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1.
Hitoshi Yoshiji Ryuichi Noguchi Kosuke Kaji Yasuhide Ikenaka Yusaku Shirai Tadashi Namisaki Mitsuteru Kitade Tatsuhiro Tsujimoto Hideto Kawaratani Hiroshi Fukui 《Journal of gastroenterology》2010,45(4):443-450
Background
Insulin resistance (IR) is reportedly involved in the progression of hepatocellular carcinoma (HCC). Because neovascularization plays an important role in HCC, including hepatocarcinogenesis, an angiostatic therapy would be a promising approach for chemoprevention against HCC. The aim of the present study was to examine the combined effect of clinically used branched-chain amino acids (BCAAs) and an angiotensin-converting enzyme inhibitor (ACE-I), in conjunction with neovascularization, on hepatocarcinogenesis under the condition of IR. 相似文献2.
Hideto Kawaratani Tatsuhiro Tsujimoto Masahisa Toyohara Kenichi Kin Tomoyasu Taniguchi Yasuyo Shirai Yasuhide Ikenaka Masaki Nakayama Hisao Fujii Hiroshi Fukui 《Digestive endoscopy》2010,22(4):373-375
Clostridium difficile toxin (CD toxin) causes antibiotic‐associated colitis, or pseudomembranous colitis (PMC). Although CD toxin is sometimes found in the stools of patients with ulcerative colitis (UC), UC is rarely complicated by PMC. We report herein a case of PMC complicating UC, and present a review of the literature. A 71‐year‐old woman was diagnosed as having UC of the left colon, and treated with prednisolone and mesalazine. Later, however, lumbar spinal stenosis was also detected. After surgery for lumbar spinal stenosis, she suffered postoperative infection of the lumbar region. After 3‐week treatment with antibiotics, she developed diarrhea, bloody stools, and abdominal pain. Colonoscopy revealed PMC of the cecum, ascending colon, sigmoid colon, and rectum. Stools were positive for CD toxin. As cefotiam hydrochloride, levofloxacin hydrate (LVFX), and prednisolone were suspected as the causative agents, she was treated with 1.5 g vancomycin (VCM) daily for 2 weeks without ceasing LVFX. Her symptoms improved, and colonoscopy confirmed resolution of PMC. The possibility of PMC should be considered in UC patients treated with antibiotics, immunosuppressive agents or corticosteroids who complain of gastrointestinal symptoms. These patients should be thoroughly investigated by several modalities, including colonoscopy and CD toxin testing. 相似文献
3.
H Yoshiji R Noguchi Y Ikenaka K Kaji Y Shirai Y Aihara J Yamao M Toyohara A Mitoro M Sawai M Yoshida C Morioka M Fujimoto M Uemura H Kawaratani T Tsujimoto H Fukui 《Oncology letters》2011,2(1):69-73
The identification of biomarkers of anti-angiogenic therapy that predict clinical benefit is of vital importance. We previously reported that a combination treatment with clinically available safe agents, specifically angiotensin-converting enzyme inhibitor (ACE-I) and vitamin K (VK), inhibited the cumulative recurrence of hepatocellular carcinoma (HCC) via suppression of the vascular endothelial growth factor (VEGF). The present study aimed to identify non-invasive biological markers that predict the clinically beneficial effect of this combination regimen. A combination of ACE-I (perindopril; 4 mg/day) and VK (menatetrenone; 45 mg/day) was administered for 54 months following curative therapy for HCC. The cumulative recurrence and several indices, which are reportedly considered as biological markers of anti-angiogenic therapies, were analyzed. The combined treatment of ACE-I and VK markedly inhibited the cumulative recurrence of HCC during the 54-month follow-up. The serum VEGF and soluble VEGF receptor (sVEGFR)-2 were significantly suppressed with this combination regimen, whereas sVEGFR-1 was not. In HCC patients without recurrence, a significant suppression of VEGF and sVEGFR-2 was achieved within 6 and 3 months after treatment, respectively. In conclusion, the combination treatment of ACE-I and VK is a potentially novel anti-angiogenic strategy for secondary chemoprevention against HCC since the two agents are widely used in clinical practice without serious side effects. Furthermore, sVEGFR-2 may become a useful clinical predictive marker of this combination treatment. 相似文献
4.
A Yamamoto T Kawaratani A Aisaka M Hashida H Sezaki 《The Journal of pharmacy and pharmacology》1991,43(1):36-39
Rats were immunized with bovine gamma-globulin-sulphanilic acid conjugate and the plasma concentration of sulphanilic acid examined after an intravenous injection of this drug. There was a significant increase in plasma half-life and AUC and a significant decrease in clearance of sulphanilic acid in the immunized rats compared with the control. In the immunized rats, binding of sulphanilic acid to macromolecules in serum, determined by ultrafiltration, decreased with increase of sulphanilic acid concentration. At low concentrations, there was a significant increase in % binding of the drug in the serum of immunized rats compared with controls. There was also a significant reduction in urinary excretion of total drug in the immunized rats compared with controls. These findings suggest that sulphanilic acid-specific antibodies in the serum of immunized animals bind [14C]sulphanilic acid, giving rise to higher serum levels thereby making it unavailable for normal excretory processes. 相似文献
5.
Naotaka Shimozato Tadashi Namisaki Kosuke Kaji Mitsuteru Kitade Yasushi Okura Shinya Sato Kei Moriya Kenichiro Seki Hideto Kawaratani Hiroaki Takaya Yasuhiko Sawada Soichiro Saikawa Keisuke Nakanishi Masanori Furukawa Yukihisa Fujinaga Takuya Kubo Kiyoshi Asada Koh Kitagawa Yuki Tsuji Daisuke Kaya Takahiro Ozutsumi Takemi Akahane Akira Mitoro Hitoshi Yoshiji 《Hepatology research》2019,49(10):1147-1161
6.
Hitoshi Yoshiji Ryuichi Noguchi Mitsuteru Kitade Kosuke Kaji Yasuhide Ikenaka Tadashi Namisaki Junichi Yoshii Koji Yanase Masaharu Yamazaki Tatsuhiro Tsujimoto Takemi Akahane Hideto Kawaratani Masahito Uemura Hiroshi Fukui 《Journal of gastroenterology》2009,44(5):483-491
Background Branched-chain amino acids (BCAAs) reportedly inhibit the incidence of hepatocellular carcinoma (HCC) in patients with liver
cirrhosis and obesity that is frequently associated with insulin resistance (IR). However, the possible mechanism is still
obscure. The aim of the present study was to examine the effect of BCAAs, especially in conjunction with angiogenesis, on
hepatocarcinogenesis under the condition of IR.
Methods The effect of BCAAs on the development of liver enzyme-altered preneoplastic lesions and angiogenesis was examined in obese
diabetic Otsuka Long-Evans Tokushima Fatty rats. We also performed an in vitro study to elucidate the possible mechanisms
involved.
Results Treatment with BCAAs markedly inhibited glutathione-S-transferase placental form (GST-P)-positive preneoplastic lesions along with suppression of neovascularization in the liver.
The hepatic expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, was also attenuated. BCAA
treatment significantly suppressed glucose- and insulin-induced in vitro angiogenesis in the presence of VEGF.
Conclusions In obese diabetic rats BCAAs exerted a chemopreventive effect against HCC, associated with the suppression of VEGF expression
and hepatic neovascularization. Since BCAA preparations are widely used in clinical practice for patients with chronic liver
diseases, this agent may represent a new strategy for chemoprevention against HCC in the future. 相似文献
7.
Platelet hyperaggregability is associated with decreased ADAMTS13 activity and enhanced endotoxemia in patients with acute cholangitis
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Hiroaki Takaya Hideto Kawaratani Takuya Kubo Kenichiro Seki Yasuhiko Sawada Kosuke Kaji Yasushi Okura Kosuke Takeda Mitsuteru Kitade Kei Moriya Tadashi Namisaki Akira Mitoro Masanori Matsumoto Hiroshi Fukui Hitoshi Yoshiji 《Hepatology research》2018,48(3):E52-E60
Aim
Insufficient ADAMTS13 activity (ADAMTS13:AC) leads to increased levels of unusually large von Willebrand factor (VWF) multimers and causes microcirculatory disturbance and multiple organ failure (MOF). Endotoxin (Et) triggers the activation of coagulation and cytokine cascades, leading to MOF in severe inflammatory response syndrome. Here, we investigated the potential role of endotoxemia‐related ADAMTS13 in acute cholangitis.Methods
Twenty‐four patients with acute cholangitis, including 7 with severe acute cholangitis, were recruited in this study. The levels of ADAMTS13:AC, VWF antigen (VWF:Ag), interleukin (IL)‐6, IL‐8, and tumor necrosis factor (TNF)‐α in each patient were determined by enzyme‐linked immunosorbent assay, whereas Et levels were determined by Et activity assay (EAA) analysis.Results
The ADAMTS13:AC and VWF:Ag levels were significantly lower and higher, respectively, in patients with acute cholangitis than in controls. The EAA levels were higher in patients with acute cholangitis than in controls, and were inversely correlated with that of ADAMTS13:AC. Patients with severe acute cholangitis had significantly lower ADAMTS13:AC and higher VWF:Ag levels than those with mild to moderate cholangitis. Notably, ADMTS13:AC was directly correlated with platelet counts and inversely correlated with IL‐6 levels, and the VWF:Ag/ADAMTS13:AC ratio was directly correlated with IL‐8 and TNF‐α levels.Conclusions
Imbalance of ADAMTS13:AC and VWF:Ag levels might be associated with severe acute cholangitis, reflecting platelet hyperaggregability. Severe acute cholangitis has severe pathophysiological features and is complicated by endotoxemia and MOF. Notably, this is the first report indicating an association between the levels of ADAMTS13:AC and VWF:Ag and those of EAA and cytokines in acute cholangitis. 相似文献8.
Hiroaki Takaya Tadashi Namisaki Mitsuteru Kitade Naotaka Shimozato Kosuke Kaji Yuki Tsuji Keisuke Nakanishi Ryuichi Noguchi Yukihisa Fujinaga Yasuhiko Sawada Soichiro Saikawa Shinya Sato Hideto Kawaratani Kei Moriya Takemi Akahane Hitoshi Yoshiji 《World journal of gastrointestinal oncology》2019,11(10):887-897
9.
Mitsuteru Kitade Hitoshi Yoshiji Ryuichi Noguchi Yasuhide Ikenaka Kosuke Kaji Yusaku Shirai Masaharu Yamazaki Masahito Uemura Junichi Yamao Masao Fujimoto Akira Mitoro Masahisa Toyohara Masayoshi Sawai Motoyuki Yoshida Chie Morioka Tatsuhiro Tsujimoto Hideto Kawaratani Hiroshi Fukui 《World journal of gastroenterology : WJG》2009,15(41):5193-5199
AIM: To elucidate the possible crosstalk between angiogenesis, cytokeratin-18 (CK-18), and insulin resistance (IR) especially in patients with non-alcoholic steatohepatitis (NASH). METHODS: Twenty-eight patients with NASH and 11 with simple fatty liver disease (FL) were enrolled in this study and underwent clinicopathological examination. The measures of angiogenesis, CK-18, and IR employed were CD34-immunopositive vessels, CK-18- immunopositive cells, and homeostasis model assessment of IR (HOMA-IR), respectively. The correlations of these factors with NASH were elucidated. RESULTS: Significant development of hepatic neovascularization was observed only in NASH, whereas almost no neovascularization could be observed in FL and healthy liver. The degree of angiogenesis was almost parallel to liver fibrosis development, and both parameters were positively correlated. Similarly, CK-18 expression and HOMA-R were significantly increased in NASH as compared with FL and healthy liver. Furthermore, CK-18 and HOMA-IR were also positively correlated with the degree of neovascularization. CONCLUSION: These results indicate that the crosstalk between angiogenesis, CK-18, and IR may play an important role in the onset and progression of NASH. 相似文献
10.
Sodium glucose cotransporter 2 inhibitor canagliflozin attenuates liver cancer cell growth and angiogenic activity by inhibiting glucose uptake
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Kosuke Kaji Norihisa Nishimura Kenichiro Seki Shinya Sato Soichiro Saikawa Keisuke Nakanishi Masanori Furukawa Hideto Kawaratani Mitsuteru Kitade Kei Moriya Tadashi Namisaki Hitoshi Yoshiji 《International journal of cancer. Journal international du cancer》2018,142(8):1712-1722
Sodium‐glucose cotransporter 2 inhibitors (SGLT2‐Is) comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules. Although a recent report demonstrated the potential ability of SGLT2‐Is to attenuate cancer growth of SGLT2‐expressing cancer cells, little is known about the effects of SGLT2‐Is on hepatocellular carcinoma (HCC). Here, we investigate the anti‐cancer properties of a SGLT2‐I, canagliflozin, against human liver cancer cells. SGTL2 mRNA and protein expression were detected in Huh7 and HepG2 cells, although not in HLE as well as primary human hepatocytes and hepatic stellate cells. Canagliflozin exerted antiproliferative effects on SGLT2‐expressing Huh7 and HepG2 cells in a dose‐dependent manner by inhibiting glycolytic metabolism including glucose uptake, lactate and intracellular ATP production. This agent also induced G2/M arrest and apoptosis with inhibited phosphorylation of ERK, p38 and AKT and cleavage of caspase3. Xenograft tumor growth assay showed that oral administration of canagliflozin (10 mg/kg/day) significantly reduced subcutaneous tumor burdens in a glycemic status‐independent manner, and attenuated intratumor vascularization in Huh7‐ and HepG2‐derived xenograft tumors in BALB/c nude mice. In vitro, canagliflozin suppressed the increased human umbilical vein endothelial cell (HUVEC) proliferation and tubular formation which were observed in Huh7 or HepG2 co‐cultures. By contrast, canagliflozin had no effect on tumor growth and intratumor angiogenesis in SGLT2‐null HLE‐derived xenograft models. These results indicate that SGLT2‐I therapy is a potential new strategy for the treatment of HCC. 相似文献