Inhibition of Pannexin 1 Reduces the Tumorigenic Properties of Human Melanoma Cells

Pannexin 1 (PANX1) is a channel-forming glycoprotein expressed in many tissues including the skin. PANX1 channels allow the passage of ions and molecules up to 1 kDa, including ATP and other metabolites. In this study, we show that PANX1 is highly expressed in human melanoma tumors at all stages of disease progression, as well as in patient-derived cells and established melanoma cell lines. Reducing PANX1 protein levels using shRNA or inhibiting channel function with the channel blockers, carbenoxolone (CBX) and probenecid (PBN), significantly decreased cell growth and migration, and increased melanin production in A375-P and A375-MA2 cell lines. Further, treatment of A375-MA2 tumors in chicken embryo xenografts with CBX or PBN significantly reduced melanoma tumor weight and invasiveness. Blocking PANX1 channels with PBN reduced ATP release in A375-P cells, suggesting a potential role for PANX1 in purinergic signaling of melanoma cells. In addition, cell-surface biotinylation assays indicate that there is an intracellular pool of PANX1 in melanoma cells. PANX1 likely modulates signaling through the Wnt/beta-catenin pathway, because beta-catenin levels were significantly decreased upon PANX1 silencing. Collectively, our findings identify a role for PANX1 in controlling growth and tumorigenic properties of melanoma cells contributing to signaling pathways that modulate melanoma progression

Anterograde colonic stent placement via a cecostomy tube site

Colonic stents have been used as a method of relieving colonic obstruction since 1991. They are classically inserted in a retrograde fashion via the rectum and are deployed under a combination of endoscopic and fluoroscopic guidance. A unique case is presented where the colonic stent was passed in an anterograde fashion through a recently created cecostomy tube site as a method of palliation to relieve an obstructing hepatic flexure tumour

The cost-effectiveness of colonic stenting as a bridge to curative surgery in patients with acute left-sided malignant colonic obstruction: A Canadian perspective

BACKGROUND: Over the past several years, colonic stenting has been advocated as an alternative to the traditional surgical approach for relieving acute malignant left-sided colonic obstruction. The aim of the present study was to determine the most cost-effective strategy in a Canadian setting

Canadian breast cancer guidelines: Have they made a difference?

BACKGROUND: A principal objective of the Canadian Clinical Practice Guidelines for the Care and Treatment of Breast Cancer was to reduce the variation in the way that breast cancer was being treated. To evaluate whether this goal has been reached, we examined variations among surgeons for 4 measures of surgical care and tested for differences in province-wide rates and in variations among surgeons before and after the guidelines were released. METHODS: We studied a population-based cohort of 7022 women living in Manitoba in whom breast cancer was diagnosed from 1995 to 2003 inclusive. Demographic, tumour and treatment information was obtained from the Manitoba Cancer Registry. We examined 4 measures of care: breast-conserving surgery, axillary assessment in invasive disease, axillary node dissection in noninvasive disease and the adequacy of axillary node dissection. Generalized linear models were used to test for significant variations in care among surgeons and to test for differences in province-wide rates and variations in these rates among surgeons before and after introduction of the guidelines. RESULTS: We found clinically significant variations in the province-wide rates of all 4 measures examined. These variations were statistically significant for all measures except axillary node dissection in noninvasive disease. No significant differences in either the province-wide rates or in variations in these rates among surgeons before and after introduction of the guidelines were found for any of the measures. INTERPRETATION: Our results suggest that the Canadian breast cancer guidelines are not meeting their stated objective. New strategies for guideline dissemination and implementation may be required