The tumor suppressive reagent taurolidine inhibits growth of malignant melanoma - a mouse model
The tumor suppressive reagent taurolidine inhibits growth of malignant melanoma - a mouse model
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DOI：
10.1016/j.jss.2007.01.041
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发表时间：
2007-12-01
影响因子：
2.2
通讯作者：
Hofmann, Maja
中科院分区：
文献类型：
--
作者：
Braumann, Chris;Jacobi, Christoph A.;Hofmann, Maja
背景资料。肿瘤抑制剂牛磺酸核苷(TRD)在体外抑制了30多种细胞系的肿瘤生长，并在动物肿瘤疾病的早期和晚期降低了肿瘤负荷。TRD已被证明在体外可以诱导黑色素瘤细胞凋亡。因此，在小鼠模型上评价了TRD对播散性黑色素瘤的作用。全麻后行正中切开，脾内植入恶性黑色素瘤细胞150万个(B78~D14)，背部植入细胞100万个(C57BL/6)。动物被随机分成两组，分别用1%、2%或3%的TRD腹腔注射(n=40，7天，12小时)或静脉注射(n=40，2天，12小时)，或用林格氏液(对照组)治疗。第28天处死所有动物，由随机双盲调查者测定肿瘤总重量和转移灶个数。IP地址。治疗对总的肿瘤生长有剂量依赖性的抑制作用(P=0.003)，对ip。肿瘤生长(P=0.001)，而皮下(S.C.)对肿瘤生长无明显影响(P=0.132)。对照组。静脉注射。治疗后肿瘤总生长量减少(P=0.013)，肿瘤体积缩小。肿瘤生长(P=0.016)，而腹腔注射。肿瘤负荷量与对照组相比差异无统计学意义(P=0.122)。两个都是IP。和静脉注射。用3%TRD治疗可显著减少转移灶总数。动物体重未受影响。IP地址。和静脉注射。治疗方法以剂量依赖的方式减少小鼠播散性恶性黑色素瘤的总肿瘤重量和转移灶数量。我们令人鼓舞的发现应该在临床研究中得到进一步证实，研究TRD对转移性恶性黑色素瘤患者的影响，这些患者的预后仍然很差。(C)2007 Elsevier Inc.保留所有权利。
Background. The tumor suppressive agent taurolidine (TRD) inhibits tumor growth of more than 30 cell lines in vitro and reduces tumor load in early and advanced stages of neoplastic disease in animals. TRD has been shown to induce apoptosis of melanoma cells in vitro. Therefore, the effects of TRD on disseminated melanoma were evaluated in a mice model.Methods. After general anesthesia, a midline laparotomy was performed and 1.5 million malignant melanoma cells (B78-D14) were applied in the spleen and I million cells at the back (C57BL/6). Animals were randomized and either treated intraperitoneally (i.p., n = 40, 7 days, 12 hourly) or intravenously (i.v., n = 40, 2 days, 12 hourly) with 1%, 2%, or 3% TRD or with Ringer's solution (control group). On day 28, all animals were sacrificed and the total tumor weight and the number of metastatic lesions were determined by two investigators blinded for randomization.Results. The i.p. therapy caused a dose-dependent inhibition of total tumor growth (P = 0.003) and i.p. tumor growth (P = < 0.001), whereas subcutaneous (s.c.) tumor growth was not affected (P = 0.132) compared with the i.p. control group. The i.v. therapy reduced the total tumor growth (P = 0.013) and the s.c. tumor growth (P = 0.016), whereas the i.p. tumor load was not reduced (P = 0.122) compared with the control group. Both i.p. and i.v. therapy with 3% TRD significantly decreased the total number of metastatic lesions. The animal weight was not affected.Conclusions. The i.p. and i.v. therapies reduce total tumor weight and number of metastatic lesions of disseminated malignant melanoma in a dose-dependent fashion in mice. Our encouraging findings should be further confirmed in clinical studies examining the influence of TRD in patients with disseminated malignant melanoma for whom prognosis still remains dismal. (c) 2007 Elsevier Inc. All rights reserved.