Du Wenlin, Hattori Yutaka, Hashiguchi Akinori, Kondoh Kensuke, Hozumi Nobumichi, Ikeda Yasuo, Sakamoto Michiie, Hata Jun-ichi, Yamada Taketo
Department of Pathology, Keio University School of Medicine, Tokyo, Japan.
Pathol Int. 2004 May;54(5):285-94. doi: 10.1111/j.1440-1827.2004.01622.x.
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.
实体瘤中的血管生成对肿瘤的生长、侵袭和转移至关重要。最近，有人提出血管生成在包括白血病和多发性骨髓瘤在内的造血系统恶性肿瘤的发展中起一定作用。我们通过计算从51例未经治疗的多发性骨髓瘤（MM）或意义未明的单克隆丙种球蛋白病（MGUS）患者的针吸活检标本中的微血管密度（MVD），评估了MM患者骨髓（BM）中的肿瘤血管生成情况。计算了移植供体和非血液系统疾病患者骨髓中的MVD作为对照。MM患者骨髓中的MVD明显增加，且在未经治疗的MM病例中，MVD与骨髓瘤细胞对骨髓的侵袭程度相关。最近有报道称沙利度胺可能对MM治疗有效。我们评估了沙利度胺对11例难治性MM患者骨髓血管生成的影响。11例患者中有7例在沙利度胺治疗后血清或尿液中的M蛋白浓度至少降低了30%，其中7例中的3例骨髓中的MVD因沙利度胺而降低。在所有11例患者服用沙利度胺前均观察到血浆碱性成纤维细胞生长因子（FGF - 2）和血管内皮生长因子（VEGF）浓度升高，治疗后这两种水平均降低。本研究证实了MM患者骨髓中血管生成增加。沙利度胺似乎通过降低FGF - 2和VEGF的产生来损害血管生成，从而对MM治疗有效。这是日本关于沙利度胺治疗前后MM患者骨髓病理证据的首次报告。
