Prognostic Impact of Genetic Polymorphism in Mineralocorticoid Receptor and Comorbidity With Hypertension in Androgen-Deprivation Therapy

Mineralocorticoid receptor (MR) signaling which is closely associated with hypertension plays important roles in resistance to antiandrogen therapy in prostate cancer. However, its impact on the prognosis in androgen-deprivation therapy (ADT) has not been elucidated. Then, we investigated the impact of genetic variation in MR and comorbidity with hypertension on the prognosis in ADT. This study included 182 Japanese patients with prostate cancer treated with ADT, whose comorbidity status with hypertension were available. The associations of MR polymorphism (rs5522) and comorbidity with hypertension with clinicopathological parameters as well as progression-free survival and overall survival were examined. Clinicopathological characteristics were comparable between genetic variation in MR. However, homozygous variant in MR was associated with shorter time to castration resistance (P = 0.014) and any-cause death (P = 0.024). In patients' background, presence of comorbidity with hypertension showed the trend with lower PSA level at diagnosis and lower biopsy Gleason score, as well as significant association with less incidence of N1. Comorbidity with hypertension was associated with longer time to castration resistance (P = 0.043) and any-cause death (P = 0.046), which was diminished on multivariate analysis including age, PSA level at diagnosis, biopsy Gleason score, clinical stage, and the modality of hormonal therapy. Genetic variation in MR (rs5522) and comorbidity with hypertension were significantly and potentially associated with prognosis when treated with ADT, respectively. This suggests that the individual intensity of MR signaling may be associated with resistance to ADT and a promising biomarker in ADT

Water and 2‑Propanol Structured on Calcite (104) Probed by Frequency-Modulation Atomic Force Microscopy

The structure of liquid water and 2-propanol on the (104) surface of calcite (CaCO₃) was probed by frequency-modulation atomic force microscopy. The microscope tip scanned each liquid to record the tip–surface force perturbed by the liquid structure at the interface. In water, the force distribution on planes cross-sectional to the surface presents a 0.5-nm-thick checkerboard-like pattern matching the corrugated topography of the calcite surface. This provides evidence that the local water density was laterally and vertically modulated. With 2-propanol, a laterally uniform, vertically layered structure was found between the first laterally structured layer and the bulk liquid. These results are consistent with the density distributions of water and ethanol proposed in earlier X-ray and simulation studies

Neoadjuvant androgen-deprivation therapy with radical prostatectomy for prostate cancer in association with age and serum testosterone

Background: We aimed to identify the candidate prostate cancer patients suitable for neoadjuvant androgen-deprivation therapy (ADT) with radical prostatectomy (RP). Materials and methods: This study included 711 Japanese patients with clinically localized prostate cancer who were treated with RP between 2000 and 2013. Patients were treated with or without neoadjuvant ADT before RP. The prognostic significance of neoadjuvant ADT on biochemical recurrence (BCR) was analyzed according to various clinicopathological characteristics. Results: BCR occurred in 186 (26.2%) of 711 patients. The group treated with neoadjuvant ADT showed higher levels of prostate-specific antigen at diagnosis and advanced clinical T-stage, but suppressed pathological T-stage. Neoadjuvant ADT was not associated with the risk of BCR. In subgroup analysis, neoadjuvant ADT was significantly associated with increased BCR in patients aged >65 years [hazard ratio (95% confidence interval), 2.04 (1.13–3.43), P = 0.020]. Among the 53 patients with available serum testosterone levels, neoadjuvant ADT was associated with the risk of BCR according to serum testosterone levels. Conclusion: This study demonstrated that neoadjuvant ADT showed potential deleterious effects in older patients and patients with lower serum testosterone levels, while a possible improved prognosis in patients with high serum testosterone levels treated with neoadjuvant ADT was suggested, warranting further exploration. Keywords: Age, Neoadjuvant androgen-deprivation therapy, Prostate cancer, Radical prostatectomy, Testosteron

Paternally Expressed Gene 10 (PEG10) Promotes Growth, Invasion and Survival of Bladder Cancer.

Paternally Expressed Gene 10 (PEG10) has been associated with neuroendocrine (NE)-muscle-invasive bladder cancer (MIBC), a subtype of the disease with the poorest survival. In this work, we further characterized the expression pattern of PEG10 in TCGA database of 412 MIBC pateints, and found that, compared to other subtypes, PEG10 mRNA level was enhanced in NE-like MIBC and highly correlats with other NE markers. PEG10 protein level also associated with NE markers in a tissue microarray (TMA) of 82 cases. In bladder cancer cell lines, PEG10 expression was induced in drug-resistant compared to parental cells, and knocking-down of PEG10 re-sensitized cells to chemotherapy. Loss of PEG10 increased protein levels of cell cycle regulators p21 and p27 and delayed G1/S transition, while over-expression of PEG10 enhanced cancer cell proliferation. PEG10 silencing also lowered levels of SLUG and SNAIL, leading to reduced invasion and migration. In an orthotopic bladder cancer model, systemic treatment with PEG10 antisense oligonucleotide delayed progression of T24 xenografts. In summary, elevated expression of PEG10 in MIBC may contribute to the disease progression by promoting survival, proliferation and metastasis. Targeting PEG10 is a novel potential therapeutic approach for a subset of bladder cancers