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Baudier, Philippe. "Les cancers du sein de type III traités par radiothérapie et chirurgie partielle". Montpellier 1, 1990. http://www.theses.fr/1990MON11276.
Pełny tekst źródłaSalomon, Alain. "Radiothérapie à visée exclusive dans le traitement du cancer du sein : à propos de 186 cas". Montpellier 1, 1989. http://www.theses.fr/1989MON11340.
Pełny tekst źródłaGasiot-Bessiere, Elisabeth. "La contribution du scanner-simulateur dans l'optimisation de la balistique d'irradiation des cancers du sein". Montpellier 1, 1997. http://www.theses.fr/1997MON11076.
Pełny tekst źródłaBrulin-Lemanski, Claire. "Récidives locales des cancers du sein après traitement conservateur par chirurgie-radiothérapie : facteurs de risque et conséquences des échecs locaux à propos de 423 cas". Montpellier 1, 1997. http://www.theses.fr/1997MON11037.
Pełny tekst źródłaBouzid, Dounia. "Simulation Monte Carlo GATE et dosimétrie en radiothérapie peropératoire pour le cancer du sein". Thesis, Brest, 2015. http://www.theses.fr/2015BRES0065.
Pełny tekst źródłaExternal radiation therapy is an important part of breast conservative treatment. The conventional calendar is to deliver a total dose of 50 Gy in 25 fractions over 5 weeks. For certain categories of women, 5 to 6 weeks of radiotherapy, with long and frequent transport is sometimes difficult to achieve. Intra-operative radiotherapy (IORT) helps to prevent the risk of local recurrence in the tumor bed, and only requires a few days of hospitalization. This study focuses on the use of a miniaturized low energy X-ray source (50kV). After surgical resection of the tumor, an applicator is inserted into the tumor bed and the system delivers a single dose of 20 Gy on its surface. However, there is no custom prescription and this is questionable since an official text recommends optimizing the individual dose. In this context, a Monte Carlo calculation makes it possible to accurately assess the dose delivered to the patient by simulating the transport of particles. This thesis proposes to assess the absorbed dose criterion as accurately as possible from a realistic model of the X-ray source and individual dose calculations using Monte Carlo simulations taking into account the tissue heterogeneities of the breast. In vivo dosimetric measurements also confirm the results of simulations
Lemay, Rosalie. "Développement de nouveaux radiosensibilisateurs bromés pour la thérapie des cellules cancéreuses du sein". Mémoire, Université de Sherbrooke, 2006. http://savoirs.usherbrooke.ca/handle/11143/3853.
Pełny tekst źródłaCavalier, Isabelle Collard. "Apport du lambeau du grand dorsal dans la chirurgie reconstructrice de la paroi thoracique : à propos de 41 cas traités au CRLC de Montpellier entre 1986 et 1990". Montpellier 1, 1990. http://www.theses.fr/1990MON11147.
Pełny tekst źródłaTo, Nhu Hanh. "Effet des radiations ionisantes sur le système immunitaire de l'hôte et de la tumeur dans un modèle murin d'allogreffe et des cancers du sein localement avancés". Electronic Thesis or Diss., Paris 12, 2022. http://www.theses.fr/2022PA120071.
Pełny tekst źródłaRadiotherapy (RT) is one of the main therapies for cancer treatment. Currently, in France, it is estimated that approximately 200,000 patients receive RT each year for different stages of the disease.The impact of RT on the immune system has been recognized for several decades for its "myeloablative" effect in patients who are candidates for bone marrow transplant (BMT), but also in victims of nuclear accidents and atomic bomb explosions who suffered from fatal bone marrow failure. Regarding therapeutic potentials, immunostimulatory effects of RT have been reported under the term "abscopal effect," corresponding to antitumor responses after RT in non-irradiated sites distant from solid tumors.My work in the laboratory(I-BIOT team of the IMRB) focused on the modulation of the immune response applied to allografts and cancer in the two following models:1. Allograft mouse model: understanding the parameters of total body irradiation (TBI) is essential for the reproducibility and reliability of experimental results in mouse models. Data from the literature have shown considerable variation in the reproduction of the results between experiments depending on the device used to deliver the ICT before BMT. The objective of this work was to compare two types of irradiation devices using different energy levels regarding post-allograft results (chimerism, graft-versus-host disease, and post-transplant tumor control). We demonstrated that TBI with low-energy photons induced more post-TBI inflammation than high-energy photons and, therefore, more post-BMT alloreactivity. This inflammation could be modulated by delaying the graft outside of the inflammatory peak and thus reducing post-BMT alloreactivity. These data should be taken into consideration for the interpretation of the results obtained according to the type of device used in the experimental model.2. Clinical model of breast cancer: the 2nd work is part of a translational study of a prospective clinical trial evaluating the place of preoperative radiotherapy (RT) in triple-negative and luminal B breast cancer. These subtypes of breast cancer are well known for their aggressiveness and their immunogenicity. In this model, the preoperative RT aimed to increase tumor responses by acting on tumor immunity. Immunity-related biomarkers derived from tumor microenvironment and peripheral blood were analyzed. In a preliminary analysis of 42 patients, we identified different potential biomarkers associated with pathologic complete response according to the preoperative therapy administered (with or without RT). These results might help to better select patients individually for this new therapeutic approach
Dommesent, Damien. "Le cancer du sein inflammatoire : à propos de 40 patientes traitées au Centre François Baclesse entre 1987 et 1992". Caen, 1993. http://www.theses.fr/1993CAEN3072.
Pełny tekst źródłaLacombe, Jérôme. "Identification de biomarqueurs par approche protéomique : application au diagnostic des formes précoces de cancer du sein et à la réaction des tissus sains aux rayonnements ionisants". Thesis, Montpellier 1, 2013. http://www.theses.fr/2013MON1T031.
Pełny tekst źródłaBreast cancer is a major public health problem. With 500,000 deaths every year around the world, it focuses on many efforts in the search for new therapies and for therapeutic monitoring, diagnosis or prognosis biomarkers. From a diagnostic point of view, mammography remains gold standard for breast cancer detection. However, it has many limitations, especially in women with significant breast density. The identification of biomarkers for early diagnosis or for prognosis of in situ tumors in this population at risk would be a valuable improvement in the breast cancer management. Considering treatment strategies, radiotherapy has become a major treatment against breast cancer. However, some patients can develop severe radiation-induced late side effects. Their prediction is a main challenge as clinicians will be able to identify patients at risk and develop individualized treatment. Despite all efforts, no biomarkers are validated and used in clinical routine for normal tissues outcomes after irradiation. The aim of my PhD work was to identify protein markers for the diagnosis and prognosis of early-stage breast cancers, and also for the prediction of radiation-induced severe late effects. With different proteomic approaches, I was able to identify three protein signatures: (1) a serum autoantibody signature for the diagnosis of DCIS and node negative early-stage breast cancers (GAL3, RACK1, PAK2, and PHB2 RUVBL1), (2) a serum autoantibody signature of ductal carcinoma in situ progression to invasive breast cancer (CIRBP, ECHDC1, HMGN1, PSRC1 and RBP-Jκ) and (3) five lymphocyte proteins (AK2, ANX1, APEX1, HSPA8 and IDH2 ) that could predict late radiation-induced toxicity. In addition, these signatures allowed to identify new molecular partners likely to be involved in the mechanisms of mammary carcinogenesis and in the late radio-induced toxicity
Konge, Julie. "Le TGF-β1 module la transition épithéliale-mésenchymateuse et le pool de cellules souches cancéreuses dans les cellules tumorales mammaires humaines : impact sur la radiosensibilité". Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS044.
Pełny tekst źródłaThis works aims at characterizing radioresistant cells within human breast cancer development that is responsible for treatment failure and cancer recurrences. Although the literature is flourishing with papers tightly linking the presence of "Cancer Stem Cells" to cancer treatment resistance, the intrinsic radioresistance of those "CSC" and the mechanism involved have yet to be established.Dr. Weinberg and his team have developed an in vitro cell model that produces mammary tumor cells noted « CD24-CD44+ » after an epithelial-to-mesenchymal transition (EMT) induced by TGF-β1. This model is based on healthy human mammary cells that have been immortalized and transformed.Within this context, my Ph.D. project has focused on using this new model in order to compare the radiosensibility of two cell lines: the « CD24-CD44+ » cells and the « CD24+CD44- » one. Underlying this choice is the fact this model allows for a comparison of two cellular populations at distinct stage of the tumor’s development.This work has shed light on apoptotic and detoxification mechanism involved in the radio resistant behavior of the « CD24-CD44+ » cells. After a brief introduction of key concepts required to the understanding of this work, this manuscript will begin by presenting the characterization of the chosen model, then a study of the radiation response that enabled a first description of the « CD24-CD44+ » cell radioresistant phenotype through a mild stop at the G2/M stage of the cell cycle, the presence of polypoid cells and a high progeny generation ability after exposure to radiation.Furthermore, this works shows implications of apoptotic mechanism of « CD24-CD44+ » cells with a radioresistance phenotype. Hence, we were able to show that reduced cell death observed for the « CD24-CD44+ » cells is linked to a lower activation of apoptotic pathways.Finally, the last part will present detoxification mechanism involved in « CD24-CD44+ » radioresistance phenotype, showing an altered transcriptional signature of two detoxication genes SOD2 and HMOX1 after exposure to radiation
Bourque, Alexandre. "Amélioration du calcul de dose TG-43 en curiethérapie à bas débit par un algorithme de dose primaire et diffusée sur processeur graphique". Thesis, Université Laval, 2012. http://www.theses.ulaval.ca/2012/29312/29312.pdf.
Pełny tekst źródłaBrachytherapy dose calculations have been relying since 1995 on a formalism that considers the whole geometry as a homogeneous water tank. This gives the opportunity to compute dose distributions within a reasonable clinical timeframe, but with considerable approximations that can influence or even change the treatment. This work presents an upgraded version of this formalism derived from the TG-43 protocol (AAPM), currently used in actual treatment planning systems. The new algorithm includes a primary and scatter dose separation using ray-tracing operation to account for heterogeneities through the medium. These modifications to the dose calculation are very power consuming and too long for the clinical needs when executed on modern CPUs. With the GPGPU technology, a GPU-driven algorithm allows a complex handling of the anatomic heterogeneities in the dose calculation and keeps execution times below 0.5 s/seed. The algorithm was named TG-43-RT for TG-43 with Ray-Tracing and accelerations factors of three order of magnitude were obtained over a regular CPU implementation. The TG-43-RT algorithm adequatly corrects dose deposition along heterogeneities and it reduces interseed attenuation effects. Dose is scored in the medium instead of water, which also applies a severe correction for high heterogeneous medium like the breast. Deviations of more than 80% in dose deposition were obtained over calcification inside the prostate when compared to Monte Carlo simulations. This kind of deviation influences DVH shape. However, the TG-43-RT was keeping those deviations within the 8.7% uncertainty range (2σ) associated with a regular TG-43 evaluation as stated in the TG-138. Monte Carlo simulations were used as a gold standard to get an absolute dose calculation reference. The algorithm was also tested in a prostate phantom with 125I seeds and in a breast phantom with 103Pd seeds to mimic real anatomic geometries and unify the applied corrections.
Bidan, Nadège. "Développement d’un système rapporteur de la plasticité des cellules cancéreuses du sein". Thesis, Lille, 2019. http://www.theses.fr/2019LIL1S110.
Pełny tekst źródłaMany solid cancers are thought to be organized hierarchically with a small number of cancer stem cells (CSCs) able to re-grow a tumor while their progeny lacks this feature. These CSCs are associated with radioresistance. Recent studies have revealed that non-cancer stem cells may undergo dedifferentiation subsequently obtaining the phenotype and functions of CSCs. Indeed, ionizing radiation reprogrammed differentiated breast cancer cells into induced cancer stem cells (iCSCs). This mechanism of reprogramming can contribute to relapse. CSCs and iCSCs cannot be distinguished as they share the same stem cell-like properties. Breast CSCs can be isolated based on their high ALDH1 activity while iCSC studies require originally sorting of ALDH1-negative cells. Such studies are limited to in vitro experiments. In vivo reprogramming studies require designing a specific CSC and iCSC identification system.During my PhD thesis, I showed that ALDH1A1 promoter can be used to identify cells with CSC. The cells identified by fluorescent protein in which expression is controlled by ALDH1A1 promoter possess self-renewal and differentiation properties. They also exhibited higher capacity to form tumors, and an increased resistance to anticancer therapies. Monitoring of these cells by fluorescence tracking facilitated the visualization of reprogramming phenomenon in real time following the irradiation. In addition, we were able to observed the strongest extravasation potential of these cells in a microvessel mimicking chip model. I have subsequently constructed an inducible expression vector based on the activity of this promoter in order to dynamically follow the different cell populations: non-CSCs, pre-existing CSCs and iCSCs. This vector consists of several systems, including the inducible TetON system, the CRE-loxP system and the Flp / FRT recombination system for monitoring cell populations by fluorescence. My thesis work has thus enabled the generation of tools that can be used for the dynamic monitoring of CSCs and CSCs induced by therapies
Colas, Séverine. "Alimentation et sensibilité des tumeurs aux traitements anti-cancéreux : influence des acides gras poly-insaturés N-3". Tours, 2005. http://www.theses.fr/2005TOUR4014.
Pełny tekst źródłaSeveral studies have shown that n-3 polyunsaturated fatty acids (PUFA) increase th eefficacy of anthracyclines. The general purpose of this thesis work was to understand th einteraction between n-3 PUFA and tumor sensitivity to treatment, using an autochthonous rat mammary tumor model. Our study showed that : alpha-tocopherol interferes with the n-3 PUFA induced chemosensitization of mammary tumors to epirubicin ; docosahexaenoic acid (DHA) sensitizes mammary tumors to radiation therapy (effect abolished by an alphatocopherol supply, suggesting that lipoperoxidation may be implied) ; the pivotal role of vascularization in tumor response to antitumoral drugs ; The DHA-induced enhancement of tumor response to epirubicin was accompanied by a decrease in tumor vascularization. Moreover, this chemosensitization was inhibited by alpha-tocopherol supply in a dose dependant manner
Bouchard, Alexanne. "La protéine de stress du réticulum endoplasmique GRP94 dans le cancer du sein triple négatif, intérêt diagnostique et thérapeutique". Electronic Thesis or Diss., Bourgogne Franche-Comté, 2023. https://nuxeo.u-bourgogne.fr/nuxeo/site/esupversions/8b1b931d-83a7-49fd-9779-012ad3949e79.
Pełny tekst źródłaTriple-negative breast cancer (TNBC) is characterized by the absence of estrogen and progesterone receptors, as well as HER2, on tumor cells. It is the most aggressive subtype of breast cancer and is associated with a higher risk of metastasis. It accounts for 15-20% of all breast cancers. Due to the lack of specific targets, hormone therapy and HER2-targeted drugs are ineffective. TNBC represents a subgroup of heterogeneous tumors that can be classified according to their molecular characteristics. A better understanding of molecular mechanisms, particularly those involved in modulating the immune response, is needed to optimize the management of this cancer. In this context, molecular imaging can represent an interesting tool: it enables the non-invasive identification and in vivo visualization of specific targets in the tumor or tumor microenvironment (TME), thanks to selective molecular probes that can be used for diagnostic and/or therapeutic purposes. In this thesis work, two specific TME targets were studied using such probes: M2-like macrophages and GARP protein, a TGF-β anchoring receptor. M2-like macrophages are recognized as having a major pro-tumoral role. The results obtained enabled us to demonstrate the presence of CD206+ M2-like macrophages in our CSTN model using in vivo multimodal imaging. In this study, we validated the efficacy of 99mTc-Tilmanocept in SPECT/CT as a probe for imaging M2-like macrophages in the TME of our TNBC model. We also demonstrated co-expression of these CD206+ M2-like macrophages with the GRP94 protein, an important chaperone involved in immune responses. Finally, inhibition of GRP94 with a specific inhibitor, PU-WS13, significantly decreased the number of M2-like macrophages as well as tumor growth in our TNBC model. Thus, SPECT imaging with 99mTc-Tilmanocept could represent an innovative method for imaging CD206+ M2-like macrophages as a potential biomarker for prognosis, therapeutic prediction and/or monitoring of solid tumors. The second target studied, the GARP protein, is expressed at the membrane of Tregs and tumor cells and plays a key role in the activation of TGF-β, a major immunosuppressive cytokine in cancer development. The development of a theranostic approach targeting GARP combining imaging (111In-DOTAGA-GARP) and targeted radionuclide therapy (TRT) (177Lu-DOTAGA-GARP) has been achieved. We showed in our preclinical TNBC model that GARP expression was increased after external radiotherapy, a classic therapeutic strategy, and could be specifically detected and quantified in the TME using in vivo SPECT/CT imaging with the 111In-DOTAGA-GARP probe. Moreover, its use in its therapeutic form (177Lu-DOTAGA-GARP) limited tumor growth. This theranostic strategy could enable the personalization of cancer treatments by identifying and treating patients likely to respond to therapy targeting Tregs via TRT
Hullo, Marie. "Place des nanoparticules pour lutter contre la radio-résistance du cancer du sein : impact de l’hétérogénéité tumorale Gold Nanoparticle Uptake in Tumor Cells: Quantification and Size Distribution by sp-ICPMS . Radiation Enhancer Effect of Platinum Nanoparticles: Experimental in Vitrolimits Andrelevant Physical Chemical Simulation". Thesis, université Paris-Saclay, 2021. http://www.theses.fr/2021UPASL004.
Pełny tekst źródłaThe use of high-Z nanoparticles to enhance radiotherapy effects has gained momentum over the last decade. Historically, as nanoparticles increase tumor density, they were thought to improve radiation dose by locally increasing the probability of interactions with ionizing radiations. Local dose enhancement is then associated with increased oxidative stress and DNA damage. Therefore, radiosensitization with nanoparticles could impair radioresistance as well as improve therapeutic index. Radiotherapy is a cornerstone of breast cancer treatment. However, mammary tumors are heterogeneous and comprise distinct populations of cancer cells that respond differently to treatments. Cancer stem cells (CSC) and epithelial to mesenchymal transition (EMT) are major factors contributing to cancer cells plasticity, tumor heterogeneity, and escape from programmed cell death (apoptosis). In breast cancer, both CSC and cells undergoing EMT are characterized by the expression of two surface markers CD24 and CD44 (CD24-/low, CD44 high). This work aims to evaluate the efficiency of high-Z nanoparticles of different nature (gold, platinum), different size (from 5 to 35 nm) and different surface charge (positive and negative) as potent radiosensitizer on several breast cancer models of different epithelial or mesenchymal state. As no significant change could initially be observed in vitro following the combination of nanoparticles with radiation compared to radiation alone, I gain insight on the influence of physical, chemical and biological parameters required for characterizing radio-enhancement. Among them, I focused on improving the diffusion of nanoparticles and their internalization in tumor cells. I showed that nanoparticles uptake by breast cancer cells was depending on their mesenchymal state: nanoparticle internalization by cancer cells is dramatically increased in mesenchymal-like cancer cells compared to epithelial-like cells across a panel of several breast cancer cell lines. Importantly this discrepancy was not affected by the charge, size or surface chemistry of the nanoparticles themselves. This strongly suggests a cell-dependent mechanism, in opposition to the current paradigm that nanoparticles uptake is mainly governed by their inherent physical/chemical properties. This study emphasized the importance of membrane and extracellular structures in nanoparticle recognition and preferential interaction with cells. Our results are of peculiar interests as the identification of genes or mechanisms facilitating nanoparticles accumulation into radioresistant cancer cells could further conception of promising therapeutic nanoparticles
Bailleul, Justine. "Etude des mécanismes impliqués dans la reprogrammation de cellules cancéreuses non-souches en cellules souches cancéreuses induite par les radiations ionisantes dans le cancer du sein". Thesis, Lille 1, 2018. http://www.theses.fr/2018LIL1S100/document.
Pełny tekst źródłaCancer stem cells (CSCs) identification in hematologic and solid tumors has paved the way to many fundamental and translational studies. However, recent studies have highlighted cancer cells plasticity. Indeed, differentiated non-cancer stem cells (non-CSCs) can generate CSCs upon various stimuli. In particular, radiotherapy (RT) induces CSCs from non-CSCs, in vitro. This reprogramming could be involved in treatments resistance and recurrence risk. Nevertheless, reprogramming mechanisms remain unknown, and identification of new targets seems essential to prevent CSC emergence. During my PhD thesis, I have shown that media from irradiated non-CSCs induces mammary CSC reprogramming. I have demonstrated that RT lead to specific chemokines secretion, as CXCL1 and CCL5. Inhibition and recombinant proteins treatments allowed me to demonstrate the involvement of CXCL1, CCL5 and their receptors in in vitro reprogramming. Moreover, in vivo inhibition of CXCL1 and CCL5, combined with RT, lead to an increased survival, in a xenografted mouse model. Finally, transcriptomic analysis of chemokines and receptors expression from clinical databases has shown a correlation with signatures of CSCs and more agressive breast cancer subtypes, as well as a decreased metastasis-free survival. These findings denote the involvement of chemokines in non-CSCs reprogramming into CSCs in breast cancer, and the potential of chemokines to constitute new therapeutics targets, in combination with conventional anti-cancer treatments
Bensimon, Julie. "Radiorésistance des cancers du sein : rôle majeur du marqueur de cellules souches cancéreuses CD24". Phd thesis, Université Paris Sud - Paris XI, 2013. http://tel.archives-ouvertes.fr/tel-00926117.
Pełny tekst źródłaDufour, Robin. "Différentes approches de l'optimisation du traitement du cancer du sein de phénotype "basal like" triple négatif par un anti-PARP : contournement des protéines "Multidrug Resistance" et traitement combiné radiothérapie / chimiothérapie. Spécialité". Thesis, Clermont-Ferrand 1, 2016. http://www.theses.fr/2016CLF1MM05/document.
Pełny tekst źródła« Triple Negative Basal-Like » (BLTN) breast cancer is particularly aggressive and of poor prognosis. It is insensitive to hormone-targeted therapies leaving conventional chemotherapy as the only treatment strategy. Therefore, new promising targeted therapies are being developed, such as Poly-ADP-Ribose-Polymerase inhibitors (anti-PARPs). In this context, our research has been directed towards optimizing the treatment of BLTN breast cancer by modelling the action of an anti-PARP model, Olaparib®, on BLTN cell line SUM1315. Firstly, the study of the co-expression of BCRP and P-gp, two major “Multidrug Resistance” proteins (MDR) in the presence of 50 µM Olaparib® showed an induction of their expression in SUM1315 cells, with a relay-type response. BCRP would establish a first line of cellular defense and its action would then be taken over by P-gp, for 24h of treatment. This mechanism is correlated with the intracellular concentration of Olaparib® measured by HPLC. All of our results suggest that it would be possible to circumvent the induced MDR resistance mechanism if a stable concentration of Olaparib® is maintained in cells in the long term. Secondly, we studied the potentiation of the action of Olaparib® combining it with low and high-energy radiations on the viability of SUM1315 cells. Comparison of the results with single Olaparib®, single irradiation, or the combination of Olaparib®/radiotherapy then demonstrated a synergistic effect of the two treatments when delivered concomitantly, on cell viability. The synergistic effect of this combination works even with low doses of Olaparib®. In this way it would be possible to reduce the anti-PARP doses while maintaining the benefits of this treatment. Finally, we have developed two techniques of cell culture in three dimensions: (i) "hanging drop" and (ii) "liquid overlay", in order to mimic more accurately the conditions of tumours in vivo. Observations of spheroids obtained by these two techniques by transmission and scanning electron microscopy demonstrated the integrity of cells within as well as the formation of cell junctions. However, the spheroids obtained by "liquid overlay" showed better ultra-structural integrity
Gutmann, Matthieu. "Optimisation de l'utilisation de l'antiestrogène EM-652 en combinaison avec la chimiothérapie et la radiothérapie pour le traitement du cancer du sein dans un modèle de souris nue porteuse de tumeurs mammaires humaines". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0020/NQ56835.pdf.
Pełny tekst źródłaDubois, Clémence. "Optimisation du traitement du cancer du sein Triple-Négatif : développement des modèles de culture cellulaire en trois dimensions, efficacité de l'Olaparib (anti-PARP1) en combinaison avec la radiothérapie et chimiorésistance instaurée par les protéines Multi Drug Résistance". Thesis, Université Clermont Auvergne (2017-2020), 2018. http://www.theses.fr/2018CLFAS018/document.
Pełny tekst źródłaBreast cancer is a very complex and heterogeneous disease. Among the different molecular subtypes, Triple-Negative (TN) breast cancers are particularly aggressive and of poor prognosis. TN tumours are characterized by a lack of estrogen receptors expression (ER), progesterone receptors expression (PR), the absence of Human Epidermal growth factor receptor 2 overexpression (HER2) of the frequent mutations on BRCA1 / 2 genes ("BRCAness" phenotype). In the absence of effective targeted therapies, many targeted therapies including poly-ADP-ribose polymerase inhibitors (anti-PARPs) are currently under development in preclinical and clinical studies. Based on the synthetic lethality concept, the anti-PARPs specifically target the BRCAness properties of TN tumors. In this context, these works were focused on the development of diagnostic tools for the optimization of TN tumours treatment with anti-PARPs. For this, firstly, 3D cell cultures formed with the Liquid Overlay technique as well as associated cytotoxicity tests were developed, from the TN breast cancer cell lines MDA-MB-231 and SUM1315. These two spheroid models were then optimized and standardized in a synthetic culture medium called OPTIPASS (BIOPASS). Secondly, the efficacy of a co-treatment combining anti-PARP1 Olaparib at low and high doses and fractioned radiotherapy (5x2 Gy) was analyzed on the two cell lines MDA-MB-231 and SUM1315 cultured in 2D and 3D conditions. These experiments clearly demonstrated a potentiating effect of Olaparib on radiotherapy (i) in presence of low doses of this anti-PARP (5 μM or inferior) (ii) at long term and (iii) in presence of the maximum fractionation (5x2 Gy). In addition, these two TN cell lines showed a heterogeneous sensitivity to the co-treatment. Thus, an in silico transcriptomic analysis revealed very different profiles of these highly metastatic and highly aggressive cell lines. Notably, the SUM1315 cell line presented a neuronal commitment, suggesting its cerebral metastatic origin. These promising results could open up new perspectives for the treatment of TN tumours brain metastases, which are very common in this subtype. Thirdly, in order to better characterize the mode of action of Olaparib on these spheroid models, a fluorescent derivative of Olaparib, Ola-FL, was synthesized and characterized. The analysis of Ola-FL penetration and distribution in MDA-MB-231 and SUM1315 spheroids showed a rapid and homogeneous distribution of the compound as well as its persistence after 3h of incubation, in all the depth of the spheroids and especially in the central hypoxic zones. Finally, the analysis of the co-expression of two major Multidrug Resistance (MDR) pumps, MRP7 and P-gp after the treatment of the two TN lines with Olaparib, revealed on 2D cultures, a relay type expression of the MRP7 and the P-gp. On spheroids treated with a low dose of Olaparib art long term (10 days), a basal expression of MRP7 and an overexpression of P-gp were detected in the peripheral residual cells of the spheroids. These results clearly highlighted the involvement of these efflux pumps in Olaparib resistance mechanisms, in these aggressive tumors. All the results resulting from the modeling of the action of Olaparib on MDA-MB-231 and SUM1315 spheroids suggest its greater efficacy at low dose and at long-term, especially in the hypoxic zones of the spheroids. This parameter might be probably at the origin of its potentiating effect with radiotherapy
Walker, Valentin. "Étude du risque de cardiotoxicité radio-induite précoce chez des patientes traitées par radiothérapie pour un cancer du sein à partir de la cohorte prospective BACCARAT Early Detection of Cardiovascular Changes After Radiotherapy for Breast Cancer: Protocol for a European Multicenter Prospective Cohort (MEDIRAD EARLY HEART Study) Early Detection of Subclinical Left Ventricular Dysfunction After Breast Cancer Radiation Therapy Using Speckle-tracking Echocardiography: Association between Cardiac Exposure and Longitudinal Strain Changes (BACCARAT Study)". Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASR003.
Pełny tekst źródłaRadiation therapy (RT), an adjuvant treatment for breast cancer, is associated with an increased risk of cardiovascular disease several years after RT. Identifying early signs of cardiotoxicity and their relationship to the dose of ionizing radiation absorbed by the heart could help predict the occurrence of cardiovascular disease and improve prevention in patients at risk.This thesis is based on the BACCARAT cohort that included a hundred of patients treated with breast RT without chemotherapy and followed during 24 months post-RT. An individual reconstitution of the doses absorbed by the heart, the left ventricle (LV) and the coronary arteries was performed.Early signs of cardiotoxicity were defined by subclinical cardiac dysfunctions evaluated by echocardiography and by changes in the concentrations of a panel of circulating biomarkers potentially involved in cardiotoxicity.With an intermediate follow-up of 6 months, the analysis of data showed a dose-response relationship between subclinical left ventricular dysfunction characterized by a >10% decrease in the myocardial contractility index (longitudinal strain) and the average dose absorbed by the LV. The alteration of fibrinogen levels at the end of RT, combined with the LV dose, improved risk prediction (based on longitudinal strain)
Haziza, Jocelyne. "Radiothérapie per-opératoire : à propos des 41 premiers patients traités, expérience de la Fondation Bergonié de juillet 1990 à mars 1993". Bordeaux 2, 1994. http://www.theses.fr/1994BOR23003.
Pełny tekst źródłaGuichard, Pierre. "Radiothérapie étendue aux aires lombo-aortiques : étude de la tolérance au traitement et estimation du bénéfice thérapeutique ou irradiation dite "en raquette" appliquée aux cancers de la prostate, cancers de l'endomètre et cancers du col utérin". Bordeaux 2, 1988. http://www.theses.fr/1988BOR25309.
Pełny tekst źródłaDebrigode, Charles. "Optimisation de la réponse à la radiothérapie". Montpellier 1, 1994. http://www.theses.fr/1994MON11158.
Pełny tekst źródłaBarbet, Nicolas. "Radio-thérapie per-opératoire dans les cancers oropharyngés étendus à la base de la langue". Saint-Etienne, 1990. http://www.theses.fr/1990STET6420.
Pełny tekst źródłaLapointe, Jacques. "Androgènes et cancer du sein". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ57940.pdf.
Pełny tekst źródłaTEISSEYRE, MONIQUE. "Le cancer intervallaire du sein". Montpellier 1, 1992. http://www.theses.fr/1992MON11220.
Pełny tekst źródłaREBENA, DUBOIS CATHERINE. "Alimentation et cancer du sein". Lille 2, 1990. http://www.theses.fr/1990LIL2M275.
Pełny tekst źródłaBondiau, Pierre-Yves. "Mise en oeuvre et évaluation d'outils de fusion d'image en radiothérapie". Nice, 2004. http://www.theses.fr/2004NICE4114.
Pełny tekst źródłaCancer is a major problem of public health. Treatment can be done in a general or loco-regional way, in which case medical images are important as they specify the localization of the tumour. The objective of the radiotherapy is to deliver a curative dose of radiation in the target volume while sparing the organs at risks (OAR). The determination of the accurate localization of the targets volume as well as OAF makes it possible to define the ballistics of irradiation beams. After the description of the principles of radiotherapy and cancers treatment, we specify the clinical stakes of ocular, cerebral and prostatic tumours. We review the state of the art image matching algorithms, with a didactic purpose for the medical community. The results of image matching techniques are presented in the framework of cerebral and prostatic radiotherapy planning in order to determine the types of applicable method in oncology. Then, we present the prospects for these methods with respect to the anatomical localization and automatic segmentation. Applications of automatic segmentation and the evaluation of the results in the framework of brain tumour are described after a review of the various segmentation methods according to anatomical localizations. An original application is the digital simulation of the virtual tumoral growth and the comparison with the real growth of a cerebral tumour presented by a patient. We conclude with the future developments possible of the tools for image processing in radiotherapy as well as the tracks of research to be explored in oncology
Clement-Colmou, Karen. "Impact du fractionnement de la radiothérapie sur le microenvironnement vasculaire tumoral". Thesis, Nantes, 2018. http://www.theses.fr/2018NANT1029/document.
Pełny tekst źródłaThe tumour blood vessels are immature and dysfunctional, limiting the distribution and efficacy of anticancer drugs. Conventional radiotherapy (2Gy / day) improves their structure, reduces hypoxia and improves the biodistribution of concomitant treatments. However, hypofractionated radiotherapy, using higher doses per fraction, tends to replace conventional schedules. Their consequences on the tumour microenvironment are poorly understood. Our goal was to define the impact of different fractionation schedules on the tumour vascular microenvironment. A fractionation scale, ranging from 2 to 12Gy per fraction, was implemented on two cancer models (prostate and lung). Several phenotypical and functional aspects of the vasculature and anti-tumour efficacy were studied. A radiation-induced vascular maturation was observed, including an increased pericyte coverage and an improved distribution of doxorubicin. In both models, tumour control was better for hypofractionated schedules. Vascular pseudo-normalization was poorly sensitive to fractionation, but hypoxia was improved in a dose-dependent manner. The depth and duration of the improvement was greater in the slow-growing prostate cancer model: hypoxia seemed to depend as much on the kinetics of repopulation of the model as on the quality of the blood supply. Our results highlight the mutual influence of tumour and vascular responses to irradiation. They will be useful to optimize the future delivery schedule of anticancer treatments
Sackett, Melanie K. "La signification pronostique de l'expression de la cyclooxygénase 2 dans le cancer du larynx glottique de stade précoce traité par radiothérapie". Thesis, Université Laval, 2009. http://www.theses.ulaval.ca/2009/26032/26032.pdf.
Pełny tekst źródłaCheylan, Haccuria Christine. "Résultats thérapeutiques de la radiothérapie endocavitaire, dans les cancers du rectum". Montpellier 1, 1988. http://www.theses.fr/1988MON11304.
Pełny tekst źródłaDiest, Paul J. van Baak Jan P. A. "Quantitative cyto- and histoprognosis in breast cancer /". Amsterdam ; London ; New York [etc.] : Elsevier, 1992. http://catalogue.bnf.fr/ark:/12148/cb373728109.
Pełny tekst źródłaThèse soutenue par P. J. van Diest. Bibliogr. à la fin de chaque chap. Index.
Martins, Helder Manuel. "Cancers broncho-pulmonaires secondaires à une radiothérapie ou à une chimiothérapie : à propos de 4 observations". Saint-Etienne, 1988. http://www.theses.fr/1988STET6051.
Pełny tekst źródłaGrimaldi, Béatrice. "Place de la radiothérapie dans le traitement des cancers de l'estomac". Montpellier 1, 1991. http://www.theses.fr/1991MON11147.
Pełny tekst źródłaSalavagione, Jean-Marc. "Les cancers intrakystiques du sein". Montpellier 1, 1991. http://www.theses.fr/1991MON11239.
Pełny tekst źródłaDe, Jong Dorine. "Characterization of the Signaling Pathways Involved in Cellular Cannibalism Elicited by Ionizing Radiation". Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS101.
Pełny tekst źródłaMany types of anticancer therapies are available to kill tumor cells. The tumoral cell death modalities may be different upon the treatment, the cell type and inter-individual sensitivity. Besides the typical cell death processes apoptosis and necrosis, cellular cannibalism has also been reported in patients’ tumoral biopsies. This cellular process is defined as the engulfment of one live cell by another live cell followed by the degradation of the inner cell. The mechanisms beyond cellular cannibalism are still partially understoof but it appears to be of clinical relevance. Indeed, we have shown that these events could be modulated by anticancer treatments and there are evidences of their utility as a potent prognostic biomarker in some cancers. This thesis presents the in vitro experiments which led to the identification of the signaling pathways involved in cellular cannibalism induced by ionizing radiation
Kubas, Abdulhameed. "Radiothérapie du carcinome hépatocellulaire : mobilité organique et impact dosimétrique du blocage respiratoire". Lyon 1, 2008. http://www.theses.fr/2008LYO10309.
Pełny tekst źródłaThe irradiation of hepatocellular carcinoma (HCC) is a challenge due to the low tolerance of the liver to the x-rays, the existence of many organs at risk (OAR) (liver, kidneys, spinal cord,stomach, and duodenum) and the presence of the underlying cirrhosis. Thanks to the conformal radiotherapy we can deliver a high curative dose to a part of the liver. However, the breath movements require the increasing of the safety margin around the liver and the OARs. The feasibility of the respiratory gating has been proved especially in the treatment of lung, breast and liver cancer : it reduces the irradiation to the healthy tissue and allows a dose-escalation to the tumor. To improve the radiotherapy treatment we propose to evaluate the benefice of the breath-hold technique in the treatment of liver cancer. We analysed the mobility of the liver cancer during the respiration to better optimize the defination of the target volumes and mostly the internal margins (IM), and also the amplitude of movements of the OARs involved in the tolerance of the HCC irradiation. We used different dosimetric analysis parameters to evaluate the benefice of respiratory gating, comparing the dosimetric plans in exhale and inhale with with the ones in free respiration. This will allow us to quantify the benefice obtained by the breath-hold technique and to determine the optimal respiratory phase of the treatment. Being involved in an extracranial stereotactic project at Lyon Sud Hospital, we realised a study about the non coplanar beam optimization to better preserve the non involved liver
Aimé, Armand Paul. "Cancer du larynx glottique T1 N0 (UICC) : à propos de 29 cas traités par radiothérapie exclusive de 1977 à 1990". Université Joseph Fourier (Grenoble), 1993. http://www.theses.fr/1993GRE16001.
Pełny tekst źródłaCorde, Stéphanie. "Développement méthodologique de l'application d'agents pharmacologiques renforçateurs de l'effet photoélectrique pour l'utilisation du rayonnement synchrotron en radiothérapie anticancéreuse". Université Joseph Fourier (Grenoble), 2002. http://www.theses.fr/2002GRE19007.
Pełny tekst źródłaGuo, Ning. "Investigation of the chemical properties of astatine at +I and –I oxydation states in aqueous solution". Thesis, Nantes, 2017. http://www.theses.fr/2017NANT4038/document.
Pełny tekst źródłaTargeted alpha therapy is an appealing method for the treatment of cancer as a complement to the current approaches. Astatine-211, with a half-life of 7.21 h, is considered as an exciting prospective candidate for this application. A pre-required condition is to fix in a stable way the radioactive isotope to the vector that is going to serve to recognize cells. This asks for a thorough knowledge of the chemical properties of astatine. Considering its position in the periodic table, it can exist under the form At− in coherence with the chemical properties of the other halogens, and also possesses a more metallic character that explains the existence of stable cationic species. The objective in this work is to identify the properties of different At species in aqueous solution. The predominance of the species At− in reducing acidic conditions was confirmed by means of a technique of electromobility. A first value of absolute mobility is then proposed. In more oxidizing conditions, the species At+ dominates. The reactivity of this species with the ions of the halogens series was studied/quantified. An exotic species IAtBr− was highlighted in particular thanks to the help of modeling tools. The peculiarity of the compound AtI to form halogen-type bonds was shown for the first time
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
Dagdemir, Aslihan Seda. "Paysage épigénétique du cancer du sein". Thesis, Clermont-Ferrand 1, 2014. http://www.theses.fr/2014CLF1MM14/document.
Pełny tekst źródłaBreast cancer remains the leading cause of cancer-related deaths in women, and is noted for conflicting clinical behaviors and patient outcomes, despite common histopathological features at diagnosis. This can be explained by the high histological and molecular heterogeneity of the disease, making it hard to choose a therapy adapted uniquely to each patient. Epigenetics refer to changes in phenotype and gene expression. Epigenetic modifications of the genome can be acquired de novo and are potentially inherited. Epigenetic mechanisms work to change the accessibility of chromatin to transcriptional regulation locally and globally via modifications of the DNA and by modifications or rearrangements of nucleosomes. Epigenetics consist in several molecular mechanisms: histone modifications, small non-coding or antisense RNAs and DNA methylation that are closely interconnected. The incidence and mortality of breast cancer is high in the Western world as compared with countries in Asia. There are also differences in the regional cancer incidence rates in Western countries. Several studies involving immigrants to Western countries suggest that lifestyle and diet are two of the main causes of these differences. In Eastern countries, the incidence of breast cancer is approximately one-third that of Western countries, whilst their high dietary intake of phytoestrogens, mainly in the form of soy products, can produce circulating levels of phytoestrogens that are known experimentally to have estrogenic effects. An increasing number of epidemiological and experimental studies have suggested that the consumption of a 4 phytoestrogen-rich diet may have protective effects on estrogen-related conditions, such as breast cancer.Based upon this information, we studied the effects of treatment phytoestrogens; genistein, daidzein and 17-β-estradiol on the post-translational modification of histones such as lysine methylation and acetylation of histones H3 and H4 in breast cancer cell lines. Subsequently, we studied the effects of histone methylation inhibitor and histone deacetylase inhibitor on histone lysine trimethylation and acetylation in breast cancer cell lines. For this study, we used two breast cancer cell lines MCF-7 and MDA-MB-231. Each cell line was treated respectively with 3-Deazaneplanocin A hydrochloride (DZNep) [5 μM] (HMTi), Sodium Butyrate (NaBu) [2 mM] (HDACi) and Suberoylanilide Hydroxamic acid (SAHA) [1 μM] (HDACi) for 48 hours. Finally, we completed studies in all cell lines with breast tumors to assess Chromatin ImmunoPrecipitation (ChIP) of selected histone modifications in cancer. The relative levels of three modified histones, including H3K27me3 (Histone 3 Lysine 27 Methylation), H3K9ac (Histone 3 Lysine 9 Acetylation), and H3K4ac (Histone 3 Lysine 4 Acetylation) will be determined in breast tumors compared to matched normal tissue according to the classification of Saint Gallen. Today, ChIP has been coupled with promoter DNA microarrays to evaluate the mechanisms of human gene regulation on a genome-wide scale. ChIP-on-chip technology could be used to investigate the alterations of global gene expression in tumorigenesis. Here, we investigated differentially expressed genes associated with modified histones H3K27me3, H3K9ac and H3K4ac in breast tumors by Agilent SurePrint G3 400kX2 microarrays containing approximately 21,000 of human transcripts. We will scan the enriched regions at each gene promoter in thirty breast tumors compared with normal tissue samples. Breast tumor samples will be classified according to their clinical profiles, especially hormone receptor status
Bonhomme, Philippe. "Aspects dermatologiques du cancer du sein". Bordeaux 2, 1995. http://www.theses.fr/1995BOR23098.
Pełny tekst źródłaBENGHANEM, FIRDAOUS LOUBNA. "Taxol et cancer du sein avance". Nantes, 1993. http://www.theses.fr/1993NANT038M.
Pełny tekst źródłaSPORTES-GERBAULT-SEUREAU, MICHELE. "Etude cytogenetique du cancer du sein". Paris 6, 1988. http://www.theses.fr/1988PA066688.
Pełny tekst źródłaMARCUZZI, LEJAY ISABELLE. "Cancer du sein : l'information en questions". Lille 2, 1994. http://www.theses.fr/1994LIL2M030.
Pełny tekst źródłaDarwiche, Jihad. "Grossesse apres cancer du sein traite". Aix-Marseille 2, 1993. http://www.theses.fr/1993AIX20027.
Pełny tekst źródłaAlibert, Didier. "Le cancer du sein chez l'homme". Dijon, 1994. http://www.theses.fr/1994DIJOM051.
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