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    • The investigated functional imaging technique has great pote

    2018-11-05

    The investigated functional imaging technique has great potentials. Diffusion-weighted MRI may provide an aid to establish the aggressiveness of prostate cancer and help predict those tumors most likely to progress rapidly. Prostate biopsies frequently underestimate the ‘true’ Gleason score of tumors found with transrectal ultrasound compared to radical prostatectomy (ranging from 30 to 50%, depending on initial Gleason score) (). This high-resolution technique may further improve lesion characterization and ultimately be used to perform MRI diffusion-weighted imaging-targeted biopsy.
    Androgen deprivation therapy (ADT) of androgen-dependent prostate cancer (PCa), which is still the gold standard treatment, was based Huggins and Hodges\' 1941 finding that the growth of PCa neurokinin 1 receptor requires the androgen, testosterone (). In addition, an increasing body of evidence has revealed that the development and progression of androgen-dependent PCa to castration-resistant prostate cancer (CRPC) have an intimate association with the androgen–androgen receptor axis (AR axis) (). The application of AR axis drugs, such as the 5α-reductase inhibitors (5ARI), finasteride and dutasteride, which decrease levels of dihydrotestosterone (DHT) in order to prevent development or progression of PCa, remains to be extensively discussed and is controversial (). The concept is driven by the results of two large, randomized, placebo-controlled trials: the Prostate Cancer Prevention Trial (PCPT) with finasteride () and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial (). In the PCPT, finasteride significantly reduced the overall risk of prostate cancer but cancers with high Gleason scores (7–10) were found in 6.4% of the tumors in the finasteride group, compared with only 5.1% of those being found in the placebo group. In a manner analogous to the PCPT trial, the REDUCE trial reported an overall reduction in the number of PCa patients (with a low Gleason score of 5–6) in those receiving dutasteride versus those given a placebo (19.9% and 25.1%, respectively); similarly, tumors with a high Gleason score (8–10) were more frequent in the dutasteride-treated group than in the placebo group. In the Reduction by Dutasteride of Clinical Progression Events in Expectant Management (REDEEM) trial, dutasteride was associated with a 38% decrease in the cancer detection rate on repeat biopsy at year 3 in men with low-grade Gleason score (5–6) prostate cancer undergoing active surveillance and who received three years of treatment with dutasteride or placebo (). Because of concerns regarding the possible induction of aggressive PCa, the US Food and Drug Administration did not grant approval of 5ARIs for the chemoprevention of PCa in December 2010 (). However, it is still unclear whether the observed increase in high-grade CaP in these trials was real or artifact (). These observations cannot be fully explained from a purely mechanistic point of view. Therefore, further basic and clinical investigations are necessary (). In this issue of , Kim et al. seek to improve biologic understanding of the grade-specific effects of the 5ARI, finasteride, by studying 183 men with localized prostate cancer, who were randomized to receive 5mg of finasteride or placebo daily for 4 to 6weeks pre-prostatectomy (). In fact, this is one of the few studies done in early prostate cancer to investigate the time it takes for changes in gene expression to occur following finasteride therapy. The primary end point was to compare the frequency of expression of a predefined high-grade molecular signature (ERβ, UBE2C, SRD5A2, and VEGF) differentiating high- and low-grade tumors in the Gleason grade (GG) 3 areas of finasteride-exposed tumors with those of placebo-exposed tumors, adjusted for Gleason score (GS) at prostatectomy. Secondary endpoints included assessment of androgen receptor (AR) levels, Ki-67, and cleaved caspase 3 to estimate the effects of finasteride on the expression of its downstream targets, cell proliferation, and apoptosis, respectively. Unfortunately, the primary endpoint could not be assessed as the predetermined molecular signature was not able to distinguish GG3 from GG4 areas in the placebo group.