HYPEROXIC RESPIRATORY CHALLENGES TO MONITOR CHEMOTHERAPY EFFECTS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 背景：当肿瘤处于低氧状态时，对肿瘤治疗的反应，如放射治疗、化疗和光动力治疗效果较差。高氧气体干预已被证明可以改善肿瘤的氧合。在此，我们报道了在顺铂治疗BRCA1和P53基因有条件失活的自发性乳腺肿瘤的过程中，氧气干预引起的血流动力学变化与肿瘤反应之间的关系。 材料和方法：对BRCA1/P53基因敲除小鼠(n=8)乳腺肿瘤给予顺铂1.2 mg/kg，每天1次，连续1周，观察治疗过程中肿瘤体积和体重的变化。我们使用光学成像系统对化疗期间的肿瘤进行成像，该系统通过将空间调制的近红外(NIR)光(650 nm到980 nm)投射到组织上并计算氧(OHB)、脱氧(RHB)、总血红蛋白(THB)浓度、组织氧饱和度(StO2)值和所有波长的散射值来量化内在光散射和吸收。在成像过程中，动物用1.5%异氟醚麻醉，每只动物吸入医用空气(33%O2)6min，然后再吸入100%氧气12min。 结果：8个肿瘤中，5个肿瘤(体积=0.38±0.1)对顺铂治疗有效，3个肿瘤(体积=0.56±0.12)对顺铂治疗无效。在氧气干预期间，对顺铂有反应的肿瘤的[OHB]和[RHB]比无反应的肿瘤增加了2倍以上(p&lt；0.05)。(图1)有反应者和无反应者之间的肿瘤大小变化(数据未显示)也有显著差异。 讨论：乳腺癌在其分子特征和治疗反应上是不同的。化疗期间高氧气体介入结合本征信号光学成像可用于评价血管反应性。我们的初步结果表明，OHB和RHB反应性肿瘤对顺铂化疗的反应明显更大。这一通用方法可以扩展到其他肿瘤治疗模式，并可以很容易地翻译到患者身上。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Background: Response to cancer treatments such as radiotherapy, chemotherapy, and photodynamic therapy are less effective when tumors are hypoxic. Hyperoxic gas intervention has been shown to improve tumor oxygenation. Here we report how hemodynamic changes due to oxygen intervention are related to the tumor response during cisplatin treatment of spontaneous mammary tumors developed in mice with conditional inactivation of the Brca1 and p53 genes. Materials and Methods: We treated mammary tumors in Brca1/p53 knockout mice (n=8) with 1.2mg/kg of Cisplatin (i. p. daily for a week), and tumor volume and body weight were monitored during treatment. We imaged tumors during chemotherapy using an optical imaging system that quantifies intrinsic light scattering and absorption by projecting spatially modulated, near infrared (NIR) light (650nm to 980nm) onto tissues and calculating oxy-(OHb), deoxy-(RHb), total hemoglobin (THb) concentrations, tissue oxygen saturation (StO2) values, and scattering values at all wavelengths. During imaging, animals were anesthetized using 1.5% isoflurane and each animal inhaled medical air (33% O2) for 6 min followed by 100% oxygen for an additional 12 min. Results: Among 8 tumors, 5 (volume=0.38¿0.1) showed response to Cisplatin treatment while the other 3 tumors (volume=0.56¿0.12) did not. Tumors responding to Cisplatin displayed greater than 2-fold increase in [OHb] and [RHb] during oxygen intervention compared to non responding tumors (p<0.05). (Fig.1) Significant differences in tumor size changes (data not shown) were also observed between responders and non-responders. Discussion: Breast cancers are heterogeneous in their molecular profiles as well as treatment response. Hyperoxic gas intervention during chemotherapy combined with intrinsic signal optical imaging can be used to evaluate vascular reactivity. Our preliminary results indicate that OHb and RHb reactive tumors are significantly more likely to respond to Cisplatin chemotherapy. This general approach can be extended to other tumor therapy models and can be readily translated to patients.