PROBING MELANOMA AGGRESSIVENESS, REDOX STATE AND AUTOPHAGY

探究黑色素瘤的侵袭性、氧化还原状态和自噬

• 批准号: 8362022
• 负责人: LIN LI
• 金额: $ 0.77万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362022
• 关键词: Apoptotic; Autophagocytosis; Biological Assay; Cells; Cellular Stress; Cessation of life; Development; Disseminated Malignant Neoplasm; Funding; Grant; Heterogeneity; Histology; Human; Imaging Techniques; Magnetic Resonance; Malignant Neoplasms; Metabolic; Mus; National Center for Research Resources; Neoplasm Metastasis; Oxidation-Reduction; Patients; Principal Investigator; Research; Research Infrastructure; Resources; Source; Starvation; TdT-Mediated dUTP Nick End Labeling Assay; Time; United States National Institutes of Health; Xenograft procedure; blood perfusion; cancer cell; cancer diagnosis; cancer therapy; cost; insight; melanoma; novel therapeutic intervention; nutrition; optical imaging; response; tumor

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. While patients with metastatic cancer usually have a variable response to treatment and time to death, understanding the mechanisms that contribute to the heterogeneity of aggressiveness remains a major issue in effective cancer diagnosis and therapy. Previous studies utilizing a set of magnetic resonance (MR) and optical imaging techniques and histology assays have characterized a panel of human melanoma mouse xenografts spanning a full range of progression to metastasis. Despite the metabolic challenges such as low blood perfusion and presumably nutrition starvation, the aggressive tumor cores contained few apoptotic cells as shown by TUNEL assay. Autophagy promotes the survival of cancer cells under starvation or under conditions of cellular stress. We hypothesize that higher autophagy is associated with more aggressive cancer and autophagy may provide new insight into the mechanisms of cancer metastasis and support the development of novel therapeutic approaches by targeting autophagy.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 虽然转移性癌症患者通常对治疗的反应和死亡时间各不相同，但了解导致侵袭性异质性的机制仍然是有效癌症诊断和治疗的主要问题。先前的研究利用一系列磁共振（MR）和光学成像技术以及组织学分析，对一组人类黑色素瘤小鼠异种移植物进行了表征，涵盖了从进展到转移的整个过程。尽管存在低血液灌注和可能的营养饥饿等代谢挑战，但 TUNEL 测定显示，侵袭性肿瘤核心含有很少的凋亡细胞。自噬促进癌细胞在饥饿或细胞应激条件下的存活。我们假设较高的自噬与更具侵袭性的癌症相关，自噬可能为癌症转移机制提供新的见解，并支持通过靶向自噬开发新的治疗方法。