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Maejima R.,Miyagi Cancer Center Research Institute | Maejima R.,Tohoku University | Tamai K.,Miyagi Cancer Center Research Institute | Shiroki T.,Miyagi Cancer Center Research Institute | And 13 more authors.
International Journal of Oncology | Year: 2016

Semaphorins and their receptors are abnormally expressed in various cancers, but little is known about the expression and function of semaphorin 3E (SEMA3E) and its receptor, plexin D1 (PLXND1), in gastric cancer development or metastasis. We evaluated SEMA3E and PLXND1 expression by quantitative RT-PCR in gastric tissues from 62 patients who underwent gastrectomy and analyzed the correlation between their expression and clinicopathological variables. To assess the function of SEMA3E, we generated human gastric cancer cell lines with suppressed or increased SEMA3E expression. The expression level of SEMA3E, but not PLXND1, was correlated with lymph node involvement and metastatic progression in gastric cancer. A significant association was observed between a high level of SEMA3E expression and poor differentiation or poor survival in the intestinal type of gastric cancer. SEMA3E knockdown in gastric cancer cells attenuated cell proliferation and metastatic ability in vitro and in vivo. Moreover, SEMA3E caused cell proliferation and anchorage-independent cell growth in the intestinal type of gastric cancer. These results suggested that SEMA3E is likely to be involved in the development of gastric cancer and might also be a therapeutic target for its treatment.


Asagi A.,Shikoku Cancer Center | Ohta K.,Gastroenterological Surgery | Nasu J.,Shikoku Cancer Center | Tanada M.,Gastroenterological Surgery | And 6 more authors.
Pancreas | Year: 2013

OBJECTIVES: Fluorodeoxyglucose (FDG)-positron emission tomography/contrast- enhanced computed tomography (PET/CE-CT) involving whole-body scanning first by non-CE-CT and FDG-PET followed by CE-CT has been used for detailed examination of pancreatic lesions. We evaluated PET/CE-CT images with regard to differential diagnosis, staging, treatment response, and postoperative recurrence in pancreatic cancer. METHODS: Positron emission tomography/CE-CT was conducted in 108 patients with pancreatic cancer and in 41 patients with other pancreatic tumor diseases. RESULTS: The maximum standardized uptake value (SUVmax) overlapped in benign and malignant cases, suggesting that differential diagnosis of pancreatic tumors based on the SUVmax is difficult. In the evaluation of staging in 31 resectable pancreatic cancer by PET/CE-CT, the diagnostic accuracy rate was more than 80% for most factors concerning local invasion and 94% for distant metastasis but only 42% for lymph node metastasis. Significant positive correlations were found between the SUVmax and tumor size/markers, suggesting that SUVmax may be a useful indicator for the treatment response. Regarding the diagnosis of the postoperative recurrence, PET/CE-CT correctly detected local recurrence in all the 11 cases of recurrence, whereas abdominal CE-CT detected only 7 of 11 cases, suggesting that PET/CE-CT is superior in this context. CONCLUSIONS: Positron emission tomography/CE-CT is useful for the clinical management of pancreatic cancer. Copyright © 2012 by Lippincott Williams & Wilkins.


Tanemura M.,Gastroenterological Surgery | Ohmura Y.,Gastroenterological Surgery | Deguchi T.,Gastroenterological Surgery | MacHida T.,Gastroenterological Surgery | And 9 more authors.
American Journal of Transplantation | Year: 2012

Autophagy is a lysosomal degradation process of redundant or faulty cell components in normal cells. However, certain diseases are associated with dysfunctional autophagy. Rapamycin, a major immunosuppressant used in islet transplantation, is an inhibitor of mammalian target of rapamycin and is known to cause induction of autophagy. The objective of this study was to evaluate the in vitro and in vivo effects of rapamycin on pancreatic β cells. Rapamycin induced upregulation of autophagy in both cultured isolated islets and pancreatic β cells of green fluorescent protein-microtubule-associated protein 1 light chain 3 transgenic mice. Rapamycin reduced the viability of isolated β cells and down-regulated their insulin function, both in vitro and in vivo. In addition, rapamycin increased the percentages of apoptotic β cells and dead cells in both isolated and in vivo intact islets. Treatment with 3-methyladenine, an inhibitor of autophagy, abrogated the effects of rapamycin and restored β-cell function in both in vitro experiments and animal experiments. We conclude that rapamycin-induced islet dysfunction is mediated through upregulation of autophagy, with associated downregulation of insulin production and apoptosis of β cells. The results also showed that the use of an autophagy inhibitor abrogated these effects and promoted islet function and survival. The study findings suggest that targeting the autophagy pathway could be beneficial in promoting islet graft survival after transplantation. © Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.


Gomes Jr. C.A.,Gastroenterological Surgery
Cochrane database of systematic reviews (Online) | Year: 2012

A number of conditions compromise the passage of food along the digestive tract. Nasogastric tube (NGT) feeding is a classic, time-proven technique, although its prolonged use can lead to complications such as lesions to the nasal wing, chronic sinusitis, gastro-oesophageal reflux, and aspiration pneumonia. Another method of infusion, percutaneous endoscopy gastrostomy (PEG), is generally used when there is a need for enteral nutrition for a longer time period. There is a high demand for PEG in patients with swallowing disorders, although there is no consistent evidence about its effectiveness and safety as compared to NGT. To evaluate the effectiveness and safety of PEG as compared to NGT for adults with swallowing disturbances, by updating our previous Cochrane review. We searched The Cochrane Library, MEDLINE, EMBASE, and LILACS from inception to September 2011, as well as contacting main authors in the subject area. There was no language restriction in the search. We planned to include randomised controlled trials comparing PEG versus NGT for adults with swallowing disturbances or dysphagia and indications for nutritional support, with any underlying diseases. The primary outcome was intervention failure (e.g. feeding interruption, blocking or leakage of the tube, no adherence to treatment). Review authors performed selection, data extraction and evaluation of methodological quality of studies. For dichotomous and continuous variables, we used risk ratio (RR) and mean difference (MD), respectively with the random-effects statistical model and 95% confidence interval (CI). We assumed statistical heterogeneity when I 2 > 50%. We included nine randomised controlled studies. We did not identify new eligible studies published after our previous review literature search date (August 2009). Intervention failure occurred in 19/156 patients in the PEG group and 63/158 patients in the NGT group (RR 0.24, 95%CI 0.08 to 0.76, P = 0.01) in favour of PEG. There was no statistically significant difference between comparison groups in complications (RR 1.00, 95%CI 0.91 to 1.11, P = 0.93). PEG was associated with a lower probability of intervention failure, suggesting the endoscopic procedure is more effective and safe as compared to NGT. There is no significant difference of mortality rates between comparison groups, and pneumonia irrespective of underlying disease (medical diagnosis). Future studies should include previously planned and executed follow-up periods, the gastrostomy technique, and the experience of the professionals to allow more detailed subgroup analysis.


Suzuki R.,Gastroenterological Surgery | Yamamoto H.,Gastroenterological Surgery | Ngan C.Y.,Gastroenterological Surgery | Ngan C.Y.,Kanazawa University | And 10 more authors.
International Journal of Oncology | Year: 2013

Anti-angiogenic therapy, inhibition of a co-operative process with vascular endothelial cells and pericytes could be an effective strategy to treat malignant tumours. Apart from vascular endothelial growth factor (VEGF), angiopoietin 2 (Ang2) is a promising target of anti-angiogenic therapy. Although inhibition of Ang2 has been shown to decrease tumour size in preclinical and phase I trials, its mechanisms of action remain largely unknown. To elucidate the mechanisms of Ang2 inhibition, we have focused on differentiation of the vessels as well as on growth of the vessels, especially in vivo. L1-10, a selective Ang2 inhibitor was used. The in vitro effects of Ang2 inhibition or addition of Ang2 using HUVECs were also examined. Growth and differentiation of tumour-associated vessels were investigated in xenografts derived from a colon cancer treated by L1-10. Effects of VEGF inhibition were also examined to discriminate Ang2-specific action on the tumour-associated vessels. In vitro studies showed that VEGF enhanced proliferation and tube formation of HUVECs, and caused a significant increase in Rac1 and CDC42 expression when cultured in the collagen matrix gel, whereas neither Ang2 nor L1-10 affected in vitro behaviour of HUVECs or levels of the proteins. In vivo, on the other hand, we found that Ang2 inhibition with treatment of L1-10 dose-dependently decreased tumour growth. Furthermore, we found that L1-10 treatment extends the tumour-associated vessels whilst it suppressed a sound lumen formation. Histological analysis on xenografts suggests that Ang2 inhibition could have disturbed in vivo vascular differentiation. Our data provide a novel aspect that Ang2 may play an essential role in in vivo vascular differentiation, thus supporting a rationale for Ang2-targeted therapy against colon cancer.


Yasueda A.,Osaka University | Shinzaki S.,Gastroenterology and Hepatology | Iijima H.,Gastroenterology and Hepatology | Mizushima T.,Gastroenterological Surgery | And 6 more authors.
Anticancer Research | Year: 2016

Background/Aim: The efficacy of omega-3 supplementation by oral capsule for patients with Crohn's disease (CD) remains controversial. We investigated the safety and efficacy of an omega-3 emulsified formulation. Patients and Methods: Six patients with CD in remission participated in this open-label clinical trial. Patients ingested one bottle (100 ml) of the test formulation (IMARK S®) daily for 28 days. After a 1-month washout period, patients ingested two bottles of the formulation daily for 28 days. Anthropometric and blood tests were performed before and after each intervention. Results: The omega-3 emulsifying formulation was safe with minimal side-effects. Body weight and body-mass index were not altered; however, CD activity index scores tended to decrease after ingested one bottle of formulation. Blood tests revealed no severe adverse effects. Conclusion: Supplementation with an omega-3 emulsifying formulation can be safe and useful for maintaining remission in patients with CD and warrants further studies.


PubMed | Gastroenterological Surgery
Type: | Journal: The Cochrane database of systematic reviews | Year: 2012

A number of conditions compromise the passage of food along the digestive tract. Nasogastric tube (NGT) feeding is a classic, time-proven technique, although its prolonged use can lead to complications such as lesions to the nasal wing, chronic sinusitis, gastro-oesophageal reflux, and aspiration pneumonia. Another method of infusion, percutaneous endoscopy gastrostomy (PEG), is generally used when there is a need for enteral nutrition for a longer time period. There is a high demand for PEG in patients with swallowing disorders, although there is no consistent evidence about its effectiveness and safety as compared to NGT.To evaluate the effectiveness and safety of PEG as compared to NGT for adults with swallowing disturbances, by updating our previous Cochrane review.We searched The Cochrane Library, MEDLINE, EMBASE, and LILACS from inception to September 2011, as well as contacting main authors in the subject area. There was no language restriction in the search.We planned to include randomised controlled trials comparing PEG versus NGT for adults with swallowing disturbances or dysphagia and indications for nutritional support, with any underlying diseases. The primary outcome was intervention failure (e.g. feeding interruption, blocking or leakage of the tube, no adherence to treatment).Review authors performed selection, data extraction and evaluation of methodological quality of studies. For dichotomous and continuous variables, we used risk ratio (RR) and mean difference (MD), respectively with the random-effects statistical model and 95% confidence interval (CI). We assumed statistical heterogeneity when I > 50%.We included nine randomised controlled studies. We did not identify new eligible studies published after our previous review literature search date (August 2009). Intervention failure occurred in 19/156 patients in the PEG group and 63/158 patients in the NGT group (RR 0.24, 95%CI 0.08 to 0.76, P = 0.01) in favour of PEG. There was no statistically significant difference between comparison groups in complications (RR 1.00, 95%CI 0.91 to 1.11, P = 0.93).PEG was associated with a lower probability of intervention failure, suggesting the endoscopic procedure is more effective and safe as compared to NGT. There is no significant difference of mortality rates between comparison groups, and pneumonia irrespective of underlying disease (medical diagnosis). Future studies should include previously planned and executed follow-up periods, the gastrostomy technique, and the experience of the professionals to allow more detailed subgroup analysis.

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