Mouse p53-deficient cancer models as platforms for obtaining genomic predictors of human cancer clinical outcomes

Mutations in the TP53 gene are very common in human cancers, and are associated with poor clinical outcome. Transgenic mouse models lacking the Trp53 gene or that express mutant Trp53 transgenes produce tumours with malignant features in many organs. We previously showed the transcriptome of a p53-deficient mouse skin carcinoma model to be similar to those of human cancers with TP53 mutations and associated with poor clinical outcomes. This report shows that much of the 682-gene signature of this murine skin carcinoma transcriptome is also present in breast and lung cancer mouse models in which p53 is inhibited. Further, we report validated gene-expression-based tests for predicting the clinical outcome of human breast and lung adenocarcinoma. It was found that human patients with cancer could be stratified based on the similarity of their transcriptome with the mouse skin carcinoma 682-gene signature. The results also provide new targets for the treatment of p53-defective tumours.

Patient-oriented computerized clinical guidelines for mobile decision support in gestational diabetes

The risks associated with gestational diabetes (GD) can be reduced with an active treatment able to improve glycemic control. Advances in mobile health can provide new patient-centric models for GD to create personalized health care services, increase patient independence and improve patients’ self-management capabilities, and potentially improve their treatment compliance. In these models, decision-support functions play an essential role. The telemedicine system MobiGuide provides personalized medical decision support for GD patients that is based on computerized clinical guidelines and adapted to a mobile environment. The patient’s access to the system is supported by a smartphone-based application that enhances the efficiency and ease of use of the system. We formalized the GD guideline into a computer-interpretable guideline (CIG). We identified several workflows that provide decision-support functionalities to patients and 4 types of personalized advice to be delivered through a mobile application at home, which is a preliminary step to providing decision-support tools in a telemedicine system: (1) therapy, to help patients to comply with medical prescriptions; (2) monitoring, to help patients to comply with monitoring instructions; (3) clinical assessment, to inform patients about their health conditions; and (4) upcoming events, to deal with patients’ personal context or special events. The whole process to specify patient-oriented decision support functionalities ensures that it is based on the knowledge contained in the GD clinical guideline and thus follows evidence-based recommendations but at the same time is patient-oriented, which could enhance clinical outcomes and patients’ acceptance of the whole system.