Beth R. Pflug, Assistant Professor
Ph.D., Georgetown University, 1997
Email: pflugbr@msx.upmc.edu
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Dr. Pflug's laboratory is interested in growth regulation and novel therapeutic and imaging targets for prostate cancer. One aspect of her research focuses on new treatment strategies such as endothelin receptor blockade to combat advanced prostate disease. Endothelin-1 (ET-1) has been identified as an important growth factor in the pathophysiology of androgen refractory prostate cancer. These findings have been applied to the clinic and trials using endothelin receptor blockade have demonstrated significant clinical benefit in patients with advanced prostate cancer. Continuation of work involving the endothelin axis include the characterization of ET-1 signaling pathways in prostate cancer and expanding the therapeutic targets for prostate cancer treatment. These studies will also help identify those patients most likely to respond to endothelin receptor blockade through analysis of the ET axis. Other research interests include co-modulation of bone and prostate cancer cell growth. Metastatic prostate cancer commonly resides in the bone during the progression of androgen refractory disease. The Pflug laboratory is interested in bone cell/prostate cancer cell interactions to further identify new mechanisms for therapeutic intervention for prostate cancer patients with metastatic disease to the bone.
In addition to the studies on the endothelin axis, the Pflug laboratory is also interested in altered cell metabolism during prostate cancer progression. Fatty acid synthase (FAS) is the major multifunctional enzyme required by cells to convert carbohydrates to fatty acids de novo. FAS protein levels and enzyme activity are low in most normal tissues but are upregulated in prostate cancer. These studies investigate the role of FAS and lipids during androgen dependent and independent prostate tumorigenesis using in vitro and transgenic mouse models and examine the effects of FAS anti-metabolite therapy on cell death and tumor regression. Overexpression of FAS in prostate cancer cells also makes this molecule a potential imaging target for positron emission tomography (PET). The Pflug laboratory is exploring the use of PET imaging for the study of FAS in local and metastatic prostate tumors. This work focuses on characterizing the role of FAS in formation of primary tumors, during metastatic relapse and imaging tumor progression/regression by PET.
Recent Publication
Pflug BR, Pecher SM, Brink AW, Nelson JB and Foster BA. (2003) Increased fatty acid synthase expression and activity during progression of prostate cancer in the TRAMP model. The Prostate 57:245-254.
Pecher S, Pflug BR, Brink AWK and Nelson JB.(2004) Endothelin A Receptor Blockade does not Affect PSA Secretion in Prostate Cancer Cell Lines The Prostate 60:175-177.
Guruli G, Pflug BR, Pecher S, Makarenkova V, Shurin MR and Nelson JB. (2004) Function and survival of dendritic cells depend on endothelin-1 and endothelin receptor autocrine loops. Blood .104:2107-2115.
Ogawa T, Kamo I, Pflug BR, Nelson JB, Seki S, Igawa Y, Nishizawa O, De Groat WC, Chancellor MB and Yoshimura N. (2004) Differential roles of peripheral and spinal endothelin receptors in the micturition reflex in rats. J Urology 172:1533-1537.
Godara G, Cannon G, Cannon G, Jr., Nelson JB and Pflug BR. (2005) Role of endothelin axis in progression to aggressive phenotype of prostate adenocarcinoma. The Prostate 65:27-34.
Nelson JB, Udan MS, Guruli G and Pflug BR. (2005) Endothelin-1 inhibits apoptosis in prostate cancer. Neoplasia 7:631-637.
Shah US, Dhir R, Gollin S, Lewis D, Chandran UR, Acquafondata M and Pflug BR. (2006) Fatty acid synthase gene expression amplification in prostate adenocarcinoma. Human Pathology 4: 401-409.
Akhavan A, McHugh KH, Guruli G, Bies RR, Zamboni WC, Strychor SA, Nelson JB and Pflug BR. (2006) Endothelin receptor A blockade enhances taxane effects in prostate cancer. Neoplasia 8: 725-732.
Pflug BR, Zheng H, Udan MS, Marshall FF, Brooks JD and Nelson JB. (2007) Endothelin-1 promotes cell survival in renal cell carcinoma through the ETA receptor. Cancer Letters 246:139-148.
