Dissertations / Theses on the topic 'Tumeurs du rein – génétique'
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Hebert, Lucie. "Etude du rôle de BAP1 dans la prédisposition aux cancers et dans la tumorigenèse." Paris 7, 2014. http://www.theses.fr/2014PA077142.
BAP1 is a tumor suppressor gene which germline mutations predispose to a cancer predisposition syndrome named "BAP1 syndrome". The BAPI-related cancers are rare and aggressive, such as uveal melanoma and malignant mesothelioma. The first axis of my work was the study of a family harboring numerous kidney and breast cancers. We identified a germline BAP1 mutation carried by aIl individuals affected by kidney cancers ii this family, and a national study showed that the risk of developing kidney cancers is significantly higher for BAP1 mutation carriers. Those results demonstrate that BAP1 germline mutations predispose to kidney cancer, and that this tumor is part of the spectrum of BAPI-related cancers syndrome. However, the role of BAP1 in breast cancer predisposition remains uncertain. The identification of several breast cancers inactivated for BAP1 showed that this event is not specific to the family we studied, but the mechanisms of BAP1 inactivation remain to be understood. The second axis of my work consisted in the analysis of proteomic profiles of two isogenic cell lined inactivated or not for BAP1. This work showed that BAP1 re-expression in this cell line model has an effect on oxidative stress response, which in turn influences the dynamic of actin cytoskeleton, cell migration and invasiveness. We propose that BAP1 poly-deubiquitinase activity plays a role in the stability of a wide range of nuclear proteins that is turn regulates the stability of cytoplasmic proteins
Nesslany, Fabrice. "Etude de la spécificité du test des comètes in vivo : application à l'étude de produits à tropisme rénal." Lille 2, 2007. http://www.theses.fr/2007LIL2S023.
Maubec, Eve. "Prédisposition génétique au mélanome : de la génétique à la recherche clinique." Thesis, Paris 11, 2012. http://www.theses.fr/2012PA11T034.
This thesis had two main objectives: 1) To define groups of patients which may benefit from genetic counseling by identifying predictors of mutations of the CDKN2A gene, a major gene predisposing to cutaneous melanoma (CM) in families with only two cases. 2) Epidemiological and clinical characterization of specific entities of melanoma with the secondary objective of contributing to the identification of susceptibility genes for these entities. Coexistence of CM with renal cell carcinoma and mucosal anogenital melanomas were studied.The study populations are a collection of 293 melanoma patients that were ascertained systematically and the French collection MELARISK which is a collection including over 3000 subjects drawn from families with multiple cases of melanoma or melanoma occurring in a particular context (association with another cancer, rare locations, occurrence before the age of 20, multiple sporadic melanomas).We investigated association of three clinical features with the presence of a CDKN2A mutation in a family by extent of CM family clustering (2 versus ≥3 CM patients among first-degree relatives in a family).The study was conducted in 483 French families including 387 families with two melanoma patients, and 96 families with three or more patients with melanoma. The factors examined individually and in a joint analysis in a family were: median age at diagnosis <50 years, ≥1 patient in a family with multiple primary melanomas (MPM) or with pancreatic cancer. The frequency of CDKN2A mutations was higher in F3+ families (32%) than in F2 families (13%). While early age at melanoma diagnosis and occurrence of MPM in ≥1 patient were significantly associated with the risk of a CDKN2A mutation in F2 families, early age at melanoma diagnosis and occurrence of pancreatic cancer in a family were significantly associated with CDKN2A mutations in F3+ families. Thus this study showed that clinical features associated with CDKN2A mutations vary, in France, a country of low incidence of melanoma, according to the degree of familial clustering. Identifying predictors of CDKN2A mutations in families with two melanoma cases has helped to define subgroups of families (early age at CM diagnosis, and/or ≥1 MPM patient) in which the frequency of CDKN2A mutations is above 20% such that these subgroups of F2 families should be offered genetic testing.The analysis of two series of patients, either patients with melanoma coexisting with renal cell carcinoma or patients with anogenital mucosal melanoma identified their clinical and histological features by comparing them to a series of melanomas that were ascertained systematically. In both series, our results suggested a genetic predisposition at least partly independent of CDKN2A. The study of the c renal cell carcinoma; coexistence of CM and renal cancer in the same patient had two practical consequences for clinicians: it suggests the interest of a dermatologic screening visit in patients with renal cell carcinoma and that abdominal ultrasonography or computed tomography scanning performed at the initial workup and during the follow-up of patients with CM may be of value for the early detection of renal cancer. Regarding genetic research, this series has contributed to the identification of a germline mutation in the MITF gene that increases the risk of developing melanoma, renal cancer or both cancers and has interesting biological properties. The study of anogenital melanoma has shown that these melanomas could be associated with cutaneous melanoma in the same patient and it has also shown a high frequency of family history of melanoma associating mucosal and CM suggesting a shared genetic predisposition. Consequently dermatological screening or monitoring must include examination of both skin and mucosa in families with multiple cases of CM; and in case of a mucosal melanoma, a dermatological examination should be offered to relatives. The genetic mechanism has to be identified
Guérin, Célia. "Caractérisation de nouvelles mutations activatrices dépendantes de l'HGF dans le lobe N-terminal du domaine kinase du récepteur MET dans le cancer du rein héréditaire." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. https://pepite-depot.univ-lille.fr/ToutIDP/EDBSL/2023/2023ULILS074.pdf.
Targeted therapies are currently revolutionizing the management of cancer patients, provided they present a targetable molecular alteration responsible for tumor progression. Receptor tyrosine kinases (RTKs) with activating mutations are major targets of targeted therapies, with EGFR as a representative example, whose mutations lead to its constitutive activation, making it independent of stimulation by its ligand.The MET receptor, another RTK in this family, has activating mutations in kidney and lung cancer. Indeed, type I papillary renal cell carcinoma (HPRC), an uncommon hereditary cancer, is unique in that over 80% of cases have MET activating mutations. In contrast, in non-small cell lung cancer (NSCLC), MET mutations lead to skipping of exon 14 encoding the juxtamembrane domain (MET ex14 mutations). This exon skipping leads to the loss of the juxtamembrane domain, a regulatory domain involved in the negative regulation of the receptor. In an original way from other RTK mutations, these mutations always require stimulation by HGF, the ligand of MET, making HGF production a parameter to be considered in the stratification of patients eligible for targeted therapies.Tyrosine kinase inhibitors (TKIs) directed against MET have very recently been approved for clinical use, offering real hope for patients with these mutations.Thanks to the development of high-throughput sequencing for diagnosis and the emergence of new resistance mutations following treatment with targeted therapies, the spectrum of mutations affecting TKIs is expanding considerably. The current challenge is no longer the detection of these mutations, but their functional interpretation, which can demonstrate their activating character or their targeting by TKIs.In this context, my thesis objective was to exploit sequencing data from patients suffering from HPRC or NSCLC to identify new MET activating mutations and characterize their activation mechanisms in order to determine their eligibility for potential treatment by TKIs.Thanks to a collaboration with the Institute Gustave Roussy, which centralizes sequencing data from HPRC patients, we have identified 8 previously undescribed mutations in a cohort of 158 patients, affecting the extracellular domain (V37A and R426P), the juxtamembrane domain (S1018P and G1086E) and the N-terminal lobe of MET kinase (H1086L, I1102T, C1125G and L1130S). In parallel, thanks to our collaboration with the Lille University Hospital, which centralizes data on 2808 NSCLC patients, we have identified 2 undescribed kinase domain mutations.First, we demonstrated in a fibroblast transformation model that the four N-terminal lobe mutations identified in HPRC are potential MET-activating mutations. Interestingly, although localized to the kinase, these mutations retain a dependence on HGF to induce cell transformation. Moreover, all four mutations are sensitive to TKIs directed against MET.In a second step, to better characterize these new activating mutations, we established T47D epithelial cell lines expressing two of the new activating mutations (H1086L and I1102T), which we compared with wild-type MET and MET ex14, known to retain its dependence on HGF. Our results confirm that both mutations require activation by HGF for activation of downstream signaling pathways and induction of responses such as cell motility. Transcriptomic analysis reveals significant similarities between the transcriptional programs of the MET I1102T, H1086L and MET exon14 mutations, highlighting their involvement in extracellular matrix remodeling and invasion. Xenografts of cells expressing these new mutations in mouse models demonstrate their ability to promote tumor growth [...]
Salzmann, Franck. "L'oncocytome rénal : à propos de quatorze observations." Montpellier 1, 1993. http://www.theses.fr/1993MON11088.
Molle, Rachel Kessler Michèle. "Risque de développer un cancer après une transplantation rénale étude rétrospective chez 504 patients transplantés au CHU de Nancy /." [S.l] : [s.n], 2004. http://www.scd.uhp-nancy.fr/docnum/SCDMED_T_2004_MOLLE_RACHEL.pdf.
Jaunait, Eric. "Adénomatose rénale : à propos de deux cas." Caen, 1990. http://www.theses.fr/1990CAEN3104.
Cales, Valérie. "Oncocytomes rénaux et tumeurs rénales à cellules éosinophiles." Bordeaux 2, 1995. http://www.theses.fr/1995BOR23025.
Ibrahim, El Chérif. "Regulation de l'expression de gene hla-g lors de la reponse au stress et analyse de l'activation selective de ce gene dans les melanomes et les carcinomes renaux." Paris 5, 2001. http://www.theses.fr/2001PA05N085.
Bensalah, Charles Karim. "La spectroscopie optique : une nouvelle approche pour l'étude des tumeurs du rein." Rennes 1, 2010. http://www.theses.fr/2010REN1B135.
The objective was to evaluate the ability of optical spectroscopy to characterize renal tumors. Reflectance optical spectroscopy measurements (ROSM) were acquired in 22 patients who underwent a nephrectomy for a renal tumor. Raman Spectroscopy measurements were made in another population of 44 patients with a suspicion of renal cancer. ROSM were analyzed in the visible and near infrared region. Raman spectra were processed with a vector support machine to create a classification tool. ROS could differenciate normal and tumoral renal tissue as well as malignant and benign tumors. Raman algorithm could classify spectra with a >80% precision as normal/tumoral, high and low grade and according to hystologic subtype. RS and ROS are non-invasive techniques that can recognize with high accuracy normal and tumoral renal tissue, benign and malignant renal tumors and characterize malignant renal tumors
Devouassoux, Shisheboran Mojgan. "Analyse génétique des tumeurs germinales : recherche d'instabilité génétique et caractéristiques génotypiques." Lyon 1, 2001. http://www.theses.fr/2001LYO1T132.
Baudouin, Didier. "Les tumeurs à rénine : à propos d'un cas." Caen, 1990. http://www.theses.fr/1990CAEN3115.
L'Hostis, Hélène. "Angiomyolipome rénal, à propos de 46 observations : étude histologique, immunohistochimique et évolutive." Bordeaux 2, 1997. http://www.theses.fr/1997BOR23077.
Nrecaj, Patrick Nucléaire Alain. "Apport du morpho-TEP au F-Fluorodeoxyglucose dans la prise en charge des cancers du rein." [S.l] : [s.n], 2004. http://www.scd.uhp-nancy.fr/docnum/SCDMED_T_2004_NREJAC_PATRICK.pdf.
Rabiller, Vincent. "Contribution à l'étude de l'hémi-hypertrophie corporelle congénitale : à propos de 3 cas." Nantes, 1985. http://www.theses.fr/1985NANT3470.
Simoneau, Maryse. "Analyse génétique des tumeurs superficielles da la vessie." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0005/NQ39395.pdf.
Armaignac, Catherine. "La polykystose rénale autosomique dominante ou la polykystose rénale de l'adulte : à propos de deux époux atteints : étude clinique et génétique de la famille." Montpellier 1, 1990. http://www.theses.fr/1990MON11281.
Vives, Olivier. "Angiomyolipome rénal de l'adulte - intérêt du diagnostic radiologique : à propos d'un cas relevé par une rupture spontanée." Bordeaux 2, 1992. http://www.theses.fr/1992BOR2M183.
GRELLAUD, RODIER ANNE. "Les tumeurs du rein bilaterales : a propos de 3 observations et d'une enquete aupres des centres d'hemodialyse." Limoges, 1988. http://www.theses.fr/1988LIMO0116.
Méjean, Arnaud. "La chirurgie conservatrice dans les tumeurs du rein de l'adulte : a propos de 47 observations." Lille 2, 1993. http://www.theses.fr/1993LIL2M191.
Bousard, Aurélie. "Etude génétique et épigénétique de l'adénocarcinome du rein à cellules claires." Thesis, Evry-Val d'Essonne, 2015. http://www.theses.fr/2015EVRY0004/document.
This thesis is composed of three projects looking to improve molecular characterization and diagnosis of clear cell renal cell carcinoma (ccRCC). The first project concern the identification of oncogenic mutations located on active regulatory elements of ccRCC. The use of whole-genome sequencing data of an hundred patients affected by ccRCC and epigenetic data (ChIP-seq and ATAC-seq) from renal cancer cell lines enabled the identification of mutation islands located in these active regulatory elements. Moreover, the use of RNA-seq data highlighted the association between some mutation islands and gene expression changes. One mutation island has been identified on a regulatory element located in the first intron of KIBRA. This gene is a member of the Hippo pathway known to be involved in ccRCC tumorigenesis. This pioneer work in integrating approach of genetic and epigenetic data consists in the first study that describes non-coding mutations located on active regulatory elements identified on a cell type relevant to the study. The second project consists of a study of the molecular alterations of the FGF/FGFR pathway, that is currently the target of clinical assays in ccRCC. It suggests an involvement of the FGF/FGFR pathway activation in ccRCC tumorigenesis and in patient prognosis, partly through the expression alterations of negative regulators of this pathway such as SEF.Finally, the set-up of a ccRCC non-invasive diagnostic test from circulating DNA has been initiated. Hypermethylated biomarkers have been identified and sensible tests based on methylation-specific qPCR have been set up in the third project
Adida, Colette. "Etude par immunohistochimie de l'expression de l'urokinase dans les tumeurs renales : a propos de 5 cas." Université Louis Pasteur (Strasbourg) (1971-2008), 1992. http://www.theses.fr/1992STR1M159.
Tuchmann, Christine. "Tumeurs multiples du rein : étude rétrospective radio-clinique de 110 observations colligées entre 1971 et 1994." Strasbourg 1, 1995. http://www.theses.fr/1995STR1M061.
Chabannes, Eric. "Tumeurs de la voie excrétrice urinaire supérieure : étude rétrospective d'une série de 105 observations et revue de la littérature." Bordeaux 2, 1993. http://www.theses.fr/1993BOR23093.
Ingels, Alexandre. "Développement de techniques d’imageries pour le diagnostic et le pronostic des tumeurs du rein." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS451/document.
The aim of this project is the development of new imaging techniques for renal cancer diagnostic and treatment.We have assessed several techniques including optical coherence tomography and molecular imaging. We assessed a series of potential markers for molecular imaging by measuring some pre-defined markers expressions by immunohistochemistry in renal cell carcinoma and their association with disease’s prognostic. Finally, we assessed two molecular imaging techniques in pre-clinical models: Molecular Magnetic Resonance Imaging and Molecular Ultrasound Imaging
Chomy, Isabelle. "Métastases rénales de tumeurs solides : à propos de trois cas de cancers broncho-pulmonaires : revue de la littérature." Bordeaux 2, 1989. http://www.theses.fr/1989BOR25227.
Labit-Bouvier, Corinne. "Marqueurs moléculaires diagnostiques et pronostiques des tumeurs neuroépithéliales." Aix-Marseille 2, 2003. http://www.theses.fr/2003AIX20691.
Laurent, Christophe. "Développement des traitements HIFU guidés par IRM de température en temps réel : étude sur le foie et le rein." Bordeaux 2, 2008. http://www.theses.fr/2008BOR21583.
The aim of this work was to propose an improvement of HIFU efficacy and safety in highly perfused and mobile organs, using rapid and volumetric MRI thermometry. A first study proposed a quantitative estimation of thermal parameters in pig kidney ex vivo, treated by HIFU, under different arterial flow condition. The excellent correspondence between rapid thermo-MRI and the BHT showed that this model is applicable for describing the spatio-temporal evolution of temperature in highly perfused organ. Secondarily, the possibility to perform rapid and volumetric temperature monitoring, in real time, of HIFU ablations in the kidney and liver was tested. This monitoring was feasible with an excellent spatio-temporal resolution and calculation of thermal dose confirmed that the letal value could be reached in highly perfused and mobile organs. Moreover, it was possible to create necrotic area in kidney and liver without skin bun. Finally, continue volumetric sonication, using thermal diffusivity, allowed an increasing of ablated tissue volume in a limited time. Recent improvements in rapid imaging techniques and optimization of the motion correction might significantly improve the performances of HIFU ablation and allow its use soon in clinical practice
Taourel, Patrice. "Rôle de l'I. R. M. . Dans l'exploration des tumeurs rénales de l'adulte : à propos de 30 cas." Montpellier 1, 1988. http://www.theses.fr/1988MON11002.
Maire, Georges. "Caractérisation génétique d'une tumeur dermique : le dermatofibrosarcoma protuberans." Nice, 2005. http://www.theses.fr/2005NICE4004.
Dermatofibrosarcoma Protuberans (DP) is a rare slow-growing infiltrating dermal neoplasm of intermediate malignancy. At the cytogenetic level, DP cells are characterized by either supernumerary ring chromosomes or t(17;22) that are most often unbalanced. Both the rings and linear der(22) contain a specific fusion of COL1A1 with PDGFB. Whereas rings have been mainly observed in adults, translocations have been reported in all paediatric cases. DP is therefore a unique example of tumor in which (i) the same molecular event occurs either on rings or linear translocation derivatives, and (ii) the chromosomal abnormalities display an age-related pattern. In all DP cases that underwent molecular investigations, the breakpoint localization in PDGFB was found to be remarkably constant in exon 2. In contrast, the COL1A1 breakpoint was found to be variably located within the exons of the alpha-helical coding region (exons 6-49)/ No preferential COL1A breakpoint and no correlation between the breakpoint location and the age of the patient or any clinical or histological particularity have been described. Congenital case as well as paediatric or adult case presented all the same COL1A1-PDGFB rearrangement. The COL1A1-PDGFB fusion is detectable by multiplex RT-PCR or dual colour FISH experiment adapted to fixed and paraffin embedded tissues. In approximately 13 % of DP cases, the COL1A1-PDGFB fusion is not found, suggesting that genes other than COL1A1 or PDGFB might be involved in a subset of cases. We identified a DP without the COL1A1-PDGFB fusion gene. We observed a t(5;8) where PTK2B gene was found rearranged. In addition, we detected a high level of PDGFRB transcription in the case
Dolley-Hitze, Thibault. "Expression et rôle du récepteur de type 1 à l'angiotensine II par les carcinomes rénaux à cellules claires." Rennes 1, 2012. http://www.theses.fr/2012REN1B010.
The prognosis of metastatic clear cell Renal Cell Carcinoma (ccRCC) is poor. Nethertheless, new targeted anti-angiogenic therapies, particularly tyrosine kinase inhibitors (TKI), improved patients’ survival. In parallel, the 2 principal angiotensin-2 receptors, type-1 and type-2 (AT1-R and AT2-R), have been described overexpressed in many aggressive tumors but never in ccRCC. Blocking AT1-R is also known to have anti-tumour properties by inhibiting neo-angiogenesis and tumour cells proliferation on cell culture and animal experiments. Associating one AT1-R blocker (ARB) with one TKI could be synergistic in the treatment of ccRCC. In this work 2 objectives are pursued: the description of AT1-R and AT2-R expressions by ccRCC and the study of associating one ARB and one TKI on ccRCC cultured cells and on ccRCC xenograft in mice. For the study of angiotensin-2 receptors expressions by ccRCC, tumours embedded in paraffin or frozen were analysed by ImmunoHistoChemistry (IHC), western blot and quantitative PCR. On the 84 tumours analysed, AT1-R and AT2-R were over-expressed by the most aggressive tumours. Their expressions were also correlated with patients’ survival. Telmisartan, one ARB, was combined with sunitinib, one TKI. For xenograft experiments, ccRCC cell lines, 786-O, were injected to nude mice. For cultured cells experiments, 786-O and Human Umbilical Vein Endothelial Cells were grown in different conditions. This association significantly increases tumour necrosis by inhibiting neo-angiogenesis. It could be explained by a decreased tumour VEGF-A secretion and by less activation of endothelial VEGFR2. In conclusion, AT1-R and AT2-R are overexpressed by the most aggressive tumours and are correlated with patients’ survival so that they could be considered as prognostic factors. AT1-R could also represent a new therapeutic target in the treatment of ccRCC. Its blockage could improve the antiangiogenic effects of sunitnib. Clinical studies are now required
Khawam, Krystel. "Evaluation du rôle du système IL-15/IL-15R dans la physiologie et la pathologie des cellules épithéliales rénales humaines." Paris 11, 2009. http://www.theses.fr/2009PA11T036.
Aubert, Sébastien. "Régulation par l'hypoxie de l'expression du gène de mucine membranaire MUC1 dans un modèle cellulaire rénal : implications potentielles de MUC1 en physiopathologie rénale." Lille 2, 2009. http://www.theses.fr/2009LIL2S036.
Basset, El Essawy Abdel. "Influence du polymorphisme des gènes impliqués dans l'hypertension artérielle tels que ACE, AGT, AT1-R et ecNOS sur les résultats en transplantation rénale." Saint-Etienne, 2005. http://www.theses.fr/2005STET014T.
Proslier, Dominique. "L'atteinte rénale dans le syndrone branchio-oto-rénal." Montpellier 1, 1988. http://www.theses.fr/1988MON11145.
Wager, Michel. "Statut moléculaire - oncogènes et gènes suppresseurs de tumeurs - des tumeurs gliales de l'adulte en relation avec le grade anatomo-pathologique et l'évolution tumorale." Poitiers, 2007. http://www.theses.fr/2007POIT1401.
Hervouet, Éric. "Mécanismes impliqués dans la régulation de la biogenèse mitochondriale de tumeurs rénales : carcinomes à cellules claires et oncocytomes." Lyon 1, 2006. http://www.theses.fr/2006LYO10089.
This thesis aimed at better understanding the origins of mitochondrial disorders in renal tumors. The CRCC that are often associated with poor prognosis in patients, and characterized by vhl invalidation, exhibit a decrease in OXPHOS complexes. This phenomenon could be due both to HIF (Hypoxia-inducible factor) stabilization induced by the lack of pVHL in CRCC and to an increase in ROS production. HIF can also be stabilized by cobalt treatment but this compound brings additional toxic effects, since it inhibits the processing of a precursor of the cytochrome c oxidase 4 subunit and therefore prevents the cytochrome c oxidase assembly. On the opposite, renal oncocytoma, that are non-malignant tumors are characterized by mitochondrial proliferation. We identified mutations in mitochondrial DNA genes of complex I or IV, which might suggest that the mitochondrial proliferation in these tumors is similar to that observed in typical mitochondrial pathologies
Bigot, Pierre. "Approche génétique et protéomique de la carcinogénèse rénale." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066077.
Kidney cancer is the 7th largest solid tumors in adults and its incidence is rising. The purpose of our research was to study renal carcinogenesis and to identify prognostic biomarkers in clear cell renal cell carcinoma.We used the isobaric tagging iTRAQ® to perform a relative quantification of kidney tumor proteins. After proteomic analysis, 928 constitutive proteins were identified and 346 had a modified expression in tumor compared with that of normal tissue. Pathway and integrated analyses indicated the presence of an up-regulation of the pentose phosphate pathway in aggressive tumors. In total, 14 proteins were excreted and could potentially become biomarkers. Among them, we confirmed that TGFBI was significantly associated with oncologic outcomes.To understand renal carcinogenesis, we investigated the 12p11.23 renal cancer susceptibility locus. The first step was to confirm this locus by an independent study. Then we performed a functional analysis of the 12p11.23 region in relation to RCC risk. Our results suggest rs7132434 is a functional SNP at 12p11.23 responsible for the GWAS RCC signal, and that this locus acts as an enhancer of SHARP1 expression by binding c-Jun. Further investigations will be necessary to understand the role of SHARP1 in renal carcinogenesis
Chauveinc, Laurent. "Etudes génétiques des tumeurs radio-induites." Paris 11, 2001. http://www.theses.fr/2001PA11T040.
Radiation induced tumors are a possible very late complications of radiotherapy. Many epidemiologist studies exists, with the evaluation of the relative risk for different tissues. But, the genetic studies are rare, and no global theory exists. With the published cases, two profiles existed, one with translocations and one with genetic material losses, evoking two different genetic evolutions. In this work, a few ways to explain the chromosomic evolution of the radiation-induced tumors were explored. In the fust part, with study of the age and the latency period of second tumor after retinoblastomas, two or more genes were modified by the irradiation. With 12 cytogenetic cases, analyzed in the laboratory, and the 25 cases of the literature, the radiation-induced tumors were characterized by genetic material losses. A anti-oncogenic evolution is probable. Only thyroid tumors did not have this evolution. The mechanism of the chromosomic material losses could be the chromosomic instability. The telomere length decreasing is a possible explanation of these phenomena. In our preliminary results, the telomere length of radiation-induced tumor did not decrease comparing to normal human cells, suggesting that telomerase activity stabilized this length
Benhassine, Manel. "Caractérisation du mode de régulation du récepteur 2B de la sérotonine (HTR2B) dans le mélanome uvéal." Master's thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/30257.
Le mélanome uvéal (MU) est la principale forme de cancer intraoculaire possédant la capacité d’engendrer des métastases au foie et aux poumons des patients atteints, cette maladie est incurable et fatale dans les 8 mois suivant le dépistage des métastases. Grâce à des analyses en profilage génique sur biopuces à ADN, une signature moléculaire de 12 gènes dérégulés permettant de subdiviser les MU en deux classes: à faible (classe 1) ou haut (classe 2) risque d’évoluer vers le stade métastatique a pu être identifiée. Parmi les 4 gènes de la classe 2, la surexpression du gène codant le récepteur 2B de la sérotonine (HTR2B) est l’indice le plus fiable menant à l’identification des patients à risque d’évoluer vers la maladie métastatique. Cette étude a pour but de caractériser le promoteur de ce gène et les mécanismes moléculaires menant à sa surexpression aberrabte dans les lignées métastatiques de MU. Différents segments du promoteur du gène HTR2B ont été clonés dans le plasmide pCATbasic, puis introduits par transfection dans les lignées cellulaires MU. Des analyses d’interférence de méthylation au diméthylsulfate (DMS) et de retard sur gel de polyacrylamide (EMSA) ont été réalisées afin de démontrer la liaison de facteurs de transcription (FTs) au promoteur HTR2B. La transfection des délétants HTR2B/CAT a permis d’identifier des régions régulatrices positives et négatives en amont du promoteur HTR2B. Les analyses EMSA et d’interférence de méthylation au DMS nous ont permis de démontrer la liaison des FTs NFI et RUNX1 au promoteur du gène HTR2B. Ce projet permettra de mieux comprendre les mécanismes moléculaires responsables de la surexpression du gène HTR2B et de définir de nouvelles cibles thérapeutiques qui pourraient permettre le dépistage des patients à risque d’évoluer vers la maladie métastatique.
Uveal melanoma (UM) is the most common type of primary intraocular tumor in the adult population. UM will propagate to the liver as the first metastatic site. Once this organ is invaded, survival becomes a matter of months for the patient as no treatment has proven to be effective. Among the candidates from the class II gene signature, the serotonin receptor-encoding gene (HTR2B) appears to be the most discriminating as its expression strongly increases in the tumors that will progress toward liver metastases. Our study aims at characterizing the molecular mechanisms that lead to this aberrant expression of HTR2B in metastatic UM cell lines. Expression of HTR2B was monitered by microarrays in a variety of UM cell lines. Various segments from the promoter and 5’-flanking sequence of the HTR2B gene were cloned upstream the CAT gene in the plasmid pCATbasic. The genomic areas of interest were 5’end-labeled and used as probes in electrophoretic mobility shift assays (EMSAs). DMS methylation interference footprinting was also used to precisely position the DNA target sites for transcription factors (TFs) that bind the HTR2B regulatory regions. Transfection analyses revealed that the upstream regulatory regions of HTR2B promoter is made up of a combination of alternative positive and negative regulatory elements. Repressive regions also bear a high number of target sites for the TF NFI. EMSA analyses provided evidence that multiple NFI isoforms can interact with the promoter of the HTR2B gene. In addition, the TF RUNX1 was shown by DMS methylation interference footprinting to bind a target site from the HTR2B distal silencer element. This project will help understand better the molecular mechanisms accounting for the abnormal expression of HTR2B in uveal melanoma. In the long term, this study will allow us to identify new potential targets that could help screening patients at high risk of evolving toward the liver metastatic disease.
FERRERO, VACHER CORINNE. "La sp 220k nouvelle protease matricielle : etude de son expression dans l'adenocarcinome renal et dans certaines tumeurs benignes renales." Nice, 1994. http://www.theses.fr/1994NICE6569.
Coste-Invernizzi, Isabelle. "La β-caténine dans les tumeurs sporadiques chez la souris." Lyon 1, 2005. http://www.theses.fr/2005LYO10043.
Morcrette, Guillaume. "GEPELIN : genomics of pediatric liver neoplasms APC germline hepatoblastomas demonstrate cisplatin induced intratumor tertiary lymphoid structures and good prognosis Molecular classification of hepatocellular adenoma associates with risk factors, bleeding, and malignant transformation." Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCB225.
El, Azzi Sandy. "Interleukine-15 et tumeurs du rein : implication de la cytokine dans la différenciation des cellules souches du cancer." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA11T094.
The ability of Interleukin-15 (IL-15) to activate many immune antitumor mechanisms makes it a good candidate for application in solid tumors therapy, particularly renal cell carcinoma which is a highly aggressive and resistant cancer. Although IL-15 is being currently used in clinical trials, the function of the cytokine on the kidney’s components is poorly described. In this work, we evaluated the role of IL-15 on renal normal and tumor epithelial cells as well as a subpopulation of cancer stem cells (CSC) highly resistant to conventional therapies. Our results show that IL-15 induces the differentiation of renal CSC in non-tumorigenic epithelial cells more sensitive to cytotoxic agents, supporting the use of the cytokine in antitumor strategies. Our experiments show, however, that IL-15 promotes epithelial-mesenchymal transition of renal cell carcinoma cells, a pro-tumor action to be highly considered in the development of new therapeutic approaches
Hoffmann, Thomas. "Association entre polymorphisme de gènes de l'immunité et évènements cliniques post-transplantation rénale." Thesis, Tours, 2009. http://www.theses.fr/2009TOUR4011/document.
In spite of the continuous progress in immunosuppressive therapy, a number of factors still interfere with the complete success of renal transplantation. Revealing some factors with impact on graft outcome may therefore have important consequences in clinical practice. In the work presented here, we studied 6 polymorphisms into immunity genes coding IL-12p40, PD-1, AIF-1, Lyp, TIM-1 and -3, and we assessed their association with several clinical events occurring after transplantation. We showed that the polymorphisms into IL-12p40, PD-1 and TIM-3 genes were associated with CMV infection, that the PD-1 gene polymorphism was associated with graft survival, and that the polymorphisms into AIF-1 and Lyp genes were associated with skin cancer and delayed graft function, respectively. These results suggest that it would be interesting to genetically stratify patients in order to better adapt treatments and patient care
Velou, Sumitra. "Syndrome WAGR (tumeur de Wilms - Aniridie - Anomalies génito-urinaires - retard mental) : à propos d'un cas." Bordeaux 2, 1990. http://www.theses.fr/1990BOR25080.
Nakache, Nicole. "Le syndrome de Stauffer : à propos de trois observations." Montpellier 1, 1989. http://www.theses.fr/1989MON11127.
De, Vries-Brilland Manon. "Caractérisation du microenvironnement immunitaire des carcinomes papillaires du rein." Electronic Thesis or Diss., Angers, 2023. http://www.theses.fr/2023ANGE0017.
Article 1: Checkpoint inhibitors in metastatic papillary renal cell carcinoma : papillary Renal Cell Carcinoma (pRCC) is the most common non-clear cell RCC (nccRCC) and a distinct entity, although heterogenous, associated with poor outcomes. The treatment landscape of metastatic pRCC (mpRCC) relied so far on targeted therapies, mimicking previous developments in metastatic clear-cell renal cell carcinoma. However, antiangiogenics as well as mTOR inhibitors retain only limited activity in mpRCC. As development of immune checkpoint inhibitors (ICI) is now underway in patients with mpRCC, we aimed at discussing early activity data and potential for future therapeutic strategies in monotherapy or combination. Expression of immune checkpoints such as PD-L1 and infiltrative immune cells in pRCC could provide insights into their potential immunogenicity, although this is currently poorly described. Based on retrospective and prospective data, efficacy of ICI as single agent remains limited. Combinations with tyrosine-kinase inhibitors, notably with anti-MET inhibitors, harbor promising response rates and may enter the standard of care in untreated patients. Collaborative work is needed to refine the molecular and immune landscape of pRCC, and pursue efforts to set up predictive biomarker-driven clinical trials in these rare tumors. Article 2 : Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma. Background : papillary Renal CellCarcinoma (pRCC) is the most common non-clear cell RCC (nccRCC), and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME) ,largely unknown, of patients with metastatic pRCC and identify potential therapeutic targets. Methods : we performed quantitative gene expression analysis of TME using MCP-counter methodology, on 2 independent cohorts of localized pRCC (n=271 and n=98). We then characterized the TME, using immunohistochemistry (n=38) and RNA-sequencing (RNA-seq) (n=30) on metastatic pRCC from the prospective AXIPAP trial cohort. Results: unsupervised clustering identified 2 "TME subtypes", in each of the cohorts : the “immune-enriched” and the “immune-low”.Within AXIPAP trial cohort, the “immune-enriched” cluster was significantly associated with a worse prognosis according to the median overall survival to 8 months (95%CI, 6-29) versus 37 months (95%CI, 20-NA,p=0.001).The 2 immune signatures, Teff and JAVELIN Renal 101 Immuno signature, predictive of response to immune checkpoint inhibitors (CPI) in ccRCC, were significantly higher in the “immune-enriched” group (adjusted p<0.05). Finally, 5 differentially overexpressed genes were identified, corresponding mainly to B lymphocyte populations. Conclusion : for the first time, using RNA-seqand IHC, we have highlighted a specific immune TME subtype of metastatic pRCC, significantly more infiltrated with T and Bimmune population. This “immune-enriched” group appears to have a worse prognosis and could have a potential predictive value for response to immunotherapy, justifying the confirmation of these results in a cohort of metastatic pRCC treated with CPI and incombination with targeted therapies
Verine, Jérôme. "Expression de l’Angiopoïétine-like 4 dans les tumeurs bénignes et malignes du rein : définition d'un biomarqueur du cancer du rein à cellules claires et lien avec les altérations du gène VHL." Paris 7, 2009. http://www.theses.fr/2009PA077244.
The laboratory identified human angiopoietin-like 4 (angptl4) as a gene with hypoxia-induced expression in endothelial cells. It showed that the levels of both mRNA and protein for ANGPTL4 increased in response to hypoxia and ANGPTL4 induced a strong proangiogenic response, independently of vascular endothelial growth factor, in the chicken chorioallantoic membrane assay. In human pathology, angptl4 mRNA is produced in ischemic tissues, in conditions such as critical leg ischemia, and in the hypoxic areas surrounding necrotic regions of différent tumors. The results of my thesis show that angptl4 is a sensitive (100%) and specific (93. 8%) marker of clear cell renal cell carcinoma (ccRCC) in a large and retrospective series of benign and malignant renal tumors, including the uncommon forms. The other renal tumors which also express angptl4 are the multilocular cystic carcinoma and the clear cell papillary rénal cell carcinoma. Thus, angptl4 can be use as a diagnostic marker of ccRCC in differential diagnosis of renal tumors. On the other hand, the angptl4 mRNA level seems not to be a prognostic marker of ccRCC. We show also that the alterations of the VHL gene are neither necessary nor sufficient to angptl4 mRNA expression by tumour cells. Nevertheless pVHL activity level seems influence the expression level ofangptl4 mRNA in ccRCC
Bouancheau, Delphine. "PPARγ et tumeurs colorectales humaines : altérations, expression et recherche de gènes cibles." Nantes, 2005. http://archive.bu.univ-nantes.fr/pollux/show.action?id=ad25116c-3684-432a-aff4-0938cd68a67b.
PPARγ (Peroxisome Proliferator Activated Receptor γ) is a member of the nuclear receptor superfamily. PPARγ agonists have anti-proliferative effects and induce cell differentiation and apoptosis of colorectal cancer cells. PPARγ was therefore proposed as a therapeutic target for colon cancer. We first aimed to search for alterations and determine the expression level of PPARγ in human colorectal tumours. We have not found mutated PPARγ gene in the samples analyzed (codon 422 and exon 6). By contrast, we have shown that deregulation of PPARγ function involved aberrant expression of PPARγ, of its co-activators, and of a splicing variant that acts as a dominant negative. The other goal of our work was to identify PPARγ targets in human colorectal epithelial cells. Our results indicate that PPARγ ligands regulate MCT1 (Monocarboxylate Transporter 1) gene expression in HT29. Cl16E cells. This is probably an indirect effect, involving NF-KB inhibition