Granulocyte colony-stimulating factor and its receptor.

FOUR colony-stimulating factors influence the survival, proliferation, differentiation, and functional activation of myeloid hematopoietic cells: macrophage colony-stimulating factor (M-CSF), granulocyte colony-stimulating factor (G-CSF), granulocytemacrophage colony-stimulating factor (GM-CSF), and interleukin-3 (formerly known as multi-colony-stimulating factor).1 2 3 Various other cytokines and factors are also implicated in these processes, including interleukins 1, 5, 6, and 11 and the recently identified Steel factor (variously designated c-kit ligand, mast-cell growth factor, and stem-cell factor).4 , 5 Of these factors, only G-CSF and GM-CSF are commercially available for clinical use. G-CSF has been approved in the United States and major European countries for the reduction of infection after . . .

https://www.nejm.org/doi/pdf/10.1056/NEJM199207023270106?listPDF=true

Granulocyte Colony-Stimulating Factor and Granulocyte-Macrophage Colony-Stimulating Factor

Abnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, the modulation of enzymes that control anabolic and catabolic pathways causes increased levels of choline-containing precursors and breakdown products of membrane phospholipids. These increased levels are associated with proliferation, and recent studies emphasize the complex reciprocal interactions between oncogenic signalling and choline metabolism. Because choline-containing compounds are detected by non-invasive magnetic resonance spectroscopy (MRS), increased levels of these compounds provide a non-invasive biomarker of transformation, staging and response to therapy. Furthermore, enzymes of choline metabolism, such as choline kinase, present novel targets for image-guided cancer therapy.

/pdf/choline-metabolism-in-malignant-transformation-4s9se90sd8.pdf

Choline metabolism in malignant transformation

Molecular physiology of granulocyte-macrophage colony-stimulating factor.

Erythropoietin is known to be a hematopoietic growth factor with a singularly specific action on the proliferation and differentiation of erythroid progenitor cells. We have observed a dose-dependent proliferative action of human recombinant erythropoietin on human umbilical vein endothelial cells and bovine adrenal capillary endothelial cells. Binding studies with radioiodinated recombinant human erythropoietin revealed a large number (approximately 27,000) of an apparent single class of receptors with an affinity in the 10(-9) M range. Linkage of the radiolabeled ligand to its receptor via a bifunctional crosslinking agent allowed us to identify an endothelial cell protein of 45 kDa as the principal receptor associated with this mitogenic effect of erythropoietin. Recombinant human erythropoietin also enhanced the migration of endothelial cells.

Erythropoietin has a mitogenic and positive chemotactic effect on endothelial cells.

Various Human Hematopoietic Growth Factors (Interleukin-3, GM-CSF, G-CSF) Stimulate Clonal Growth of Nonhematopoietic Tumor Cells

A clinical phase I trial with an oral formulation of miltefosine (MIL) was performed in patients with various advanced malignant diseases. The capsulated drug (50 mg or 100 mg capsules) was given once a week over a period of twelve hours with a starting dose of 100 mg (2x50 mg). Dose escalation proceeded up to 300 mg per week. At least three patients were treated at each dose level for eight weeks or until progressive disease or dose limiting toxicity occurred. 34 patients entered this study with 26 patients completing one eight-week course of therapy. Only gastrointestinal side effects were seen, namely nausea and vomiting or diarrhea up to grade III (WHO). Severity of these side effects was dose-related, but there was considerable individual variation. MTD was reached at the 300 mg dose level. Pharmacokinetic studies performed at this dose level showed peak plasma levels of approx. 15 nmol/ml and a plasma half life in excess of eight days after application on one single day. No objective remission has been seen in the patients of this study.

Phase I Study of Weekly Oral Miltefosine (Hexadecyl-Phosphocholine) in Cancer Patients

Antitumoral activity of a xanthate compound. I. Cytotoxicity studies with neoplastic cell lines in vitro.

Therapeutic activity of 1-β-D-arabinofuranosylcytosine conjugates of lipids in WEHI-3B leukemia in mice

Background: Production of Erythropoietin has been reported for various tumor cell lines in vitro. Also, a number of clinical reports indicate aberrant synthesis and release of erythropoietin, particul

S. Danhauser-Riedl

Papers

Various Human Hematopoietic Growth Factors (Interleukin-3, GM-CSF, G-CSF) Stimulate Clonal Growth of Nonhematopoietic Tumor Cells

Phase I Study of Weekly Oral Miltefosine (Hexadecyl-Phosphocholine) in Cancer Patients

Antitumoral activity of a xanthate compound. I. Cytotoxicity studies with neoplastic cell lines in vitro.

Therapeutic activity of 1-β-D-arabinofuranosylcytosine conjugates of lipids in WEHI-3B leukemia in mice

Effects of Recombinant Human Erythropoietin on Clonogenic Growth of Primary Human Tumor Specimens in vitro