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Halofuginone: From veterinary use to human therapy
Year:
2000
Source of publication :
Drug Development Research
Authors :
Pines, Mark
;
.
Volume :
50
Co-Authors:
Pines, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel, Institute of Animal Science, ARO, Volcani Center, Bet Dagan 50250, Israel
Vlodavsky, I., Department of Oncology, Hadassah University Hospital, Jerusalem, Israel
Nagler, A., Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel
Facilitators :
From page:
371
To page:
378
(
Total pages:
8
)
Abstract:
At present, halofuginone is the only known inhibitor of collagen synthesis that is type specific. Halofuginone was found to inhibit collagen α1 (I) gene expression and collagen synthesis in vitro in cell cultures and in various animal models in vivo characterized by excessive deposition of collagen, which results in fibrosis. Toxicity studies both in animals and in normal volunteers revealed no major side effects. Halofuginone was successfully used topically in a patient with chronic graft-versus-host disease and at present is being tested in a clinical trial of patients with scleroderma. Collagen is an important component of the stroma and is involved in endothelial cell migration and assembly to form and recruit new blood vessels - angiogenesis. Both stromal support and angiogenesis are critical for tumor growth. Based on this rationale, using various tumor models such as bladder carcinoma, prostate cancer, and glioma, we demonstrated that inhibition of collagen α1 (I) gene expression by halofuginone caused inhibition of angiogenesis, which resulted in arrest of tumor growth. Thus, inhibition of collagen type I synthesis provides an attractive new target for cancer therapy. Many of the possible targets for halofuginone therapy pose enormous clinical problems, most of them without solutions. The ability of extremely low concentrations of halofuginone, given orally, locally or injected intraperitoneally, to inhibit collagen α1 (I) synthesis specifically and transiently at the transcriptional level suggests that this compound fulfills the criteria for a successful and effective antifibrotic and anticancer therapy. (C) 2000 Wiley-Liss, Inc.
Note:
Related Files :
drug effect
endothelium cell
Fibrosis
gene expression
glioma
graft versus host reaction
Review
veterinary drug
Show More
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More details
DOI :
Article number:
Affiliations:
Database:
Scopus
Publication Type:
Review
;
.
Language:
English
Editors' remarks:
ID:
25341
Last updated date:
02/03/2022 17:27
Creation date:
17/04/2018 00:14
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Scientific Publication
Halofuginone: From veterinary use to human therapy
50
Pines, M., Institute of Animal Science, Agricultural Research Organization, Volcani Center, Bet Dagan, Israel, Institute of Animal Science, ARO, Volcani Center, Bet Dagan 50250, Israel
Vlodavsky, I., Department of Oncology, Hadassah University Hospital, Jerusalem, Israel
Nagler, A., Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel
Halofuginone: From veterinary use to human therapy
At present, halofuginone is the only known inhibitor of collagen synthesis that is type specific. Halofuginone was found to inhibit collagen α1 (I) gene expression and collagen synthesis in vitro in cell cultures and in various animal models in vivo characterized by excessive deposition of collagen, which results in fibrosis. Toxicity studies both in animals and in normal volunteers revealed no major side effects. Halofuginone was successfully used topically in a patient with chronic graft-versus-host disease and at present is being tested in a clinical trial of patients with scleroderma. Collagen is an important component of the stroma and is involved in endothelial cell migration and assembly to form and recruit new blood vessels - angiogenesis. Both stromal support and angiogenesis are critical for tumor growth. Based on this rationale, using various tumor models such as bladder carcinoma, prostate cancer, and glioma, we demonstrated that inhibition of collagen α1 (I) gene expression by halofuginone caused inhibition of angiogenesis, which resulted in arrest of tumor growth. Thus, inhibition of collagen type I synthesis provides an attractive new target for cancer therapy. Many of the possible targets for halofuginone therapy pose enormous clinical problems, most of them without solutions. The ability of extremely low concentrations of halofuginone, given orally, locally or injected intraperitoneally, to inhibit collagen α1 (I) synthesis specifically and transiently at the transcriptional level suggests that this compound fulfills the criteria for a successful and effective antifibrotic and anticancer therapy. (C) 2000 Wiley-Liss, Inc.
Scientific Publication
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