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在局部肿瘤治疗中给予最佳剂量的L-精氨酸

Administering the Optimum Dose of l-Arginine in Regional Tumor Therapy.

作者信息

Moawad Emad Y

机构信息

Faculty of Engineering, Ain Shams University, Cairo, Egypt ; 217 Alhegaz Street, Alnozha, Cairo, 11351 Egypt.

出版信息

Indian J Clin Biochem. 2014 Oct;29(4):442-51. doi: 10.1007/s12291-013-0379-z. Epub 2013 Sep 15.

Abstract

The purpose of this study is optimizing the l-arginine (l-Arg) doses on the basis of chemical structure in regional accessible tumor therapy to settle down a new protocol for the treatment of cancer. (3)H-thymidine-based cell proliferation assay was performed in vitro on tumor cell lines of fibrosarcoma (FS), lymphosarcoma-ascitic and on normal cell line of NIH 3T3 after treatment with different concentrations of l-Arg in phosphate buffered saline (PBS). The cultures were harvested after 22 h and the incorporated radioactivity was counted to identify their histologic grades as described in earlier studies. In vivo therapy of murine tumors was conducted where FS cells injected subcutaneously at ventro-lateral position of mice. Various drug delivery schedules were injected into the centre of tumor base, once a day for 4 days. Tumor diameter and survivals were monitored where the day of sacrifice was considered for monitoring the survival period. By identifying the histologic grades of the treated cultures in vitro and in vivo by different concentrations of l-Arg, the corresponding energy of such concentrations were determined. An efficient model with a good fit (R(2) = 0.98) was established to describe the energy yield by l-Arg dose. The equivalence between the tumor histologic grade and energy of the l-Arg dose delivered in saline (PBS) environment is the optimum condition for regional tumor therapy achieves higher survival rate. The selective cytotoxicity to tumor cells with minimal damage to normal cells by l-Arg due to its chemical structure suggests to be considered the most promising drug for regional therapy of the accessible tumors like breast cancers of early stage with no distant metastasis.

摘要

本研究的目的是在区域可及性肿瘤治疗中,基于化学结构优化L-精氨酸(L-Arg)剂量,以制定一种新的癌症治疗方案。在用不同浓度的L-Arg于磷酸盐缓冲盐水(PBS)中处理后,对纤维肉瘤(FS)、腹水型淋巴肉瘤的肿瘤细胞系以及NIH 3T3正常细胞系进行了基于(3)H-胸腺嘧啶核苷的体外细胞增殖测定。22小时后收获培养物,并对掺入的放射性进行计数,以按照早期研究中所述确定其组织学分级。对小鼠肿瘤进行体内治疗,将FS细胞皮下注射到小鼠腹侧位置。将各种给药方案注射到肿瘤基部中心,每天一次,共4天。监测肿瘤直径和存活率,将处死日视为监测存活期。通过确定不同浓度L-Arg在体外和体内处理的培养物的组织学分级,确定了这些浓度相应的能量。建立了一个拟合良好(R(2) = 0.98)的有效模型来描述L-Arg剂量产生的能量。在盐水(PBS)环境中肿瘤组织学分级与L-Arg剂量能量之间的等效性是区域肿瘤治疗实现更高存活率的最佳条件。L-Arg因其化学结构对肿瘤细胞具有选择性细胞毒性,对正常细胞的损伤最小,这表明它被认为是治疗早期无远处转移的可及性肿瘤(如乳腺癌)的最有前景的药物。

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