Endothelial Cells Promote the Colorectal Cancer Stem Cell Phenotype through a Soluble Form of Jagged-1

SummaryWe report a paracrine effect whereby endothelial cells (ECs) promote the cancer stem cell (CSC) phenotype of human colorectal cancer (CRC) cells. We showed that, without direct cell-cell contact, ECs secrete factors that promoted the CSC phenotype in CRC cells via Notch activation. In human CRC specimens, CD133 and Notch intracellular domain-positive CRC cells colocalized in perivascular regions. An EC-derived, soluble form of Jagged-1, via ADAM17 proteolytic activity, led to Notch activation in CRC cells in a paracrine manner; these effects were blocked by immunodepletion of Jagged-1 in EC-conditioned medium or blockade of ADAM17 activity. Collectively, ECs play an active role in promoting Notch signaling and the CSC phenotype by secreting soluble Jagged-1

Pancreatic adenocarcinoma in a patient with Situs Inversus: a case report of this rare coincidence

<p>Abstract</p> <p>Background</p> <p><it>Situs inversus </it>(SI) is a relatively rare occurrence in patients with pancreatic adenocarcinoma. Pancreatic resection in these patients has rarely been described. CT scan imaging is a principle modality for detecting pancreatic cancer and its use in SI patients is seldom reported.</p> <p>Case Presentation</p> <p>We report a 48 year old woman with SI who, despite normal CT scan 8 months earlier, presented with obstructive jaundice and a pancreatic head mass requiring a pancreaticoduodenectomy. The surgical pathology report demonstrated pancreatic adenocarcinoma.</p> <p>Conclusion</p> <p>SI is a rare condition with concurrent pancreatic cancer being even rarer. Despite the rarity, pancreaticoduodenectomy in these patients for resectable lesions is safe as long as special consideration to the anatomy is taken. Additionally, radiographic imaging has significantly improved detection of early pancreatic cancer; however, there continues to be a need for improved detection of small neoplasms.</p

Clinical implications of DNA methylation in hepatocellular carcinoma

AbstractBackgroundEpigenetics is a rapidly evolving field of genetic study applicable to nearly every aspect of genome-related research. The importance of epigenetics has been recognised in human hepatocellular carcinoma (HCC). Changes in DNA methylation patterns, including global hypomethylation and promoter hypermethylation, are thought to be early events in hepatocarcinogenesis.ObjectivesThis review aimed to summarise the role of epigenetics in HCC, to describe the mechanisms of epigenetic changes in HCC and to examine the clinical relevance of epigenetics in HCC.MethodsThis review examines the role of CpG-rich regions and DNA methylation, and describes an epigenetic model of cancer, tumour type-specific methylation, the relationships among methylation, cirrhosis and hepatocarcinogenesis, and the role of DNA methylation in HCC. The clinical implications of epigenetics in HCC are discussed.ResultsA multivariate predictor model based on traditional clinical factors and DNA methylation profile may have important applications in the early detection of neoplastic transformation in populations at high risk for HCC. CpG methylation may be valuable in HCC prognostics. DNA methylation profiles may enable clinical prediction in pre-therapy patient biopsies, paraffin-embedded samples or plasma DNA.ConclusionsEpigenetic changes and profiles may correlate to the biological behaviour of tumours and clinical outcome of HCC patients. The use of DNA methylation profiles as a surrogate biomarker remains an active area of clinical cancer research