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Larrouy, Anne. "Antibioprophylaxie en chirurgie carcinologique des voies aérodigestives supérieures". Bordeaux 2, 1994. http://www.theses.fr/1994BOR2M070.
Pełny tekst źródłaBlons, Hélène. "Altérations génétiques et cancers des voies aérodigestives supérieures, corrélations anatomo-cliniques". Paris 5, 1999. http://www.theses.fr/1999PA05P041.
Pełny tekst źródłaBozec, Alexandre. "Apport préclinique aux thérapeutiques moléculaires ciblées dans les carcinomes épidermoïdes des voies aérodigestives supérieures". Aix-Marseille 2, 2007. http://www.theses.fr/2007AIX20664.
Pełny tekst źródłaLemaire, Frédéric. "Caractérisation de l'expression génique des tumeurs des voies aérodigestives supérieures : perspectives diagnostiques et thérapeutiques". Paris, Institut national d'agronomie de Paris Grignon, 2004. https://pastel.archives-ouvertes.fr/pastel-00000629.
Pełny tekst źródłaLemaire, Frédéric Jean Laurent. "Caractérisation de l'expression génique des tumeurs des voies aérodigestives supérieures: perspectives diagnostiques et thérapeutiques". Phd thesis, INAPG (AgroParisTech), 2004. http://pastel.archives-ouvertes.fr/pastel-00000629.
Pełny tekst źródłaCromer, Anne. "Identification et caractérisation des gènes différentiellement exprimés dans les cancers des voies aérodigestives supérieures". Université Louis Pasteur (Strasbourg) (1971-2008), 2004. http://www.theses.fr/2004STR13149.
Pełny tekst źródłaHead and neck cancer is responsible for 12% of cancer deaths in men in France. Despite thérapeutical improvement, 5-year survival rates have remained largely unchanged in the last few decades and patients frequently present with locoregional recurrence and metastatic disease (30-50%). The work presented here aimed at identifying genes differentially expressed in HNSCC tumorigenesis, as well as in metastasis progression. Two complementary transcriptome screens were performed using Differential Display and Affymetrix microarrays. Around 3 000 genes were identified that are differentially expressed between hypopharyngeal carcinoma and normal uvula. In addition, we identified 164 genes with distinct expression levels in tumours with different metastatic outcomes. The involvement of some of these genes in cancer have already been decribed (eg. MMPs, CXCR4), whereas others are unknown in public databases. Furthermore, we functional characterized two of these 'unkown' genes: 0656D/LL5b, which encodes a protein binding phosphoinositides (3,4,5) triphosphates, and h1655E, an homolog of NudC, a protein involved in nuclear migration. The sequences we isolated are an exhaustive list of tumorigenesis and metastatic invasion markers in HNSCC. These are potential diagnostic or prognostic markers, and potential therapeutic targets
Thomas, Fabienne. "Mécanismes d'action et de résistance de l'erlotinib dans les cancers des voies aérodigestives supérieures". Toulouse 3, 2007. http://thesesups.ups-tlse.fr/746/.
Pełny tekst źródłaOur work aims to study the action of an EGFR inhibitor (erlotinib) in patients with HNSCC; and to identify predictive markers of response in order to select patients that can benefit of the treatment. Immunochemistry analyses were performed on tumor tissues and show that basal p21waf expression (CDK-cyclins inhibitor) was positively associated with tumor response. EGFR mutations and Kras mutations were not detected in HNSCC patients of our study. . The EGFR gene copy number, that has been identified as a factor linked with tyrosine kinase inhibitors sensitivity in lung cancer, did not correlate with clinical response. We also studied erlotinib pharmacokinetics and try to establish pharmacokinetics/pharmacodynamics relationships (PK /PD relationships). Pharmacokinetic analysis show that the smoking status, the hepatic function and age were relevant covariates to predict erlotinib elimination. Moreover, there is a relationship between drug exposure and toxicity but not between exposure and response. The last part of this work consisted in analysing genomic expression of the tumors before and after treatment by using microarrays (Affymetrix HG U133A GeneChip(r)) to identify genes differentially expressed in responders versus non responders and to characterize erlotinib effect on genes expression
Combes, Jean-Damien. "Epidémiologie des infections à papillomavirus humains et cancers des voies aérodigestives supérieures : enjeux et perspectives de prévention". Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10367.
Pełny tekst źródłaAt least one out of six cancers worldwide is caused by infectious agents, of which human papillomaviruses (HPV) are responsible for around 600 000 cancer cases each year. HPV are recognized as a necessary cause of cervical cancer, and the cause of a fraction of cancers of the anus, vulva, vagina, penis, but also the oropharynx. Recent epidemiological data report an alarming increase in the incidence of HPV-induced oropharyngeal cancers in some devel- oped countries, as in North America and North Europe. In cervical cancer, extended knowledge of the natural history of HPV infection and associat- ed lesions has led to the implementation of cervical pap smear screening resulting in a sub- stantial decrease in cervical cancer incidence. Conversely, in HPV-induced head and neck cancers, very few data on the natural history of the disease are available. Today, the mode of transmission of HPV infection and the steps in cancerisation of head and neck tissues are still poorly understood. Although vaccination against HPV should impact the incidence of HPV- induced cancers other than in the cervix, vaccine coverage is insufficient in many countries to generate herd immunity, and to date no other method for prevention of HPV-induced head and neck cancers is available. The main objectives of this work are: (i) to better define the oncogenic potential of the differ- ent HPV types [Articles I, II and III]; (ii) to improve the knowledge of the role of HPV in can- cers of the head and neck [Articles IV and V]; and (iii) to understand the natural history of HPV infection and associated lesions in the oropharynx [Projects I and II]
Carton, Matthieu. "Facteurs de risque professionnels des cancers des voies aérodigestives supérieures chez les femmes : analyse des données de l’étude Icare". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLV002/document.
Pełny tekst źródłaBackground : Few occupational studies have addressed head and neck cancer, and these studies have been predominantly conducted in men. Objective : Our objective was to investigate the associations between head and neck cancer and occupational exposures in women Population and methods : ICARE, a French population-based case–control study, included 296 squamous cell carcinomas of the head and neck (HNSCC) in women and 775 female controls. Lifelong occupational history was collected. Job-exposure matrices were used to assess exposure to five chlorinated solvents (carbon tetrachloride; chloroform; methylene chloride; perchloroethylene; trichloroethylene), 5 petroleum solvents (benzene; special petroleum product; gasoline; white-spirits and other light aromatic mixtures; diesel, fuels and kerosene), 5 oxygenated solvents (alcohols; ketones and esters; ethylene glycol; diethyl ether; tetrahydrofuran) and 7 fibers and dusts (asbestos, flour dust, leather dust, refractory ceramic fibers, cement dust, mineral wools and silica) . An analysis by job title was conducted, and then associations with specific occupational exposures were investigated.Odds ratio (ORs) and 95% confidence intervals (CI), adjusted for smoking, alcohol drinking, age and residence area, were estimated with logistic models. Results : Significantly increased HNSCC risks were found for several jobs and industries. Some of these occupations (food and beverage processors, electrical and electronic equipment assemblers, welders and flame cutters) may entail exposure to agents such as solvents, metals, welding fumes and various dusts. Analyses for specific occupational exposures showed a significantly elevated risk of HNSCC associated with exposure to trichloroethylene and perchloroethylene. There is no clear evidence that petroleum or oxygenated solvents, some of them commonly used by women, are risk factors for HNSCC. Exposure to flour dust increased significantly HNSCC risk. Probable exposure to asbestos was associated with a moderate, non-significant elevation in risk. Analyses by cancer site (oral cavity, pharynx, larynx) were hampered by small numbers and did to reveal any specific association.Conclusion : These findings suggest that occupational exposure to perchloroethylene, trichloroethylene and flour dust may increase the risk of HNSCC in women
Jehl, Aude. "Cavéoline-1 prédictive de la métastase et de la rechute locorégionale des cancers des voies aérodigestives supérieures". Thesis, Strasbourg, 2022. http://www.theses.fr/2022STRAJ070.
Pełny tekst źródłaThis translational research project on head and neck cancers has identified caveolin-1 (Cav1) as a prognostic biomarker for the evolution of a primary tumor of these cancers. Indeed, an overexpression of this protein favors a locoregional relapse whereas a deficiency of Cav1 engages the tumor towards a metastatic process. Moreover, we have highlighted the involvement of the Cav1 / EREG / YAP axis in the resistance to treatment (cetuximab and radiotherapy). Finally, we identified epiregulin (EREG) as the key protein in cetuximab resistance. Thus, a deficiency of EREG sensitizes cells to cetuximab by activation of ferroptosis and the association of this target therapy with the RSL3 molecule or metformin drastically restricts cell survival by accentuating this programmed cell death. These last results could be confirmed thanks to a complex 3D model recapitulating the intra- and inter-tumoral heterogeneity, namely the tumoroid model established from surgical parts of patients with head and neck cancer
Mouawad, François. "Evaluation de combinaisons thérapeutiques ciblées en cancérologie des voies aérodigestives supérieures. Mise au point d’un modèle tumoral in vivo". Thesis, Lille 2, 2014. http://www.theses.fr/2014LIL2S028/document.
Pełny tekst źródłaHead and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide. The treatment of advanced stages HNSCC is based on surgical treatment combined with radiotherapy and chemotherapy or concomitant chemo-radiotherapy. However, the 5-year survival remains poor for advanced stages HNSCC and the development of new targeted therapies is eagerly awaited. F14512 combines an epipodophyllotoxin core-targeting topoisomerase II with a spermine moiety introduced as a cell delivery vector. This spermine moiety facilitates selective uptake by tumor cells via the Polyamine Transport System (PTS) and reinforces topoisomerase II poisoning. Here we report the evaluation of F14512 toward HNSCC.Four cell lines representative of head and neck cancer localizations were used: Fadu (pharynx), SQ20B (larynx), CAL33 and CAL27 (base of the tongue). PTS activity and specificity were evaluated by confocal microscopy and flow cytometry using the fluorescent probe F17073 which contains the same spermine moiety as F14512. Cytotoxicity, alone or in association with standard chemotherapeutic agents (cisplatin, 5FU), and radio-sensitizing effects were investigated using MTS and clonogenic assays, respectively. F14512 efficiency and PTS activity were also measured under hypoxic conditions (1% O2).In all 4 tested HNSCC lines, an active PTS was evidenced providing a specific and rapid transfer of spermine-coupled compounds into cell nuclei. Interestingly, F14512 presents a 1.6 to 11 fold higher cytotoxic effect than the reference compound etoposide (lacking the spermine chain). It appears also more cytotoxic than 5FU and cisplatin in all cell lines. Competition experiments with spermine confirmed the essential role of the PTS in the cell uptake and cytotoxicity of F14512. Hypoxia had almost no impact on the drug cytotoxicity. The combination of F14512 with cisplatin, but not 5FU, was found to be synergistic and, for the first time, we demonstrated the significant radio-sensitizing potential of F14512. The spermine moiety of F14512 confers a targeted effect and a much better efficacy than etoposide in HNSCC lines. The synergistic effect observed in association with cisplatin and radiotherapy augurs well for the potential development of F14512 in HNSCC
Zahner, Martine. "Oblitérations artérielles et chimiothérapie 5 fluorouracile-cisplatine des cancers des voies aéro-digestives supérieures : à propos de cinq observations". Saint-Etienne, 1989. http://www.theses.fr/1989STET6217.
Pełny tekst źródłaCabelguenne, Arnauld. "GSTP1 et p53 : marqueurs prédictifs de la réponse à la chimiothérapie associant le 5-Fluorouracile et le Cisplatine dans les cancers des voies aérodigestives supérieures". Paris 5, 2003. http://www.theses.fr/2003PA05N109.
Pełny tekst źródłaOptimization of therapeutic strategy requires prior determination of predictive parameters of patients' response to anti-cancer drugs. In head and neck cancer patients treated by induction chemotherapy based on Cisplatin and 5-Fluorouracil, we showed a link between the presence of allelic GSTP1105val and the more important presence of mutations in p53 gene, that GSTM1 gene deletion was a risk factor of laryngeal cancers (2,6 times), that chemotherapy response is associated with a low plasma level of GSTP1. Presence of p53 mutations led to a decrease of chemo-sensibility to CDDP and to 5-FU. We identified a significant difference between the presence of p53 mutations in responder patients and non-responder patients (61% versus 81%). Predict the response to chemotherapy is now possible
Coliat, Pierre. "Stratégie de sensibilisation des tumeurs des voies aérodigestives supérieures aux anti-EGFR et résistance induite : induction de HIF-2 et opportunité thérapeutique". Thesis, Strasbourg, 2015. http://www.theses.fr/2015STRAJ067/document.
Pełny tekst źródłaManagement of HNSCC relies on surgery, radiotherapy, and chemotherapy. Despite these treatments, the 5 years overall survival of patient is lower than 50%. Main causes of therapeutic failure are due to the profile of resistance of tumors. The efficacy of a combination rapalogues and anti-EGFR therapies in targeting the EGFR/mTOR/HIF-1 axis in solid tumors was shown previously. In this PhD work, we have evaluated the impact of a low-dose drug combination on head and neck cancer cells lines with a pharmacological and molecular approach. We show that the combination of rapamycine (5nM) and cetuximab (2,5μg/ml) efficiently inhibits the HIF-1 transcription factor and impairs cell clonogenic survival. The efficacy of radiation therapy is improved by this drug combination. However, cell resistance to the treatment is acquired via the induction of HIF-2 in our resistant model cell line. This induction is associated with more tumor relapse in tumors mice xenograft. The inhibition of HIF-2 achieves a dramatic drop of cell clonogenic survival to < 1%
Verillaud, Benjamin. "Propriétés biologiques du récepteur TLR3 dans les carcinomes des voies aérodigestives supérieures : contribution à l’oncogénèse et intérêt comme cible thérapeutique". Thesis, Paris 11, 2015. http://www.theses.fr/2015PA11T006/document.
Pełny tekst źródłaBackground. Head and Neck (HN) carcinomas are the 6th most frequent type of cancer worldwide. The role of the TLR3 receptor in HN carcinomas remains poorly understood.Objectives and Methods. 1) To assess the expression level of TLR3 in HN carcinoma cell lines and biopsies by Western blot and immunohistochemistry, respectively. 2) To study the role of TLR3 in tumour growth using specific cell lines with conditional knock-down of TLR3. 3). To assess in vitro the cytotoxic effects of artificial ligands of TLR3 used either alone or in combination with an IAP (inhibitor of apoptosis protein) inhibitor.Results. TLR3 protein was detected at a high level by Western blot analysis in HN carcinoma cell lines, by comparison with a panel of other human epithelial cancer cell lines. TLR3 was also consistently detected by immunohistochemistry in tumour biopsies. TLR3 seem to play a role in HN carcinoma cell growth: under certain culture conditions (hypoxic or low fetal calf serum/low nutrient culture conditions), TLR3 stimulation by a synthetic ligand, the poly(A:U), favours tumour cell growth. We investigated the effects of TLR3 stimulation on glucose metabolism using a Seahorse® analyzer, which measures the oxygen consumption and the proton production in living cells. Our results indicate that TLR3 stimulation induces an increase in anaerobic metabolism (extra-mitochondrial glycolysis). A metabolomic study revealed significant changes in the metabolic profile of cancer cells treated by poly(A:U) by comparison with untreated cells. We also showed that under TLR3 stimulation, HIF1 became detectable by Western blot analysis, even in normoxia. Given the fact that RNA fragments released by dying cells are able to trigger TLR3, one can assume that TLR3 might favour cancer cell survival in hypoxic areas located near the necrotic core of the tumour. However, TLR3 expression is also a factor of vulnerability for HN carcinoma cells: indeed, the combination of TLR3 artificial ligands with an IAP inhibitor has a strong cytotoxic effect on HN carcinoma cells in vitro
Gilormini, Marion. "Inhibition des protéines anti-apoptotiques de la famille Bcl-2 par l'ABT-737 : intérêt pour le traitement des cancers des voies aérodigestives supérieures". Thesis, Lyon 1, 2015. http://www.theses.fr/2015LYO10277/document.
Pełny tekst źródłaHead and neck squamous cell carcinomas (HNSCC) are frequently characterized by chemotherapy and radiation resistance and 5-year survival rates have lingered around 50% for several decades. The frequent resistance of HNSCC is due, in large part, to aberrant inhibition of apoptosis and overexpression of antiapoptotic members of the Bcl-2 protein family. The aim of this study was to examine, in association with radiation, the impact of ABT-737, a potent small-molecule inhibitor of Bcl-XL and Bcl-2, on HNSCC cells and cancer stem cells (CSC).The first part of our work demonstrated that ABT-737 strongly synergized with radiotherapy to promote HNSCC cell death and loss of clonogenic survival. This effect involves mitochondrial damage, modulates ceramide metabolism and modify the expression of some proteins of the Bcl-2 family whose interactions with other family members determine cell fate. Moreover, we found that this combination is able to significantly slow tumor growth.The second part of our work revealed that ABT-737, even without radiation, had a preferential cytotoxic activity in vitro towards CSC. Thus, as CSC have a greater capacity for tumor relapse, increased motility and invasiveness, our data suggest that ABT-737 could effectively complement a first line of therapy with chemotherapy or radiotherapy in order to target residual quiescent HNSCC CSC
Rebucci, Magali. "Mécanismes de résistance au cetuximab et influence des associations de traitement dans des lignées cellulaires de cancers de voies aérodigestives supérieures". Phd thesis, Université du Droit et de la Santé - Lille II, 2010. http://tel.archives-ouvertes.fr/tel-00576444.
Pełny tekst źródłaMagné, Nicolas Charles. "Le récepteur d'EGF [Epidermal Growth Factor] : facteur pronostique dans les cancers épidermoïdes des voies aérodigestives supérieures et explorations pré-cliniques de son ciblage thérapeutique". Aix-Marseille 2, 2002. http://theses.univ-amu.fr.lama.univ-amu.fr/2002AIX20667.pdf.
Pełny tekst źródłaNizard, Mevyn. "Optimisation d'un vaccin thérapeutique dans les tumeurs des voies aérodigestives supérieures associées aux papillomavirus : rôle de l'induction d'une immunité muqueuse et de la combinaison à la radiothérapie". Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015PA05T027/document.
Pełny tekst źródłaCancer is the second mortality cause worldwide while mucosal cancers (lung, stomac, …) is the first mortality cause from. The majority of cancer vaccines against mucosal tumors have not given rise yet to significant clinical results. In this work we developed a strong immunotherapy based on the nontoxic subunit B from shiga toxin and showed for the first time that the localization of the immunization is crucial to induce potent and effective anti-tumoral responses. In a preclinical model a systemic immunization failed to induce a therapeutical protection against mucosal tumor challenge while intranasal immunization completely succeed. We identified a CD8 T lymphocyte population as a required cells in this protection and more precisely the T resident memory (Trm) cells. This Trm showed the classical CD103 phenotype as well as the CD49a which can play a specific role in the retention or the migration of this cells in the tumor tissue and might play a role in the survival. We also demonstrate that dendritic cells from the mucosal parenchyma was required to induce the CD49a expression on CD8 T cells while dendritic cells from the spleen was not. Our work shows that the Trm number as an impact in the anti-tumoral protection. We were able to reduce the Trm number in vivo using an anti-TGF-β antibody. This number diminution was correlated with a less efficient anti-tumoral protection. Patients with head and neck cancers are treated with radiotherapy. In this situation we showed that the combination of radiotherapy and our immunotherapy was associated with a better protection than radiotherapy alone or immunotherapy alone thanks to a vascular normalization. These results might rapidly lead to clinical trials and might open new ways to work with immunotherapies
Blanchard, Pierre. "Méta-analyses sur données individuelles d’essais randomisés dans les cancers des voies aéro-digestives supérieures. Développements méthodologiques et cliniques". Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T065/document.
Pełny tekst źródłaHead and neck cancers represent the fifth cause of death from cancer in France. They are often diagnosed at an advanced stage. The poor prognosis of these diseases has led to the introduction of intensified treatments. Numerous randomized trials have evaluated the benefits of the addition of chemotherapy to locoregional treatment and of the modification of radiotherapy fractionation. The results of these trials have been synthesized in two individual patient data meta-analyses coordinated by the Meta-Analysis Unit of Gustave Roussy Cancer Center. However these meta-analyses bring up clinical and methodological questions, some of which are dealt with in this thesis. First we have studied by different means the interaction between patient level covariate, tumor site and treatment effect. We have also adapted the methodology of network meta-analyses to survival data to perform a global analysis of the entire meta-analysis database, and to rank treatments according to their efficacy, including some treatments that had not been directly compared. Some of these results were eventually confirmed by subsequently published randomized trials. We have reviewed the advantages and limits of network meta-analysis. We have also launched the update of all these meta-analyses in order to produce results consistent with actual clinical practice, update patient follow-up, and collect additional data regarding treatment efficacy, toxicity and compliance. The final results of the taxane induction meta-analysis are presented in this manuscript
BLANCHARD, Pierre. "Méta-analyses sur données individuelles d'essais randomisés dans les cancers des voies aéro-digestives supérieures. Développements méthodologiques et cliniques". Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-00983478.
Pełny tekst źródłaDanoy, Patrick. "Gènes de la réparation de l'ADN chez l'homme : outils pour les études génétiques et fonctionnelles". Paris 6, 2007. http://www.theses.fr/2007PA066133.
Pełny tekst źródłaDesoutter, Aline. "Modèle d’irradiation mandibulaire chez le lapin et évaluation d’un traitement par ultrasons pulsés de faible intensité sur la régénération osseuse". Electronic Thesis or Diss., Lyon 1, 2022. http://www.theses.fr/2022LYO10152.
Pełny tekst źródłaExternal radiotherapy is widely used in the treatment of cancers of head and neck cancers. The main side effect is osteoradionecrosis, which can lead to a major deterioration in the quality of life. Low-intensity pulsed ultrasound (LIPUS) has been described in the stimulation of bone healing in traumatology and orthopaedics. They would have an effect on the early vascular phase of bone consolidation. We therefore wanted to study, through an animal study, their impact on the healing of irradiated maxillary bones. For this, we have developed a model of radiotherapy in rabbits, in order to study the healing after creation of a bone defect on an irradiated mandible. Irradiation was performed according to the following protocol : 8.5Gy/week, with one session per week, for 5 weeks, for a total dose of 42.5Gy. Mandibular surgery consisted of performing a standardized bone defect immediately after irradiation. A control group benefited from the same surgery, without prior irradiation. With this model we obtained an alteration in bone healing, confirmed by histology and microscanner. Once the radio-induced bone alterations were highlighted, we were able to renew the protocol by adding an additional step of applying LIPUS to the surgical sites. The protocol consisted of the postoperative application of LIPUS, for 10 sessions, during 20 minutes, with the following parameters : 30mW/cm², pulse 1:4, 20 min, 1MHz. Application of LIPUS on the irradiated rabbit model did not appear to have a beneficial effect on bone healing : in histology, healing did not appear to be improved after application of LIPUS ; on the microscan, some parameters even seemed to be negatively impacted by LIPUS. We can however assume an interesting effect on the general state of health of the animals, with in particular an increase in their weight and their water consumption. Our results should be interpreted with great caution. Indeed, the sample studied is very small, and there is a lot of heterogeneity between the different subjects. In addition, several limitations that could question the validity of this study should also be taken into consideration. In the end, even if the LIPUS technology does not seem beneficial on bone healing in irradiated terrain with regard to the results that we obtained, this work validates an animal radiotherapy model. This model could be used to test other possible therapies in the future
Delahaye-Sourdeix, Manon. "Moving beyond Genome-Wide Association Studies". Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10238.
Pełny tekst źródłaGenome-wide association (GWA) studies consist in testing up to one million (or more) single nucleotide polymorphisms (SNPs) for their association with cancer risk in thousands of individuals, without requiring any prior knowledge on the functional significance of these variants. These studies have been valuable for establishing etiological hypotheses and understanding the underlying genetic architecture of human diseases. However, most of the heritable factors of these traits remain unexplained. Part of this variation may come from rarer variants that are not targeted by current genotyping arrays or variants with moderate to low effects for which detection by current GWA studies is impractical. In this context and as illustrated in this thesis, GWA studies can now serve as starting points towards further discoveries, looking for new strategies to study both rarer variants and rarer diseases. We have specifically explored these approaches in the context of lung cancer, head and neck cancer and Hodgkin's lymphoma. The use of bioinformatics to combine recent GWA study results with other sources of information, the integration of different types of genomic data as well as the investigation of the interrelationship between germline and somatic alterations represent the main opportunities pursued in this thesis work
Sandoval, Federico. "Optimisation d’un vaccin thérapeutique contre les tumeurs des voies aérodigestives supérieures associées au virus de papilloma humain (HPV) : Mise en évidence du rôle de la compartimentalisation de la réponse immunitaire antitumorale". Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05T012.
Pełny tekst źródłaRecent clinical trials have shown the therapeutic benefits of new promising immunotherapies (Sipoleucel T for prostate cancer, Ipilimumab in melanoma…). But by far, the majority of cancer vaccine clinical trials have shown modest clinical effects on cancer patients, contrasting with results found in preclinical models. Those preclinical models of cancer rely on subcutaneous grafts of tumor cells which do not mimic the true anatomic location of tumor lesions. In addition, in most cases cancer vaccines are administrated by systemic route, eliciting systemic antitumor responses and therapeutic effects. The antitumor response elicited by those vaccine strategies at the local environment of tumor location and their antitumor effect on orthotopic tumor models has not yet been addressed in preclinical cancer models. Since the majority of human tumors develop at mucosal surfaces, we addressed the question of the effect of the immunization route in the induction of local mucosal antitumor CD8+T cell responses by comparing a systemic intramuscular (i.m.) and intranasal (i.n.) route of administration of cancer vaccine. This vaccine consists of a non-replicative vaccine strategy that targets tumor antigen in vivo to dendritic cells developed at our laboratory and composed of the B subunit of the Shiga toxin (STxB) associated to a tumor antigen (E7 protein of HPV16). We also analyzed the antitumor effect of these vaccinations on two mucosal orthotopic tumor models of head and neck and lung cancer expressing the E7 antigen. We found that intranasal vaccination induced stronger specific CD8+T cell responses and antitumor effects at mucosal sites than systemic immunization, and, that mucosal vaccination induced a mucosal imprinting phenotype on mucosal derived antigen specific T cells as they expressed the mucosal integrins CD103 and CD49a, as opposed to systemic specific CD8+T cells or tumor infiltrating T cells in subcutaneous tumors. Inhibition of CD49a reduced the antitumor efficacy of the nasal vaccine and the number of tumor infiltrating CD8+T cells on orthotopic mucosal tumors. Our results showed that systemic antigen-specific T cell responses as typically assessed did not predict the quality of local mucosal immune response. Our observations provide direct evidence for the compartmentalization of mucosal tumor immunity, a critical finding for the rational design of better cancer vaccines
Abgral, Ronan. "Tomographie par émission de positons au 18F-fluorodesoxyglucose et carcinome épidermoïde des voies aérodigestives supérieures réfractaire au traitement". Phd thesis, Université de Bretagne occidentale - Brest, 2013. http://tel.archives-ouvertes.fr/tel-00952418.
Pełny tekst źródłaMastronicola, Romina. "Étude de la dissémination des cellules tumorales liée à l’acte chirurgical dans les carcinomes epidermoïdes des voies aérodigestives supérieures". Thesis, Université de Lorraine, 2015. http://www.theses.fr/2015LORR0186/document.
Pełny tekst źródłaMetastasis is defined as the development of secondary tumor sites related to the ability of tumor cells to detach from primary tumor, to implant in another organ and to proliferate. From the primary site, a micrometastatic dissemination can occur through the release in blood stream or lymph system of isolated tumor cells or of small cell clusters. These micrometastases can proliferate and grow into metastases. The detection of isolated or microclustered tumor cells, the evaluation of the prognosis value, and their metastatic potential encounter difficulties. In this study, we focused mainly on the metastatic process related to surgery in epidermoid cancers of the upper aerodigestive tract (…). Indeed, in this type of cancers, the best method to establish diagnosis is the biopsy assessed by the anatomo-pathological analysis of a sample. The main physical barrier preventing cells from migrating is the membrane of the malignant tissue. During surgery, these barriers are destroyed, facilitating the invasion of the vascular system. Therefore tumor cells can locate in vessels and proliferate at distance from the primitive site, thus forming secondary tumors. Generally, metastases are detected by imaging or serology at a very advanced stage of cancer disease. The aim of this study was to detect isolated or disseminated cells (CTCs) of CEDVADS in blood stream by three different approaches : 1) the study of molecular markers for the diagnosis of node involvement of epidermoid carcinomas of the upper aerodigestive tract using quantitative PCR in real time and OSNA. 2) Screening of tumoral cells disseminated in Redon drains after cervical curettage 3) Detection of circulating tumor cells after surgery for epidermoid carcinomas of stage III and IV VADS. This protocol will allow to validate the detection of CTCs in clinic setting and to develop prospective studies for the diagnosis and prognosis of CTCs of CEVADS
Salavert, Marianne. "Les plasmocytomes des voies aéro-digestives supérieures : à propos de quatre observations". Montpellier 1, 1988. http://www.theses.fr/1988MON11282.
Pełny tekst źródłaBarul, Christine. "Exposition professionnelle aux solvants et risque de cancer des voies aéro-digestives supérieures". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS588/document.
Pełny tekst źródłaBackground : The role of occupational exposure to solvents in the risk of head and neck cancer has been suggested in some studies but has been few investigated, despite their widespread use in the workplace. Objective: The objective of this thesis was to examine the associations between occupational exposure to solvents and the risk of head and neck cancer. Methods: This work is based on data from the ICARE study, a large population-based case-control study conducted in France between 2001 and 2007. The analysis was restricted to men and included 1,857 cases of squamous cell carcinoma of the oral cavity, pharynx and larynx and 2,780 controls. Detailed occupational lifetime as well as alcohol and tobacco consumptions were collected by questionnaires. Exposure to solvents was assessed by job exposure matrices and included five chlorinated solvents (perchloroethylene, trichloroethylene, methylene chloride, chloroform, carbon tetrachloride), five petroleum-based solvents (benzene; gasoline; diesel, fuels and kerosene; special petroleum products; white spirits) and five oxygenated solvents (ketones and esters; alcohols; diethyl ether; ethylene glycol; tetrahydrofuran). Odds-ratios adjusted for smoking, alcohol drinking and other potential confounders and 95% confidence intervals were estimated with logistic models. Results: No significant association was found between occupational exposure to chlorinated, petroleum-based and oxygenated solvents and the risk of head and neck cancer overall. In subsite analysis, the risk of laryngeal cancer increased with cumulative exposure to perchloroethylene. Non-significantly elevated risks of hypopharyngeal cancer were found in men exposed to high cumulative levels of methylene chloride, white spirits and tetrahydrofuran. An association between exposure to tetrahydrofuran and oral cavity cancer was also suggested. No other clear association was found for the other solvents under study, for any cancer site. Conclusion: Although positive associations were observed for several solvents, overall the results do not suggest a substantial role of exposure to solvents in head and neck cancer risk
Agueznay, Nour El Houda. "Récepteur soluble de l'IL-2 et de l'IL-15 dans les tumeurs des voies aérodigestives supérieures : mécanismes de production, activités biologiques et rôles pronostiques". Paris 6, 2008. http://www.theses.fr/2008PA066100.
Pełny tekst źródłaLallemant, Benjamin. "Etude de modifications transcriptionnelles dans les carcinomes des voies aéro-digestives supérieures". Montpellier 1, 2009. http://www.theses.fr/2009MON1T033.
Pełny tekst źródłaHead and neck squamous cell carcinoma (HNSCC) prognosis is globally poor. The development of new tools for the management of this disease is urgent. Gene expression profiling is a promising biologiCai approach that has been extensively used in cancer research. Examples include elucidating the biological mechanisms involved in tumorigenesis and metastatic progression, identifying potential biological targets for the development of new drugs, identifying biological pathways involved in tumour resistance to chemotherapy or radiotherapy and improving tumour staging and patient outcome prediction. With gene expression profiling, it is possible to observe and quantify gene expression deregulation in tumour cells or their surrounding environment. Two technologies are currently used: DNA microarrays and RT-qPCR. Based on a comprehensive review of the literature and original researches this work presents an updated state of the art of the potential clinical applications of gene expression profiling in the field of HNSCC. In the study "Clinical relevance of nine transcriptiory!al molecular markers for the diagnosis of head and neck squamouscell carcinoma in tissue and saliva rinse" we found that ILIRN, MAL and 11MPI are prospective tumor diagnostic markers for HNSCC. :M1vfPl overexpression is the most promising marker, and its detection could help identify tumor cells in tissue or saliva. In the study "Reference gene selection for head and neck squamous cell carcinoma gene expression studies" we found that in HNSCC and/or normal mucosa, the four best normalizat!on genes were ALAS, GAPDH, RPS18 and SHAD and the most stable combination of two genes was GAPDH-SHAD. We recommend using KALPHA-TBP for the study of Tl-T2 tumors, RPL27 -SHAD for T3-T4 tumors, KALPHA-SHAD for NO tumors, and ALAS-TBP for N+ tumors
Lallmahamood, Nizaar. "Facteurs de retard de diagnostic et approche clinique dans la prise en charge des patients atteints des cancers des voies aéro-digestives supérieures". Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCC037.
Pełny tekst źródłaStarting from the meetings with patients suffering from head and neck cancer, this research shows that this disease is much more complicated that we think. Cancers are diseases with a such complexity that do not allow us to think that it is a result of factors that leeds to this disease. We can assume for example that a head and neck cancer is due to a drug addiction or a precariousness, but those two factors are not the unique reason. A lecture of the 4 cases, will highlight the psychical and physical effects of such a disease and the way we take care of those patients
Mougin, Jean-Luc. "Les cancers primitifs multiples de l'oesophage et des voies aéro-digestives supérieures : réflexions à propos de 113 cas". Université Louis Pasteur (Strasbourg) (1971-2008), 1988. http://www.theses.fr/1988STR1M122.
Pełny tekst źródłaRedon, Richard. "Contribution au modèle génétique de progression tumorale des cancers des voies aéro-digestives supérieures : Application de la technologie des puces à ADN au criblage génomique des tumeurs". Université Louis Pasteur (Strasbourg) (1971-2008), 2002. http://www.theses.fr/2002STR13105.
Pełny tekst źródłaCéruse, Philippe. "Intérêt d'un nouveau marqueur tumoral sérique le Cyfra 21-1 dans les carcinomes des voies aéro-digestives supérieures". Lyon 1, 2003. http://www.theses.fr/2003LYO1T188.
Pełny tekst źródłaGuillet, Julie. "Les papillomavirus Humains dans les cancers des Voies Aéro-Digestives Supérieures : optimisation de méthodes de détection et étude de populations à risque". Thesis, Université de Lorraine, 2016. http://www.theses.fr/2016LORR0050/document.
Pełny tekst źródłaThe Human Papillomavirus (HPV) are involved in almost 100% of cervical cancers. Recently, HPVs have been recognized as the cause of tumors of the upper aerodigestive tract, especially of squamous cell carcinoma of the oropharynx. In France, the proportion of oropharyngeal HPV-related tumors is unknown, partly because viral testing is not in guidelines. Moreover, assess the proportion of HPV-positive tumors in tumor banks is difficult because the tumor samples were fixed in formalin and embedded in paraffin (FFPE), which complicates detection techniques. We tested a high risk HPV detection method, indicated for liquid based pap smear, on FFPE samples. We compared this technique to the gold-standard : PCR (Polymerase Chain Reaction) followed by electrophoresis. Our results indicate that this technique is applicable to FFPE samples and even appears to be more sensitive. The majority of French patients (2/3) with head and neck consult with an advanced stage of disease. This is explained in part by the lack of organized screening of these cancers, contrary to breast, prostate, cervical, or colorectal cancers. But an early treatment is essential to increase the survival rate. We therefore conducted a prospective study on patients with head and neck tumors to test the oral brushing as screening cancer and HPV detection. We found tumor and/or dystrophic cells in 97.8% of patients with biopsy, and in 88.9% of patients by brushing. Compared with biopsy, our results suggested that smear has similar specificity for HPV detection in tumors (94.4%), but lower sensitivity (66.7%). This study has shown an HPV-related tumor in 12.2% of cases. Among them, we detected by brushing (in healthy area) an oral infection by high-risk HPV in 53.3% of cases. WHO has classified HPV as carcinogenic agents since 1995, and determined that patients who developed cervical cancer are six-times more likely to develop another HPV-related tumor. In this context, we have planned a multicenter prospective study to detect oral HPV infection in patients with a pre-neoplastic or neoplastic lesion of the cervix. Co-infection rate of the two anatomical sites is unknown in women infected with genital level. Insofar oral infection could be the cause of a second tumor location, it seems important to know how much women are co-infected to propose thereafter a special monitoring. The preventive vaccination, which exists against HPV 16 and 18 in the prevention of cervical cancer, is a future perspective. Because HPV 16 is found in 90% of HPV-related squamous cell carcinoma of the oropharynx, extending vaccine recommendations emerge as a new public health issue
Paget-Bailly, Sophie. "Facteurs de risque professionnels des cancers des voies aéro-digestives supérieures : Synthèse des données épidémiologiques et analyse d’une étude cas-témoins, l’étude Icare". Thesis, Paris 11, 2012. http://www.theses.fr/2012PA11T061/document.
Pełny tekst źródłaBackground: There is sufficient evidence that asbestos causes laryngeal cancer, but overall the role of occupational exposures in the etiology of head and neck cancer (HNC) remains largely unknown. Although several studies have reported associations between occupational exposures and HNC, it is difficult to draw firm conclusions. Objectives: (1) To summarize available epidemiologic data on occupational exposures and cancers of the oral cavity (OC), pharynx and larynx (the most frequent HNC); (2) using data from a large case-control study, to identify occupations and industries with an increased risk of HNC, then to investigate the role of some suspected occupational exposures (asbestos, mineral wools (MW), cement dust, silica). Methods: (1) A literature research and a series of meta-analyses were performed. (2) The Icare study is a French population-based case-control study including 2415 HNC cases and 3555 controls. Complete and detailed occupational histories were collected. Analyses by job title were conducted. Job exposure matrices, developed by the Occupational Health Department of the French Institute for Public Health Surveillance (InVS), were used to assess lifetime occupational exposure to asbestos, MW, cement dust and silica. Results: Significantly increased meta-relative risks (meta-RR) were obtained considering laryngeal cancer and exposures to polycyclic aromatic hydrocarbons (PAH), engine exhausts, working in the textile industry and the rubber industry, and for cancer of the OC and pharynx and exposures to asbestos, PAH and engine exhausts. Significantly increased risks were found for several jobs and industries, some of them entailing exposures to agents for which meta-RR were increased. Analyses for specific occupational exposures confirmed the association between asbestos and laryngeal cancer and showed an association with the risk of oral cavity and pharyngeal cancer. An association with exposure to cement dust was also suggested. The results did not support an association between HNC risk and exposure to MW or silica. Conclusion: This work emphasizes the role of occupational exposures in HNC. Overall, our results suggest associations between HNC and exposure to asbestos, PAH, cement dust, and work in the rubber industry
Auguste, Aviane. "Epidemiologie des cancers des voies aéro-digestives supérieures aux Antilles françaises : facteurs de risque comportementaux, viraux et environnementaux". Thesis, Rennes 1, 2019. http://www.theses.fr/2019REN1B048.
Pełny tekst źródłaThe objective was to assess the potential influence of a large spectrum of risk factors on head and neck cancer (HNC) development in the French West Indies (FWI). As a first step, we used data from a cross-sectional health survey to describe the prevalence of tobacco smoking, alcohol drinking and obesity. This work highlighted significant social disparities in these risk factors in the population. We then analysed data from a population-based case-control study conducted in Martinique and Guadeloupe between 2013 and 2016, including 145 cases of HNC and 405 controls. The study revealed a high prevalence of oral infection with human papillomavirus (HPV) in the population, and a specific distribution of HPV genotypes. HPV52 was the most prevalent type and HPV16 was found in only 4% of cases. Tobacco smoking and alcohol drinking increased the risk of HNC, with a synergetic combined effect. High risk HPV (Hr-HPV) was associated with a significant increase in HNC risk, particularly in non-smokers and non-drinkers. Elevated risks of HNC were found in several occupations. A low body mass index (BMI) and family history of HNC were also associated with an increased risk of HNC. Condom use was found to decrease the risk of HNC, independently of oral HPV. In women, exposure to hormones, notably having menarche before 13, was associated with a decrease in HNC risk. Consumptions of tea, coffee, fruits and vegetables were not associated with HNC. In the population, the majority of HNC cases were attributable to tobacco smoking (62.5%) and alcohol (55.4%). About 14% of the cases were attributable to Hr-HPV, 11% to low BMI, 27% to occupation and 7% to family history of HNC. Given the predominant role of modifiable factors in HNC aetiology, there are many opportunities for prevention in this population
Servagi-Vernat, Stéphanie. "Etude dosimétrique et évaluation de fonctions objectives développées en radiothérapie externe : application à la validation d'une nouvelle technique en radiothérapie". Thesis, Besançon, 2014. http://www.theses.fr/2014BESA2078/document.
Pełny tekst źródłaThe main objectif of our work was to assess two new technologies, arctherapy by Rapid'Arc technology from Varian Medical System® and helical irradiation with Tomotherapy Hi-Art, Accuray® in Head and Neck cancer. First, we showed that these 2 techniques were equivalent in terms of dose delivery from theoretical cases (30 cases), but also in vivo from a population of patients analyzed prospectively included in the national study ARTORL (115 cases). Then, we tried to increase the therapeutic ratio by combining one of these 2 techniques with new techniques for stereotactic irradiation (Cyberknife of Accuray® and Vero Brainlab®). We then studied the most common toxicity in our population, ie xerostomia. No predictif factor could be highlighted. However, we were able to create a predictive model of the recovery function of the sub-mandibular gland, they tend to be less well protected. All these results confirm the "conformational" capacity of these two new innovative techniques, their equivalences dosimetric and especially clinically. These results were confirmed in an another location in the prospective study ARTPELVIS. Subsequent monitoring of these populations will confirm the clinical equivalence of these new technologies
Hussenet, Thomas. "Toward the identification of oncogenes by high resolution mapping of gene amplifications of the 3q25-qter region in malignant fibrous histiocytoma and squamous cell carcinoma". Strasbourg 1, 2005. https://publication-theses.unistra.fr/public/theses_doctorat/2005/HUSSENET_Thomas_2005.pdf.
Pełny tekst źródłaThis thesis work specifically applied the positional cloning strategy to the high resolution mapping of chromosome 3 aberrations in different tumour types to identify new candidate oncogenes located at 3q, amplified and consequently over-expressed. A first part was dedicated to Malignant Fibrous Histiocytomas (MFH). We first characterized overlapping amplicons at 3q28 in a MFH cell line and two other MFH primary tumours. From this region, we identified a microRNA encoding gene, hsa-miR-28 as an oncogene candidate and further identified three targets of miR-28 which all play roles in cell cycle regulation. A second part was dedicated to Squamous Cell Carcinoma (SCC). We analyzed chromosome 3 aberrations in a series of 25 lung SCC using array CGH and delineated a common region of high-level amplifications at 3q26. 3 for 20% of the tumours. Further high-resolution mapping pinpoint a 2 Mb consensus region. Analyses of the transcriptional consequences of these high-level amplifications were carried out for 9 genes. Most of them are recurrently over-expressed but two, SOX2 and SOX2OT, likely represent the 3q26. 3 amplification driver genes. Our strategy also enabled us to isolate cyclin L1 (CCNL1) gene at 3q25. 3 as a candidate oncogene in head and neck SCC (HNSCC). Investigations of CCNL1 gene alterations in a large series of HNSCC revealed consistent copy number gains and over-expression. Using array CGH we finally delineated several high-level amplifications at 3q in a series of 25 analyzed HNSCC, defining a common region overlapping with the consensus region defined for lung SCC thus suggesting that similar genes at 3q26. 3 may be involved in SCC pathogenesis independently of the localization. In conclusion we were able to isolate several candidate oncogenes located at 3q in different tumour types, illustrating the power of the positional cloning strategy applied to tumour genomes. Further investigations are needed to assess their oncogenic status
Gamelin, Erick. "Pharmacologie clinique du 5-fluorouracile et de certains sels de platine chez des patients souffrant de cancers du tractus digestif et des voies aéro-digestives supérieures". Bordeaux 2, 1997. http://www.theses.fr/1997BOR28484.
Pełny tekst źródłaBalosso, Jacques. "Les associations radio-chimiothérapiques concomitantes en cancérologie : une étude fondamentale et revue des applications cliniques". Montpellier 1, 1990. http://www.theses.fr/1990MON11169.
Pełny tekst źródłaPaget-Bailly, Sophie. "Facteurs de risque professionnels des cancers des voies aéro-digestives supérieures : Synthèse des données épidémiologiques et analyse d'une étude cas-témoins, l'étude Icare". Phd thesis, Université Paris Sud - Paris XI, 2012. http://tel.archives-ouvertes.fr/tel-00873568.
Pełny tekst źródłaBadoual, Cécile. "Rôle pronostique des lymphocytes T CD4+CD25+ intratumoraux et analyse des mécanismes de production du CD25 soluble dans les tumeurs des voies aéro-digestives supérieures". Paris 6, 2005. http://www.theses.fr/2005PA066467.
Pełny tekst źródłaMourareau, Céline. "Bio-CAD - Etude de biomarqueurs de progression tumorale dans les cancers des voies aéro-digestives supérieures en fonction de leur statut HPV". Thesis, Reims, 2016. http://www.theses.fr/2016REIMS029/document.
Pełny tekst źródłaEach year, 610,000 cancers are diagnosed worldwide attributed to high risk human papillomavirus (HR-HPV) infection. Although head and neck squamous cell carcinoma (HNSCC) is mainly associated with tobacco and/or alcohol consumption, 20 to 25% are caused by HPV infection, particularly HPV type 16. Although patients with HPV+ tumors present a better overall survival, they are diagnosed with more lymph node metastasis than HPV-negative patients.Through a study of HNSCC derived cell lines, we showed that all HPV-positives cell lines harbored HPV genome integration through host genome, with different integration profiles. Cell lines identified as good HPV+ and HPV- tumors models are UPCI:SCC090 and FaDu respectively. The first one by its migratory and proliferative properties, the second through its poor aggressiveness and mutation of p53 cellular gene.In a study on a retrospective series of oropharyngeal carcinomas with surgical resection, 6 out of 40 cancers shown HPV16 active infection (expressing E6*I mRNA). We studied epithelial-to-mesenchymal transition (EMT) markers on this oropharyngeal cancers, according to HPV status. We found a larger loss of epithelial marker E-cadherin in HPV+ group and loss of this marker is associated with a worse overall survival.We showed that HPV and EMT status seem to be two independent factors that could combine differently to define different prognostic levels
Macedo, Gonzales Rodney. "Development of therapeutic vaccine strategies and pre-clinical animal tumor models for head and neck cancers". Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066269/document.
Pełny tekst źródłaHead and neck squamous cell cancer (HNSCC) associated with alcohol and tobacco consumption, and recently with human papillomavirus-16 (HPV-16), have bad prognosis despite current therapies. Development of innovative vaccine strategies and adequate pre-clinical tumor models are required to better evaluate HNSCCs. We developed a DNA vaccination that creates non-infectious virus-like particles, which express HPV-16 E7 oncoprotein (pVLP-E7). Results showed that pVLP-E7 induced an E7-specific immune response in vivo and in vitro. Moreover, using an ectopic model of HNSCC that expresses E6/E7 (TC-1), we found that pVLP-E7 intradermic (ID) immunizations induced anti-tumoral responses at early stages. For larger established tumors, pVLP-E7 vaccines were only efficient when administered with TLR-7 and TLR-9 agonists. In an orthotopic model that shares anatomical and inflammatory features with human HNSCC we observed that intra-cheek (IC) infusion of either TC-1 or NR-S1 cells into mice elicited higher numbers of inflammatory infiltrates in the tumor compared to ectopic models. Using this orthotopic IC model, we found that mucosal IC pVLP-E7 vaccination elicited better vaccine-specific CD8+ T-cell responses than ID administration in naive and tumor-bearing mice. Furthermore, pVLP-E7 IC immunizations in combination with TLR agonists led to rejection of established tumors and long-term protection, both of which were associated with E7-specific CD8+ T cell infiltration in tumors and lymph nodes. Our findings demonstrate that pVLP-E7 IC vaccination with adjuvants is efficient against these tumor models and together provides a valuable therapeutic strategy for HNSCCs
Wozny, Anne-sophie. "Mécanismes moléculaires spécifiques de la réponse aux ions carbone dans les cellules tumorales (souches et non souches) des cancers des Voies Aéro-Digestives Supérieures". Thesis, Lyon, 2018. https://n2t.net/ark:/47881/m6m044rb.
Pełny tekst źródłaHadrontherapy using carbon ions is an alternative to photon irradiation in the treatment of Head and Neck cancers, because of accurate ballistics and high biological efficiency, including hypoxic tumor areas. These cancers are of poor prognosis because of a high risk of recurrences related to the presence of cancer stem cells (CSCs).The aim of this work was to determine the molecular specificities of the response to carbon ion irradiations compared to photons in two cancer cell lines and their CSCs’ subpopulation, in hypoxic and normoxic conditions. This work focused on the role of the HIF-1α protein in cell survival, since hypoxia promotes its stabilization, but also in the radioresistance; the epithelial-mesenchymal transition (EMT) and the detection and repair of DNA double-strand breaks (DSBs). HIF-1α is stabilized earlier in CSCs compared to non-CSCs. Its activation, as well as the EMT pathways (STAT3, MEK/p38/JNK and Akt/mTOR), are dependent on reactive oxygen species (ROS), whose production is homogeneous in response to photons. At the opposite, the ROS produced in the carbon ion tracks are insufficient to activate HIF-1α and the upstream EMT pathways. Under hypoxic conditions, a relationship has been established between HIF-1α activation and that of the DSBs detection (ATM) and repair (Rad51) pathways (Homologous Recombination). These studies demonstrate that the therapeutic advantage of carbon ions is based on the spatial ROS distribution at the nanoscale and consequently on the non-activation of key pathways involved in tumor cell defense
Bertrand, Gérald. "Caractérisation et ciblage thérapeutique d'une sous-population de cellules souches cancéreuses dans un modèle cellulaire de carcinome épidermoïde de la tête et du cou résistant à l'irradiation par photon et ions carbone". Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10118/document.
Pełny tekst źródłaHead and neck squamous cell carcinomas (HNSCC) have a poor prognosis, due to their resistance to standard treatments. In most cases, locoregional recurrence or metastases occur. This study has focused on the role of cancer stem cells (CSC) in the radioresistance of the SQ20B HNSCC cell line and their therapeutic targeting in association with photon or carbon ions irradiation. A subpopulation of SQ20B-CSC has been isolated by cell sorting based on 3 specific characteristics of HNSCC-CSC : Hoechst 33342 exclusion, CD44 expression and high aldehyde dehydrogenase activity (ALDH). SQ20B/SP/CD44high/ALDHhigh cells show the CSC characteristics (in vitro and in vivo tumorigenesis, high radioresistance). The response of CSC to both types of irradiation was compared to the non-“stem cells” SQ20B/SP/CD44low sub-population. The observed radioresistance involves a decrease in apoptotic cell death, an increase in proliferative capacities and an overexpression of the Bmi1 self-renewing signaling pathway. The radiosensitizing effects of 3 molecules targeting the CSC has been demonstrated : an induction of apoptotic cell death by the inhibition of the G2/M phase arrest after a treatment with UCN01 ; an inhibition of proliferative capacities using the all-trans-retinoic acid (ATRA) which induce their differentiation ; and an inhibition of Bmi1 by artesunate. These treatments, alone or in combination (UCN01+ATRA) have a synergistic effect with photon or carbon ion irradiation to overcome CSC radioresistance. Preclinical and clinical studies should confirm the benefit of targeting CSC and improve the control of tumor escape in patients with radioresistant HNSCC cancers
Hoffmann, Caroline. "Dendritic Cells in Head and Neck Cancer Microenvironment : From Mechanisms to Biomarkers". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS308/document.
Pełny tekst źródłaThe objective of the thesis was to decipher the molecular state of tumor infiltrating dendritic cell (DC) and their relation to the tumor microenvironment. By combining the analysis of human tumor samples by flow cytometry and RNA sequencing, of tumor secretome and of a large dataset of in vitro DC-Tcell interactions I obtained 2 main findings. First, we reported a novel classification of human activated DC, that are either “secretory” that is specialized in secreting cytokines and chemokines, or “helper” that is specialized at inducing the secretion of a broad range of T helper cytokines after cell co-culture. DC infiltrating inflamed human head and neck cancer matched the “secretory” phenotypic and transcriptomic signatures. Beyond this novel biological concept, this classification is of importance as a theoretical basis for adjuvant-based immunotherapy. Secondly, we showed that tumor inflammation was not the main prognostic factor for oral cavity cancer (OCC) patients, but that MMP2 and the presence of extra-nodal extension were independent predictors of reduced disease-specific survival. We could stratify OCC into 4 prognostic groups and showed that they had similar expected rates of response to immunotherapy. Our data may serve to design a biomarker-driven clinical trial proposing neoadjuvant chemotherapy or immunotherapy to high-risk patients, with the goal of reducing the percentage of OCC patients that will present with early and severe recurrences
Mirghani, Haitham. "Analyse comparative du transcriptome et miRNone des cancers de l'oropharynx en fonction du statut HPV16". Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066230.
Pełny tekst źródłaHead and neck squamous cell carcinomas (HNSCCs) represent the sixth most common form of cancer with an annual incidence of approximately 600,000 new cases worldwide. Tobacco and alcohol abuse are the traditional risk factors. Whilst the incidence of oral cavity, larynx and hypopharynx cancers is stabilizing or falling, because of a drop in tobacco consumption, those arising in the oropharynx are on the increase. This epidemiologic change has been attributed to high-risk human papillomavirus and particularly to type 16 (HPV16), which is now recognized as a causative agent in a growing subset of oropharyngeal squamous cell carcinomas (OPSCCs).HPV-induced OPSCCs represent a distinct subgroup, separate from other HNSCCs, with unique epidemiologic, clinical, pathological and molecular characteristics. They affect young patients, are highly lymphophilic and have markedly improved survival outcomes compared to those with HPV-negative HNSCC. The emergence of these cancers demands special attention, as in the coming years diagnosis, treatment and follow up in HNSCC may vary according to HPV status. However, these objectives will not be fully achieved without a better understanding of their natural history and specific oncogenic mechanisms. The goal of this work is to contribute to a better understanding of the biological basis that differentiates HPV-induced OPSCCs from their HPV-negative counterparts. To this end, we have investigated global changes in gene expression in a cohort of 38 strictly selected OPSCCs. We have identified a set of mRNA and miRNA that discriminated between OPSCCs solely according to HPV16 status. The functional analysis of these 2 sets confirms that the biological basis of OPSCCs varies according to their HPV status and consolidates at the molecular level known or suspected clinical and pathological data (e.g tumoral differentiation, lymphoid infiltrations…). This study highlights the potential role of several pathways that, once deregulated, could contribute to the development of HPV-induced OPSCC. Further investigation is required for a more comprehensive understanding of the biological properties of HPV related OPSCCs. These properties may be exploited to develop novel therapeutic agents