title: Thalidomide downregulates angiogenic genes in bone marrow endothelial cells of patients with active multiple myeloma.
abstract: OBJECTIVE
  To study the antiangiogenic effect of thalidomide.
  
  
  METHODS
  The expression of key angiogenic genes was studied in bone marrow endothelial cells (ECs) of patients with active and nonactive multiple myeloma (MM), monoclonal gammopathies unattributed/unassociated (MG[u]), diffuse large B-cell non-Hodgkin's lymphoma, in a Kaposi's sarcoma (KS) cell line, and in healthy human umbilical vein ECs (HUVECs) following exposure to therapeutic doses of thalidomide.
  
  
  RESULTS
  Thalidomide markedly downregulates the genes in a dose-dependent fashion in active MMECs and KS cell line, but upregulates them or is ineffective in nonactive MMECs, MG(u)ECs, NHL-ECs, and in HUVECs. Secretion of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and hepatocyte growth factor also diminishes according to the dose in culture conditioned media (CM) of active MMECs and KS, whereas it does not change in the other CM.
  
  
  CONCLUSIONS
  Inhibition by thalidomide is probably confined to the genes of active MMECs and KS. This would account for its higher efficacy in these diseases.
authors.affiliation: Department of Internal Medicine and Clinical Oncology, Policlinico-Piazza Giulio Cesare, University of Medical School Bari, Italy. a.vacca@dimo.uniba.it
authors.forename: Angelo
authors.initials: A
authors.lastname: Vacca
authors.forename: Claudio
authors.initials: C
authors.lastname: Scavelli
authors.forename: Vittorio
authors.initials: V
authors.lastname: Montefusco
authors.forename: Giulia
authors.initials: G
authors.lastname: Di Pietro
authors.forename: Antonino
authors.initials: A
authors.lastname: Neri
authors.forename: Michela
authors.initials: M
authors.lastname: Mattioli
authors.forename: Silvio
authors.initials: S
authors.lastname: Bicciato
authors.forename: Beatrice
authors.initials: B
authors.lastname: Nico
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.forename: Franco
authors.initials: F
authors.lastname: Dammacco
authors.forename: Paolo
authors.initials: P
authors.lastname: Corradini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010265:Paraproteinemias / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D013792:Thalidomide / Q000494:pharmacology*; D014471:Umbilical Veins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide; D017228:Hepatocyte Growth Factor