In the hospitals and pharmaceutical industry effluents, as well as in wastewater-treatment plants and more generally in wastewaters, diverse pollutants were able to be identified, genotoxics (hydrocarbons), endocrine disruptors (personal care products) or plastics (Bisphenol A )) The anticancerous molecules, although in lesser quantity represent an increasing danger. Anticancerous substances administered to the patients in great quantities are rejected trough urines, and are only partially degraded and eliminated by wastewater treatment plants. Considerable contents of these metabolites can be found in rivers and possibly in irrigation water, even in drinking water. The known consequences of their occurrence in the environment go from allergy to cancer by way of fertility losses even teratogenics effects. Within the project “Toxeaubam” (2005, ANR “blanc”) we demonstrated the feasibility of a laboratory scale membrane bioreactor, we have also adapted ecotoxicity tests on a model molecule (the cyclophosphamide) and its main metabolites, added in a domestic wastewater. The effect of these molecules on the biodegradation and the filterability of biological sludge is also quantified, leading to propositions of operating conditions The aims of this project, PANACEE, bring an opening to the previous one. They are split into 3 interdependent objectives: 1) the evaluation of the occurrence of molecules, used in the treatments of cancers, in the effluents of the corresponding services (and associated molecules within the therapies, typically disinfection ones); 2) The measure and quantification of the toxic effects, (geno / cytotoxic and endocrine disruptors) of these effluents and the contribution of the molecules and their metabolites, as well as products of disinfection in these effects; 3) the development of an hybrid process constituted by a combination of biological and physical-chemical treatments (coupling of a membrane bioreactor with adsorption / oxidation processes or nanofiltration). The efficiency of the treatment will be quantified within the framework of a technical-economic balance assessment by the evaluation of the disappearance of the global toxic effects (finalized in task 2)), the analysis of the life cycle of molecules and the energy performances of the process. This project with vocation of industrial research, and anticipation on the eco-responsible needs of decontamination bound to discharges legislations under elaboration.

The project entitled “INNODIAG” focuses on two complementary axes. On one hand; it deals with the selection and validation of new biomarkers genes in the treatment of breast cancer through the application of novel learning methods using fuzzy logic developed by the group DISCO LAAS. This tool used for the first time on data sets of tumors of breast cancer was found to have a gain rose 10% on the reliability of prognosis compared to those obtained by other existing tests, including in particular the using DNA microarray "Mammaprint®” fabricated with 70 genes selected by methods of hierarchical classification. Alongside this work, a prototype next-generation microarray, designed by the application of innovative technologies by soft lithography and detection by optical diffraction free of labeling will be build up. This development will represent a major breakthrough in bringing the microarray to the Market diagnosis by reducing its manufacturing costs, simplification of the reading system and speed in acquiring information. It will be used to design a first pre-prototype biochips to test the prediction of breast cancer carrying the biomarker genes previously identified and validated by 'classical' microarray methods. Because of its simplicity, robustness , and low cost it will be made available to clinical laboratories, and this new type of microarray is expected to fully enter into personalized medicine and help the clinician and oncologist to determine the most appropriate treatment for cancer and, more broadly, it should bring the current microarray as a tool of diagnosis. This project will be in a strategic context for the integration of converging technologies BIO-NANO-INFO in the field of Life Sciences in making the best use of potential public and private research for economic development regionally and nationally. This project covers both the component 'Experimental development' (developing a new technology for manufacturing biochips generic, up to the market between 2 and 4 years) and 'Industrial research' (pre-clinical research with the ability develop a new test this prediction based on DNA microarray previously developed and may lead to the market within 5 to 10 years). In addition, this project fits perfectly with the thematic focus 3 “Tools and innovative products in health diagnosis” and focus theme 4 "Technology Tools".

Background : Head and Neck cancers are common, 4th ranking in terms of incidence. Total (pharyngo) laryngectomy (T(P)L) is a common surgery for the treatment of pharyngo-laryngeal cancers and results in the definitive separation of the respiratory and digestive (neo-pharyngeal) tracts. The main issue with this surgery is salivary fistula (SF) (incidence of 20 to 65%), causing leaks of saliva between the sutures of the neo-pharynx. One of the main risk factors is a history of irradiation. Saliva, by flowing into the neck, causes high morbidity i.e. increased length of hospitalization, surgical revision, risk of vascular rupture and death i.e. incidence of carotid blowout syndrome around 3%. There is no current solution to reduce the incidence of SF. Objectives and means: The BIOFISS project aims to develop an innovative biomaterial (MD) in the form of a double-layer film based on biopolymers, alginate and chitosan, for the prevention of SF. The project brings together a suitable consortium with a hospital specialized in oncology (IUCT-O), 2 academic research laboratories specialized in biomaterials (CIRIMAT and INSERM UMR 1121) and 2 industrial partners (RESCOLL and Brothier) including a MD manufacturer specialized in alginate, one of the constituents of the MD. This project is based on preliminary results concerning the design of alginate-based biomaterials (CIRIMAT laboratory). The 4 main objectives of the BIOFISS project are 1) development of MD to obtain the physico-chemical and biological properties suitable for the prevention of SF; 2) characterization of its in vitro properties (biocompatibility, mechanical properties, bioadhesion, degradation time); 3) in vivo evaluation; 4) transfer and valorization Materials and Methods: This project is planned over a total of 48 months and is divided into 5 scientific axes (WP): 1. WP0: project coordination (IUCT-O/all partners) 2. WP1: Optimization of MD for SF prevention with 2 tasks: 1) development of the impermeable layer; 2) development of the absorbent layer. This axis will be coordinated by CIRIMAT using the technologies of RESCOLL and INSERM UMR 1121. Brothier will provide the alginate and will contribute its knowledge on these materials. 3. WP2: in vitro characterization of the physicochemical properties of MD; this axis will be coordinated by INSERM 1121 in collaboration with CIRIMAT. 3 tasks will be carried out: 1) evaluation of biocompatibility; 2) evaluation of healing properties; 3) evaluation of antimicrobial properties. 4. WP 3: in vivo evaluation (IUCT-O) with 4 tasks: 1) evaluation of biocompatibility and bioadhesion in a rat pharyngotomy model; 2) development of an irradiated mini-pig model; 3) development of a laryngectomized mini-pig model; 4) evaluation of the efficacy of MD on laryngectomized pigs with or without irradiation with a control group. 5. WP4: Evaluation of results, transfer and valorisation of technologies (Brothier laboratory) Expected results: In accordance with the ANR Call for Proposals, the goal of our project is to design an innovative MD aimed to reduce the rate of SF in T(P)L patients undergoing T(P)L surgery. Based on a strong consortium, all data collected during the project will provide evidence of the efficacy and safety of the new MD for the initiation of a clinical trial in the prevention of the risk of SF after neck surgery. The field of use of the biomaterial could be wider than the T(P)L, i.e. useful for many cervico-facial surgeries (cancer or not) or even in digestive surgery. BIOFISS will make it possible to perpetuate the collaboration between industrial partners for the commercialization of this new biomaterial. A new production line, which will require the recruitment of qualified personnel, will be created within Brothier for the manufacture of this new MD.