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Areas of Research Strength: Sinha, Quast, Wilson, Fernandes, Reddy, Ewing and Gleason published their work on identification of aggressive human prostate cancer by ratios of cathepsin B to stefin A (CANCER 2002:94:3141-3149). This work generated considerable interest in the popular media and scientific literature and has been reviewed in about 250 media articles. This approach can be extended to other cancers in breast, colon, lung, and other solid organs. A patent application is pending. Targeting of treatment is very difficult because the drug(s) are usually not delivered selectively and specifically to cancer cells. Sinha et al. utilized a unique approach of conjugating antibody against PSA (prostate specific antigen) with the chemotherapeutic drug 5 fluoro-2’-deoxyuridine, and delivered this immunoconjugate to prostate cancer cell tumors in nude mice (Sinha, Quast, Reddy, Elson, and Wilson, Anticancer Research, 19: 893-902, 1999). Sinha received a U. S. Patent 6,379-669. Selective and specific delivery of immunoconjugate induced cell death and inhibited DNA synthesis only in prostate cancer tumors. This work is ready for clinical trial. back to top |
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Research Techniques: Immunogold electron microscopy immunofluorescence confocal microscopy immunohistochemistry Elisa assay laser capture microdissection tissue microarray isolation of cell fractions measurements of proteins organ and cell culture chemotaxis back to top |
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Research Interests: Sinha et al. are studying a variety of markers on tissue microarray sections and prostate tissue sections. Sinha and his collaborators are currently investigating protease cathepsin B, inhibitor stefin A and their ratios for identifying aggressive prostate cancer. Their study on cell proliferation and cell death has the potential of further defining aggressive prostate cancer; study in progress. Targeting of treatment to prostate cancer is progressing slowly. Targeting of prostate cancer by immunoconjugate (antibody against PSA: prostate specific antigen) conjugated to chemotherapeutic, drug 5 fluoro-2’-deoxyuridine) has led to the delivery of this conjugate specifically to prostate cancer cells. This work is ready for clinical trial. back to top |
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Selected Publications: Sinha, A. A., Morgan, J. L., Wood, N., Betre, K., Reddy, A., Wilson, M. J., Ramnani, D.: Heterogeneity of Cathepsin B and Stefin A Expression in Gleason Pattern 3+3 (Score 6) Prostate Cancer in Needle Biopsies. In press, Anticancer Research, volume 27 (3): 3-9, 2007. Kube, D. M., Savci-Heijink, C. D., Lamblin, A-F., Kosari, F., Vasmatzis, G., Cheville, J. C., Connelly, D. P. and Klee, G. G.: Optimization of laser capture microdissection and RNA amplification for gene expression profiling of prostate cancer. B.M.C. Molec. Biol., 8:1-14, 2007. Wilson, M. J., Haller, R., Shelby, Y. L., Slaton, J. W., Sinha, A. A., Wasserman N. F: Elevation of dipeptidylpeptiase IV in the prostate peripheral zone and prostatic secretions in men with prostate cancer: possible prostate cancer disease marker. J. Urol., 174: 1124-1128, 2005 Sinha, A. A., Quast, B. J., Reddy, P. K., Lall, V., Wilson, M. J., Qian, J., Bostwick, D. G.: Microvessel density as a molecular marker for identifying high grade prostatic intraepithelial neoplasia (HGPIN) precursors to prostate cancer. Exptl. Molec. Pathol., 77: 153-159, 2004. Wilson, M. J., Jiang, A., Wiehr, C., Wang, X., Sinha, A. A., Pei, D.: Limited processing of pro-matrix metalloprotease-2 (Gelatinase A) overexpressed by transfection in PC-3 human prostate tumor cells: Association with restricted cell surface localization on membrane-type matrix metalloproteinase-1. J. Androl., 25:274-285, 2004. Wilson, M. J., Haller, R., Slaton, J. W., Wasserman, N. F., Sinha, A. A.: Dipeptidylpeptidase IV activities in prostatic secretions. In Dipeptidyl Aminopeptidases in Health and Disease, edited by M. Hildebrandt et al., Kluwer Academic/Plenum Publishers, New York, NY, 257-260, 2003. Sinha, A. A., Quast, B. J., Wilson, M. J., Fernandes, E. T., Reddy, P. K., Ewing, S. L., Gleason, D. F.: Prediction of pelvic lymph node metastasis by the ratio of cathepsin B to stefin A in patients with prostate carcinoma. Cancer 94: 3141-3149, 2002. Sinha, A. A., Jamuar, M. P., Wilson, M. J., Rozhin, J., Sloane, B. F.: Plasma membrane association of cathepsin B in human prostate cancer: Biochemical and immunogold electron microscopic analysis. The Prostate, 49:172-184, 2001. Sinha, A. A., Quast, B. J., Wilson, M. J., Fernandes, E. T., Reddy, P. K., Ewing, S. L., Sloane, B. F., Gleason, D. F.: Ratio of cathepsin B to stefin A identifies heterogeneity within a Gleason histologic score for human prostate cancer. The Prostate, 48:274-284, 2001. Wilson, M. J., Ruhland, A. R., Quast, B. J., Reddy, P. K., Ewing, S. L., Sinha, A. A.: Dipeptidylpeptidase IV activities are elevated in prostate cancers and adjacent benign hyperplastic glands. J. Androl., 21:220-226, 2000. Sinha, A. A., Quast, B. J., Reddy, P. K., Elson, M. K., Wilson, M. J.: Intravenous injection of an immunoconjugate (anti-PSA-IgG conjugated to 5-fluoro-2'-deoxyuridine) selectively inhibits cell proliferation and induces cell death in human prostate cancer cell tumors grown in nude mice. Anticancer Res., 19:893-902, 1999. Sinha, A. A., Quast, B. J., Korkowski, J. C., Wilson, M. J., Reddy, P. K., Ewing, S. L., Sloane, B. F., Gleason, D. F.: The relationship of cathepsin B and stefin A mRNA localization identifies a potentially aggressive variant of human prostate cancer within a Gleason histologic score. Anticancer Res., 19: 2821-2830, 1999. Sinha, A. A., Quast, B. J., Wilson, M. J., Reddy, P. K., Gleason, D. F., Sloane, B. F.: Codistribution of procathepsin B and mature cathepsin B forms in human prostate tumors detected by confocal and immunofluorescence microscopy. Anat. Rec., 252:281-289, 1998. Sinha, A. A., Quast, B. J., Wilson, M. J., Reddy, P. K., Fernandes, E T., Ewing, S. L., Gleason, D. F.: Immunocytochemical localization of an immunoconjugate (antibody IgG against prostatic acid phosphatase conjugated to 5-fluoro-2'-deoxyuridine) in human prostate tumors: Anticancer Res., 18: 1385-1392, 1998. Wilson, M. J., Ruhland, A. R., Pryor, J. L., Ercole, C., Sinha, A. A., Hensleigh, H., Kaye, K. W., Dawkins, H. J. S., Wasserman, N. F., Reddy, P., Ahmed, K.: Prostate specific origin of dipeptidylpeptidase IV (CD-26) in human seminal plasma. J. Urol., 160:1905-1909, 1998. Wilson, M. J., Sinha, A. A: Human prostate tumor angiogenesis in nude mice: Metalloprotease and plasminogen activator activities during tumor growth and neovascularization of subcutaneously injected matrigel impregnated with human prostate tumor cells. Anat. Rec., 249:63-73, 1997. Sinha, A. A., Sackrison, J. L., DeLeon, O. F., Wilson, M. J., Gleason, D. F.: Antibody immunoglobulin G (IgG) against human prostatic specific antigen (PSA) as a carrier protein for chemotherapeutic drugs to human prostatic tumors: Part 1. A double immunofluorescence analysis. Anat. Rec., 245:652-661, 1996. To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed search menu should say PubMed type Sinha AA in the avaliable line back to top |
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Micrograph illustrates estrogen treated human prostate cancer cells invading the adjacent stroma, connective tissue and smooth muscle fibers |
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Photomicrograph illustrates co-localization of pro-cathepsin B and cathepsin B (yellow fluorescence) in cancerous human prostate glands by confocal microscopy. Fluorescein isothiocyanate (FITC) localized active (mature) form of cathepsin B (green fluorescence). |
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