SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

T U M O R C E L L B I O L O G Y P R O G R A M
Lokeshwar, BL , Selzer, MG, Zhu, BQ, Block,
NL, and Golub, LM. Inhibition of cell proliferation,
invasion, tumor growth and metastasis by
an oral non-antimicrobial tetracycline analog
(COL-3) in a metastatic prostate cancer model.
International Journal of Cancer 98:297-309,
2002.
Whitlatch, LW, Young, MV, Schwartz, GG,
Flanagan, JN, Burnstein, KL, Lokeshwar, BL ,
Rich, ES, Holick, MF, and Chen, TC. 25-
Hydroxyvitamin D-1alpha-hydroxylase activity is
diminished in human prostate cancer cells and is
enhanced by gene transfer. Journal of Steroid Biochemistry
and Molecular Biology 81:135-40,
2002.
2003
Chen, TC, Holick, MF, Lokeshwar, BL ,
Burnstein, KL, and Schwartz, GG. Evaluation of
vitamin D analogs as therapeutic agents for prostate
cancer. Recent Results in Cancer Research
164:273-88, 2003.
Li, de Q, Shang, TY, Kim, HS, Solomon, A,
Lokeshwar, BL , and Pflugfelder, SC. Regulated
expression of collagenases MMP-1, -8, and -13
and stromelysins MMP-3, -10, and -11 by human
corneal epithelial cells. Investigative Ophthalmology
& Visual Science 44:2928-36, 2003.
Dandekar, DS, Lokeshwar, VB, Cevallos-
Arellano, E, Soloway, MS, and Lokeshwar, BL .
An orally active Amazonian plant extract (BIRM)
inhibits prostate cancer growth and metastasis.
Cancer Chemotherapy and Pharmacology
52(1):59-66, 2003.
HIGHLIGHTS/DISCOVERIES
• Demonstrated that an imbalance exists between
the levels of MMPs (overproduction) and their
natural inhibitors (underproduction) in invasive
prostate cancer cells.
• Identified a novel, chemically modified nonantimicrobial
tetracycline (COL-3) as an effective
anti-metastatic drug with the potential to
treat prostate cancer metastatic to bone. The
NCI has completed the phase I trial of this
drug and is awaiting further trials. Other novel
agents are being tested in Dr. Lokeshwar’s laboratory,
not only for controlling cancer, but also
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 the State University of New
York at Stony Brook. Meanwhile, two patents
are pending on the new application of his
research findings.
• Identified a potential application of CMTs to
treat the meibomian gland dysfunction that
leads to the ocular rosacea. This was done in
collaboration with Stephen C. Pfulgfelder,
M.D., Baylor College of Medicine, Houston,
Texas.
VINATA B. LOKESHWAR, PH.D.
Associate Professor of Urology
DESCRIPTION OF RESEARCH
Dr. Lokeshwar’s research focuses on understanding
the mechanism of cancer progression
and tumor angiogenesis. 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
laboratory is trying to understand how ECM
affects tumor metastasis and angiogenesis.
Work in Dr. Lokeshwar’s laboratory demonstrates
that an ECM component, hyaluronic acid
(HA, which is a glycosaminoglycan), and its degrading
enzyme, hyaluronidase (HAase), are
closely associated with the biology of cancers of
the bladder and prostate. 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,
UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 85