Therapy of oral cancer from chemo-resistance to side effects: nutraceuticals and new perspectives

Terapia del tumore del cavo orale dalla chemio-resistenza agli effetti collaterali: nutraceutici e nuove prospettive Il carcinoma a cellule squamose rappresenta il 90% dei tumori maligni che colpiscono il cavo orale e il 3% di quelli del corpo umano. Il tasso di sopravvivenza 5 anni rimane stabile sotto il 50% e non è migliorato negli ultimi decenni. Il trattamento chirurgico rappresenta ancora il gold-standard per il carcinoma a cellule squamose del cavo orale seguito da radioterapia e chemioterapia. L’introduzione della chemioterapia di induzione è stata altamente promettente per il trattamento del tumore. La riduzione del volume del tumore prima del trattamento con la radioterapia poteva aumentare l’efficacia e la tollerabilità con la riduzione degli effetti sfiguranti della chirurgia e delle radiazioni. Tuttavia l’emergere delle resistenze è uno dei grandi problemi del trattamento del tumore. I nutraceutici sono composti chimici o naturali che oltre ad un ruolo nutrizionale hanno un ruolo nella terapia di diverse patologie e nella loro prevenzione. Studi su queste sostanze hanno provato il loro ruolo nel modulare le pathway di trasduzione e nel controllo della crescita e replicazione cellulare, apoptosi, infiammazione, angiogenesi e metastasi. L’obiettivo di questo progetto di ricerca è approfondire il potenziale ruolo dei nutraceutici nel superamento delle resistenze ai chemioterapici nelle cellule di carcinoma orale a cellule squamose ed in particolare del Resveratrolo sulle linee cellulari HSC-3 e SAS.Therapy of oral cancer from chemo-resistance to side effects: nutraceuticals and new perspectives Oral squamous cell carcinoma represents the 90% of malignancies affecting the oral cavity and the 3% of all human malignancies. The 5-year survival rate remained stable below 50% and has not improved in the past two decades. Surgery still represents treatment of choice for OSCC followed by radiotherapy and chemotherapy. The breakthrough of induction chemotherapy was highly promising for treatment of oral cancer. Reducing volume tumor prior to treatment with radiotherapy could enhance efficacy and tolerability with the reduction of the disfiguring effects of surgery and radiation. However the emergence of chemotherapy resistances is one of the biggest issues in treatment of cancer. This can be due to several molecular mechanisms and can play a significant role in reducing the survival of OSCC patients. Nutraceuticals are natural or chemical compounds which have other than a nutritional role, also have health promoting, disease curing or prevention properties. Studies on nutraceuticals proved their role in modulating signal transduction pathways that control cell division and growth, apoptosis, inflammation, angiogenesis and metastasis The purpose of this research project was to evaluate the potential role of resveratrol in overcoming cisplatin and 5- fluorouracil resistance in different human squamous oral carcinoma cell lines, and in particular the role of Resveratrol on HSC-3 and SAS cell lines

Carrot or stick: CSR disclosures by Southeast Asian companies

Purpose – Motivated by legitimacy theory, this paper comprehensively examines CSR disclosure in Southeast Asian (ASEAN) countries with the aim of disentangling whether such disclosures are the result of a proactive stance or a reaction to regulations. Design/methodology/approach – After a content analysis of CSR stand-alone reports that relies on the Global Reporting Initiative (GRI) as the basis for comparison, a multivariate analysis is carried out while controlling for firm-specific incentives and industry, country and year fixed effects. Findings – The paper finds that CSR disclosure increased across the entire ASEAN. Although this increase cannot be directly ascribed to the introduction of regulations in Indonesia and Malaysia, the latter may have impacted choices of disclosure media. In countries where reporting requirements have become mandated, mandatory reporters show low levels, and voluntary reporters high levels, of CSR disclosure. The paper also finds that the attainment of CSR awards is related to disclosure. Additional analyses reveal a substitution effect between voluntary and mandatory incentives in countries with high levels of law enforcement. Originality/value – The paper analyzes not only the level and breadth of CSR disclosure, but also the motivation for its use across the still under-investigated ASEAN area, thus allowing an examination of the influence of institutional incentives above and beyond the firm-specific factors that drive CSR activities. Practical implications – The evidence suggests that the introduction of regulations can be effective in improving the level and breadth of CSR reporting only in the presence of institutions that ensure the enforcement of the disclosure regulations

Carrot or stick: CSR disclosures by South East Asian companies [Abstract]

Carrot or stick: CSR disclosures by South East Asian companies [Abstract

Towards sustainable development: The role of directors' international orientation and their diversity for non‐financial disclosure

Drawing on resource dependency and upper echelons theories, we examine the relationship between directors' international orientation (IO) and the scope of non-financial disclosures (NFD) in a two-tier board structure. Evidence from a regression analysis on a sample of non-financial firms listed on the Warsaw Stock Exchange for the 2014–2018 period shows that the IO of supervisory board members significantly and positively impacts the scope of NFD. We also find that women with IO influence the scope of NFD, whereas accounting and finance experience decreases the focus on NFD elements, especially environmental information. The results imply that both the IO of the supervisory board and the bundle of characteristics facilitate the move toward sustainable development. The findings of our study should be of interest to companies, regulators and policymakers to integrate sustainability practices into their corporate strategies

Interleukin-1 blockade in recently decompensated systolic heart failure: study design of the recently decompensated heart failure anakinra response trial (RED-HART)

Heart Failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, and poor exercise capacity due to impaired cardiac function. The incidence of HF is increasing and represents the leading cause of hospitalization in the United States among patients > 65 years of age. Neurohormonal blockade has proven to reduce morbidity and mortality; however the persistent toll of HF demonstrates the urgent need to continue to develop novel drugs that target other pathophysiological paradigms. The presence of inflammation in cardiovascular disease has been well-established and interleukin-1 (IL-1), the prototypical proinflammatory agent, has been shown in preclinical animal models to induce cardiac dysfunction. The current study will investigate the role of IL-1 as an inflammatory mediator of HF progression and investigate whether IL-1 blockade with anakinra, recombinant human IL-1 receptor antagonist, improves aerobic exercise performance in patients with recently decompensated systolic HF. This study will be composed of 3 treatment arms (20 patients each): 1) anakinra 100mg daily for 12 weeks; 2) anakinra 100mg daily for 2 weeks followed by placebo for 10 weeks; or 3) placebo for 12 weeks. All patients will be followed for at least 24 weeks. The co-primary endpoints will be placebo-corrected interval changes in peak oxygen consumption (VO2) and ventilatory efficiency (VE/VCO2 slope) measured by Cardiopulmonary Exercise Testing (CPX) after 2 weeks of anakinra treatment. Secondary endpoints will include interval changes in 1) CPX variables at 4, 12 and 24 weeks; 2) echocardiographic measures of cardiac dimension/function; 3) quality of life assessments; 4) inflammatory biomarkers; and 5) clinical outcome including days alive outside of the hospital and survival free of re-hospitalization for HF. The RED-HART study will be the first study to address the potential benefits of IL-1 blockade on aerobic exercise performance in patients with recently decompensated HF

Compensation Committee Quality and Effective Executive Remuneration

Grounding in the agency theory, this paper questions whether high quality compensation committee influences the design of executive remuneration towards the alignment of the contrasting interests between managers and shareholders. Relying on a comprehensive approach that captures the compensation committee quality based on different attributes (i.e. independence, interlocking directorates, directors appointed by minorities) we conduct a two-step empirical analysis. First, we illustrate the evolution over time of the stock option plan characteristics and construct an illustrative diagram that shows the linkages between the attributes of the compensation committee quality and the elements of the option plans. Second, we run a probit regression analysis to deeply investigate the picture emerging from the diagram. Our results document that the quality of compensation committee significantly affects the assignment of incentive stock option plans. The paper evidence advances the knowledge in the literature on compensation committee and executive remuneration, by highlighting that structural characteristics of the committee other than independence of its members play a pivotal role in writing effective remuneration contracts for the executives. Our findings are also useful for investors and policymakers

Interleukin-1 blockade in heart failure with preserved ejection fraction: rationale and design of the Diastolic Heart Failure Anakinra Response Trial 2 (D-HART2)

Heart failure with preserved ejection fraction (HFpEF) now accounts for the majority of con-firmed HF cases in the United States. However, there are no highly effective evidence-basedtreatments currently available for these patients. Inflammation correlates positively withadverse outcomes in HF patients. Interleukin (IL)-1, a prototypical inflammatory cytokine, hasbeen implicated as a driver of diastolic dysfunction in preclinical animal models and a pilot clini-cal trial. The Diastolic Heart Failure Anakinra Response Trial 2 (D-HART2) is a phase 2, 2:1 ran-domized, double-blind, placebo-controlled clinical trial that will test the hypothesis that IL-1blockade with anakinra (recombinant human IL-1 receptor antagonist) improves (1) cardiorespi-ratory fitness, (2) objective evidence of diastolic dysfunction, and (3) elevated inflammation inpatients with HFpEF (http://www.ClinicalTrials.gov NCT02173548). The co–primary endpointswill be placebo-corrected interval changes in peak oxygen consumption and ventilatory effi-ciency at week 12. In addition, secondary and exploratory analyses will investigate the effectsof IL-1 blockade on cardiac structure and function, systemic inflammation, endothelial function,quality of life, body composition, nutritional status, and clinical outcomes. The D-HART2 clinicaltrial will add to the growing body of evidence on the role of inflammation in cardiovascular dis-ease, specifically focusing on patients with HFpEF

the influence of blockholders bondholders and families on the venturers accounting behavior

Relying on the opportunistic view of contracting theory, the paper explores the influence of blockholders, bondholders and families on the managerial accounting for interests in jointly controlled entities. In particular, it assumes that the equity method is an opportunistic accounting choice as it improves firm performance and induces managerial self-dealing rather than efficient contracting. The paper examines a sample of Italian listed companies holding interests in jointly controlled entities through a logistic regression analysis. Findings show that the family influence encourages the opportunistic choice of equity method, while the monitoring role played by blockholders and bondholders discourages the use of the performance-improving technique. The research contributes to the literature on contracting theory and corporate governance and has also practical implications for evaluating the appropriateness of IFRS 11.</p