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人颅内肿瘤中前列腺素和血栓素的合成

Prostaglandin and thromboxane synthesis by human intracranial tumors.

作者信息

Castelli M G, Chiabrando C, Fanelli R, Martelli L, Butti G, Gaetani P, Paoletti P

机构信息

Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

出版信息

Cancer Res. 1989 Mar 15;49(6):1505-8.

PMID:2493982
Abstract

Prostaglandin (PG) and thromboxane (TX) production by homogenates of human intracranial tumors (33 gliomas, 32 meningiomas, six brain metastases) and "normal" brain (n = 26) from tumor-bearing patients was studied. PGF2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha (the hydrolysis product of PGI2) and TXB2 (the hydrolysis product of TXA2) were determined by high-resolution gas chromatography-mass spectrometry after ex vivo metabolism of endogenous arachidonic acid. Prostanoid profiles (relative abundance of each metabolite) were different for gliomas and meningiomas, but similar for gliomas and their nontumoral counterpart, i.e., "normal" brain. Mean overall prostanoid production was significantly higher in gliomas (539 +/- 95) and meningiomas (523 +/- 69) than in "normal" brain (198 +/- 23). Prostanoid synthesis significantly increased with anaplastic grade (glioblastomas greater than anaplastic astrocytomas greater than slow-growing astrocytomas greater than "normal" brain), while profiles did not substantially change (TXB2 was the most and 6-keto-PGF1 alpha the least abundant product). Meningioma profiles showed no marked prevalence of any particular metabolite and no major differences between histological subgroups. All brain metastases from different carcinomas (n = 5) showed a prevalence of TXB2 and PGE2 and very low PGD2 synthesis.

摘要

研究了来自患肿瘤患者的人类颅内肿瘤(33例胶质瘤、32例脑膜瘤、6例脑转移瘤)和“正常”脑(n = 26)匀浆中前列腺素(PG)和血栓素(TX)的生成情况。内源性花生四烯酸经体外代谢后,通过高分辨率气相色谱 - 质谱法测定前列腺素F2α、前列腺素E2、前列腺素D2、6 - 酮 - 前列腺素F1α(前列环素I2的水解产物)和血栓素B2(血栓素A2的水解产物)。胶质瘤和脑膜瘤的类前列腺素谱(每种代谢产物的相对丰度)不同,但胶质瘤与其非肿瘤对应物,即“正常”脑的类前列腺素谱相似。胶质瘤(539±95)和脑膜瘤(523±69)中的类前列腺素平均总生成量显著高于“正常”脑(198±23)。类前列腺素合成随间变程度显著增加(胶质母细胞瘤>间变性星形细胞瘤>生长缓慢的星形细胞瘤>“正常”脑),而谱图没有实质性变化(血栓素B2含量最高,6 - 酮 - 前列腺素F1α含量最低)。脑膜瘤谱图未显示任何特定代谢产物的明显优势,且组织学亚组之间无重大差异。来自不同癌的所有脑转移瘤(n = 5)均显示血栓素B2和前列腺素E2占优势,且前列腺素D2合成非常低。

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