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分化剂N-甲基甲酰胺在小鼠肿瘤系统中的抗肿瘤和抗转移活性。

Antitumor and antimetastatic activity of the differentiating agent N-methylformamide in murine tumor systems.

作者信息

Iwakawa M, Tofilon P J, Hunter N, Stephens L C, Milas L

机构信息

Department of Experimental Radiotherapy, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston 77030.

出版信息

Clin Exp Metastasis. 1987 Oct-Dec;5(4):289-300. doi: 10.1007/BF00120724.

DOI:10.1007/BF00120724
PMID:3665221
Abstract

N-Methylformamide (NMF), a cell-differentiating agent, was assessed for its antitumor activity against a fibrosarcoma (FSA), a hepatocarcinoma (HCA-I) and a mammary carcinoma (MCA-K), syngeneic to C3Hf/Kam mice. Tumors were grown as solitary tumors in the leg or as artificial or spontaneous micrometastases in the lung. NMF, at a dose of 300 mg/kg, was administered i.p. daily for 6 to 18 days. NMF slowed the growth of FSA and HCA-I tumors and totally inhibited the growth of the MCA-K tumor. However, the effect was transient; tumors resumed their pretreatment growth rate upon cessation of the treatment. Histologically, MCA-K tumors treated with NMF (300 mg/kg daily for six days) underwent considerable cell depopulation and reduction in mitotic activity. The number of artificial metastases, as well as the incidence and the number of spontaneous metastases, were markedly reduced by NMF. This resulted in a prolongation of the survival of mice that had artificial metastases of MCA-K tumor. The in vitro clonogenicity of MCA-K, but not of FSA or HCA-I cells, was reduced. However, in vivo reduction of MCA-K cell clonogenicity was minimal, if any. Thus, NMF is effective in restricting the growth of both solitary tumors and metastases, but the degree of response is highly dependent on tumor type.

摘要

N-甲基甲酰胺(NMF)是一种细胞分化剂,对C3Hf/Kam小鼠同基因的纤维肉瘤(FSA)、肝癌(HCA-I)和乳腺癌(MCA-K)进行了抗肿瘤活性评估。肿瘤以腿部孤立肿瘤或肺部人工或自发微转移的形式生长。以300mg/kg的剂量腹腔注射NMF,每天给药,持续6至18天。NMF减缓了FSA和HCA-I肿瘤的生长,并完全抑制了MCA-K肿瘤的生长。然而,这种效果是短暂的;治疗停止后,肿瘤恢复到治疗前的生长速度。组织学上,用NMF治疗的MCA-K肿瘤(每天300mg/kg,持续6天)经历了显著的细胞减少和有丝分裂活性降低。NMF显著减少了人工转移灶的数量以及自发转移灶的发生率和数量。这导致了患有MCA-K肿瘤人工转移灶的小鼠存活期延长。MCA-K细胞的体外克隆形成能力降低,但FSA或HCA-I细胞未出现这种情况。然而,在体内,MCA-K细胞克隆形成能力的降低即使有也是最小的。因此,NMF在限制孤立肿瘤和转移灶的生长方面是有效的,但反应程度高度依赖于肿瘤类型。

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本文引用的文献

1
N-methylformamide: antitumour activity and metabolism in mice.N-甲基甲酰胺:小鼠体内的抗肿瘤活性及代谢
Br J Cancer. 1982 Jun;45(6):843-50. doi: 10.1038/bjc.1982.136.
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Inhibition of the growth of human colon cancer xenografts by polar solvents.极性溶剂对人结肠癌异种移植瘤生长的抑制作用
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Enhancement by N-methylformamide of the effect of ionizing radiation on a human colon tumor xenografted in nude mice.N-甲基甲酰胺对电离辐射作用于裸鼠移植人结肠肿瘤的增强效应。
加速的基因不稳定和休眠:转移细胞耐药性的两种不同原因;临床影响及治疗方法
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N-methylformamide affects spontaneous metastases of 3LL lines and increases natural killer activity of tumor-bearing mice.N-甲基甲酰胺影响3LL细胞系的自发性转移,并增强荷瘤小鼠的自然杀伤活性。
Clin Exp Metastasis. 1990 Mar-Apr;8(2):153-63. doi: 10.1007/BF00117788.
Cancer Res. 1984 Nov;44(11):4942-6.
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The chemosensitivity of a new experimental model--the M5076 reticulum cell sarcoma.一种新的实验模型——M5076网状细胞肉瘤的化学敏感性
Eur J Cancer Clin Oncol. 1984 May;20(5):699-705. doi: 10.1016/0277-5379(84)90019-1.
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Polar solvents: a novel class of antineoplastic agents.极性溶剂:一类新型抗肿瘤药物。
J Clin Oncol. 1984 Mar;2(3):227-41. doi: 10.1200/JCO.1984.2.3.227.
6
Immunologic status of host and response of a methylcholanthrene-induced sarcoma to local x-irradiation.宿主的免疫状态以及甲基胆蒽诱导的肉瘤对局部X线照射的反应。
Cancer. 1970 Jul;26(1):232-8. doi: 10.1002/1097-0142(197007)26:1<232::aid-cncr2820260129>3.0.co;2-d.
7
Immunological resistance to pulmonary metastases in C3Hf-Bu mice bearing syngeneic fibrosarcoma of different sizes.携带不同大小同基因纤维肉瘤的C3Hf-Bu小鼠对肺转移的免疫抗性
Cancer Res. 1974 Jan;34(1):61-71.
8
N-Methylformamide (NSC 3051): a potential candidate for combination chemotherapy.N-甲基甲酰胺(NSC 3051):联合化疗的潜在候选药物。
Eur J Cancer Clin Oncol. 1985 Jun;21(6):745-52. doi: 10.1016/0277-5379(85)90273-1.
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The antitumour effect and toxicity of cis-platinum and N-methylformamide in combination.顺铂与N-甲基甲酰胺联合使用的抗肿瘤作用及毒性
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