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CD98 is a promising prognostic biomarker in biliary tract cancer

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Hepatobiliary & Pancreatic Diseases International 2014年第6期13卷 654-657页

作者： Kyoichi Kaira Yutaka Sunose Noboru Oriuchi Yoshikatsu Kanai izumi takeyoshi Department of Medicine and Molecular Science Gunma University Graduate School of Medicine Showa-machi Maebashi Gunma Japan Department of Thoracic and Visceral Surgery Gunma University Graduate School of Medicine Showa-machi Maebashi Gunma Japan Department of Diagnostic Radiology and Nuclear Medicine Gunma University Graduate School of Medicine Showa-machi Maebashi Gunma Japan Division of Biosystem Pharmacology Department of Pharmacology Graduate School of Medicine Osaka University Osaka Japan

ABSTRACT： CD98 has been described to play a crucial role in tumor progression and survival. However, the role of CD98 in biliary tract cancer remains unclear. We found that 36.7% of all patients with biliary tract cancer had a high CD98 expression. Statistical analysis using Spearman＇s rank correlation showed that CD98 was significantly correlated with L-type amino acid transporter 1 （LAT1, r=0.562, P〈0.001）, Ki-67 （r=0.230, P=0.006） and CD34 （r=0.290, P=0.005）. Multivariate analysis confirmed that a high CD98 expression was an independent prognostic factor for predicting poor outcome. CD98 is closely associated with tumor growth, biological aggressiveness, and survival of patients. With these data we proposed that CD98 expression is necessary for the development and pathogenesis of biliary tract cancer.

关键词： CD98 biliary tract cancer amino acid transporter prognostic factor

Effect of ONO-4057 and tacrolimus on ischemia-reperfusion injury of the liver

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World Journal of Gastroenterology 2009年第45期15卷 5712-5715页

作者： Takayuki Takeichi Shinji Uemoto Sachiko Minamiguchi izumi takeyoshi Yukihiro Inomata Koichi Tanaka Eiji Kobayashi Department of Transplantation and Immunology Kyoto University Hospital 54 Kawara-cho ShogoinSakyo-ku Kyoto 606-8507 Japan Second Department of Surgery Gunma University School of Medicine 3-39-15 Showa-machi Maebashi Gunma 371-8511 Japan Department of Trans-plantation and Pediatric Surgery Postgraduate School of Medical Science Kumamoto University Kumamoto 1-1-1 Honjyo Ku-mamoto 860-8556 Japan Laboratory of Anatomic Pathology Kyoto University Hospital 54 Kawara-cho Shogoin Sakyo-ku Kyoto 606-8507 Japan Division of Organ Replacement Research Center for Molecular Medicine Jichi Medical School Minami-kawachi-machi Kawachi-gun Tochigi 329-0498 Japan

AIM: To investigate the effects of a novel Leukotriene B4 receptor antagonist and/or tacrolimus on ischemia-reperfusion in a rat liver model. METHODS: Male Lewis rats were pretreated with ONO-4057 (100 mg/kg) and/or tacrolimus (1 mg/kg) orally, and divided into four experimental groups; group 1 (control), group 2 (ONO-4057), group 3 (tacrolimus), group 4 (ONO-4057 + tacrolimus). RESULTS: There was a tendency for long survival in the groups treated with tacrolimus alone and ONO-4057 plus tacrolimus. Post-reperfusion serum aspartate aminotransferase levels decreased more signif icantly in ONO-4057 plus tacrolimus group (P < 0.01), than in the tacrolimus alone group (P < 0.05), compared to controls. CONCLUSION: This study demonstrated that pretreat-ment with ONO-4057 in combination with tacrolimus produced additive effects in a rat model of liver isch-emia-reperfusion injury.

关键词：再灌注损伤缺血再灌注肝损伤大鼠模型受体拮抗剂谷草转氨酶联合生产加性效应

Pharmacokinetics of paclitaxel in a hemodialysis patient with advanced gastric cancer: A case report

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World Journal of Gastroenterology 2006年第32期12卷 5237-5239页

作者： Susumu Kawate izumi takeyoshi Yasuo Morishita Department of Thoracic and Visceral Organ Surgery Gunma University Graduate School of Medicine MaebashiGunma 371-8511Japan

我们第一次为一个病人报导每周的 paclitaxel 化疗的可能性与先进， nonresectable 胃的癌症经历牙齿过敏细胞溶解。有长期的肾衰竭的一个 50 岁的人由于双边的 polycystic，一个星期经历牙齿过敏细胞溶解三次 5 年了，在 2004 年 12 ... 详细信息

我们第一次为一个病人报导每周的 paclitaxel 化疗的可能性与先进， nonresectable 胃的癌症经历牙齿过敏细胞溶解。有长期的肾衰竭的一个 50 岁的人由于双边的 polycystic，一个星期经历牙齿过敏细胞溶解三次 5 年了，在 2004 年 12 月与吐血介绍了。与淋巴节点转移基于胃的癌症的诊断，外科被执行。在第 15 手术后的天，病人用 paclitaxel 与化疗被对待。Paclitaxel 在 saline 的 250 mL 作为 1 h iv 注入在 60 mg/m2 的剂量被管理。血液透析被开始在 paclitaxel 注入的结束以后的 1 h 并且为 3 h 被执行。Paclitaxel 在 d 上每周被管理 1， 8，和 15 在 28-d 上骑车。paclitaxel 的最大的血浆集中是 1390 microg/L。在 paclitaxel 的曲线下面的区域是 4398.6 microg x h/L。等级 2 白细胞减少在第一个周期期间被遇到。到在注入以后的超过 24 h 的从 6 的 paclitaxel 的血浆集中是在我们的病人的 0.01 ～ 0.1 micromol/L，并且这些集中被显示了在没有在病人生产不利副作用，禁止胃的癌症房间的生长上有效。paclitaxel 的血浆集中没被牙齿过敏细胞溶解影响。我们断定 paclitaxel 的 pharmacokinetics 没与肾衰竭在一个病人被改变，并且那每周的 paclitaxel 是为有先进胃的癌症的牙齿过敏细胞溶解病人的合适的治疗政体。

关键词：药物代谢动力学血液透析胃癌临床

Direct hemoperfusion with a polymyxin B-immobilized cartridge in intestinal warm ischemia reperfusion

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World Journal of Gastroenterology 2008年第35期14卷 5436-5441页

作者： Hiroaki Sato Kazuhisa Arakawa Katsumi Kobayashi Hodaka Yamazaki Yujin Suto izumi takeyoshi Kiyohiro Oshima Department of Thoracic and Visceral Organ Surgery Gunma University Graduate School of MedicineMaebashiGunma 371-8511Japan Intensive Care Unit Gunma University HospitalMaebashiGunma 371-8511Japan

AIM: To investigate the effectiveness of direct hemo- perfusion with polymyxin B-immobilized fibers (DHP- PMX therapy) on warm ischemia-reperfusion (I/R) injury of the small intestine. METHODS: The proximal jejunum and distal ileum of mongrel dogs were resected. Warm ischemia was performed by clamping the superior mesenteric artery (SMA) and vein (SMV) for 2 h. Blood flow to the proximal small intestine was restored 1 h after reperfusion, and the distal small intestine was used as a stoma. The experiment was discontinued 6 h after reperfusion. The dogs were divided into two groups: the DHP-PMX group (n = 6, DHP-PMX was performed for 180 min; from 10 min prior to reperfusion to 170 min after reperfusion) and the control group (n = 5). The rate pressure product (RPP), SMA blood flow, mucosal tissue blood flow, and intramucosal pH (pHi) were compared between the two groups. The serum interleukin (IL)-10 levels measured 170 min after reperfusion were also compared. RESULTS: The RPP at 6 h after reperfusion was significantly higher in the PMX group than in the control group (12 174 ± 1832 mmHg/min vs 8929 ± 1797 mmHg/min, P < 0.05). The recovery rates ofthe SMA blood flow at 1 and 6 h after reperfusion were significantly better in the PMX group than in the control group (61% ± 7% vs 44% ± 4%, P < 0.05, and 59% ± 5% vs 35% ± 5%, P < 0.05, respectively). The recovery rate of the mucosal tissue blood flow and the pHi levels at 6 h after reperfusion were significantly higher in the PMX group (61% ± 8% vs 31% ± 3%, P < 0.05 and 7.91 ± 0.06 vs 7.69 ± 0.08, P < 0.05, respectively). In addition, the serum IL-10 levels just before DHP-PMX removal were significantly higher in the PMX group than in the control group (1 569 ± 253 pg/mL vs 211 ± 40 pg/mL, P < 0.05). CONCLUSION: DHP-PMX therapy reduced warm I/R injury of the small intestine. IL-10 may play a role in inhibiting I/R injury during DHP-PMX therapy.

关键词：肠疾病缺血/再灌注损伤多粘菌素消化系统疾病

Effect of atrial natriuretic peptide on ischemia-reperfusion injury in a porcine total hepatic vascular exclusion model

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World Journal of Gastroenterology 2007年第25期13卷 3487-3492页

作者： Katsumi Kobayashi Kiyohiro Oshima Masato Muraoka Takahiko Akao Osamu Totsuka Hisashi Shimizu Hiroaki Sato Kazumi Tanaka Kenjiro Konno Koshi Matsumoto izumi takeyoshi Department of Thoracic and Visceral Organ Surgery Gunma University Graduate School of Medicine 3-39-15 Showa-Machi Maebashi Gunma 371-8511 Japan Intensive Care Unit Gunma University Hospital 3-39-15 Showa-Machi Maebashi Gunma 371-8511 Japan Animal Resource Project Center for Molecular Medicine Jichi Medical University Institute 3311-1 Yakushiji Shimotsuke Tochigi 329-0498 Japan Department of Pathology Nippon Medical School Musashi-Kosugi Hospital 1-396 Kosugi-chou Nakaharaku Kawasaki Kanagawa 211-8533 Japan

AIM: To evaluate the effect of ANP on warm I/R injury in a porcine THVE model. METHODS: Miniature pigs (mini-pigs) weighing 16-24 kg were observed for 120 min after reperfusion following 120 min of THVE. The animals were divided into two groups. ANP (0.1 μg/kg per min) was administered to the ANP group (n = 7), and vehicle was administered to the control group (n = 7). Either vehicle or ANP was intravenously administered from 30 min before the THVE to the end of the experiment. Arterial blood was collected to measure AST, LDH, and TNF-α. Hepatic tissue blood ? ow (HTBF) was also measured. Liver specimens were harvested for p38 MAPK analysis and histological study. Those results were compared between the two groups. RESULTS: The AST and LDH levels were lower in the ANP group than in the control group; the AST levels were signifi cantly different between the two groups (60 min: 568.7 ± 113.3 vs 321.6 ± 60.1, P = 0.038 < 0.05, 120 min: 673.6 ± 148.2 vs 281.1 ± 44.8, P = 0.004 < 0.01). No signifi cant difference was observed in the TNF-α levels between the two groups. HTBF was higher in the ANP group, but the difference was not signif icant. A signifi cantly higher level of phosphorylated p38 MAPK was observed in the ANP group compared to the controlgroup (0 min: 2.92 ± 1.1 vs 6.38 ± 1.1, P = 0.011 < 0.05).Histological tissue damage was milder in the ANP group than in the control group. CONCLUSION: Our results show that ANP has a protective role in I/R injury with p38 MAPK activation in a porcine THVE model.

关键词：促尿钠排泄缩氨酸缺血损伤肝疾病

Prognostic significance of BMP and activin membrane-bound inhibitor in colorectal cancer

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World Journal of Gastroenterology 2008年第31期14卷 4880-4888页

作者： Nozomi Togo Susumu Ohwada Shinji Sakurai Hiroyuki Toya Ichiro Sakamoto Tatsuya Yamada Tetsuhiro Nakano Ken Muroya izumi takeyoshi Takashi Nakajima Takashi Sekiya Yusuke Yamazumi Tsutomu Nakamura Tetsu Akiyama Departments of Surgery Graduate School of Medicine Gunma University Gunma 371-8511 Japan Departments of Tumor Pathology Graduate School of Medicine Gunma University Gunma 371-8511 Japan Laboratory of Molecular and Genetic Information Institute for Molecular and Cellular Biosciences University of Tokyo Tokyo 113-0032 Japan

AIM: To investigate the clinical significance of BMP and activin membrane-bound inhibitor (BAMBI) which is a pseudoreceptor of transforming growth factor-beta (TGF-β) type Ⅰreceptors and acts as a negative regulator of TGF-β signaling and expression aberrantly elevated in colorectal cancers (CRCs). We studied BAMBI expression in CRCs. METHODS: We studied BAMBI expression in 183 surgically resected CRCs by immunochemical and immunoblotting analyses using a generated monoclonal anti-BAMBI antibody. Commercially available anti-β-catenin and anti-p53 antibodies were also applied for immunochemical analyses as a comparison ***: Immunohistochemical analysis revealed that BAMBI expression was observed in 148 (80.8%), and strong BAMBI expression was observed in 46% of the CRCs. Strong BAMBI expression was positively correlated with histological type, depth of invasion, lymph node metastases, and tumor node metastasis (TNM) stage (P < 0.05). Clear associations were found between BAMBI and β-catenin (P = 0.035) and p53 (P = 0.049) expression. In curatively resected CRC, 5-year recurrence-free survival was 51.9% (P = 0.037) for strong BAMBI expression compared to 79.8% for weak BAMBI expression. In the Cox’s multivariate analysis, lymph node metastases (RR 6.685; P < 0.001) and depth of invasion (RR 14.0; P = 0.013) were signifi cant indicators for recurrence, and strong BAMBI expression (RR 2.26; P = 0.057) tended to be signifi cant. CONCLUSION: BAMBI was linked to a potentially aggressive tumor phenotype and predicted tumor recurrence and cancer-related death in CRC. BAMBI expression might be applicable in the routine clinical setting of CRC.

关键词：转换生长因子结肠癌直肠癌治疗方法