multi functional role of stem cells in disease

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Multifunctional Role of Pancreatic Differentiation 2  PD2  in Pancreatic Cancer
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Cancer is a devastating disease that claims the lives of countless people due to its uncontrolled growth pattern. Among various cancers, pancreatic cancer is one of the most lethal cancers due to its aggressive nature, lack of early symptoms and resistance to chemotherapy. The molecular profile of this deadly malignancy is not completely understood. Malignancy arises due to loss or gain of function in genes involved in cell cycle progression leading to disruption of tightly regulated transitions. In addition the evolving concept of cancer throws light on a small population of cells within the tumor known as the cancer stem cells (CSCs) or tumor-initiating cells that are resistant to all drugs treatment and contributes towards tumor initiation and recurrence. Several studies have been carried out to identify specific markers for the cancer stem cell population including that of pancreatic cancer. Pancreatic Differentiation 2 (PD2) or human Polymerase Associated Factor 1 (hPaf1) is an important component of the multifunctional PAF1 complex initially identified to play a crucial role in transcriptional elongation of genes. During the last decade, several papers on PD2 showed that it is a multifaceted molecule playing roles in cell cycle regulation, stem cell maintenance, histone methylation, chromatin remodeling and acinar-to-ductal metaplasia. In this dissertation, the first goal was to investigate the role of PD2 in pancreatic cancer stem cells. Initially, we analyzed the expression and function of PD2 in pancreatic cancer stem cells isolated from pancreatic cancer cell lines, Kras (G12D); Pdx1 (Cre)(KC), Kras (G12D); Trp53 (R172H/+.); Pdx1(Cre) (KPC) mouse models and human pancreatic tumors. Furthermore, the expression of PD2 was significantly higher in CSCs isolated from pancreatic cancer cells along with CSC markers. These cells were shown to exhibit a cobblestone appearance, increased tumorsphere formation and significant tumor growth, characteristic of the CSC phenotype. interestingly, PD2 was found to be specifically overexpressed in a subpopulation of cells within mouse KC, KPC and human pancreatic tumors, which co-express CSC markers. The drug resistance property was impaired upon knockdown of PD2 with simultaneous alteration in the CSC phenotype and reduction in CD133 and MDR2 gene expression. Overall, my study identified that PD2 has a role in self-renewal and drug resistance of pancreatic CSCs. The second part of my dissertation was primarily focused at exploring the functional role of PD2 in pancreatic cancer cells. The ectopic overexpression of PD2 resulted in increased growth rate of tumor cells both in vitro and in vivo. Overexpression of PD2 led to increased growth, colony formation and migration. Interestingly, elevated expression of PD2 also increased the percentage of CSCs. Furthermore, in vivo studies revealed that PD2 overexpression leads to increased tumor volume and metastasis to distant secondary sites. These results were corroborated at the protein level where elevated expression of PD2 led to the up-regulation of c-Myc which is an important player in tumorigenesis and metastasis. In addition, the expression of PD2 in pancreatic cancer tissues and in vitro pancreatic progression model was elucidated. We demonstrated that the expression of PD2 was increased in the ducts present in the pancreatic cancer tissues when compared to the normal tissues. Likewise, the expression of PD2 was elevated in the transformed Human Pancreatic Nestin expressing (HPNE) cells when compared to the untransformed HPNE cells. Understanding the role of PD2 through cell lines led to my next aim to generate PD2 conditional knockout mice in order to substantiate our earlier work in cancer stem cells and acinar to ductal metaplasia during PC initiation. The animal model would be an important resource for understanding the role of PD2 in detail. Taken together, our findings demonstrate that PD2 is an essential member of the oncogene family that plays a significant role in facilitating drug resistance and cancer stem cell maintenance thereby acting as a positive regulator of cancer.

Multifunctional Role of Pancreatic Differentiation 2  PD2  in Pancreatic Cancer

Cancer is a devastating disease that claims the lives of countless people due to its uncontrolled growth pattern. Among various cancers, pancreatic cancer is one of the most lethal cancers due to its aggressive nature, lack of early symptoms and resistance to chemotherapy. The molecular profile of this deadly malignancy

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Stem Cells

The second edition of Stem Cells: Scientific Facts and Fiction provides the non-stem cell expert with an understandable review of the history, current state of affairs, and facts and fiction of the promises of stem cells. Building on success of its award-winning preceding edition, the second edition features new chapters

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The Pulmonary Neuroepithelial Body Microenvironment

This monograph sheds new light on pulmonary sensory receptors. Diving into the pulmonary microenvironment, the book focuses on the role of pulmonary neuroepithelial bodies (NEBs) as potential receptors and effectors, able to store and release neurotransmitters. It explores NEBs as potential stem cell niche and highlights the multidisciplinary approach taken

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Stem Cells and Cancer Stem Cells  Volume 13

This is the thirteenth volume in a series which presents current understanding of stem cells and cancer stem cells. This book presents many relevant topics including the different sources of cancer stem cells: the features, roles and clinical potential of stem cells emerge from engaging with this comprehensive work. Chapters

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Plasticity and Reconstruction of Neural Network in Brain Injury

Download or read online Plasticity and Reconstruction of Neural Network in Brain Injury written by Zhang Pengyue,Yuchuan Ding,Yulong Bai,Xiangjian Zhang,Yunping Deng, published by Frontiers Media SA which was released on 2021-08-24. Get Plasticity and Reconstruction of Neural Network in Brain Injury Books now! Available in

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Stem Cells and Human Diseases

The main objective of this book is to provide a comprehensive review on stem cells and their role in tissue regeneration, homeostasis and therapy. In addition, the role of cancer stem cells in cancer initiation, progression and drug resistance are discussed. The cell signaling pathways and microRNA regulating stem cell

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Proteoglycans in Stem Cells

This book provides a state-of-the-art compendium on the role of proteoglycans and glycosaminoglycans during development and in cancer. It also suggests directions for novel therapeutic and biotechnological applications in stem cell biology. Proteoglycans and glycosaminoglycans, as part of the extracellular matrix, are multifunctional modulators of growth factor, cytokine, integrin and

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Stem Cells as Targeted Drug Delivery Vehicles

Topic Editor RL is a patent inventor on exosome-related patents, PCT/AU2017/050821 and PCT/AU2016/050468. All other Topic Editors declare no competing interests with regards to the Research Topic subject.

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Multifunctional Nanoparticles for Drug Delivery Applications

This book presents the medical challenges that can be reduced or even overcome by recent advances in nanoscale drug delivery. Each chapter highlights recent progress in the design and engineering of select multifunctional nanoparticles.

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Calcium Signaling in the Cardiac Differentiation of Mouse Embryonic Stem Cells

This dissertation, "Calcium Signaling in the Cardiac Differentiation of Mouse Embryonic Stem Cells" by Wenjie, Wei, 魏闻捷, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any

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Multifunctional Nanomaterials for Advanced Molecular Imaging and Cancer Therapy

Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused

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Stem Cells and Cancer Stem Cells  Volume 6

The difference among pluripotent stem cells, multipotent stem cells, and unipotent stem cells is pointed out. Vast therapeutic applications of the following specific stem cells in disease and tissue injury are discussed: human embryonic stem cells, human mesenchymal stem cells, germ cell-derived pluripotent stem cells, induced pluripotent stem cells, human

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Rational Design and Characterization of Innovative Multifunctional Biomimetic Materials

Download or read online Rational Design and Characterization of Innovative Multifunctional Biomimetic Materials written by Lia Rimondini,Lorenzo Moroni,Andrea Cochis, published by Frontiers Media SA which was released on 2021-04-13. Get Rational Design and Characterization of Innovative Multifunctional Biomimetic Materials Books now! Available in PDF, ePub and Kindle.

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The Mast Cell

Mast cells (MC) are phylogenetically old cells which are distributed throughout the human organism. MC are found in almost all of the major organs and tissues of the body, particularly in association with connective tissue structures such as blood vessels, lymphatic vessels and nerves, and in proximity to surfaces that

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Advanced Cell Culture Technologies to Boost Cell Based Therapies

Dr. Correa is the founder of Lumos Biomed Consulting and holds shares in Cryovida Stem Cell Bank (Mexico). Dr O’Brien holds patents related to regeneration technology and was a co-founder of SurgaColl Technologies. All other Topic Editors declare no competing interests with regard to the Research Topic subject.

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