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Epithelioid sarcoma producing granulocyte colony-stimulating factor.

H Sonobe·Y Ohtsuki·E Ido·M Furihata·J Iwata·H Enzan·T Sugimoto·Y Asahi·I Kubonishi
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Abstract

An epithelioid sarcoma of the perineum of a 60-year-old man with widespread metastases produced leukocytosis, myeloid hyperplasia of the bone marrow, and splenomegaly. High titers of granulocyte colony-stimulating factor (G-CSF) were found in the patient's serum and primary culture medium of the tumor tissue. The tumor tissue extract contained m-RNA for G-CSF in large quantities, proving that the tumor was the source of this cytokine.

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Granulocyte Colony-Stimulating FactorHumansInguinal CanalLung NeoplasmsLymph NodesLymphatic MetastasisMaleMiddle AgedNeoplasm Recurrence, LocalPerineumSarcomaCase ReportsJournal Article

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H Sonobe, Y Ohtsuki, E Ido, M Furihata, J Iwata, H Enzan, T Sugimoto, Y Asahi, I Kubonishi. 1997. Epithelioid sarcoma producing granulocyte colony-stimulating factor.. https://doi.org/10.1016/s0046-8177(97)90236-7

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Severe congenital neutropenia: inheritance and pathophysiology.

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PubMed2006

Comparative oxidation studies of methionine residues reflect a structural effect on chemical kinetics in rhG-CSF.

The effect of protein conformation on the rate of chemical degradation is poorly understood. To address the role of structure on chemical degradation kinetics, comparative oxidation studies of methionine residues in recombinant human granulocyte colony-stimulating factor (rhG-CSF) were performed. The kinetics of oxidation of methionine residues by hydrogen peroxide (H2O2) in rhG-CSF and corresponding chemically synthesized peptides thereof was measured at different temperatures. To assess structural effects, equilibrium denaturation experiments also were conducted on rhG-CSF, yielding the free energy of unfolding as a function of temperature. A comparison of the relative rates of oxidation of methionine residues in short peptides with those of corresponding methionine residues in rhG-CSF yields an understanding of how protein tertiary structure affects oxidation reactions. For the temperature range that was studied, 4-45 degrees C, the oxidation rate constants followed an Arrhenius equation quite well, suggesting the lack of temperature-induced local structural perturbations that affect chemical degradation rates. One of the four methionine residues, Met 122, exhibited an activation energy significantly different from that of the corresponding peptide. Extrapolation of kinetic data predicts non-Arrhenius behavior around the melting temperature. Three phenomenological models based on different mechanisms are discussed, and an application to shelf life prediction of pharmaceuticals is presented.

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