IGF-I induced genes in stromal fibroblasts predict the clinical outcome of breast and lung cancer patients

<p>Abstract</p> <p>Background</p> <p>Insulin-like growth factor-1 (IGF-I) signalling is important for cancer initiation and progression. Given the emerging evidence for the role of the stroma in these processes, we aimed to characterize the effects of IGF-I on cancer cells and stromal cells separately.</p> <p>Methods</p> <p>We used an <it>ex vivo </it>culture model and measured gene expression changes after IGF-I stimulation with cDNA microarrays. <it>In vitro </it>data were correlated with <it>in vivo </it>findings by comparing the results with published expression datasets on human cancer biopsies.</p> <p>Results</p> <p>Upon stimulation with IGF-I, breast cancer cells and stromal fibroblasts show some common and other distinct response patterns. Among the up-regulated genes in the stromal fibroblasts we observed a significant enrichment in proliferation associated genes. The expression of the IGF-I induced genes was coherent and it provided a basis for the segregation of the patients into two groups. Patients with tumours with highly expressed IGF-I induced genes had a significantly lower survival rate than patients whose tumours showed lower levels of IGF-I induced gene expression (<it>P </it>= 0.029 - Norway/Stanford and <it>P </it>= 7.96e-09 - NKI dataset). Furthermore, based on an IGF-I induced gene expression signature derived from primary lung fibroblasts, a separation of prognostically different lung cancers was possible (<it>P </it>= 0.007 - Bhattacharjee and <it>P </it>= 0.008 - Garber dataset).</p> <p>Conclusion</p> <p>Expression patterns of genes induced by IGF-I in primary breast and lung fibroblasts accurately predict outcomes in breast and lung cancer patients. Furthermore, these IGF-I induced gene signatures derived from stromal fibroblasts might be promising predictors for the response to IGF-I targeted therapies.</p> <p>See the related commentary by Werner and Bruchim: <url>http://www.biomedcentral.com/1741-7015/8/2</url></p

Geo-Climatic Early-Design Tools and Indicators

he paper introduces a simple methodology to include passive cooling dissipative solutions in early design phases. In order to fulfil this objective, specific Key Performance Indicators (KPI), which are able to analyse the geo-climatic potential of heat sinks, are reported. These indicators are based on the calculation of residual local climate cooling demand—such as introduced by the author in previous works. The specific techniques considered in this paper are natural ventilation, both for comfort and environmental cooling, direct evaporative systems and earth-to-air heat exchangers. The presented method compares these solutions using typical local climate conditions and can be applied before the definition of specific building, from early-design phases. These indicators may be included in bioclimatic tools to optimise the use of passive solutions in early-design phases such as building programming. In addition, an analysis based on a set of reference locations in the Mediterranean area will be included by considering a performance-driven approach to early design, in order to combine KPI in both an environmental and a technological design approach. In this analysis, specific requirements for each considered technology will be defined in order to include a guideline for designers. Finally, climate-change weather forecast will be considered in order to analyse the resilience of the proposed passive cooling solutions under future climate scenarios defined by IPCC. For this analysis, the software Meteonorm is used to generate the morphed typical weather conditions, and the proposed indicators will be applied to study the effect of climate change on the local geo-climatic potential of passive cooling dissipative systems

Development and Initial Validation of a Patient-Reported Adverse Drug Event Questionnaire

<p>Background Direct patient reporting of adverse drug events (ADEs) is relevant for the evaluation of drug safety. To collect such data in clinical trials and postmarketing studies, a valid questionnaire is needed that can measure all possible ADEs experienced by patients.</p><p>Objective Our aim was to develop and test a generic questionnaire to identify ADEs and quantify their nature and causality as reported by patients.</p><p>Methods We created a draft list of common ADEs in lay-terms, which were classified in body categories and mapped to the Medical Dictionary for Regulatory Activities (MedDRA (R)) terminology. Questions about the nature and causality were derived from existing questionnaires and causality scales. Content validity was tested through cognitive debriefing, revising the questionnaire in an iterative process. Feasibility and reliability were assessed using a Web-based version of the questionnaire. Patients received the questionnaire twice. Feasibility was assessed by the reported time needed for completion and ease of use. Reliability was calculated using Cohen's kappa and proportion of positive agreement (PPA) on: (1) any AIDE at patient level; (2) similar ADEs at MedDRA (R) System Organ Class level; and (3) the same AIDE at AIDE-specific level.</p><p>Results In the development phase, 28 patients with type 2 diabetes or asthma/chronic obstructive pulmonary disease (COPD) participated. Questions and answer options were rephrased, layout was improved, and changes were made in the classification of ADEs. The final questionnaire consisted of 252 ADEs organized in 16 body categories, and included 14 questions per reported AIDE. A total of 135 patients using a median of five different drugs completed the Web-based questionnaire twice. The median completion time was 15 mm for patients not reporting any AIDE, and 30 mm for patients reporting at least one AIDE. Three quarters of the patients found the questionnaire easy to use. Test-retest reliability was acceptable at patient level (kappa = 0.50, PPA 0.64) and at MedDRA (R) System Organ Class level (kappa = 0.52, PPA 0.54), but was low at ADE-specific level (kappa = 0.38, PPA 0.38).</p><p>Conclusion We developed a generic patient-reported AIDE questionnaire and confirmed its content validity. The questionnaire was feasible and reliable for reporting any AIDE and similar ADEs at MedDRA (R) System Organ Class level. Additional work is, however, needed to reliably quantify specific ADEs reported by patients.</p>

A Wellness Program for Cancer Survivors and Caregivers: Developing an Integrative Pilot Program with Exercise, Nutrition, and Complementary Medicine

The Integrative Wellness Program (IWP) at the University of Miami Sylvester Comprehensive Cancer Center (SCCC) sought to provide integrative wellness education to cancer patients, survivors, and caregivers by offering instruction in exercise, nutrition, and complementary and alternative medicine. The objective of this study was to assess the impact of the IWP on the overall wellness of the individuals participating in the program. Three different 10-week versions of the IWP were conducted over a 1-year period. Each session focused on a different wellness topic presented through interactive lectures and applied activities. A series of self-report questionnaires were administered at baseline and again at the completion of the program to assess improvements in physical activity levels, dietary habits, sleep hygiene, and quality of life. Participants were generally older, Caucasian, female, had higher levels of education, and still currently receiving treatment. Significant changes were observed in two measures: Starting the Conversation (-2.0 ± 2.40, p = .037) and the Sticking To It subscale of the Self-Efficacy and Eating Habits Survey (1.7 ± 1.22, p = .0013). A trend for improvement in the Reducing Fat subscale of the Self-Efficacy Eating Habits (0.44 ± 0.60, p = .056) was also observed. Participant satisfaction surveys indicated high levels of satisfaction and applicability of the material presented. The significant improvements detected related to dietary habits, combined with the responses from the participant satisfaction surveys, suggest that the IWP was well received and can positively impact the overall wellness of cancer patients, survivors, and their caregivers