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Translational and Basic Science Research
Hirak S. Basu, PhD
Wade Bushman, MD, PhD
Andreas Friedl, MD
David F. Jarrard, MD
Glenn Liu, MD
Douglas G. McNeel, MD, PhD
Terry Oberley, MD, PhD
Richard Peterson, PhD
Mark Ritter, MD, PhD
John Svaren, PhD
George Wilding, MD
Weixiong Zhong, MD
David F. Jarrard, MD
Associate Professor
600 Highland Ave G5/347
Madison WI 53792
jarrard@surgery.wisc.edu
Clinical research projects include developing methods of maximizing cavernous
(erectile) nerve function after surgery and investigating alternative
methods for treatment salvage after primary prostate cancer treatment
failure.
The long-term goal of our basic research program is to identify better
markers for prostate cancer that will enable us to diagnose the disease
at an earlier time-point and predict its progression. This information
will additionally permit us to develop new approaches to treating prostate
cancer.
Our basic research laboratory is focused on two areas relating to prostate
cancer development and progression. The first is the epigenetic regulation
of gene expression. Many environmental aspects, such as oxidative stress
and hormonal influences, may affect epigenetic marks at imprinted loci.
We are currently investigating alterations in imprinting in both an
in vitro human prostate epithelial cell model and in vivo in a mouse
model of aging. We theorize that a loss of imprinting of IGF-II, a growth
factor, contributes to the development of prostate cancer with aging.
DNA methylation is a candidate underlying these alterations in imprinting.
A second area of interest is in the genetic and epigenetic events that
characterize overcoming or bypassing senescence. We have characterized
a number of these genetic events and pathways that occur in this process
in normal human prostate epithelial cells that have been immortalized.
These pathways are being examined in human prostate cancer samples for
their use as prognostic markers and therapeutic targets. A number of
novel pathways for arresting cancer cell growth are being examined based
on pathways activated in senescence.
RECENT PUBLICATIONS:
Schwarze SR, DePrimo SE, Grabert LM, Fu V, Brooks JD, Jarrard DF.
Novel Pathways Associated with Bypassing Cellular Senescence in Human
Prostate Epithelial Cells. Journal of Biological Chemistry 2002; 277
(17): 14877-14883.
Jarrard DF, Modder J, Fadden P, Fu V, Sebree L, Heisey D, Schwarze
SR, Friedl A. Inactivation of the p16/pRb Senescence Checkpoint Occurs
Commonly in Human Prostate Cancer. Cancer Letters (in press).
Mark Ritter, MD, PhD
Associate Professor of Medicine
600 Highland Ave K4B100
Madison WI 53792
ritter@humonc.wisc.edu
The focus of laboratory investigations is to identify and investigate molecular markers of radioresistance in prostate cancer. The long-term goal
is to develop assays that will allow prediction of a patient's response to radiation therapy, thereby permitting treatment selection most appropriate
to an individual tumor's biology.
Clinical investigations include, among others, projects focusing upon enhancing the conformal delivery of radiation therapy through the use
of novel treatment delivery technology; exploiting the unique radiobiology of prostate cancer through altered radiation fractionation; describing
and quantifying prostate brachytherapy toxicities with respect to implant dosimetry; and exploring the utility of MRI spectroscopy in localizing
prostate cancer and prostate cancer recurrences.
RECENT PUBLICATIONS:
Fowler J, Chappell R, Ritter M. Is alpha/beta for prostate tumors really low? Int J Radiat Oncol Biol Phys 2001;50:1021-1031.
Ritter M, Gilchrist K, Voytovich M, Chappell R, Verhoven BM. The role of p53 in radiation therapy outcomes for favorable-to-intermediate risk prostate cancer. Int J Radiat Biol Oncol Phys (in press) 2002.
George Wilding, MD
Professor of Medicine
600 Highland Ave K6/548
Madison WI 53792
gxw@medicine.wisc.edu
Dr. Wilding's laboratory interests are to identify potential areas of
prevention of prostate cancer and more effective therapies for advanced
prostate cancer. Current studies include the evaluation of:
1) the
effect of androgen on prostate cell redox, what role this plays in
prostate cancer development, and what interventions might affect this
process (eg antioxidants as a preventive therapy),
2) the efficacy
of
novel porphyrin-polycation conjugates against human prostate cancer
xenografts (a collaboration with Hirak Basu / S'LIL Biomedical Corp.)
and 3) the efficacy and associated molecular effects of Vitamin D
compounds in varied schedules and in combination with docetaxel against
human prostate cancer cells and xenografts.
RECENT PUBLICATIONS:
Ripple MO, Henry WF, Schwarze SR, Wilding G, Weindruch R. Effect of
antioxidants on androgen-induced AP-1 and NF-KB DNA-binding activity
in
prostate carcinoma cells. JNCI 1999;91(14):1227-1232.
Ripple MO, Henry WF, Rago RP, Wilding G. Prooxidant-antioxidant shift
induced by androgen treatment of human prostate carcinoma cells. JNCI
1997;89(1):40-48.
Wade Bushman, MD, PhD
Associate Professor
600 Highland Ave G5/350
Madison WI 53792
bushman@surgery.wisc.edu
Specializes in female urology, pelvic floor and bladder dysfunction,
neurourology, and urodynamics. Dr. Bushman treats both men and women
with bladder problems including overactive bladder, urinary incontinence,
and neurogenic bladder dysfunction. Detailed information regarding options
for evaluation and treatment can be found on the Bladder
Clinic website. Dr. Bushman also treats patients with pelvic floor
dysfunction. The pelvic floor is made of up muscles and ligaments that
support the pelvic organs. Many women and some men experience problems
related to the pelvic floor – including pain, urinary and/or fecal
incontinence, difficulty with urinary or fecal evacuation, and pelvic
organ prolapse. The Multidisciplinary Pelvic Floor Center is a collaborative
effort of specialists in Urology, Gynecology, Colo-rectal Surgery, and
Physical Therapy to provide coordinated evaluation and treatment of
complex pelvic floor problems.
Dr. Bushman's research interests include clinical research in bladder
and pelvic floor dysfunction and basic research in prostate development
and prostate cancer. Visit
Dr. Bushman's lab website for more information about what he is
currently working on.
Hirak S. Basu, PhD
Associate Scientist
University of Wisconsin Comprehensive Cancer Center
600 Highland Avenue
Madison , WI 53792-5669
Human prostate tumors show an enhanced level of oxidative stress, which is a major player in prostate carcinogenesis. Dr. Basu focuses on identifying the biochemical pathway that generates oxidative stress specifically in prostate cells. He is developing novel prostate targeted agents that specifically inhibit this pathway and reduce oxidative stress in the prostate. These prostate directed anti-oxidants are currently being evaluated in preclinical animal models for clinical use as an adjuvant in the treatment of early and late stage prostate cancer. He is also investigating the role of chromatin structure in regulating this pathway and evaluating effect of anti-cancer agents that are known to alter chromatin structure on the oxidative stress in prostate tissue.
RECENT PUBLICATIONS:
Church DR, Lee E, Thompson TA, Basu HS, Ripple MO, Ariazi EA, Wilding G. Induction of AP-1 activity by androgen activation of the androgen receptor in LNCaP human prostate carcinoma cells. Prostate 2005 63 (2):155-68.
Frydman B, Bhattacharya S, Sarkar A, Drandarov K, Chesnov S, Guggisberg A, Popaj K, Sergeyev S, Yurdakul A, Hesse M, Basu HS, Marton LJ. Macrocyclic polyamines deplete cellular ATP levels and inhibit cell growth in human prostate cancer cells. J Med Chem 2004 47 (4):1051-9.
Frydman B, Blokhin AV, Brummel S, Wilding G, Maxuitenko Y, Sarkar A, Bhattacharya S, Church D, Reddy VK, Kink JA, Marton LJ, Valasinas A, Basu HS. Cyclopropane-containing polyamine analogues are efficient growth inhibitors of a human prostate tumor xenograft in nude mice. J Med Chem 2003 46 (21):4586-600.
Valasinas A, Reddy VK, Blokhin AV, Basu HS, Bhattacharya S, Sarkar A, Marton LJ, Frydman B. Long-chain polyamines (oligoamines) exhibit strong cytotoxicities against human prostate cancer cells. Bioorg Med Chem 2003 11 (18):4121-31.
Frydman B, Porter CW, Maxuitenko Y, Sarkar A, Bhattacharya S, Valasinas A, Reddy VK, Kisiel N, Marton LJ, Basu HS. A novel polyamine analog (SL-11093) inhibits growth of human prostate tumor xenografts in nude mice. Cancer Chemother Pharmacol 2003 51 (6):488-92.
Andreas Friedl, MD
Assistant Professor of Pathology and Laboratory Medicine
afriedl@facstaff.wisc.edu
Glenn Liu, MD
Assistant Professor, Section of Medical Oncology
600 Highland Ave K6/534
Madison, WI 53792
gxl@medicine.wisc.edu
Dr. Liu joined the faculty at the University of Wisconsin in the Department of Medicine in July 2002. Dr. Liu received his BA in biotechnological engineering at Dartmouth College and completed his master's degree at Boston University. He then went on to medical school at Jefferson Medical College before moving to Wisconsin to complete both his Internal Medicine residency and Medical Oncology fellowship at the University of Wisconsin Hospital and Clinics. Dr. Liu specializes in the treatment of genitourinary cancers as well as drug development (Phase I trials), with a particular interest in angiogenesis inhibition and the use imaging to assess early pharmacodynamic response towards novel compounds. Dr. Liu is a member of the Eastern Cooperative Oncology Group (ECOG) Genitourinary Oncology Committee and serves as the Genitourinary Oncology Liaison for the ECOG Developmental Therapeutics Committee for which he is also a member. In addition, he currently is the Genitourinary Oncology Disease Group Leader for a NCI-designated Phase 2 Consortium (Mayo/JHU/UW/UCSF/Wayne/Howard). Dr. Liu is active in clinical research in all phases of development and currently serves as the principle investigator for a number of local, regional, and national trials.
RECENT PUBLICATIONS:
Liu G, Oettel K, Bailey H, VanUmmersen L, Tutsch KD, Staab MJ, Horvath D, Alberti D, Arzoomanian R, Rezazadeh H, McGovern T, Robinson E, Demets D, Wilding G. Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer. Investigational New Drugs 21:367-372, 2003.
Liu G, Wilding G, Staab MJ, Horvath D, Miller K, Dresen A, Alberti D, Arzoomanian R, Chappell R, Bailey HH. Phase II Study of 1 a -Hydroxyvitamin D 2 (1 a -OH-D 2 ) in the Treatment of Advanced Androgen Independent Prostate Cancer. Clin Cancer Res 9(11):4077-4083, 2003.
Liu G, Kantoff P, Oh W, Gandara D, Lara P, Raghavan D, Doroshow JH, Twardowski P, Kim KM, Wilding G. A Phase II Trial of Flavopiridol (NSC# 649890) in Patients with Previously Untreated Metastatic Androgen Independent Prostate Cancer. Clin Cancer Res 10:924-928, 2004.
Liu G, Rugo HS, Wilding G, McShane TM, Evelhoch JL, Ng C, Jackson E, Kelcz F, Yeh BM, Lee FT, Charnsangavej C, Park JW, Ashton EA, Steinfeldt HM, Pithavala YK, Reich SD, Herbst RS. Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Pharmacodynamic Measure of Response After Acute Dosing of AG-013736, an Oral Angiogenesis Inhibitor, in Patients With Advanced Solid Tumors: Results From a Phase I Study. J Clin Oncol 23(24):5464-73, 2005.
Rugo HS, Herbst RS, Liu G, Park JW, Kies MS, Steinfeldt HM, Pithavala YK, Reich SD , Freddo JL, Wilding G. Phase I Trial of the Oral Anti-angiogenesis Agent AG-013736 in Patients with Advanced Solid Tumors – Pharmacokinetic and Clinical Results. J Clin Oncol 23(24):5474-83, 2005.
Sweeney C, Liu G, Yiannoutsos C, Kolesar J, Horvath D, Staab MJ, Fife K, Armstrong V, Treston A, Sidor C, Wilding G. A Phase II Multicenter, Randomized, Double-Blind, Safety Trial Assessing the Pharmacokinetics, Pharmacodynamics and Efficacy of Oral 2-Methoxyestradiol Capsules in Hormone Refractory Prostate Cancer. Clin Cancer Res 11(18):6625-33, 2005.
Douglas G. McNeel, MD, PhD
Assistant Professor of Medicine
600 Highland Ave. K4/518 CSC
Madison, WI 53792
Phone: (608) 263-4198
Fax: (608) 265-8133
dm3@medicine.wisc.edu
Dr. McNeel joined the faculty at the University of Wisconsin as an Assistant Professor in the Department of Medicine in July 2001. He is a member of the Experimental Therapeutics and Immunology and Immunotherapeutics groups within the UW Comprehensive Cancer Center, where his clinical and laboratory interests focus on the treatment of prostate cancer. Dr. McNeel received his BA in Chemistry and Music at Whitman College in 1986. He then pursued graduate training under a Medical Scientist Training Award at the University of Chicago, and received his PhD (Biochemistry and Molecular Biology) in 1992 and MD in 1994. His PhD studies were in the laboratory of Fuyuhiko Tamanoi, PhD. He completed an Internal Medicine residency at the University of Washington on a Clinical Investigator Pathway and a Medical Oncology fellowship at the University of Washington and Fred Hutchinson Cancer Research Center in 2000. After his clinical fellowship, he joined the Tumor Vaccine Group at the University of Washington in the laboratory of Mary (Nora) Disis, MD for four years as a postdoctoral fellow and junior faculty member, studying the immunology of human prostate cancer. At the University of Wisconsin, Dr. McNeel continues to focus on the immunology of prostate cancer with the goal of developing tumor vaccines for prostate cancer. His laboratory is focused on the identification of proteins that could be the targets for prostate cancer vaccines, testing vaccines in the laboratory, and translating these findings to human clinical trials.
RECENT PUBLICATIONS:
Hoeppner LH, Dubovsky JA, Dunphy EJ, McNeel DG. (2006) Humoral immune responses to testis antigens in sera from patients with prostate cancer. Cancer Immun. 6:1-7.
Johnson LE, Frye TP, Arnot AR , Marquette C, Couture LA, Gendron-Fitzpatrick A, McNeel DG . (2006) Safety and immunological efficacy of a prostate cancer plasmid DNA vaccine encoding prostatic acid phosphatase (PAP). Vaccine 24:293-303.
Zlotocha S, Staab MJ, Horvath D, Straus J, Dobratz J, Oliver K, Wasielewski S, Alberti D, Liu G, Wilding G, Eickhoff J, McNeel DG. (2005) A phase I study of a DNA vaccine targeting prostatic acid phosphatase (PAP) in patients with stage D0 prostate cancer. Clin. Genitourinary Cancer 4:215-218.
Dunphy EJ, McNeel DG. (2005) Antigen-specific IgG elicited in subjects with prostate cancer treated with flt3 ligand.J. Immunotherapy 28:268-275.
Dunphy EJ, Eickhoff JC, Muller CH, Berger RE, McNeel DG. (2004) Identification of antigen-specific IgG in sera from patients with chronic prostatitis. J. Clin. Immunol. 24:492-502.
Terry Oberley, MD, PhD
Professor of Pathology
600 Highland Ave K4/814
Madison WI 53792
toberley@facstaff.wisc.edu
Dr. Oberley's laboratory is studying the role of cell redox on growth of normal
and malignant prostate cancer epithelial cells. The approach is two-fold:
1) to determine the effects of alterations in cell redox on cell cycle progression by study of cells which overexpress proteins affecting cell
redox (antioxidant proteins)using gene transfection techniques, and 2) to determine cell redox state in vivo and in vitro using specific
antibodies to proteins regulated by redox state and specific antibodies to oxidative and nitrosative damage products. It is hoped that these
combined techniques will provide unique insights into differences in redox control of cell cycle in normal verusus malignant prostate epithelium.
RECENT PUBLICATIONS:
Zhong W, Oberley TD. Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line. Cancer
Res 2001;61:7071-7078.
Oberley TD. Oxidative damage and cancer. Am J Pathol 2002;160:403-408.
Richard Peterson, PhD
Professor of Pharmcology & Toxicology
Pharmaceutical Sciences Division
School of Pharmacy
777 Highland Ave Rm 5109 53705-2222
repeterson@pharmacy.wisc.edu
Prostate development is exceptionally sensitive to the ubiquitous
environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Major objectives of our research are to elucidate the mechanisms responsible
for TCDD-induced abnormalities in mouse prostate development and to
determine the life-long consequences of in utero and lactational TCDD
exposure on prostate health in the mouse.
The nature and severity of the effects of in utero and lactational
TCDD exposure vary from one prostate lobe to another, with the greatest
effects on the ventral prostate. Abnormalities in early prostate development
are due largely to effects of TCDD on the number, position, and size
of the prostatic epithelial buds that develop from urogenital sinus
(UGS) and ultimately develop into the various prostate lobes. A single
maternal TCDD dose delays the appearance of dorsal, lateral, and anterior
buds by about one day, reduces dorsolateral bud number, changes the
position of dorsal and lateral buds, and prevents ventral buds from
forming. These effects are mediated by aryl hydrocarbon receptors (AhR)
in UGS mesenchyme but not UGS epithelium, and do not appear to be due
to effects on androgen signaling. A variety of approaches are being
used to identify the genes whose altered regulation causes the region-specific
effects of TCDD on UGS and ultimately prostate development.
In utero and lactational TCDD exposure also increases the incidence
of precancerous lesions in the dorsolateral prostate of senescence mice,
while the AhR itself appears to be a tumor suppressor in the prostate.
We our conducting research to elucidate the biochemical basis for effects
of the AhR signaling pathway on prostate cancer, and are beginning the
in vivo testing of selective AhR agonists as a possible new therapeutic
strategy for treating this disease.
RECENT PUBLICATIONS:
Peterson Lab Urogenital Sinus & Prostate Development Publications
Mably TA, Moore RW, Peterson RE (1992). In utero and lactational exposure
of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin. 1. Effects on androgenic
status. Toxicol. Appl. Pharmacol. 114, 97-107.
Bjerke DL, Peterson RE (1994). Reproductive toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin
in male rats: different effects of in utero versus lactational exposure.
Toxicol. Appl. Pharmacol. 127, 241-249.
Bjerke DL, Sommer RJ, Moore RW, Peterson RE (1994). Effects of in
utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on
responsiveness of the male rat reproductive system to testosterone stimulation
in adulthood. Toxicol. Appl. Pharmacol. 127, 250-257.
Roman BL, Sommer RJ, Shinomiya K, Peterson RE (1995). In utero and
lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p-dioxin:
impaired prostate growth and development without inhibited androgen
production. Toxicol. Appl. Pharmacol. 134, 241-250.
Theobald HM, Peterson RE (1997). In utero and lactational exposure
to 2,3,7,8-tetrachlorodibenzo-p-dioxin: effects on development of the
male and female reproductive system of the mouse. Toxicol. Appl. Pharmacol.
145, 124-135.
Roman BL, Pollenz RS, Peterson RE (1998). Responsiveness of the adult
male rat reproductive tract to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure:
Ah receptor and ARNT expression, CYP1A1 induction, and Ah receptor down-regulation.
Toxicol. Appl. Pharmacol. 150, 228-239.
Roman BL, Peterson RE (1998). In utero and lactational exposure of
the male rat to 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs prostate
development. 1. Effects on gene expression. Toxicol. Appl. Pharmacol. 150, 240-253.
Roman BL, Timms BG, Prins GS, Peterson RE (1998). In utero and lactational
exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs
prostate development. 2. Effects on growth and cytodifferentiation.
Toxicol. Appl. Pharmacol. 150, 254-270.
Loeffler IK, Peterson RE (1999). Interactive effects of TCDD and p,p'-DDE
on male reproductive tract development in in utero and lactationally
exposed rats. Toxicol. Appl. Pharmacol. 154, 28-39.
Sommer RJ, Sojka KM, Pollenz RS, Cooke PS, Peterson RE (1999). Ah
receptor and ARNT protein and mRNA concentrations in rat prostate: effects
of stage of development and 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment.
Toxicol. Appl. Pharmacol. 155, 177-189.
Theobald HM, Roman BL, Lin T-M, Ohtani S, Chen SW, Peterson RE (2000).
2,3,7,8-tetrachlorodibenzo-p-dioxin inhibits luminal cell differentiation
and androgen responsiveness of the ventral prostate without inhibiting
prostatic 5a-dihydrotestosterone formation or testicular androgen production
in rat offspring. Toxicol. Sci. 58, 324-338.
Theobald HM, Lin T-M, Peterson RE (2000). In utero and lactational
exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin decreases
androgen responsiveness of the dorsolateral prostate without inhibiting
dihydrotestosterone formation. Organohalogen Compd. 49, 359-362.
Moore RW, Rudy TA, Lin T-M, Ko K, Peterson RE (2001). Abnormalities
of sexual development in male rats with in utero and lactational exposure
to the antiandrogenic plasticizer di(2-ethylhexyl) phthalate. Environ.
Health Perspect. 109, 229-237.
Lin T-M, Simanainen U, Rasmussen NT, Ko K, Peterson RE (2001). In
utero and lactational TCDD exposure in the mouse: impaired prostate
development and function. Organohalogen Compd. 53, 291-294.
Timms BG, Peterson RE, vom Saal FS (2002). 2,3,7,8-Tetrachlorodibenzo-p-dioxin
interacts with endogenous estradiol to disrupt prostate gland morphogenesis
in male rat fetuses. Toxicol. Sci. 67, 264-274.
Lin T-M, Ko K, Moore RW, Simanainen U, Oberley TD, Peterson RE (2002).
Effects of aryl hydrocarbon receptor null mutation and in utero and
lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on prostate
and seminal vesicle development in C57BL/6 mice. Toxicol. Sci. 68, 479-487.
Lin T-M, Simanainen U, Moore RW, Peterson RE (2002). Critical windows
of vulnerability for effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin
on prostate and seminal vesicle development in C57BL/6 mice. Toxicol.
Sci. 69, 202-209.
Ko K, Theobald HM, Peterson RE (2002). In utero and lactational exposure
to 2,3,7,8-tetrachlorodibenzo-p-dioxin in the C57BL/6J mouse prostate:
lobe-specific effects on branching morphogenesis. Toxicol. Sci. 70,
227-237.
Theobald HM, Kimmel GL, Peterson RE (2003). Developmental and reproductive
toxicity of dioxins and related chemicals. In: Dioxins and Health, 2nd
Edition. A Schecter and TA Gasiewicz, Eds., pp. 329-431. John Wiley
and Sons, Hoboken, NJ.
Lin T-M, Rasmussen NT, Moore RW, Albrecht RM, Peterson RE (2003).
Region-specific inhibition of prostatic epithelial bud formation in
the urogenital sinus of C57BL/6 mice exposed in utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
Toxicol. Sci. 76, 171-181.
Abbott BD, Lin T-M, Rasmussen NT, Albrecht RM, Schmid JE, Peterson
RE (2003). Lack of expression of EGF and TGF-a in the fetal mouse alters
formation of prostatic epithelial buds and influences the response to
TCDD. Toxicol. Sci. 76, 427-436.
Ko K, Moore RW, Peterson RE (2004). Aryl hydrocarbon receptors in
urogenital sinus mesenchyme mediate the inhibition of prostatic epithelial
bud formation by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Appl.
Pharmacol. 196, 149-155.
Lin T-M, Rasmussen NT, Moore RW, Albrecht RM, Peterson RE (2004).
2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits prostatic epithelial bud
formation by acting directly on the urogenital sinus. J. Urol. (in press).
Ko K, Theobald HM, Moore RW, Peterson RE (2004). Evidence that inhibited
prostatic epithelial bud formation in 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed
C57BL/6J fetal mice is not due to interruption of androgen signaling
in the urogenital sinus. Toxicol. Sci. (in press).
Simanainen U, Haavisto T, Tuomisto JT, Paranko J, Toppari J, Tuomisto
J, Peterson RE, Viluksela M (2004). Pattern of male reproductive system
effects after in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD) exposure in three differentially TCDD-sensitive rat lines. Toxicol.
Sci. (in press).
John Svaren, PhD
Assistant Professor of the Dept of Comparitive Biosciences
School of Veterinary Medicine
2015 Linden Dr. Rm3174
Madison WI, 53706
jpsvaren@facstaff.wisc.edu
Weixiong Zhong, MD
Assistant Professor of Pathology and Laboratory Medicine
600 Highland Ave K4/868
Madison WI, 53792
wzhong3@facstaff.wisc.edu
Dr. Zhong's laboratory is studying redox effects of selenium in prostate cancer chemoprevention. Current studies are focused on: 1) to determine whether slenium has differential redox effects in normal prostate epithelial cells, immortalized epithelial cells, and cancer cells by analyses of cellular antioxidant status, production of reactive oxygen species (ROS), oxidative stress, cell growth inhibition, and apoptosis following s e lenium treatment ; 2) to determine whether superoxide radical plays a major role in redox effects of selenium on p53 activation, cell growth inhibition, and apoptosis and whether mitochondria are the primary targets or pathways for cell apoptosis ; 3) to determine the role of p53 and Bax and p21(Waf1) in selenium -induced superoxide production, apoptosis, and cell cycle arrest using gene transfection and RNA interference techologies to increase or decrease p53, Bax, and p21(Waf1) ; and 4) to validate the in vitro effects of selenium reflect its in vivo effects using tumor xenergrafts in athymic nude mice.
RECENT PUBLICATIONS:
Li N, Oberley TD, Oberley LW, Zhong W. Overexpression of manganese superoxide dismutase in DU145 human prostate carcinoma cells has multiple effects on cell phenotype. Prostate 35:221 - 233, 1998.
Li N, Oberley TD, Oberley LW, Zhong W. Inhibition of cell growth in NIH3T3 fibroblasts by overexpression of manganese superoxide dismutase: Mechanistic studies. J Cell Physiol 175:359 - 369, 1998.
Bostwick DG, Alexander EE, Singh R, Shan A, Qian J, Sabtella RM, Oberley LW, Yan T, Zhong W, Jiang X, Oberley TD. Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer. Cancer 89: 123–134, 2000.
Oberley TD, Verwiebe E, Zhong W, Kang SW, Rhee SG. Localization of the thioredoxin system in normal rat kidney. Free Radic Biol Med 30:412–424, 2001.
Zhong W, Oberley TD. Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cells. Cancer Res 61:7071–7078, 2001.
Plymate SR, Haugk KH, Sprenger CC, Nelson PS, Tennant MK, Zhang Y, Oberley LW, Zhong W, Drivdahl R, Oberley TD. Increased manganese superoxide dismutase (SOD-2) is part of the mechanism for prostate tumor suppression by Mac25/insulin-like growth factor binding-protein-related protein 1. Oncogene 22:1024–1034, 2003.
Zhong W, Yan T, Webber MM, Oberley TD. Alteration of cellular phenotype and responses to oxidative stress by manganese superoxide dismutase and a superoxide dismutase mimic in RWPE-2 human prostate adenocarcinoma cells. Antioxid Redox Signal 6:513-522, 2004.
Zha o R , Xian g N, Doman n FE, Zhong W. Expression of p53 Enhances Selenite-Induced Superoxide Production and Apoptosis in Human Prostate Cancer Cells. Cancer Res (in press) 2006.
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