The insulin-like growth factor (IGF) axis is a molecular pathway intensively investigated in cancer research. Clinical trials targeting the IGF1 receptor (IGF1R) in different tumors, including prostate cancer, are under way. Although studies on the IGF axis in prostate cancer have already entered into clinical trials, the expression and functional role of the IGF axis in benign prostate and in prostate cancer needs to be better defined. We determined mRNA expression levels of the IGF axis in microdissected tissue specimens of local prostate cancer using quantitative PCR. All members of the IGF axis, including IGF1, IGF2, IGF binding proteins 1 through 6, and insulin receptor, were measured in both the stromal and epithelial compartments of the prostate. IGF1, IGF2, IGF1R, and insulin receptor were down-regulated in local prostate cancer tissue compared with matched benign tissue, suggesting that the IGF axis is not induced during prostate cancer development. Using a new prostate epithelial differentiation model, we demonstrate that the expression of the IGF axis is enhanced during normal prostate epithelial differentiation and regulated by tumor growth factor (TGF)-. Our data reveal a functional role of the IGF axis in prostate differentiation, underscoring the importance of the IGF axis in normal development and emphasizing the importance of accurate target validation before moving to advanced clinical trials.
INTRODUCTION AND OBJECTIVES: Chlamydia trachomatis (CT) is one of the pathogens of sexually transmitted diseases and is widely spread particularly among young generations. As is well known, considerable number of men with CT infection are asymptomatic, so that men who have infection chances with CT-positive women have to be screened for possible infection of CT, even if they are free from any symptoms suggesting urethritis. The present study was conducted to characterize CT infection in asymptomatic male partners of CT-positive female patients and additionally to reveal predictive factors for possible CT infection in Japan.METHODS: A total number of 612 male patients (16 -60 years old, mean 30.7 years), who had CT-positive heterosexual partners, visited our clinic. None of them had any symptoms suggesting CT infection including urethritis. When urinalysis on the first voided urine sediments revealed 5 or more leucocytes/hpf, patients were diagnosed as having pyuria. CT was examined using PCR (Amplicore STD1) in the first voided urine. Results of PCR for CT were compared with clinical parameters including urinalysis.RESULTS: In 211 (34%) out of 612 patients, urine samples were positive for CT. Patients with CT infection were significantly younger than those without CT infection (29.3 vs 31.4 years old, pϽ0.005). The positive rates for CT decreased with increasing age, and were 52% (12/23), 39% (112/284), 29% (63/215) and 26% (24/90) in patients aged less than 19, 20 -29, 30 -39 and more than 40 years, respectively. More importantly, CT infection depended on the results of urinalysis. The majority of patients with pyuria (107/119, 90%) had CT infection, while only 21% (104/493) of those without pyuria was positive for CT (pϽ0.0001).CONCLUSIONS: Male patients who had CT-positive heterosexual partners are likely suffered from urethral infection of CT with high probability (90%) when they had pyuria. In dealing with male partners of CT-positive female, curative treatments for CT should be readily performed before microbiological confirmation when pyuria is recognized.
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