2015
DOI: 10.18632/aging.100831
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Abstract: Medulloblastoma (MB), a primitive neuroectodermal tumor, is the most common malignant childhood brain tumor and remains incurable in about a third of patients. Currently, survivors carry a significant burden of late treatment effects. The p53 tumor suppressor protein plays a crucial role in influencing cell survival in response to cellular stress and while the p53 pathway is considered a key determinant of anti-tumor responses in many tumors, its role in cell survival in MB is much less well defined. Herein, w… Show more

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Cited by 16 publications
(20 citation statements)
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References 55 publications
(88 reference statements)
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“…In HCT116 colon carcinoma cells treated with oxaliplatin, for example, moderate concentrations that are typically used in the colony formation assay (e.g., <5 μM) [ 68 ] result in significant growth arrest (e.g., determined by the MTS cell proliferation assay) but virtually no apoptosis [ 67 ], whereas >20 μM concentrations of oxaliplatin are required to trigger apoptosis [ 67 ] (also see Figure 2 ). Similar discrepancy between growth-inhibitory and apoptosis-inducing concentrations has been reported for cisplatin (reviewed in [ 66 ] for a large number of cancer cell lines), paclitaxel [ 65 ] and doxorubicin [ 62 , 63 , 64 ]. When examined, moderate (sub-apoptotic) concentrations of these agents trigger a high degree of SIPS [ 66 , 70 , 71 ].…”
Section: Cancer Cell Response To Genotoxic Stress: Reversible Growsupporting
confidence: 71%
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“…In HCT116 colon carcinoma cells treated with oxaliplatin, for example, moderate concentrations that are typically used in the colony formation assay (e.g., <5 μM) [ 68 ] result in significant growth arrest (e.g., determined by the MTS cell proliferation assay) but virtually no apoptosis [ 67 ], whereas >20 μM concentrations of oxaliplatin are required to trigger apoptosis [ 67 ] (also see Figure 2 ). Similar discrepancy between growth-inhibitory and apoptosis-inducing concentrations has been reported for cisplatin (reviewed in [ 66 ] for a large number of cancer cell lines), paclitaxel [ 65 ] and doxorubicin [ 62 , 63 , 64 ]. When examined, moderate (sub-apoptotic) concentrations of these agents trigger a high degree of SIPS [ 66 , 70 , 71 ].…”
Section: Cancer Cell Response To Genotoxic Stress: Reversible Growsupporting
confidence: 71%
“…Numerous studies reported since the 1990s, some from our laboratory [ 53 , 54 , 55 , 56 , 57 ], have established the presence of a threshold mechanism for stress-induced growth arrest versus apoptosis in human cells with different p53 status, with moderate doses of DNA-damaging agents predominantly (if not solely) triggering growth arrest (e.g., SIPS) in some cell types. This threshold effect has been observed for ionizing radiation [ 54 , 55 , 56 , 57 , 58 , 59 ], 254 nm ultraviolet light (UV) [ 53 , 54 , 60 , 61 ] and chemotherapeutic agents [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ].…”
Section: Cancer Cell Response To Genotoxic Stress: Reversible Growmentioning
confidence: 99%
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“…Ray and colleagues found that p53 immunoreactivity was predictive of poor outcome in a large group of MB patients 22 . Experimental studies also propose that p53 protects against drug-induced cell death in medulloblastoma cells and play role in chemotherapy resistance 23 . However, in few other studies p53 expression was not statistically associated with patient survival 24 .…”
Section: Discussionmentioning
confidence: 99%
“…13 papers were identified in both of these searches. 11 papers presented evidence of autophagy manipulation on brain tumor models; of which seven presented evidence specific to the pediatric brain tumors rather than adult pathology; with two finding no effect of autophagy modulation on cell survival [ 9 , 81 ]. Abbreviations: chloroquine, CQ; knockout, KO.…”
Section: Relevance To Pediatric Brain Tumorsmentioning
confidence: 99%