PROBING MELANOMA AGGRESSIVENESS, REDOX STATE AND AUTOPHAGY

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 虽然转移性癌症患者通常对治疗和死亡时间有不同的反应，但了解导致侵袭性异质性的机制仍然是有效的癌症诊断和治疗的主要问题。以前的研究利用了一套磁共振(MR)和光学成像技术以及组织学分析，表征了一组人黑色素瘤小鼠异种移植瘤的全过程。尽管存在新陈代谢方面的挑战，如低血液灌注率和可能的营养饥饿，但TUNEL分析显示，侵袭性肿瘤核心包含的凋亡细胞很少。自噬促进了癌细胞在饥饿或细胞应激条件下的存活。我们假设更高的自噬与更具侵袭性的癌症相关，自噬可能为肿瘤转移的机制提供新的见解，并支持通过靶向自噬来开发新的治疗方法。

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.