The effect of blood flow modification on intra- and extracellular pH measured by 31P magnetic resonance spectroscopy in murine tumours.
The effect of blood flow modification on intra- and extracellular pH measured by 31P magnetic resonance spectroscopy in murine tumours.
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DOI：
10.1038/bjc.1995.431
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发表时间：
1995-10
影响因子：
8.8
通讯作者：
Stubbs M
中科院分区：
文献类型：
--
作者：
McCoy CL;Parkins CS;Chaplin DJ;Griffiths JR;Rodrigues LM;Stubbs M
内和细胞外的pH值（pHi和pHe），同时测量的31 P磁共振波谱（MRS）在CaNT肿瘤的血流修改之前和之后。修饰前，pHi为7.1 +/- 0.09（n = 11），pHe [用MRS可见的细胞外标记物3-氨基丙基膦酸酯（3-APP）测量]为6.7 +/- 0.05（n = 8）。化学位移成像和局部MRS实验表明，3-APP信号仅来自肿瘤，而不是周围组织。在通过血管闭塞进行修饰后，与肿瘤是否保持在室温（22-24摄氏度）或保持温暖（33-35摄氏度）无关，pHi和pHe均降低，其中pHi降低的程度更大。使用黄酮乙酸（FAA）作为血流调节剂发现了类似的结果;九个肿瘤中只有四个对FAA有反应。伴随着修饰后pH梯度的降低，腺嘌呤核苷酸的磷酸化状态降低，其通过MRS或肿瘤提取物中的[ATP]/[ADP][P（i）]测量为ATP/Pi。这些结果表明，依赖于跨膜pH梯度的化疗药物的细胞内摄取在由于血管关闭而造成缺血的细胞中不会增强。
Intra- and extracellular pH (pHi and pHe) were measured simultaneously by 31P magnetic resonance spectroscopy (MRS) in CaNT tumours before and after blood flow modification. Before modification, pHi was 7.1 +/- 0.09 (n = 11) and pHe [measured with an MRS-visible extracellular marker, 3-aminopropyl phosphonate (3-APP)] was 6.7 +/- 0.05 (n = 8). Chemical shift imaging and localised MRS experiments showed that the 3-APP signal was only from the tumour, not surrounding tissue. After modification by vascular occlusion, independent of whether tumours were maintained at room temperature (22-24 degrees C) or kept warm (33-35 degrees C), there was a decrease in pHi and pHe with pHi decreasing to a greater extent. Qualitatively similar results were found using flavone acetic acid (FAA) as a blood flow modifier; only four out of nine tumours responded to FAA. Concomitant with the reduction of the pH gradient after modification was a decrease in the phosphorylation state of the adenine nucleotides measured either as ATP/Pi by MRS or [ATP]/[ADP][P(i)] in tumour extracts. These results indicate that the intracellular uptake of chemotherapeutic drugs which are dependent on the transmembrane pH gradient will not be enhanced in cells made ischaemic as a result of vascular shutdown.
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影响因子：
8.8
作者：
Stubbs, M;Rodrigues, L M;Griffiths, J R
通讯作者：
Griffiths, J R
DOI：
10.1073/pnas.80.9.2748
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
PRICHARD, JW;ALGER, JR;SHULMAN, RG
通讯作者：
SHULMAN, RG
DOI：
10.1073/pnas.81.20.6496
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
EVELHOCH, JL;SAPARETO, SA;ACKERMAN, JJH
通讯作者：
ACKERMAN, JJH
影响因子：
--
作者：
GILLIES, RJ;LIU, Z;BHUJWALLA, Z
通讯作者：
BHUJWALLA, Z
影响因子：
2.9
作者：
NEGENDANK, W
通讯作者：
NEGENDANK, W