By George Morstyn (auth.), Graham Molineux, MaryAnn Foote, Tara Arvedson (eds.)
Granulocyte colony-stimulating issue (G-CSF or GCSF) is a secreted glycoprotein that stimulates the proliferation and differentiation of granulocyte precursor cells, and induces mobilization of peripheral blood progenitor cells from the bone marrow. improvement of recombinant human G-CSF has had a profound influence at the remedy of many illnesses, together with critical power neutropenia and melanoma, and has enabled peripheral stem telephone transplantation to supplant bone marrow transplantation within the autologous environment.
This Milestones in Drug Therapy quantity describes the event of the final twenty years of therapy with recombinant human G-CSF, together with the fundamental technological know-how, using recombinant human G-CSF in either the oncology and nononcology settings, and the protection and economics of its use. a number of the authors have been the unique investigators of recombinant human G-CSF and different authors are key researchers who supply their outlook for the following two decades to be used of and learn with recombinant human G-CSF.
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Additional resources for Twenty Years of G-CSF: Clinical and Nonclinical Discoveries
The absolute numbers of lymphocytes increased approximately twofold, but the number of monocytes, eosinophils, reticulocytes, and platelets did not change significantly. In the spleen, foci of extramedullary hematopoiesis were observed. No other organs demonstrated evidence of hematopoietic activities. The neutrophils functioned normally in standard tests for chemotaxis and there was evidence of enhanced ability to kill phagocytized bacteria . We further investigated whether or not rG-CSF might be of benefit in chemotherapy-induced neutropenia and after bone marrow transplantation.
A challenge that was also faced was the duration of development, and the number of patients needed for safety studies continued to increase from several hundred in the regulatory submissions for rHuEPO and rHuG-CSF to over a thousand for darbepoetin alfa and pegfilgrastim. During the 5 years taken for development and the time taken for label extensions of the hematopoietic growth factors, the clinical settings and the hurdles for successful development changed. In the period 1987–2000, AIDS became a treatable disease and neutropenia became a rare event, and the development of filgrastim in this setting became less feasible.
Metcalf et al. showed that in G-CSFÀ/À mice, neutrophil recruitment into the peritoneal cavity in response to casein-induced inflammation was normal . However, G-CSFRÀ/À neutrophils have selected defects in mature neutrophil function. Whereas neutrophil superoxide generation and degranulation are normal, chemotaxis and adhesion of G-CSFRÀ/À neutrophils are impaired, likely due to defective  integrin activation . Likewise, neutrophil recruitment to an inflamed knee joint and the number of adherent neutrophils in synovial blood vessels in a collagen-induced arthritis model are reduced in G-CSFÀ/À and G-CSFRÀ/À mice .
Twenty Years of G-CSF: Clinical and Nonclinical Discoveries by George Morstyn (auth.), Graham Molineux, MaryAnn Foote, Tara Arvedson (eds.)