Effect of a Dipeptidyl Peptidase-IV Inhibitor, Des-Fluoro-Sitagliptin, on Neointimal Formation after Balloon Injury in Rats

Background: Recently, it has been suggested that enhancement of incretin effect improves cardiac function. We investigated the effect of a DPP-IV inhibitor, des-fluoro-sitagliptin, in reducing occurrence of restenosis in carotid artery in response to balloon injury and the related mechanisms. Methods and Findings: Otsuka Long-Evans Tokushima Fatty rats were grouped into four: control (normal saline) and sitagliptin 100, 250 and 500 mg/kg per day (n = 10 per group). Sitagliptin or normal saline were given orally from 1 week before to 2 weeks after carotid injury. After 3 weeks of treatment, sitagliptin treatment caused a significant and dose-dependent reduction in intima-media ratio (IMR) in obese diabetic rats. This effect was accompanied by improved glucose homeostasis, decreased circulating levels of high-sensitivity C-reactive protein (hsCRP) and increased adiponectin level. Moreover, decreased IMR was correlated significantly with reduced hsCRP, tumor necrosis factor-$\alpha$ and monocyte chemoattractant protein-1 levels and plasminogen activator inhibitor-1 activity. In vitro evidence with vascular smooth muscle cells (VSMCs) demonstrated that proliferation and migration were decreased significantly after sitagliptin treatment. In addition, sitagliptin increased caspase-3 activity and decreased monocyte adhesion and NFκB activation in VSMCs. Conclusions: Sitagliptin has protective properties against restenosis after carotid injury and therapeutic implications for treating macrovascular complications of diabetes

The genetic polymorphisms of HER-2 and the risk of lung cancer in a Korean population

<p>Abstract</p> <p>Background</p> <p>Human Epidermal Growth Factor Receptor 2 (HER-2; also known as erbB-2 or neu), a proto-oncogene of the receptor tyrosine kinase superfamily, has been associated with carcinogenesis and prognosis of human cancers, acting as a binding partner of other epidermal growth factor receptor (EGFR) family in the activation of EGFR signaling. Amplification of the HER-2 gene has been reported in lung cancer, where it has been associated with poor prognosis. In this study, we investigated whether the four polymorphisms (-3444C>T, -1985 G>T, I655A A>G and P1170A C>G) of the HER-2 gene are associated with the risk of lung cancer in Korean populations.</p> <p>Methods</p> <p>The frequencies of 4 polymorphisms of the HER-2 gene were examined by the polymerase chain reaction-restriction fragment length polymorphism or the single-nucleotide polymorphism-identification technology assay in the 407 lung cancer patients and 407 healthy controls.</p> <p>Results</p> <p>The frequencies of the 4 polymorphisms were not significantly different between patient and control groups in overall subjects. However, in the subgroup analysis, the 3 single nucleotide polymorphisms (-3444C>T, -1985G>T and P1170A C>G) showed statistically significant differences in the subgroups of females, non-smokers, and non-drinkers (<it>p </it>< 0.05). Additionally, we found the association between the risk of lung cancer and the polymorphisms of HER-2 gene in non-smoker subgroups with adenocarcinoma (<it>p </it>< 0.05).</p> <p>Conclusion</p> <p>Our results suggest that the polymorphisms of the HER-2 gene are associated with an increased susceptibility to lung cancer in females, non-smokers and non-drinkers subgroups in the Korean population.</p

Clinical significances of preoperative serum interleukin-6 and C-reactive protein level in operable gastric cancer

<p>Abstract</p> <p>Background</p> <p>The interleukin-6 (IL-6) pathway is one of the mechanisms that link inflammation and angiogenesis to malignancy. Because the C-reactive protein (CRP) is a representative marker for inflammation, CRP has recently been associated with the progression of disease in many cancer types. The principal objective of this study was to determine the preoperative serum levels of IL-6 and CRP in gastric carcinoma, and to correlate them with disease status and prognosis.</p> <p>Methods</p> <p>A total of 115 patients who underwent gastrectomy were enrolled in this study. Serum levels of IL-6 were assessed via Enzyme-Linked Immuno-Sorbent Assay (ELISA), and CRP was measured via immunoturbidimetry. Histological findings included tumor size, depth of tumor invasion, lymph node (LN) metastasis, and TNM stage (6th AJCC Stage Groupings: The staging systems; Primary tumor, regional LN, metastasis).</p> <p>Results</p> <p>Increases in cancer invasion and staging are generally associated with increases in preoperative serum IL-6 levels. IL-6 and CRP levels were correlated with invasion depth (<it>P </it>< 0.001, <it>P </it>= 0.001), LN metastasis (<it>P </it>< 0.001, <it>P </it>= 0.024) and TNM stage (<it>P </it>< 0.001, <it>P </it>< 0.001). The presence of peritoneal seeding metastasis is associated with IL-6 levels (<it>P </it>= 0.012). When we established the cutoff value for IL-6 level (6.77 pg/dL) by ROC curve, we noted significant differences in time to progression (TTP; <it>P </it>< 0.001) and overall survival (OS; <it>P </it>= 0.010). However, CRP evidenced no significance with regard to patients' TTP and OS levels. Serum IL-6 levels were correlated positively with CRP levels (<it>r</it>²= 0.049, <it>P </it>= 0.018).</p> <p>Conclusion</p> <p>Preoperative serum IL-6 and CRP levels might be markers of tumor invasion, LN metastasis, and TNM stage. Preoperative high IL-6 levels were proposed as a poor prognostic factor for disease recurrence and overall survival in patients with gastric cancers.</p

A randomized controlled trial of physical activity, dietary habit, and distress management with the Leadership and Coaching for Health (LEACH) program for disease-free cancer survivors

Abstract Background We aimed to evaluate the potential benefits of the Leadership and Coaching for Health (LEACH) program on physical activity (PA), dietary habits, and distress management in cancer survivors. Methods We randomly assigned 248 cancer survivors with an allocation ratio of two-to-one to the LEACH program (LP) group, coached by long-term survivors, or the usual care (UC) group. At baseline, 3, 6, and 12 months, we used PA scores, the intake of vegetables and fruits (VF), and the Post Traumatic Growth Inventory (PTGI) as primary outcomes and, for secondary outcomes, the Ten Rules for Highly Effective Health Behavior adhered to and quality of life (QOL), the Hospital Anxiety and Depression Scale (HADS), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Results For primary outcomes, the two groups did not significantly differ in PA scores or VF intake but differed marginally in PTGI. For secondary outcomes, the LP group showed a significantly greater improvement in the HADS anxiety score, the social functioning score, and the appetite loss and financial difficulties scores of the EORTC QLQ-C30 scales from baseline to 3 months. From baseline to 12 months, the LP group showed a significantly greater decrease in the EORTC QLQ-C30 fatigue score and a significantly greater increase in the number of the Ten Rules for Highly Effective Health Behavior. Conclusion Our findings indicate that the LEACH program, coached by long-term survivors, can provide effective management of the QOL of cancer survivors but not of their PA or dietary habits. Trial registration Clinical trial information can be found for the following: NCT01527409 (the date when the trial was registered: February 2012)