Cell biology

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  • This is the first book to cover the history, structure, and application of atomic force microscopy in cell biology. Presented in the clear, well-illustrated style of the Methods in Cell Biology series, it introduces the atomic force microscope (AFM) to its readers and enables them to tap the power and scope of this technology to further their own research. A practical laboratory guide for use of the atomic force and photonic force microscopes, it provides updated technology and methods in force spectroscopy.

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  • Harrison's Internal Medicine Chapter 66. Stem Cell Biology Stem Cell Biology: Introduction Stem cell biology is a relatively new field that explores the characteristics and possible clinical applications of the different types of pluripotential cells that serve as the progenitors of more differentiated cell types. In addition to potential therapeutic applications (Chap. 67), patient-derived stem cells can also provide disease models and a means to test drug effectiveness.

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  • Harrison's Internal Medicine Chapter 67. Applications of Stem Cell Biology in Clinical Medicine Applications of Stem Cell Biology in Clinical Medicine: Introduction Organ damage and the resultant inflammatory responses initiate a series of repair processes, including stem cell proliferation, migration, and differentiation, often in combination with angiogenesis and remodeling of the extracellular matrix. Endogenous stem cells in tissues such as liver and skin have a remarkable ability to regenerate the organs, whereas heart and brain have a much more limited capability for self-repair.

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  • In this 3rd edition of Anatomy, Histology, and Cell Biology: PreTest Self-Assessment and Review, a significant number of changes and improvements have been made. This PreTest reviews all of the anatomical disciplines encompassing early embryology, cell biology, histology of the tissues and organs, as well as regional human anatomy of the head and neck, thorax, abdomen, pelvis, extremities, and spine. This edition represents a comprehensive effort to integrate the anatomical disciplines with clinical scenarios and cases.

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  • Harrison's Internal Medicine Chapter 80. Cancer Cell Biology and Angiogenesis Cancer Cell Biology and Angiogenesis: Introduction Two characteristic features define a cancer: unregulated cell growth and tissue invasion/metastasis. Unregulated cell growth without invasion is a feature of benign neoplasms, or new growths. Cancer is a synonym for malignant neoplasm. Cancers of epithelial tissues are called carcinomas; cancers of nonepithelial (mesenchymal) tissues are called sarcomas. Cancers arising from hematopoietic or lymphoid cells are called leukemias or lymphomas.

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  • Cancer Cell Biology The treatment of most human cancers with conventional cytoreductive agents has been unsuccessful due to the Gompertzian-like growth kinetics of solid tumors (i.e., tumor growth is exponential in small tumors, with increasing doubling times as tumors expand; since conventional chemotherapeutic agents target proliferating cells, noncycling cells in large tumors are relatively resistant). Genetic instability is inherent in most cancer cells and predisposes to the development of intrinsic and acquired drug resistance. Thus, although tumors arise from a single cell (i.e.

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  • Cell biology of carbohydrate metabolism: Regulation of metabolic pathways, glucose as a regulator of metabolism, a carbohydrate response element (ChoRE) consists of 2 E-box like elements separated by 5 nucleotides, metabolic control analysis,...

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  • This volume is the first book-length survey of caveolae and lipid rafts. Interest has developed rapidly in the role of these surface microdomains in such diverse fields as transmembrane signaling, cell locomotion, vascular relaxation, senescence, and the uptake and exit from cells of viruses and bacteria. Individual chapters in this volume cover areas as diverse as the forces that induce and maintain membrane invaginations, and the clinical relevance of multiprotein complexes at the cell surface, defects in which are associated with cancer, and Alzheimer’s and prion-dependent diseases....

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  • Self-Renewal and Proliferation of Stem Cells Symmetric and Asymmetric Cell Division The most widely accepted stem cell definition is a cell with a unique capacity to produce unaltered daughter cells (self-renewal) and to generate specialized cell types (potency). Self-renewal can be achieved in two ways. Asymmetric cell division produces one daughter cell that is identical to the parental cell and one daughter cell that is different from the parental cell and is a progenitor or differentiated cell. Asymmetric cell division does not increase the number of stem cells.

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  • Diabetes Mellitus The success of islet cell and pancreas transplantation provides proof of concept for a cell-based approach for type I diabetes. However, the demand for donor pancreata far exceeds the number available, and maintenance of long-term graft survival remains a problem. The search for a renewable source of stem cells capable of regenerating pancreatic islets has therefore been intensive. Pancreatic βcell turnover occurs in the normal pancreas, although the source of the new βcells is controversial.

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  • Strategies for Stem Cell Replacement Stem cell transplantation is not a new concept and it is already part of established medical practice. Hematopoietic stem cells (HSCs) (Chap. 68) are responsible for the long-term repopulation of all blood elements in bone marrow transplant recipients. HSC transplantation is now the gold standard against which other stem cell transplantation therapies will be measured. Transplantation of differentiated cells is also a clinical reality, as donated organs (e.g., liver, kidney) and tissues (i.e.

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  • Nuclear Reprogramming Development naturally progresses from totipotent fertilized eggs to pluripotent epiblast cells, to multipotent cells, and finally to terminally differentiated cells. According to Waddington's epigenetic landscape, this is analogous to a ball moving down a slope. The reversal of the terminally differentiated cells to totipotent or pluripotent cells (called nuclear reprogramming) can thus be seen as an uphill gradient that never occurs in normal conditions.

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  • Other Organ Systems and the Future The use of stem cells in regenerative medicine has been studied for many other organ systems and cell types, including skin, eye, cartilage, bone, kidney, lung, endometrium, vascular endothelium, smooth muscle, striated muscle, and others. In fact, the potential for stem cell regeneration of damaged organs and tissues is virtually limitless. However, numerous obstacles must be overcome before stem cell therapies can become a widespread clinical reality.

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  • Telomerase DNA polymerase is unable to replicate the tips of chromosomes, resulting in the loss of DNA at the specialized ends of chromosomes (called telomeres) with each replication cycle. At birth, human telomeres are 15- to 20-kb pairs long and are composed of tandem repeats of a six-nucleotide sequence (TTAGGG) that associate with specialized telomere-binding proteins to form a T-loop structure that protects the ends of chromosomes from being mistakenly recognized as damaged.

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  • Tumor angiogenesis is a complex process involving many different cell types that must proliferate, migrate, invade, and differentiate in response to signals from the tumor microenvironment. Endothelial cells (ECs) sprout from host vessels in response to VEGF, bFGF, Ang2, and other proangiogenic stimuli. Sprouting is stimulated by VEGF/VEGFR2, Ang2/Tie-2, and integrin/extracellular matrix (ECM) interactions.

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  • Figure 80-1 Induction of p53 by the DNA damage and oncogene checkpoints. In response to noxious stimuli, p53 and mdm2 are phosphorylated by the ataxia telangiectasia mutated (ATM) and related ATR serine/threonine kinases, as well as the immediated downstream checkpoint kinases, Chk1 and Chk2. This causes dissociation of p53 from mdm2, leading to increased p53 protein levels and transcription of genes leading to cell cycle arrest (p21Cip1/Waf1) or apoptosis (e.g., the proapoptotic Bcl-2 family members Noxa and Puma).

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  • VEGF and its receptors are required for vasculogenesis (the de novo formation of blood vessels from differentiating endothelial cells, as occurs during embryonic development) and angiogenesis under normal (wound healing, corpus luteum formation) and pathologic processes (tumor angiogenesis, inflammatory conditions such as rheumatoid arthritis).

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  • Antiangiogenic Therapy Understanding the molecular mechanisms that regulate tumor angiogenesis may provide unique opportunities for cancer treatment. Acquired drug resistance of tumor cells due to their high intrinsic mutation rate is a major cause of treatment failure in human cancers. ECs comprising the tumor vasculature are genetically stable and do not share genetic changes with tumor cells; the EC apoptosis pathways are therefore intact.

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  • Imatinib has also demonstrated targeted activity in other diseases, including gastrointestinal stromal tumors (GIST), rare mesenchymal tumors of the GI tract (stomach and small intestine). The pathogenic molecular event for most patients with this disease is mutation of the proto-oncogene c-Kit, leading to the constitutive activation of this receptor tyrosine kinase without the binding of its physiologic ligand, stem cell factor. About 10% of GISTs encode activating mutations of the PDGFRα instead of c-Kit.

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  • PI3K is a heterodimeric lipid kinase that catalyses the conversion of phosphatidylinositol bisphosphate (PIP2) to phosphatidylinositol trisphosphate (PIP3), which acts as a plasma membrane docking site for proteins that contain a pleckstrin homology (PH) domain. These include the serine/threonine kinases Akt and PDK1 that are key downstream effectors of PI3K action (Fig. 80-2). The PI3K pathway is activated in 30–40% of human cancers and is thought to play a critical role in tumor cell survival, proliferation, growth, and glucose utilization.

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