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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 尽管转移性癌症患者通常对治疗和死亡时间有可变的反应，但了解导致侵略性异质性的机制仍然是有效癌症诊断和治疗的主要问题。先前利用一组磁共振（MR）和光学成像技术和组织学测定法的研究表征了人类黑色素瘤小鼠异种移植物，涵盖了转移到转移的全范围。尽管如Tunel Assay所示，尽管血液灌注和营养饥饿之类的代谢挑战，例如血液灌注和营养饥饿，但侵袭性的肿瘤核心很少有凋亡细胞。自噬可在饥饿或细胞应激条件下促进癌细胞的存活。我们假设较高的自噬与更具侵略性的癌症有关，并且自噬可能会提供对癌症转移机制的新见解，并通过靶向自噬来支持新型治疗方法的发展。