Inherited mutations in DNA-repair genes were found in nearly 12% of men with metastatic prostate cancer, as compared with 2.7% in an unselected general population.
Carcinoma of the prostate is a ...common cancer with a wide spectrum of clinical behavior that ranges from decades of indolence to rapid metastatic progression and lethality.
1
,
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Prostate cancer is also among the most heritable of human cancers, with 57% (95% confidence interval CI, 51 to 63) of the interindividual variation in risk attributed to genetic factors.
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Thus far, genomewide association studies have identified more than 100 common variants that account for approximately 33% of the excess familial prostate cancer risk.
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–
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Mutations in other genes, including
BRCA1, BRCA2, MSH2,
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–
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and
HOXB13,
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account for a small proportion of . . .
In this study, the androgen-receptor inhibitor enzalutamide improved progression-free and overall survival in men with castration-resistant metastatic prostate cancer who had not received ...chemotherapy.
Prostate cancer is the most commonly diagnosed cancer and the sixth leading cause of cancer-related death among men worldwide.
1
Strategies to block androgen-receptor signaling have formed the backbone of prostate-cancer therapy since the first description of the hormonal dependence of this cancer in 1941.
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Advances in endocrine therapies have improved survival in men with high-risk locoregional prostate cancer.
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,
4
However, new hormonal agents have been shown to extend survival in men with metastatic castration-resistant disease.
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–
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In most patients who are treated for advanced recurrent prostate cancer with androgen-deprivation therapy (comprising a luteinizing hormone–releasing hormone LHRH analogue or orchiectomy with . . .
The road ahead in genetics and genomics McGuire, Amy L; Gabriel, Stacey; Tishkoff, Sarah A ...
Nature reviews. Genetics,
10/2020, Letnik:
21, Številka:
10
Journal Article
Recenzirano
Odprti dostop
In celebration of the 20th anniversary of Nature Reviews Genetics, we asked 12 leading researchers to reflect on the key challenges and opportunities faced by the field of genetics and genomics. ...Keeping their particular research area in mind, they take stock of the current state of play and emphasize the work that remains to be done over the next few years so that, ultimately, the benefits of genetic and genomic research can be felt by everyone.
Abstract Background Reproductive factors reflective of endogenous sex hormone exposure might have an effect on cardiac remodeling and the development of heart failure (HF). Objectives This study ...examined the association between key reproductive factors and the incidence of HF. Methods Women from a cohort of the Women's Health Initiative were systematically evaluated for the incidence of HF hospitalization from study enrollment through 2014. Reproductive factors (number of live births, age at first pregnancy, and total reproductive duration time from menarche to menopause) were self-reported at study baseline in 1993 to 1998. We employed Cox proportional hazards regression analysis in age- and multivariable-adjusted models. Results Among 28,516 women, with an average age of 62.7 ± 7.1 years at baseline, 1,494 (5.2%) had an adjudicated incident HF hospitalization during an average follow-up of 13.1 years. After adjusting for covariates, total reproductive duration in years was inversely associated with incident HF: hazard ratios (HRs) of 0.99 per year (95% confidence interval CI: 0.98 to 0.99 per year) and 0.95 per 5 years (95% CI: 0.91 to 0.99 per 5 years). Conversely, early age at first pregnancy and nulliparity were significantly associated with incident HF in age-adjusted models, but not after multivariable adjustment. Notably, nulliparity was associated with incident HF with preserved ejection fraction in the fully adjusted model (HR: 2.75; 95% CI: 1.16 to 6.52). Conclusions In post-menopausal women, shorter total reproductive duration was associated with higher risk of incident HF, and nulliparity was associated with higher risk for incident HF with preserved ejection fraction. Whether exposure to endogenous sex hormones underlies this relationship should be investigated in future studies.
The Kuiper Belt is a broad, torus-shaped region in the outer Solar System beyond Neptune’s orbit. It contains primordial planetary building blocks and dwarf planets. NASA’s New Horizons spacecraft ...conducted a flyby of Pluto and its system of moons on 14 July 2015. New Horizons then continued farther into the Kuiper Belt, adjusting its trajectory to fly close to the small Kuiper Belt object (486958) 2014 MU69 (henceforth MU69; also informally known as Ultima Thule). Stellar occultation observations in 2017 showed that MU69 was ~25 to 35 km in diameter, and therefore smaller than the diameter of Pluto (2375 km) by a factor of ~100 and less massive than Pluto by a factor of ~106. MU69 is located about 1.6 billion kilometers farther from the Sun than Pluto was at the time of the New Horizons flyby. MU69’s orbit indicates that it is a “cold classical” Kuiper Belt object, thought to be the least dynamically evolved population in the Solar System. A major goal of flying past this target is to investigate accretion processes in the outer Solar System and how those processes led to the formation of the planets. Because no small Kuiper Belt object had previously been explored by spacecraft, we also sought to provide a close-up look at such a body’s geology and composition, and to search for satellites, rings, and evidence of present or past atmosphere. We report initial scientific results and interpretations from that flyby.
► We examined separate cognitive processes that underlie the task of driving. ► Simulated driving and cognitive tasks were assessed after sleep deprivation. ► Psychomotor vigilance was a key ...component of the variation in driving impairment.
Driving is a complex task, which can be broken down into specific cognitive processes. In order to determine which components contribute to drowsy driving impairments, the current study examined simulated driving and neurocognitive performance after one night of sleep deprivation. Nineteen professional drivers (age 45.3±9.1) underwent two experimental sessions in randomised order: one after normal sleep and one after 27h total sleep deprivation. A simulated driving task (AusEd), the psychomotor vigilance test (PVT), and neurocognitive tasks selected from the Cognitive Drug Research computerised neurocognitive assessment battery (simple and choice RT, Stroop Task, Digit Symbol Substitution Task, and Digit Vigilance Task) were administered at 10:00h in both sessions. Mixed-effects ANOVAs were performed to examine the effect of sleep deprivation versus normal sleep on performance measures. To determine if any neurocognitive tests predicted driving performance (lane position variability, speed variability, braking RT), neurocognitive measures that were significantly affected by sleep deprivation were then added as a covariate to the ANOVAs for driving performance. Simulated driving performance and neurocognitive measures of vigilance and reaction time were impaired after sleep deprivation (p<0.05), whereas tasks examining processing speed and executive functioning were not significantly affected by sleep loss. PVT performance significantly predicted specific aspects of simulated driving performance. Thus, psychomotor vigilance impairment may be a key cognitive component of driving impairment when sleep deprived. The generalisability of this finding to real-world driving remains to be investigated.
Ghrelin, a stomach-derived orexigenic hormone, has stimulated great interest as a potential target for obesity control. Pharmacological evidence indicates that ghrelin’s effects on food intake are ...mediated by neuropeptide Y (NPY) and agouti-related protein (AgRP) in the central nervous system. These include intracerebroventricular application of antibodies to neutralize NPY and AgRP, and the application of an NPY Y1 receptor antagonist, which blocks some of the orexigenic effects of ghrelin. Here we describe treatment of Agrp−/−;Npy−/− and Mc3r−/−;Mc4r−/− double knockout mice as well as Npy−/− and Agrp−/− single knockout mice with either ghrelin or an orally active nonpeptide ghrelin agonist. The data demonstrate that NPY and AgRP are required for the orexigenic effects of ghrelin, as well as the involvement of the melanocortin pathway in ghrelin signaling. Our results outline a functional interaction between the NPY and AgRP pathways. Although deletion of either NPY or AgRP caused only a modest or nondetectable effect, ablation of both ligands completely abolished the orexigenic action of ghrelin. Our results establish an in vivo orexigenic function for NPY and AgRP, mediating the effect of ghrelin.
The Pluto system was recently explored by NASA's New Horizons spacecraft, making closest approach on 14 July 2015. Pluto's surface displays diverse landforms, terrain ages, albedos, colors, and ...composition gradients. Evidence is found for a water-ice crust, geologically young surface units, surface ice convection, wind streaks, volatile transport, and glacial flow. Pluto's atmosphere is highly extended, with trace hydrocarbons, a global haze layer, and a surface pressure near 10 microbars. Pluto's diverse surface geology and long-term activity raise fundamental questions about how small planets remain active many billions of years after formation. Pluto's large moon Charon displays tectonics and evidence for a heterogeneous crustal composition; its north pole displays puzzling dark terrain. Small satellites Hydra and Nix have higher albedos than expected.
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