Tumor progression has been linked to changes in the stromal environment. Myofibroblasts are stromal cells that are often increased in tumors but their contribution to cancer progression is not well understood. Here, we show that the secretomes of myofibroblasts derived from gastric cancers [cancer-associated myofibroblasts (CAMs)] differ in a functionally significant manner from those derived from adjacent tissue [adjacent tissue myofibroblasts (ATMs)]. CAMs showed increased rates of migration and proliferation compared with ATMs or normal tissue myofibroblasts (NTMs). Moreover, conditioned medium (CM) from CAMs significantly stimulated migration, invasion and proliferation of gastric cancer cells compared with CM from ATMs or NTMs. Proteomic analysis of myofibroblast secretomes revealed decreased abundance of the extracellular matrix (ECM) adaptor protein like transforming growth factor-β-induced gene-h3 (TGFβig-h3) in CAMs, which was correlated with lymph node involvement and shorter survival. TGFβig-h3 inhibited IGF-II-stimulated migration and proliferation of both cancer cells and myofibroblasts, and suppressed IGF-II activation of p42/44 MAPkinase; TGFβig-h3 knockdown increased IGF-II- and CM-stimulated migration. Furthermore, administration of TGFβig-h3 inhibited myofibroblast-stimulated growth of gastric cancer xenografts. We conclude that stromal cells exert inhibitory as well as stimulatory effects on tumor cells; TGFβig-h3 is a stromal inhibitory factor that is decreased with progression of gastric cancers.
The GPs perceive the routine use of risk scores as infeasible because of regulatory constraints and the nature of the physician-patient relationship. These factors need to be considered to increase risk-score use. Training of physicians could also help somewhat to overcome underuse. Use of computerized approaches that enable the prediction of risks for several chronic diseases simultaneously and improved computer-generated visual presentation may increase acceptance. Risk profiles should further be related to recommendations for health-behavior modification.
BackgroundPatients often seek other patients’ experiences with the disease. The Internet provides a wide range of opportunities to share and learn about other people’s health and illness experiences via blogs or patient-initiated online discussion groups. There also exists a range of medical information devices that include experiential patient information. However, there are serious concerns about the use of such experiential information because narratives of others may be powerful and pervasive tools that may hinder informed decision making. The international research network DIPEx (Database of Individual Patients’ Experiences) aims to provide scientifically based online information on people’s experiences with health and illness to fulfill patients’ needs for experiential information, while ensuring that the presented information includes a wide variety of possible experiences.ObjectiveThe aim is to evaluate the colorectal cancer module of the German DIPEx website krankheitserfahrungen.de with regard to self-efficacy for coping with cancer and patient competence.MethodsIn 2015, a Web-based randomized controlled trial was conducted using a two-group between-subjects design and repeated measures. The study sample consisted of individuals who had been diagnosed with colorectal cancer within the past 3 years or who had metastasis or recurrent disease. Outcome measures included self-efficacy for coping with cancer and patient competence. Participants were randomly assigned to either an intervention group that had immediate access to the colorectal cancer module for 2 weeks or to a waiting list control group. Outcome criteria were measured at baseline before randomization and at 2 weeks and 6 weeksResultsThe study randomized 212 persons. On average, participants were 54 (SD 11.1) years old, 58.8% (124/211) were female, and 73.6% (156/212) had read or heard stories of other patients online before entering the study, thus excluding any influence of the colorectal cancer module on krankheitserfahrungen.de. No intervention effects were found at 2 and 6 weeks after baseline.ConclusionsThe results of this study do not support the hypothesis that the website studied may increase self-efficacy for coping with cancer or patient competencies such as self-regulation or managing emotional distress. Possible explanations may involve characteristics of the website itself, its use by participants, or methodological reasons. Future studies aimed at evaluating potential effects of websites providing patient experiences on the basis of methodological principles such as those of DIPEx might profit from extending the range of outcome measures, from including additional measures of website usage behavior and users’ motivation, and from expanding concepts, such as patient competency to include items that more directly reflect patients’ perceived effects of using such a website.Trial RegistrationClinicaltrials.gov NCT02157454; https://clinicaltrials.gov/ct2/show/NCT02157454 (Archived by WebCite at http://www.webcitation.org/6syrvwXxi)
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