The glycosphingolipid globotriaosylceramide in the metastatic transformation of colon cancer

The most devastating aspect of cancer is the emergence of metastases. Thus, identification of potentially metastatic cells among a tumor cell population and the underlying molecular changes that switch cells to a metastatic state are among the most important issues in cancer biology. Here we show that, although normal human colonic epithelial cells lack the glycosphingolipid globotriaosylceramide (Gb3), this molecule is highly expressed in metastatic colon cancer. In addition, a subpopulation of cells that are greatly enriched in Gb3 and have an invasive phenotype was identified in human colon cancer cell lines. In epithelial cells in culture, Gb3 was necessary and sufficient for cell invasiveness. Transfection of Gb3 synthase, resulting in Gb3 expression in noncancerous polarized epithelial cells lacking endogenous Gb3, induced cell invasiveness. Furthermore, Gb3 knockdown by small inhibitory RNA in colon cancer epithelial cells inhibited cell invasiveness. Gb3 is the plasma membrane receptor for Shiga toxin 1. The noncatalytic B subunit of Shiga toxin 1 causes apoptosis of human colon cancer cells expressing Gb3. Injections of the B subunit of Shiga toxin 1 into HT29 human colon cancer cells engrafted into the flanks of nude mice inhibited tumor growth. These data demonstrate the appearance of a subpopulation of Gb3 containing epithelial cells in the metastatic stage of human colon cancer and suggest their possible role in colon cancer invasiveness

The Impact of Postoperative Complications on the Administration of Adjuvant Therapy Following Pancreaticoduodenectomy for Adenocarcinoma

ABSTRACT Background. The impact of postoperative complications on the administration of adjuvant therapy following pancreaticoduodenectomy (PD) for adenocarcinoma is still unclear. Methods. A retrospective review of all patients undergoing PD at our institution between 1995 and 2011 was performed. Clinicopathological data, including ClavienDindo complication grade, time to adjuvant therapy (TTA), and survival, were analyzed. Approximately 45,200 cases of pancreatic cancer (PC) are diagnosed yearly in the US, with 38,500-attributable cancer-related deaths. 1 The overall 5-year survival rate for PC is only 6 %, 1 and even for resectable cancers, the 5-year survival rate following pancreaticoduodenectomy (PD) is less than 20 %. 2-7 Local and systemic recurrence are common following PD, suggesting both systemic and local adjuvant therapy are necessary to improve outcomes