Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

Exploring Action Dynamics as an Index of Paired-Associate Learning

Much evidence exists supporting a richer interaction between cognition and action than commonly assumed. Such findings demonstrate that short-timescale processes, such as motor execution, may relate in systematic ways to longer-timescale cognitive processes, such as learning. We further substantiate one direction of this interaction: the flow of cognition into action systems. Two experiments explored match-to-sample paired-associate learning, in which participants learned randomized pairs of unfamiliar symbols. During the experiments, their hand movements were continuously tracked using the Nintendo Wiimote. Across learning, participant arm movements are initiated and completed more quickly, exhibit lower fluctuation, and exert more perturbation on the Wiimote during the button press. A second experiment demonstrated that action dynamics index novel learning scenarios, and not simply acclimatization to the Wiimote interface. Results support a graded and systematic covariation between cognition and action, and recommend ways in which this theoretical perspective may contribute to applied learning contexts

Nanobiopolymer for Direct Targeting and Inhibition of EGFR Expression in Triple Negative Breast Cancer

Treatment options for triple negative breast cancer (TNBC) are generally limited to cytotoxic chemotherapy. Recently, anti-epidermal growth factor receptor (EGFR) therapy has been introduced for TNBC patients. We engineered a novel nanobioconjugate based on a poly(β-L-malic acid) (PMLA) nanoplatform for TNBC treatment. The nanobioconjugate carries anti-tumor nucleosome-specific monoclonal antibody (mAb) 2C5 to target breast cancer cells, anti-mouse transferrin receptor (TfR) antibody for drug delivery through the host endothelial system, and Morpholino antisense oligonucleotide (AON) to inhibit EGFR synthesis. The nanobioconjugates variants were: (1) P (BioPolymer) with AON, 2C5 and anti-TfR for tumor endothelial and cancer cell targeting, and EGFR suppression (P/AON/2C5/TfR), and (2) P with AON and 2C5 (P/AON/2C5). Controls included (3) P with 2C5 but without AON (P/2C5), (4) PBS, and (5) P with PEG and leucine ester (LOEt) for endosomal escape (P/mPEG/LOEt). Drugs were injected intravenously to MDA-MB-468 TNBC bearing mice. Tissue accumulation of injected nanobioconjugates labeled with Alexa Fluor 680 was examined by Xenogen IVIS 200 (live imaging) and confocal microscopy of tissue sections. Levels of EGFR, phosphorylated and total Akt in tumor samples were detected by western blotting

Counterfactual thinking and regulatory fit

According to regulatory fit theory (Higgins, 2000), when people make decisions with strategies that sustain their regulatory focus orientation, they ``feel right'' about what they are doing, and this ``feeling-right'' experience then transfers to subsequent choices, decisions, and evaluations. The present research was designed to link the concept of regulatory fit to functional accounts of counterfactual thinking. In the present study, participants generated counterfactuals about their anagram performance, after which persistence on a second set of anagrams was measured. Under promotion framing (i.e., find 90\% or more of all the possible words) upward counterfactual thinking in general elicited larger increases in persistence than did downward counterfactual thinking in general, but under prevention framing (i.e., avoid failing to find 90\% or more of all the possible words) upward evaluation (comparing reality to a better reality) elicited larger increases in persistence than did upward reflection (focusing on a better reality), whereas downward reflection (focusing on a worse reality) elicited larger increases in persistence than did downward evaluation (comparing reality to a worse reality). In all, the present findings suggest that the generation of counterfactuals enhances the likelihood that individuals will engage in courses of action that fit with their regulatory focus orientation

Momentum sequence and environmental climate influence levels of perceived psychological momentum within a sport competition

The present study examined the influence of momentum sequence (positive vs. negative) and environmental climate (hot-wet vs. neutral) on supporters' (i.e. virtual observers') reported levels of perceived psychological momentum (PM) during a simulated cycling competition. Participants supported one of two competing cyclists involved in a race that was displayed on a screen in a lecture hall. The race scenario was manipulated so that the supported cyclist appeared to undergo either a positive or negative momentum sequence. In addition, participants were either exposed to a hot-wet environmental climate or to a neutral environmental climate while observing the race scenario. According to the results, reported levels of PM were higher in the positive momentum sequence condition than in the negative momentum sequence condition, consistent with the notion that supporters' PM is influenced by a positivity bias, and reported levels of PM were also found to be higher in the hot-wet climate condition than in the neutral climate condition, consistent with the notion that environmental climate is a contextual factor that influences PM through the operation of a causal augmenting mechanism.Scopu

Counterfactual thinking and regulatory fit

According to regulatory fit theory (Higgins, 2000), when people make decisions with strategies that sustain their regulatory focus orientation, they ``feel right'' about what they are doing, and this ``feeling-right'' experience then transfers to subsequent choices, decisions, and evaluations. The present research was designed to link the concept of regulatory fit to functional accounts of counterfactual thinking. In the present study, participants generated counterfactuals about their anagram performance, after which persistence on a second set of anagrams was measured. Under promotion framing (i.e., find 90\% or more of all the possible words) upward counterfactual thinking in general elicited larger increases in persistence than did downward counterfactual thinking in general, but under prevention framing (i.e., avoid failing to find 90\% or more of all the possible words) upward evaluation (comparing reality to a better reality) elicited larger increases in persistence than did upward reflection (focusing on a better reality), whereas downward reflection (focusing on a worse reality) elicited larger increases in persistence than did downward evaluation (comparing reality to a worse reality). In all, the present findings suggest that the generation of counterfactuals enhances the likelihood that individuals will engage in courses of action that fit with their regulatory focus orientation.Counterfactual, regulatory fit, assimilation, contrast, motivation.

Differential reactions of virtual actors and observers to the triggering and interruption of psychological momentum

International audienceThe present study compared virtual actors' and observers' perceptions of positive and negative psychological momentum (PM) and their responses to sudden interruptions of momentum. Participants with experience playing competitive table tennis imagined that they were playing a table tennis game (virtual actors), whereas participants who lacked experience playing competitive table tennis imagined that they were observing a table tennis game (observers). While viewing an audiovisual simulation of a table tennis match, participants were exposed to either an ascending (i.e., positive momentum) or descending (i.e., negative momentum) scoring sequence that was either suddenly interrupted or not interrupted at all. Participants' PM perceptions were measured at the conclusion of the simulation. Results indicated that observers' PM perceptions were lower than were virtual actors' following the negative momentum sequence. More generally, interrupting positive momentum lowered PM perceptions, whereas interrupting negative momentum increased PM perceptions. Implications for the study of PM in sport are discussed