Alan Coss
University of British Columbia
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Featured researches published by Alan Coss.
International Journal of Cancer | 2009
Shane Sullivan; Miriam Tosetto; David Kevans; Alan Coss; Laimun Wang; Diarmuid P. O'Donoghue; John Hyland; Kieran Sheahan; Hugh Mulcahy; Jacintha O'Sullivan
Previous in vitro studies have identified a nuclear isoform of Cathepsin L. The aim of this study was to examine if nuclear Cathepsin L exists in vivo and examine its association with clinical, pathological and patient outcome data. Cellular localization (nuclear and cytoplasmic) and expression levels v of Cathespin L in 186 colorectal cancer cases using immunohistochemistry. The molecular weight and activity of nuclear and cytoplasmic Cathepsin L in vivo and in vitro were assessed by Western blotting and ELISA, respectively. Epithelial nuclear staining percentage (p = 0.04) and intensity (p = 0.006) increased with advancing tumor stage, whereas stromal cytoplasmic staining decreased (p = 0.02). Using multivariate statistical analysis, survival was inversely associated with staining intensity in the epithelial cytoplasm (p = 0.01) and stromal nuclei (p = 0.007). In different colorectal cell lines and in vivo tumors, pro‐ and active Cathepsin L isoforms were present in both the cytoplasm and nuclear samples, with pro‐Cathepsin L at 50 kDa and active Cathepsin L at 25 kDa. Purified nuclear and cytoplasmic fractions from cell lines and tumors showed active Cathepsin L activity. The identification of nuclear Cathepsin L may play an important prognostic role in colorectal disease progression and patient outcome. Moreover, these findings suggest that altering active nuclear Cathepsin L may significantly influence disease progression.
Cancer Letters | 2009
Alan Coss; Miriam Tosetto; Edward J. Fox; Beata Sapetto-Rebow; Sheeona Gorman; Breandán N. Kennedy; Andrew T. Lloyd; John Hyland; D. P. O’Donoghue; Kieran Sheahan; Dermot Leahy; Hugh Mulcahy; Jacintha O’Sullivan
Topoisomerase IIalpha is a nuclear enzyme that regulates the tertiary structure of DNA. The influence of topoisomerase IIalpha gene (TOP2A) or protein alterations on disease progression and treatment response in colorectal cancer (CRC) is unknown. The study investigated the clinical relevance of topoisomerase IIalpha in CRC using in vivo and in vitro models. Differentially expressed genes in early and late-stage CRC were identified by array comparative genomic hybridization (CGH). Cellular location of gene amplifications was determined by fluorescence in situ hybridization (FISH). Topoisomerase IIalpha levels, proliferation index, and HER2 expression were examined in 228 colorectal tumors by immunohistochemistry. Overexpression of topoisomerase IIalpha in vitro was achieved by liposome-based transfection. Cell growth inhibition and apoptosis were quantified using the crystal violet assay and flow cytometry, respectively, in response to drug treatment. Amplification of TOP2A was identified in 3 (7.7%) tumors using array CGH and confirmed using FISH. At the protein level, topoisomerase IIalpha staining was observed in 157 (69%) tumors, and both staining and intensity levels were associated with an aggressive tumor phenotype (p values 0.04 and 0.005, respectively). Using logistic regression analysis, topoisomerase IIalpha remained significantly associated with advanced tumor stage when corrected for tumor proliferation (p=0.007) and differentiation (p=0.001). No association was identified between topoisomerase IIalpha and HER2. In vitro, overexpression of topoisomerase IIalpha was associated with resistance to irinotecan (p=0.001) and etoposide chemotherapy (p=0.03), an effect mediated by inhibition of apoptosis. Topoisomerase IIalpha overexpression is significantly associated with alterations in tumor behavior and response to drug treatment in CRC. Our results suggest that gene amplification may represent an important mechanism underlying these changes.
Hepatobiliary & Pancreatic Diseases International | 2013
Calvin Chan; Fergal Donnellan; Michael F. Byrne; Alan Coss; Mazhar Haque; Holly Wiesenger; Charles H. Scudamore; Urs P. Steinbrecher; Alan Weiss; Eric M. Yoshida
BACKGROUND Endoscopic therapy has been successful in the management of biliary complications after both deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT). LDLT is thought to be associated with higher rates of biliary complications, but there are few studies comparing the success of endoscopic management of anastomotic strictures between the two groups. This study aims to compare our experience in the endoscopic management of anastomotic strictures in DDLT versus LDLT. METHODS This is a retrospective database review of all liver transplant patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) after liver transplantation. The frequency of anastomotic stricture and the time to develop and to resolve anastomotic stricture were compared between DDLT and LDLT. The response of anastomotic stricture to endoscopic therapy was also analyzed. RESULTS A total of 362 patients underwent liver transplantation between 2003 and 2011, with 125 requiring ERCP to manage biliary complications. Thirty-three (9.9%) cases of DDLT and 8 (27.6%) of LDLT (P=0.01) were found to have anastomotic stricture. When comparing DDLT and LDLT, there was no difference in the mean time to the development of anastomotic strictures (98+/-17 vs 172+/-65 days, P=0.11), likelihood of response to ERCP [22 (66.7%) vs 6 (75.0%), P=0.69], mean time to the resolution of anastomotic strictures (268+/-77 vs 125+/-37 days, P=0.34), and the number of ERCPs required to achieve resolution (3.9+/-0.4 vs 4.7+/-0.9, P=0.38). CONCLUSIONS Endoscopic therapy is effective in the majority of biliary complications relating to liver transplantation. Anastomotic strictures occur more frequently in LDLT compared with DDLT, with equivalent endoscopic treatment response and outcomes for both groups.
Canadian Journal of Gastroenterology & Hepatology | 2010
Alan Coss; Chen Zhou; Michael F. Byrne; Alan Weiss
Pancreatic infiltration is a rare feature of multiple myeloma. A case of a 74-year-old man presenting with symptomatic biliary obstruction two years after the original diagnosis of myeloma is described. Confirmation of pancreatic infiltration with myeloma cells was performed by endoscopic ultrasound-guided fine-needle aspiration. Biliary stenting was performed at endoscopic retrograde cholangiopancreatography. Resolution of the pancreatic mass and the associated biliary stricture was observed after radiation and chemotherapy.
Case Reports in Gastroenterology | 2007
James B. Canavan; Alan Coss; Mary Leader; Stephen Patchett
Mesenteric inflammatory veno-occlusive disease (MIVOD) is an uncommon but important cause of bowel inflammation. MIVOD is characterised by lymphocytic inflammation and non-thrombotic occlusion of the mesenteric venules and veins. We present the case of a young man who presented with acute fulminant colitis, requiring colectomy. The differential diagnosis, pathogenesis and treatment are discussed. This case illustrates the rapid progression from ‘well’ to ‘colectomy’ that can occur with MIVOD. MIVOD should be considered in the differential diagnosis of colitis that does not respond to conventional medical treatment.
Canadian Journal of Gastroenterology & Hepatology | 2010
Jaber Al-Ali; Monika Pawlowska; Alan Coss; Sigrid Svarta; Michael F. Byrne; Robert Enns
International Journal of Colorectal Disease | 2014
Aoibhlinn O’Toole; Alan Coss; Grainne Holleran; Denise Keegan; Glen A. Doherty; Kieran Sheahan; Hugh Mulcahy; D. P. O’Donoghue
Current Gastroenterology Reports | 2009
Alan Coss; Robert Enns
Gastrointestinal Endoscopy | 2010
Marcus W Chin; Alan Coss; Mark Mcloughlin; Michael F. Byrne; Robert Enns; Jennifer J. Telford; Eric C. Lam
Current Gastroenterology Reports | 2009
Alan Coss; Michael F. Byrne