Hypermethylation and global remodelling of DNA methylation is associated with acquired cisplatin resistance in testicular germ cell tumours

Testicular germ cell tumours (TGCTs) respond well to cisplatin-based therapy. However, cisplatin resistance and poor outcomes do occur. It has been suggested that a shift towards DNA hypermethylation mediates cisplatin resistance in TGCT cells, although there is little direct evidence to support this claim. Here we utilized a series of isogenic cisplatin-resistant cell models and observed a strong association between cisplatin resistance in TGCT cells and a net increase in global CpG and non-CpG DNA methylation spanning regulatory, intergenic, genic and repeat elements. Hypermethylated loci were significantly enriched for repressive DNA segments, CTCF and RAD21 sites and lamina associated domains, suggesting that global nuclear reorganization of chromatin structure occurred in resistant cells. Hypomethylated CpG loci were significantly enriched for EZH2 and SUZ12 binding and H3K27me3 sites. Integrative transcriptome and methylome analyses showed a strong negative correlation between gene promoter and CpG island methylation and gene expression in resistant cells and a weaker positive correlation between gene body methylation and gene expression. A bidirectional shift between gene promoter and gene body DNA methylation occurred within multiple genes that was associated with upregulation of polycomb targets and downregulation of tumour suppressor genes. These data support the hypothesis that global remodelling of DNA methylation is a key factor in mediating cisplatin hypersensitivity and chemoresistance of TGCTs and furthers the rationale for hypomethylation therapy for refractory TGCT patients

The Teaching of Occupational Health within a Clinical Presentation Curriculum

Prior to 1996, the taching of occupational health at the University of Calgary was in three 4-hour blocks within the Adult Lifestyles section of the Family Course. With the changes in curriculm to a clinical presentation model, blocks of time within the lecture schedule were no longer available. the challenge was to integrate the teaching of occupational health into the clinical presentations of several different courses over the first two years of the curriculum

Alberta Occupational Medicine Newsletter: Summer 1999

Editorial Comments -- The Teaching of Occupational Health witin a Clinical Presentation Curriculum. Medical Advisory Guidelines on WCB website -- New Causation model to assist in injury evaluatio

Alberta Occupational Medicine Newsletter: Fall 1997

Editorial Comments -- Fetotoxic Chemicals in the Workplace: A Draft Guideline for Physicians -- Highlights: Annual Scientific Conference, Vancouver 1997. Shiftwork and Aging -- Occupational and Environmental Medical Association of Canada, 1997 Membership Development Committee Report -- Southern Alberta Occupational Medicine Page -- Upcoming Conference

Alberta Occupational Medicine Newsletter:Winter 1998

Editorial Comments -- Management for Risk of Hepatitis C --Canadian Centre for Occupational Health and Safety (CCOHS)News -- Second North American Occupational Safety and Health Week -- Southern Alberta Occupational Medicine Page (Statistics) -- Upcoming Conference

Alberta Occupational Medicine Newsletter: Fall 1998

Editiorial Comments -- Health Effects of Welding and Cutting Fume: An Update --WCB ALberta News -- Upcoming Course

Alberta Occupational Medicine Newsletter: Fall 2000

Editorial Comments -- Flight Deck Occupational Exposures -- Course Announcement -- Upcoming Conference

Alberta Occupational Medicine Newsletter: Fall 1999

Editorial Comments -- Hand-Arm Vibration Syndrome (HAVS)-- Let's Back Up a Bit: Some Truths about Back Belts --Upcoming Conference

Alberta Occupational Medicine Newsletter: Fall 1993

Editor's Comments -- Good Year for Canada's First Residency in Occupational Medicine: First Graduate and Royal College Approval -- Occupational Health and Safety: Where do we go from here? -- Occupational Health and Safety Publications from Alberta Labou