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Author Zhan, Q.; Fan, S.; Bae, I.; Guillouf, C.; Liebermann, D.A.; O'Connor, P.M.; Fornace, A.J.J. file  url
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Title Induction of bax by genotoxic stress in human cells correlates with normal p53 status and apoptosis Type Journal Article
Year 1994 Publication Oncogene Abbreviated Journal Oncogene  
Volume 9 Issue 12 Pages 3743-3751  
Keywords Apoptosis/*genetics; Gene Expression Regulation/*drug effects/genetics/radiation effects; *Genes, p53; Humans; Mutagens/*toxicity; Neoplasms/genetics; Proto-Oncogene Proteins/*genetics; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured; bcl-2-Associated X Protein  
Abstract DNA-damaging agents such as ionizing radiation (IR) activate the tumor suppressor p53 and in some cases can cause apoptosis. M1 cells, which do not express the endogenous tumor suppressor gene p53, undergo apoptosis following activation of a temperature sensitive p53 transgene, where it has been shown that bax, an important mediator of apoptosis, is a p53 target gene (Selvakumaran et al, Oncogene 9, 1791-8, 1994). Since p53 can function as a transcription factor after activation by IR, the genetic response to this stress was examined in a panel of human cells with defined p53 status. Like the p53-regulated gene gadd45, bax was rapidly induced, as measured by increased mRNA levels, in the p53 wt (wild type) human myeloid line ML-1, and it was not induced in cells lacking functional p53. However, unlike other p53-regulated genes, bax was only induced in p53 wt cells in which IR also triggered apoptosis. In the case of bcl2, which opposes bax function, mRNA levels were reduced in ML-1 cells after IR. Thus, bax appears to be an unique p53-regulated gene in that its induction by IR not only requires functional p53 but also requires that the cells be apoptosis “proficient.”  
Call Number Serial 2172  
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Author Naxerova, K.; Jain, R.K. file  url
openurl 
Title Using tumour phylogenetics to identify the roots of metastasis in humans Type Journal Article
Year 2015 Publication Nature Reviews. Clinical Oncology Abbreviated Journal Nat Rev Clin Oncol  
Volume 12 Issue 5 Pages 258-272  
Keywords Disease Progression; Epigenomics; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Microsatellite Repeats; Models, Biological; Neoplasm Metastasis/genetics/*pathology; Neoplasms/genetics; Neoplastic Cells, Circulating/pathology; Phylogeny; Polymorphism, Single Nucleotide  
Abstract In cancer, much uncertainty remains regarding the origins of metastatic disease. Models of metastatic progression offer competing views on when dissemination occurs (at an early or late stage of tumour development), whether metastases at different sites arise independently and directly from the primary tumour or give rise to each other, and whether dynamic cell exchange occurs between synchronously growing lesions. Although it is probable that many routes can lead to the establishment of systemic disease, clinical observations suggest that distinct modes of metastasis might prevail in different tumour types. Gaining a more-comprehensive understanding of the evolutionary processes that underlie metastasis is not only relevant from a basic biological perspective, but also has profound clinical implications. The 'tree of life' of metastatic cancer contains answers to many outstanding questions about the development of systemic disease, but has only been reconstructed in a limited number of patients. Here we review available data on the phylogenetic relationships between primary solid tumours and their metastases, and examine to what degree they support different models of metastatic progression. We provide a description of experimental methods for lineage tracing in human cancer, ranging from broad DNA-sequencing approaches to more-targeted techniques, and discuss their respective benefits and caveats. Finally, we propose future research questions in the area of cancer phylogenetics.  
Call Number Serial 1928  
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