Sunnybrook Health Sciences Centre

About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Medicine. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.

Expression of CD44 3′-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis

Abstract: The non-coding 3'-untranslated region (UTR) plays an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs Here, we show the 3'-UTR of CD44 is able to antagonize cytoplasmic miRNAs, and result in the increased translation of CD44 and downstream target mRNA, CDC42 A series of cell function assays in the human breast cancer cell line, MT-1, have shown that the CD44 3'-UTR inhibits proliferation, colony formation and tumor growth Furthermore, it modulated endothelial cell activities, favored angiogenesis, induced tumor cell apoptosis and increased sensitivity to Docetaxel These results are due to the interaction of the CD44 3'-UTR with multiple miRNAs Computational algorithms have predicted three miRNAs, miR-216a, miR-330 and miR-608, can bind to both the CD44 and CDC42 3'-UTRs This was confirmed with luciferase assays, western blotting and immunohistochemical staining and correlated with a series of siRNA assays Thus, the non-coding CD44 3'-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed

Prevention of myeloma cell apoptosis by ectopic bcl-2 expression or interleukin 6-mediated up-regulation of bcl-xL.

Abstract: Upon cytokine withdrawal, interleukin (IL) 6-dependent murine plasmacytoma/hybridoma (myeloma) cells die in a way characteristic of apoptosis. Although gene transfer-mediated elevation in Bcl-2 protein levels has been demonstrated to repress a number of apoptotic death programs, it has been reported that ectopic bcl-2 expression is unable to prolong the survival of IL-6-deprived myeloma cells. In view of the recent identification of Bax as a protein that antagonizes the anti-apoptotic function of Bcl-2, we sought to determine whether the inability of transfected bcl-2 to protect against myeloma cell apoptosis might simply be due to insufficient levels of Bcl-2 protein produced to counteract this inhibitor. We show here that high-level expression of an exogenous bcl-2 gene, introduced into IL-6-dependent B9 myeloma cells via retroviral or bovine papilloma virus-based vectors, is indeed able to suppress apoptotic death following cytokine deprivation, with the extent of protection provided correlating with the amount of Bcl-2 protein synthesized in relation to the amount of endogenous Bax protein present in the cells. Of note, however, we found that IL-6-mediated suppression of B9 apoptosis does not involve induction of endogenous bcl-2 expression but is associated instead with the up-regulation of cellular bcl-x mRNA and Bcl-xL protein. These results thus extend the apoptotic death mechanisms that are inhibitable by both bcl-2 and bcl-xL to include that operative in IL-6-dependent cells and suggest that apoptosis in other cell types using the gp130 subunit of the IL-6 receptor might also be bcl-2 regulable or bcl-xL dependent.

Information needs of women during early treatment for breast cancer.

Abstract: This study assessed the information needs of 70 women with breast cancer being treated by surgery, chemotherapy or radiation therapy. Information needs were measured by the breast cancer version of the Toronto Informational Needs Questionnaire (TINQ-BC). All women had high information needs, irrespective of type of treatment received. They mainly wanted information about their disease, treatments and investigative tests. An examination of individual items on the TINQ-BC revealed that all women wanted information about recurrence, specifically they wanted to know if the cancer would come back and how to tell if it had recurred. The results provide nurses with some direction as to what information to give women receiving early treatment for breast cancer.

PANCREOX: A Randomized Phase III Study of Fluorouracil/Leucovorin With or Without Oxaliplatin for Second-Line Advanced Pancreatic Cancer in Patients Who Have Received Gemcitabine-Based Chemotherapy.

Abstract: Purpose The standard of care for second-line therapy in patients with advanced pancreatic cancer after gemcitabine-based therapy is not clearly defined. The CONKO-003 phase III study reported a survival benefit with second-line fluorouracil (FU) and oxaliplatin using the oxaliplatin, folinic acid, and FU (OFF) regimen. 1 PANCREOX was a phase III multicenter trial to evaluate the benefit of FU and oxaliplatin administered as modified FOLFOX6 (mFOLFOX6; infusional fluorouracil, leucovorin, and oxaliplatin) versus infusional FU/leucovorin (LV) in this setting. Patients and Methods Patients with confirmed advanced pancreatic cancer who were previously treated with gemcitabine therapy and with an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. A total of 108 patients were randomly assigned to receive biweekly mFOLFOX6 or infusional FU/LV until progression. Progression-free survival (PFS) was the primary end point. Results Baseline patient characteristics were similar in both arms. No difference was observed in PFS (median, 3.1 months v 2.9 months; P = .99). Overall survival (OS) was inferior in patients assigned to mFOLFOX6 (median, 6.1 months v 9.9 months; P = .02). Increased toxicity was observed with the addition of oxaliplatin, with grade 3/4 adverse events occurring in 63% of patients who received mFOLFOX6 and 11% of those who received FU/LV. More patients in the mFOLFOX6 arm withdrew from study due to adverse events than in the FU/LV arm (20% v 2%), whereas the use of postprogression therapy was significantly higher in the FU/LV arm (25% v 7%; P = .015). No significant differences were observed in time to deterioration on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 global health scale. Conclusion No benefit was observed with the addition of oxaliplatin, administered as mFOLFOX6, versus infusional FU/LV in patients with advanced pancreatic cancer previously treated with first-line gemcitabine.