The major focus of the laboratory is the study
of tumor angiogenesis as a potential target for cancer therapy. Tumors, like any
other tissue, must have a functional blood supply in order to survive and grow.
Deprivation of that supply can lead to loss of tumor viability or integrity similar
to events following myocardial infarction or stroke. Cancer may be considered as a
two- compartment system in which tumor cells and vascular endothelial cells interact in a
paracrine fashion. Treating both of these compartments instead of only the tumor
cells may offer the best hope for therapeutic advances. Tumor angiogenesis is influenced
by a number of both positive and negative regulatory factors. Studies in the
laboratory are designed to elucidate the role of angiogenesis, particularly in the
setting of lung cancer and hematopoietic malignancies. The angiogenic factors of
importance in lung cancer have not been fully elucidated. Studies are underway to examine
the role of vascular endothelial cell growth factor (VEGF), a multifunctional cytokine
which acts both as a potent inducer of vascular permeability as well as serving as a
selective endothelial cell mitogen. Additional studies in the laboratory are aimed
at identifying novel mechanisms of multidrug resistance to antineoplastic agents. My
laboratory has also been involved in the development of an automated approach to the
technique of in situ hybridization, a technique which allows an investigator to examine
gene expression in specific cells without compromising the cellular morphology. We have
the capability of detecting several gene transcripts through the use of either riboprobe
or oligonucleotide probes and have set up several collaborations with other investigators
through out the Arizona Health Science Center.
Bellamy WT, Richter L, Frutiger Y, Grogan TM. Expression of vascular
endothelial growth factor (VEGF) and its receptors in hematopoietic
malignancies. Cancer Research 59:728-733, 1999.
Grogan T, Fenoglio-Prieser C, Zahen R, Bellamy W, Frutiger Y,
Vela E, Richter L, Powis G. Thioredoxin, a putative oncogene product,
is overexpressed in gastric carcinoma and associated with increased
proliferation and increased cell survival. Human Pathology,31:475-481,
2000.
Bellamy WT, Richter L, Sirjani D, Roxas C, Glinsmann-Gibson B,
Frutiger Y, Grogan TM, List AF. Vascular endothelial cell growth
factor (VEGF) is an autocrine promoter of abnormal localized immature
myeloid precursors (ALIP) and leukemia progenitor formation in
myelodysplastic syndromes. 97: 1427-1434, Blood, 2001.
Bellamy WT. The expression of vascular endothelial growth factor
(VEGF) and its receptors in multiple myeloma and other hematopoietic
malignancies. Sem Oncol. 28:551-559, 2001.
Welsh SJ, Bellamy WT, Briehl MM, Powis G. The redox protein thioredoxin-1
increases hypoxia-inducible factor 1a protein expression: Trx-1
overexpression results in increased vascular endothelial growth
factor production and enhanced tumor angiogenesis. Cancer Research
62:5089-5095, 2002
