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Full-Text Articles in Medicine and Health Sciences
Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang
Microenvironment-Induced Pten Loss By Exosomal Microrna Primes Brain Metastasis Outgrowth, Lin Zhang
Dissertations & Theses (Open Access)
Development of life-threatening cancer metastases at distant organs requires disseminated tumor cells’ adaptation to and co-evolution with the drastically different microenvironments of metastatic sites. Cancer cells of common origin manifest distinct gene expression patterns after metastasizing to different organs. Clearly, the dynamic interplay between metastatic tumor cells and extrinsic signals at individual metastatic organ sites critically impacts the subsequent metastatic outgrowth. Yet, it is unclear when and how disseminated tumor cells acquire the essential traits from the microenvironment of metastatic organs that prime their subsequent outgrowth. Here we show that primary tumor cells with normal expression of PTEN, an important …
In Vivo Kinome Screen Reveals Non-Canonical Cdk-Driven Metabolic Adaptation In Brain Metastasis, Frank J. Lowery Iii
In Vivo Kinome Screen Reveals Non-Canonical Cdk-Driven Metabolic Adaptation In Brain Metastasis, Frank J. Lowery Iii
Dissertations & Theses (Open Access)
Brain metastasis, which frequently arises from breast cancer, lung cancer, melanoma, and colorectal cancer, remains a severely unmet medical need and its incidence continues to rise while treatment options remain palliative. To better understand the biology underlying its aggressive, incurable nature, I performed an unbiased in vivo kinome screen to identify potential driver kinases of experimental brain metastasis in a nude xenograft model using the human breast cancer cell line MDA-MB-231. Several of the kinase pools led to decreased brain metastasis-specific survival in nude mice, shortening survival time by up to 50% relative to controls. Targeted next-generation sequencing (NGS) was …