Characterization of breast cancers and therapy response by MRS and quantitative gene expression profiling in the choline pathway.
Characterization of breast cancers and therapy response by MRS and quantitative gene expression profiling in the choline pathway.
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DOI：
10.1002/nbm.1318
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发表时间：
2009-01
影响因子：
2.9
通讯作者：
Gillies, Robert J.
中科院分区：
文献类型：
--
作者：
Morse, David L.;Carroll, Danielle;Day, Sam;Gray, Heather;Sadarangani, Pooja;Murthi, Shiva;Job, Constantin;Baggett, Brenda;Raghunand, Natarajan;Gillies, Robert J.
肿瘤胆碱代谢物有可能用作乳腺癌进展的诊断指标，并且可以通过磁共振波谱在体内进行无创监测。1H MRS检测到的31P MR可见磷酸单酯峰（~3.9 ppm）和总胆碱代谢物峰（~3.2 ppm）在人乳腺肿瘤中均升高。如肿瘤提取物研究所确定的，这些峰的主要诊断成分是磷酸胆碱（PCo），膜磷脂的生物合成前体，磷脂酰胆碱（PtdCho）。在人乳腺细胞提取物中，PCo和PtdCho分解产物甘油磷酸胆碱在转移潜能增加的细胞系中逐渐增加。在体内分辨和定量PCho的能力将提高这种假定的诊断工具的精度。此外，确定这些代谢紊乱的生化机制将提高对转移性癌症的理解，并可能为药物开发提供潜在的分子靶点。本文报道的是通过图像引导的31P MR光谱法在SCID小鼠的乳腺癌异种移植模型中对PCho的体内分辨率和定量，定位于小的体素。还报道了增加癌症进展的乳腺癌细胞中的细胞溶质和脂质代谢物的定量，以及根据癌症侵袭性程度鉴定细胞系之间不同的代谢物。这些代谢差异与胆碱代谢途径的基因表达差异相关。紫杉烷治疗后的基因表达变化也与先前报道的相同肿瘤模型中相同治疗后胆碱代谢物的变化相关。解释代谢变化的生物化学模型进行了讨论。
Tumor choline metabolites have potential for use as diagnostic indicators of breast cancer progression and can be non-invasively monitored in vivo by magnetic resonance spectroscopy. Both a 31P MR visible phosphomonoester peak (~3.9 ppm) and a total choline metabolite peak (~3.2 ppm) detected by 1H MRS are elevated in human breast tumors. As determined by tumor extract studies, the principle diagnostic component of these peaks is phosphocholine (PCho), the biosynthetic precursor to the membrane phospholipid, phosphatidylcholine (PtdCho). In extracts of human breast cells, PCho and the PtdCho breakdown product, glycerophosphocholine, are incrementally increased in cell lines of increasing metastatic potential. The ability to resolve and quantify PCho in vivo would improve the precision of this putative diagnostic tool. Additionally, determining the biochemical mechanisms underlying these metabolic perturbations will improve the understanding of metastatic cancer and could suggest potential molecular targets for drug development. Reported herein is the in vivo resolution and quantification of PCho in a breast cancer xenograft model in SCID mice via image-guided 31P MR spectroscopy, localized to small voxels. Also reported is the quantification of cytosolic and lipid metabolites in breast cancer cells of increasing cancer progression, and the identification of metabolites that differ amongst cell lines by degree of cancer aggressiveness. These metabolic differences are correlated with differences in expression of genes of the choline metabolic pathway. Gene expression changes following taxane therapy are also correlated with previously reported changes in choline metabolites following the same therapy in the same tumor model. Biochemical models explaining the metabolic changes are discussed.
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影响因子：
2.2
作者：
CONNELLY, A;COUNSELL, C;ORDIDGE, RJ
通讯作者：
ORDIDGE, RJ
DOI：
10.1016/s0005-2760(97)00118-5
发表时间：
1997-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM
影响因子：
--
作者：
Ishidate, K
通讯作者：
Ishidate, K
影响因子：
6.4
作者：
Eliyahu, Galit;Kreizman, Tamar;Degani, Hadassa
通讯作者：
Degani, Hadassa
影响因子：
11.2
作者：
Glunde, K;Jie, C;Bhujwalla, ZM
通讯作者：
Bhujwalla, ZM
影响因子：
3.9
作者：
Kim, JK;Park, SH;Kim, OD
通讯作者：
Kim, OD