Abstract:
:The cancer stem cell hypothesis suggests that rare populations of tumor-initiating cells may be resistant to therapy, lead to tumor relapse and contribute to poor prognosis for cancer patients. We previously demonstrated the feasibility of p53 pathway restoration in p53-deficient tumor cell populations using small molecules including ellipticine or its derivatives. We now establish a single cell p53-regulated green fluorescent protein (EGFP)-reporter system in human DLD1 colon tumor cells expressing mutant p53 protein. We use these p53-EGFP reporter DLD1 cells to investigate the status of p53 transcriptional activity in putative colon cancer stem cell populations following exposure to p53 pathway-restoring drugs and/or classical chemotherapy. We demonstrate induction of p53-specific EGFP reporter fluorescence following overexpression of p53 family member p73 by an Adenovirus vector. We further show that p53-reporter activity is induced in DLD1 putative cancer stem cell side-populations analyzed by their Hoechst dye efflux properties following treatment with the p53 pathway restoring drug ellipticine. Combination of ellipticine with the cytotoxic agent 5-fluorouracil resulted in increased cytotoxicity as compared to either agent alone and this was associated with depletion of putative cancer stem cell populations as compared with 5-FU alone treatment. Our results support the feasibility of therapeutic targeting of mutant p53 in putative cancer stem cells as well as the potential to enhance cytotoxic chemotherapy.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Huang C,Zhang XM,Tavaluc RT,Hart LS,Dicker DT,Wang W,El-Deiry WSdoi
10.4161/cbt.8.22.10446subject
Has Abstractpub_date
2009-11-01 00:00:00pages
2186-93issue
22eissn
1538-4047issn
1555-8576pii
10446journal_volume
8pub_type
杂志文章abstract::The androgen receptor is one of the central factors in mediating prostate cancer progression and is an important target for treatment. Several possible mechanisms have been put forth as to how it promotes this process. In the January 2004 issue of Nature Medicine, Chen et al. report that the androgen receptor is consi...
journal_title:Cancer biology & therapy
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doi:10.4161/cbt.3.3.785
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abstract::Targeting FGFRs is one of the most promising therapeutic strategies in squamous non-small cell lung cancer (SQCC). However, different FGFR genomic aberrations can be associated with distinct biological characteristics that result in different clinical outcomes or therapeutic consequences. Currently, the full spectrum ...
journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.11.1176
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abstract::Hypoxia, a common phenomenon in human solid tumors, is associated with invasion and metastasis in various tumors. Hypoxia inducible factors (HIFs) are key molecules in the hypoxic response, and regulate the activation of specific genes, which mediate many of the adaptations to hypoxia. CC chemokine receptor 7 (CCR7) h...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.4.7332
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
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abstract::The surprising results published by FIRE-3 revealed that the overall survival (OS) of RAS wild-type metastatic colorectal cancer (mCRC) patients treated with Cetuximab(Cmab) and FOLFIRI combination was prolonged to 33.1 months. The substantial increase in testing and treatment costs, however, impose a considerable hea...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1095398
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journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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doi:10.4161/cbt.3.9.1039
更新日期:2004-09-01 00:00:00
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journal_title:Cancer biology & therapy
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doi:10.4161/cbt.26725
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.2.5.452
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journal_title:Cancer biology & therapy
pub_type: 评论,杂志文章
doi:10.4161/cbt.5.12.3737
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.9.1968
更新日期:2005-09-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1040957
更新日期:2015-01-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.22256
更新日期:2012-12-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.3.12.1235
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1071739
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.11.4.14178
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journal_title:Cancer biology & therapy
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更新日期:2011-06-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.7.2.5332
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
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更新日期:2006-04-01 00:00:00
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journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.3.7386
更新日期:2009-02-01 00:00:00