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在环磷酰胺和酵母多糖联合治疗的小鼠淋巴肉瘤模型中组织蛋白酶B、L和D活性的调节

Regulation of activity of cathepsins B, L, and D in murine lymphosarcoma model at a combined treatment with cyclophosphamide and yeast polysaccharide.

作者信息

Khalikova Tatyana A, Zhanaeva Svetlana Ya, Korolenko Tatyana A, Kaledin Vassilij I, Kogan Grigorij

机构信息

Institute of Physiology, Siberian Branch of Russian Academy of Medical Sciences, 630117 Novosibirsk, Russia.

出版信息

Cancer Lett. 2005 Jun 1;223(1):77-83. doi: 10.1016/j.canlet.2004.10.028. Epub 2004 Dec 7.

Abstract

Changes in the activity of cysteine (cathepsins B and L) and aspartyl (cathepsin D) proteases were investigated at the development of susceptible and resistant variants of murine lymphosarcoma (LS). It has been demonstrated that the variant resistant to the cyclophosphamide treatment is characterized by a lower activity of all three cathepsins in the tumor tissue. Application of a higher dose of cyclophosphamide led to a more pronounced increase of the studied enzymatic activity in mice with a resistant variant of LS, than in those with a susceptible one. Administration of a yeast polysaccharide derivative - sulfoethyl glucan - enhanced therapeutic effect of cyclophosphamide in mice with both variants of LS, while the most efficient dose was found to be that of 10mg/kg body mass. In the intact mice, usage of both cyclophosphamide and sulfoethyl glucan led to a similar increase of the cathepsins activity in liver and spleen.

摘要

在小鼠淋巴肉瘤(LS)敏感和抗性变体的发展过程中,研究了半胱氨酸蛋白酶(组织蛋白酶B和L)和天冬氨酸蛋白酶(组织蛋白酶D)活性的变化。已证明,对环磷酰胺治疗有抗性的变体在肿瘤组织中所有三种组织蛋白酶的活性较低。与敏感变体的小鼠相比,应用更高剂量的环磷酰胺导致具有抗性变体的LS小鼠中所研究的酶活性有更明显的增加。给予酵母多糖衍生物——磺基乙基葡聚糖——可增强环磷酰胺对两种LS变体小鼠的治疗效果,而最有效的剂量为10mg/kg体重。在未受影响的小鼠中,使用环磷酰胺和磺基乙基葡聚糖均导致肝脏和脾脏中组织蛋白酶活性有类似的增加。

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