These findings demonstrate that PSMA is widely distributed in normal tissues, and, depending on the tumors, its expression is up- or down-regulated, or unchanged. The broad distribution of PSMA may make it suitable for the diagnosis and therapy of a wide variety of tumors.
A variety of carcinogenic heterocyclic amines are produced during the cooking of meat at high temperatures. These carcinogens are metabolized by Nacetyltransferases (NAT), which are polymorphic in the population. This study examined associations between prostate cancer (PCa) and the consumption of different kinds of meat, heterocyclic amine intake and NAT genotypes. PCa patients and controls were recruited in the Syracuse, NY area. Levels of meat and heterocyclic amine intakes were determined from validated surveys and NAT genotypes were determined by the sequences of PCR-amplified DNA from buccal swabs. A total of 152 cases and 161 controls were eligible for analysis. There was an association between PCa and history of PCa in the first-degree blood relatives (OR ¼ 4.59, 95% CI 2.21-9.70), and family history of bladder cancer (Po0.02). However, there was no association with the history of other cancers. There was no association between PCa and either 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) intake, or NAT1 and NAT2 genotypes. However, there was a trend of association with MeIQx and with rapid NAT2 and NAT1 * 10 in combination with PhIP. A new NAT1 allele with a frequency of one out of 544 chromosomes was found in the Caucasian subjects.
Patients with PCa have higher incidence of bladder cancer and those with bladder cancer have a higher incidence of PCa. This study has clinical implications in the care of these patients and it may stimulate research interest that may identify common pathways of carcinogenesis.
Prostate-specific membrane antigen (PSMA) is a target for immunotherapy of prostate cancer. It has been shown that antibodies against PSMA inhibited the in vivo growth of LNCaP tumor. In the present study, monoclonal antibodies against four epitopes in PSMA were raised. MAb 24.4E6 (IgG1), specific for the epitope (residues 638-657) in PSMA, significantly reduced the growth rate of established LNCaP tumor in SCID mice. Mouse IgG was detected in the tumor of mice treated with 24.4E6, but not with an unrelated MAb. These results suggest that this epitope may be the main target in PSMA for antibody therapy of prostate cancer.
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