activities
The main activities:
- Obtaining living cell cultures, the biological substrate for the study models. The tissues, peripheral blood and other body fluids collected by P7 will be processed to perform primary tumoral and metastatic cell cultures. P6 will provide biologic material: living cell suspensions, tissue homogenate, cell lysate to P5, P7 and P4, who will determine the incorporation of the metal and metallic aducts in the cell.
-Cytotoxicity and genotoxicity studies and apoptosis tests will be performed (P6)
- The formation of DNA-metal and protein-metal adducts will be estimated (P4, P6).
- Metal compounds action on immune response will be pursued (P6)
-the oxidative stress induced by the novel synthesized compounds and the modulation (downregulation) of metalloprotease expression, especially that from matrix metalloproteinase family (MMPs) involved in cancer proliferation and metastasis will be studied through zimography. The mutual influence of metal compounds and the generation of reactive oxygen species (ROS) and nitric oxide (NO) and feed-back effects will be followed (P6, P5).
- The modulation of the level of the protein species and expression of genes involved in the metal induced apoptosis and multidrug resistance will be evaluated (P6).
In stage S8, partner 7 will ensure:
- collection of tissue and peripheral blood collection from patients, carrying out the follow-up of patients biologic and physiologic parameters during the chemotherapeutic and platin neoadjuvant assisted radio-chemotherapeutic procedures, constituting databases regarding the evolution of the monitorized patients and treatment efficacy, quantified using biostatistic parameters such as remission and survival
- the synergic effect of metal-based treatment with irradiation will be observed. Irradiation of the biologic samples provided by P6 will be made using a Theratron cobalt therapy radiation source. Comparative and correlation studies will be performed on the chemosensibilisation effects of the novel synthesized metal-based drugs and the standard neoadjuvant platin-based drugs.
- molecular mechanisms of cellular immune response and will design specific chemotherapy and radiotherapy markers in order to individualize the cancer patient treatment with metal-based drugs. This study will correlate the data supplied by P6 on the in vitro chemosensitivity test results and that provided by P3, P4 and P5 regarding metal-DNA adducts with the oncology treatment results.