Welchpittman8979

Primary prevention of hormonally insensitive breast cancers remains an important clinical need and repurposing existing low-toxicity drugs represents a low-cost, efficient strategy for meeting this goal. This study targeted the cholesterol pathway using fluvastatin, a cholesterol-lowering drug, and aspirin, an AMPK activator that acts as a brake in the cholesterol pathway, in a transgenic mouse model of triple-negative breast cancer (TNBC).

Using SV40C3 TAg mice, the efficacy and mechanism of fluvastatin, aspirin, or both in combination were compared with vehicle alone.

Sixteen-weeks of fluvastatin treatment resulted in significant delay in onset of tumors (20weeks vs. 16.8weeks in vehicle treatment, p = 0.01) and inhibited tumor incidence and tumor multiplicity by 50% relative to the vehicle control. In animals that developed tumors, fluvastatin treatment inhibited tumor weight by 75% relative to vehicle control. Aspirin alone did not significantly affect tumor latency, tumor incidence or tumor burden compared to vehicle control. Fluvastatin and aspirin in combination delayed the onset of tumors but failed to inhibit tumor incidence and tumor multiplicity. The growth-inhibitory effects of fluvastatin were mediated through increased FAS/FASL mediated apoptotic cell death that was characterized by increased cleaved PARP and driven in part by depletion of an isoprenoid, geranyl geranyl pyrophosphate (GGPP).

In line with NCI's emphasis to repurpose low-toxicity drugs for prevention of cancer, fluvastatin was effective for prevention of TNBC and warrants further clinical testing. Aspirin did not provide chemopreventive benefit.

In line with NCI's emphasis to repurpose low-toxicity drugs for prevention of cancer, fluvastatin was effective for prevention of TNBC and warrants further clinical testing. Aspirin did not provide chemopreventive benefit.

Most reports describing the risk of late relapse in breast cancer (BC) have been based on selected patients enrolled into clinical trials. We examined population-based long-term risks of BC-specific mortality (BCSM), the risks of BCSM conditional on having survived 5years, and factors associated with late BCSM.

Using SEER, we identified women diagnosed with BC (T1-T2, N0-N2, M0) between 1990 and 2005 with known hormone receptor (HR) status. Kaplan-Meier analyses determined cumulative risks of BCSM. We performed Fine and Gray regression stratified by HR status.

We included 202,080 patients (median follow-up of 14.17years). Of all BC deaths, the proportion that occurred after 5years was 65% for HR-positive vs 28% for HR-negative (p < 0.001) BC. In HR-positive BC, the cumulative risks of BCSM during years 5-20 were 9.9%, 21.9%, and 38% for N0, N1, and N2 disease. For HR-negative BC, the risks were 7.9%, 12.2%, and 19.9%, respectively. For T1a/b, N0, HR-positive BC, the risk of BCSM was 6 times lower than the risk of non-BCSM. In N2, HR-positive BC, the risk of BCSM was 43% higher than the risk of non-BCSM. In adjusted Fine and Gray models stratified by HR status, the risks of BCSM conditional on having survived 5years for both HR-positive and HR-negative depended on T-N status, age, and year of diagnosis. In HR-positive, the risks also depended on race and grade.

The risks of BCSM beyond 5years, although different, remain important for both HR-positive and HR-negative BC. Strategies to prevent early and late recurrences are warranted.

The risks of BCSM beyond 5 years, although different, remain important for both HR-positive and HR-negative BC. Strategies to prevent early and late recurrences are warranted.

The previous analysis of systematic reviews and meta-analyses have illustrated that obstructive sleep apnea (OSA) is correlated with multiple health outcomes. In the present research, our main aim was to execute an umbrella review to assess the available evidence for the associations between OSA and health outcomes.

Herein, a meta-analysis of previous observational investigations that have reported associations between OSA and health outcomes in all human populations and settings was performed. We used these studies to execute an umbrella review of available meta-analyses and systematic reviews.

Sixty-six articles comprising 136 unique outcomes were enrolled in this analysis. Of the 136 unique outcomes, 111 unique outcomes had significant associations (p < 0.05). Only 7 outcomes (coronary revascularization after PCI, postoperative respiratory failure, steatosis, alaninetrans aminase (ALT) elevation, metabolic syndrome (MS), psoriasis, and Parkinson's disease) had a high quality of evidence. click here Twenty-four outcomes had a moderate quality of evidence, and the remaining 80 outcomes had a weak quality of evidence. Sixty-nine outcomes exhibited significant heterogeneity. Twenty-five outcomes exhibited publication bias. Sixty-three (95%) studies showed critically low methodological quality.

Among the 66 meta-analyses exploring 136 unique outcomes, only 7 statistically significant outcomes were rated as high quality of evidence. OSA may correlate with an increased risk of coronary revascularization after PCI, postoperative respiratory failure, steatosis, ALT elevation, MS, psoriasis, and Parkinson's disease.

Among the 66 meta-analyses exploring 136 unique outcomes, only 7 statistically significant outcomes were rated as high quality of evidence. OSA may correlate with an increased risk of coronary revascularization after PCI, postoperative respiratory failure, steatosis, ALT elevation, MS, psoriasis, and Parkinson's disease.Cognitive intervention includes cognitive stimulation, cognitive training, and cognitive rehabilitation. This systematic review was performed to re-assess the efficacy of cognitive intervention for the patients with Alzheimer's disease (AD). Twenty studies (2012 participants) were eventually included. For global cognitive function, the combined mean difference (MD) in eight studies was 1.67 (95% Confidence Interval 0.45, 2.89, p = 0.007; Q = 33.28, df = 8, p  less then  0.0001, τ2 = 2.17, I2 = 76%) for the short term. The pooled standardized mean difference (SMD) of six RCTs was 1.61 (95% Confidence Interval 0.65, 2.56, p = 0.0009; Q = 127.66, df = 6, p  less then  0.00001, τ2 = 1.56, I2 = 95%) for the medium term. The pooled SMD of seven studies was 0.79 (95% Confidence Interval 0.33, 1.25, p = 0.0008; Q = 35.10, df = 7, p  less then  0.0001, τ2 = 0.33, I2 = 80%) for the long term. For depression, the pooled SMD of two trials was -0.48 (95% Confidence Interval -0.71, -0.24; p  less then  0.0001, I2 = 4%) for the short term.