Definition of the malignant transformation event is central to a distinction between neural stem cells and cancer stem cells. In such manner, the descriptive analysis of various tumors such as gliomas would allow for ...Definition of the malignant transformation event is central to a distinction between neural stem cells and cancer stem cells. In such manner, the descriptive analysis of various tumors such as gliomas would allow for the distinction of genetic injury and probably epigenetic events that transform gene transcription pathways. Hypoxia is a major conditioning influence acting on stem cell niche microenvironments that evolve in terms particularly of micro-vascular dynamics. The incremental involvement of entire fields of cancerization allows for the establishment of permissive conditions of repetitive nature and within the contextual involvement of multiple clones of injured cells that condition, in turn, the stem cell niche. In view of the establishment of progressive malignant change, it is significant to view the cancerization as an integral involvement of both sequential and concurrent events in defining the roles of stem cells and cancer stem cells in terms of a primal process of dedifferentiation beyond simple markers of morphologic transformation.展开更多
Glioma incidence rates in the United States are near 20000 new cases per year, with a median survival time of 14.6 mo for high-grade gliomas due to limited therapeutic options. The origins of these tumors and their ma...Glioma incidence rates in the United States are near 20000 new cases per year, with a median survival time of 14.6 mo for high-grade gliomas due to limited therapeutic options. The origins of these tumors and their many subtypes remain a matter of investigation. Evidence from mouse models of glioma and human clinical data have provided clues about the cell types and initiating oncogenic mutations that drive gliomagenesis, a topic we review here. There has been mixed evidence as to whether or not the cells of origin are neural stem cells, progenitor cells or differentiated progeny. Many of the existing murine models target cell populations defined by lineage-specific promoters or employ lineagetracing methods to track the potential cells of origin. Our ability to target specific cell populations will likely increase concurrently with the knowledge gleaned from an understanding of neurogenesis in the adult brain. The cell of origin is one variable in tumorigenesis, as oncogenes or tumor suppressor genes may differentially transform the neuroglial cell types. Knowledge of key driver mutations and susceptible cell types will allow us to understand cancer biology from a developmental standpoint and enable early interventional strategies and biomarker discovery.展开更多
文摘Definition of the malignant transformation event is central to a distinction between neural stem cells and cancer stem cells. In such manner, the descriptive analysis of various tumors such as gliomas would allow for the distinction of genetic injury and probably epigenetic events that transform gene transcription pathways. Hypoxia is a major conditioning influence acting on stem cell niche microenvironments that evolve in terms particularly of micro-vascular dynamics. The incremental involvement of entire fields of cancerization allows for the establishment of permissive conditions of repetitive nature and within the contextual involvement of multiple clones of injured cells that condition, in turn, the stem cell niche. In view of the establishment of progressive malignant change, it is significant to view the cancerization as an integral involvement of both sequential and concurrent events in defining the roles of stem cells and cancer stem cells in terms of a primal process of dedifferentiation beyond simple markers of morphologic transformation.
基金Supported by The Medical Scientist Training Program at NYU School of Medicine to Modrek ASNYSTEM Institutional training grant#CO26880 to Bayin NS+1 种基金NIH/NINDS(1 R21 NS087241-01)the NYU Cancer Institute Developmental Projects Program and the NYU Clinical and Translational Science Institute(NYU CTSA grant#UL1TR000038 from the National Center for the Advancement of Translational Science NCATS,NIH)to Placantonakis DG
文摘Glioma incidence rates in the United States are near 20000 new cases per year, with a median survival time of 14.6 mo for high-grade gliomas due to limited therapeutic options. The origins of these tumors and their many subtypes remain a matter of investigation. Evidence from mouse models of glioma and human clinical data have provided clues about the cell types and initiating oncogenic mutations that drive gliomagenesis, a topic we review here. There has been mixed evidence as to whether or not the cells of origin are neural stem cells, progenitor cells or differentiated progeny. Many of the existing murine models target cell populations defined by lineage-specific promoters or employ lineagetracing methods to track the potential cells of origin. Our ability to target specific cell populations will likely increase concurrently with the knowledge gleaned from an understanding of neurogenesis in the adult brain. The cell of origin is one variable in tumorigenesis, as oncogenes or tumor suppressor genes may differentially transform the neuroglial cell types. Knowledge of key driver mutations and susceptible cell types will allow us to understand cancer biology from a developmental standpoint and enable early interventional strategies and biomarker discovery.
