Soluble vs Membrane Associated SCF

The possibility of soluble and membrane-associated forms of SCF (see Subheading 4.) raised questions as to their comparative functions. The fact that Sld Sld and Sl Sld mutant mice (see Subheading 5.) display the classical pleiotropic Sl mutant defects implied that absence of membrane-associated SCF is detrimental (but the overall level of expression of functional SCF is probably much reduced in these mice as well 35,36 ). Furthermore, cells expressing SCF248 maintain substantial steady-state...

CSFs in Patients With Acute Leukemia and Myelodysplastic Syndromes

Most patients receiving induction or consolidation therapies for acute leukemia develop febrile neutropenia. These therapies have other complications, including coag-ulopathy, thrombocytopenic hemorrhage, fungal infections, and amphotericin-induced renal damage. These complications are particularly more severe in older patients. The ASCOs guidelines note that several randomized clinical trials have studied the administration of CSFs in this setting and that the studies show a reduction in the...

References

Filgrastim (r-metHuG-CSF) in the chemotherapy setting. In Morstyn G, Dexter T, eds., Filgrastim (r-metHuG-CSF) in Clinical Practice. New York Marcel Dekker. 1994 103-116. 2. Hughes WT, Armstrong D, Bodey GP, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002 34 730-751. 3. Dale DC, McCarter GC, Crawford J et al. Myelotoxicity and dose intensity of chemotherapy reporting practices from randomized clinical...

Severe Chronic Neutropenia Patients

The longest exposure to daily administration of filgrastim has been in patients with SCN. Daily subcutaneous injections of filgrastim for > 10 yr in over 1000 patients worldwide, documented in the Severe Chronic Neutropenia International Registry (SCNIR), lead to neither exhaustion of myelopoiesis nor to anti-G-CSF antibody production. Chronic daily administration of filgrastim to patients with SCN neither exhausts myelopoiesis nor produces anti-G-CSF antibodies, and causes relatively few...

RHuIL11

Oprelvekin is a recombinant form of IL-11 produced in E. coli by recombinant DNA technology (10) and approved by the Food and Drug Administration (FDA) to prevent severe thrombocytopenia and reduce the need for platelet transfusions after myelosuppressive chemotherapy in patients with nonmyeloid cancers. rHuIL-11 increases the size and DNA content of megakaryocytes and stimulates throm-bopoiesis, increasing production and release of normally functioning platelets (10,11). Its nonhematologic...

Acronyms and Selected Abbreviations

ABV chemotherapy with doxorubicin, bleomycin, and vincristine ABVD chemotherapy with doxorubicin, bleomycin, vincristine, and dacarbazine AC chemotherapy with doxorubicin and cyclophosphamide ACE angiotensin-converting enzyme ADCC antibody-dependent cell-mediated cytotoxicity AIDS acquired immunodeficiency syndrome ALL acute lymphoblastic lymphocytic leukemia AlloBMT allogeneic bone marrow transplantation AML acute myeloid myelogenous leukemia APL acute promyelocytic leukemia ASCO American...

The Jakstat Signaling Pathway

Interferon Family

The proliferation and differentiation of peripheral blood progenitor cell PBPC populations to form myeloid, erythroid, and lymphoid populations is controlled by the actions of cytokines. Most cytokine receptors consist of a cytokine-specific binding subunit as well as a signal-transducing subunit, but, unlike many growth factor receptors, such as those for macrophage colony-stimulating factor M-CSF and epidermal growth factor EGF , they generally lack intrinsic kinase activity, rather, cytokine...

Economic Models of CSF in High Risk Populations 751 Clinical Prediction Risk Models

Diagram Febrile Neutropenia

The use of CSFs in all patients at risk for severe neutropenia or its complications has been considered cost-prohibitive. Selecting patients for CSF use has generally been based on the previous occurrence of such complications, the intensity of the chemotherapy regimen selected, or the clinical perception of risk. Several investigators have attempted to complement such considerations to improve the ability to predict those at greatest risk of neutropenia. Clinical prediction or risk models...

Scf Gene And Protein Interactions Between Scf And cKit

In 1990 three research groups simultaneously reported the cloning of cDNAs for factors that proved to be the mouse 15,16 , rat 17 , and human 17 homologs of the ligand for c-kit 4,6,7 . Each of these groups also showed that the gene for the mouse factor, like the Sl gene, mapped to mouse chromosome 10 that mutant Sl genes corresponded to structural alterations in the cloned mouse gene that the natural and recombinant factors could bind to cell surface c-kit and that the natural and recombinant...

Oncogenic Capacity Of The Jakstat Signaling Pathway

Oncogenesis is a discontinuous, progressive transformation of cells into a malignant and metastatic cell population. Tumor development depends on alterations in the genome and aberrant proliferation owing to autonomous growth-promoting signals, unresponsiveness to extracellular and intracellular growth-inhibitory signals, and evasion of apoptosis. Subsequent progression of the cancer into a malignant and metastatic phenotype relies on unrestrained replicative potential, avoidance of immune...

Pharmacodynamics of Darbepoetin Alfa in Patients

Clinical studies with darbepoetin alfa have been conducted in the United States, European Union, Australia, Canada, and Mexico. Several studies in the nephrology setting showed that darbepoetin alfa was effective at correcting anemia at a reduced dosing frequency. Randomized dose escalation studies compared once-weekly darbepoetin alfa 0.45 Mg kg with twice-weekly rHuEPO 50 U kg in rHuEPO-naive predialysis patients 123 . Drug dosages were adjusted, as necessary, to maintain Hb concentrations in...

Pharmacokinetics and Pharmacodynamics of Darbepoetin Alfa 931 Animal Studies

Pharmacokinetic parameters of darbepoetin alfa were measured in rats and dogs 59 . The terminal half-life of darbepoetin alfa was increased relative to rHuEPO by almost three-fold in rats 6.9 vs 2.5 h , and the clearance decreased 3.7-fold 17.7 vs 48. mL kg h . The volumes of distribution of darbepoetin alfa and rHuEPO were the same and roughly equivalent to the volume of the serum compartment, approx 34 mL kg, suggesting that distribution of the two proteins in the animal was similar. Similar...

Granulocyte Colony Stimulating Factor

Neutralizing polyclonal 33 and monoclonal 34 antibodies MAbs to HuG-CSF have been available they formed the basis for determination of immunoreactive HuG-CSF levels and for showing specificity in HuG-CSF bioassays 35 . A polyclonal neutralizing antiserum to murine Mu G-CSF has been used for G-CSF neutralization in vitro 36 . Despite the availability of these reagents, no attempts to neutralize endogenous MuG-CSF in vivo were reported. One experiment in rats involved passive immunization with a...