Tumor angiogenesis in the bone marrow of multiple myeloma patients and its alteration by thalidomide treatment
Tumor angiogenesis in the bone marrow of multiple myeloma patients and its alteration by thalidomide treatment
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DOI：
10.1111/j.1440-1827.2004.01622.x
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发表时间：
2004-05-01
影响因子：
2.2
通讯作者：
Yamada, T
中科院分区：
文献类型：
--
作者：
Du, WL;Hattori, Y;Yamada, T
血管生成在实体瘤的生长、侵袭和转移中起重要作用。近年来研究表明，血管生成在造血系统恶性肿瘤（包括白血病和多发性骨髓瘤）的发生发展中起一定作用。我们通过计算51例未经治疗的多发性骨髓瘤（MM）或意义不明的单克隆丙种球蛋白病（MGUS）的穿刺活检标本中的微血管密度（MVD），评估了多发性骨髓瘤（MM）患者骨髓（BM）中的肿瘤血管生成。计算移植供者和非血液病患者骨髓中的MVD作为对照。MM患者骨髓中MVD明显增高，且MVD与MM患者骨髓中骨髓瘤细胞浸润程度相关。最近有报道说，沙利度胺可能是有效的治疗MM。我们评估了沙利度胺对血管生成的影响，在BM治疗11例难治性MM。在血清或尿液中的M-蛋白的浓度的11例患者中的7例沙利度胺治疗后，至少减少了30%，并在BM中的MVD减少了这7例中的3例反应沙利度胺。在沙利度胺给药前，所有11例患者的碱性成纤维细胞生长因子（FGF-2）和血管内皮生长因子（VEGF）血浆浓度均升高，沙利度胺治疗后，这两种水平均降低。本研究证实MM患者骨髓中血管生成增强。沙利度胺似乎通过减少FGF-2和VEGF的产生而损害血管生成，从而有效治疗MM。这是日本首次报告沙利度胺治疗前后MM骨髓中的病理学证据。
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.