p53 Gene status in relation to ex vivo chemosensitivity of non-small cell lung cancer

Vogt, U.; Żaczek, Anna; Klinke, F.; Granetzny, A.; Bielawski, Krzysztof Piotr; Falkiewicz, Bogdan

doi:10.1007/s00432-001-0305-2

Cited by 31 publications

(23 citation statements)

References 36 publications

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“…7 Accumulating evidence, however, suggests that mutant TP53 confers the chemo-resistance of cancer cells in vitro and vivo. 8,9 The research by Ludovini et al 10 showed that mutant TP53 is apparently related to the recurrence of NSCLC, indicating its function as a poor prognostic factor. Key words: non-small cell lung cancer, targeted therapy, p53, hypoxia, TAT, oxygen-dependent degradation domain, solid tumor…”

Section: Introductionmentioning

confidence: 99%

Introduction of hypoxia-targeting p53 fusion protein for the selective therapy of non-small cell lung cancer

Zhao¹,

Wu²,

et al. 2011

Cancer Biology & Therapy

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Section: Introductionmentioning

confidence: 99%

Introduction of hypoxia-targeting p53 fusion protein for the selective therapy of non-small cell lung cancer

Zhao¹,

Wu²,

et al. 2011

Cancer Biology & Therapy

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“…Mutations of this gene often result in loss of p53 function and p53 inactivation (12,13), contributing to aggressive tumor behavior and therapeutic resistance (14). Several reports have shown that the expression of wild-type p53 is necessary for the cytotoxic response to chemotherapeutic agents (15)(16)(17), although there are some conflicting results (18,19).…”

Section: Introductionmentioning

confidence: 99%

p53 Enhances Gefitinib-Induced Growth Inhibition and Apoptosis by Regulation of Fas in Non–Small Cell Lung Cancer

Rho

Choi²,

Ryoo³

et al. 2007

Cancer Research

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Treatment with gefitinib, a specific inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK), has resulted in dramatic responses in some patients with nonsmall cell lung cancer (NSCLC). Most patients who respond to gefitinib have EGFR-TK mutations; however, >10% of patients with EGFR-TK mutations do not respond. Similarly, some patients without EGFR-TK mutations respond to this drug, suggesting that other factors determine sensitivity to gefitinib. Aberrations of the tumor suppressor gene p53 are frequently associated with drug resistance. In this study, we investigated the role of p53 in growth-inhibitory and apoptotic effects of gefitinib in the human NSCLC cell lines NCI-H1299 and A549, which have no EGFR-TK mutations. NCI-H1299 cells, which had a p53-null genotype, were more resistant to gefitinib compared with A549 cells, which were wild-type p53 (IC 50 , 40 Mmol/L in NCI-H1299 and 5 Mmol/L in A549). Treatment of A549 with gefitinib resulted in the translocation of p53 from cytosol to nucleus and the up-regulation of Fas, which was localized to the plasma membrane. In the stable H1299 cell line with tetracycline-inducible p53 expression, induced p53 enhanced growth inhibition and apoptosis by gefitinib through the up-regulation of Fas and restoration of caspase activation. A caspase inhibitor, Z-VAD-fmk, reduced these effects. Conversely, inhibition of p53 using antisense oligonucleotide in A549 caused a significant decrease in apoptosis by gefitinib and down-regulation of Fas under the same conditions. In conclusion, p53 may play a role in determining gefitinib sensitivity by regulating Fas expression in NSCLC.

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“…Usually, wild-type p53 expression predisposes cells to a more rapid rate of cell death after DNA damage. Previous studies have reported that non-small cell lung cancer cells having p53 mutations showed significantly poorer response to intensive chemotherapy that included etoposide and epirubicin (Vogt et al, 2002). In addition, treatment of MCF-7 with doxorubicin resulted in an increase of p53 expression, confirming a p53-mediated response to doxorubicin in cells containing a wildtype p53 gene product (Liem et al, 2003).…”

Section: Discussionmentioning

confidence: 62%

Comparative analysis of xanafide cytotoxicity in breast cancer cell lines

Alami

Paterson²,

Bélanger

et al. 2007

Br J Cancer

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Xanafide, a DNA-intercalating agent and topoisomerase II inhibitor, has previously demonstrated comparable cytotoxicity to the parent drug amonafide (NSC 308847). The current study was conducted to investigate further the anti-proliferative effects of xanafide in human breast cancer cell lines, in vitro and in vivo. The in vitro activity of xanafide against MCF-7, MDA-MB-231, SKBR-3 and T47D cell lines was compared to that of paclitaxel, docetaxel, gemcitabine, vinorelbine and doxorubicin. In MCF-7, xanafide demonstrated comparable total growth inhibition (TGI) concentrations to the taxanes and lower TGI values than gemcitabine, vinorelbine and doxorubicin. MCF-7 (oestrogen receptor (ER) þ /p53 wild-type) was the most sensitive cell line to xanafide. MDA-MB-231 and SKBR-3 exhibited similar sensitivity to xanafide. T47 D (ER þ /p53 mutated), showed no response to this agent. The in vivo activity of xanafide was further compared to that of docetaxel in MCF-7 and MDA-MB-231 cell lines using the hollow fibre assay. Xanafide was slightly more potent than docetaxel, at its highest dose in MCF-7 cell line, whereas docetaxel was more effective than xanafide in MDA-MB-231 cell line. Our results show that there is no relationship between sensitivity of these cell lines to xanafide and cellular levels of both isoforms of topoisomerase II and suggest that ER and p53 status and their crosstalk may predict the responsiveness or resistance of breast cancer patients to xanafide.

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p53 Gene status in relation to ex vivo chemosensitivity of non-small cell lung cancer

Cited by 31 publications

References 36 publications

Introduction of hypoxia-targeting p53 fusion protein for the selective therapy of non-small cell lung cancer

Introduction of hypoxia-targeting p53 fusion protein for the selective therapy of non-small cell lung cancer

p53 Enhances Gefitinib-Induced Growth Inhibition and Apoptosis by Regulation of Fas in Non–Small Cell Lung Cancer

Comparative analysis of xanafide cytotoxicity in breast cancer cell lines

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