Proliferation Growth factors

Recent research has demonstrated that adult human corneal endothelial cells can be grown in culture and transplanted into recipient corneas. Because human endothelial cells retain the capacity to proliferate, growth factors and inhibitors are under study as a potential method for regenerating damaged endothelial cells and increasing cell density to restore endothelial layer function. 

One possible mechanism responsible for the abiHty of trenbolone acetate to stimulate skeletal muscle hypertrophy may be through enhanced proliferation and differentiation of satelHte ceUs as the result of increased sensitivity to insuHn-Hke growth factor-I (IGE-1) and fibroblast growth factor (43). 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

Proliferation of osteoblast precursors is an important event at the remodeling site. This is also likely to be enhanced by local osteoblast growth factors released... 

Inhibition of hematopoietic growth factors Imatinib (Glivec ) is applied to treat chronic myeloid leukemia in Philadelphia-chromosome positive patients. In these patients, translocation of parts of chromosomes 9 and 22 results in the expression of a fusion protein with increased tyrosine kinase activity, called Bcr-Abl. Imatinib is a small Mw inhibitor selective for the tyrosine kinase activity of Bcr-Abl. Thereby, it inhibits the Bcr-Abl induced cell cycle progression and the uncontrolled proliferation of tumor cells. 

Hematopoietic (blood) cells transport oxygen and carbon dioxide, contribute to host immunity, and facilitate blood clotting [1], A complex, interrelated, and multistep process, called hematopoiesis, controls the production as well as the development of specific marrow cells from immature precursor cells to functional mature blood cells. This well-regulated process also allows for replacement of cells lost through daily physiologic activities. The proliferation of precursor cells, the maturation of these into mature cells, and the survival of hematopoietic cells require the presence of specific growth factors. 

All mature blood cells arise from primitive hematopoietic cells in the bone marrow, the pluripotent stem cells. Approximately 0.1% of the nucleated cells of the bone marrow are pluripotent stem cells and approximately 5% of these cells may be actively cycling at any one time. The stem cell pool maintains itself through a process of asymmetrical cell division when a stem cell divides, one daughter cell remains a stem cell and the other becomes a committed colony-forming cell (CFC). The proliferation and differentiation of CFCs are controlled by hematopoietic growth factors. The hematopoietic growth factors stimulate cell division, differentiation and maturation, and convert the dividing cells into a population of terminally differentiated functional cells. 

SCF (recombinant product ancestim) is an early-acting hematopoietic growth factor that stimulates the proliferation of primitive hematopoietic and nonhema-topoietic cells [7]. In vitro, SCF has minimal effect on hematopoietic and nonhematopoietic progenitor cells, but it synergistically increases the activity of other hematopoietic growth factors, such as G-CSF, GM-CSF, and EPO. SCF stimulates the generation of dendritic cells in vitro and mast cells in vivo. 

Gx to S phase cell-cycle transition. Transition is required for the onset of IL-2 induced T-cell proliferation. Additionally, SRL also attenuates growth factor induced proliferation of several nonimmune cells and also inhibits metastatic tumor growth and angiogenesis. 

Besides the cytokine receptors that lack intrinsic kinase activity but have associated JAK kinases, STAT proteins can be activated by a variety of G-protein coupled receptors and growth factor receptors with intrinsic tyrosine kinase activity (for example EGF, PDGF, CSF-1, and angiotensin receptor). Increasing evidence suggests a critical role for STAT family members in oncogenesis and aberrant cell proliferation. Constitutively activated STATs have been found in many transformed cell lines and a wide variety of human tumor entities. Numerous non-receptor tyrosine kinases and viral oncoproteins, such as v-Src, v-Abl, v-Sis, and v-Eyk, have been identified to induce DNA-binding activity of STAT proteins. 

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