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J Cebon

Publications and source records attributed to J Cebon.

62 records · Page 4Linked to original sources
PubMed1989

Pharmacology of the colony-stimulating factors.

Leukocyte production is influenced by a family of glycoproteins called colony-stimulating factors. Two of these have been purified, cloned and produced in quantities sufficient for clinical use. Granulocyte colony-stimulating factor (G-CSF) preferentially stimulates neutrophil production and has been shown to reduce the duration of neutropenia following chemotherapy. G-CSF therapy also has beneficial effects in a variety of other neutropenic states. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates neutrophil, monocyte and eosinophil production and function. GM-CSF is associated with more diverse haematological and clinical effects. George Morstyn and colleagues summarize the promising results from the early clinical trials with these new therapeutic agents.

Animals↗
PubMed1989

Clinical experience with recombinant human granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor.

Bacterially synthesized human granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) have been studied to determine if they could prevent or reduce the neutropenia caused by chemotherapy. Our studies suggest that 10 micrograms/kg/day of G-CSF administered as a continuous subcutaneous infusion abrogates the neutropenia associated with a standard dose of melphalan. G-CSF produced a rapid increase of neutrophil levels, was well-tolerated, and was associated with only one frequent adverse effect: bone pain. GM-CSF, administered in doses ranging from 3 to 15 micrograms/kg/day subcutaneously, appeared to be useful in abrogating the neutropenia associated with chemotherapy, producing elevations in neutrophils, eosinophils, and monocytes. Although GM-CSF was relatively well-tolerated, several adverse effects, including bone pain, rashes, and fluid retention, were observed. The initial dose of GM-CSF in some patients produced a reaction that was characterized by hypoxia.

Clinical Trials as Topic↗
PubMed1989

Characterization of the clinical effects after the first dose of bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor.

Bacterially synthesized recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) is an agent with therapeutic potential for neutropenic states, but even at doses below the maximal tolerated dose adverse effects occur during short courses of administration. We have recognized a syndrome of hypoxia and hypotension that follows the first but not subsequent doses of rhGM-CSF. Thirteen of 42 patients receiving rhGM-CSF in phase I studies and 4 of 6 patients in a phase II study developed a reaction that occurred after the first dose of 24 of 78 cycles of rhGM-CSF therapy. The reaction was characterized by flushing (16 of 24), tachycardia (16 of 24), hypotension (14 of 24), musculoskeletal pain (13 of 24), dyspnea (12 of 24), nausea and vomiting (11 of 24), rigors (5 of 24), involuntary leg spasms (3 of 24), and syncope (3 of 24). The reaction did not occur after any of more than 600 second and subsequent consecutive rhGM-CSF doses. Oxygen saturation decreased during first-dose reactions by 8% +/- 4% as compared with 3% +/- 1% on first days without reactions (P less than .001) and 2% +/- 1% on subsequent days (P less than .001). Pulmonary dysfunction was characterized by hypoxemia (59 +/- 9 mm Hg, mean +/- SD) that was fully correctable with supplementary oxygen, decreased single-breath carbon monoxide diffusion capacity, and increased alveolar-arterial oxygen gradients (25 +/- 6 to 60 +/- 4 mm Hg, mean +/- SD), but no significant abnormalities on chest roentgenogram or lung perfusion scan. Factors predisposing to reactions were rhGM-CSF dose greater than or equal to 3 micrograms/kg (P less than .01), intravenous (IV) rather than subcutaneous (SC) administration (P less than .05), occurrence of a reaction after the first dose of a previous cycle of rhGM-CSF therapy (P less than .01), and for patients receiving 15 micrograms/kg/d by SC bolus, the presence of lung cancer (P less than .05). Administration of 15 micrograms/kg/d rhGM-CSF by 24-hour SC infusion rather than SC bolus resulted in a delayed onset of reaction from 30 +/- 8 minutes to 240 +/- 190 minutes (mean +/- SD, P less than .001), and a slower rate of initial transient decrease in neutrophil levels and a more prolonged duration of transient leukopenia. The time of onset of reactions correlated with the rate of rise of rhGM-CSF levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Colony-Stimulating Factors↗
PubMed1989

Haemopoietic growth factor control of normal and neoplastic cellular proliferation.

Endotoxin induces the appearance of granulocyte colony stimulating factor (G-CSF) and macrophage (M)-CSF in the serum of mice. No GM-CSF was detectable in endotoxin serum. Phytohaemagglutinin stimulated human T-lymphocytes to secrete three major forms of GM-CSF. All of the haemopoietic growth factors (HGFs) are active in vivo, but the cellular responses are different for each HGF. Prolonged administration of G-CSF increases the number of circulating neutrophils and does not lead to adverse side-effects. Chronic exposure to GM-CSF induces an accumulation of activated macrophages which can cause considerable tissue destruction. Although the 'src-like' oncogenes induce HGF production by chicken myeloblasts, factor-dependent murine cells can be converted to a tumorigenic phenotype without autocrine growth factor production.

Animals↗
PubMed1988

Clinical studies with granulocyte colony stimulating factor (G-CSF) in patients receiving cytotoxic chemotherapy.

Bacterially synthesised human granulocyte colony-stimulating factor (G-CSF) was administered to patients with advanced cancer. The immediate effect of G-CSF was a fall in the level of circulating neutrophils followed by a rise after 4 hours that was sustained during G-CSF administration. The rise in neutrophil level was less in patients who had been treated previously with chemotherapy and/or radiotherapy. G-CSF was also administered to patients following melphalan and this resulted in a reduction in the duration of the neutropenia that invariably follows melphalan. G-CSF was well tolerated and did not have to be stopped in any patient.

Colony-Stimulating Factors↗
PubMed1988

Pharmacokinetics of human granulocyte-macrophage colony-stimulating factor using a sensitive immunoassay.

A sensitive and reliable sandwich enzyme-linked immunosorbent assay (ELISA) has been developed for recombinant human granulocyte-macrophage colony-stimulating factor (hGM-CSF). The assay is quantitative between 100 pg/mL and 2.5 ng/mL for bacterially synthesized hGM-CSF in human serum and is more sensitive and specific than the semisolid agar bioassay. As part of a phase I study, the pharmacokinetics of intravenous (IV) bolus injection and subcutaneous (SC) administration of hGM-CSF were studied. Following a single IV dose, an initial high blood level of hGM-CSF occurred, followed by a rapid decrease occurring in two apparent phases with a half-life (t1/2)alpha of less than five minutes and a t1/2 beta of 150 minutes. After an SC injection, detectable serum levels occurred within 15 to 30 minutes, and serum levels were sustained for a variable time depending on the dose. At the highest SC dose (10 micrograms/kg), a serum level of greater than 1 ng/mL (65 pmol/L) was maintained for greater than 12 hours after a single injection. This corresponds to the concentration of hGM-CSF supporting near-maximum proliferation in vitro.

Adult↗