Optimization of aminolevulinic acid-protoporphyrin IX for fluorescence-guided tumor resection and treatment

荧光引导肿瘤切除和治疗中氨基乙酰丙酸-原卟啉 IX 的优化

• 批准号: 10818914
• 负责人: BIN CHEN
• 金额: $ 11.9万
• 依托单位: SAINT JOSEPH'S UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10818914
• 关键词: ABCG2 gene; Address; Aminolevulinic Acid; Clinical; Detection; Doctor of Philosophy; Excision; FDA approved; Family; Female; First Generation College Students; Fluorescence; Fluorescent Probes; Funding; Future; Generations; Goals; Heterogeneity; Inter-tumoral heterogeneity; Knowledge; Malignant Neoplasms; Mediating; Metabolic; Minority; Molecular Probes; Normal tissue morphology; PUVA Photochemotherapy; Pathway interactions; Research; Research Personnel; Research Project Grants; Research Support; Training; Variant; Woman; Work; anticancer research; cancer imaging; cancer therapy; career; college; fluorescence imaging; heme biosynthesis; neoplastic cell; parent grant; protoporphyrin IX; skills; tumor; tumor heterogeneity

NCI Diversity Supplement Application Parent grant: Optimization of aminolevulinic acid-protoporphyrin IX for fluorescence-guided tumor resection and treatment (R15CA268200-02, PI: Bin Chen) This diversity supplement application is to support Ms. Jordyn Olsen, a first-generation college graduate in her family, to pursue PhD training in cancer research with the goal of promoting women and minorities in cancer research workforce. Aminolevulinic acid (ALA) is one of a few FDA-approved intraoperative fluorescent probes and the only molecular probe based on the metabolic alterations in tumor cells. ALA has no fluorescence on its own and needs to be metabolized in the heme biosynthesis pathway in tumor cells to produce a fluorescent and photosensitizing metabolite protoporphyrin IX (PpIX), which enables tumor fluorescence imaging for tumor detection and photodynamic therapy (PDT) for cancer treatment. Although ALA-PpIX has been clinically used for fluorescence-guided tumor resection and cancer treatment, its applications are limited by low tumor PpIX fluorescence, high tumor fluorescence heterogeneity, and low tumor-to-normal tissue fluorescence contrast. Research supported by the parent grant has led to the identification of ABCG2 transporter activity as a critical factor in reducing tumor PpIX fluorescence. More importantly, we have identified clinically used agents to suppress ABCG2 activity to enhance tumor PpIX fluorescence. In this supplement research, Jordyn will determine whether variation in ABCG2 expression results in intra-tumor and inter-tumor heterogeneity in ALA- PpIX fluorescence. In addition, she will investigate whether PpIX fluorescence heterogeneity in tumor cells can be suppressed by ABCG2 inhibition. This proposed research is related to the on-going work supported by the parent grant funding and will further expand scope of parent grant research. Support from this supplement funding will enable Jordyn to complete the necessary training in cancer research so that she will have the knowledge and skills to start her career as a cancer researcher.

NCI 多样性补充申请 家长资助：优化氨基乙酰丙酸-原卟啉 IX 用于荧光引导肿瘤的方法 切除和治疗（R15CA268200-02，PI：陈斌） 这个多样性补充申请是为了支持乔丁·奥尔森女士，她是她所在的第一代大学毕业生。 家庭，接受癌症研究的博士培训，目标是促进妇女和少数族裔抗击癌症 研究人员。氨基乙酰丙酸 (ALA) 是 FDA 批准的少数术中荧光探针之一 也是唯一基于肿瘤细胞代谢变化的分子探针。 ALA 表面无荧光 自身并需要在肿瘤细胞的血红素生物合成途径中代谢以产生荧光和 光敏代谢物原卟啉 IX (PpIX)，可实现肿瘤荧光成像 用于癌症治疗的检测和光动力疗法（PDT）。尽管ALA-PpIX已应用于临床 用于荧光引导肿瘤切除和癌症治疗，其应用受到低肿瘤PpIX的限制 荧光，肿瘤荧光异质性高，肿瘤与正常组织荧光对比度低。 由家长资助支持的研究已确定 ABCG2 转运蛋白活性是一个关键的 减少肿瘤 PpIX 荧光的因素。更重要的是，我们已经确定了临床使用的药物 抑制 ABCG2 活性以增强肿瘤 PpIX 荧光。在这项补充研究中，乔丁将 确定 ABCG2 表达的变化是否会导致 ALA 的肿瘤内和肿瘤间异质性 PpIX 荧光。此外，她还将研究肿瘤细胞中的PpIX荧光异质性是否可以 被 ABCG2 抑制所抑制。这项拟议的研究与正在进行的工作有关 家长补助资金并将进一步扩大家长补助研究的范围。本补充的支持 资金将使乔丁能够完成癌症研究方面的必要培训，以便她能够 知识和技能来开始她作为癌症研究员的职业生涯。