Feras M. Ghazawi

Bio: Feras M. Ghazawi is an academic researcher from University of Ottawa. The author has contributed to research in topics: Incidence (epidemiology) & Population. The author has an hindex of 18, co-authored 70 publications receiving 813 citations. Previous affiliations of Feras M. Ghazawi include McGill University & McGill University Health Centre.

Valproic acid and butyrate induce apoptosis in human cancer cells through inhibition of gene expression of Akt/protein kinase B.

Abstract: Background In eukaryotic cells, the genomic DNA is packed with histones to form the nucleosome and chromatin structure. Reversible acetylation of the histone tails plays an important role in the control of specific gene expression. Mounting evidence has established that histone deacetylase inhibitors selectively induce cellular differentiation, growth arrest and apoptosis in variety of cancer cells, making them a promising class of anticancer drugs. However, the molecular mechanisms of the anti-cancer effects of these inhibitors have yet to be understood.

Insights into the Pathophysiology of Hypertrophic Scars and Keloids: How Do They Differ?

Abstract: GENERAL PURPOSE:To provide information about the clinical presentation of hypertrophic scars and keloids based on their varied structural components.TARGET AUDIENCE:This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest i

Comprehensive analysis of cutaneous T-cell lymphoma (CTCL) incidence and mortality in Canada reveals changing trends and geographic clustering for this malignancy

Abstract: BACKGROUND Previous reports of geographic clustering of cutaneous T-cell lymphoma (CTCL) in Texas, Pittsburgh, and Sweden as well as the occurrence of CTCL in married couples and family members raise a possibility of the existence of an external and potentially preventable trigger(s) for this rare skin cancer. METHODS The authors studied CTCL incidence and mortality in Canada using 3 distinct population-based cancer databases. Data on patients' sex, age at the time of diagnosis, subtype of CTCL malignancy, reporting province, city, and postal code were analyzed. CTCL cases were mapped across Canada using geographic information systems software. RESULTS In total, 6685 patients with CTCL were identified in Canada during 1992 through 2010 (CTCL incidence rate, 11.32 cases per million individuals per year), of which 58% were males. The mean age at diagnosis was 59.4 ± 21.5 years. Geographic analysis of patients revealed increased CTCL incidence on the provincial and city levels in several eastern provinces and in Manitoba. An analysis according to postal codes (Forward Sortation Area [FSA]) identified select communities in which several high-incidence FSAs were contiguous or adjacent. Several of these FSAs were located in industrial regions of Canadian cities. Conversely, 3 of 8 low-incidence FSAs were clustered in Ottawa, Ontario, which has very little industrial presence. An analysis of CTCL mortality in Canada corroborated the current incidence findings. CONCLUSIONS The current results provide a comprehensive analysis of CTCL burden in Canada and highlight several important areas of geographic case clustering. These findings argue that industrial exposures may play an important role in promoting CTCL pathogenesis. Cancer 2017;123:3550-67. © 2017 American Cancer Society.

Cutaneous malignant melanoma incidence and mortality trends in Canada: A comprehensive population-based study

Abstract: Background The incidence of cutaneous malignant melanoma (CMM) is on the rise in many parts of the world. However, there is limited knowledge on the epidemiology of CMM in Canada. Objective To conduct a comprehensive population-based study of CMM in Canada. Methods We examined patient clinical and pathologic characteristics as well as the incidence and mortality trends of CMM in Canada using 3 independent population-based registries. Results In total, 72,565 Canadian patients were given CMM diagnoses during 1992-2010; 47.5% were women. Average age at the time of diagnosis was 56.5 years for women and 60.4 years for men. We report a steady increase in CMM incidence and mortality rates in both sexes. The overall incidence rate of CMM in Canada was 12.29 cases/100,000 person-years. We also report important differences in the incidence and mortality rates between Canadian provinces and territories; the highest incidence of this cancer was documented in Nova Scotia and Prince Edward Island. Limitations Data on race, clinical disease stage, and Breslow depth of CMM was not available. Conclusion This study, for the first time, defines the disease burden of CMM in Canada and highlights important longitudinal, geographic, and spatial differences in the distribution of CMM in this country.

Uveal melanoma incidence trends in Canada: a national comprehensive population-based study

Abstract: Background In the developed countries, uveal melanoma is the most common primary intraocular malignancy in adults. Little is known about the epidemiological and geographical distribution of uveal melanoma in Canada. Methods To determine the incidence patterns and geographical distribution of uveal melanoma cases in Canada, we conducted the first comprehensive, population-based national study of this malignancy across all Canadian provinces and territories during 1992–2010 years. We examined two independent population-based registries: the Canadian Cancer Registry and Le Registre Quebecois du Cancer using corresponding International Classification of Diseases for Oncology-3rd edition codes for all histological subtypes of uveal melanoma. Results We report that 2215 patients were diagnosed with uveal melanoma, of which 52.1% were males. The average -annual incidence rate of uveal melanoma in Canada was 3.75 cases per million individuals per year (95% CI 3.60 to 3.91). Overall, we report a steady increase in uveal melanoma incidence with an annual increase of 0.074 cases per million individuals per year. Significant differences in the incidence rates of uveal melanoma between Canadian provinces and territories were noted, where the highest crude incidence was in British Columbia and Saskatchewan with rates of 6.38 and 5.47 cases per million individuals per year, respectively. Conclusions This work, for the first time, defines the disease burden of uveal melanoma in Canada and highlights important longitudinal, geographical and spatial differences in the distribution of uveal melanoma in Canada.

Landscape of genomic alterations in cervical carcinomas

Abstract: Cervical cancer is responsible for 10-15% of cancer-related deaths in women worldwide. The aetiological role of infection with high-risk human papilloma viruses (HPVs) in cervical carcinomas is well established. Previous studies have also implicated somatic mutations in PIK3CA, PTEN, TP53, STK11 and KRAS as well as several copy-number alterations in the pathogenesis of cervical carcinomas. Here we report whole-exome sequencing analysis of 115 cervical carcinoma-normal paired samples, transcriptome sequencing of 79 cases and whole-genome sequencing of 14 tumour-normal pairs. Previously unknown somatic mutations in 79 primary squamous cell carcinomas include recurrent E322K substitutions in the MAPK1 gene (8%), inactivating mutations in the HLA-B gene (9%), and mutations in EP300 (16%), FBXW7 (15%), NFE2L2 (4%), TP53 (5%) and ERBB2 (6%). We also observe somatic ELF3 (13%) and CBFB (8%) mutations in 24 adenocarcinomas. Squamous cell carcinomas have higher frequencies of somatic nucleotide substitutions occurring at cytosines preceded by thymines (Tp*C sites) than adenocarcinomas. Gene expression levels at HPV integration sites were statistically significantly higher in tumours with HPV integration compared with expression of the same genes in tumours without viral integration at the same site. These data demonstrate several recurrent genomic alterations in cervical carcinomas that suggest new strategies to combat this disease.

Microbial genes, brain & behaviour - epigenetic regulation of the gut-brain axis.

Abstract: To date, there is rapidly increasing evidence for host-microbe interaction at virtually all levels of complexity, ranging from direct cell-to-cell communication to extensive systemic signalling, and involving various organs and organ systems, including the central nervous system As such, the discovery that differential microbial composition is associated with alterations in behaviour and cognition has significantly contributed to establishing the microbiota-gut-brain axis as an extension of the well-accepted gut-brain axis concept Many efforts have been focused on delineating a role for this axis in health and disease, ranging from stress-related disorders such as depression, anxiety and irritable bowel syndrome to neurodevelopmental disorders such as autism There is also a growing appreciation of the role of epigenetic mechanisms in shaping brain and behaviour However, the role of epigenetics in informing host-microbe interactions has received little attention to date This is despite the fact that there are many plausible routes of interaction between epigenetic mechanisms and the host-microbiota dialogue From this new perspective we put forward novel, yet testable, hypotheses Firstly, we suggest that gut-microbial products can affect chromatin plasticity within their host's brain that in turn leads to changes in neuronal transcription and eventually alters host behaviour Secondly, we argue that the microbiota is an important mediator of gene-environment interactions Finally, we reason that the microbiota itself may be viewed as an epigenetic entity In conclusion, the fields of (neuro)epigenetics and microbiology are converging at many levels and more interdisciplinary studies are necessary to unravel the full range of this interaction