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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/β-catenin pathway, because β-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.

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The cancer list was developed in partnership with the Canadian Society of Surgical Oncology, Canadian Association of Medical Oncologists, and Canadian Association of Radiation Oncology. Using knowledge translation and exchange efforts, this list should empower patients with cancer and physicians to assist in a targeted conversation about the appropriateness and quality of individual patient care.

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The cost-effectiveness of colonic stenting as a bridge to curative surgery in patients with acute left-sided malignant colonic obstruction: A Canadian perspective. Can J Gastroenterol 2006;20(12):779-785.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. PATIENTS AND METHODS: A decision analytical model was developed to compare three competing strategies: CS -emergent colonic stenting followed by elective resective surgery and reanastomosis; RS -emergent resective surgery followed by creation of either a diverting colostomy or primary reanastomosis; and DC -emergent diverting colostomy followed by elective resective surgery and reanastomosis. The costs were estimated from the perspective of the Manitoba provincial health plan. RESULTS: The use of CS resulted in fewer total operative procedures per patient (mean CS 1.03, RS 1.32, DC 1.9), lower mortality rate (CS 5%, RS 11%, DC 13%) and lower likelihood of requiring a permanent stoma (CS 7%, RS 14%, DC 14%). CS is slightly more expensive than DC, but less costly than RS (DC $11,851, CS $13,164, RS $13,820). The incremental cost-effectiveness ratio associated with the use of CS versus DC is $1,415 to prevent a temporary stoma, $1,516 to prevent an additional operation and $15,734 to prevent an additional death. CONCLUSIONS: Colonic stenting for patients with acute colonic obstruction secondary to a resectable colonic tumour is comparable in cost with surgical options, and reduces the likelihood of requiring both temporary and permanent stomas. Colonic stenting should be offered as the initial therapeutic modality for Canadian colorectal cancer patients presenting with acute obstruction as a bridge to definitive RS.

Care should be used in interpreting results where cosmetic outcomes have been obtained from a single evaluator. Panel scores can be used to significantly improve inter-rater, but not intra rater reliability, for the scales studied. Comparable reliability, in combination with simplicity of use and interpretation, would favour the four-point scale for breast cosmetic evaluation over the multi-item scale.

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