HYPEROXIC RESPIRATORY CHALLENGES TO MONITOR CHEMOTHERAPY EFFECTS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 背景：当肿瘤缺氧时，对癌症治疗如放疗、化疗和光动力疗法的反应较低。高氧气体干预已被证明可以改善肿瘤氧合。在这里，我们报告如何血流动力学的变化，由于氧干预与顺铂治疗自发性乳腺肿瘤的小鼠Brca 1和p53基因的条件失活的肿瘤反应。 材料和方法：我们用1.2mg/kg顺铂（i.每天p.，持续一周），并在治疗期间监测肿瘤体积和体重。我们在化疗期间使用光学成像系统对肿瘤进行成像，该光学成像系统通过将空间调制的近红外（NIR）光（650 nm至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（StO 2）值和所有波长的散射值来量化固有光散射和吸收。在成像过程中，使用1.5%异氟烷麻醉动物，每只动物吸入医用空气（33% O2）6分钟，然后再吸入100%氧气12分钟。 结果：8例肿瘤中，5例（体积=0.38 <$0.1）对顺铂治疗有反应，3例（体积=0.56 <$0.12）对顺铂治疗无反应。与无反应肿瘤相比，在氧干预期间，对顺铂有反应的肿瘤显示[OHb]和[RHb]增加超过2倍（p<0.05）。（图1）在应答者和非应答者之间也观察到肿瘤大小变化的显著差异（数据未显示）。 讨论：乳腺癌在分子特征和治疗反应方面具有异质性。化疗期间的高氧气体干预结合固有信号光学成像可用于评估血管反应性。我们的初步结果表明，OHb和RHb反应性肿瘤更可能对顺铂化疗反应。 这种通用方法可以扩展到其他肿瘤治疗模型，并且可以很容易地转化为患者。

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.