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[小鼠不同组织发生肿瘤中花生四烯酸级联类二十烷酸的合成]

[Synthesis of arachidonic acid cascade eicosanoids in tumors of various histogenesis in mice].

作者信息

Kudriavtsev I A, Miasishcheva N V

出版信息

Vestn Ross Akad Med Nauk. 1995(4):42-5.

PMID:7780341
Abstract

The investigation was undertaken to characterize the profile of arachidonic acid metabolites in different spontaneous and transplantable tumors in mice. The five metabolites via the cyclooxygenase pathway (PGE2, PGF2 alpha, PGD2, TxB2, 6-keto-PGF1 alpha), as well as the three lipoxygenase products (5-HETE, 12-HETE, and 15-HETE) were monitored by thin layer chromatography and high performance liquid chromatography after "ex vivo" metabolism of exogenous [1-C14]-arachidonic acid by homogenates of tumor tissues. It was shown that all tumors had a unique profile of eicosanoids. The most cyclooxygenase activity along with the significant synthesis of PGE2, PGF2 alpha, and 6-keto-PGF1 alpha was noted in lung tumors. The antitumor effect of indomethacin was directly related to the ability of tumors to produce PGE2. On the other hand, there were varying lipoxygenase activities in tumors. In some cases, the extremely high levels of 15- and 12-HETE synthesis in neoplastic tissue could indicate that there was a basic possibility of using lipoxygenase inhibitors for suppressing malignant tumors.

摘要

开展这项研究是为了描绘小鼠不同自发性肿瘤和可移植性肿瘤中花生四烯酸代谢物的概况。通过薄层色谱法和高效液相色谱法,在肿瘤组织匀浆对[1-C14] -花生四烯酸进行“离体”代谢后,监测了经由环氧化酶途径产生的五种代谢物(前列腺素E2、前列腺素F2α、前列腺素D2、血栓素B2、6-酮-前列腺素F1α)以及三种脂氧合酶产物(5-羟基二十碳四烯酸、12-羟基二十碳四烯酸和15-羟基二十碳四烯酸)。结果表明,所有肿瘤都有独特的类花生酸概况。在肺肿瘤中观察到最高的环氧化酶活性以及前列腺素E2、前列腺素F2α和6-酮-前列腺素F1α的显著合成。吲哚美辛的抗肿瘤作用与肿瘤产生前列腺素E2的能力直接相关。另一方面,肿瘤中的脂氧合酶活性各不相同。在某些情况下,肿瘤组织中15-羟基二十碳四烯酸和12-羟基二十碳四烯酸的极高合成水平可能表明,使用脂氧合酶抑制剂抑制恶性肿瘤存在根本可能性。

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