Advanced Medical Research Institute of Canada AMRIC

Greater Sudbury, Canada

Advanced Medical Research Institute of Canada AMRIC

Greater Sudbury, Canada
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Rivera R.,University of California at Davis | Kang K.H.,University of California at Davis | Gardner M.B.,University of California at Davis | Anderson D.E.,University of California at Davis | And 6 more authors.
Revista Brasileira de Gestao e Desenvolvimento Regional | Year: 2016

Our long-term goal is to discover the combination of host parameters that help some HIV-infected individuals to resist progression to AIDS. In this study, we examined antibody responses using multiple samples obtained from a cohort of Long-Term Non-Progressors (LTNPs). Our hypothesis is that antibody responses to variable regions of the HIV-1 envelope glycoprotein are involved in reducing the viral load associated with LTNPs and that these specific immune responses influence susceptibility to disease progression. Multiple plasma samples were obtained from patients identified as LTNPs with the objective of characterizing humoral immune response directed to the five hypervariable regions of the envelope glycoprotein. Antibody binding was tested against peptides representing the five hypervariable regions of gp120, as well as against analog peptides representing different isolates of HIV-1 and against recombinant envelope glycoprotein. LTNPs have specific antibodies to the hypervariable regions of the envelope glycoprotein and develop different patterns of antibody recognition to variable epitopes of envelope glycoprotein. These antibodies can be detected using HIV peptides as capture antigens. © 2016 Rebecca Rivera, Kyung Hee Kang, Murray B. Gardner, David E. Anderson, Santiago Collado-Chastel, Eddy Rios-Olivares, Yasuhiro Yamamura, Francisco Diaz-Mitoma, Xia Li and José V. Torres.


Telpalo-Carpio S.A.,Advanced Medical Research Institute of Canada AMRIC | Diaz-Mitoma F.,Advanced Medical Research Institute of Canada AMRIC | Moreno-Cuevas J.E.,Monterrey Institute of Technology | Aguilar-Yanez J.M.,Advanced Medical Research Institute of Canada AMRIC | Aguilar-Yanez J.M.,Monterrey Institute of Technology
Biochemical and Biophysical Research Communications | Year: 2015

In eukaryotes, IRES sequences aid the recruitment of factors needed for translation to occur, enabling protein production independent of 5′ capped mRNA. Many patents and commercially available plasmids exploit their properties for polycistronic expression of recombinant proteins. However, these applications have been restricted to eukaryotic organisms, since it was thought that elements of this origin were essential for their activity. Here, using two tricistronic vectors designed for expression in mammalian hosts, we present evidence of EMCV IRES activity in prokaryotes. This finding enables the development of new and more versatile plasmid vectors for the production of recombinant proteins in multiple hosts from a single construct. Additionally, it provides new hints for the elaboration of alternative models describing the molecular mechanism of EMCV IRES mediated translation, in the absence of eukaryotic elements that were considered indispensable for its function. © 2015 Elsevier Inc. All rights reserved.


PubMed | Monterrey Institute of Technology and Advanced Medical Research Institute of Canada AMRIC
Type: Journal Article | Journal: Biochemical and biophysical research communications | Year: 2015

In eukaryotes, IRES sequences aid the recruitment of factors needed for translation to occur, enabling protein production independent of 5 capped mRNA. Many patents and commercially available plasmids exploit their properties for polycistronic expression of recombinant proteins. However, these applications have been restricted to eukaryotic organisms, since it was thought that elements of this origin were essential for their activity. Here, using two tricistronic vectors designed for expression in mammalian hosts, we present evidence of EMCV IRES activity in prokaryotes. This finding enables the development of new and more versatile plasmid vectors for the production of recombinant proteins in multiple hosts from a single construct. Additionally, it provides new hints for the elaboration of alternative models describing the molecular mechanism of EMCV IRES mediated translation, in the absence of eukaryotic elements that were considered indispensable for its function.


PubMed | University of Toronto, University of Ottawa, Queen's University and Advanced Medical Research Institute of Canada AMRIC
Type: | Journal: SpringerPlus | Year: 2015

This phase I/II neoadjuvant trial (ClinicalTrials.gov identifier NCT00066443) determined maximally-tolerated doses (MTD), dose-limiting toxicities, response-to-therapy, and explored the role of novel response biomarkers. MA.22 accrued T3N0, any N2 or N3, and T4 breast cancer patients. Treatment was 6 cycles of 3-weekly (Schedule A; N=47) or 8 cycles of 2-weekly (Schedule B; N=46) epirubicin/docetaxel chemotherapy in sequential phase I/II studies, with growth factor support. In phase I of each schedule, MTDs were based on DLT. In phase II, clinical responses (CR/PR) and pathologic complete responses (pCR) were assessed. Tumor biopsy cores were obtained pre-, mid-, and post-treatment: 3 for pathologic assessment; 3 for microarray studies. DLT for Schedule A was febrile neutropenia at 105mg/m(2) epirubicin and 75mg/m(2) docetaxel; for schedule B, it was fatigue at 75mg/m(2) for both agents. Phase II doses were 90mg/m(2) epirubicin/75mg/m(2) docetaxel for Schedule A and 60mg/m(2) (both agents) for Schedule B. Schedule A CR/PR and pCR rates were 90 and 10%, with large reductions in tumor RNA content and integrity following treatment; Schedule B results were 93 and 0%, with smaller reductions in RNA quality. Pre-treatment expression of several genes was associated with clinical response, including those within a likely amplicon at 17q12 (ERBB2, TCAP, GSDMB, and PNMT). The combination regimens had acceptable toxicity, good clinical response, induction of changes in tumor RNA content and integrity. Pre-treatment expression of particular genes was associated with clinical responses, including several near 17q12, which with ERBB2, may better identify chemoresponsiveness.

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