All men, almost, suffer from prostatic disorders in average life expectancy. In the year of 1950s, the first autopsy of prostate gland discovered the link between Benign prostatic hyperplasia (BPH) and Prostate Cancer (PCa). After that, many histology, biochemistry, epidemiology studies explained the association and associated risk factor for the same. From the various scientific evidence, it is proved that both diseases share some common transcription factors and signalling pathways. Still, BPH cannot be considered as the first step of PCa progression. To define, the relationship between both of the diseases, a well-defined large epidemiological study is needed. Along with androgen signalling, imbalanced apoptosis, oxidative stress, and microbial infection also crucial factors that significantly affect the pathogenesis of BPH. Various signalling pathways are involved in the progression of BPH. Androgen signalling is the driving force for the progress of PCa. In PCa androgen signalling is upregulated as compared to a healthy prostate. Some dominant Androgen-regulated genes and their functions have been discussed in this work.
Background
Whole-body (WB) MRI, which includes diffusion-weighted imaging (DWI) and T1-w Dixon, permits sensitive detection of marrow disease in addition to qualitative and quantitative measurements of disease and response to treatment of bone marrow. We report on the first study to embed standardised WB-MRI within a prospective, multi-centre myeloma clinical trial (IMAGIMM trial, sub-study of OPTIMUM/MUKnine) to explore the use of WB-MRI to detect minimal residual disease after treatment.
Methods
The standardised MY-RADS WB-MRI protocol was set up on a local 1.5 T scanner. An imaging manual describing the MR protocol, quality assurance/control procedures and data transfer was produced and provided to sites. For non-identical scanners (different vendor or magnet strength), site visits from our physics team were organised to support protocol optimisation. The site qualification process included review of phantom and volunteer data acquired at each site and a teleconference to brief the multidisciplinary team. Image quality of initial patients at each site was assessed.
Results
WB-MRI was successfully set up at 12 UK sites involving 3 vendor systems and two field strengths. Four main protocols (1.5 T Siemens, 3 T Siemens, 1.5 T Philips and 3 T GE scanners) were generated. Scanner limitations (hardware and software) and scanning time constraint required protocol modifications for 4 sites. Nevertheless, shared methodology and imaging protocols enabled other centres to obtain images suitable for qualitative and quantitative analysis.
Conclusions
Standardised WB-MRI protocols can be implemented and supported in prospective multi-centre clinical trials.
Trial registration NCT 03188172 clinicaltrials.gov; registration date 15th June 2017 https://clinicaltrials.gov/ct2/show/study/NCT03188172
Resveratrol obtained in grape seed and skin is structurally similar to a synthetic estrogen diethylstilbestrol. The endogenous estrogen, 17β-estradiol, induces cellular responses by binding to the estrogen receptor alpha and beta. The bone fracture due to decreased bone mineral density in postmenopausal women is linked to reduced estrogen. The adverse drug reactions of hormone replacement therapy warrant identifying unique natural compounds with ER-subtype specificity to improve bone health. Resveratrol is considered a phytoestrogen; however, its isoform selectivity has not yet been established on osteoblast cell lines. Therefore, in vitro and in silico docking studies were performed to analyze the binding affinity and selectivity of resveratrol towards receptor alpha and β-isoforms. Resveratrol was evaluated for its actions on the proliferation and differentiation in the primary rat calvarial osteoblasts and bone marrow cells. Osteoblasts specifically increased receptor alpha expression in rat calvarial osteoblasts cells; however, there was no effect on receptor beta expression. In silico studies further confirmed receptor alpha isoform specificity. The observed differences in the orientation, interaction pattern, and binding affinity of resveratrol at the active site of receptor alpha and beta are supported by the western blot analysis. The estrogen mimetic action of resveratrol suggests its therapeutic potential as a bone anabolic agent for postmenopausal osteoporosis.
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