The Prostate
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3β-hydroxysteroid dehydrogenase type 1 (3βHSD1), which is a rate-limiting enzyme that catalyzes the conversion of adrenal-derived steroid dehydroepiandrosterone to dihydrotestosterone (DHT), may be a promising target for treating castration-resistant prostate cancer (CRPC). ⋯ Prostate cancer patients who harbored the heterozygous variant HSD3B1 (1245C) are more likely to develop to CRPC, but do not have shorter time to biochemical recurrence, shorter survival time or higher mortality risk.
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The pathogenesis of chronic prostatitis/chronic pelvic pain syndrome is unknown and factors including the host's immune response and the nervous system have been attributed to the development of CP/CPPS. We previously demonstrated that mast cells and chemokines such as CCL2 and CCL3 play an important role in mediating prostatitis. Here, we examined the role of neuroinflammation and microglia in the CNS in the development of chronic pelvic pain. ⋯ Our data show that prostatitis leads to inflammation in the spinal cord and the activation and expansion of microglia, mechanisms that may contribute to the development and maintenance of chronic pelvic pain.
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Pain due to bone metastases of prostatic origin is a relevant clinical issue. We study here the nociceptive responses obtained in mice receiving the intratibial inoculation of RM1 prostate cancer cells. ⋯ The intratibial inoculation of RM1 cells in immunocompetent mice induces hypernociceptive responses and can be useful to perform studies of bone cancer induced pain related to androgen-independent prostate cancer. The antinociceptive role derived from the blockade of the CCR2 chemokine receptors is further envisaged.
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Two randomized clinical trials have demonstrated a survival advantage with enzalutamide over placebo in both docetaxel (D)-pretreated and D-naïve metastatic castration-resistant prostate cancer (mCRPC) patients. Cross-resistance between androgen receptor-directed therapies and taxanes has been suggested, possibly leading to lower efficacy of enzalutamide in the post-D setting. ⋯ The clinical activity of enzalutamide appears to be blunted in patients who have previously received docetaxel chemotherapy. These results support the concept of cross-resistance between these two agents.
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Questions about optimal sequencing of systemic therapy in metastatic castration-resistant prostate cancer (mCRPC) and whether cross-resistance occurs between different drugs remain largely unanswered. Previous studies have produced conflicting data on the activity of docetaxel in patients who did not attain a prostate-specific antigen (PSA) response to abiraterone acetate (abiraterone). We investigated whether the biochemical response to abiraterone is associated with efficacy of subsequent docetaxel therapy. ⋯ Activity of docetaxel was not associated with the biochemical response to prior abiraterone therapy. These data suggest that prior response to abiraterone should not influence decisions on subsequent use of docetaxel in mCRPC.