title: Tumor angiogenesis in the bone marrow of multiple myeloma patients and its alteration by thalidomide treatment.
abstract: Angiogenesis in solid tumors is important to tumor growth, invasion and metastasis. Recently, it has been suggested that angiogenesis plays a certain role in the development of hematopoietic malignancies, including leukemia and multiple myeloma. We evaluated tumor angiogenesis in the bone marrow (BM) of multiple myeloma (MM) patients by calculating microvessel density (MVD) in needle-biopsy specimens obtained from 51 cases of untreated MM or monoclonal gammopathy of undetermined significance (MGUS). The MVD in the BM of donors for transplantation and patients with non-hematological diseases was calculated as a control. There was an obvious increase in MVD in the BM of MM patients, and the MVD correlated with the grade of myeloma cell invasion of the BM in the untreated MM cases. It was recently reported that thalidomide might be effective for the treatment of MM. We assessed the effect of thalidomide on angiogenesis in BM treatment of 11 patients with refractory MM. The concentration of M-protein in the serum or urine of seven of the 11 patients was reduced by at least 30% after thalidomide treatment, and MVD in the BM decreased in three of these seven cases in response to thalidomide. Increased plasma concentrations of basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF) were observed in all 11 cases before thalidomide administration and both levels were reduced after treatment with thalidomide. Augmented angiogenesis in the bone marrow of MM patients was confirmed in the present study. It seems that thalidomide is effective in the treatment of MM through the impairment of angiogenesis by decreasing FGF-2 and VEGF production. This is the first report on pathological evidence in the bone marrow of MM before and after thalidomide treatment, in Japan.
authors.affiliation: Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Du
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hattori
authors.forename: Akinori
authors.initials: A
authors.lastname: Hashiguchi
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kondoh
authors.forename: Nobumichi
authors.initials: N
authors.lastname: Hozumi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Michiie
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Hata
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001798:Blood Proteins / Q000187:drug effects / Q000652:urine; D001853:Bone Marrow / Q000098:blood supply* / Q000187:drug effects; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000187:drug effects; D006801:Humans; D007136:Immunoglobulins / Q000097:blood / Q000187:drug effects / Q000652:urine; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D013792:Thalidomide / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D001798:Blood Proteins; D007136:Immunoglobulins; C009823:M-proteins (Myeloma); D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide