Global ETD Search

41	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
42	Transdifferentiation of pancreatic cells by loss of contact-mediated signaling de Back, Walter, Zimm, Roland, Brusch, Lutz 22 January 2014 (has links) (PDF) Background: Replacement of dysfunctional β-cells in the islets of Langerhans by transdifferentiation of pancreatic acinar cells has been proposed as a regenerative therapy for diabetes. Adult acinar cells spontaneously revert to a multipotent state upon tissue dissociation in vitro and can be stimulated to redifferentiate into β-cells. Despite accumulating evidence that contact-mediated signals are involved, the mechanisms regulating acinar-to-islet cell transdifferentiation remain poorly understood. Results: In this study, we propose that the crosstalk between two contact-mediated signaling mechanisms, lateral inhibition and lateral stabilization, controls cell fate stability and transdifferentiation of pancreatic cells. Analysis of a mathematical model combining gene regulation with contact-mediated signaling reveals the multistability of acinar and islet cell fates. Inhibition of one or both modes of signaling results in transdifferentiation from the acinar to the islet cell fate, either by dedifferentiation to a multipotent state or by direct lineage switching. Conclusions: This study provides a theoretical framework to understand the role of contact-mediated signaling in pancreatic cell fate control that may help to improve acinar-to-islet cell transdifferentiation strategies for β-cell neogenesis. Interzelluläre Kommunikation Umprogrammierung Pankreas Azinuszellen Inselzellen mathematisches Modell multizelluläre Systeme TU Dresden Publikationsfonds Lineage conversion Intercellular communication Reprogramming Pancreas Acinar cells Islet cells Mathematical model Multicellular systems biology Technical University Dresden Publication funds ddc:570 ddc:610 rvk:WA 15000 rvk:XA 10000
43	Transdifferentiation of pancreatic cells by loss of contact-mediated signaling de Back, Walter, Zimm, Roland, Brusch, Lutz 22 January 2014 (has links) Background: Replacement of dysfunctional β-cells in the islets of Langerhans by transdifferentiation of pancreatic acinar cells has been proposed as a regenerative therapy for diabetes. Adult acinar cells spontaneously revert to a multipotent state upon tissue dissociation in vitro and can be stimulated to redifferentiate into β-cells. Despite accumulating evidence that contact-mediated signals are involved, the mechanisms regulating acinar-to-islet cell transdifferentiation remain poorly understood. Results: In this study, we propose that the crosstalk between two contact-mediated signaling mechanisms, lateral inhibition and lateral stabilization, controls cell fate stability and transdifferentiation of pancreatic cells. Analysis of a mathematical model combining gene regulation with contact-mediated signaling reveals the multistability of acinar and islet cell fates. Inhibition of one or both modes of signaling results in transdifferentiation from the acinar to the islet cell fate, either by dedifferentiation to a multipotent state or by direct lineage switching. Conclusions: This study provides a theoretical framework to understand the role of contact-mediated signaling in pancreatic cell fate control that may help to improve acinar-to-islet cell transdifferentiation strategies for β-cell neogenesis. info:eu-repo/classification/ddc/570 ddc:570 info:eu-repo/classification/ddc/610 ddc:610
44	INVESTIGATION OF DIFFERENTIALLY EXPRESSED NONCODING RNAS IN PANCREATIC DUCTAL ADENOCARCINOMA Sutaria, Dhruvitkumar S January 2016 (has links) No description available. Pharmaceuticals Pharmacy Sciences Nanoscience Molecular Biology Oncology Pharmacology Noncoding RNA microRNA Long non coding RNA exosomes extracellular vesicles therapeutic delivery pancreatic cancer TAT TAR interaction protein engineering mouse models

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