Cetuximab Augments Cytotoxicity with Poly (ADP-Ribose) Polymerase Inhibition in Head and Neck Cancer

Overexpression of the epidermal growth factor receptor (EGFR) is a hallmark of head and neck cancers and confers increased resistance and inferior survival rates. Despite targeted agents against EGFR, such as cetuximab (C225), almost half of treated patients fail this therapy, necessitating novel therapeutic strategies. Poly (ADP-Ribose) polymerase (PARP) inhibitors (PARPi) have gained recent attention due to their unique selectivity in killing tumors with defective DNA repair. In this study, we demonstrate that C225 enhances cytotoxicity with the PARPi ABT-888 in UM-SCC1, UM-SCC6, and FaDu head and neck cancer cells. The mechanism of increased susceptibility to C225 and PARPi involves C225-mediated reduction of non-homologous end-joining (NHEJ)- and homologous recombination (HR)-mediated DNA double strand break (DSB) repair, the subsequent persistence of DNA damage, and activation of the intrinsic apoptotic pathway. By generating a DSB repair deficiency, C225 can render head and neck tumor cells susceptible to PARP inhibition. The combination of C225 and the PARPi ABT-888 can thus be an innovative treatment strategy to potentially improve outcomes in head and neck cancer patients. Furthermore, this strategy may also be feasible for other EGFR overexpressing tumors, including lung and brain cancers

Caregiving process and caregiver burden: Conceptual models to guide research and practice

BACKGROUND: Parental care for a child with a developmental disability is an enormous responsibility, one that can far exceed that of typical parental care. While most parents adapt well to the situation of caring for a child with a disability, some do not. To understand parents' adaptations to their children's disabilities, the complex nature of stress processes must be accounted for and the constructs and factors that play a role in the caregiving must be considered. DISCUSSION: Evidence suggests that there is considerable variation in how caregivers adapt to their caregiving demands. Many studies have sought to qualify the association between caregiving and health outcomes of the caregivers. Contextual factors such as SES, child factors such as child behaviour problems and severity of disability, intra-psychic factors such as mastery and self-esteem, coping strategies and social supports have all been associated with psychological and/or physical outcome or parents or primary caregivers. In reviewing these issues, the literature appears to be limited by the use of traditional analytic approaches which examine the relationship between a factor and an outcome. It is clear, however, that changes to single factors, as represented in these studies, occur very rarely even in the experimental context. The literature has also been limited by lack of reliance on specific theoretical frameworks. SUMMARY: This conceptual paper documents the state of current knowledge and explores the current theoretical frameworks that have been used to describe the caregiving process from two diverse fields, pediatrics and geriatrics. Integration of these models into one comprehensive model suitable for this population of children with disabilities and their caregivers is proposed. This model may guide future research in this area

The Use of Low-Level Laser Therapy to Reduce Postoperative Morbidity After Third Molar Surgery: A Systematic Review and Meta-Analysis

Purpose Surgical removal of third molars carries morbidity and significantly affects patients' quality-of-life. This study aims to investigate whether administration of low-level laser therapy (LLLT) is effective in reducing postoperative morbidity in patients undergoing surgical removal of mandibular third molars compared with placebo. Material and Methods A systematic review and meta-analysis involving a comprehensive search strategy implemented across 5 electronic databases. This was supplemented by hand searching and contacting international experts and grey literature. Titles, abstracts, and full articles were scrutinized for studies meeting the inclusion criteria. All randomized controlled trials comparing treatment group of LLLT with a placebo control group were eligible for inclusion. The outcomes variables were postoperative pain, swelling, and trismus. Risk of bias and methodological quality assessment was carried out. We pooled data statistically, and meta-analyses were carried out using a random-effects model. Results Seventeen randomized controlled trials were included in this systematic review, all of which were considered to have a low risk of bias. Participants, aged 13 to 70 years, and 35% women, totaled 1064. Meta-analyses found significant reductions in standardized mean differences (SMDs) in swelling at day 2 and day 7 postoperatively (SMD, −0.611; 95% confidence interval, −0.968, −0.234 and SMD, −0.532; 95% confidence interval, −0.795, −0.269). There were nonsignificant reductions in SMD in pain and trismus at day 2 and day 7 postoperatively. Conclusions LLLT significantly reduces swelling after extraction of mandibular third molars compared with placebo. LLLT has not shown to reduce postoperative pain and trismus. LLLT does not cause adverse effects. There is currently insufficient evidence available, to promote the investment in LLLT vs the net clinical benefit. Randomized controlled trials with larger sample size and standardized study design and outcome measures are required, to make definitive recommendations to clinicians on its use on patients

Do the "haves" come out ahead in shanghai courts?

Drawing on 2,724 documents of adjudication decisions from Shanghai courts, this article tests the Galanter thesis that the stronger party tends to prevail over the weaker party in litigation. We find that the stronger parties not only win more often, but also do so by a large margin. Overall, institutional litigants fare better than individual litigants. When the litigants are classified by their organizational and social status, government agencies or government-related companies are the biggest winners, enjoying an enormous advantage, and farmers are the most disadvantaged underdogs, with other individuals and companies in between. When controlling for legal representation, these winning gaps remain significant and sizable. The edge of the stronger parties recurs across categories of cases in different issue areas of the law. Echoing previous comparative studies, we cast doubt on the party capability theory. We speculate that the causes of judicial inequality in China lie not only in resource gaps but also in the roots of the law and the nature of the court. © 2013, the Authors. Journal compilation © 2013, Cornell Law School and Wiley Periodicals, Inc.Link_to_subscribed_fulltex