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锰超氧化物歧化酶作为人类疾病生物标志物的功能作用以及一种新型人类重组锰超氧化物歧化酶亚型的治疗潜力。

The functional role of MnSOD as a biomarker of human diseases and therapeutic potential of a new isoform of a human recombinant MnSOD.

作者信息

Borrelli Antonella, Schiattarella Antonietta, Bonelli Patrizia, Tuccillo Franca Maria, Buonaguro Franco Maria, Mancini Aldo

机构信息

Molecular Biology and Viral Oncology Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione G. Pascale"-IRCCS, Naples, Italy.

出版信息

Biomed Res Int. 2014;2014:476789. doi: 10.1155/2014/476789. Epub 2014 Jan 6.

Abstract

Reactive oxygen species (ROS) are generated as a consequence of metabolic reactions in the mitochondria of eukaryotic cells. This work describes the role of the manganese superoxide dismutase (MnSOD) as a biomarker of different human diseases and proposes a new therapeutic application for the prevention of cancer and its treatment. The paper also describes how a new form of human MnSOD was discovered, its initial application, and its clinical potentials. The MnSOD isolated from a human liposarcoma cell line (LSA) was able to kill cancer cells expressing estrogen receptors, but it did not have cytotoxic effects on normal cells. Together with its oncotoxic activity, the recombinant MnSOD (rMnSOD) exerts a radioprotective effect on normal cells irradiated with X-rays. The rMnSOD is characterized by the presence of a leader peptide, which allows the protein to enter cells: this unique property can be used in the radiodiagnosis of cancer or chemotherapy, conjugating radioactive substances or chemotherapic drugs to the leader peptide of the MnSOD. Compared to traditional chemotherapic agents, the drugs conjugated with the leader peptide of MnSOD can selectively reach and enter cancer cells, thus reducing the side effects of traditional treatments.

摘要

活性氧(ROS)是真核细胞线粒体代谢反应的产物。这项工作描述了锰超氧化物歧化酶(MnSOD)作为不同人类疾病生物标志物的作用,并提出了预防癌症及其治疗的新治疗应用。该论文还描述了一种新型人类MnSOD的发现过程、其初步应用及其临床潜力。从人脂肪肉瘤细胞系(LSA)中分离出的MnSOD能够杀死表达雌激素受体的癌细胞,但对正常细胞没有细胞毒性作用。重组MnSOD(rMnSOD)除了具有致癌毒性活性外,还对受X射线照射的正常细胞具有辐射保护作用。rMnSOD的特征是存在一个前导肽,该前导肽可使蛋白质进入细胞:这种独特特性可用于癌症的放射诊断或化疗,即将放射性物质或化疗药物与MnSOD的前导肽结合。与传统化疗药物相比,与MnSOD前导肽结合的药物可以选择性地到达并进入癌细胞,从而减少传统治疗的副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3afc/3913005/8cd5b43cd84a/BMRI2014-476789.001.jpg

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