SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

C L I N I C A L O N C O L O G Y R E S E A R C H P R O G R A M
SELECTED PUBLICATIONS
2002
Ding, Z, Tang, S-C, Weerasinghe, P, Yang, X,
Pater, A, and Liepins, A. The alkaloid sanguinarine
is effective against multi-drug resistance in
human cervical cells via bimodal cell death. Biochemical
Pharmacology 63:1415-21, 2002.
Ding, Z, Green, AG, Yang, X, Chernenko, G,
Tang, S-C, and Pater, A. Retinoic acid inhibits
telomerase activity and downregulates expression
but does not affect splicing of hTERT: correlation
with cell growth rate inhibition in an in vitro
cervical carcinogenesis/multidrug-resistance
model. Experimental Cell Research 272:185-91,
2002.
Ding, Z, Tang, S-C, Weerasinghe, P, Yang, X,
Chernenko, G, Pater, A, and Liepins, A. The alkaloid
sanguirine is effective against multidrug
resistance in human cervical cells via bimodal cell
death. Biochemical Pharmacology 63:1415-21,
2002.
Tang, S-C. BAG-1, an anti-apoptotic tumor
marker. (Invited Review) IUBMB Life 53:99-
105, 2002.
Chen, J, Chernenko, G, Xiong, J and Tang, S-C.
Distinct BAG-1 isoforms have different antiapoptotic
functions in BAG-1-transfected C33A
human cervical carcinoma cell line. Oncogene
21:7050-59, 2002.
2003
Tang, S-C. Differential anti-apoptotic function
of BAG-1 isoforms in human malignancy. Recent
Research and Development in Biophysics and
Biochemistry 3:427-44, 2003.
HIGHLIGHTS/DISCOVERIES
• Cloned mouse and human BAG-1 genes and its
promoter.
• Discovered the mechanism by which four BAG-
1 isoforms are generated.
• Discovered the possible prognostic value of
BAG-1 in breast and lung cancer.
• Generated BAG-1-isoform-specific Mab’s
(patent pending).
• Generated BAG-1 antisense cDNA and siRNA.
• Discovered BAG-1’s involvement in chemotherapy
resistance.
• Developed Eastern Cooperative Oncology
Group (ECOG) protocol using BAG-1 as predictive
marker in the treatment of NSCLC.
KHALED A. TOLBA, M.D.
Assistant Professor of Medicine
DESCRIPTION OF RESEARCH
During the past five years, Dr. Tolba has been
developing immunotherapeutic strategies for
B-cell hematologic malignancies, with particular
interest in chronic lymphocytic leukemia (CLL).
CLL is the most common leukemia in the Western
hemisphere. As a relatively slow-progressing
tumor with readily accessible tumor cells, it offers
an opportunity to develop and test immunotherapeutic
interventions. A number of profound
immunologic deficiencies affecting both the B
and T-cell responses, however, have posed a challenge
to immune therapy of CLL.
The laboratory has co-developed and
adapted the use of herpes simplex virus (HSV)
amplicons for gene transduction of CLL cells.
Using CD40L as an effector molecule, they have
shown robust induction of co-stimulatory molecules
on transduced and bystander cells and in
roughly one-third of tested patients demonstrated
the capacity to generate cytotoxic T lymphocytes
(CTL) activity. This capacity to elicit autologous
CTL response, however, was not universal as
more than half the patients tested failed to mount
UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 61