Browsing by Author "Troyer, Dean A."
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Item Nonhuman Primates as Models for Studies of Prostate Specific Antigen and Prostatic Diseases(The Prostate, 2008) Mubiru, James N.; Hubbard, Gene B.; Dick, Edward J.; Furman, Jaime; Troyer, Dean A.; Rogers, JeffreyBecause prostate specific antigen (PSA) is released at increased levels into the blood early in the development of prostate cancer, benign prostatic hyperplasia (BPH) and prostatitis, it is widely used as a marker for these diseases. However, PSAhas clinical limitations as a screen for prostatic diseases due to its low sensitivity and specificity. There is a strong need to better understand the biology of PSA and factors affecting its serum levels. METHODS. Weevaluated cynomolgus macaques, rhesus macaques, baboons, and marmosets for their suitability as models for the study of PSA biology and prostatic diseases. RESULTS. Prostates of several nonhuman primates are anatomically similar to the human counterpart. Anti-human PSA antibody detected PSA antigens in all the Old World monkeys (cynomolgus macaques, rhesus macaques, and baboons) but not in marmosets. Of the Old World monkeys, cynomolgus macaques have the highest serum PSA levels; baboons have the lowest. Serum PSA levels from macaques includes a number of outlier samples with unusually high values. We also report two cases of abnormal pathologies in macaques accompanied by high serum PSA levels. One case consisted of prostatic hyperplasia involving both glandular and basal cells in a cynomolgus macaque and another of glandular hyperplasia and atrophy in a rhesus macaque. The finding that pathological changes in the prostate of macaques may lead to increases in serum PSA is worthy of further exploration. CONCLUSION. Cynomolgus macaques and rhesus macaques are promising animal models for PSA biology studies.Item A Preliminary Study of the Baboon Prostate Pathophysiology(The Prostate, 2007) Mubiru, James N.; Hubbard, Gene B.; Dick Jr., Edward J.; Butler, Stephanie D.; Valente, Anthony J.; Troyer, Dean A.; Rogers, JeffreyProstate cancer, benign prostatic hyperplasia, and prostatitis frequently affect men worldwide. At present there are no suitable animal models for these diseases. This study explores the potential use of the baboon as a model for prostatic diseases. METHODS. Prostates of 48 baboons of different ages were studied. Prostate specific antigen (PSA) and alpha-methyl-acyl-CoA racemase (AMACR) were localized in the different lobes of the prostate by Western blotting and immunohistochemistry. PSA in baboon serum was demonstrated by radioimmunoassay and western blotting. BaboonAMACRcDNA was cloned and its expression assayed in baboon tissues. RESULTS. The baboon prostate is anatomically and histologically similar to its human counterpart, with cranial and caudal lobes corresponding to central and peripheral zones of the human prostate. We found lymphocytic infiltration (91%), and sclerosing/atrophic lesions (34%). PSA tissue immunostaining intensity and alpha-methyl-acyl-CoA racemase (AMACR) gene expression levels differed between the cranial and caudal lobes of the prostate. The cloned baboon AMACR cDNA showed 96% homology with its human counterpart. Anti-human AMACR, PSA and basal keratin antibodies stained intracellular and basement membrane structures in the baboon prostate. The sclerosing/atrophic lesions were comparable to their human counterparts. CONCLUSIONS. The similarity of baboon prostate to its human counterpart and the fact that human antibodies (AMACR, PSA, basal keratin) are reactive to baboon prostatic proteins indicates that the baboon is a promising model for human prostatic diseases.