Tumor pO₂ as a surrogate marker to identify therapeutic window during metronomic chemotherapy of 9L gliomas.
Tumor pO₂ as a surrogate marker to identify therapeutic window during metronomic chemotherapy of 9L gliomas.
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DOI：
10.1007/978-1-4419-7756-4_15
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发表时间：
2011
影响因子：
--
通讯作者：
Khan, Nadeem
中科院分区：
文献类型：
--
作者：
Mupparaju, Sriram;Hou, Huagang;Lariviere, Jean P.;Swartz, Harold M.;Khan, Nadeem
胶质母细胞瘤是侵袭性和高度血管化的原发性脑肿瘤，5年生存率低于10%。抗血管生成的方法正在研究这种致命的恶性肿瘤的潜在治疗效益。然而，缺乏合适的标记物，可用于监测治疗过程中的治疗效果，限制了他们的优化。我们专注于开发肿瘤pO 2作为替代标志物，以确定抗血管生成方法（如节拍化疗）的治疗窗口。我们报告了化疗药物环磷酰胺（140 mg/Kg，i.p）每周4次给药对SCID小鼠皮下9 L肿瘤pO 2和生长的影响。使用体内EPR血氧测定法重复测量肿瘤pO 2。皮下9 L肿瘤缺氧，第0天处理前肿瘤pO 2为5.1 ± 1 mmHg，肿瘤体积为236 ± 45 mm 3。第10天，肿瘤pO 2显著升高至26.2 ± 2 mmHg，并在每周环磷酰胺治疗期间保持在升高水平直至第31天。第43天，肿瘤pO 2下降至20 ± 9 mmHg。对照组的肿瘤体积显著增加，肿瘤pO 2在几天内没有变化。结果表明，在9 L胶质瘤的节拍化疗期间，肿瘤pO 2短暂增加，并且可能用作节拍化疗期间识别血管正常化的标志物。使用EPR血氧测定法非侵入性地识别治疗窗口的能力可能对临床方案的优化具有显著影响。体内EPR血氧测定法目前正在浅表肿瘤患者中进行重复pO 2测量。
Glioblastomas are aggressive and highly vascularized primary brain tumors with a 5-year survival rate of less than 10%. Anti-angiogenic approaches are being investigated for potential therapeutic benefits for this fatal malignancy. However, lack of suitable markers that can be used to monitor therapeutic effects during such treatments has restricted their optimization. We have focused on the development of tumor pO2 as a surrogate marker to identify therapeutic window during anti-angiogenic approaches, such as metronomic chemotherapy. We report the effect of four weekly administrations of cyclophosphamide (140 mg/Kg, i.p), a chemo drug, on tumor pO2 and growth of subcutaneous 9L tumors in SCID mice. The repeated measurement of tumor pO2 was carried out using in vivo EPR oximetry. The subcutaneous 9L tumors were hypoxic with a pre-treatment tumor pO2 of 5.1 ± 1 mmHg and a tumor volume of 236 ± 45 mm3 on day 0. The tumor pO2 increased significantly to 26.2 ± 2 mmHg on day 10, and remained at an elevated level till day 31 during weekly treatments with cyclophosphamide. The tumor pO2 then declined to 20 ± 9 mmHg on day 43. The tumor volume of the control group increased significantly with no change in tumor pO2 over days. Results indicate a transient increase in tumor pO2 during metronomic chemotherapy of 9L gliomas and could be potentially used as a marker to identify vessel normalization during metronomic chemotherapy. The ability to identify therapeutic window non-invasively using EPR oximetry could have a significant impact on the optimization of clinical protocols. In vivo EPR oximetry is currently being tested for repeated pO2 measurements in patients with superficial tumors.
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影响因子：
3.5
作者：
Swartz, HM;Clarkson, RB
通讯作者：
Clarkson, RB
影响因子：
3.4
作者：
Hou, Huagang;Khan, Nadeem;Swartz, Harold M.
通讯作者：
Swartz, Harold M.
影响因子：
5.7
作者：
Hou, Huagang;Lariviere, Jean P.;Khan, Nadeem
通讯作者：
Khan, Nadeem
DOI：
10.1124/jpet.106.118265
发表时间：
2007-04-01
影响因子：
3.5
作者：
Zhou, Qingyu;Guo, Ping;Gallo, James M.
通讯作者：
Gallo, James M.
影响因子：
4
作者：
Buckner, JC
通讯作者：
Buckner, JC