Digestive Diseases and Sciences (Dig Dis Sci)

Publications in this journal

• Article: Erratum to: BMP7 Expression in Esophageal Squamous Cell Carcinoma and Its Potential Role in Modulating Metastasis.

  Guanghui Xu, Shanhong Tang, Jianjun Yang, Kang Chen, Jianqin Kang, Guohong Zhao, Fan Feng, Xuewen Yang, Lina Zhao, Qun Lu, Li Sun, Liu Hong, Taiqian Gong, Hongwei Zhang
  Digestive Diseases and Sciences 05/2013;
• Article: The Phenotypic Expression of Inflammatory Bowel Disease in Patients with Primary Sclerosing Cholangitis Differs in the Distribution of Colitis.

  David F Schaeffer, Lay Lay Win, Sara Hafezi-Bakhtiari, Maria Cino, Gideon M Hirschfield, Hala El-Zimaity
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  ABSTRACT: BACKGROUND: Inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC) is reported to be mild and prone to right-side predominance with rectal sparing. However, no dedicated studies evaluating patterns of presentation of liver disease with respect to IBD are available. METHODS: We performed a detailed histological examination of the colonic biopsies in the context of PSC, identifying 97 patients [89 with ulcerative colitis and ten with Crohn's disease (CD)] stratified into two groups, based on their initial disease presentation: hepatic/biliary (group 1-PSC-IBD; n = 56) versus colonic (group 2-IBD-PSC; n = 41). RESULTS: Inflammatory bowel disease that preceded PSC had a tendency to have a "pan-colitis" distribution; this group included all patients with CD. Inflammatory bowel disease diagnosis that followed PSC presentation was more likely to be right-sided, sparing the descending, sigmoid and rectal regions (p = 0.002). In both groups, colitis was mild with focal deep plasmacytosis and occasional mild cryptitis. Active cryptitis with crypt abscesses, surface erosion and ulceration were not identified in any of the patients. CONCLUSION: Colitis associated with PSC shows mild disease activity and the colitis pattern is associated with disease presentation, i.e. colitis preceding PSC (IBD-PSC cohort) typically have a pancolitic distribution, while colitis following PSC (PSC-IBD cohort) demonstrates right-sided predominance. Awareness by pathologists and clinicians of these patterns of inflammatory bowel disease is important and of use in directing appropriate investigations for patients.
  Digestive Diseases and Sciences 05/2013;
• Article: Semaphorin 5A Promotes Gastric Cancer Invasion/Metastasis via Urokinase-Type Plasminogen Activator/Phosphoinositide 3-Kinase/Protein Kinase B.

  Guoqing Pan, Zhu Zhu, Jian Huang, Chenggang Yang, Ying Yang, Yingxia Wang, Xiaoyu Tuo, Guomiao Su, Xiangling Zhang, Zhi Yang, Tao Liu
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  ABSTRACT: BACKGROUND: Semaphorin 5A, a member of the semaphorin family, was originally identified as an axonal guidance factor functioning during neuronal development. Previously, we showed that the expression of semaphorin 5A might contribute to the metastasis of gastric cancer. However, less information is currently available as to the involvement of uPA in the semaphorin 5A-induced metastasis and invasion of gastric cancer cells. AIM: The present study was designed to test whether semaphorin 5A mediates the invasion and metastasis of gastric cancer via PI3K/Akt/uPA signaling. METHODS: The semaphorin 5A-overexpressing cell was established from the gastric cancer cell line AGS. The effect of semaphorin 5A on the expression of uPA was evaluated by ELISA and Western blotting as well as RT-PCR assays, respectively. Synthetic or natural inhibitors and dominant-negative mutants were used to determine the hierarchical relationship between semaphorin 5A, PI3K/Akt and uPA in the invasion and metastasis of gastric cancer. RESULTS: Overpression of semaphorin 5A enhanced the expression of uPA, and synthetic or natural inhibitors of uPA abolished semaphorin 5A-induced cell migration and invasion. Semaphorin 5A overexpression promoted the phosphorylation of Akt. Blocking effects of PI3K/Akt using pharmacologic inhibitors, dominant-negative mutants abolished the ability of semaphorin 5A to induce uPA expression and cell invasion and migration. CONCLUSION: Semaphorin 5A could promote invasion and metastasis of gastric cancer through the PI3K/Akt/uPA signal transduction pathway. Semaphorin 5A and its regulated molecules could be the potential targets for cancer therapy.
  Digestive Diseases and Sciences 05/2013;
• Article: Effect of Amiloride on Experimental Acid-Induced Heartburn in Non-erosive Reflux Disease.

  William J Bulsiewicz, Nicholas J Shaheen, Mark B Hansen, Amy Pruitt, Roy C Orlando
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  ABSTRACT: BACKGROUND: Acid-sensing ion channels (ASICs) are esophageal nociceptors that are candidates to mediate heartburn in non-erosive reflux disease (NERD). Amiloride, a diuretic, is known to inhibit ASICs. For this reason, we sought a role for ASICs in mediating heartburn by determining whether amiloride could block heartburn in NERD induced by esophageal acid perfusion. METHODS: In a randomized double-blind crossover study, we perfused the esophagus with amiloride or (saline) placebo prior to eliciting acid-induced heartburn in patients with a history of proton pump inhibitor-responsive NERD. Those with NERD and positive modified Bernstein test were randomized to perfusion with amiloride, 1 mmol/l, or placebo for 5 min, followed by repeat acid-perfusion. Heartburn severity and time to onset was measured and the process repeated following crossover to the alternative agent. RESULTS: 14 subjects completed the study. Amiloride did not reduce the frequency (100 vs. 100 %) or severity of acid-induced heartburn (Mean 2.50 ± SEM 0.33 vs. 2.64 ± 0.45), respectively. There was a trend towards longer time to onset of heartburn for amiloride versus placebo (Mean 2.93 ± SEM 0.3 vs. 2.36 ± 0.29 min, respectively), though these differences did not reach statistical significance (p > 0.05). CONCLUSIONS: Amiloride had no significant effect on acid-induced heartburn frequency or severity in NERD, although there was a trend towards prolonged time to onset of symptoms.
  Digestive Diseases and Sciences 05/2013;
• Article: Reactive Increase in Gastric Mucus Secretion Is an Adaptive Defense Mechanism Against Low-Dose Aspirin-Induced Gastropathy.

  K Iijima, T Iwabuchi, N Ara, T Koike, H Shinkai, Y Kamata, T Ichikawa, K Ishihara, T Shimosegawa
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  ABSTRACT: BACKGROUND: Gastric mucus is considered to play an essential role in gastric mucosal defense mechanisms, especially when irritants are present in the stomach. AIM: To investigate the relationship between low-dose aspirin-induced gastropathy and gastric secretory function, especially gastric mucus secretion, in healthy volunteers. METHODS: Thirty male, asymptomatic, Helicobacter pylori pylori-negative healthy volunteers were asked to take 100 mg of enteric-coated aspirin (Bayaspirin) once a day for 10 days. Endoscopic examination was performed before and 3 and 10 days after drug administration. The extent of endoscopically assessed gastric mucosal injury was semi-quantitatively evaluated according to the modified Lanza score. The pentagastrin-stimulated gastric juice was collected for 10 min during the endoscopic examination and subjected to analysis for gastric acid (mEq/10 min) or mucus (mg hexose/10 min) output. RESULTS: Overall, the 10-day aspirin treatment significantly increased gastric mucus secretion from 0.8 (interquartile range 1.7) to 1.6 (1.6) mg hexose/10 min (P < 0.05), with a concomitant and significant decrease in the gastric acid/mucus ratio from 4.3 (5.2) to 2.9 (4.7) (P < 0.01). Subsequent analysis of two subgroups of volunteers categorized according to their endoscopic status ("severe gastropathy" vs. "modest gastropathy") revealed that changes in gastric secretory parameters occurred exclusively in those subjects without severe gastric injury; there was no alteration in these parameters in subjects with severe gastric injury. CONCLUSIONS: The results of this study suggest that the reactive increase in gastric mucus secretion is an adaptive defense mechanism against low-dose aspirin-induced gastropathy. In some individuals, such a response may be insufficient to prevent the development of severe mucosal injury and even ulcers and their complications.
  Digestive Diseases and Sciences 05/2013;
• Article: Small Intestinal Bacterial Overgrowth and Orocecal Transit Time in Patients of Inflammatory Bowel Disease.

  S V Rana, S Sharma, A Malik, J Kaur, K K Prasad, S K Sinha, K Singh
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  ABSTRACT: BACKGROUND: Inflammatory bowel disease (IBD) consists of Ulcerative colitis (UC) and Crohn's disease (CD). These two conditions share many common features-diarrhea, bloody stools, weight loss, abdominal pain, fever and fatigue. Small intestinal bacterial overgrowth (SIBO) is frequent in patients with CD but it has not been studied in UC Indian patients. AIM: The study was planned to measure orocecal transit time (OCTT) and SIBO in UC and CD patients. METHODS: One hundred thirty-seven patients of IBD (95 UC and 42 CD) and 115 healthy controls were enrolled. OCTT and SIBO were measured by lactulose and glucose hydrogen breath test respectively. Concentration of hydrogen and methane were measured by SC microlyser from Quintron, USA. RESULTS: Mean ± standard deviation (SD) of OCTT in patients of IBD was significantly higher as compared to controls. Furthermore, OCTT was significantly higher in CD patients as compared to UC patients. It was also observed that occurrence of SIBO was significantly higher in IBD patients as compared to controls. The occurrence of SIBO in CD (45.2 %) was significantly higher as compared to patients in UC (17.8 %) group. Percentage of methane positive IBD patients (2.9 %) was significantly lower as compared to methane positive controls (24.4 %). CONCLUSION: OCTT was significantly delayed in IBD patients as compared to controls and in CD patients as compared to UC patients. OCTT was significantly higher in SIBO positive IBD patients as compared to SIBO negative patients. Thus, we can suggest that delayed OCTT would have been the cause of increased SIBO in these patients.
  Digestive Diseases and Sciences 05/2013;
• Article: Trying to Prevent the Clogged Drain: Optimizing the Yield and Function of Portal Vein-Infused Islets.

  A N Balamurugan, Timothy L Pruett
  Digestive Diseases and Sciences 05/2013;
• Article: Refractory Bleeding from a Malignant Duodenal Ulcer Treated with Placement of a Fully-Covered Gastroduodenal Stent.

  Pernilla M D'Souza, Gurpal S Sandha, Christopher W Teshima
  Digestive Diseases and Sciences 05/2013;
• Article: Infliximab-Related Hepatitis: A Case Study and Literature Review.

  Francisco Colina, Aída Molero, Begoña Casís, Pilar Martínez-Montiel
  Digestive Diseases and Sciences 05/2013;
• Article: The Myc 3' Wnt Responsive Element Regulates Neutrophil Recruitment After Acute Colonic Injury in Mice.

  Wesley M Konsavage, Jennifer N Roper, Faoud T Ishmael, Gregory S Yochum
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  ABSTRACT: BACKGROUND: The Wnt/β-catenin pathway regulates intestinal development, homeostasis, and regeneration after injury. Wnt/β-catenin signaling drives intestinal proliferation by activating expression of the c-Myc proto-oncogene (Myc) through the Myc 3' Wnt responsive DNA element (Myc 3' WRE). In a previous study, we found that deletion of the Myc 3' WRE in mice caused increased MYC expression and increased cellular proliferation in the colon. When damaged by dextran sodium sulfate (DSS), the increased proliferative capacity of Myc 3' WRE(-/-) colonocytes resulted in a more rapid recovery compared with wild-type (WT) mice. In that study, we did not examine involvement of the immune system in colonic regeneration. PURPOSE: To characterize the innate immune response in Myc 3' WRE(-/-) and WT mice during and after DSS-induced colonic injury. METHODS: Mice were fed 2.5 % DSS in their drinking water for five days to induce colonic damage and were then returned to normal water for two or four days to recover. Colonic sections were prepared and neutrophils and macrophages were analyzed by immunohistochemistry. Cytokine and chemokine levels were analyzed by probing a cytokine array with colonic lysates. RESULTS: In comparison with WT mice, there was enhanced leukocyte infiltration into the colonic mucosal and submucosal layers of Myc 3' WRE(-/-) mice after DSS damage. Levels of activated neutrophils were substantially increased in damaged Myc 3' WRE(-/-) colons as were levels of the neutrophil chemoattractants C5/C5a, CXCL1, and CXCL2. CONCLUSION: The Myc 3' WRE regulates neutrophil infiltration into DSS-damaged colons.
  Digestive Diseases and Sciences 05/2013;
• Article: Gastrointestinal Stromal Tumor: An Unusual Cause of Gastrointestinal Bleeding.

  Robert J Wong, Teri A Longacre, George Poultsides, Walter Park, Michael E Rothenberg
  Digestive Diseases and Sciences 04/2013;
• Article: A High Level of TM4SF5 Is Associated with Human Esophageal Cancer Progression and Poor Patient Survival.

  Yong-Bing Wu, You-Sheng Huang, Ya-Ping Xu, Yu-Fang Sun, Dong-Liang Yu, Xiao-Qiang Zhang, Xiang Long, Shu-Qiang Zhu, Jiang-Liang Zhou, Jian-Jun Xu
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  ABSTRACT: PURPOSE: We investigated expression of TM4SF5 and its involvement in human esophageal cancer (HEC). METHODS: We analyzed TM4SF5 expression in normal esophageal epithelial cells (HEEC), in four HEC cell lines, and in 20 HEC clinical tissue samples and matched nontumor samples. The effect of TM4SF5 on HEC cell proliferation and metastasis and invasion was assessed, and the relationship between TM4SF5 and integrin β1 was determined. Finally, TM4SF5 and integrin β1 expression were further examined by use of immunohistochemistry (IHC) and tissue microarray analysis, and the prognostic use of TM4SF5 and integrin β1 in HEC was evaluated. RESULTS: TM4SF5 was more highly expressed in HEC cells and in HEC tissues than in HEEC and matched nontumor tissues. Down-regulation of TM4SF5 in KYSE150 cells reduced cell proliferation and metastasis and invasion whereas metastasis and invasion by KYSE510 increased after TM4SF5 cDNA transfection. In HEC cells, TM4SF5 formed a complex with integrin β1, and interference with integrin β1 in KYSE510-TM4SF5 cells markedly inhibited cell invasion on laminin 5. Our findings also showed that TM4SF5 and integrin β1 overexpression correlated with low differentiation and high stage (p < 0.05, respectively). Postoperative 5-year overall survival of patients with TM4SF5(low) and/or integrin β1(low) was higher than for patients with TM4SF5(high) and/or integrin β1(high). Multivariate analysis demonstrated that TM4SF5 and integrin β1 co-overexpression was an independent prognostic marker for HEC. CONCLUSION: TM4SF5 is positively associated with HEC invasiveness. The combination of TM4SF5 with integrin β1 could potentially serve as a novel marker for predicting HEC prognosis.
  Digestive Diseases and Sciences 04/2013;
• Article: Losartan Supports Liver Regrowth via Distinct Boost of Portal Vein Pressure in Rodents with 90 % Portal Branch Ligation.

  Kezhou Li, Xiaohong Qi, Jiaying Yang, Jianping Gong, Chunlu Tan, Qingjie Xia, Jieran Long, Zhongdin Wang
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  ABSTRACT: OBJECTIVES: The study used a model of 90 % portal branch ligation (PBL) in rats to study the effect of losartan on portal vein pressure (PVP) and liver regeneration in rats after PBL. METHODS: A total of 144 male Sprague-Dawley rats were arbitrarily designated into three treatment method groups: a sham operation group (Sham), a PBL treatment group (PBL), and a PBL plus losartan treatment group (PBL + L). Losartan (2 mg/day) was intragastrically gavaged 3 days before the PBL or sham operation to time points of study. RESULTS: Both the PBL and PBL + L groups showed an intense surge in PVP after PBL treatment, peaking at 12 h postsurgery, then lessening progressively afterwards. PVP was substantially greater in these two groups compared with the Sham group at 6-72 h postsurgery (p < 0.01). Compared with the PBL group, the PBL + L group showed a noticeable reduction in PVP 6-48 h postsurgery (p < 0.05); the PBL group showed considerably raised levels of plasma ALT and AST 6-72 h postsurgery (p < 0.01). Compared to the PBL group, the PBL + L group showed drastically reduced plasma ALT and AST levels 12-72 h postsurgery (p < 0.05). CONCLUSIONS: Losartan supports liver regeneration in 90 % of rats that underwent PBL. The mechanism may be related to losartan's ability to regulate PVP and increase serum hepatocyte growth factor levels.
  Digestive Diseases and Sciences 04/2013;
• Article: Disrupted Circadian Rhythmicity of the Intestinal Glucose Transporter SGLT1 in Zucker Diabetic Fatty Rats.

  Hina Y Bhutta, Tara E Deelman, Stanley W Ashley, David B Rhoads, Ali Tavakkoli
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  ABSTRACT: BACKGROUND: Intestinal absorptive capacity shows a circadian rhythm synchronized with eating patterns. Disrupting these coordinated rhythms, e.g., with shift work, may contribute to metabolic disease. Circadian expression of nutrient transporters has not been studied in metabolic disease. We studied the circadian rhythm of intestinal transporter sodium glucose co-transporter type 1 (SGLT1) in an obese diabetic rat. METHODS: We compared obese Zucker diabetic fatty (ZDF) rats to lean ZDF littermates. Temporal feeding patterns were assessed, then rats were harvested at Zeitgeber (ZT, ZT0 = 7:00 a.m.) 3, 9, or 15 to measure insulin resistance, SGLT1 expression and intestinal glucose absorption capacity. Regulators of SGLT1 (sweet taste receptor T1R2/3; clock genes) were measured to elucidate underlying mechanisms. RESULTS: Both groups exhibited altered circadian food intake. Obese ZDF rats lost circadian rhythmicity of SGLT1 mRNA expression and functional activity. Lean ZDF rats maintained rhythmicity of SGLT1 mRNA expression but that of functional glucose absorption was blunted. Circadian rhythms of intestinal clock genes were maintained in both groups. Neither group had discernible rhythms of intestinal GLUT2 (glucose transporter) or T1R2 (sweet taste receptor component) mRNA expression. In summary, lean and obese ZDF rats exhibited similar disruptions in circadian feeding. Glucose intolerance was evident in lean rats, but only obese rats further developed diabetes and exhibited disrupted circadian rhythmicity of both SGLT1 mRNA expression and function. CONCLUSIONS: Our findings suggest that disrupted circadian feeding rhythms contribute to glucose intolerance, but additional factors (genetics, changes in nutrient sensing/transport) are needed to lead to full diabetes.
  Digestive Diseases and Sciences 04/2013;
• Article: Endoscopic Mucosal Resection Results in Change of Histologic Diagnosis in Barrett's Esophagus Patients with Visible and Flat Neoplasia: A Multicenter Cohort Study.

  Sachin Wani, Julian Abrams, Steven A Edmundowicz, Srinivas Gaddam, Christine E Hovis, Daniel Green, Neil Gupta, April Higbee, Ajay Bansal, Amit Rastogi, Dayna Early, Charles J Lightdale, Prateek Sharma
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  ABSTRACT: BACKGROUND: There are limited data on the effect of endoscopic mucosal resection (EMR) on changes of histopathologic diagnosis for Barrett's esophagus (BE) patients undergoing endoscopic eradication therapy (EET); especially those without visible lesions. AIM: To compare the frequency of changes of diagnosis by EMR compared with pre-EMR biopsy diagnosis for patients with and without visible lesions. METHODS: In this multicenter outcomes project, patients with Barrett's-related neoplasia undergoing EET at three tertiary-care centers were included. Patients undergoing biopsies followed by EMR within six months were included. The main outcome measures were frequency of overall change of histopathologic diagnosis, change based on pre-EMR biopsy diagnosis, and change based on the presence of visible lesions. RESULTS: One-hundred and thirty-eight BE patients (low-grade dysplasia (LGD) 15 (10.9 %), high-grade dysplasia (HGD) 87 (63 %), esophageal adenocarcinoma (EAC) 36 (26.1 %)) were included; 114 (82.6 %) patients had visible lesions. EMR resulted in a change of diagnosis for 43 (31.1 %) patients (upgrade 14 (10.1 %); downgrade 29 (21 %)). For HGD patients, EMR downstaged dysplasia grade for 17 (19.5 %) cases and upstaged it to EAC for nine (10.3 %) cases. There was a change of diagnosis for 26 (29.9 %) HGD patients, irrespective of the presence or absence of visible lesions (p = 0.76). For EAC patients, EMR downstaged dysplasia grade in 10 (27.8 %) cases. There was a change of diagnosis for 10 (27.8 %) EAC patients, irrespective of the presence or absence of endoscopically visible lesions (p = 0.48). CONCLUSIONS: EMR results in a change of diagnosis for approximately 30 % of BE patients with early neoplasia (with and without visible lesions) referred for EET.
  Digestive Diseases and Sciences 04/2013;
• Article: Catechins in Dietary Supplements and Hepatotoxicity.

  Victor J Navarro, Herbert L Bonkovsky, Sun-Il Hwang, Maricruz Vega, Huiman Barnhart, Jose Serrano
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  ABSTRACT: BACKGROUND: Many herbal dietary supplements (HDS) contain green tea extract (GTE) and its component catechins, although their presence may not always be indicated on the product label. PURPOSE: Because GTE and catechins have been implicated in human hepatotoxicity in several case reports, our objective was to determine whether catechins were present in HDS that were implicated in hepatotoxicity, even if not identified among the labeled ingredients, and whether these compounds could be associated with liver injury. METHODS: We assayed 97 HDS implicated in human hepatotoxicity for catechins. RESULTS: We found that 29 of 73 HDS (39.7 %) that did not identify GTE or any of its component catechins on their label contained catechins. Among patients with confirmed hepatotoxicity, there was no statistically significant association between the presence of catechin or the dose consumed and liver injury causality score, severity, or pattern of liver injury. Catechin levels tended to be highest in products used for weight loss, although catechin concentrations were low in most products. CONCLUSIONS: Many HDS commonly contain catechins that are implicated in hepatotoxicity, although their presence may not be indicated on the product label. Although our results did not establish an association between GTE or catechins with hepatotoxicity, they highlight some of the many complexities and uncertainties that surround the attribution of drug-induced liver injury (DILI) to HDS.
  Digestive Diseases and Sciences 04/2013;
• Article: Parallel TIPS for Treatment of Refractory Ascites and Hepatic Hydrothorax.

  Ahmad Parvinian, Ron C Gaba
  Digestive Diseases and Sciences 04/2013;
• Article: Granulomas of Intestinal Tuberculosis and Crohn's Disease Can Be Differentiated by CD73 Cell Surface Marker Expression: A Pilot Study.

  Rupa Banerjee, M Balaji, M Sasikala, S Anuradha, G V Rao, D Nageshwar Reddy
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  ABSTRACT: BACKGROUND: Intestinal tuberculosis (ITB) and Crohn's disease are similar granulomatous disorders. Granulomas are present in both and difficult to differentiate on histopathology alone. A recent study demonstrated recruitment of mesenchymal cells (MSCs) at the periphery of granulomas in lymph node tuberculosis which suppressed T cell responses. We hypothesized that granulomas of ITB would also recruit MSCs to evade host immune response. AIM: The purpose of this study was to demonstrate MSC markers in granulomas of ITB and evaluate whether distribution of MSC markers could differentiate between granulomas of Crohn's and ITB. METHODS: We initially retrospectively enrolled 17 patients with confirmed ITB (8) or Crohn's (9) with granulomas on histopathology. Tissues were evaluated by immunofluorescence for MSC markers CD29, CD90, CD73 and absence of haematopoietic markers CD31, CD34, CD45 and CD14. Double-staining was done to confirm presence of MSCs. Subsequently, 23 postoperative specimens of Crohn's (18) and ITB (5) were analyzed for validation. RESULTS: Overall, 27 Crohn's and 13 ITB cases were assessed. CD29 and CD90 positive cells were noted around both ITB and Crohn's granulomas. MSC marker CD73 was expressed around the granulomas of ITB alone and was completely absent in the Crohn's. The subsequent assessment of granulomas in postoperative specimens of Crohn's and ITB also showed similar results. CONCLUSION: Granulomas of ITB and Crohn's disease can be differentiated by CD73 MSC surface marker expression. The differential CD73 expression around ITB granuloma indicates that Mycobacterium tuberculosis evades host immunity by recruiting MSCs with CD73 expression. MSCs with increased CD73 expression could be the future for therapeutic intervention in Crohn's.
  Digestive Diseases and Sciences 04/2013;
• Article: Increased α-Tubulin1b Expression Indicates Poor Prognosis and Resistance to Chemotherapy in Hepatocellular Carcinoma.

  Cuihua Lu, Jing Zhang, Song He, Chunhua Wan, Aidong Shan, Yingying Wang, Litao Yu, Guoliang Liu, Ken Chen, Jing Shi, Yixin Zhang, Runzhou Ni
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  ABSTRACT: BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. It is important to understand molecular mechanisms of HCC progression and to develop clinically useful biomarkers for the disease. AIM: We aimed to investigate the possible involvement of α-tubulin1b (TUBA1B) in HCC pathology. METHODS: Tissue specimens were obtained from 114 HCC patients during hepatectomy. Immunohistochemistry and western blot analysis were used to detect TUBA1B expression in HCC tissues and cell lines. TUBA1B was knocked down in HCC cells by siRNA transfection. CCK-8 assay and flow cytometry were applied to determine cell proliferation and cell cycle progression, respectively. The efficacy of paclitaxel chemotherapy was evaluated by plate colony formation assay. RESULTS: TUBA1B was higher expressed in HCC tumor tissues than in adjacent nontumor tissues. TUBA1B and Ki-67 expressions were positively related to each other, and both their expressions were significantly associated with histological grade of HCC patients. Univariate and multivariate survival analyses revealed that TUBA1B was a significant predictor for overall survival of HCC patients. TUBA1B expression was increased in HCC cells during the G1- to S-phase transition. TUBA1B knockout in HCC cells inhibited cell proliferation, and attenuated resistance to paclitaxel. CONCLUSIONS: Our results indicated that TUBA1B expression was upregulated in HCC tumor tissues and proliferating HCC cells, and an increased TUBA1B expression was associated with poor overall survival and resistance to paclitaxel of HCC patients.
  Digestive Diseases and Sciences 04/2013;