(31) P and (1) H MRS of DB-1 melanoma xenografts: lonidamine selectively decreases tumor intracellular pH and energy status and sensitizes tumors to melphalan.
(31) P and (1) H MRS of DB-1 melanoma xenografts: lonidamine selectively decreases tumor intracellular pH and energy status and sensitizes tumors to melphalan.
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DOI：
10.1002/nbm.2824
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发表时间：
2013-01
影响因子：
2.9
通讯作者：
Glickson, Jerry D.
中科院分区：
文献类型：
--
作者：
Nath, Kavindra;Nelson, David S.;Ho, Andrew M.;Lee, Seung-Cheol;Darpolor, Moses M.;Pickup, Stephen;Zhou, Rong;Heitjan, Daniel F.;Leeper, Dennis B.;Glickson, Jerry D.
体内~(31)P磁共振波谱显示，人黑色素瘤移植瘤免疫抑制小鼠注射氯硝胺(LND，100 mg/kg，i.p)。与基线水平相比，细胞内pH(Phi)从6.90±0.05降至6.33±0.10(p<；0.001)，细胞外pH(Phe)从7.00±0.04微降至6.80±0.07(p<；0.001)，生物能(Ntp/PI)单调下降66.8±5.7%(p<；0.001)。在LND治疗后，生物能量学和PHI的下降都持续了至少3小时。LND后20min，肝脏出现短暂的细胞内酸化，pH值单位(p>；0.05)为0.2±0.1pH单位(p>；0.05)，Phe无明显变化，40min时，生物能值有小幅下降，为32.9±10.6%(p>；0.05)。在LND后至少120分钟内，在脑(Phi，BioEnergy tics；p>；0.1)或骨骼肌(Phi，Phe，BioEnergy tics；p>；0.1)中没有检测到Phi或ATP/PI的变化。用具有阿达玛定位的选择性多量子脉冲序列的~1H MRS监测的稳态肿瘤乳酸增加了~3倍(p=0.009)。LND治疗增加了系统性黑色素瘤对马法兰(LPAM；7.5 mg/kg，静脉注射)的反应。其生长延迟时间为19.9±2.0d(肿瘤倍增时间为6.15±0.31 d，log10细胞杀伤为0.975±0.110，细胞杀伤为89.4±2.2%)，而LND为1.1±0.1d，LPAM为4.0±0.0d。研究表明，LND对肿瘤PHi的影响和生物能量学可能使黑色素瘤对pH依赖的药物如烷化剂化疗或热疗增敏。
In vivo 31P MRS demonstrates that human melanoma xenografts in immunosuppressed mice treated with lonidamine (LND, 100 mg/kg, i.p.) exhibit a decrease in intracellular pH (pHi) from 6.90 ± 0.05 to 6.33 ± 0.10 (p < 0.001), a slight decrease in extracellular pH (pHe) from 7.00 ± 0.04 to 6.80 ± 0.07 (p > 0.05), and a monotonic decline in bioenergetics (NTP/Pi) by 66.8 ± 5.7% (p < 0.001) relative to the baseline level. Both bioenergetics and pHi decreases were sustained for at least 3 hr following LND treatment. Liver exhibited a transient intracellular acidification by 0.2 ± 0.1 pH units (p > 0.05) at 20 min post-LND with no significant change in pHe and a small transient decrease in bioenergetics, 32.9 ± 10.6 % (p > 0.05), at 40 min post-LND. No changes in pHi or ATP/Pi were detected in the brain (pHi, bioenergetics; p > 0.1) or skeletal muscle (pHi, pHe, bioenergetics; p > 0.1) for at least 120 min post-LND. Steady-state tumor lactate monitored by 1H MRS with a selective multiquantum pulse sequence with Hadamard localization increased ~3-fold (p = 0.009). Treatment with LND increased systemic melanoma response to melphalan (LPAM; 7.5 mg/kg, i.v.) producing a growth delay of 19.9 ± 2.0 d (tumor doubling time = 6.15 ± 0.31d, log10 cell-kill = 0.975 ± 0.110, cell-kill = 89.4 ± 2.2%) compared to LND alone of 1.1 ± 0.1 d and LPAM alone of 4.0 ± 0.0 d. The study demonstrates that the effects of LND on tumor pHi and bioenergetics may sensitize melanoma to pH-dependent therapeutics such as chemotherapy with alkylating agents or hyperthermia.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
8.8
作者：
McCoy CL;Parkins CS;Chaplin DJ;Griffiths JR;Rodrigues LM;Stubbs M
通讯作者：
Stubbs M
影响因子：
--
作者：
GILLIES, RJ;LIU, Z;BHUJWALLA, Z
通讯作者：
BHUJWALLA, Z
影响因子：
8.4
作者：
JAHDE, E;ROSZINSKI, S;RAJEWSKY, MF
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RAJEWSKY, MF
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DOI：
10.1016/j.bbrc.2008.10.005
发表时间：
2008-12-12
影响因子：
3.1
作者：
Lu, Ying;Pang, Tianxiang;Wakabayashi, Shigeo
通讯作者：
Wakabayashi, Shigeo