Network-guided modeling allows tumor-type independent prediction of sensitivity to all-trans-retinoic acid.

Background: All-trans-retinoic acid (ATRA) is a differentiating agent used in the treatment of acute-promyelocytic-leukemia (APL) and it is under-exploited in other malignancies despite its low systemic toxicity. A rational/personalized use of ATRA requires the development of predictive tools allowing identification of sensitive cancer types and responsive individuals. Materials and methods: RNA-sequencing data for 10 080 patients and 33 different tumor types were derived from the TCGA and Leucegene datasets and completely re-processed. The study was carried out using machine learning methods and network analysis. Results: We profiled a large panel of breast-cancer cell-lines for in vitro sensitivity to ATRA and exploited the associated basal gene-expression data to initially generate a model predicting ATRA-sensitivity in this disease. Starting from these results and using a network-guided approach, we developed a generalized model (ATRA-21) whose validity extends to tumor types other than breast cancer. ATRA-21 predictions correlate with experimentally determined sensitivity in a large panel of cell-lines representative of numerous tumor types. In patients, ATRA-21 correctly identifies APL as the most sensitive acute-myelogenous-leukemia subtype and indicates that uveal-melanoma and low-grade glioma are top-ranking diseases as for average predicted responsiveness to ATRA. There is a consistent number of tumor types for which higher ATRA-21 predictions are associated with better outcomes. Conclusions: In summary, we generated a tumor-type independent ATRA-sensitivity predictor which consists of a restricted number of genes and has the potential to be applied in the clinics. Identification of the tumor types that are likely to be generally sensitive to the action of ATRA paves the way to the design of clinical studies in the context of these diseases. In addition, ATRA-21 may represent an important diagnostic tool for the selection of individual patients who may benefit from ATRA-based therapeutic strategies also in tumors characterized by lower average sensitivity.

Management of a clinical and surgical centre in rural Cambodia (2006-2011).

The activities of the Bambino Gesù Paediatric Clinical and Surgical Centre Takeo in Cambodia started in May 2006, after the signature of a formal agreement between the Royal Government of Cambodia and the hospital. The paediatric centre is currently composed of an out-patients section with diagnostic ultrasound facilities and an obstetrics and gynaecology section, 3 consulting rooms, 20 beds for clinical activities, 13 beds for surgery, 7 beds for the paediatric intensive care unit, 2 dressing rooms, 1 out-patients sterile section, a library for off- and on-line consultation, a playroom and laundry facilities, and an administration office. For the last five years its activity has neen steadily on the increase, and the local population are beginning to look on the Centre as a full-scale local and regional referral hospital. From the 190 cases handled in 2006, the Centre increased to 669 surgical procedures in 2010 and 341 in the first four months of 2011, with good prospects of exceeding 1000 operations before the end of 2012. Takeo Centre also developed a Mobile Clinic Project to assist children directly in rural areas lacking health facilities. Today the Centre is a new reality in Cambodia's healthcare system.