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Purpose
Currently, several therapeutic options for castration-resistant prostate cancer (CRPC) are available, for which predictive biomarkers have not been established. Therefore, we aimed to reveal the association between pretreatment serum testosterone level and antitumor outcomes when treated with androgen receptor axis-targeting agents and taxane chemotherapies for CRPC.Patients and methods
The present study included Japanese patients with metastatic prostate cancer whose serum testosterone levels during androgen-deprivation therapy were available. The antitumor outcomes when treated with enzalutamide, abiraterone, docetaxel, and cabazitaxel with clinicopathological parameters including serum testosterone levels during androgen-deprivation therapy, as well as prognoses including progression-free survival and overall survival, were examined.Results
Progression-free survival among men with higher serum testosterone level was superior to that among men with lower serum testosterone level when treated with enzalutamide. On the contrary, progression-free survival and overall survival among men with higher serum testosterone level were significantly inferior to those among men with lower serum testosterone level when treated with docetaxel and cabazitaxel, respectively.Conclusions
The present study indicated distinct prognostic values of serum testosterone level when treated with androgen receptor axis-targeting agent and taxane chemotherapy for CRPC, suggesting that serum testosterone level may be useful predictive biomarker to navigate the appropriate therapy in patients with CRPC. 相似文献Background
Despite facet joints being three-dimensional structures, previous computed tomography and magnetic resonance imaging studies have evaluated facet joint orientation in only the axial plane. Facet joint orientation in the sagittal plane has rarely been studied using these imaging techniques. The aim of this study was to elucidate facet joint orientation in both the axial and sagittal planes on computed tomography.Methods
A total of 568 patients (343 men, 225 women) (excluding orthopedic outpatients) for whom abdominal and pelvic computed tomography scans were obtained at our hospital between September 2010 and October 2012 were included. Mean age was 63 (range 21–90) years. Patients were divided into a degenerative spondylolisthesis group (67 patients; 30 men, 37 women) and a control group (313 patients; 313 men, 188 women). Facet joint orientation was evaluated in the control group according to patient age (≤50, 51–60, 61–70, or ≥71 years). The findings in the control group were then compared with those in the degenerative spondylolisthesis group. The orientation of the lumbar facet joints at each level was measured in the axial and sagittal planes on computed tomography images.Results
Facet joint angles decreased with age at L4/5 and L5/S1 in women in the axial plane and at L4/5 in men and L3/4 and L4/5 in women in the sagittal plane. The variation in facet joint angle was greatest at L4/5 in women. Patients with degenerative spondylolisthesis showed more sagittally and horizontally oriented facet joints in the axial and sagittal planes; facet tropism showed an association with degenerative spondylolisthesis in the axial plane.Conclusions
The axial and sagittal orientation of facet joints in the lower lumbar vertebra, especially L4/5, was negatively correlated with age. This finding could help to explain why older people are more prone to degenerative spondylolisthesis. 相似文献Methods: Hybrid cells containing a fragment of human chromosome 8 in scid cells (RD13B2) were used. DNA-PK activity was measured by an in vitro assay. Immunoprecipitation of the nuclear extract was performed with an anti-Ku80 antibody. Proteins co-precipitated with Ku80 were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and detected by Western blotting using anti-heat shock protein (HSP)72 and anti-heat shock cognate protein (HSC)73 antibodies. HSC73 was overexpressed with the pcDNA3.1 vector. Short hairpin (sh)RNA was used to downregulate HSC73 and HSP72.
Results: The activity of heat-inactivated DNA-PK recovered to about 50% of control during an additional incubation at 37?°C after heat treatment at 44?°C for 15?min in the presence of cycloheximide (which inhibits de novo protein synthesis). Maximal recovery was observed within 3?h of incubation at 37?°C after heat treatment. Constitutively expressed HSC73, which folds newly synthesized proteins, reached maximal levels 3?h after heat treatment using a co-immunoprecipitation assay with the Ku80 protein. Inhibiting HSC73, but not HSP72, expression with shRNA decreased the recovery of DNA-PK activity after heat treatment.
Conclusions: These results suggest that de novo protein synthesis is unnecessary for recovery of some heat-inactivated DNA-PK. Rather, it might be reactivated by the molecular chaperone activity of HSC73, but not HSP72. 相似文献