The DATEL (diagnosis for territorial action environment and longevity), a territorial diagnosis for a future with our elders

The territorial structure is such that it is necessary to go through a step of diagnosis. Ageing must be apprehended in all its aspects, but the multiplicity of actors involved prevents the local powers from getting a comprehensive vision of the stakes and from implementing the adequate policies. The gerontop?le of "Pays de Loire" has developed an original method of diagnosis consisting in a comprehensive approach so called DATEL (diagnosis for territorial action environment and longevity). It is based on three aspects: an analysis of the geographical areas, a diagnosis shared by citizens and local councilors according to the Vancouver method, and a prospective review of the medico-social and health situation which integrates all services and forces at work and their potential demographic evolution. This DATEL aims to give local politicians the means to take well-informed decisions that will sustain the rapid demographic evolution of the ageing population and will maintain a good quality of life for our elders.     

F-18 fluorodeoxyglucose (FDG) PET in the diagnosis of malignant transformation of fibrous dysplasia in the pelvic bones

Fibrous dysplasia (FD) is a benign dysplastic pathology of bone-forming mesenchymal cells, resulting in replacement of trabecular bone by abnormal fibrous and immature osseous tissue. FD can be either monostotic or polyostotic, is more often unilateral, and can be part of the McCune-Albright syndrome (MIM 174800). Sarcomatous degeneration in FD is rare, ranging from less than 1% in monostotic forms to 4% in the McCune-Albright syndrome. We report the case of a 59-year-old woman with monostotic FD of the left ischium, known for over 30 years, who developed sarcomatous transformation in a low-grade spindle-cell sarcoma. The value of F-18 fluorodeoxyglucose positron emission tomography in the early diagnosis of malignant transformation, the evaluation of distant metastasis, as well as monitoring the efficacy of chemotherapy are discussed.     

Delivery of small interfering RNA. A review and an example of application to a junction oncogene

RNA interference strategies using small interfering RNA is one of the most important discoveries in biology in recent years. This technology alongside antisense oligonucleotides is very promising and our group has focused its work on the targeting of junction oncogenes with these molecules. We have taken, as first example, papillary thyroid carcinoma. But there is a great need in delivery methods for these molecules in the treatment of cancers. Indeed, many studies have shown that small interfering RNA and antisense oligonucleotides are made efficient by various innovative delivery methods and, under these conditions, offer a powerful new therapeutic tool in cancer treatment.     

A 38-gene expression signature to predict metastasis risk in node-positive breast cancer after systemic adjuvant chemotherapy: a genomic substudy of PACS01 clinical trial

Currently, no prognostic gene-expression signature (GES) established from node-positive breast cancer cohorts, able to predict evolution after systemic adjuvant chemotherapy, exists. Gene-expression profiles of 252 node-positive breast cancer patients (median follow-up: 7.7 years), mostly included in a randomized clinical trial (PACS01), receiving systemic adjuvant regimen, were determined by means of cDNA custom array. In the training cohort, we established a GES composed of 38 genes (38-GES) for the purpose of predicting metastasis-free survival. The 38-GES yielded unadjusted hazard ratio (HR) of 4.86 (95% confidence interval = 2.76–8.56). Even when adjusted with the best two clinicopathological prognostic indexes: Nottingham prognostic index (NPI) and Adjuvant!, 38-GES HRs were 3.30 (1.81–5.99) and 3.40 (1.85–6.24), respectively. Furthermore, 38-GES improved NPI and Adjuvant! classification. In particular, NPI intermediate-risk patients were divided into 2/3 close to low-risk group and 1/3 close to high-risk group (HR = 6.97 [2.51–19.36]). Similarly, Adjuvant! intermediate-risk patients were divided into 2/3 close to low-risk group and 1/3 close to high-risk group (HR = 4.34 [1.64–11.48]). The 38-GES was validated on gene-expression datasets from three external node-positive breast cancer subcohorts (n = 224) generated from different microarray platforms, with HR = 2.95 (1.74–5.01). Moreover, 38-GES showed prognostic performance in supplementary cohorts with different lymph-node status and endpoints (1,040 new patients). The 38-GES represents a robust tool able to type systemic adjuvant treated node-positive patients at high risk of metastatic relapse, and is especially powerful to refine NPI and Adjuvant! classification for those patients.