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 水标记作为区分不同乳腺亚型的代谢指纹工具 癌症，并使用多光子荧光显微镜检测天然荧光信号 从关键代谢分子（胶原蛋白，色氨酸，NADH，黄素等）在侵略性和 侵袭性较低的肿瘤。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， 肿瘤中的代谢途径和肿瘤灌注。后者至关重要，因为 灌注将导致营养物和氧气输送的改变，这将改变肿瘤 代谢（糖酵解和氧化磷酸化之间的平衡），并可能解释 在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 每个机构都是互补的，对解决乳腺肿瘤检测问题至关重要， 通过光学技术，并了解这些发现背后的机制。它还 代表了利用科学资源的成功合作的延续， 这两个机构，以加强乳腺癌的护理，并提供机会， 代表CCNY的少数民族可以获得科学和临床资源 MSKCC。因此，灌注和乳酸代谢的MSKCC研究至关重要 补充Shi/Alfano博士在CCNY的研究，以了解其背后的机制 肿瘤代谢的差异。这将使这种方法扩展到其他类型 乳腺癌的早期诊断，最终送到诊所库彻博士的实验室，特别是博士。 Ackerstaff，在MSKCC已经开发了将肿瘤灌注与肿瘤细胞的增殖相关的方法。 微环境和定量乳酸浓度。阿尔法诺/施博士是唯一适合 为了进行光学研究，已经实施了必要的技术来进行 他们的实验。