title: Production of proangiogenic cytokines during thalidomide treatment of multiple myeloma.
abstract: Recently a growing number of studies have suggested the efficacy of thalidomide (THAL) in the treatment of relapsed or resistant multiple myeloma. Some of these studies indicate that the thalidomide antimyeloma effect is associated with decreased vessel density. Here we first present our experience with THAL treatment and then focus on the determination of the role of proangiogenic cytokines during THAL therapy. Thirty relapsing or resistant multiple myeloma (MM) patients were treated with THAL at a median dose of 400 mg/daily. Eighteen responded to THAL therapy and 12 were resistant or intolerant to THAL. We determined the plasma level of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) as the main biological parameters associated with tumour angiogenesis. In addition I1-6 and TNFalpha levels were also assayed. Assessment of peripheral blood (PB) and bone marrow (BM) cytokine levels were done before and during THAL treatment at weeks 4 and 8 of therapy. In the responder group VEGF, bFGF I1-6 and TNFalpha concentrations were significantly decreased after four weeks of therapy both in PB and BM. In the non-responder group no significant changes in bFGF and VEGF levels were observed. However, a significant increase in IL-6 and TNF concentrations was evident. We conclude that the significant decrease of VEGF, bFGF, I1-6 and TNFalpha concentrations reflected response to THAL therapy. Also it seems that VEGF is a better marker of response to treatment than bFGF.
authors: Department of Haematology, University School of Medicine, Lublin, Poland. dmoszann@free.med.pl
authors: Anna
authors: A
authors: Dmoszyńska
authors: Agnieszka
authors: A
authors: Bojarska-Junak
authors: Damian
authors: D
authors: Domański
authors: Jacek
authors: J
authors: Roliński
authors: Marek
authors: M
authors: Hus
authors: Maria
authors: M
authors: Soroka-Wojtaszko
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D004341:Drug Evaluation; D016228:Endothelial Growth Factors / Q000097:blood; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000187:drug effects; D006133:Growth Substances / Q000097:blood*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008222:Lymphokines / Q000097:blood / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000097:blood / Q000188:drug therapy; D013792:Thalidomide / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D016228:Endothelial Growth Factors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide