Project 2: Early Detection of Breast Cancer Subtypes by Raman Spectroscopy with Heavy Water Labeling and MultiPhoton Microscopy

该项目的目标是使用共振拉曼光谱(RRS)和重型 水标记作为区分不同乳房亚型的代谢指纹工具 癌症，并使用多光子荧光显微镜来检测自然荧光信号 来自关键代谢分子(胶原、色氨酸、NADH、黄素等)在咄咄逼人的 侵袭性较弱的肿瘤。我们将进一步探索新陈代谢差异的机制 通过体内糖酵解变化的测量来研究肿瘤的代谢，一个关键的 肿瘤的代谢途径和肿瘤的血流灌注。后者至关重要，因为 血流灌注将导致营养和氧气供应的改变，从而改变肿瘤 代谢(糖酵解和氧化磷酸化之间的平衡)，并可能解释 共振拉曼光谱和多光子显微镜之间的差异 不同的肿瘤模型。这种合作努力在科学上是合理的，因为从 每个机构都是相辅相成的，对解决检测乳腺肿瘤的问题至关重要 通过光学技术，并理解这些发现背后的机制。它还 代表着成功合作的延续，利用 这两个机构都加强了乳腺癌的护理，并为未成年儿童提供机会 代表少数族裔在CCNY获得科学和临床资源 MSKCC。因此，MSKCC对血流和乳酸代谢的研究是至关重要的。 补充史/阿尔法诺博士在CCNY的研究，以了解背后的机制 肿瘤新陈代谢的差异。这将允许该方法扩展到其他类型 乳腺癌，并最终送到临床。库彻博士的实验室，尤其是库彻博士。 在MSKCC，AckerStaff开发了将肿瘤血流灌注与 用于微环境和乳酸浓度的定量测定。阿尔法诺/史博士是独一无二的 用于执行光学研究，已经实施了必要的技术来执行 他们的实验。

The goals of the project are to are to use resonance Raman spectroscopy (RRS) and heavy water labeling as a metabolic fingerprinting tool to distinguish different subtypes of breast cancer, and to use multiphoton fluorescence microscopy to detect native fluorescence signals from critical metabolic molecules (collagen, tryptophan, NADH, flavin, etc.) in aggressive and less aggressive tumors. We will further explore the mechanism for the differences in metabolism by studying tumor metabolism by in vivo measurements of glycolytic changes, a critical metabolic pathway in tumors, and tumor perfusion. The latter is critical since changes in perfusion will lead to alterations in nutrient and oxygen delivery which will alter tumor metabolism (balance between glycolysis and oxidative phosphorylation) and may explain differences in the resonance Raman spectra and multiphoton microscopy that occur between different tumor models. This collaborative effort is scientifically sound since the data derived at each institution is complementary and critical to addressing the issue of detecting breast tumors by optical techniques, and understanding the mechanism behind these findings. It also represents a continuation of a successful collaboration making use of the scientific resources of both institutions to enhance breast cancer care and to provide opportunities for under- represented minorities at CCNY to have access to both the scientific and clinical resources at MSKCC. Thus, MSKCC studies of perfusion and lactate metabolism are critically complementary to Drs. Shi/Alfano's studies at CCNY to understand the mechanism behind differences in tumor metabolism. This will allow this methodology to be expanded to other types of breast cancer and eventually to the clinic. Dr. Koutcher's laboratory, particularly Dr. Ackerstaff, at MSKCC has developed the methodologies to relate tumor perfusion to the microenvironment and to quantitate lactate concentrations. Drs. Alfano/Shi are uniquely suited for performing the optical studies, having implemented the necessary technology to perform their experiments.