Alexandersenstiles5222

BACKGROUND In prostate cancer (PCa), lower education level is associated with less screening, more advanced stage at diagnosis and worse survival. The aim of this study was to estimate the association between education level and treatment modality and subsequently survival. METHODS The 9255 men diagnosed with PCa in the Finnish Randomized Study of Screening for Prostate Cancer were included. Cancer stage, comorbidity, education level and primary treatment modality were extracted from the patient records, the Finnish Cancer Registry, Statistics Finland and the National Institute of Health and Welfare, and these covariates were used in logistic regression (treatment selection) and Cox regression (survival analysis). RESULTS In high-risk cancers, men with tertiary education were more likely to be treated with radical prostatectomy (odds ratio [OR] = 1.76; 95% confidence interval [CI] = 1.27-2.44) than men with primary education. Men with secondary (OR = 0.57; 95% CI = 0.38-0.84) or tertiary (OR = 0.42; 95% CI = 0.29-0.60) education were managed less frequently with mere hormonal therapy. In locally advanced cases, tertiary education was associated with more curatively aimed therapies and less hormonal therapy (OR for radical prostatectomy = 2.34; 95% CI = 1.49-3.66; OR for radiotherapy = 1.42; 95% CI = 1.09-1.85; OR for hormonal therapy = 0.45; 95% CI = 0.33-0.60). The hazard ratio for PCa death was lower in men with secondary (0.81; 95% CI = 0.69-0.95) and tertiary (0.75; 95% CI = 0.65-0.87) education than in the patients with primary education. CONCLUSIONS When controlled for the cancer risk group, comorbidity and patient's age, low education level is independently associated with less curatively aimed treatment in men with high-risk or locally advanced PCa and subsequently worse prognosis. BACKGROUND Immune checkpoint inhibitors (ICPis) induce various immune-related adverse events (irAEs), despite their beneficial effects in treating various advanced cancers. ICPi-induced secondary adrenal insufficiency is described as a prevalent and serious 'pituitary irAE.' However, its precise mechanism remains unclear, and no definitive predictive markers have been reported. PATIENTS AND METHODS We enrolled and studied 11 patients with advanced cancer (aged 39-70 years; 6 male patients) receiving nivolumab, pembrolizumab or ipilimumab who developed pituitary irAEs. Their clinical data, including endocrine functions, were retrospectively assessed and human leucocyte antigen (HLA) genotypes were determined to compare the HLA allele frequencies in these patients and healthy controls. RESULTS Among 11 patients, 7, 3 and 1 patients exhibited malignant melanoma, non-small-cell lung cancer and gastric cancer, respectively. HLA type screening results revealed that HLA-DR15, B52 and Cw12 were observed in 9, 7, and 7 patients with pituitary irAE, respectively. DR15, B52 and Cw12 were significantly more prevalent in our group than in the healthy control group from the Japanese HLA-haplotype database (this study vs healthy control group); DR15 81.8% vs 33.5% (n = 11, P = 0.0014), B52 63.6% vs 21.0% (n = 11, P = 0.0026) and Cw12 70% vs 21.3% (n = 10, P = 0.0013). CONCLUSIONS HLA-DR15, B52 and Cw12 are possible predisposing factors for pituitary irAEs. HLA-DR15 is reportedly associated with autoimmune disease via interleukin-17 regulation, suggesting its involvement in pituitary irAE development. Using HLA haplotypes as pituitary irAE predictive markers, we could provide safe ICPi treatment and understand irAE pathogenesis. This paper presented a new method of preparing porous glass-ceramics by high-temperature pore-forming using coal fly ash and asbestos tailings as raw materials. find more The effects of the content of asbestos tailings and sintering temperature on the phase composition, microstructure and properties of the porous glass-ceramics had been systematically discussed, furthermore, the pore formation mechanism was also expounded. Compared with T0, porous glass-ceramics from T1, T2 and T3 experienced more violent self-expansion during the sintering process due to the addition of asbestos tailings. The porosity of porous glass-ceramics from T3 was 51%, the bulk density was 1.42 g/cm3, the flexure strength was 19 MPa, the main crystal phase was indialite, along with several secondary phases such as anorthite, enstatite, and forsterite. Due to the high strength, the material was expected to be used as a porous construction material with load-bearing function. This work provided a convenient and promising method for the utilization of coal fly ash and asbestos tailings to prepare porous glass-ceramics without adding foaming agents. BACKGROUND Clinical studies have reported overexpression of PDE5 and elevation of intracellular cyclic GMP in various types of cancer cells. ABCC5 transports cGMP out of the cells with high affinity. PDE5 inhibitors prevent both cellular metabolism and cGMP efflux by inhibiting ABCC5 as well as PDE5. Increasing intracellular cGMP is hypothesized to promote apoptosis and growth restriction in tumor cells and also has potential for clinical use in treatment of cardiovascular disease and erectile dysfunction. Vardenafil is a potent inhibitor of both PDE5 and ABCC5-mediated cGMP cellular efflux. Nineteen novel vardenafil analogs that have been predicted as potent inhibitors by VLS were chosen for tests of their ability to inhibit ATP- dependent transport of cGMP by measuring the accumulation of cyclic GMP in inside-out vesicles. AIM In this study, we investigated the ability of nineteen new compounds to inhibit ABCC5- mediated cGMP transport. We also determined the Ki values of the six most potent compounds. METHODS Preparation of human erythrocyte inside out vesicles and transport assay. RESULTS Ki values for six of nineteen compounds that showed more than 50 % inhibition of cGMP transport in the screening test were determined and ranged from 1.1 to 23.1 μM. One compound was significantly more potent than the positive control, sildenafil. CONCLUSION Our findings show that computational screening correctly identified vardenafil-analogues that potently inhibit cGMP efflux-pumps from cytosol and could have substantial clinical potential in treatment of patients with diverse disorders.