Dissertations / Theses on the topic 'Tumeurs du pancréas – étiologie'
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Maurin, Lucas. "A multi-omics approach to identify key genes in the endocrine and exocrine pancreas and their role in T2D." Electronic Thesis or Diss., Université de Lille (2022-....), 2024. http://www.theses.fr/2024ULILS068.
Full textType 2 diabetes (T2D) is a multifactorial, complex disease characterised by chronic elevated blood glucose, and caused by genetic and environmental factors, such as ageing. While genome-wide association studies (GWAS) have successfully identified the genetic causes of T2D, epigenome-wide association studies (EWAS) have had limited success in capturing the environmental impact due to the tissue-specificity of epigenetic changes, very small sample sizes, and the lack of functional studies. Furthermore, the extent of the interaction between genetic and epigenetic variation remains poorly understood. The objective of this thesis was to contribute to our understanding of how environmental factors contribute to T2D pathogenesis, and its progression towards related complications, notably pancreatic ductal adenocarcinoma (PDAC).In the first project, we investigated the interplay between age and T2D-associated epigenetic changes and genetic variation in pancreatic islets of 124 individuals, of which 16 had T2D. We developed a novel integrative approach combining DNA methylation, gene expression, and genotyping to identify triad associations, examining whether genetic and epigenetic influence each other. We identified 301 and 743 CpGs associated with age and T2D, respectively, which impacted nearby gene expression (within a 2 Mb window). Of these, less than 10 % were influenced by nearby genetic variants, suggesting that environmentally-driven epigenetic changes operate largely independently of genetic variation. Notably, only three genes, SIX3, ST6GAL1, and TIPIN, were found to co-localise with T2D GWAS risk variants, and were also under epigenetic regulation. Characterisation of the epigenetically-regulated genes highlighted key T2D candidates, including OPRD1 and MEG3. Importantly, adding methylation risk scores (MRS) to polygenic risk scores (PGS) improved T2D risk prediction, underscoring the additive value of epigenetic studies. Our findings suggest that most genes are regulated either by genetic or epigenetic factors, but rarely both.In the second project, we explored the epigenetic influence of T2D in the exocrine pancreas, to explore why T2D individuals are at a higher risk of developing pancreatic disease, notably PDAC, one of the deadliest cancers. We performed an EWAS for T2D (25 T2D individuals and 116 non-diabetic) and identified a single hypermethylation in cg15549216, located in the Pancreatic Lipase Related Protein 1 (PNLIPRP1) gene, which was corelated with a decreased expression of the gene. Knockdown of Pnliprp1 in the rat acinar cell line AR42J increased cholesterol levels, reduced proliferation, and induced acinar-to-ductal metaplasia (ADM), hallmarks of the early stages of PDAC. Notably, this effect was reversed by treatment of statin, highlighting the translational potential of these findings. Additionally, a rare variant analysis using the UKBiobank linked PNLIPRP1 to LDL-cholesterol, confirming the functional results. We propose a model where epigenetic and genetic mechanisms act independently but synergise to promote pancreas injury and disease progression.This thesis underscores the importance of studying DNA methylation as an unbiased approach for identifying environmental factors that contribute to disease. Our findings reveal that these epigenetic alterations are largely independent of genetic factors, underscoring their complementary role T2D pathogenesis. Additionally, PNLIPRP1 serves as an example of how epigenomic studies can indeed identify novel biomarkers with a translational relevance, offering new insights into disease mechanisms and progression
Neuzillet, Cindy. "Inter- and intra-tumoral heterogeneity and dynamics of cancer-associated fibroblasts in pancreatic ductal adenocarcinoma." Thesis, Sorbonne Paris Cité, 2018. https://theses.md.univ-paris-diderot.fr/NEUZILLET_Cindy_2_va_20181015.zip.
Full textCancer-associated fibroblasts (CAF) are orchestrators of the pancreatic ductal adenocarcinoma (PDAC) microenvironment. Stromal heterogeneity may explain differential pathophysiological roles of the stroma (pro- vs. anti-tumoral) in PDAC. We hypothesised that multiple CAF subtypes exist in PDAC that contribute to stromal heterogeneity through interactions with cancer and immune cells. This project comprised three parts:- In Part 1, by applying extended bioinformatics analysis and a wide range of in vitro assays to human PDAC-derived primary CAF cultures, we demonstrated the biological diversity of human pancreatic CAFs; we identified four CAF subtypes (A-D) with specific molecular and functional features (matrix- and immune-related signatures, vimentin and ?-smooth muscle actin expression, proliferation rate), and we showed that CAF heterogeneity had an impact on the interactions with cancer cells in mini-organotypic models.- In Part 2, we showed that the combination of CAF sub-populations was associated with distinct phenotypic characteristics of the tumours (tumour molecular subtype and grade, stromal abundance and activity, immune infiltrates, angiogenesis) and patient survival, in silico in the ICGC dataset and by immunohistochemistry in an extensively characterised patient cohort.- In Part 3, we showed that several CAF subtypes may emerge in vitro (conditioned media experiments) and in vivo (orthotopic xenografts) from the dynamic interactions of pancreatic stellate cells with cancer cells, through an “imprinting” process, and may be further modulated by other factors and/or cellular partners in the tumour microenvironment; in addition, we confirmed in a murine setting our findings about the association between CAF subtype marker expression and immune phenotype observed in human tumours.This unique classification for pancreatic CAFs (pCAFassigner) demonstrates the inter- and intra-tumoral phenotypic heterogeneity of CAFs in human PDAC. Our results provide a framework for future functional studies and pave the way for the development of therapies targeting specific CAF sub-populations in PDAC
Mège, Diane. "Microparticles in colorectal and pancreatic cancers." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM5038.
Full textColorectal cancer (CRC) is the most common gastrointestinal cancer. It is less serious and less frequently associated with thrombo-embolic event than pancreatic cancer (PC). Microparticles (MPs) are small vesicles produced and released by exocytic blebbing of the activated and apoptotic cell membrane from most, if not all, types of cells. They are known to be implicated in the tumor growth, the development of metastases and the cancer-associated procoagulant activity. Our objectives were to identify and to characterize the different concentrations of circulating MPs in CRC and PC, in order to describe a MPs hallmark, and to evaluate their implication in the occurrence of a venous thromboembolism. We have thus reported a specific hallmark of MPs in CRC and PC, comparing to benign colorectal and pancreatic diseases and healthy subjects, so-called the “microparticulosome”. We have observed that microparticulosome changed with the evolution of the disease, and tended to the signature observed for benign diseases or healthy subject in case of CRC remission. We also reported variations in the microparticulosome in case of an occurrence of a thrombo-embolic event.In conclusion, MPs may constitute new pertinent biomarkers in cancers, in the diagnosis, the survival prognostic and the prognostic of the occurrence of thrombo-embolic events. Understanding the interactions of MPs with tumor environment will allow to find efficient treatments against tumor growth and metastases development
Durand, Luc. "Les tumeurs kystiques du pancréas." Montpellier 1, 1993. http://www.theses.fr/1993MON11052.
Full textDURIEUX, OLIVIER. "Imagerie des tumeurs du pancréas : logiciel d'autoapprentissage." Aix-Marseille 2, 1994. http://www.theses.fr/1994AIX20845.
Full textBEAURAIN, PATRICK. "Tumeurs à sécrétion mucineuse du pancréas : à propos de 9 cas." Aix-Marseille 2, 1989. http://www.theses.fr/1989AIX20027.
Full textRaynaud, Jean. "Les lésions tumorales du pancréas endocrine avec syndrome d'insulinome : étude de 10 cas par les techniques immunocytochimiques." Bordeaux 2, 1989. http://www.theses.fr/1989BOR25185.
Full textOuaïssi, Mehdi. "Histones désacétylases et cancer du pancréas." Aix-Marseille 2, 2008. http://www.theses.fr/2008AIX20708.
Full textIn the first part of the work we analyze some of the current data related to the deacetylase enzymes as a possible target for drug development in cancer. Given the structural differences among members of this family of enzymes, development of specific inhibitors will not only allow selective therapeutic intervention, but may also provide a powerful tool for functional study of these enzymes. In the second step, attempts were made for the first time to explore the level of expression of members of histone deacetylase encoding genes (HDACs) in four pancreatic tumor cell lines: Panc-1, BxPC-3, SOJ-6 and MiaPaCa-2; and two non-related tumor cells: Jurkat and HeLa. The possible relationship between the levels of HDACs expression and the sensitivity/resistance to HDAC inhibitors (TSA, Nicotinamide and Sirtinol) was further analyzed. Although a slight variation in the profiles of gene expression among cell lines could be evidenced, HDACs protein synthesis seem to be similar. Furthermore, the cells were equally sensitive to inhibition by Sirtinol whereas some variation in the IC50 could be seen in the case of TSA. We also demonstrate that the drugs had the capacity to induce the death of cells by apoptosis. Taken together, our data support the notion that the level of cell sensitivity to the HDIs might be related to the level of expression of genes such as those encoding proteins playing a role in cell cycle checkpoints control but not HDAC per se. In a third part of work, we have evaluated the expression levels of members of class I, II and III in a set of surgically resected pancreatic tissues. Total RNA was isolated from 11 pancreatic adenocarcinomas (PA): Stage 0 (n=1), IB (n=1), IIB (n=6), III (n=1), IV (n=2), one serous cystadenoma (SC), one intraductal papillary mucinous tumor of the pancreas (IMPN), one complicating chronic pancreatitis (CP) and normal pancreatic biopsy (NP) obtained during donor liver transplantation. In addition, four samples of control tissues taken from the surgical specimens from different patients with PA, and two samples from patients with adenocarcinomas of biliary duct (BD) were also included in this study. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was conducted and gene expression was quantified by qPCR. Protein expression levels were analyzed by Western blot and their localization by immunohistochemistry analyses of cancer tissues sections. The expression of class I and II members of HDACs showed that all the samples from PA, CP, SC and IMPN had decreased levels of HDAC 1, -2, -3 and -4 transcripts. Remarkably, 9 of the 11 PA (≅ 81%) showed significant increase of HDAC7 mRNA levels. The Western blot analysis showed increased expression of HDAC7 protein in 9 out of 11 PA samples in agreement with the qPCR data. Most of the PA tissue sections examined showed intense labeling in the cytoplasm when reacted against antibodies to HDAC7. The data showed alteration of HDACs gene expression in pancreatic cancer. Therefore, increased expression of HDAC7 discriminates PA from other pancreatic tumors
Rosty, Christophe. "Recherche de marqueurs diagnostiques précoces de l'adénocarcinome du pancréas par l'étude du transcriptome et du protéome." Paris 5, 2002. http://www.theses.fr/2002PA05N129.
Full textPancreatic cancer is the 4th leadind cause of cancer death in human. To improve the poor prognosis of pancreatic cancer, new diagnosic markers need to be discovered in order to detect small pancreatic lesions. We used serial analysis of gene expression (SAGE) to identify 3 overexpressed genes that could potentially be used as cancer markers : PSCA (Prostate Stem Cell Antigen), S100A4 protein and mesothelin. Using a proteomic SELDI (Surface Enhanced Laser Desorption Ionization) - based technology on pancreatic juice samples, we identified HIP/PAP-I (Hepatocarcinoma Intestine Pancréas/Pancreatitis-Associated-Protein I) as an overexpressed protein in cancer samples
Heymann, Marie-Françoise. "Etude anatomopathologique avec immunohistochimie de 61 tumeurs pancréatiques chez 16 patients atteints de néoplasies endocriennes multiples de type 1." Nantes, 1995. http://www.theses.fr/1995NANT209M.
Full textMoutardier, Vincent. "Adénocarcinomes de la tête pancréatique résécables : que peut-on attendre de l'association radiochimiothérapie néoadjuvante et chirurgie ?" Aix-Marseille 2, 2003. http://www.theses.fr/2003AIX20693.
Full textRestany, Alain. "Les tumeurs endocrines du pancréas à sécrétions multiples : considérations pathogéniques et thérapeutiques." Montpellier 1, 1988. http://www.theses.fr/1988MON11263.
Full textCilleros, Celia. "Développement d’un traitement par ultrasons focalisés de haute intensité par voie peropératoire pour les tumeurs pancréatiques." Electronic Thesis or Diss., Lyon, 2021. http://www.theses.fr/2021LYSE1089.
Full textCurrently, management options for locally advanced pancreatic tumors are extremely limited. Surgical resection cannot be considered due to the non-reconstructible vascular involvement of the tumor. High intensity focused ultrasound (HIFU) treatments have demonstrated their potential in the palliative treatment of pancreatic cancers. The thesis project focuses on the definition of HIFU treatment parameters that induce necrosis of the targeted pancreatic parenchyma while preserving the vascular permeability of an artery included in the destroyed area, using an intraoperative therapy probe with a toroidal transducer and an integrated ultrasound imaging probe. For the assessment of arterial flow, real-time Doppler imaging monitoring was developed during the HIFU procedure. Treatment parameters were chosen to allow acquisition of the Doppler signal between HIFU emission phases with a duty cycle of 40% therapy time and 60% imaging time, for a total duration of 900 seconds. A perfused model was used to evaluate the impact of in vitro treatment parameters on the lesion induced. The lesions obtained with the application of the duty cycle were on average 20% smaller than the lesions without duty cycle, but this reduction was considered acceptable regarding to the safety benefit of treatment with Doppler imaging. A first preclinical study demonstrated the occurrence of reversible arterial spasm following repeated HIFU treatments on the targeted artery. Thermal ablations of approximately 20 mm in diameter were generated around the targeted artery without causing definitive vascular occlusion or thrombosis in the short and medium term. Nevertheless, with a perspective of using this HIFU treatment in humans and thus with the objective of ensuring the safety of the treatment, a predictive tool for arterial spasm has been developed. New studies have identified alterations in the arterial signal during HIFU treatment, reflected by the appearance of a turbulent component upstream of the treated area before the arterial spasm occurs. A tool based on signal dissimilarity was developed and patented based on these signal changes. The acceleration of these modifications allowed to anticipate the arterial spasm in real time and thus a feedback on the HIFU treatment. Preclinical studies allowed to define a threshold on this acceleration beyond which the appearance of stenosis seemed systematic if the treatment was carried out. Depending on the parameters applied, tissue necrosis up to 17 mm in diameter was induced in the pancreatic tissue and around the target vessel without induction of arterial spasm and while maintaining vascular patency. Doppler imaging associated with the real-time tool confirmed the persistence of arterial flow during HIFU treatments. These safe and effective preclinical treatments allow us to consider a Phase I-II clinical trial evaluating HIFU destruction of locally advanced tumors of 10 to 15 mm in diameter in humans
Martin, Denis. "Le vipome pancréatique : à propos d'un cas." Montpellier 1, 1988. http://www.theses.fr/1988MON11373.
Full textAl, Shoukr Faisal. "Ciblage radioisotopique de tumeurs exprimant le récepteur de la neurotensine NTSR1." Paris 5, 2010. http://www.theses.fr/2010PA05P629.
Full textIndisputable successes of scintigraphy and targeted radiotherapy of gastro-entero-pancreatic neuroendocrine tumors (GEP) have been obtained with somatostatin analogues labeled with radiometals. Positron emission tomography (PET) with 68Ga potentially provides higher diagnostic efficacy than single photon emission computed tomography (SPECT) with 111In. Therapy with these analogues labeled with 90Y or 177Lu affords symptomatic improvement, prolonged survival and better quality of life in some instances. However, some tumors such as pancreatic adenocarcinoma have little or no somatostatin receptors, but over-express the high affinity neurotensin receptor (NTSR1). We developed in this study new neurotensin analogues for radioisotope targeting to NTSR1 positive tumors. These ligands bear a poly(aminocarboxylate) chelating agent (DTPA or DOTA) which allows labeling with radiometals such as 111In, 68Ga, 90Y or 177Lu. DTPA(111In)- and DOTA(111In)-analogues of neurotensin 6-13 displayed a high stability in vivo and a strong affinity for NTSR1. They provide a higher tumor uptake and/or higher tumor to kidney uptake ratio, than DTPA- or DOTA-neurotensin analogues previously described in the literature. Labeled with 111In they provide high contrast planar and SPECT images. PET imaging with DOTA analogues labeled with 68Ga visualized tumors of 20-40 mm3 in animals. The affinity of DOTA(Y) analogues are higher than those of their DOTA (In) counterpart. These neurotensin analogs are potential tools for SPECT or PET imaging and for targeted radiotherapy of tumors expressing NTSR1
Delpu, Yannick. "Méthylation de l'ADN et expression des microARNs dans la carcinogénèse pancréatique." Toulouse 3, 2013. http://thesesups.ups-tlse.fr/2128/.
Full textPancreatic cancer is the fourth leading cause of cancer death in Western countries. This cancer involves changes in DNA methylation patterns and overexpression of enzymes responsible for its implementation : the DNA methyltransferases. However, the exact role of these proteins in carcinogenesis remains to be proven. We first aimed to determine the changing in the DNA methylation pattern through the study of the expression of a specific microRNA : miR- 148a. We confirmed the repression of miR- 148a by DNA hypermethylation in several cell lines derived from pancreatic cancer as well as in human tumor samples, and we shown the usefulness of this mark in the differential diagnosis between pancreatic cancer and chronic pancreatitis. We also evaluated the therapeutic potential of miR- 148a gene transfer in vitro and in vivo. We observed no significant changes in the behavior of cells / tumors overexpressing miR- 148a. This indicates that its repression is a minor alteration accompanying carcinogenesis rather than a crucial phenomenon of tumor development. Finally, we extended our study to determine whether the single overexpression of DNA methyltransferases can transform normal pancreatic cells. We observed that the stable overexpression of these proteins significantly affects the behavior of cells in vitro, their methylation patterns and gene expression. These results strongly suggest that DNA methylation facilitates carcinogenesis, but is not sufficient to trigger the formation of tumors. This work contributes to a better understanding of pancreatic carcinogenesis, the role of DNA methylation and open new horizons for the potential oncogenic role of DNA methylation
Nicolescu-Catargi, Bogdan. "Apport du pancréas artificiel au diagnostic et au traitement des insulinomes : 24 cas." Bordeaux 2, 1993. http://www.theses.fr/1993BOR23076.
Full textVillard, Pierre-Henri. "Effet de la fumée de tabac sur l'expression hépatique pulmonaire et rénale des cytochromes P450 impliqués dans la cancérogenèse." Aix-Marseille 2, 1998. http://theses.univ-amu.fr.lama.univ-amu.fr/PHA_1998_1506.pdf.
Full textBarone, Jean-Luc. "Douleur thoracique en urgence : problèmes diagnostiques à propos d'un cas de tumeur neuroendocrine du pancréas." Montpellier 1, 1998. http://www.theses.fr/1998MON11003.
Full textMaltese, Jean-Yves. "Etude de l'expression d'un enzyme d'amidation dans le pancréas normal et tumoral." Aix-Marseille 3, 1990. http://www.theses.fr/1990AIX30059.
Full textLherisson, Christine. "Analyse des formes moléculaires de somatostatine sécrétées par une lignée de cellules tumorales endocrines de pancréas de rat (RIN T3) : immunodétection et purification d'un précurseur." Toulouse 3, 1990. http://www.theses.fr/1990TOU30036.
Full textGmyr, Valéry. "Reproduction in vitro chez l'homme de la néogenèse des cellules insulino-sécrétantes : recherche d'une source abondante de cellules précurseurs par transdifférenciation acinocanalaire." Lille 1, 2000. https://pepite-depot.univ-lille.fr/RESTREINT/Th_Num/2000/50376-2000-392.pdf.
Full textClément, Nathalie. "Les tumeurs papillaires du pancréas : étude histologique, immunohistochimique et ultrastructurale : à propos de trois observations." Aix-Marseille 2, 1988. http://www.theses.fr/1988AIX20296.
Full textDe, Vries Luc. "Etude de la régulation de l'ornithine décarboxylase par des peptides gastro-intestinaux et des facteurs de croissance dans les cellules pancréatiques AR4-2J." Toulouse 3, 1990. http://www.theses.fr/1990TOU30020.
Full textDelvaulx, Michel. "Antiport Na+/H+ des cellules acineuses pancréatiques : régulation par les peptides neuro-digestifs et rôle dans la prolifération cellulaire." Toulouse 3, 1990. http://www.theses.fr/1990TOU30009.
Full textPalis, Elisabeth. "Localisation des insulinomes." Caen, 1990. http://www.theses.fr/1990CAEN3032.
Full textSaupe, Falk. "Impact of the extracellular matrix molecule tenascine-C in the microenvironment on tumor progression and angiogenesis." Strasbourg, 2011. https://publication-theses.unistra.fr/public/theses_doctorat/2011/SAUPE_Falk_2011_ED414.pdf.
Full textThe tumor microenvironment plays an instrumental role in cancer progression. The extracellular matrix molecule tenascin-C (TNC) is a major component of the cancer specific matrix. It is prominently expressed in the tumor microenvironment of several human cancer types and plays a promoting role in malignant tumor progression towards metastasis. The objective of this thesis was to investigate the role of TNC during tumor progression in the immune-competent Rip1-Tag2 mouse model of pancreatic neuroendocrine tumorigenesis. Gain- and loss-of-function strategies were used to analyze the impact of TNC on tumor progression, angiogenesis and formation of metastasis. For the first time we demonstrate in an immune-competent model of spontaneous tumor formation that TNC expression levels determine the extent of cell proliferation, tumor invasion, tumor angiogenesis and metastasis. The data obtained in these models showed that TNC plays an important role in tumor onset and during the angiogenic switch. The implication of the Wnt inhibitor DKK1 provides a mechanistic basis for the described TNC actions. TNC also had a structural function determining tumor vessel architecture and formation of matrix conduits as an additional program to drive tumor malignancy. Based on these observations TNC presents an attractive target for blocking tumor angiogenesis. Therefore, the presented well characterized stochastic tumorigenesis models with different TNC expression could serve as an excellent preclinical model for evaluating the efficacy of drugs targeting human TNC and downstream signaling pathways for repressing tumor angiogenesis and metastasis
Segretin, Catherine. "Les lymphomes testiculaires : à propos de 14 observations." Bordeaux 2, 1990. http://www.theses.fr/1990BOR23007.
Full textTaieb, David. "Fonction antitumorale d'ARGBP2 dans le cancer du pancreas par inhibition de l'adhésion et de la migration cellulaire." Aix-Marseille 2, 2009. http://theses.univ-amu.fr.lama.univ-amu.fr/2009AIX22027.pdf.
Full textGiannone, Codiglione Fabio. "Multidisciplinary perioperative strategies for improving short and long-term outcomes in hepato-biliary and pancreatic cancers." Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ004.
Full textThis thesis is a comprehensive exploration of the multidisciplinary management of hepatobiliarypancreatic tumors (HBP), and how this approach can improve oncological outcomes for the patient.This work is developed in three chapters, each covering a specific domain of this discipline. Each chapter also reveals significant collaboration between surgeons, oncologists, researchers, and various medical personalities, paving the way for the advancement of HBP tumor management. The refined treatment strategies and personalized medicine approaches described in this thesis are not theoretical constructs but tools ready to be integrated into patient care. The spirit of collaboration sustained throughout this work resonates in the improvement of care for patients with HBP tumors, ensuring that research advancements translate into tangible clinical improvements
Birnbaum, David. "Altérations moléculaires dans l'adénocarcinome du pancréas." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM5088.
Full textPancreatic adenocarcinoma (PDCA) is a major public health problem in France and worldwide. The inoperability and the poor prognosis of the PDCA are due to late diagnosis, rapid tumor progression (>80% of patients displayed metastases at diagnosis), early recurrences after resection, and poor response to available therapies. Innovative approaches and a comprehensive characterization of molecular genetic alterations are dearly needed to help develop techniques of early detection, identify new molecular targets and devise novel targeted-therapies (Hidalgo, 2010). Using high-resolution array-comparative genomic hybridization (aCGH), we studied the genome alterations of 39 fine-needle aspirations from PDCA. Recurrent losses were observed and comprised several known tumor suppressor genes. We identified frequent genetic gains. With this study, we decided to go one step further by identifying genes that might also be deregulated at the transcriptomic level. We started our analysis with a population of PDCA (n=419) versus normal pancreas (n = 105). Among the 352 genes found amplified and/or gained by aCGH, 170 (48%) were up regulated at the transcriptional level in PDCA compared to normal pancreatic tissues. Major pathways involved were cell cycle, TP53 and TGFß. Among the genes located in regions of losses, 141 (41%) were down regulated in PDCA compared to normal tissues. Furthermore, some genes were found related to a patients' survival With this study, we highlighted novels genes associated to PDCA oncogenesis. Some of those candidates should be further investigated as prognosis markers or as potential targets for new therapeutic approaches
Ristorcelli, Elodie. "Nanoparticules et apoptose : cas des cellules tumorales pancréatiques." Aix-Marseille 2, 2008. http://www.theses.fr/2008AIX20681.
Full textWe showed that pancreatic tumoral cells expressed nanoparticles. Proteins and lipids presents in these particles were charaterized. They were enriched in sphingomyelin and cholesterol. Nanoparticles interact with membrane of target cells to disorganize the Notch-1 receptor complex. Challenging tumoral cells with nanoparticles triggers PTEN activation which form complexes with inactive GSK-3b and actin. This complex sequesters active b-catenin, which may no longer be able to translocate to the nucleus to activate target genes to promote survival. Within the complex PTEN plays a pivotal role activating GSK-3b and inhibiting the PDH activity. This process increases the expression of pro-apoptotic Bax and decreases anti-apoptotic Bcl-2 proteins. In turn this activates caspase-9 and -3, leading to PARP cleavage. Activation of the GSK-3b inhibition of the g-secretase complex leads to a decrease in Hes-1 and cyclin D1 expression. All these events drive tumoral cells towards apoptosis
Crescence, Lydie. "Propriétés thérapeutiques de l'anticorps monoclonal 16D10 sur les cellules tumorales pancréatiques humaines." Aix-Marseille 2, 2009. http://www.theses.fr/2009AIX20695.
Full textPerrin-Vidoz, Laure. "Étude de la dégradation des ARN messagers porteurs d'un codon de terminaison prématuré : implication dans la prédisposition génétique au cancer du sein et de l'ovaire chez les patients porteurs de mutations germinales du gène BRCA1." Lyon 1, 2003. http://www.theses.fr/2003LYO10038.
Full textBoilève, Alice. "La médecine de précision dans le cancer du pancréas." Electronic Thesis or Diss., université Paris-Saclay, 2024. http://www.theses.fr/2024UPASL013.
Full textPancreatic ductal adenocarcinoma (PDAC) is an increasingly common cancer with limited therapeutic options and a poor prognosis. Conventional chemotherapies have limited efficacy, emphasizing the need for new therapeutic approaches. Genomic precision medicine, made possible by advances in high-throughput sequencing technologies, has seen significant development in oncology over the past decade. However, the utility of molecular profiling in PDAC has not yet been established, despite improved overall survival when patients receive molecularly matched treatment. Functional precision medicine (FPM) is another promising strategy that relies on testing a panel of drugs on live tumor cells to identify the sensitivity and resistance profile of each tumor. Organoids are robust and promising tools for assessing a specific tumor's sensitivity to various drugs and identifying the best therapeutic option for each patient.Three axes were developed in this thesis. First, a translational axis evaluated the impact of organoids as tools for functional precision medicine in pancreatic cancer. The primary objective of this project was to establish a framework for integrating organoid-based drug sensitivity testing into the clinical management of PDAC patients. Organoid responses to a panel of anticancer drugs were correlated with clinical responses in patients, suggesting potential clinical benefits. Additionally, the contribution of organoids to preclinical studies was tested by assessing the efficacy of a KRASG12D inhibitor, MRTX1133, in monotherapy and in combination with other inhibitors. The combination of MRTX1133 and anti-EGFR proved to be the most promising.Secondly, a clinical axis assessed the impact of KRAS mutation in PDAC in terms of clinical and molecular characteristics, treatment response, and prognosis, particularly in cases where targeted treatment was received. Comparing non-mutated KRAS tumors to mutated KRAS tumors revealed clinical differences and better prognosis for non-mutated tumors. Furthermore, the impact of different KRAS mutated codons was studied by comparing KRASG12 mutated tumors versus other KRAS mutations. KRASG12 mutations were associated with a worse prognosis, although there was no difference in treatment sensitivity.Finally, a fundamental axis investigated the invasive phenotype of PDAC. A new "onco-morphogenetic" program was identified as a mediator of metastatic dissemination in colorectal cancers (CRC) through TSIPs (tumor spheres with reversed polarity, malignant tumor intermediates). The presence of TSIPs in pancreatic cancers was confirmed, and their transcriptional program and chemosensitivity were characterized using organoids. However, the clinical and prognostic impact of TSIP presence in pancreatic cancer appears to be minor.In conclusion, this doctoral project aimed to develop a comprehensive framework for the use of PDOs as a tool for modeling PDAC (fundamental axis), selecting personalized treatments, and conducting preclinical drug tests (translational and clinical axes). By bridging the gap between preclinical trials and clinical practice, this project aims to bring us closer to precision medicine in managing PDAC
El, Kadiri Mouna. "Cancers après transplantation rénale : à propos de 1242 greffés rénaux." Bordeaux 2, 2000. http://www.theses.fr/2000BOR23060.
Full textReviron, Sophie. "Le syndrome du glucagonome : à propos d'une observation." Bordeaux 2, 1993. http://www.theses.fr/1993BOR2M018.
Full textHajjar, Moufid. "Tumeurs malignes inhabituelles dans une cohorte hospitalière de patients infectés par le VIH. Bordeaux, France 1985-1991." Bordeaux 2, 1992. http://www.theses.fr/1992BOR23027.
Full textRybarczyk, Pierre. "Implication du canal TRPM7 dans le développement tumoral de l'adénocarcinome canalaire pancréatique." Amiens, 2013. http://www.theses.fr/2013AMIED006.
Full textPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers leading to metastasis and low survival rates. We showed that the Transient Receptor Potential Melastatin-related 7 (TRPM7) channel expression is higher in human PDAC tissues compared to exocrine pancreatic tissues form healthy donors. TRPM7 expression is upregulated in undifferentiated, tumours and the patient’s overall survival was inversely correlated to the TRPM7 expression. Role of TRPM7 was also assessed in the moderately differentiated BxPC-3 and in the more undifferentiated Panc-1 human PDAC cell lines. In both cell lines, a Magnesium-Inhibited Cation (MIC) current was recorded by patch-clamp. While TRPM7 silencing decreased BxPC-3 cell migration, which is restored by the Mg2+ supplementation, it reduced Panc-1 cell invasiveness in a Mg2+ independent manner. TRPM7 belongs to the chanzyme family of ion channels and is fused with a kinase domain. Although the role of ion homeostasis is now well known in cancer, the function of the kinase domain of TRPM7 is not well understood. Our preliminary data shows that overexpression of wt-TRPM7 or TRPM7 mutant lacking the kinase domain induces different roles regarding the cell line used. This data suggests that TRPM7 regulates pancreatic cancer cell migration and invasion by regulating magnesium homeostasis and/or kinase function. Thus, TRPM7 could represent a promising biomarker of PDAC but its role in pancreatic carcinogenesis needs further investigation
Battini, Stéphanie. "Métabolomique par spectroscopie RMN HRMAS appliquée à l’hyperparathyroïdie et aux tumeurs pancréatiques." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ005/document.
Full textHigh Resolution Magic Angle Spinning (HRMAS) NMR spectroscopy allows metabolomics of intact tissues. Metabolomics profiling of hyperfunctioning parathyroid glands were characterized were characterized by using HRMAS NMR spectroscopy. Primary hyperparathy- roidism (PHPT) was compared to renal HPT. Among PHPT, we distinguished single gland disease from multiple gland disease. Pancreatic parenchyma and adenocarcinoma were compared. Thus, long-term and short-term survival patients were distinguished. The relationship between the survival of patients and their metabolic phenotype was studied. Metabolomics profiling of IPMN was also examined. IPMN with no degeneration and de- generated IPMN were compared. Finally, the risk of degeneration was correlated with the metabolomics profile. Our results show that HRMAS NMR spectroscopy is a promising technique in view of studying metabolomic profiling of HPT and pancreatic diseases
Laklai, Hanane. "Mécanismes anti-angiogéniques du récepteur de la somatostatine SST2, dans le cancer du pancréas : implication de la thrombospondine-1 et du TGF-beta." Toulouse 3, 2009. http://www.theses.fr/2009TOU30093.
Full textSomatostatin receptor sst2 behaves as a tumor suppressor when expressed and stimulated by its ligand somatostatin in pancreatic cancer cells. Re-introducing sst2 into the human pancreatic cancer cells results in a decrease of tumor progression and angiogenesis. However, the intracellular mechanisms responsible for sst2-dependent inhibition of tumor angiogenesis are unknown. We first showed that sst2 up-regulates the expression of the secreted angio-inhibitory factor thrombospondin-1 (TSP-1) in pancreatic cancer cells. The chick chorioallantoic membrane was used as an experimental in vivo model to demonstrate that TSP-1 is a critical effector of sst2 inhibitory role on neoangiogenesis and oncogenesis induced by pancreatic cancer cells. TSP-1 inhibited tumor cell-induced neoangiogenesis by inducing endothelial cell apoptosis and by directly sequestering the proangiogenic factor VEGF, and subsequently inactivating its angiogenic action on endothelial cells. Using human pancreatic tissue-microarrays, we have shown An up-regulation of both sst2 and TSP-1 tumor suppressors in precancerous lesions which may function as an early negative feedback to restrain pancreatic carcinogenesis. As an alternative mechanism underlying sst2 angio-inhibitory activity, we also showed that this receptor decreases the activation of the pro-angiogenic factor TGF-beta1 secreted by BxPC-3 cells. Sst2 blocks TGF-ß1 activation by down-regulating the expression of the matrix metalloproteinase-9 (MMP-9), a protease which cleaves and activates the secreted latent form of TGF-beta1 in an active form
Tahiri-Jouti, Nadia. "Contribution à l'étude du mécanisme antiprolifératif de la somatostatine sur la lignée cellulaire pancréatique tumorale AR4-2J : mise en évidence d'une activite phosphotyrosine protéine phosphatase." Toulouse 3, 1990. http://www.theses.fr/1990TOU30045.
Full textMalicet, Cédric. "Contribution de p8 dans le cancer pancréatique." Aix-Marseille 2, 2005. http://theses.univ-amu.fr.lama.univ-amu.fr/2006AIX22026.pdf.
Full textThe main objective of our laboratory is to identify new molecules involved in the cellular stress response, especially during acute pancreatitis. We used DNA microarray analysis to identify the genes showing significant changes in their expression during acute pancreatitis. One of them was found of special interest because of its very early transcriptional induction in acinar cells during acute pancreatitis. We called it p8. In vivo several stress agents induce p8. Furthermore the fact that this gene could be also induced in vitro by several stress agents demonstrates its participation to a general stress response. For instance p8 is involved in cell-cycle regulation, by its ability to modulate some MAP kinase pathways (Article1) and by its role in p27Kip1 (Article2), and involved in apoptosis (Article3). P8 functions are modulated by its localization, nuclear or cytoplasmic, and by the different post-translational modifications which can modulate its half-life. In conclusion this work allowed characterisation of a gene involved in stress response, p8. This gene is overexpresed during a stress and controls several cellular mechanisms, which may explain its function in tumorigenesis
Senesse, Pierre. "Alimentation et cancérogénèse colorectale : de l'adénome au cancer." Montpellier 1, 2003. http://www.theses.fr/2003MON1T018.
Full textMagen-Kunzelmann, Valérie. "Expression de la chromogranine A et de ses sous-unités dans les tumeurs endocrines du pancréas : à propos de 21 cas." Montpellier 1, 1999. http://www.theses.fr/1999MON11030.
Full textArnaud, Camille. "Caractérisation biochimique et fonctionnelle du complexe protéique MCC1/Scrib dans les cellules épithéliales." Aix-Marseille 2, 2007. http://www.theses.fr/2007AIX20712.
Full textThis study focuses on the interaction that we have identified between the proteins Scrib and MCC1. Scrib belongs to the LAP family, implicated in epithelial cell polarity. MCC1 is mutated in some sporadic colorectal cancers. We show that PDZ 1 and 3 bind to the carboxy-sequence ETSL found in MCC1 and that Scrib targets MCC1 to the plasma membrane of T47D epithelial cells. Because of the role of Scrib in cell migration and the potential functions of MCC1 in the NF-kappaB pathway and cell cycle suggested by the literature, we analyzed the contribution of this complex in these processes. We find that the complex MCC1/Scrib could have an influence on the NF-kappaB pathway activity. Moreover we show that MCC1 plays a role in heregulin dependant migration of epithelial cells. Unfortunately, our results fail to identify a link between these two proteins in this cellular process
Rejiba, Soukaïna. "Thérapie génique et virothérapie pour le traitement de l'adénocarcinome du pancréas et la chimiosensibilitation à la gemcitabine." Université Louis Pasteur (Strasbourg) (1971-2008), 2007. http://www.theses.fr/2007STR13079.
Full textGemcitabine is the treatment of choice for pancreatic adenocarcinoma, but comes up against appearance of chemoresistance. The current work aimed to improve gemcitabine efficacy using gene therapy. We first demonstrated that inhibition of k-ras oncogene resulted in a sensitization of cells to gemcitabine treatment. We were also interested to genes involved in alteration of the gemcitabine prodrug metabolism. Our results demonstrated that overexpression of the dCK::UMK fusion protein and inhibition of TS and RR genes restored tumor cell sensitivity to gemcitabine. Finally, we exploited the oncolytic and oncotropic natural properties of H-1 parvovirus. A recombinant parvovirus expressing the yeast cytosine deaminase suicide gene under the control of the carcinoembryonic specific promoter showed increased cytotoxic effects restricted to pancreatic tumor cells
Nlend, Tjomb Albert. "Une thrombose veineuse profonde révélatrice d'un glucagonome pancréatique." Bordeaux 2, 1995. http://www.theses.fr/1995BOR2M188.
Full textLahdaoui, Fatima. "Régulation de l’expression de la mucine MUC4 par les miARN et identification de nouveaux miARN dans le cancer du pancréas." Thesis, Lille 2, 2014. http://www.theses.fr/2014LIL2S020/document.
Full textThe MUC4 mucin is an important actor of pancreatic tumorigenesis as it contributes to tumor progression and its expression correlates with a poor prognosis. It has also been shown that MUC4 is involved in resistance of cells to chemotherapies. In this context, MUC4 is a potential therapeutic target in pancreatic cancer. MUC4 neoexpression at early stages of carcinogenesis confers to this mucin a potential interest as an early marker. Molecular mechanisms responsible for MUC4 induction of expression are not well defined. Thus, studying MUC4 gene expression regulation would contribute to better understand its role in tumorigenesis. MUC4 gene is regulated at the transcriptional level and epigenetically by DNA methylation and histone modifications mechanisms. However, MUC4 post-transcriptional regulation notably by miRNA is largely unknown. Our work aimed at (i) identifying miRNA dysregulated in pancreatic cancer and/or potentially targeting MUC4, (ii) determining miRNA(s) inhibiting MUC4 expression and its (their) impact on pancreatic carcinogenesis and finally (iii) identifying miRNAs involved in chemoresistance mediated by MUC4 in pancreatic cancer.First, using miRNA microarrays we established the miRNA expression profile of normal and cancerous pancreatic cell lines. We showed a cancer-specific miRNA signature which allows us to validate our cellular models. Then, performing in silico studies with TargetScan, Microcosm and MiRanda databases led us to identify miRNA potentially targeting MUC4. Analysis by qRT-PCR showed that miR-145 and miR-219-1-3p were downregulated in human pancreatic cancer cell lines. Finally, only miR-219-1-3p inhibited MUC4 expression thus we focused on its role in pancreatic cancer.We observed a loss of miR-219-1-3p expression in pancreatic cancer tissues. Complementary approaches overexpressing (transiently or stably) and inhibiting miR-219-1-3p expression, led us to show that miR-219-1-3p represses MUC4 protein expression by interacting directly with its 3’-UTR. We observed a decrease of cell migration and cell proliferation which was associated with an inhibition of cyclin D1 expression and an inhibition of Akt and Erk activation. Tumor growth in scid mice was strongly slowed down following miR-219-1-3p intratumoral injection. In the Pdx1-Cre;LSL-KrasG12D mouse model of PanIN, loss of miR-219-1-3p expression was an early event as soon as PanIN1/2 and miR-219-1-3p expression was conversely correlated to Muc4 expression.While the strong induction of miR-219-1-3p following gemcitabine treatment of pancreatic cancer cells suggests a potential role of this miRNA in sensitivity of cells,miR-219-1-3p has no effect on survival rate of cells treated with gemcitabine. We then established the miRNA expression profile of MUC4 knocked-down (MUC4-KD) cells and control cells (Mock) and showed a dysregulation of miRNA expression in MUC4-KD compared to Mock cells.To conclude, our results indicate that miR-219-1-3p, downregulated in pancreatic cancer, negatively regulates MUC4 expression, alters cancer cell biological properties and has an antimoral effect in vivo. Altogether, these results propose miR-219-1-3p as tumor suppressor in pancreatic cancer. Loss of MUC4 leads to an aberrant miRNA expression profile suggesting a potential role of miRNA as markers of chemoresistance in pancreatic cancer
Seillan, Claire. "Synthèse et application de systèmes π conjugués comportant le motif benzoquinonediimine." Aix-Marseille 2, 2009. http://www.theses.fr/2009AIX22068.
Full textQuinoid compounds represent an important class of organic molecules, with a wide range of applications. These PhD works are based on the synthesis of compounds having a benzoquinonediimine moiety and study of their semiconductor and antitumor properties. Only few usymmetrical 2. 5-diamino-p-benzoquinonediimines are described in the litterature. The development of two strategies giving access to new unsymmetrical quinones, revealed an unstability od the reduced species and some difficulties to isolate them. Incorporation of the o-benzoquinonediimine moiety in extended conjugated π systems was successful. On the one hand, nine DHTAPs, with various symmetries, have been synthezised, for organic transistor application. Mobility and conductivity measurements on the unsubstituted DHTAP showed an insultating character, contrary to the protonated DHTAP upon doping. On the other hand, several phenazines, belonging to phenazine-2-ol, phenazine-2. 3-diol and 2. 3-dialkoxyphenazine families have been synthetized. Considering the phenazines'potentialin cancer and the limiting number of chematherapeutic agents for pancreas cancer treatment, these compounds have been tested in vivtro on tumor cells of pancreas. Some of them chowed a good in vitro activity