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Parent N.,Institute Du Cancer Of Montreal | Scherer M.,University of Regensburg | Liebisch G.,University of Regensburg | Schmitz G.,University of Regensburg | And 2 more authors.
International Journal of Oncology | Year: 2011

A lysosomal pathway, characterized by the partial rupture or labilization of lysosomal membranes (LLM) and cathepsin release into the cytosol, is evoked during the early events of 20-S-camptothecin lactone (CPT)-induced apoptosis in human cancer cells, including human histiocytic lymphoma U-937 cells. These lysosomal events begin rapidly and simultaneously with mitochondrial permeabilization and caspase activation within 3 h after drug treatment. Recently, in a comparative proteomics analysis performed on highlyenriched lysosomal extracts, we identified proteins whose translocation to lysosomes correlated with LLM induction after CPT treatment, including protein kinase C-δ (PKC-δ). In this study, we show that the PKC-δ translocation to lysosomes is required for LLM, as silencing its expression with RNA interference or suppressing its activity with the inhibitor, rottlerin, prevents CPT-induced LLM. PKC-δ translocation to lysosomes is associated with lysosomal acidic sphingomyelinase (ASM) phosphorylation and activation, which in turn leads to an increase in ceramide (CER) content in lysosomes. The accumulation of endogenous CER in lysosomes is a critical event for CPT-induced LLM as suppressing PKC-δ or ASM activity reduces both the CPT-mediated CER generation in lysosomes and CPT-induced LLM. These findings reveal a novel mechanism by which PKC-δ mediates ASM phosphorylation/activation and CER accumulation in lysosomes in CPT-induced LLM, rapidly activating the lysosomal pathway of apoptosis after CPT treatment. Source


Saad F.,University of Montreal | Saad F.,Institute Du Cancer Of Montreal | Pantel K.,University of Hamburg
Future Oncology | Year: 2012

Prostate-specific antigen (PSA) has been used for over two decades as a serum marker for adenocarcinoma of the prostate. Although PSA screening remains an important part of disease screening and monitoring in early prostate cancer (PC), its utility in monitoring disease progression in advanced PC is undetermined. Furthermore, the role of PSA monitoring in the management of patients with PC and bone metastases appears limited. The purpose of this review is to evaluate the role of circulating tumor cells (CTCs) as potential novel biomarkers in advanced PC. We present a review of CTC testing and the clinical data supporting the prognostic potential of CTCs in this setting. We propose that combination of CTCs and PSA velocity or doubling-time assessments may offer insights into the prognosis and management of advanced PC. © 2012 Future Medicine Ltd. Source


Barnes R.,Cancer Care Manitoba | Albert M.,Ontario Cancer Institute | Damaraju S.,Alberta Health Services | De Sousa-Hitzler J.,Ryerson University | And 4 more authors.
Biopreservation and Biobanking | Year: 2013

Despite the integral role of biorepositories in fueling translational research and the advancement of medicine, there are significant gaps in harmonization of biobanking practices, resulting in variable biospecimen collection, storage, and processing. This significantly impacts accurate downstream analysis and, in particular, creates a problem for biorepository networks or consortia. The Canadian Tumour Repository Network (CTRNet; www.ctrnet.ca) is a consortium of Canadian tumor biorepositories that aims to enhance biobanking capacity and quality through standardization. To minimize the issue of variable biobanking practices throughout its network, CTRNet has developed and maintained a comprehensive set of 45 standard operating procedures (SOPs). There were four key elements to the CTRNet SOP development process: 1) an SOP development team was formed from members across CTRNet to co-produce each SOP; 2) a principal author was appointed with responsibility for overall coordination of the SOP development process; 3) the CTRNet Management Committee (composed of principal investigators for each member biorepository) reviewed/revised each SOP completed by the development team; and 4) external expert reviewers provided feedback and recommendations on each SOP. Once final Management Committee approval was obtained, the ratified SOP was published on the CTRNet website for public access. Since the SOPs were first published on the CTRNet website (June 2008), there have been approximately 15,000 downloads of one or more CTRNet SOPs/Policies by users from over 60 countries. In accordance with biobanking best practices, CTRNet performs an exhaustive review of its SOPs at set intervals, to coincide with each granting cycle. The last revision was completed in May 2012. © 2013, Mary Ann Liebert, Inc. Source


Rodier F.,Institute Du Cancer Of Montreal
Methods in Molecular Biology | Year: 2013

Cellular senescence suppresses cancer by eliminating potentially oncogenic cells, participates in tissue repair, contributes to cancer therapy, and promotes organismal aging. Numerous activities of senescent cells depend on the aptitude of these cells to secrete myriads of bioactive molecules, a behavior termed the senescence-associated secretory phenotype (SASP). The SASP supports cell-autonomous functions like the senescence-associated growth arrest, and mediates paracrine interactions between senescent cells and their surrounding microenvironment. The biological functions and the regulation of the SASP are beginning to emerge, and current SASP assessment techniques include the analysis of SASP factors at the mRNA level, the direct measurement of factors inside or outside the cell (i.e., secreted), and the detection of SASPprovoked cellular responses. Here, we focus on a simple approach to collect SASP-conditioned media in order to directly measure secreted SASP factors using sandwich enzyme-linked immunosorbent assay. As an example, we discuss the assessment of the major SASP factor interleukin-6 in senescent human fibroblasts. Supplemental notes are provided to easily adapt this procedure to other SASP factors, change cell types, or scale the techniques for different volumes or high-throughput measurements. These techniques should facilitate the discovery of novel functions and regulators of the SASP. © Springer Science+Business Media New York 2013. Source


Braun L.,BC Cancer Agency | Lesperance M.,BC Cancer Agency | Mes-Massons A.-M.,Institute Du Cancer Of Montreal | Mes-Massons A.-M.,University of Montreal | And 2 more authors.
Biopreservation and Biobanking | Year: 2014

Background: Establishing targets for case accrual is an important component of a strategic plan for a biobank. We have previously assessed overall patterns of biospecimen use in cancer research publications in selected journals. Here we extend this analysis to consider patterns of biospecimen use in relation to cancer research programs developed by individual investigators. Methods: We selected three individual cancer research investigators whose independent research programs began circa 1986, have been characterized by extensive use of human tumor biospecimens, and have primarily involved translational research in the areas of breast, lung, and ovarian cancer. We analyzed biospecimen and data usage in their career publications categorized by numbers, type, and format, and accompanying annotating data in terms of conformance with BRISQ reporting and ethics related criteria. Results: Biospecimens were used in 313/474 (66%) of publications analyzed. The average number of biospecimens used by these research programs increased six-fold from less than 1000 in 2001-2003 to greater than 6000 in 2010-2012, and the average cohort sizes per article also increased from approximately 50 to 200 cases per study over the same period in most biospecimen categories (p<0.05). The relative proportions of different formats of biospecimens used has varied significantly and continues to change with the emergence of digital biospecimen derived data. In these three translational research programs, BRISQ elements relating to 'Biobank' categories were significantly less well reported for biospecimens used in publications than data corresponding to 'Clinical chart' categories (p<0001). Conclusions: This study shows that overall use of biospecimens in cancer research has increased significantly and that dynamic variation in the relative use of different biospecimen formats has also occurred. This study also confirms our previous findings on patterns of biospecimen use and also those concerning incomplete reporting of relevant data elements that has not improved in the past decade. © Mary Ann Liebert, Inc. 2014. Source

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