The next steps in improving the outcomes of advanced ovarian cancer

Worldwide ovarian cancer affects over 200,000 women per year. Overall survival rates are poor due to two predominate reasons. First, the majority of patients present with advanced disease creating significant difficulty with effecting disease eradication. Second, acquisition of chemotherapy resistance results in untreatable progressive disease. Advances in treatment of advanced ovarian cancer involve a spectrum of interventions including improvements in frontline debulking surgery and combination chemotherapy. Anti-angiogenic factors have been shown to have activity in frontline and recurrent disease while novel chemotherapeutic agents and targeted treatments are in development particularly for disease that is resistant to platinum-based chemotherapy. These developments aim to improve the progression-free and overall survival of women with advanced ovarian cancer

Response to sunitinib (Sutent) in chemotherapy refractory clear cell ovarian cancer

• Case describes a response to sunitinib in clear cell ovarian cancer. • Discussion of unique molecular characteristics of clear cell ovarian cancers; • Practical points regarding dosing and toxicity when using sunitinib discussed

Updating beliefs about pain following advice: Trustworthiness of social advice predicts pain expectations and experience

Prior expectations influence pain experience. These expectations, in turn, rely on prior pain experience, but they may also be socially influenced. Yet, most research has focused on self rather than social expectations about pain, and hardly any studies examined their combined effects on pain. Here, we adopted a Bayesian learning perspective to investigate how explicitly communicated social expectations (‘advice about pain tolerance’) affect own pain expectations, and ultimately pain tolerance, under varying conditions of social epistemic uncertainty (trustworthiness of the advice). N = 72 female participants took part in a coldpressor (cold water) task before (self-learning baseline) and after (socially-influenced learning) receiving advice about their likely pain tolerance from a confederate, the trustworthiness of whom was experimentally manipulated. We used path analysis to test the hypothesis that social advice from a highly trustworthy confederate would influence participants' expectations about pain more than advice from a less trustworthy source, and that the degree of this social influence would in turn predict pain tolerance. We further used a simplified, Bayesian learning, computational approach for explicit belief updating to examine the role of latent parameters of precision optimisation in how participants subsequently changed their future pain expectations (prospective posterior beliefs) based on the combined effect of the confederate's advice on their own pain expectations, and their own task experience. Results confirmed that participants adjusted their pain expectations towards the confederate's advice more in the high- vs. low-trustworthiness condition, and this advice taking predicted their pain tolerance. Furthermore, the confederate's trustworthiness influenced how participants weighted the confederate's advice in relation to their own expectations and task experience in forming prospective posterior beliefs. When participants received advice from a less trustworthy confederate, their own sensory experience was weighted more highly than their socially-influenced prior expectations. Thus, explicit social advice appears to impact pain by influencing one's own pain expectations, but low social trustworthiness leads to these expectations becoming more malleable to novel, sensory learning

Embodied Precision : Intranasal Oxytocin Modulates Multisensory Integration

© 2018 Massachusetts Institute of Technology.Multisensory integration processes are fundamental to our sense of self as embodied beings. Bodily illusions, such as the rubber hand illusion (RHI) and the size-weight illusion (SWI), allow us to investigate how the brain resolves conflicting multisensory evidence during perceptual inference in relation to different facets of body representation. In the RHI, synchronous tactile stimulation of a participant's hidden hand and a visible rubber hand creates illusory body ownership; in the SWI, the perceived size of the body can modulate the estimated weight of external objects. According to Bayesian models, such illusions arise as an attempt to explain the causes of multisensory perception and may reflect the attenuation of somatosensory precision, which is required to resolve perceptual hypotheses about conflicting multisensory input. Recent hypotheses propose that the precision of sensorimotor representations is determined by modulators of synaptic gain, like dopamine, acetylcholine, and oxytocin. However, these neuromodulatory hypotheses have not been tested in the context of embodied multisensory integration. The present, double-blind, placebo-controlled, crossover study ( N = 41 healthy volunteers) aimed to investigate the effect of intranasal oxytocin (IN-OT) on multisensory integration processes, tested by means of the RHI and the SWI. Results showed that IN-OT enhanced the subjective feeling of ownership in the RHI, only when synchronous tactile stimulation was involved. Furthermore, IN-OT increased an embodied version of the SWI (quantified as estimation error during a weight estimation task). These findings suggest that oxytocin might modulate processes of visuotactile multisensory integration by increasing the precision of top-down signals against bottom-up sensory input.Peer reviewedFinal Accepted Versio

Affective regulation through touch: homeostatic and allostatic mechanisms

We focus on social touch as a paradigmatic case of the embodied, cognitive, and metacognitive processes involved in social, affective regulation. Social touch appears to contribute three interrelated but distinct functions to affective regulation. First, it regulates affects by fulfilling embodied predictions about social proximity and attachment. Second, caregiving touch, such as warming an infant, regulates affect by socially enacting homeostatic control and co-regulation of physiological states. Third, affective touch such as gentle stroking or tickling regulates affect by allostatic regulation of the salience and epistemic gain of particular experiences in given contexts and timescales. These three functions of affective touch are most likely mediated, at least partly, by different neurobiological processes, including convergent hedonic, dopaminergic and analgesic, opioidergic pathways for the attachment function, ‘calming’ autonomic and endocrine pathways for the homeostatic function, while the allostatic function may be mediated by oxytocin release and related ‘salience’ neuromodulators and circuits

Menopausal hormone therapy and pancreatic cancer risk in women : a population-based matched cohort study

Background: The role of menopausal hormone therapy (MHT) in the development of pancreatic cancer is inconclusive owing to small studies and lack of proper study design. Methods: This population-based matched cohort study included all Swedish women who used systemic MHT between 1 July 2005 and 31 December 2012. For each user of MHT, three never-users of MHT were randomly selected, matched for childbirth, history of thromboembolic events, and previous hysterectomy, as well as for year of birth, diabetes, obesity, and smoking- or alcohol-related disorders. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between MHT use and pancreatic cancer. The effect of MHT duration on pancreatic cancer development was calculated using multivariable Poisson regression. Results: There were 290,186 ever-users of MHT and 870,165 matched never-users. During the follow-up, 311 (0.0011%) ever-users of MHT and 1220 (0.0014) never-users developed pancreatic cancer. In a multivariable adjusted model, ever-users had a 23% reduced risk (OR 0.77; 95% CI: 0.68-0.87) of pancreatic cancer. This risk decreased by 35% (incidence rate ratio (IRR) 0.65; 95% CI: 0.33-1.27) in women who used MHT 1-2 years and by 60% (IRR 0.40; 95% CI: 0.18-0.88) in women who used MHT3 years compared to women with <1 year of MHT use. The type of MHT did not change the results. Conclusion: Systemic MHT use might reduce the risk of pancreatic cancer

Novel ex vivo models of epithelial ovarian cancer: the future of biomarker and therapeutic research

Epithelial ovarian cancer (EOC) is a heterogenous disease associated with variations in presentation, pathology and prognosis. Advanced EOC is typified by frequent relapse and a historical 5-year survival of less than 30% despite improvements in surgical and systemic treatment. The advent of next generation sequencing has led to notable advances in the field of personalised medicine for many cancer types. Success in achieving cure in advanced EOC has however been limited, although significant prolongation of survival has been demonstrated. Development of novel research platforms is therefore necessary to address the rapidly advancing field of early diagnostics and therapeutics, whilst also acknowledging the significant tumour heterogeneity associated with EOC. Within available tumour models, patient-derived organoids (PDO) and explant tumour slices have demonstrated particular promise as novel ex vivo systems to model different cancer types including ovarian cancer. PDOs are organ specific 3D tumour cultures that can accurately represent the histology and genomics of their native tumour, as well as offer the possibility as models for pharmaceutical drug testing platforms, offering timing advantages and potential use as prospective personalised models to guide clinical decision-making. Such applications could maximise the benefit of drug treatments to patients on an individual level whilst minimising use of less effective, yet toxic, therapies. PDOs are likely to play a greater role in both academic research and drug development in the future and have the potential to revolutionise future patient treatment and clinical trial pathways. Similarly, ex vivo tumour slices or explants have also shown recent renewed promise in their ability to provide a fast, specific, platform for drug testing that accurately represents in vivo tumour response. Tumour explants retain tissue architecture, and thus incorporate the majority of tumour microenvironment making them an attractive method to re-capitulate in vivo conditions, again with significant timing and personalisation of treatment advantages for patients. This review will discuss the current treatment landscape and research models for EOC, their development and new advances towards the discovery of novel biomarkers or combinational therapeutic strategies to increase treatment options for women with ovarian cancer

Self–other distinction and borderline personality disorder features: Evidence for egocentric and altercentric bias in a self–other facial morphing task

Self–other distinction (SOD) refers to the ability to distinguish one’s own body, actions, and mental representations from those of others. Problems with SOD are considered to be a key feature of borderline personality disorder (BPD). However, empirical studies on SOD in BPD are scarce. Here, we present a study providing preliminary support for the usefulness and validity of a self–other facial morphing task to capture the capacity for SOD in a sample of nonclinical participants high (n = 30) and low (n = 32) in BPD features. Participants had to watch a video sequence in which their own face was gradually morphed into the face of an unfamiliar other (self-to-other) or vice versa (other-to-self), requiring them to indicate at which point they judged the morph to look more like the target face than the starting face. Consistent with predictions, results showed that participants in the high-BPD group judged the morph to look like themselves for longer in the self-to-other direction (suggestive of egocentric bias), but only with a relatively more attractive target face. In the other-to-self direction, the high-BPD group had more difficulty recognizing their own face (i.e., an altercentric bias), but this time only with the relatively less attractive face. Further research is needed to replicate these findings in clinical samples, but overall they suggest that the current task might be suited to investigate SOD problems in BPD. (PsycInfo Database Record (c) 2020 APA, all rights reserved