tumor cell biology program - Sylvester Comprehensive Cancer Center

Chen, T, Schwartz, G, Burnstein,
KL, Lokeshwar, BL and Holick, MF. The
in vitro evaluation of 25-hydroxy vitamin
D3 and 19-nor-1, 25-hydroxyvitamin
D2 as therapeutic agents for
prostate cancer. Clinical Cancer Research
6:901, 2000.
Krishan, A, Oppenheimer, A, You,
W, Dubbin, R, Sharma, D and
Lokeshwar, BL. Flow cytometric analysis
of androgen receptor expression in
human prostate tumors and benign tissues.
Clinical Cancer Research 6:1922,
2000.
Lokeshwar, BL, Escatel, E and Zhu,
B. Cytotoxic activity and inhibition of
tumor cell invasion by derivatives of a
chemically modified tetracycline CMT-
3 (COL-3). Current Medical Chemistry
8:271, 2001.
Schwartz, GG, Lokeshwar, BL and
Burnstein, KL. Correspondence re: S. E.
Blutt, T. C. Polek, L. V. Stewart, M. W.
Kattan, and N. L. Weigel, A Calcitriol
Analogue, EB1089, inhibits the growth
of LNCaP tumors in nude mice. Cancer
Research 61:4294, 2001.
Lokeshwar, VB, Rubinowicz, D,
Schroeder, GL, Forgacs, E, Minna, JD,
Block, NL, Nadji, M and Lokeshwar,
BL. Stromal and epithelial expression of
tumor markers hyaluronic acid and
HYAL1 hyaluronidase in prostate cancer.
Journal of Biological Chemistry
276:11922, 2001.
INVENTIONS AND PATENTS
Title: “Method of inhibiting cancer
growth.” Principal Inventor: B.L.
Lokeshwar, Co-Inventors: Marie G.
Seizer, Norman L Block, (University
of Miami), and L.M. Golub, T.M.
McNamara, N.S., Ramamurthy, H-M.
Lee, S. Simon (State University of New
York, Stony Brook, NY). U.S. Patent No.
US 58,37696.
Title: “Method for prevention and
treatment of cancer.” Inventors: Gary G.
Schwartz, B.L. Lokeshwar (University of
Miami); Michael F. Holick, Tai C. Chen,
Lyman W. Whitlash (Boston University)
Temp. U.S. Patent No. 6474-2, March
25, 1999.
Title: “Method for treating meibomian
gland disease.” Inventors: S.G.
Pflugfelder, B.L. Lokeshwar, M.G. Seizer
U.S. Patent Application S.N. 60/
084,873 (revised filing May 8, 1999).
HIGHLIGHTS/DISCOVERIES
• An imbalance exists between the levels
of MMPs (overproduction) and their
natural inhibitors (under production)
in invasive prostate cancer cells.
• A novel chemically modified nonantimicrobial
tetracycline (COL-3) has
been identified as an effective antimetastatic
drug with potential to treat
prostate cancer metastatic to bone. The
National Cancer Institute has completed
the Phase I trial of this drug and
awaiting further trials. Other novel
agents are being tested in Dr.
Lokeshwar’s laboratory not only for
controlling cancer but other chronic
diseases such as chronic ocular surface
inflammation. Dr. Lokeshwar’s research
has brought in one patent to the University
of Miami jointly with State
University of New York at Stony
Brook, and two patents are pending
on the new application of his research
findings.
• In collaboration with Dr. Stephen
Pflugfelder, Department of Ophthalmology,
University of Miami, Dr.
Lokeshwar has identified a potential
application of CMTs to treat the Meibomian
gland dysfunction that leads to
the Ocular rosacea.
Vinata B. Lokeshwar, Ph.D.
Assistant Professor of Urology
DESCRIPTION OF RESEARCH
Dr. Lokeshwar’s research focuses on
understanding the mechanism of
cancer progression with a special emphasis
on tumor angiogenesis, i.e., neovascularization.
Angiogenesis is a process
that is required to nurture tumor growth
both at the primary and secondary metastatic
sites. Recent advances in cancer
research have elucidated that the components
of extracellular matrix (ECM)
and ECM-degrading enzymes play a crucial
role in regulating both, the metastatic
progression of localized tumors and tumor
angiogenesis. Using bladder and
prostate cancer model systems, her team
is trying to understand how ECM affects
tumor metastasis and angiogenesis.
Recent advances show that an ECM
component, hyaluronic acid (HA; which
is a glycosaminoglycan), and its degrading
enzyme, hyaluronidase (HAase), are
closely associated with the biology of
bladder cancer. They observed that elevated
urinary HA and HAase levels are
diagnostic indicators of bladder cancer
and its grade, respectively. This finding
has led to the development of a simple,
noninvasive, highly sensitive, and specific
urine test (HA-HAase test; 90 percent
accuracy) for detecting bladder cancer
and monitoring its recurrence.
Their studies on prostate cancer
showed that immunohistochemical localization
of both HA and HAase in prostate
cancer tissues is > 85% accurate in
predicting prognosis for prostate cancer
patients. Thus, use of these markers in
biopsy specimens may help clinicians to
make individualized treatment decisions
and improve patients’ prognosis.
This finding led to the identification,
purification, and cloning of the first
tumor-derived HAase. Furthermore, the
research has demonstrated that this tumor-derived
HAase degrades tumorassociated
HA into small angiogenic frag-
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UM/Sylvester Comprehensive Cancer Center Scientific Report 2002