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Toronto, Canada

Pritzker K.P.H.,University of Toronto | Pritzker L.B.,Rna Diagnostics Inc.
Expert Opinion on Medical Diagnostics | Year: 2012

Bioinformatics tools, techniques and resources are critical to biomarker discovery, assessment, validation, qualification, standardization and market acceptance into clinical practice. Huge scientific effort and economic investment over the past 20 years have resulted in thousands of new candidate biomarkers for diseases, yet relatively few biomarkers have entered clinical practice. Bioinformatics is central to all stages of biomarker development and implementation. Areas covered: This review examines bioinformatics advances that bear on each stage of biomarker development and suggests bioinformatics strategies to assist biomarkers towards clinical practice. This paper focuses on the steps of clinical biomarker development with an emphasis on the review literature from 2000 to June 2011. The intent of this paper is to describe the present role of bioinformatics in biomarker development including the controversies associated with various developmental stages. Expert opinion: The key message is that more effective biomarker development requires database input of higher quality, improved bioinformatics tools to identify more clearly the acceptable criteria for each development step, as well as more and better database linkages. © 2012 Informa UK, Ltd. Source

Rna Diagnostics Inc. and Laurentian University | Date: 2011-08-10

Provided are methods of determining a response to a chemotherapeutic agent in a subject with ovarian cancer, comprising: determining a RNA integrity value of a sample comprising ovarian cancer cell RNA from the subject after the subject has received one or more doses of the chemotherapeutic agent; wherein a low RNA integrity value and/or RNA degradation of the cancer cell RNA is indicative that the cancer is responding to the chemotherapeutic agent and/or a high RNA integrity value and/or stable RNA integrity of the ovarian cancer cell RNA is indicative that the cancer is resistant to the chemotherapeutic agent.

Rna Diagnostics Inc. | Date: 2013-12-03

A method of evaluating a cancer cell sample, the method comprising: a. obtaining a cancer cell sample, optionally a breast cancer cell sample or an ovarian cancer cell sample, after the cancer cells have been exposed to a radiation dose; b. assaying the cancer cell sample to obtain a RNA integrity value and/or a RNA concentration of the cancer cell sample.

Foroni C.,U.O. Multidisciplinare di Patologia Mammaria | Milan M.,U.O. Multidisciplinare di Patologia Mammaria | Strina C.,U.O. Multidisciplinare di Patologia Mammaria | Cappelletti M.,U.O. Multidisciplinare di Patologia Mammaria | And 15 more authors.
Breast Cancer Research and Treatment | Year: 2014

The study investigated the anti-tumour effect of zoledronic acid (ZA) administered alone in a biological window therapy in naïve bone-only metastatic and locally advanced breast cancer (LABC) patients. 33 patients with LABC (Group 1) and 20 patients with a first diagnosis of bone metastasis only (Group 2) received 4 mg single dose of ZA, 14 days (biological window) before starting any treatment. In Group 1, Ki67, CD34, p53/bcl-2 and caspase 3 expression along with the adenosine triphosphate (ATP) levels and RNA disruption index were evaluated as markers of tumor growth in tumour specimens obtained before and after ZA administration (basal, day 14). In Group 2, the total enumeration of circulating tumour cells (CTCs), and of M30+ve CTCs along with the soluble marker of cell death (M30/M65) were carried-out as markers of tumor dissemination at baseline, at 48 h and day 14th. In Group 1, there was a significant reduction in Ki67, CD34, bcl-2 expression after 14 days ZA based-treatment (p = 0.0032; p = 0.0001, p < 0.00001 respectively). ZA showed a significant increase of RNA disruption (p < 0.0076). In Group 2, we observed a significant reduction of CTCs number after 48 h (p = 0.0012), followed by a significant rebound at 14 days (p = 0.012). The apoptotic CTCs/M30+ve and M65 levels significantly increased under treatment (p = 0.018 and p = 0.039 respectively) after drug administration when compared to the baseline. These results are the first prospective in vivo data showing the direct pure anti-tumour effect (either on the tumour cell or on CTCs) of ZA. © 2014 Springer Science+Business Media New York. Source

Neschadim A.,View Inc | Pritzker L.B.,Rna Diagnostics Inc. | Pritzker K.P.H.,Rna Diagnostics Inc. | Pritzker K.P.H.,University of Toronto | And 9 more authors.
Endocrine-Related Cancer | Year: 2014

Androgen hormones and the androgen receptor (AR) pathway are the main targets of anti-hormonal therapies for prostate cancer. However, resistance inevitably develops to treatments aimedat theARpathway resultinginandrogen- independentorhormone-refractory prostate cancer (HRPC). Therefore, there is a significant unmet need for new, non-androgen anti-hormonal strategies for themanagement of prostate cancer.We demonstrate that a relaxin hormone receptor antagonist, AT-001, an analog of humanH2 relaxin, represents a first-in-class anti-hormonal candidate treatment designed to significantly curtail the growth of androgenindependent human prostate tumor xenografts. Chemically synthesized AT-001, administered subcutaneously, suppressed PC3 xenograft growth by up to 60%. AT-001 also synergized with docetaxel, standard first-line chemotherapy for HRPC, to suppress tumor growth by more than 98%in PC3 xenografts via a mechanism involving the downregulation of hypoxia-inducible factor 1 alpha and the hypoxia-induced response. Our data support developing AT-001 for clinical use as an anti-relaxin hormonal therapy for advanced prostate cancer. © 2014 Society for Endocrinology. Source

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