Research

Below, you will find information on a sampling of research projects that are ongoing in the department of urology. If you need specific research information, please consult the Faculty listing.

Pediatric Urology
Jyoti Upadhyay, MD, Chief of Pediatric Urology, Assistant Professor

Bladder diseases caused by prenatal obstructive processes (posterior urethral valves and neurogenic bladder) are common causes of childhood bladder failure. The bladder undergoes a damage response associated initially with excessive urine evacuation pressures, and later with excessive storage pressures. This excess tension incites a fibroproliferative response that progressively destroys the bladder’s ability to store and expel urine at safe pressures, erodes urinary continence, and subsequently can lead to upper tract deterioration and renal failure.

At present no available therapy exists to reverse or terminate this fibroproliferative disease process due to high-pressure bladder injury. Advances in this area have been in the arena of “bladder replacement” or augmentation cystoplasty. However, there is little understanding of the cellular and molecular processes that drive the fiboproliferative disease process.

We are testing the hypothesis that stretch activates specific receptors (Integrins- relay information about the structural and biochemical nature of the ECM into the cell.) on bladder smooth muscle cells (SMC) that recognize components in the extracellular matrix (ECM) leading to excessive cell growth and matrix deposition. These signaling receptors have been shown to mediate cell stress responses in the heart, vessels and lung. We study how specific integrin receptors regulate the activity of bladder hypertrophy/hyperplasia in response to abnormal bladder wall tension.

We predict tht perturbation of such molecular targets can favorable alter the fiboproliferative process. If experimentally blocking integrin function predictably alters these downstream events, this would suggest a primary treatment strategy for fibroproliferative bladder disease.

Antibody Therapy for Prostate Cancer
Ching Y. Wang, D.V.M., Ph.D., Professor and Director of Research of Urology
D.V.M., 1964, Taiwan University, Ph.D., 1970, Auburn University

Prostate cancer has the highest cancer incidence and the second leading cause of cancer death in men. Response to androgen ablation in early-stage disease is temporary and palliative in most cases. Of the patients diagnosed with small clinically palpable lesions, 30 to 35% develop metastases. Traditional chemotherapy and radiation therapy have very limited efficacy for metastatic disease. New treatment modalities are clearly needed.

Prostate-specific membrane antigen (PSMA) has been targeted for immunotherapy of this cancer because it is relatively specific for prostate epithelial cells and its expression is upregulated during malignant process. PSMA is a transmembrane protein with folate hydrolase activity. Its biological function in prostate epithelium is not known. Using computer-aided analyses, we have identified several antigenic epitopes in the extracellular domain of PSMA. We have prepared oligopeptides for immunization and prepared monoclonal antibodies against these specific epitopes. Preliminary results suggest that these antibodies are cytotoxic to the PSMA-positive human prostate cancer but not to PSMA-negative cancer cells.

Our investigation is now focused on (1) humanization of the monoclonal antibodies, (2) preparation of toxin-conjugated antibodies, and (3) mechanisms of antitumor activity by these antibodies and immunotoxins. The human antibodies and immunotoxins have potential clinical use.

References

K. Kuratsukuri, C. Y. Wang, T. Sone, N. Nishisaka, R. F. Jones and G. P. Haas. Induction of antibodies against prostate-specific membrane antigen (PSMA)
by vaccination with a PSMA DNA vector. Eur. Urol. 120:1-7, 2002.

K. Kuratsukuri, T. Sone, C. Y. Wang, N. Nishisaka, R. F. Jones and G. P. Haas. Inhibition of prostate-specific membrane antigen (PSMA)-positive tumor growth by vaccination with either full-length or the C-terminal end of PSMA. Int. J. Cancer (in press), 2002.

Kinoshita, Y., Kuratsukur, K., Newman, N., Rovito, P.M.,Jr., Kaumaya, P.T.P, Wang, C.Y., and Haas, G.P. Targeting epitopes of prostate-specific membrane antigen for antibody therapy of prostate cancer. Prostate Cancer & Prostatic Diseases. In press, 2005.

Laparoscopy / Endourology
Bijan Shekarriz, MD, Associate Professor.

We perform advanced and state of the art laparoscopic surgery for various urological malignancies including kidney cancer, prostate cancer and testicular cancer. Laparoscopic surgery has the advantage of decreased postoperative pain and shorter recovery time. Furthermore, no large incision is made to perform the surgery. SUNY is one of the few centers across the United State, which offers laparoscopic radical prostatectomy.

Similar to laparoscopy, kidney stones can be treated effectively by endoscopic procedures including ureteroscopy, and percutaneous procedures. We utilize laser surgery and other state of the art lithotripsy modalities to break the stones and remove them. Utilizing these modalities, the need for an open stone surgery is extremely low at present.

The current research focuses on the use of new technologies for performing laparoscopic partial nephrectomy. The use of various modalities including laser, Hydro-Jet, and tissue sealant have been shown to be effective for partial nephrectomy. In the animal laboratory, we are currently exploring new techniques using this modalities to improve our ability to perform laparoscopic resection of a large segment of kidney without significant blood loss.

Epidemiology of prostate cancer
Gabriel P. Haas, M.D., Professor and Chairman

Despite the fact that prostate cancer is the most prevalent malignancy in men, little is known about the etiology of this malignancy. Clinical and laboratory studies are ongoing in order to identify genetic and environmental factors that may be related to this disease.

References:

Kinoshita, Y., Singh, A., Rovito, P.M. Jr., Wang, C.Y. and Haas, G.P. Double primary cancers of the prostate and bladder: A literature review. Clin Prostate Cancer 3:83-86, 2004.

Singh, A., Kinoshita, Y.. Rovito, P.M., Jr., Landas, S., Silberstein, J., Nsouli, I., Wang, C.Y..and Haas, G.P. Higher than expected association of clinical prostate and bladder cancers. J Urol, 173:1526-9, 2005.

Rovito, P.M, Jr., Morse, P.D., Spinek, K., Newman, N., Jones, R.F., Wang, C.Y., and Gabriel P. Haas. Heterocyclic Amines and Genotype of N-acetyltransferases as Risk Factors for Prostate Cancer. Prostate Cancer & Prostatic Diseases. 8:69-74, 2005.

Detection of occult prostate cancers in elderly men
Gabriel P. Haas, M.D., Professor and Chairman

The prevalence of occult prostate cancer increases with the increase in age. The cancer is present in American men as young as early their 20's,and the prevalence increases with each decade to 65 to 70% of 60-60 years old, regardless of race. Low grade tumors of less than 0.5 cc are generally considered to be biologically unimportant and most such tumors do not progress to clinical significance. Increasingly sensitive PSA tests and more biopsies will lead to the diagnosis of many clinically insignificant cancers that should not be treated. In the absence of benefit, the aging population will incur only the morbidity of the diagnosis and unnecessary treatment. The objective of this study is to delineate the relationship between sensitive PSA tests, extensive biopsies and the detection of occult cancers.

Reference:

Jones, R.F.. Sunheimer, R., Friedman, H., Miller, D., Ginsburg, R., Jumbelic, M., Threatte, G., and Haas, G.P. Comparison of ante- and post-mortem PSA levels for epidemiological studies. Anticancer Reh. 25:1263-7, 2005.