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101.
Onishi Y Mori S Kusumoto S Sugimoto K Akahane D Morita-Hoshi Y Kim SW Fukuda T Heike Y Tanosaki R Tobinai K Takaue Y 《International journal of hematology》2007,85(3):256-263
We investigated the feasibility of reduced-intensity conditioning with 4 Gy total body irradiation, fludarabine (30 mg/m2 for 6 days), and busulfan (4 mg/kg for 2 days) for bone marrow transplantation from a serologically HLA-matched unrelated donor. Seventeen adult patients (median age, 55 years; range, 27-67 years) with various hematologic malignancies (6 in remission, 11 not in remission) were treated. Successful engraftment was achieved in all patients at a median of day 18 (range, day 14-35) after transplantation, although subsequent secondary graft failure was observed in 2 patients. The cumulative incidence of acute graft-versus-host disease (GVHD) of grades II to IV at day 100 was 48%. With a median follow-up of 286 days (range, 56-687 days), the rates of 1-year overall survival, 100-day nonrelapse mortality, and 1-year nonrelapse mortality were 41%, 14%, and 46%, respectively. Eleven patients died, and the causes of death were relapse (n = 4), pulmonary complications (n = 4), acute GVHD (n = 2), and sepsis (n = 1). The remaining 6 patients (at transplantation, 2 were in remission, and 4 were not in remission) are currently still in remission. These results suggest that this regimen reduces the risk of graft failure, but further studies are needed to ameliorate transplantation-related toxicities, primarily GVHD and/or pulmonary complications. 相似文献
102.
Hisamitsu Miyaaki Tatsuki Ichikawa Kazuhiko Nakao Hiroshi Yatsuhashi Ryuji Furukawa Kazuo Ohba Katsuhisa Omagari Yukio Kusumoto Kenji Yanagi Osami Inoue Noboru Kinoshita Hiromi Ishibashi Michitami Yano Katsumi Eguchi 《Liver international》2008,28(4):519-524
Background/Aims: We evaluated patients with nonalcoholic fatty liver disease (NAFLD) and compared the clinical and pathological features to identify the risk factors for NAFLD with severe fibrosis. Methods: One hundred and eighty‐two patients with biopsy‐confirmed NAFLD from various medical centres were recruited into this study. Results: The variables that were significantly associated with severe steatosis were male gender (mild:severe=36%:53%, P=0.02), younger age (mild:severe=57%:82%, P>0.001) and absence of type 2 diabetes (mild:severe=43%:71%, P>0.001). There was no significant difference in the degree of inflammation among the clinical groups. The variables that were significantly associated with severe fibrosis were female gender (mild:severe=54%:84%, P=0.002), older age (≥60 years old) (mild:severe=29%:53%, P=0.020), type 2 diabetes (mild:severe=42%:71%, P=0.020) and hypertension (mild:severe=24%:53%, P=0.002). Although there were more obese patients in the group with severe fibrosis, the association was not statistically significant (mild:severe=67%:78%, P=0.229). The prevalence of high serum triglyceride levels was similar between the two groups. The N (Nippon) score (total number of risk factor) could significantly predict severe fibrosis in NAFLD patients (1.48 ± 1.14 vs. 2.66 ± 0.94, P<0.001). Conclusions: The N score can be used to predict severe fibrosis in cases of NAFLD. 相似文献
103.
Kobayashi H Yoshida R Kanada Y Fukuda Y Yagyu T Inagaki K Kondo T Kurita N Suzuki M Kanayama N Terao T 《Journal of cancer research and clinical oncology》2005,131(8):527-538
Purpose: The Basidiomycete fungus Agaricus blazei Murill has traditionally been used as a health food for the prevention of cancer. Methods: We examined whether beta-(1–6)-D-glucan extracted from A. blazei is a potential anticancer agent in an in vitro and in vivo animal model. Results: Here we show that (1) beta-glucan had cytotoxic effect against human ovarian cancer HRA cells, but not against murine Lewis lung cancer 3LL cells, in vitro; (2) beta-glucan promotes p38 MAPK activity for suppressing HRA cell proliferation and amplifying the apoptosis cascade; (3) beta-glucan stimulates translocation of the proapoptotic protein, Bax, from the cytosol to mitochondria, cytochrome c release, and subsequent caspase-9 activation; (4) treatment with SB203580, a p38 MAPK-specific inhibitor, suppresses beta-glucan-induced effects, indicating that activation of p38 MAPK is involved in the suppression of cell proliferation and mitochondrial activation-mediated cell death pathway; (5) in mice, oral supplementation with beta-glucan reduces pulmonary metastasis of 3LL cells and peritoneal disseminated metastasis of HRA cells and inhibits the growth of these metastatic tumors in lung or peritoneal cavity, in part, by suppressing uPA expression; and (6) in an in vivo experimental metastasis assay, however, the oral supplementation with beta-glucan after i.v. tumor cell inoculation did not reduce the number of lung tumor colonies. Conclusion: Treatment with beta-glucan may be beneficial for cancer patients with or at risk for metastasis. The beta-glucan-dependent signaling pathways are critical for our understanding of anticancer events and development of cancer therapeutic agents. 相似文献
104.
Tetsuo Kubota Ryuji Koike 《Modern rheumatology / the Japan Rheumatism Association》2010,20(3):213-221
Cryopyrin-associated periodic syndromes (CAPS) are caused by mutations of the gene encoding the NLR family protein NLRP3,
which together with caspase-1 and adaptor proteins constitutes a protein complex termed the inflammasome. In innate immune
reactions, a variety of stimuli activate the NLRP3 inflammasome, triggering caspase-1 to process proIL-1 and thus to produce
mature IL-1. Excessive production of IL-1 by monocytes/macrophages is the central pathophysiology of CAPS, and daily injection
of the IL-1 receptor antagonist anakinra rapidly ameliorates the inflammatory symptoms in most cases. Furthermore, double-blind,
placebo-controlled clinical trials have recently confirmed the efficacy and safety of rilonacept, a fusion protein of the
IL-1 receptor and IgG Fc, and canakinumab, a human anti-IL-1 monoclonal antibody, as novel long-lasting agents for treating
CAPS. 相似文献
105.
106.
Christian Wittekmd Paul Hermanek Yoshifumi Kawarada Kentaro Yamagiwa Shuji Isaji Ryuji Mizumoto Di Carlo Valerio Zerbi Alessandro Balzano Gianpaolo Tsunoda Tsukasa Eto Toshifumi Tsuchiya Ryoichi Ishikawa Osamu Ohigashi Hiroaki Nakamori Shoji Imaoka Shingi H. G. Beger M. H. Schoenberg D. Birk Eugene P. DiMagno Tomioka Tsutomu Kanematsu Takashi Ariyama Joe Yamamoto Masahiro Ohashi Osamu Hidehumi Ishida Takashi Kamigaki Hirohiko Onoyama Yoichi Saitoh 《Journal of gastrointestinal cancer》1994,16(1):99-120
107.
Role of reactive oxygen in synthetic estrogen induction of hepatocellular carcinomas in rats and preventive effect of vitamins 总被引:1,自引:2,他引:1
Ogawa Tomoko; Higashi Shunsaku; Kawarada Yoshifumi; Mizumoto Ryuji 《Carcinogenesis》1995,16(4):831-836
We have established an experimental model of oral contraceptive-inducedhepatocellular carcinomas (HCCs) in female Wistar rats, revealingthat ethynylestradiol (EE) and norethindrone acetate have actionsas both initiators and promoters. The present timesequencestudy was undertaken to clarify the role of free radicals inestrogen induction of HCC by measuring detoxifying enzyme activitiesand levels of 8-hydroxydeoxyguanosine (8-OH-dG) and by assessingthe effects of concomitant vitamin C, vitamin E or ß-caroteneadministration on hepatocarcinogenesis. During 12 months oraladministration of EE (0.075 or 0.75 mg/day), the 8-OH-dG levelsreached peak values after 1 month, when they were significantlyelevated as compared with the controls. Glutathione peroxidasedemonstrated a tendency to decrease. Histologically, pre-neoplasticlesions assessed by immunohistochemical staining for placentalglutathione S-transferase (GST-P) were first observed at 2 monthsin the groups given 0.075 and 0.75 mg/day of EE alone, withincidences of HCC at 12 months being 8.7% and 38.5% respectively.Combined administration of vitamins with 0.075 mg EE/day reducedthe elevation of the 8-OH-dG levels. GST-P-positive lesionswere first observed at 4 months in the vitamin E group and at6 months in the vitamin C and ß-carotene groups. Ascompared with the value in the 0.075 mg EE alone group, vitaminadministration significantly reduced the numbers of GST-P-positivefoci after 12 months of treatment The incidences of HCC at 12months were 0% in the vitamin C group, 4.5% in the vitamin Egroup and 4.8% in the ß-carotene group, i.e. administrationof the vitamins inhibited the development of GST-P-positivefoci, with suppression of HCC. The results thus suggest thatfree radicals play an important role in the induction of HCCby estrogen. 相似文献
108.
109.
Akazawa A Nishikawa K Suzuki K Asano R Kumadaki I Satoh H Hagiwara K Shin SJ Yano T 《Japanese journal of pharmacology》2002,89(4):417-421
The overexpression of ErbB-2 receptor relates to malignant transformation of breast cancer. The present study was carried out to establish the usefulness of alpha-tocopheryloxybutyric acid (TE) as a chemotherapeutic agent for human breast cancer. TE caused induction of apoptosis in MDA-MB-453 cells overexpressing the ErbB-2 receptor. TE reduced levels of activated ErbB-2 receptor and Akt. In contrast, TE induced the activation of p38, and SB203580, a specific inhibitor for p38, attenuated the TE-induced apoptosis. These data indicate that simultaneous occurrences of Akt inhibition and p38 activation by TE result in the cell death. 相似文献
110.
Kato R Ooi K Takeda K Mashimo K Fujimura Y Kusumoto M Ueno K 《Drug metabolism and pharmacokinetics》2002,17(4):363-366
The effect of calcium polycarbophil on the absorption of cefdinir, cephalosporin derivative, was evaluated in both in vitro and in vivo studies. In the in vitro study, the release of cefdinir from a cellulose membrane in the presence or absence of metal cations was measured using the dissolution test procedure. In the in vivo study, volunteers and a randomized crossover design with two phases were used. In the first phase, the volunteers received 200 mg of cefdinir alone (Study 1); in the other phase, they received 200 mg of cefdinir and 1200 mg of fine calcium polycarbophil granules concomitantly (Study 2). The cefdinir concentrations in the samples or serum were measured by an UV-VIS spectrophotometer or high-performance liquid chromatography. Release in the presence of iron ions was slower than that in the absence of metal ions, however no difference was observed between release in the presence of calcium ions and that in the absence of metal ions. No difference was observed in AUC(0-10), C(max) and t(max) between Study 1 and Study 2. The absorption of cefdinir was not affected by co-administration of calcium polycarbophil. Moreover, the in vitro study on the release of drugs from a cellulose membrane may predict the absorption of a drug caused by the formation of chelate complexes between the drug and metal ions. 相似文献