145 research outputs found

    Zero-gravity venting of three refrigerants

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    An experimental investigation of venting cylindrical containers partially filled with initially saturated liquids under zero-gravity conditions was conducted in the NASA Lewis Research Center 5-second zero-gravity facility. The effect of interfacial mass transfer on the ullage pressure response during venting was analytically determined, based on a conduction analysis applied to an infinitely planer (flat) liquid-vapor interface. This pressure response was compared with both the experimental results and an adiabatic decompression computation

    Metabolic reprogramming ensures cancer cell survival despite oncogenic signaling blockade

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    There is limited knowledge about the metabolic reprogramming induced by cancer therapies, and how this contributes to therapeutic resistance. Here we show that although inhibition of PI3K-AKT-mTOR signaling markedly decreased glycolysis and restrained tumor growth, these signaling and metabolic restrictions triggered autophagy, which supplied the metabolites required for the maintenance of mitochondrial respiration and redox homeostasis. Specifically, we found that survival of cancer cells was critically dependent on phospholipase A2 (PLA2) to mobilize lysophospholipids and free fatty acids to sustain fatty acid oxidation and oxidative phosphorylation. Consistent with this, we observed significantly increased lipid droplets, with subsequent mobilization to mitochondria. These changes were abrogated in cells deficient for the essential autophagy gene, ATG5. Accordingly, inhibition of PLA2 significantly decreased lipid droplets, decreased oxidative phosphorylation and increased apoptosis. Together, these results describe how treatment-induced autophagy provides nutrients for cancer cell survival and identifies novel co-treatment strategies to override this survival advantage

    Estrogen receptor beta expression in prostate adenocarcinoma

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    <p>Abstract</p> <p>Background</p> <p>Prostate cancer is the most commonly diagnosed cancer in men and the second leading cause of cancer death in men. Estrogen induction of cell proliferation is a crucial step in carcinogenesis of gynecologic target tissues, and there are many studies recently done, showing that prostate cancer growth is also influenced by estrogen. The characterization of estrogen receptor beta (ER-b) brought new insight into the mechanisms underlying estrogen signalling. In the present study, we investigated the expression of estrogen receptor-b (ER-b) in human prostate cancer tissues.</p> <p>Methods</p> <p>We selected 52 paraffin-embedded blocks of prostate needle biopsies in a cross-sectional study to determine frequency and rate of ER-b expression in different grades of prostate adenocarcinoma according to Gleason grading system. Immunohistochemical staining of tissue sections by monoclonal anti ER-b antibody was performed using an Envision method visualising system.</p> <p>Results</p> <p>ER-b expression was seen in tumoral cells of prostatic carcinoma in all 29 cases with low and intermediate tumors (100%) and 19 of 23 cases with high grade tumor (83%). Mean rate of ER-b expression in low & intermediate grade cancers was 68.41% (SD = 25.63) whereas high grade cancers showed 49.48% rate of expression (SD = 28.79).</p> <p>Conclusions</p> <p>ER-b expression is reduced in high grade prostate cancers compared to low & intermediate grade ones (<it>P </it>value 0.027).</p

    Prostate Cancer Postoperative Nomogram Scores and Obesity

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    Nomograms are tools used in clinical practice to predict cancer outcomes and to help make decisions regarding management of disease. Since its conception, utility of the prostate cancer nomogram has more than tripled. Limited information is available on the relation between the nomograms' predicted probabilities and obesity. The purpose of this study was to examine whether the predictions from a validated postoperative prostate cancer nomogram were associated with obesity.We carried out a cross-sectional analysis of 1220 patients who underwent radical prostatectomy (RP) in southern California from 2000 to 2008. Progression-free probabilities (PFPs) were ascertained from the 10-year Kattan postoperative nomogram. Multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs).In the present study, aggressive prostate cancer (Gleason ≥7), but not advanced stage, was associated with obesity (p = 0.01). After adjusting for age, black race, family history of prostate cancer and current smoking, an inverse association was observed for 10-year progression-free predictions (OR = 0.50; 95% CI = 0.28–0.90) and positive associations were observed for preoperative PSA levels (OR = 1.23; 95% CI = 1.01–1.50) and Gleason >7 (OR = 1.45; 95% CI = 1.11–1.90).Obese RP patients were more likely to have lower PFP values than non-obese patients, suggesting a higher risk of experiencing prostate cancer progression. Identifying men with potentially higher risks due to obesity may improve disease prognosis and treatment decision-making

    Lifestyle behaviors, obesity, and perceived health among men with and without a diagnosis of prostate cancer: A population-based, cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>A better understanding of how prostate cancer survivors differ from men without prostate cancer and whether these potential differences vary across demographic subgroups will help to focus and prioritize future public health interventions for improving the health and well-being of prostate cancer survivors. Therefore, our study aims were to compare lifestyle behaviors, body mass index (BMI), and perceived health in men with and without a diagnosis of prostate cancer in a national, population-based sample and to explore whether these comparisons differ for demographic subgroups.</p> <p>Methods</p> <p>In a cross-sectional study, men aged ≥ 40 were identified from the Behavioral Risk Factor Surveillance System (BRFSS) 2002 data (n = 63,662). Respondents reporting history of prostate cancer (n = 2,524) were compared with non prostate cancer controls (n = 61,138) with regard to daily fruit and vegetable servings (FVPD), smoking, alcohol, sedentary behavior, BMI, and perceived health. Multivariable logistic regression calculated adjusted odds ratios (OR) and 95% confidence intervals (CI) for the entire sample and for age, race, education, and urbanicity subgroups.</p> <p>Results</p> <p>Men with prostate cancer did not differ from men without prostate cancer with regard to smoking, alcohol, sedentary behavior, and obesity but were more likely to consume ≥ 5 FVPD (OR, 95% CI: 1.30, 1.09–1.56) and report poor or fair health (OR, 95% CI: 1.62, 1.33–1.97). Subgroup analyses demonstrated attenuation of the higher likelihood of ≥ 5 FVPD among prostate cancer survivors in rural respondents (OR, 95% CI: 0.98, 0.72–1.33). Poorer perceived health was greatest if ≤ 65 years of age (OR, 95% CI: 2.54, 1.79–3.60) and nonsignificant if black (OR, 95% CI: 1.41, 0.70–2.82). Smoking and alcohol which were not significant for the sample as a whole, demonstrated significant associations in certain subgroups.</p> <p>Conclusion</p> <p>Although efforts to enhance perceived health and healthy lifestyle behaviors among prostate cancer survivors are warranted, demographic subgroups such as prostate cancer survivors ≤ 65 and rural populations may require more aggressive interventions.</p

    Trabecular Reorganization in Consecutive Iliac Crest Biopsies when Switching from Bisphosphonate to Strontium Ranelate Treatment

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    BACKGROUND: Several agents are available to treat osteoporosis while addressing patient-specific medical needs. Individuals' residual risk to severe fracture may require changes in treatment strategy. Data at osseous cellular and microstructural levels due to a therapy switch between agents with different modes of action are rare. Our study on a series of five consecutively taken bone biopsies from an osteoporotic individual over a six-year period analyzes changes in cellular characteristics, bone microstructure and mineralization caused by a therapy switch from an antiresorptive (bisphosphonate) to a dual action bone agent (strontium ranelate). METHODOLOGY/PRINCIPAL FINDINGS: Biopsies were progressively taken from the iliac crest of a female patient. Four biopsies were taken during bisphosphonate therapy and one biopsy was taken after one year of strontium ranelate (SR) treatment. Furthermore, serum bone markers and dual x-ray absorptiometry measurements were acquired. Undecalcified histology was used to assess osteoid parameters and bone turnover. Structural indices and degree of mineralization were determined using microcomputed tomography, quantitative backscattered electron imaging, and combined energy dispersive x-ray/µ-x-ray-fluorescence microanalysis. CONCLUSIONS/SIGNIFICANCE: Microstructural data revealed a notable increase in bone volume fraction after one year of SR treatment compared to the bisphosphonate treatment period. Indices of connectivity density, structure model index and trabecular bone pattern factor were predominantly enhanced indicating that the architectural transformation from trabecular rods to plates was responsible for the bone volume increase and less due to changes in trabecular thickness and number. Administration of SR following bisphosphonates led to a maintained mineralization profile with an uptake of strontium on the bone surface level. Reactivated osteoclasts designed tunneling, hook-like intratrabecular resorption sites. The appearance of tunneling resorption lacunae and the formation of both mini-modeling units and osteon-like structures within increased plate-like cancellous bone mass provides additional information on the mechanisms of strontium ranelate following bisphosphonate treatment, which may deserve special attention when monitoring a treatment switch

    Age-Related Changes in the Epithelial and Stromal Compartments of the Mammary Gland in Normocalcemic Mice Lacking the Vitamin D3 Receptor

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    The vitamin D3 receptor (VDR) serves as a negative growth regulator during mammary gland development via suppression of branching morphogenesis during puberty and modulation of differentiation and apoptosis during pregnancy, lactation and involution. To assess the role of the VDR in the aging mammary gland, we utilized 12, 14, and 16 month old VDR knockout (KO) and wild type (WT) mice for assessment of integrity of the epithelial and stromal compartments, steroid hormone levels and signaling pathways. Our data indicate that VDR ablation is associated with ductal ectasia of the primary mammary ducts, loss of secondary and tertiary ductal branches and atrophy of the mammary fat pad. In association with loss of the white adipose tissue compartment, smooth muscle actin staining is increased in glands from VDR KO mice, suggesting a change in the stromal microenviroment. Activation of caspase-3 and increased Bax expression in mammary tissue of VDR KO mice suggests that enhanced apoptosis may contribute to loss of ductal branching. These morphological changes in the glands of VDR KO mice are associated with ovarian failure and reduced serum 17β-estradiol. VDR KO mice also exhibit progressive loss of adipose tissue stores, hypoleptinemia and increased metabolic rate with age. These developmental studies indicate that, under normocalcemic conditions, loss of VDR signaling is associated with age-related estrogen deficiency, disruption of epithelial ductal branching, abnormal energy expenditure and atrophy of the mammary adipose compartment
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