Akhouri Sinha, PhD

Areas of Research Strength:

Sinha and his collaborators (Wilson, Fernandes, Reddy, and Ewing) are investigating differences in characteristics of prostate cancer stem cells in invasion and metastasis.  They defined aggressiveness of human prostate cancer by ratios of cathepsin B to stefin A (CANCER 2002:94:3141-3149).

Sinha et al. utilized a unique approach for 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 et al., Anticancer Research, 19: 893-902, 1999).  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.  U. S. Patent 6,379-669 was granted to Sinha.

Research Techniques:

He has used a variety of techniques.  Some of them are: immunogold electron microscopy; autoradiography, immunofluorescence; immunohistochemistry; laser capture microdissection; tissue microarray; inverted capsule embedding, isolation of cell fractions; organ and cell culture; chemotaxis of cancer cells, measurements of proteins and Elisa assay

Research Interests:

Sinha et al. are currently studying characteristics of prostate cancer stem cells and aggressiveness of  prostate cancer in addition to cell proliferation and cell death. 

Selected Publications:

Qian, J, Bostwick, DG., Iczkowski KA, Lang K, Betre K, Wilson MJ, Le C, Sinha AA: Characterization of  prostate cancer in needle biopsy by cathepsin B, cell proliferation, and DNA ploidy.  In Press, Anticancer Research, February 2010. 

Phillips JL and Sinha AA: Patterns, Art, and Context:Donald Floyd Gleason and the Development of the Gleason Grading System. Urology 74: 497–504, 2009.  Pub Med ID: 19376571

Wang X, Wilson, MJ, Slaton JW, Sinha AA, Ewing SL, Pei D: Increased aggressiveness of human prostate PC-3 tumor cells expresssing cell surface membrane type-1 matrix metalloproteinase (MT1-MMP). J. Androl. 30: 259-274, 2009.  Pub Med ID: 19136391

Sinha, A. A., Morgan, J. L., Betre, K., Wilson, M. J., Le, C. and Marks, L. S.: Cathepsin B expression in Native Japanese and Japanese-American prostate cancer patients:  An immunohistochemical study.  Anticancer Res., 28:2271-2278, 2008. Pub Med ID: 18751406

Wilson, M. J. and Sinha, A. A.: Matrix degradation in prostate cancer.  In: Cancer Metastasis-Biology and Treatment, Metastasis of Prostate Cancer. Volume 10, Ablin, R. J. and Mason, M.D. editors, Springer Science and Business Media B.V., Dordrecht, The Netherlands, 2008, pages 221-251.  Peer reviewed. 

Sinha AA, Morgan JL, Buus RJ, Ewing SL, Fernandes ET, Le C, Wilson MJ: Cathepsin B Expression is Similar in African-American and Caucasian Prostate Cancer Patients. 
Anticancer Res. 27:3135-3142, 2007.  Pub Med ID: 17970054.

This is the first study to match African-American and Caucasian men with prostate cancer by four clinical criteria (Gleason grade, age, prostate specific antigen: PSA levels and clinical stage).  When samples were matched, we found that cancer was similar in both races.  In contrast, previous studies during the last 70 years have shown that black men have more aggressive prostate cancer than white men.  We concluded that prostate cancer is not race-dependent. 

Sinha AA, Quast BJ, Wilson MJ, Fernandes ET, Reddy PK, Ewing SL, Gleason DF: Prediction of pelvic lymph node metastasis by the ratio of cathepsin B to stefin (cystatin) A in human prostate cancer.  Cancer 94: 3141-3149, 2002.  Pub Med ID: 12115346.

Using an enzyme cathepsin B (CB) and its endogenous inhibitor stefin A, we showed that the ratio of CB to stefin A could distinguish aggressive prostate cancer in patients.  Prostate cancer with pelvic lymph node invasion had higher ratios than those without node involvement.  This approach could also be used for breast and colon cancers.

Sinha AA, Quast BJ, Reddy PK, Elson MK, Wilson MJ:  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 Research, 19: 893-902, 1999.  Pub Med ID­­­: 10368631.

This is the first study to report successful delivery of an immunoconjugate to PSA-producing LNCaP prostate tumors in nude mice.  Selective delivery an immunoconjugate (anti-PSA-IgG-5-fu-2'-d) produced cytotoxic effects on PSA-producing prostate cancer cells indicated by decreased cell proliferation and increased cell death.  The drug conjugate did not produce cytotoxic effects on liver, spleen and kidney in nude mice. 

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, and Gleason D F: Antibody immunoglobulin (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.  Pub Med ID: 8837723. U. S. Patent 6,379,669 to Sinha in 2002.

This is the first study to show that when an antibody against human prostatic-specific antigen (PSA) was conjugated to a chemotherapeutic drug, the immunoconjugate, was bound to prostate cancer cells without binding to non-PSA producing organs.  Immunoconjugate is selective for prostate cancer and can be used in small dosages for reducing side effects in patients.

Sinha AA, Blackard CE, Seal US:  A critical analysis of tumor morphology and hormone treatments in the untreated and estrogen-treated responsive and refractory human prostatic carcinoma.  Cancer 40:2836-2850, 1977.  Pub Med ID: 4693598.

This is the first study to show that prostate cancer is a heterogeneous tumor because it contains hormone-sensitive and hormone-insensitive cancer cells from the onset of cancer.  We suggested that estrogen therapy can reduce tumor burden by inducing death in hormone-sensitive cells, but not in hormone-insensitive cells.

Sinha, A. A., Doe, R. P., Blackard, C. E., Seal, U. S.:  The in vitro localization of H3 estradiol in human prostatic carcinoma.  An electron microscopic radioautographic study.  Cancer, 31: 682-688, 1973.  Pub Med ID: 201356.

This is the first study to show binding of isotopic estrogen to human prostate cancer cells. This also indicated that estrogen treatment would directly affect cancer cells and reduce tumor burden.

To view these and other publications visit http://www.ncbi.nlm.nih.gov/PubMed
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