Global ETD Search

31	Nuclear NFATc1/Smad3 complexes in Smad4-deficient pancreatic cancer Hasselluhn, Marie Christin 21 May 2019 (has links) No description available. 610 pancreatic cancer PDAC TGFβ signaling NFATc1 signaling translational medicine GOK-MEDIZIN
32	Mutant KRAS promotes CIP2A-mediated suppression of PP2A-B56a to initiate development of pancreatic ductal adenocarcinoma Samantha Lauren Tinsley (15349120) 02 August 2023 (has links) <p>Oncogenic mutations in KRAS are present in approximately 95% of patients diagnosed with pancreatic ductal adenocarcinoma (<b>PDAC</b>) and are considered the initiating event during the development of pancreatic intraepithelial neoplasia (<b>PanIN</b>) precursor lesions. While it is well established that KRAS mutations can drive the initiation of pancreatic oncogenesis, the effects of oncogenic KRAS signaling on regulation of phosphatases during this process is not fully appreciated. Protein Phosphatase 2A (<b>PP2A</b>) has been implicated in suppressing KRAS-driven cellular transformation. However, low PP2A activity is observed in PDAC cells compared to non-transformed cells, suggesting that suppression of PP2A activity is an important step in the overall development of PDAC. In the current study, we demonstrate that KRASG12D induces the expression of both Cancerous Inhibitor of PP2A (<b>CIP2A</b>), an endogenous inhibitor of PP2A activity, and the PP2A target, c-MYC. Consistent with these findings, KRASG12D sequestered the specific PP2A subunit responsible for c-MYC degradation, B56a, away from the active PP2A holoenzyme in a CIP2A-dependent manner. During PDAC initiation <i>in vivo</i>, knockout of B56a promoted KRASG12D tumorigenesis by accelerating acinar-to-ductal metaplasia (<b>ADM</b>) and the formation of PanIN lesions. The process of ADM was attenuated <i>ex vivo</i> in response to pharmacological re-activation of PP2A utilizing direct small molecule activators of PP2A (<b>SMAP</b>s). Together, the results of this study suggest that suppression of PP2A-B56a through KRAS signaling can promote Myc-driven initiation of pancreatic tumorigenesis.</p> Signal transduction Cancer cell biology PP2A KRAS CIP2A MYC PDAC Pancreatic Cancer ADM Transdifferentiation Epigenetic Regulation Cancer Development
33	Ferroptosis as a Lytic Form of Cell Death in Pancreatic Ductal Adenocarcinoma Cell Lines Taylor, Natalie M. 26 May 2023 (has links) No description available. Physiology Cellular Biology ferroptosis pancreatic ductal adenocarcinoma PDAC pancreatic cancer Ninjurin-1 MIA PaCa-2 PANC-1
34	How are pancreatic tumors innervated? / Les tumeurs pancréatiques sont elles innervées? Nguyen, Thi Trang Huyen 21 December 2017 (has links) L’adénocarcinome canalaire du pancréas (PDAC) est un des cancers les plus agressifs avec un taux de survie à 5 ans de moins de 5 %. Une des raisons est l’absence de traitement thérapeutique efficace. Des efforts afin d’identifier de nouvelles cibles pour le traitement du PDAC sont donc nécessaires. Il a été démontré que la dénervation du pancréas régule la progression des PDAC dans des modèles murins. De plus, on a rapporté que les axones du système nerveux périphérique (SNP) innervent les tumeurs pancréatiques, mais l'identité précise des fibres infiltrant la tumeur est inconnue.Ici, nous avons caractérisé le remodelage des principales divisions du SNP, y compris les systèmes autonomes et sensoriels, dans des modèles murins qui récapitulent la maladie humaine. Nous avons aussi commencé à caractériser l'innervation des PDAC dans des échantillons humains. Nous avons observé une augmentation de la densité des fibres sympathiques positives pour la tyrosine hydroxylase (TH) dans les lésions pré-tumorales du pancréas, alors qu'une forte densité de fibres sensorielles positives pour le peptide lié au gène de la calcitonine (CGRP) a été observée dans les PDAC. Fait intéressant, alors que dans tissus normaux les axones sympathiques et sensoriels sont principalement associés aux vaisseaux sanguins, ils sont majoritairement isolés dans les lésions pré-tumorales et les PDAC. Ces données suggèrent que la plasticité axonale survient aux stades précoces du développement tumoral pour les fibres sympathiques et à un stade plus tardif pour les fibres sensorielles. Ce travail suggère de nouvelles cibles potentielles pour le traitement des PDAC. / Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with 5-year survival rate of less than 5%. One reason to explain this poor outcome is that there has been no effective therapeutic treatment for PDAC patients. Thus, efforts to identify novel targets for PDAC treatment are required. Denervation of the pancreas has been shown to regulate PDAC progression in murine models. In addition, axons of the peripheral nervous system (PNS) have been reported to innervate pancreatic tumors, but the precise identity of the tumor-infiltrating fibers is unknown. Here we characterized the remodeling of the main divisions of the PNS, including autonomic and sensory systems, in mouse models, which recapitulate the human disease. We also started to characterize the innervation of human PDAC samples. We observed an increased density of tyrosine hydroxylase (TH)-positive sympathetic fibers in pre-tumoral lesions of the pancreas, while a high density of calcitonin gene-related peptide (CGRP)-positive sensory fibers was seen within PDAC. Interestingly, whereas in the normal tissues TH+ and CGRP+ axons were mostly associated to blood vessels, they were mainly isolated in lesions and PDAC. These data suggest that axonal plasticity occurs at the early stage of tumor development for sympathetic fibers and at the late stage for sensory fibers. This work suggests potential novel targets for the treatment of PDAC. Système nerveux périphérique Des modèles murins La plasticité axonale Pancreatic ductal adenocarcinoma Peripheral nervous system Mouse models Axonal plasticity 570
35	Cellular immunotherapy of pancreatic ductal adenocarcinoma: Discovery and evaluation of novel target candidates Schäfer, Daniel 26 March 2021 (has links) No description available. 610
36	Combined Systemic Drug Treatment with Proton Therapy: Investigations on Patient-Derived Organoids Naumann, Max, Czempiel, Tabea, Lößner, Anna Jana, Pape, Kristin, Beyreuther, Elke, Löck, Steffen, Drukewitz, Stephan, Hennig, Alexander, von Neubeck, Cläre, Klink, Barbara, Krause, Mechthild, William, Doreen, E. Stange, Daniel, Bütof, Rebecca, Dietrich, Antje 06 December 2023 (has links) To optimize neoadjuvant radiochemotherapy of pancreatic ductal adenocarcinoma (PDAC), the value of new irradiation modalities such as proton therapy needs to be investigated in relevant preclinical models. We studied individual treatment responses to RCT using patient-derived PDAC organoids (PDO). Four PDO lines were treated with gemcitabine, 5-fluorouracile (5FU), photon and proton irradiation and combined RCT. Therapy response was subsequently measured via viability assays. In addition, treatment-naive PDOs were characterized via whole exome sequencing and tumorigenicity was investigated in NMRI Foxn1nu/nu mice. We found a mutational pattern containing common mutations associated with PDAC within the PDOs. Although we could unravel potential complications of the viability assay for PDOs in radiobiology, distinct synergistic effects of gemcitabine and 5FU with proton irradiation were observed in two PDO lines that may lead to further mechanistical studies. We could demonstrate that PDOs are a powerful tool for translational proton radiation research. info:eu-repo/classification/ddc/571.978 ddc:571.978
37	Industrial Applications of Plant Secondary Metabolites Lin, Yun 03 August 2017 (has links) No description available. Agriculture Biochemistry Biology Plant Sciences Plant secondary metabolite GC-MS HPLC LC-MS anti-microbial 2,4-D herbicide drift phospholipid fatty acid phenolic compound DIMBOA PDAC lipid biomarker
38	Biological functions of microRNA-216 and microRNA-217 during the development of pancreatic cancer Azevedo-Pouly, Ana Clara P. 17 October 2013 (has links) No description available. Pharmaceuticals Oncology Molecular Biology microRNA miR-217 miR-216a miR-216b cancer pancreas pancreatic cancer development PDAC REST CDH1 Zeb1 embryonic lethality GEMM mouse models ADM acinar ductal
39	Polycomb group proteins Bmi1 and Ring1B are involved in cell plasticity and tumorigenesis of the pancreas Martínez Romero, Carles 21 December 2009 (has links) L'adenocarcinoma ductal pancreàtic (PDAC) és un dels càncers més letals. Per tal de millorar el diagnòstic precoç, s'estan investigant les etapes inicials de la formació del càncer, com és el cas de les lesions preneoplàstiques, i es vol desxifrar l'origen cel·lular de la malaltia. Les proteïnes Polycomb constitueixen una família de silenciadors epigenètics que es troben en una varietat de tumors sòlids. La hipòtesi principal és que Polycomb pot estar participant en els processos preneoplàstics del pàncreas i en l'aparició i progressió del tumor. La expressió de Bmi1 i Ring1B fou analitzada durant el desenvolupament del pàncreas, en teixit pancreàtic de diferents models murins de la malaltia i en mostres humans de teixit pancreàtic. Es va dur a terme l'anàlisi del mecanisme de Bmi1 mitjançant models in vitro i induint la depleció de Bmi1. Bmi1 i Ring1B s'expressaren en precursors pancreàtics durant etapes primerenques del desenvolupament i en cèl·lules ductals i dels illots,però no en els acins, en el pàncrees adult. Bmi1 s'induí en cèl·lules acinars durant lesió aguda, en lesions metaplàstiques acinoductals, en neoplàsies intraepitelials pancreàtiques (PanIN) i en PDAC. Ring1B s'incrementà significativament en PanINs de grau alt i en PDAC. La disminució dels nivells de Bmi1 en la línia cel·lular acinar canvià l'expressió dels enzims digestius pancreàtics. Aquests resultats suggereixen que Bmi1 i Ring1B podrien estar contribuint de diferent manera en la progressió tumoral. / Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. To improve early diagnosis, research efforts are focused in characterising early events of cancer formation like preneoplastic lesions and deciphering the cell origin of the malignancy. Polycomb proteins constitute a family of epigenetic silencers found in a variety of solid tumours. The main hypothesis is that Polycomb might play a role in preneoplastic states in the pancreas and in tumour development and progression. The expression of Bmi1 and RingB was analysed during pancreatic development, in pancreatic tissue from mouse models of disease and in human pancreatic tissue samples. Mechanistic insights of Bmi1 were performed using in vitro models and with induced Bmi1 depletion. Bmi1 and Ring1B were expressed in pancreatic exocrine precursors during early development and in ductal and islet cells, but not in acinar cells, in the adult pancreas. Bmi1 was induced in acinar cells during acute injury, in acinar-ductal metaplastic lesions, in pancreatic intraepithelial neoplasia (PanIN) and PDAC. In contrast, Ring1B was significantly increased in high-grade PanINs and in PDAC. Bmi1 knockdown in acinar cell line changed the expression of pancreatic digestive enzymes. These results suggest that Bmi1 and Ring1B could contribute differently to tumour development. embrió rata ratolí humà PDAC tumor Ring1B Bmi1 Polycomb epigenètica cancer ductal acinar Pàncrees immunohistochemistry primary culture western blot PCR protein DNA RNA knockdown transdifferentiation acinoductal metaplasia KRAS PanIN caerulein pancreatitis preneoplastic embryo rat mouse human PDAC tumour Ring1B Bmi1 Polycomb epigenetics cancer ductal acinar Pancreas preneoplàsic pancreatitis ceruleïna PanIN KRAS metaplàsia acinoductal transdiferenciació "knockdown" ARN ADN proteïna PCR western blot cultiu primari immunohistoquímica 57
40	Genetische Polymorphismen in Typ-III-Interferon-Genen und deren prognostische Signifikanz für das hepatozelluläre Karzinom und das duktale Pankreasadenokarzinom / Interferon-lambda germline variations and their significance for hepatocellular carcinoma and pancreatic ductal adenocarcinoma progression Huschka, Henriette 31 December 1100 (has links) No description available. 610 Interferon-lambda4 IFNL4 IFNL4 rs368234815 hepatozelluläres Karzinom HCC duktales Pankreasadenokarzinom PDAC antitumorale Wirtsantwort progressionfreies Intervall PFI spezifisches progressionfreies Intervall PFI.2 Gesamtüberlebensdauer OS Typ-III-Interferon interferon-lambda4 IFNL4 IFNL4 rs368234815 type III interferons hepatocellular carcinoma HCC pancreatic ductal adenocarcinoma PDAC antitumor host response progression free interval PFI specific progression free interval PFI.2 overall survival OS Medizin (PPN619874732)

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