 |
||
 |
||
 |
||
 |
||
 |
||
 |
||
 |
|
|
|||
|
|
------------------------------------------------------------------------------------------------- Curriculum Vitae B.S.,
Bombay University ------------------------------------------------------------------------------------------------- Research Interests Do we have a PSA for bladder cancer: Every year, in the United States, 54,000 new cases of bladder cancer are detected, and nearly 12,000 deaths are blamed on this disease. Public Health studies show that certain groups of people, such as smokers, are at a 6 to 8 fold increased risk for bladder cancer. The majority of deaths and the suffering related to bladder cancer are a result of the spread of cancer (metastasis) to other organs and its interference with the body's vital functions. Bladder tumors also recur frequently, and, therefore, patients have to be monitored often (every 3 to 6 months) despite having been treated successfully for the initial tumor. Currently, the standard protocol for detecting and monitoring bladder cancer involves cystoscopy (an endoscopic procedure) and biopsy of the suspicious area. Although these are sensitive and accurate procedures for detecting bladder cancer, they can be invasive, expensive, and painful. At present, a simple, non-invasive and accurate diagnostic test for bladder cancer, like the PSA for prostate cancer detection, is not available. Finding a PSA for bladder cancer: After years of research Lokeshwar patented a urine test (HA-HAase test) that detects bladder cancer and evaluates its severity. This test measures concentrations of a particular sugar polymer, hyaluronic acid (HA) and its degrading enzyme, hyaluronidase (HAase), in the urine of bladder cancer patients. In collaboration with Mark Soloway and Norman Block, Lokeshwar's group demonstrated that the HA-HAase test is 90 percent accurate in detecting bladder cancer and monitoring its recurrence. This means that 90 percent of the time, a positive test indicates bladder cancer. In many patients the HA-HAase test can detect bladder cancer recurrence even before the tumor becomes clinically noticeable by cystoscopy. The research shows that a positive HA-HAase test in the absence of clinically detectable bladder tumor indicates a ten-fold increased risk of developing bladder cancer within five months. Thus, the HA-HAase test is a highly accurate method of bladder cancer detection and monitoring its recurrence. When working on the HA-HAase test, Lokeshwar realized that HA and HAase cannot be accurate markers for bladder cancer if they do not play a role in its growth and metastasis. With this idea in mind, Lokeshwar's group linked HAase to cancer biology for the first time and established it as one of the culprits involved in the growth and spread of cancer. Their recent work demonstrates that inhibition of HAase production by bladder tumor cells, using genetic engineering techniques, inhibits tumor growth and formation of muscle invasive bladder tumors. Muscle invasion by bladder tumors is ominous, as 60 percent of patients with muscle invasive tumors die within five years regardless of treatment. By working on chemical inhibitors of HAase, Lokeshwar hopes that, in the future, there may be novel treatments that not only block bladder tumor growth but also its progression to muscle invasion. How to decide which prostate cancer is aggressive: The spread (metastasis) of prostate cancer (CaP) is associated with extraordinary pain, and, in some cases, paraplegia (due to bone metastasis) and eventual death. At the time of initial diagnosis, if urologists could be more exact in determining which clinically localized prostate cancers are more likely to metastasize in the future, they could design more effective treatment and improve outcome. Existing tools, such as PSA measurement or evaluation of tumor architecture (Gleason score), provide a "ball-park" estimate of the prognosis for CaP patients. Tests or markers, that determine the aggressiveness of the tumor, and, thereby, accurately predict the prognosis for CaP patients could help the clinicians to make appropriate treatment decisions. With the success of the HA-HAase test and understanding that many tumors share similar characteristics in terms of growth and metastasis, Lokeshwar's group decided to examine whether HA and HAase can predict the prognosis for prostate cancer patients. The work conducted in collaboration with her colleagues demonstrates that HA and HAase are promising tumor markers that can predict prognosis for prostate cancer patients with 85 percent accuracy. Moreover, the research shows that there is a 20-fold increased risk of progression within five years if prostate cancer tissues recovered after radical surgery show high expression of HA and HAase. Such a priori knowledge regarding disease progression will help urologists to identify patients who will need more treatment after surgery, in order to stop prostate cancer metastasis. A woman researcher to tackle a woman's urological disease: Some of the other urology-related projects going on in Lokeshwar's laboratory include finding objective diagnostic and monitoring methods for interstitial cystitis. Interstitial cystitis or IC, for short, is a painful, irritative bladder syndrome. Since this disease mainly affects women, it is often perceived that women imagine this disease or they have a psychological problem, which makes them feel bladder pain and frequency and urgency of urination. Lokeshwar decided to investigate this disease. In collaboration with her colleague, Angelo Gousse, the investigation led to the finding that women with IC have an imbalance in the sugar polymer coating present inside the bladder wall. This coating protects the bladder in healthy people from toxic substances present in urine. An imbalance in this coating will induce irritation, pain and frequency of urination. Thus, the investigation demonstrates that IC is a real physiological disease and not a figment of imagination of psychologically distressed women. Furthermore, the investigation has led to the design of a urine test for objectively diagnosing and monitoring IC patients. Contributors and collaborators: The Department of Urology at University of Miami is a unique place where successful researchers (i.e., Drs. Vinata and Bal Lokeshwar) work closely with several like-minded hard working clinicians. The urologists provide clinical material and valuable clinical insights to Dr. Vinata Lokeshwar, enabling her to successfully conduct urological research. Her close collaborators within the department include Drs. Mark Soloway, Norman Block, Angelo Gousse and Francisco Civantos. Some of Lokeshwar's collaborators outside the department include, Drs. Robert Duncan (University of Miami), Maria Fernanda Lorenzo-Gomez (University of Salamanca, Spain), and Stefan Hautmann (University of Hamburg, Germany) ------------------------------------------------------------------------------------------------- Selected Publications ( 2001 to present) Lokeshwar, V.B. *, Rubinowicz, D., and Schroeder, G. L., Forgacs, E., Minna, J.D., Block, N.L., Lokeshwar, B.L., and Nadji, M. (2001) Stromal and epithelial expression of tumor markers hyaluronic acid and hyaluronidase in prostate cancer. J. Biol. Chem. 276: 11922-11932. Lokeshwar, V.B.*, Schroeder, G.L., Selzer, M.G., Hautmann, S.H., Posey, J.T., Duncan, R.C., Watson, R., Rose, L., Markowitz, S., and Mark S. Soloway, M.S. (2002) Bladder tumor markers for monitoring recurrence and screening: comparison of hyaluronic acid hyaluronidase and BTA-Stat tests. Cancer 95: 61-72. Lokeshwar, V.B.*, Schroeder, G.L., Carey, R., Soloway, M.S. and Iida, N. (2002). Regulation of hyaluronidase activity by alternative mRNA splicing. J. Biol. Chem. 277: 33654 - 33663. Posey, J.T., Soloway, M.S., Ekici, S., Sofer, M., Civantos, F., Duncan, R.C., and Lokeshwar, V.B.* (2003) Evaluation of the prognostic potential of hyaluronic acid and hyaluronidase (HYAL1) for prostate cancer. Cancer Research 63: 2638-2644. Franzmann, E., Schroeder, G.L., Goodwin, G.J., Weed, D., and Lokeshwar, V.B.* (2003) Expression of tumor markers, hyaluronic acid and hyaluronidase, in head and neck tumors. Int. J. Cancer 106:438-45. Ekici, S., Cerwinka, W. H., Duncan, R.C., Gomez, P., Civantos, F., Soloway, M.S., Lokeshwar, V.B.* (2004) Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL-1), CD44v6 and microvessel density for prostate cancer. Int J Cancer 112: 121-129. Lokeshwar, V.B.* and Civantos F. (2004) Tumor markers: Current Status. In American Cancer Society Atlas of Clinical Oncology: Bladder Cancer (Droller MJ (ed)) Ontario Canada: Hamilton, pp: 160 - 205. Schroeder, G. L., Lorenzo-Gomez, M.F. Hautmann, S.H., Friedrich, M.G., Ekici, S., Huland, Lokeshwar, V.B.* (2004) A side-by-side comparison of cytology and biomarkers for bladder cancer detection. J. Urology 172: 1123 - 1126. Lokeshwar, V.B.*, Cerwinka, W.H., Lokeshwar, B.L. (2005) HYAL1 hyaluronidase: a molecular determinant of bladder tumor growth and invasion. Cancer Research 65: 2243 - 2250. Lokeshwar, V.B.*, Habuchi, T., Grossman, H.B., Murphy, W.M., Hatumann, S.H., Hemstreet III, G.P., Bono, A.V., Getzenberg, R.H., Goebell, P., Schmitz-Drager, B.J., Schalken, J.A., Fradet, Y., Marberger, M., Messing, E., and Droller, M.J. (2005) Bladder tumor markers beyond cytology: Bladder Cancer Consensus Panel, Society for International Urology (In Press).
View more published research articles by Dr. Lokeshwar in the National Library of Medicine ------------------------------------------------------------------------------------------------- |
|
Copyright ©2002-2008, University of Miami, All Rights Reserved. Terms of Use | Privacy Statement | Contact Webmaster |