Expression and promoter methylation status of hMLH1, MGMT,APC, and CDH1 genes in patients with colon adenocarcinoma

Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide. CRC development is the result of genetic and epigenetic alterations accumulation in the epithelial cells of colon mucosa. In the present study, DNA methylation, an epigenetic event, was evaluated in tumoral and matching normal epithelium in a cohort of 61 CRC patients. The results confirmed and expanded knowledge for the tumor suppressor genes hMLH1, MGMT, APC, and CDH1. Promoter methylation was observed for all the examined genes in different percentage. A total of 71% and 10% of the examined cases were found to be methylated in two or more and in all genes, respectively. mRNA and protein levels were also evaluated. Promoter methylation of hMLH1, MGMT, APC, and CDH1 genes was present at the early stages of tumor’s formation and it could also be detected in the normal mucosa. Correlations of the methylated genes with patient’s age and tumor’s clinicopathological characteristics were also observed. Our findings suggest that DNA methylation is a useful marker for tumor progression monitoring and that promoter methylation in certain genes is associated with more advanced tumor stage, poor differentiation, and metastasis.     

Clinical significance of FAK expression in human neoplasia

Focal Adhesion Kinase is a 119-121 kDa nonreceptor protein kinase widely expressed in various tissues and cell types. Several studies showed that FAK plays an important role in integrin signaling. Once activated by integrin and non-integrin stimuli, it binds and activates several other molecules, such as Src, p130Cas, Grb2, PI3K and paxillin, thus promoting signaling transduction. In normal cells FAK activity is under constant regulation by mechanisms such as gene amplification, alternative splicing and action of phosphatases. On the contrary, in vitro studies showed that in transformed cells unopposed FAK signaling promoted cancer cells' malignant characteristics. FAK was held responsible for cancer cells' uninhibited proliferation, protection from apoptosis, invasion, migration, adhesion and spreading, as well as tumor angiogenesis. Several in vivo studies supported the above observations and further correlated FAK expression with various clinicopathological parameters of several types of human malignancies. The purpose of this article is a comprehensive review of the existing data on FAK expression and signaling and their clinical significance in human malignancy.     

Down-regulation of integrin alpha(v)beta(3) expression and integrin-mediated signaling in glioma cells by adenovirus-mediated transfer of antisense urokinase-type plasminogen activator receptor (uPAR) and sense p16 genes

Interaction between the extracellular matrix and integrin receptors on cell surfaces leads not only to cell adhesion but also to intracellular signaling events that affect cell migration, proliferation, and survival. The vitronectin receptor alpha(v)beta(3) integrin is of key importance in glioma cell biology. The expression of urokinase-type plasminogen activator receptor (uPAR) was recently shown to co-regulate with the expression of alpha(v)beta(3) integrin. Moreover, restoration of the p16 protein in glioma cells inhibits the alpha(v)beta(3) integrin-mediated spreading of those cells on vitronectin. Thus we hypothesized that adenovirus-mediated down-regulation of uPAR and overexpression of p16 might down-regulate the expression of alpha(v)beta(3) integrin and the integrin-mediated signaling in glioma cells, thereby defeating the malignant phenotype. In this study, we used replication-deficient adenovirus vectors that contain either a uPAR antisense expression cassette (Ad-uPAR) or wild-type p16 cDNA (Ad-p16) and a bicistronic adenovirus construct in which both the uPAR antisense and p16 sense expression cassettes (Ad-uPAR/p16) are inserted in the E1-deleted region of the vector. Infecting the malignant glioma cell line SNB19 with Ad-uPAR, Ad-p16, or Ad-uPAR/p16 in the presence of vitronectin resulted in decreased alpha(v)beta(3) integrin expression and integrin-mediated biological effects, including adhesion, migration, proliferation, and survival Our results support the therapeutic potential of simultaneously targeting uPAR and p16 in the treatment of gliomas.     

Variable Pringle Maneuvers and Effect on Intestinal Epithelium in Rats. A Pilot Experimental Study in Rats

Background

It is observed that combined liver and colon surgery especially when this includes major liver resection with Pringle maneuver (PM) performance does not have a favorable outcome. Aim of our experimental study is to investigate the impact of portal triad occlusion on the large bowel and intra-abdominal inflammation and potent protective effects of the variants of (PM) in the combined surgical cases.

Materials and Methods

Forty-four rats were divided into four groups. In group A (control group), 1cm of the left partial colon was resected and then an end-to-end anastomosis was performed. In group B, a continuous PM for 30 minutes was performed followed by resection of 1cm of the left colon and an end-to-end anastomosis. In group C, the left colonic resection and anastomosis was performed after intermittent PM (IPM), which was 10 minutes PM followed by 5 minutes reperfusion repeated for three circles. In group D, an ischemic preconditioning for 10 minutes was initially performed followed by 5 minutes reperfusion and then continuous PM for 30 minutes. Finally the rats in group D underwent a 1cm left colonic resection and an end-to-end anastomosis.

Results

The percentage of colitis was higher in the B group (P = 0,19). The percentage of inflammation was not significantly higher even when we compared all “occlusion” groups (B+C+D) with the sham group. No evidence of pancreatitis was found in the sham group whereas amylase and lipase levels were higher in Groups B, C and D together (P = 0,0267). The comparison of group A to group B showed a significant difference (P = 0,0014) caused by continuous PM for 30 minutes, but there was no such result after IPM.

Conclusions

Major liver resections are performed with PM in order to minimize intra-operative blood loss. In the combined cases of colon surgery and major liver resections where PM is needed our results showed that IPM presents with better outcome and could be preferred compared with the other PM variants.     

Unique presentation of a giant mediastinal tumor as kyphosis: a case report

Introduction

Homonymous quadrantanopsia results from retrochiasmal lesions in the visual pathway. Invasive mole is a benign tumor that arises from myometrial invasion of a hydatidiform mole via direct extension through tissue or venous channels. Cerebral metastasis of invasive mole is rare and there has been no report demonstrating homonymous quadrantanopsia as the first manifestation of metastasis in any trophoblastic neoplasms.

Case presentation

We report the case of a 31-year-old Asian woman who presented with right homonymous inferior quadrantanopsia from the mass effect of a solitary cerebral metastasis from an invasive mole. A magnetic resonance image (MRI) of the brain showed a metastatic tumor in the left occipital lobe. The visual field improved slightly after chemotherapy. There was a reduction in the tumor size and the surrounding edema. This is the first case report demonstrating that homonymous quadrantanopsia should be included in the manifestations of the metastasis of an invasive mole.

Conclusions

The presentation of homonymous quadrantanopsia must alert ophthalmologists to conduct a complete medical history and arrange specialist consultation.     

Clinical significance of Src expression and activity in human neoplasia

Src, a 60 kDa non-receptor tyrosine kinase, is the product of normal c-src of the human genome and member of the Src protein tyrosine kinases family (SFK). As described by Martin and Rous, a genetic recombination between c-src and the RSV oncogene of Rous sarcoma virus results in a modified Src protein, with increased intrinsic activity and transforming potential in animal and human tissues. Several in vitro and in vivo studies supported this theory providing insight in the signalling pathways involved. Accumulating evidence from studies on clinical samples supported the role of Src in the process of carcinogenesis and disease progression in several human malignancies. Some studies have further reinforced the significance of the kinase in malignacy by correlating its expression and/or activity with important clinicopathological parameters, such as tumour stage, histopathological grade, proliferative capacity and most importantly patient's survival. This review is a comprehensive report of the published evidence on the expression and clinical significance of Src in human malignancy, which constitutes the background of the current studies and clinical trials on the use of Src inhibitors as novel potent antineoplastic strategy.     

Multimodal analgesia protocol for pain management after total knee arthroplasty: comparison of three different regional analgesic techniques

Objectives:To evaluate three different analgesic techniques, continuous epidural analgesia (EA), continuous intra-articular (IA) infusion analgesia and continuous femoral nerve block (FNB) in postoperative pain management, length of hospital stay (LOS), and time of patient mobilization after total knee arthroplasty (TKA).Methods:Seventy-two patients undergoing TKA were randomly allocated into three groups according to the analgesic technique used for postoperative pain management. Group EA patients received epidural analgesia (control group), group IA received intra-articular infusion and group FNB received femoral nerve block.Results:Upon analyzing the Numerical Rating Scale (NRS) scores at rest, at passive and active movement, up to 3 days postoperatively, we observed no statistically significant differences at any time point among the three groups. Similarly, no association among these analgesic techniques (EA, IA, FNB) was revealed regarding LOS. However, significant differences emerged concerning the time of mobilization. Patients who received IA achieved earlier mobilization compared to FNB and EA.Conclusions:Both IA and FNB generate similar analgesic effect with EA for postoperative pain management after TKA. However, IA appears to be significantly more effective in early mobilization compared to EA and FNB. Finally, no clinically important differences could be detected regarding LOS among the techniques studied.