancer genomic alteration. Actionable/druggable cancer genomic alterations were determined by the F1CDx report. An institutional molecular tumor board determined the molecular‐based recommended therapies. A total of 197 patients were enrolled from October 2018 to June 2019. CGP success rate was 76.6% (151 of 197 patients), and median turnaround time was 19 days (range: 10‐329 days). Actionable and druggable cancer genomic alterations were reported in 145 (73.6%) and 124 (62.9%) patients, respectively. The highest detection rate of druggable genomic alterations in gastrointestinal cancers was 80% in colorectal cancer (48 of 60 patients). Molecular‐based recommended therapies were determined in 46 patients (23.4%). CGP testing would be a useful tool for the identification of a potentially effective first‐line chemotherapy. 相似文献
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Injection of IL-12 gene-transduced dendritic cells into mouse liver tumor lesions activates both innate and acquired immunity 总被引:4,自引:0,他引:4
Tatsumi T Takehara T Yamaguchi S Sasakawa A Miyagi T Jinushi M Sakamori R Kohga K Uemura A Ohkawa K Storkus WJ Hayashi N 《Gene therapy》2007,14(11):863-871
Dendritic cell (DC)-based vaccines have been applied clinically in the setting of advanced-stage cancer. To date, the clinical efficacy of these vaccines has been limited, possibly owing to the impairment of transferred DC function in cancer-bearing patients. In this study, we examined the therapeutic efficacy of interleukin-12 (IL-12) gene-transfected DCs isolated from tumor-bearing hosts against liver tumor. The endogenous DCs isolated from subcutaneous (s.c.) CMS4 tumor-bearing mice (CMS4DC) exhibited decreased expression levels of antigen-presenting molecules and low-allostimulatory capacity. CMS4DC produced less IL-12p70 than DCs isolated from normal mice. Adenoviral transfection of IL-12 gene into CMS4DC (AdIL12DC) restored the expression of antigen-presenting molecules and allostimulatory capacity. Intratumoral (i.t.) delivery of AdIL12DC resulted in complete rejection of intrahepatic CMS4 tumors and activation of innate and acquired immune cells. Antibody depletion studies revealed that both CD4(+) and CD8(+) T cells as well as natural killer cells play critical roles in mediating liver tumor rejection. I.t. treatment of AdIL12DC resulted in long-term protection against s.c. rechallenge with CMS4 tumor cells. These results revealed that IL-12 gene transfer is capable of improving the impaired functions of DC isolated from tumor-bearing hosts, and support the preclinical therapeutic efficacy of intrahepatic injection of AdIL12DC. 相似文献
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Keisuke Kohga Hinako Tsunematsu Satoshi Aono Satoshi Shimizu Takahiro Kodama Takatoshi Nawa Minoru Shigekawa Hayato Hikita Ryotaro Sakamori Atsushi Hosui Takuya Miyagi Naoki Hiramatsu Tatsuya Kanto Norio Hayashi Tetsuo Takehara 《International journal of cancer. Journal international du cancer》2013,133(5):1126-1134
α‐Galactosylceramide (α‐GalCer) has been reported to be therapeutic against metastatic liver tumors in mice. However, little is known regarding the efficacy of combined chemo‐immunotherapy using α‐GalCer and anticancer drugs. In this study, we evaluated the antitumor effect of the combination therapy of α‐GalCer and 5‐fluorouracil (5‐FU) against liver tumors of MC38 colon cancer cells. The liver weights of tumor‐bearing mice treated with the combination were significantly lower than those of nontreated mice and of mice treated with 5‐FU or α‐GalCer alone. No toxic effects on the liver and renal functions were observed in any of the treatment groups. α‐GalCer treatment induced significant activation of liver NK cells in vivo, but 5‐FU treatment did not. 5‐FU treatment resulted in a significant upregulation of NKG2D activating molecules (Rae‐1 and H60) and DNAM‐1 ligands (CD112 and CD155) on MC38 cells, but α‐GalCer did not. The cytolytic activity of α‐GalCer‐activated liver mononuclear cells against 5‐FU‐treated MC38 cells was significantly higher than that against nontreated cells. The increase of the cytolytic activity induced by 5‐FU partially depended on NKG2D‐Rae‐1 or H60 signals. Depletion of NK cells significantly inhibited the antitumor efficacy of 5‐FU against MC38 liver tumors, which suggested that the antitumor effect of 5‐FU partially depended on the cytolytic activity of NK cells. These results demonstrated that the combination therapy of α‐GalCer and 5‐FU produced synergistic antitumor effects against liver tumors by increasing the expression of NK activating molecules on cancer cells. This study suggests a promising new chemo‐immunotherapy against metastatic liver cancer. 相似文献
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Sakamori R Das S Yu S Feng S Stypulkowski E Guan Y Douard V Tang W Ferraris RP Harada A Brakebusch C Guo W Gao N 《The Journal of clinical investigation》2012,122(3):1052-1065
The constant self renewal and differentiation of adult intestinal stem cells maintains a functional intestinal mucosa for a lifetime. However, the molecular mechanisms that regulate intestinal stem cell division and epithelial homeostasis are largely undefined. We report here that the small GTPases Cdc42 and Rab8a are critical regulators of these processes in mice. Conditional ablation of Cdc42 in the mouse intestinal epithelium resulted in the formation of large intracellular vacuolar structures containing microvilli (microvillus inclusion bodies) in epithelial enterocytes, a phenotype reminiscent of human microvillus inclusion disease (MVID), a devastating congenital intestinal disorder that results in severe nutrient deprivation. Further analysis revealed that Cdc42-deficient stem cells had cell division defects, reduced capacity for clonal expansion and differentiation into Paneth cells, and increased apoptosis. Cdc42 deficiency impaired Rab8a activation and its association with multiple effectors, and prevented trafficking of Rab8a vesicles to the midbody. This impeded cytokinesis, triggering crypt apoptosis and disrupting epithelial morphogenesis. Rab8a was also required for Cdc42-GTP activity in the intestinal epithelium, where continued cell division takes place. Furthermore, mice haploinsufficient for both Cdc42 and Rab8a in the intestine demonstrated abnormal crypt morphogenesis and epithelial transporter physiology, further supporting their functional interaction. These data suggest that defects of the stem cell niche can cause MVID. This hypothesis represents a conceptual departure from the conventional view of this disease, which has focused on the affected enterocytes, and suggests stem cell-based approaches could be beneficial to infants with this often lethal condition. 相似文献
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Katsuhiro Masago Shiro Fujita Young Hak Kim Yukimasa Hatachi Akiko Fukuhara Kaoru Irisa Hiroki Nagai Yuichi Sakamori Yosuke Togashi Tadashi Mio Michiaki Mishima 《Cancer chemotherapy and pharmacology》2011,67(2):325-330