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You searched for subject:(pancreatic lineage). Showing records 1 – 3 of 3 total matches.

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University of Pennsylvania

1. Aiello, Nicole. Coming Full Circle: Epithelial Plasticity And The Natural History Of Metastasis.

Degree: 2016, University of Pennsylvania

The primary cause of cancer-related deaths is metastasis— the spread of cancer cells to distant organs— and yet the mechanisms underlying this process remain elusive due to the difficulty in detecting early metastatic events, which are rare, stochastic and microscopic. To investigate the cellular and molecular mechanisms of metastasis, I utilized an autochthonous mouse model of pancreatic cancer (KPCY) in which all tumor cells are genetically labeled with yellow fluorescent protein (YFP). The YFP lineage label allows for the detection and isolation of disseminated tumor cells as they delaminate from epithelial structures within the primary tumor, invade into the stroma and circulation, and colonize distal organs. Using this system, I characterized the development of metastatic lesions from single disseminated cells to grossly macroscopic lesions in the murine liver. I found that gross metastases closely resembled primary tumors in terms of differentiation and microenvironment— these large lesions are well differentiated, containing primarily epithelial tumor cells, and accumulate stroma consisting of myofibroblasts, leukocytes and extracellular matrix (ECM). In contrast, single disseminated cells tend to be poorly differentiated and lack any association with stromal cells, and must build up a microenvironment around them as they grow. Despite the presumably protective stroma surrounding large lesions, gross metastasis was significantly reduced with chemotherapy, while single cells were unaffected. Interestingly, residual lesions were enriched for epithelial features, suggesting that EMT confers chemosensitivity in this context. I also used the KPCY model to investigate the molecular mechanisms of epithelial-mesenchymal transition (EMT), which is widely considered to be the first step in the metastatic cascade. The YFP lineage label made it possible to identify and isolate tumor cells that have undergone EMT for transcriptional profiling. Surprisingly, I found that in a majority of pancreatic tumors, conventional transcriptional repressors were not involved in EMT. Although a mesenchymal transcriptional program was significantly enriched in cells that had undergone this “non-canonical” mechanism of EMT, the epithelial program was downregulated at the protein level by a mechanism involving protein internalization. Because cells retain both epithelial and mesenchymal properties during non-canonical EMT, this phenomenon represents an attractive explanation for the ability of tumor cells to cycle between epithelial and mesenchymal states and adapt to the changing microenvironment on their way to metastatic sites. The journey from primary tumor to metastatic site requires cancer cells to overcome many obstacles and a better understanding of how they navigate the numerous steps of the metastatic cascade could open the door to desperately needed anti-metastatic therapies.

Subjects/Keywords: epithelial mesenchymal transition; lineage tracing; liver metastasis; pancreatic cancer; Cell Biology; Molecular Biology; Oncology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Aiello, N. (2016). Coming Full Circle: Epithelial Plasticity And The Natural History Of Metastasis. (Thesis). University of Pennsylvania. Retrieved from https://repository.upenn.edu/edissertations/2160

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Aiello, Nicole. “Coming Full Circle: Epithelial Plasticity And The Natural History Of Metastasis.” 2016. Thesis, University of Pennsylvania. Accessed November 15, 2019. https://repository.upenn.edu/edissertations/2160.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Aiello, Nicole. “Coming Full Circle: Epithelial Plasticity And The Natural History Of Metastasis.” 2016. Web. 15 Nov 2019.

Vancouver:

Aiello N. Coming Full Circle: Epithelial Plasticity And The Natural History Of Metastasis. [Internet] [Thesis]. University of Pennsylvania; 2016. [cited 2019 Nov 15]. Available from: https://repository.upenn.edu/edissertations/2160.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Aiello N. Coming Full Circle: Epithelial Plasticity And The Natural History Of Metastasis. [Thesis]. University of Pennsylvania; 2016. Available from: https://repository.upenn.edu/edissertations/2160

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

2. Yeo, Wendy Wai Yeng. Differentiation of skeletal muscle-derived stem cells into beta pancreatic lineage : Différenciation des cellules souches dérivées du muscle squelettique vers le lignage des cellules pancréatiques beta.

Degree: Docteur es, Biologie Santé, 2015, Montpellier; Universiti Putra Malaysia (Serdang, Malaisie). Galeri Serdang

Le diabète de type 1 (DT1) est caractérisé par des niveaux élevés de glucose en raison de la destruction des cellules ß pancréatiques sécrétrices d'insuline. Cependant, les thérapies actuelles de remplacement des cellules bêta du pancréas impliquant la transplantation d'îlots pancréatiques sont techniquement difficiles et limitées par la disponibilité de don d'organes. Bien que les cellules souches embryonnaires et les cellules souches pluripotentes induites soient intensément étudiées, aucune de ces deux sources de cellules souches ne peut être utilisée directement sans le risque de développement de tumeurs. Les cellules souches dérivées du muscle squelettique (MDSC) sont une source de cellules alternative intéressante car elles sont multi-potentes et peuvent donc se différencier vers plusieurs lignages cellulaires tels que des cellules cardiaques à battement autonome “pacemaker-like” et des cellules neuronales. Par conséquent, nous avons émis l'hypothèse qu'elles pourraient se différencier en lignées de type pancréatique. Les objectifs de cette étude étaient donc d'étudier le potentiel des MDSC (1) à se différencier in vitro en cellules beta pancréatiques exprimant l'insuline et (2) à se différentier in vivo dans le pancréas et ainsi réduire l'hyperglycémie chez la souris modèle d'un diabète de type 1. Dans cette étude, les MDSC de muscle de souris ont été isolées via une série de passages des cellules les moins adhérentes en culture. Les cellules souches ainsi isolées peuvent adhérer sur une couche de cellules de types fibroblastes ou sur une matrice extra-cellulaire de type laminine pour ensuite se différentier in vitro ou bien être utilisées comme cellules souches MDSC non-adhérentes et non différentiées pour les études in vivo. In vitro, les MDSC peuvent se différencier spontanément en agrégats de cellules formant des îlots et exprimant des marqueurs de cellules bêta identifiés par immunofluorescence et analyse “PCR transcription inverse”. Ceci a été confirmé par immuno-analyse montrant l'expression des protéines nécessaires à la fonction des cellules ß, comme Nkx6.1, MafA et Glut2. Les MDSC différenciées en aggrégats cellulaires de type îlots pancréatiques montrent une sécrétion d'insuline en réponse au glucose in vitro. Cependant, dans des modèles murins de DT1 induit par la streptozotocine, l'injection intra-péritonéale des MDSC n'a pas permis de rétablir chez les souris diabétiques une normoglycémie du glucose sanguin en dépit d'un engreffement des MDSC dans les tissus pancréatiques. Ces données montrent que les MDSC peuvent constituer une source de cellules souches alternative intéressante pour le traitement du diabète.

Type 1 Diabetes (T1D) is characterized by high and poorly controlled glucose levels due to the destruction of insulin-secreting pancreatic ß-cells. However, current ß-cell replacement therapies, involving pancreas and pancreatic islet transplantation are technically demanding and limited by donor availability. While embryonic stem cells and induced pluripotent stem cells are intensely…

Advisors/Committee Members: Fernandez, Anne (thesis director), Abdallah, Syahril Nizam (thesis director).

Subjects/Keywords: Biologie cellulaire; Cellules souches; Différenciation cellulaire; Muscle squelettique; Lignage beta pancréatique; Cell Biology; Stem Cells; Cell Differentiation; Skeletal Muscle; Beta-Pancreatic lineage

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Yeo, W. W. Y. (2015). Differentiation of skeletal muscle-derived stem cells into beta pancreatic lineage : Différenciation des cellules souches dérivées du muscle squelettique vers le lignage des cellules pancréatiques beta. (Doctoral Dissertation). Montpellier; Universiti Putra Malaysia (Serdang, Malaisie). Galeri Serdang. Retrieved from http://www.theses.fr/2015MONTS091

Chicago Manual of Style (16th Edition):

Yeo, Wendy Wai Yeng. “Differentiation of skeletal muscle-derived stem cells into beta pancreatic lineage : Différenciation des cellules souches dérivées du muscle squelettique vers le lignage des cellules pancréatiques beta.” 2015. Doctoral Dissertation, Montpellier; Universiti Putra Malaysia (Serdang, Malaisie). Galeri Serdang. Accessed November 15, 2019. http://www.theses.fr/2015MONTS091.

MLA Handbook (7th Edition):

Yeo, Wendy Wai Yeng. “Differentiation of skeletal muscle-derived stem cells into beta pancreatic lineage : Différenciation des cellules souches dérivées du muscle squelettique vers le lignage des cellules pancréatiques beta.” 2015. Web. 15 Nov 2019.

Vancouver:

Yeo WWY. Differentiation of skeletal muscle-derived stem cells into beta pancreatic lineage : Différenciation des cellules souches dérivées du muscle squelettique vers le lignage des cellules pancréatiques beta. [Internet] [Doctoral dissertation]. Montpellier; Universiti Putra Malaysia (Serdang, Malaisie). Galeri Serdang; 2015. [cited 2019 Nov 15]. Available from: http://www.theses.fr/2015MONTS091.

Council of Science Editors:

Yeo WWY. Differentiation of skeletal muscle-derived stem cells into beta pancreatic lineage : Différenciation des cellules souches dérivées du muscle squelettique vers le lignage des cellules pancréatiques beta. [Doctoral Dissertation]. Montpellier; Universiti Putra Malaysia (Serdang, Malaisie). Galeri Serdang; 2015. Available from: http://www.theses.fr/2015MONTS091


Dublin City University

3. Gammell, Patrick. The molecular and cellular biology of pancreatic ß cell differentiation in vitro.

Degree: School of Biotechnology, 2002, Dublin City University

Previous studies have revealed that embryonic stem (ES) cells are capable of differentiating spontaneously towards pancreatic P cells. The use of growth factors and specific agents, such as nicotinamide, can further enhance this effect in a process known as directed differentiation. In vivo monitoring of pancreatic development indicates that the pancreas is derived from an endodermal lineage. This thesis investigated the differentiation of an embryonic carcinoma cell line, F9, which is characterised as having minimal spontaneous differentiation, towards endoderm and from there, on to pancreatic lineages. Treatment of monolayer F9 cells with 10'7 M retinoic acid (RA) or a combination of retinoic acid and 10'3M dibutyryl cyclic adenosine monophosphate (db cAMP) for 72 hours generates both primitive and parietal endodermal types. Culture of F9 cells in suspension leads to the formation of embryoid bodies (EBs). Treatment of these aggregates with RA generates visceral endoderm on the outer surface of the EB. These endodermal subtypes were found to express the full catalogue of cytokeratins (CKs) associated with the pancreatic islets i.e. CKs 8, 18, 7 & 19. The F9-derived endoderm was then treated with agents that have been shown to promote endocrine differentiation from progenitor cells i.e. activin A, betacellulin hepatocyte growth factor (HGF), nicotinamide and sodium butyrate. Certain treatments were found to increase the levels of important pancreatic mRNAs i.e. a combination of HGF and activin A increased pancreatic and duodenal homeobox gene 1 (PDX1) and preproinsulin (PPI) expression in RA-treated F9 monolayers. Sodium butyrate was shown to have positive effects on the expression of somatostatin and pancreatic polypeptide (PP) mRNAs. Other p cell genes detected in differentiating F9 cells include Pax6 and indian hedgehog (Ihh). To further study the role of the transcription factor PDX1 in pancreatic development, cell trapping was employed. In this system, a specialised construct was designed with the zeocin resistance gene (Sh ble) under the control of the PDX1 promoter region. This construct was shown to be capable of selectively maintaining the viability of F9 cells with the capability to drive the PDX1 promoter, in the presence of zeocin. The cells purified using this technique were found to exhibit increased levels of PDX1 mRNA and in certain cases PPI also, even though PDX1 protein was not detected. Further evidence for the presence of functional PDX1 in cell trapped lines was provided by the observation that these cell lines co-expressed somatostatin, which is known to be transactivated by PDX1. Upon culturing p cells for prolonged periods in vitro it has been noticed that these cells lose the ability to secrete insulin in response to environmental glucose signals (glucose stimulated insulin secretion, GSIS), in a process sometimes referred to as dedifferentiation. Upon culturing the murine P cell line, Min6, for 40 passages similar effects were noticed. Analysis of the gene expression profiles in… Advisors/Committee Members: Clynes, Martin, O'Driscoll, Lorraine.

Subjects/Keywords: Biotechnology; embryonic stem (ES) cells; directed differentiation; embryonic carcinoma cell line; endoderm lineage; pancreatic lineage

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Gammell, P. (2002). The molecular and cellular biology of pancreatic ß cell differentiation in vitro. (Thesis). Dublin City University. Retrieved from http://doras.dcu.ie/17379/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Gammell, Patrick. “The molecular and cellular biology of pancreatic ß cell differentiation in vitro.” 2002. Thesis, Dublin City University. Accessed November 15, 2019. http://doras.dcu.ie/17379/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Gammell, Patrick. “The molecular and cellular biology of pancreatic ß cell differentiation in vitro.” 2002. Web. 15 Nov 2019.

Vancouver:

Gammell P. The molecular and cellular biology of pancreatic ß cell differentiation in vitro. [Internet] [Thesis]. Dublin City University; 2002. [cited 2019 Nov 15]. Available from: http://doras.dcu.ie/17379/.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gammell P. The molecular and cellular biology of pancreatic ß cell differentiation in vitro. [Thesis]. Dublin City University; 2002. Available from: http://doras.dcu.ie/17379/

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.