Gharbaran R.,Hackensack University Medical Center |
Goy A.,Hackensack University Medical Center |
Tanaka T.,Thomas Jefferson University |
Park J.,Hackensack University Medical Center |
And 9 more authors.
Journal of Hematology and Oncology | Year: 2013
Background: High risk, unfavorable classical Hodgkin lymphoma (cHL) includes those patients with primary refractory or early relapse, and progressive disease. To improve the availability of biomarkers for this group of patients, we investigated both tumor biopsies and peripheral blood leukocytes (PBL) of untreated (chemo-naïve, CN) Nodular Sclerosis Classic Hodgkin Lymphoma (NS-cHL) patients for consistent biomarkers that can predict the outcome prior to frontline treatment. Methods and materials. Bioinformatics data mining was used to generate 151 candidate biomarkers, which were screened against a library of 10 HL cell lines. Expression of FGF2 and SDC1 by CD30+ cells from HL patient samples representing good and poor outcomes were analyzed by qRT-PCR, immunohistochemical (IHC), and immunofluorescence analyses. Results: To identify predictive HL-specific biomarkers, potential marker genes selected using bioinformatics approaches were screened against HL cell lines and HL patient samples. Fibroblast Growth Factor-2 (FGF2) and Syndecan-1 (SDC1) were overexpressed in all HL cell lines, and the overexpression was HL-specific when compared to 116 non-Hodgkin lymphoma tissues. In the analysis of stratified NS-cHL patient samples, expression of FGF2 and SDC1 were 245 fold and 91 fold higher, respectively, in the poor outcome (PO) group than in the good outcome (GO) group. The PO group exhibited higher expression of the HL marker CD30, the macrophage marker CD68, and metastatic markers TGFβ1 and MMP9 compared to the GO group. This expression signature was confirmed by qualitative immunohistochemical and immunofluorescent data. A Kaplan-Meier analysis indicated that samples in which the CD30+ cells carried an FGF2+/SDC1+ immunophenotype showed shortened survival. Analysis of chemo-naive HL blood samples suggested that in the PO group a subset of CD30+ HL cells had entered the circulation. These cells significantly overexpressed FGF2 and SDC1 compared to the GO group. The PO group showed significant down-regulation of markers for monocytes, T-cells, and B-cells. These expression signatures were eliminated in heavily pretreated patients. Conclusion: The results suggest that small subsets of circulating CD30+/CD15+ cells expressing FGF2 and SDC1 represent biomarkers that identify NS-cHL patients who will experience a poor outcome (primary refractory and early relapsing). © 2013 Gharbaran et al.; licensee BioMed Central Ltd. Source
Tamir A.,Hackensack University Medical Center |
Jag U.,Hackensack University Medical Center |
Sarojini S.,Hackensack University Medical Center |
Schindewolf C.,Hackensack University Medical Center |
And 13 more authors.
Journal of ovarian research | Year: 2014
BACKGROUND: Early detection of ovarian cancer remains a challenge due to widespread metastases and a lack of biomarkers for early-stage disease. This study was conducted to identify relevant biomarkers for both laparoscopic and serum diagnostics in ovarian cancer.METHODS: Bioinformatics analysis and expression screening in ovarian cancer cell lines were employed. Selected biomarkers were further validated in bio-specimens of diverse cancer types and ovarian cancer subtypes. For non-invasive detection, biomarker proteins were evaluated in serum samples from ovarian cancer patients.RESULTS: Two kallikrein (KLK) serine protease family members (KLK6 and KLK7) were found to be significantly overexpressed relative to normal controls in most of the ovarian cancer cell lines examined. Overexpression of KLK6 and KLK7 mRNA was specific to ovarian cancer, in particular to serous and papillary serous subtypes. In situ hybridization and histopathology further confirmed significantly elevated levels of KLK6 and KLK7 mRNA and proteins in tissue epithelium and a lack of expression in neighboring stroma. Lastly, KLK6 and KLK7 protein levels were significantly elevated in serum samples from serous and papillary serous subtypes in the early stages of ovarian cancer, and therefore could potentially decrease the high "false negative" rates found in the same patients with the common ovarian cancer biomarkers human epididymis protein 4 (HE4) and cancer antigen 125 (CA-125).CONCLUSION: KLK6 and KLK7 mRNA and protein overexpression is directly associated with early-stage ovarian tumors and can be measured in patient tissue and serum samples. Assays based on KLK6 and KLK7 expression may provide specific and sensitive information for early detection of ovarian cancer. Source
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 749.11K | Year: 2010
To date, there is no single, well-maintained, up-to-date repository containing all clinically relevant cancer biomarker information. Researchers often face the daunting, tedious task of searching increasing numbers of databases that often provide inaccurate, incomplete, out-of-date, fragmented information. This directly results in wasted time and delays in finding cures for cancer. In Phase I, Sophic scientists developed a prototype central biomarker repository, the Integrated Cancer Biomarker KnowledgeBase (ICSK) that can mitigate this problem. In Phase" Sophic will continue to collaborate with a scientific advisory team of respected cancer researchers who will provide recommendations, feedback on the project. The advisors will help maintain the scientific Integrity of the ICBK in a cancer community that is in constant flux. Prototype Sophic Cancer BIomarker Objects (SCBDs) will be extended and enriched with biomarker related molecular information mined from target sources and curated by Sophic Scientists. The 2,116 biomarker genes mined from IBM Medline Abstracts and manually curated by PhD. scientists during the 5-year Ncr Cancer Gene Index Project will be the foundation for the SCBOs. Enriched SCBDs will be integrated In lCBK and provide scientists with detailed molecular information on Individual biomarker genes and panels of genes. A powerful, easy to use Knowledge Management System will be configured allow non-technical researchers to mine. explore and graphically display complex networks of biomarker, disease and scientific element relationships. The aims of the project are to improve the accuracy of disease diagnosis, increase the effectiveness of treatments and accelerate the discovery of drugs to cure cancer.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 149.99K | Year: 2008
During the past two decades growing volumes of experimental biomarker data have accumulated within massive databases dispersed worldwide. Today, there is no single, well maintained and up-to-date repository containing all clinically relevant biomarker information that translates into accelerated drug discovery and the work toward personalized medicine. Scientists and physicians face the daunting, tedious task of searching increasing numbers of databases that often provide, inaccurate, incomplete, out of date, one-dimensional information. In Phase I, the team will review a sample of biomarker databases to determine the quality of the data, identify common data elements, and design a "biomarker object" model that can be integrated into a Biomarker KnowledgBase (IBK). We will add end-user query, mining, modeling and visualization tools that allow scientists and physicians to find and use up-to-date biomarker information. Knowledge management tools will provide with "lateral integration" of "biomarker objects" to explore the semantic and clinical relationships between clusters of biomarkers for a specific type of cancer. The IBK and tools will support researchers, oncologists and program mangers. IBK will be commercialized by adding the product to the existing portfolio of Sophic products and services for the cancer community and expanded to support biomarker research for other complex diseases.
Sophic Systems Alliance, Inc. | Date: 2011-11-16
Software applications in the life sciences field. Providing business consultation services in the field of health care; management of grants and research for others in the medical research field. Providing software as a service (SAAS) services featuring software for the mining, reporting and analysis of health information; providing database services for others; scientific and medical research in the field of biomarker discovery, characterization and development.