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

项目2：通过重水标记拉曼光谱和多光子显微镜早期检测乳腺癌亚型

• 批准号: 10021578
• 负责人: JASON Arthur KOUTCHER
• 金额: $ 8.01万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-26 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10021578
• 关键词: Address; African American; Behavior; Breast Cancer Early Detection; Cancer Detection; Carbon; Cause of Death; Cells; Cellular Metabolic Process; Cellular Structures; Chemicals; Clinic; Clinical; Collaborations; Collagen; Community Outreach; Complex; DNA; Data; Detection; Deuterium; Deuterium Oxide; Diagnostic; ERBB2 gene; Early Diagnosis; Early treatment; Education and Outreach; Environment; Equilibrium; Exhibits; Fingerprint; Flavins; Fluorescence; Fluorescence Microscopy; Fluorescence Spectroscopy; Glycolysis; Goals; Healthcare; Hour; Image; Income; Institution; Label; Laboratories; Lead; Lipids; Magnetic Resonance Imaging; Malignant Neoplasms; Mammary Neoplasms; Measurement; Measures; Memorial Sloan-Kettering Cancer Center; Metabolic; Metabolic Pathway; Metabolism; Methodology; Modeling; Molecular; Multiphoton Fluorescence Microscopy; Mus; NADH; NMR Spectroscopy; Neoplasm Metastasis; Normal tissue morphology; Nucleic Acids; Nutrient; Optical Biopsy; Optics; Oxidative Phosphorylation; Oxygen; Pathologic; Perfusion; Proteins; Raman Spectrum Analysis; Research; Resources; Signal Transduction; Spectrum Analysis; System; Techniques; Technology; Therapeutic; Tissues; Treatment outcome; Tryptophan; Tumor Subtype; Underrepresented Minority; Woman; absorption; anticancer research; cancer care; cancer cell; cancer imaging; cancer subtypes; chemotherapy; experimental study; fluorescence imaging; in vivo; light scattering; malignant breast neoplasm; metabolic abnormality assessment; mortality; multiphoton imaging; multiphoton microscopy; novel; screening; sound; tool; tumor; tumor metabolism; ultraviolet; vibration

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.

该项目的目标是使用共振拉曼光谱（RRS）和重 水标记作为代谢指纹分析工具来区分不同的乳房亚型 癌症，并使用多光子荧光显微镜检测天然荧光信号 来自关键代谢分子（胶原蛋白、色氨酸、NADH、黄素等） 侵袭性较小的肿瘤。我们将进一步探讨代谢差异的机制 通过体内糖酵解变化的测量来研究肿瘤代谢，这是一个关键的 肿瘤的代谢途径和肿瘤灌注。后者至关重要，因为变化 灌注将导致营养和氧气输送的改变，从而改变肿瘤 代谢（糖酵解和氧化磷酸化之间的平衡）并可以解释 共振拉曼光谱和多光子显微镜之间发生的差异 不同的肿瘤模型。这种合作努力在科学上是合理的，因为数据来源于 每个机构对于解决乳腺肿瘤检测问题都是互补且至关重要的 通过光学技术，并了解这些发现背后的机制。它还 代表着利用科学资源的成功合作的延续 两个机构都致力于加强乳腺癌护理并为弱势群体提供机会 代表 CCNY 的少数群体能够获得以下机构的科学和临床资源 MSKCC。因此，MSKCC 对灌注和乳酸代谢的研究至关重要 补充博士。 Shi/Alfano 在 CCNY 的研究了解背后的机制 肿瘤代谢的差异。这将使该方法扩展到其他类型 乳腺癌并最终到达诊所。 Koutcher 博士的实验室，特别是 Dr. MSKCC 的 Ackerstaff 开发了将肿瘤灌注与 微环境并定量乳酸浓度。博士。 Alfano/Shi 非常适合 为了进行光学研究，已经实施了必要的技术来执行 他们的实验。