Reasons for delay in timely administration of adjuvant chemotherapy for patients with stage III colon cancer: a multicentre cohort study from the McGill University Department of Oncology.

Purpose: Adjuvant chemotherapy within 56 or 84 days following curative resection is globally accepted as the standard of care for stage III colon cancer as it has been associated with improved overall survival. Initiation of adjuvant chemotherapy within this time frame is therefore recommended by clinical practice guidelines, including the European Society for Medical Oncology. The objective of this study was to evaluate adherence to these clinical practice guidelines for patients with stage III colon cancer across the Rossy Cancer Network (RCN); a partnership of McGill University's Faculty of Medicine, McGill University Health Centre, Jewish General Hospital and St Mary's Hospital Center.

Expression of leukemia-associated fusion proteins increases sensitivity to histone deacetylase inhibitor-induced DNA damage and apoptosis.

Histone deacetylase inhibitors (HDI) show activity in a broad range of hematologic and solid malignancies, yet the percentage of patients in any given malignancy who experience a meaningful clinical response remains small. In this study, we sought to investigate HDI efficacy in acute myeloid leukemia (AML) cells expressing leukemia-associated fusion proteins (LAFP). HDIs have been shown to induce apoptosis, in part, through accumulation of DNA damage and inhibition of DNA repair.

Metformin reduces endogenous reactive oxygen species and associated DNA damage.

Pharmacoepidemiologic studies provide evidence that use of metformin, a drug commonly prescribed for type II diabetes, is associated with a substantial reduction in cancer risk. Experimental models show that metformin inhibits the growth of certain neoplasms by cell autonomous mechanisms such as activation of AMP kinase with secondary inhibition of protein synthesis or by an indirect mechanism involving reduction in gluconeogenesis leading to a decline in insulin levels and reduced proliferation of insulin-responsive cancers. Here, we show that metformin attenuates paraquat-induced elevations in reactive oxygen species (ROS), and related DNA damage and mutations, but has no effect on similar changes induced by H(2)0(2), indicating a reduction in endogenous ROS production.

Vorinostat induces reactive oxygen species and DNA damage in acute myeloid leukemia cells.

Histone deacetylase inhibitors (HDACi) are promising anti-cancer agents, however, their mechanisms of action remain unclear. In acute myeloid leukemia (AML) cells, HDACi have been reported to arrest growth and induce apoptosis. In this study, we elucidate details of the DNA damage induced by the HDACi vorinostat in AML cells.

Lysyl oxidase expression and inhibition in uveal melanoma.

Lysyl oxidase is a marker of poor prognosis in several malignancies and is hypothesized to promote a migratory phenotype in hypoxic breast carcinomas. This study aims to characterize the expression of the lysyl oxidase and lysyl oxidase-like proteins in human uveal melanoma cell lines and archival choroidal melanomas using immunohistochemistry. The transcriptional control of lysyl oxidase will also be investigated under simulated hypoxic conditions using cobalt chloride.

Expanding PML's functional repertoire through post-translational mechanisms.

Post-translational modifications, such as acetylation and ubiquitination, can greatly expand the functionality of a particular protein. The promyelocytic leukemia (PML) protein is a functionally promiscuous protein with proposed roles in many cellular processes. Its cellular headquarters are the macromolecular structures termed PML nuclear bodies.

Inhibition of DNA methyltransferase activates tumor necrosis factor alpha-induced monocytic differentiation in acute myeloid leukemia cells.

Transcriptional silencing via promoter methylation of genes important for cell growth and differentiation plays a key role in myeloid leukemogenesis. We find that clinically achievable levels of 5-aza-2'-deoxycytidine (5-AZA-dC), a potent inhibitor of DNA methylation, can modify chromatin and restore the ability of tumor necrosis factor alpha (TNFalpha) to induce monocytic differentiation of the acute myeloid leukemia cells NB4 and U937. Although 5-AZA-dC cannot fully induce differentiation, we show that 5-AZA-dC acts directly on TNFalpha-responsive promoters to facilitate TNFalpha-induced transcriptional pathways leading to differentiation.