Monitoring oxygen levels in orthotopic human glioma xenograft following carbogen inhalation and chemotherapy by implantable resonator-based oximetry.
Monitoring oxygen levels in orthotopic human glioma xenograft following carbogen inhalation and chemotherapy by implantable resonator-based oximetry.
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DOI：
10.1002/ijc.29132
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发表时间：
2015-04-01
影响因子：
6.4
通讯作者：
Khan, Nadeem
中科院分区：
文献类型：
--
作者：
Hou, Huagang;Nemani, Venkata Krishnamurthy;Du, Gaixin;Montano, Ryan;Song, Rui;Gimi, Barjor;Swartz, Harold M.;Eastman, Alan;Khan, Nadeem
缺氧是胶质瘤的重要标志，并显著影响治疗效果。不幸的是，用于监测神经胶质瘤pO 2，以促进翻译研究的技术是缺乏的。此外，恶性胶质瘤，特别是多形性胶质母细胞瘤患者的预后差，需要有效的策略，可以抑制缺氧和改善治疗结果。使用植入式谐振器的EPR血氧仪用于监测小鼠正常脑组织和U251胶质瘤中的pO 2。在正常脑和胶质瘤异种移植物中测试呼吸碳原（95%O2 + 5%CO2）的高氧。还研究了通过合理组合吉西他滨和细胞周期检查点抑制剂MK-8776来抑制胶质瘤生长的新策略。正常小鼠脑组织中左右半球的平均pO 2约为56 ~ 69 mmHg。在测量的第1天和第5天，U251胶质瘤的平均基线pO 2分别为21.9 ± 3.7和14.1 ± 2.4 mmHg。平均脑pO 2（包括胶质瘤）在吸入carbogen后至少增加100%，尽管动物之间的反应在几天内有所不同。通过MRI评估，吉西他滨+ MK-8776治疗显著增加pO 2并抑制胶质瘤生长。总之，植入式共振器的EPR血氧饱和度可以用于监测卡波津吸入和化疗对小鼠原位胶质瘤的疗效。呼吸卡波津提高小鼠脑胶质瘤pO 2可用于改善治疗效果。吉西他滨+ MK-8776治疗是一种有前景的策略，值得进一步研究。
Hypoxia is a critical hallmark of glioma, and significantly compromises treatment efficacy. Unfortunately, techniques for monitoring glioma pO2 to facilitate translational research are lacking. Furthermore, poor prognoses of patients with malignant glioma, in particular glioblastoma multiforme, warrant effective strategies that can inhibit hypoxia and improve treatment outcome. EPR oximetry using implantable resonators was implemented for monitoring pO2 in normal cerebral tissue and U251 glioma in mice. Breathing carbogen (95% O2 + 5% CO2) was tested for hyperoxia in the normal brain and glioma xenografts. A new strategy to inhibit glioma growth by rationally combining gemcitabine and MK-8776, a cell cycle checkpoint inhibitor, was also investigated. The mean pO2 of left and right hemisphere were approximately 56 – 69 mmHg in the normal cerebral tissue of mice. The mean baseline pO2 of U251 glioma on the first and fifth day of measurement was 21.9 ± 3.7 and 14.1 ± 2.4 mmHg, respectively. The mean brain pO2 including glioma increased by at least 100% on carbogen inhalation, although the response varied between the animals over days. Treatment with gemcitabine + MK-8776 significantly increased pO2 and inhibited glioma growth assessed by MRI. In conclusion, EPR oximetry with implantable resonators can be used to monitor the efficacy of carbogen inhalation and chemotherapy on orthotopic glioma in mice. The increase in glioma pO2 of mice breathing carbogen can be used to improve treatment outcome. The treatment with gemcitabine + MK-8776 is a promising strategy that warrants further investigation.
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影响因子：
3.8
作者：
Montano R;Thompson R;Chung I;Hou H;Khan N;Eastman A
通讯作者：
Eastman A
影响因子：
3.3
作者：
Ashkanian, M.;Borghammer, P.;Vafaee, M.
通讯作者：
Vafaee, M.
影响因子：
3.9
作者：
Fabi, Alessandra;Mirri, Alessandra;Carapella, Carmine Maria
通讯作者：
Carapella, Carmine Maria
影响因子：
5.7
作者：
Montano R;Chung I;Garner KM;Parry D;Eastman A
通讯作者：
Eastman A
影响因子：
5.6
作者：
Jordan BF;Sonveaux P
通讯作者：
Sonveaux P