Search results for "thérapie"
showing 10 items of 41 documents
HSP70 inhibition : a new therapeutic target against cancer
2013
Heat shock proteins (HSPs) were first discovered in Drosophila by Ritossa in 1962. As stress proteins, HSPs are induced in response to a wide variety of physiological and environmental insults. HSPs have a cyto-protective function and act as molecular chaperones by assisting the folding of nascent or misfolded proteins and by preventing their aggregation. Mammalian HSPs have been classified into 5 families according to their molecular weight: HSP110, HSP90, HSP70, HSP60 and the family of small HSPs such as HSP27 (Kampinga et al., 2009). The most well-known inducible stress chaperone HSP70 is hardly detectable at basal level in normal “non-stressed” cells, but in cancer cells HSP70 is consti…
Design of molecular imaging and theranostic agents for the detection and targeted therapy of cancers
2020
Despite significant advances in cancer detection and treatment, cancer is now the second leading cause of death worldwide. The aim of this thesis project was to design and optimize imaging agents for the diagnosis and/or therapy of various cancers.The first axis of this thesis focused on the development of a bimodal PET/fluorescence imaging agent capable of targeting neurotensin NTS1 receptors overexpressed in certain cancers. PET imaging would allow efficient detection of tumors and their metastases, while fluorescence imaging would facilitate the evaluation of tumor margins during surgery. Several compounds were synthesized, labelled with gallium-68 and studied in preclinical studies in a…
Évaluation par questionnaire des pratiques de la curiethérapie de prostate en France
2017
Resume Introduction La curietherapie des cancers de la prostate s’est progressivement implantee dans l’arsenal therapeutique comme une alternative a la prostatectomie radicale et a la radiotherapie externe. Dans le groupe des patients presentant un cancer de pronostic favorable, les survies specifiques depassent 95 % a 10 ans. L’objectif de cette etude est de decrire la place actuelle et les pratiques de la curietherapie en France. Materiel et methodes Un questionnaire realise en association avec l’Association francaise d’urologie (AFU) et la Societe francaise de radiotherapie oncologique (SFRO) et evaluant les differentes pratiques de la curietherapie en France a ete adresse a tous les uro…
Etude de la régulation transcriptionnelle des lymphocytes T CD4 dans un contexte de cancer : application en immunothérapie anticancéreuse
2015
Immune surveillance of tumors is based on the ability of effector cells of the immune system to detect and eliminate the cancer cells. Notwithstanding, the complete and spontaneous regression of established cancers was observed only in very few cases. The failure of cancer resolution by the immune system could result from the combination of several factors: i) inadequate immune response related to a low tumor immunogenicity, ii) incompetent immune system consecutively to induced or acquired immunodeficiencies and iii) the selection of resistant tumor variants able to thwart immune surveillance or subverting immune responses. Developing novel cancer immunotherapy strategies leading to potent…
Role of heat shock protein in myeloproliferative neoplasms : involvement of HSP27 in myelofibrosis
2017
Myelofibrosis (MF) is the most aggressive myeloproliferative neoplasms (MPN) with the highest degree of morbidity and mortality, including progressive bone marrow fibrosis resulting into bone marrow failure. JAK2 kinase inhibitors have been successfully used for a few years in MPN and more particularly for MF treatment. Nevertheless, their beneficial effects are mainly restricted on symptoms and not on the course of the disease. Recently, heat shock protein 90 (HSP90) - known to stabilize JAK2 - has been reported as a promising therapeutic target in MPN. However HSP90 inhibitors show toxicity and induce the expression of stress-inducible proteins such as HSP70 and, most likely HSP27 as prev…
Association de radiothérapie externe et de curiethérapie pour les cancers de la prostate
2017
International audience; Brachytherapy as sole treatment is standard of care for D’Amico classification low-risk prostate cancer. For intermediate and high-risk patients, brachytherapy can be associated to external beam radiation therapy to better take into account the risk of extracapsular effraction and/or seminal vesicle involvement. Three randomized studies have shown that this association increases freedom from relapse survival compared to exclusive external beam radiation therapy. This benefit is not shown for overall survival. The addition of a hormonal therapy to this association is most likely mandatory for high-risk patients, and needs to be confirmed for intermediate risk patients…
Rôle de l’hypotonie dans la réponse à la chimiothérapie intra-péritonéale : étude des effets sur les cellules cancéreuses et la mort immunogène indui…
2018
IntraPeritoneal Chemotherapy (IPEC) is commonly used to treat colorectal cancer metastases. However there is no standardized protocol.The aim of this work was to model this chemotherapy in vitro and to understand the role of hypotonic conditions in this model and its impact on cell death.We determined that the optimal treatment parameters on HCT116 human colon cancer cells, were an exposure of the cells for 30 minutes to 400μM of oxaliplatin under hypotonic conditions (G2.5%) at 37 °C. These results have been validated on various human and murine colic cancer cell lines. We have also shown that these treatment conditions are also able to increase the cytotoxicity of other platinum derivativ…
Mécanismes de résistance à l'apoptose induite par TRAIL dans les cellules cancéreuses : restauration de la sensibiltié à TRAIL par la chimiothérapie …
2010
The TNF-family member TRAIL (TNF-related apoptosis inducing ligand) is a cytokine involved in immune anti-tumour surveillance. TRAIL is one of the most promising agents currently under investigation, as it exhibits efficient anti-cancer cytotoxicity with limited side effects on healthy cells. The problem in current cancer therapy is that some cancer cells are already resistant, or can become resistant to TRAIL-induced cell death. The aim of my thesis was to study the mechanisms of resistance to TRAIL, and to find a way to bypass it. First, we were interested in the TRAIL-R4 antagonistic receptor, which is known to bind TRAIL without inducing a death signal. We have demonstrated for the firs…
Assessment of diaphragm and lung ultrasound interest as a diagnostic and monitoring tool in acute respiratory diseases by the physiotherapist in crit…
2021
Thoracic ultrasound is a non-invasive, ionization-free and easily available tool at the bedside of the critical care patient. The aim of this thesis is to assess the lung and diaphragm ultrasound interest in the diagnosis and monitoring of the acute pulmonary disorders by the critical care physiotherapist.Our narrative review showed a high diagnostic accuracy of lung ultrasound to diagnose acute pulmonary disorders commonly encountered by the physiotherapist. The review of the lung ultrasound semiology allowed us to propose a chest physiotherapy strategy depending the ultrasound findings in the patients. Our multicenter clinical trial enrolled 151 ICU patients and highlighted the high impac…
Identification of predictive biomarkers for the efficacy of nivolumab in patients with advanced non-small cell cancer.
2019
The recent introduction of immunotherapy has disrupted the management of non-small cell lung cancer (NSCLC). Nivolumab, an antibody targeting the immune checkpoint inhibitor PD-1, has shown remarkable results in seconde-line setting after failure of standard first-line chemotherapy. However, only a quarter of patients benefits from this therapy. To date, no predictive biomarker of the therapeutic efficacy of nivolumab has been identified in a clear and consensual manner. The research for predictive biomarkers of efficacy or resistance to this treatment is, therefore, a major challenge.The emergence of high-throughput sequencing over the past decade has had a significant impact on clinical a…