Clinical trials update: endocrine and biological therapy combinations in the treatment of breast cancer

A greater understanding of the biological mechanisms responsible for de novo and acquired endocrine resistance has led to the rational design of clinical trials exploring the benefit of combining hormonal therapies with novel biological agents in an effort to enhance the efficacy of ER+ breast cancer treatment. These studies are increasingly including parallel biological analyses to elucidate the molecular characteristics of those tumors that are most likely to respond to specific targeted/endocrine combinations in an effort to develop a tailored approach to the management of individual patients. Unfortunately despite encouraging preclinical data, some of these combinations have yielded disappointing results in the clinical setting. This article will review the results of clinical trials of endocrine/biological combinations conducted in early and advanced breast cancer as well as provide an update on ongoing studies

Promoter Hypermethylation-Related Reduced Somatostatin Production Promotes Uncontrolled Cell Proliferation in Colorectal Cancer.

BACKGROUND: Somatostatin (SST) has anti-proliferative and pro-apoptotic effects. Our aims were to analyze and compare the SST expression during normal aging and colorectal carcinogenesis at mRNA and protein levels. Furthermore, we tested the methylation status of SST in biopsy samples, and the cell growth inhibitory effect of the SST analogue octreotide in human colorectal adenocarcinoma cell line. METHODS: Colonic samples were collected from healthy children (n1 = 6), healthy adults (n2 = 41) and colorectal cancer patients (CRCs) (n3 = 34) for SST mRNA expression analysis, using HGU133 Plus2.0 microarrays. Results were validated both on original (n1 = 6; n2 = 6; n3 = 6) and independent samples ((n1 = 6; n2 = 6; n3 = 6) by real-time PCR. SST expressing cells were detected by immunohistochemistry on colonic biopsy samples (n1 = 14; n2 = 20; n3 = 23). The effect of octreotide on cell growth was tested on Caco-2 cell line. SST methylation percentage in biopsy samples (n1 = 5; n2 = 5; n3 = 9) was defined using methylation-sensitive restriction enzyme digestion. RESULTS: In case of normal aging SST mRNA expression did not alter, but decreased in cancer (p<0.05). The ratio of SST immunoreactive cells was significantly higher in children (0.70%+/-0.79%) compared to CRC (0%+/-0%) (p<0.05). Octreotide significantly increased the proportion of apoptotic Caco-2 cells. SST showed significantly higher methylation level in tumor samples (30.2%+/-11.6%) compared to healthy young individuals (3.5%+/-1.9%) (p<0.05). CONCLUSIONS: In cancerous colonic mucosa the reduced SST production may contribute to the uncontrolled cell proliferation. Our observation that in colon cancer cells octreotide significantly enhanced cell death and attenuated cell proliferation suggests that SST may act as a regulator of epithelial cell kinetics. The inhibition of SST expression in CRC can be epigenetically regulated by promoter hypermethylation

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Construct Dimensionality of Personal Energy at Work and Its Relationship with Health, Absenteeism and Productivity

Personal energy at work has become a popular topic among HRM scholars and practitioners because it has proven to impact performance. Based on the outcomes of previous research and the call for further exploration of the construct of personal energy at work, we executed this quantitative study. We explored the factor structure of the construct and its relationships with health and productivity by examining the construct that addresses four dimensions: physical, emotional, mental and spiritual energy. Data were collected from 256 employees in an international health tech company and used to analyze construct dimensionality and relationships with health, absenteeism and productivity. The results provided support for the four-dimensional structure of personal energy at work and show that the construct of personal energy at work is related to the outcomes of health, absenteeism and productivity. Implications for theory and practice, as well as directions for future research, are discussed

Patients' preferences in the treatment of depressive disorder in primary care

Patients' preferences in the treatment of depression are important in clinical practice and in research. Antidepressant medication is often prescribed, but adherence is low. This may be caused by patients preferring psychotherapy, which is often not available in primary care. In randomized clinical trials, patients' preferences may affect the external validity. The aim of this article is to study patients' preferences regarding psychotherapy and antidepressant medication and the impact of these preferences on treatment outcome. A systematic review of the literature was performed. The majority of patients preferred psychotherapy in all available studies. Antidepressants were often regarded as addictive and psychotherapy was assumed to solve the cause of depression. Discussing and supporting preferences as part of a quality improvement program of depression care, resulted in more patients receiving the treatment that was most suitable to them. In two patient-preference trials, preferences did not influence treatment outcome. It can be concluded that a substantial percentage of well-informed patients prefer psychotherapy. Patients with strong preferences, mostly for psychotherapy, are likely not to enter antidepressant treatment or randomized clinical trials if their preferences are not supported

Rationale, design and methods for a staggered-entry, waitlist controlled clinical trial of the impact of a community-based, family-centred, multidisciplinary program focussed on activity, food and attitude habits (Curtin Universitys activity, food and att

Background: Current estimates place just under one quarter of adolescents in Australia as overweight or obese. Adolescence has been identified as a critical period for the development of obesity, yet despite this recognition, there is limited systematic research into or evaluation of interventions for overweight adolescents. Reviews have concluded that there is a substantive evidence gap for effective intervention, but physical activity, lifestyle change and family involvement have been identified as promising foci for treatment. Methods: This paper reports on the development of a staggered-entry, waitlist controlled clinical trial to assess the impact of a multidisciplinary intervention aiming to change the poor health trajectory of overweight adolescents and help them avoid morbid obesity in adulthoodCurtin Universitys Activity, Food and Attitudes Program (CAFAP). 96 adolescents, aged 1116 years, and parents, will attend twice weekly during an 8 week intensive multidisciplinary program with maintenance follow-up focussed on improving activity, food and attitude habits. Follow-up assessments will be conducted immediately after completing the intensive program, and at 3, 6 and 12 months post intensive program. Main outcomes will be objectively-measured physical activity, sedentary behaviour and activity behaviours; food intake (measured by 3 day diary) and food behaviours; body composition, fitness and physical function; mental and social well-being (quality of life, mood and attitudes), and family functioning. Discussion: This trial will provide important information to understand whether a community based multidisciplinary intervention can have short and medium term effects on activity and food habits, attitudes, and physical and mental health status of overweight adolescents. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12611001187932