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囊性恶性脑肿瘤的囊液:肿瘤细胞的营养物质储存库,包括类生长因子营养物质

Cyst Fluid From Cystic, Malignant Brain Tumors: A Reservoir of Nutrients, Including Growth Factor-Like Nutrients, for Tumor Cells.

作者信息

Dahlberg Daniel, Struys Eduard A, Jansen Erwin E, Mørkrid Lars, Midttun Øivind, Hassel Bjørnar

机构信息

Department of Neurosurgery, Oslo University Hospital and University of Oslo, Oslo, Norway.

Metabolic Unit, Clinical Chemistry, VUmc Medical Center, HV Amsterdam, The Netherlands.

出版信息

Neurosurgery. 2017 Jun 1;80(6):917-924. doi: 10.1093/neuros/nyw101.

Abstract

BACKGROUND

Brain tumors may have cysts, whose content of nutrients could influence tumor cell microenvironment and growth.

OBJECTIVE

To measure nutrients in cyst fluid from glioblastoma multiforme (GBM) and metastatic brain tumors.

METHODS

Quantification of nutrients in cyst fluid from 12 to 18 GBMs and 4 to 10 metastatic brain tumors.

RESULTS

GBM cysts contained glucose at 2.2 mmol/L (median value; range <0.8-3.5) and glutamine at 1.04 mmol/L (0.17-4.2). Lactate was 7.1 mmol/L (2.4-12.5) and correlated inversely with glucose level (r = -0.77; P < .001). Amino acids, including glutamate, varied greatly, but median values were similar to previously published serum values. Ammonia was 75 μmol/L (11-241). B vitamins were present at previously published serum values, and riboflavin, nicotinamide, pyridoxal 5΄-phosphate, and cobalamin were higher in cyst fluid than in cerebrospinal fluid. Inorganic phosphate was 1.25 mmol/L (0.34-3.44), which was >3 times higher than in ventricular cerebrospinal fluid: 0.35 mmol/L (0.22-0.66; P < .001). Tricarboxylic acid cycle intermediates were in the low micromolar range, except for citrate, which was 240 μmol/L (140-590). In cystic metastatic malignant melanomas and lung tumors values were similar to those in GBMs.

CONCLUSION

Tumor cysts may be a nutrient reservoir for brain tumors, securing tumor energy metabolism and synthesis of cell constituents. Serum is one likely source of cyst fluid nutrients. Nutrient levels in tumor cyst fluid are highly variable, which could differentially stimulate tumor growth. Cyst fluid glutamate, lactate, and phosphate may act as tumor growth factors; these compounds have previously been shown to stimulate tumor growth at concentrations found in tumor cyst fluid.

摘要

背景

脑肿瘤可能含有囊肿,其营养成分会影响肿瘤细胞的微环境和生长。

目的

测量多形性胶质母细胞瘤(GBM)和脑转移瘤囊液中的营养物质。

方法

对12至18个GBM和4至10个脑转移瘤的囊液中的营养物质进行定量分析。

结果

GBM囊肿中葡萄糖含量为2.2 mmol/L(中位数;范围<0.8 - 3.5),谷氨酰胺含量为1.04 mmol/L(0.17 - 4.2)。乳酸含量为7.1 mmol/L(2.4 - 12.5),且与葡萄糖水平呈负相关(r = -0.77;P <.001)。包括谷氨酸在内的氨基酸含量差异很大,但中位数与先前发表的血清值相似。氨含量为75 μmol/L(11 - 241)。B族维生素含量与先前发表的血清值一致,且囊液中核黄素、烟酰胺、5΄-磷酸吡哆醛和钴胺素的含量高于脑脊液。无机磷酸盐含量为1.25 mmol/L(0.34 - 3.44),比脑室脑脊液中的含量高3倍以上:0.35 mmol/L(0.22 - 0.66;P <.001)。三羧酸循环中间产物处于低微摩尔范围,除了柠檬酸盐为240 μmol/L(140 - 590)。囊性转移性恶性黑色素瘤和肺肿瘤中的值与GBM中的相似。

结论

肿瘤囊肿可能是脑肿瘤的营养储存库,保障肿瘤的能量代谢和细胞成分的合成。血清可能是囊液营养物质的一个来源。肿瘤囊液中的营养水平高度可变,这可能会对肿瘤生长产生不同的刺激。囊液中的谷氨酸、乳酸和磷酸盐可能作为肿瘤生长因子;先前已证明这些化合物在肿瘤囊液中发现的浓度下可刺激肿瘤生长。

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