Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Chronic pain and sex differences:Women accept and move, while men feel blue

Purpose The aim of this study is to explore differences between male and female patients entering a rehabilitation program at a pain clinic in order to gain a greater understanding of different approaches to be used in rehabilitation. Method 1371 patients referred to a specialty pain rehabilitation clinic, completed sociodemographic and pain related questionnaires. They rated their pain acceptance (CPAQ-8), their kinesiophobia (TSK), the impact of pain in their life (MPI), anxiety and depression levels (HAD) and quality of life scales: the SF-36, LiSat-11, and the EQ-5D. Because of the large sample size of the study, the significance level was set at the p amp;lt;= .01. Results Analysis by t-test showed that when both sexes experience the same pain severity, women report significantly higher activity level, pain acceptance and social support while men report higher kinesiophobia, mood disturbances and lower activity level. Conclusion Pain acceptance (CPAQ-8) and kinesiophobia (TSK) showed the clearest differences between men and women. Pain acceptance and kinesiophobia are behaviorally defined and have the potential to be changed.Funding Agencies|Swedish Association of Local Authorities and Regions (SALAR); Vardal Foundation; RehSAM; AFA insurance, Sweden; Swedish Association for Survivors of Accident and Injury (RTP); Renee Eanders Foundation</p