Enhancing chemosensitivity to gemcitabine via RNA interference targeting the catalytic subunits of protein kinase CK2 in human pancreatic cancer cells

<p>Abstract</p> <p>Background</p> <p>Pancreatic cancer is a complex genetic disorder that is characterized by rapid progression, invasiveness, resistance to treatment and high molecular heterogeneity. Various agents have been used in clinical trials showing only modest improvements with respect to gemcitabine-based chemotherapy, which continues to be the standard first-line treatment for this disease. However, owing to the overwhelming molecular alterations that have been reported in pancreatic cancer, there is increasing focus on targeting molecular pathways and networks, rather than individual genes or gene-products with a combination of novel chemotherapeutic agents.</p> <p>Methods</p> <p>Cells were transfected with small interfering RNAs (siRNAs) targeting the individual CK2 subunits. The CK2 protein expression levels were determined and the effect of its down-regulation on chemosensitization of pancreatic cancer cells was investigated.</p> <p>Results</p> <p>The present study examined the impact on cell death following depletion of the individual protein kinase CK2 catalytic subunits alone or in combination with gemcitabine and the molecular mechanisms by which this effect is achieved. Depletion of the CK2α or -α' subunits in combination with gemcitabine resulted in marked apoptotic and necrotic cell death in PANC-1 cells. We show that the mechanism of cell death is associated with deregulation of distinct survival signaling pathways. Cellular depletion of CK2α leads to phosphorylation and activation of MKK4/JNK while down-regulation of CK2α' exerts major effects on the PI3K/AKT pathway.</p> <p>Conclusions</p> <p>Results reported here show that the two catalytic subunits of CK2 contribute differently to enhance gemcitabine-induced cell death, the reduced level of CK2α' being the most effective and that simultaneous reduction in the expression of CK2 and other survival factors might be an effective therapeutic strategy for enhancing the sensitivity of human pancreatic cancer towards chemotherapeutic agents.</p

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

The effect of growth regulators on sex expression in melon (Cucumis melo L.)

Seven traits related to flowering and sex expression in melon were studied and their reaction to application of two growth regulators (ethrel and gibberellic acid) was observed. Four monoecious genotypes (Sesame, ED-3, ED-4, Pobeditel) and four andromonoecious genotypes (Chinese muskmelon, Anannas, Fiata, A2-3lb) had been used for experiments. According to the results, ethrel had higher effects on the investigated traits than gibberellic acid. Ethrel increased the number of perfect flowers per plant for 7.18 (31.42%), reduced the number of male flowers per plant for 21.47 (17.98%), affected earlier appearance of the first pistillate/perfect flower for 3.68 days, and delayed the appearance of the first staminate flower for 16.07 days. Changes in the last two traits caused an extension of the period from the emergence of the first pistillate/perfect to the first staminate flower from 0.1 to 21.57 days, which represents the strongest effect of ethrel. Gibberellic acid had generally opposite effects on the studied traits

Sex and race/ethnic disparities in the cross-sectional association between depressive symptoms and muscle mass: the Multi-ethnic Study of Atherosclerosis

BACKGROUND: The cross-sectional area of total muscle mass has been reported to decrease by about 40% for those 20–60 years of age. Depressive symptoms may discourage motivation to engage in physical activity such as strength training shown to negate muscle loss. Inflammation related to depressive symptoms may also contribute to muscle atrophy. Physiological differences by sex and race/ethnicity may also modify the association between depression and muscle mass. Evidence on the relationship between depression (or depressive symptoms) and adiposity has been mounting; however, little is known about the depressive symptoms-muscle mass association. We sought to determine the association between elevated depressive symptoms (EDS) and lean muscle mass and whether this varies by sex and race/ethnicity. METHODS: Evaluating 1605 adults (45–84 years of age) from the Multi-ethnic Study of Atherosclerosis Abdominal Body Composition, Inflammation and Cardiovascular Disease Study, we examined the cross-sectional association between EDS (Center for Epidemiologic Studies for Depression Scale score ≥ 16 and/or antidepressant use) and computed tomography-measured abdominal lean muscle mass using linear regression. Muscles were evaluated as a whole and by functionality (locomotion vs. stabilization/posture). Covariates included height, body mass index, sociodemographics, comorbidities, inflammatory markers and health behaviors (pack-years of smoking, alcohol locomotion compared to men, total intentional exercise, daily caloric intake). Sex and race/ethnicity were assessed as potential modifiers. Statistical significance was at a p < 0.05 for main effects and < 0.20 for interaction. RESULTS: Men with elevated depressive symptoms had 5.9 cm(2) lower lean muscle mass for locomotion compared to men without EDS, fully-adjusted (CI = −10.5, −1.4, p = 0.011). This was statistically significantly different from the null finding among women (interaction p = 0.05). Chinese participants with EDS had 10.2 cm(2) lower abdominal lean muscle mass for locomotion compared to those without EDS (fully-adjusted, CI = −18.3, −2.1, p = 0.014), which was significantly different from the null relationship among White participants (interaction p = 0.04). No association was observed between elevated depressive symptoms and muscle for stabilization/posture evaluating the whole population or stratified by sex or race/ethnicity. CONCLUSIONS: In the presence of elevated depressive symptoms, men and Chinese participants may have lower muscle mass, particularly for locomotion. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12888-015-0604-9) contains supplementary material, which is available to authorized users