P53 mutation correlates with cisplatin sensitivity in head and neck squamous cell carcinoma lines

Bradford, Carol R.; Zhu, Shaobo; Ogawa, Haruko; Ogawa, Tetsuya; Ubell, Matthew L.; Narayan, Alison R. H.; Johnson, Garfield; Wolf, Gregory T.; Fisher, Susan G.; Carey, Thomas E.

doi:10.1002/hed.10274

Cited by 144 publications

(114 citation statements)

References 27 publications

(29 reference statements)

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“…The prognostic role of p53 in head and neck cancers is controversial [28]. Some authors found negative correlation between p53 expression and prognosis [29], while others including this study could not prove this finding [30,31].…”

Section: Discussionmentioning

confidence: 54%

Correlations Between Prognosis and Regional Biomarker Profiles in Head and Neck Squamous Cell Carcinomas

Szentkúti

Dános

Brauswetter³

et al. 2014

Pathol. Oncol. Res.

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Head and neck squamous cell carcinomas (HNSC C) show diverse clinicopathological features and are mostly linked with poor outcome. In this study, we tested if the expression of tumor growth, cell cycle and basement membrane anchorage related biomarkers allow prognostic and clinicopathological stratification of HNSCC. Archived HNSCC samples from 226 patients included into tissue microarrays (TMA) were tested using immunohistochemistry. Histopathological evaluation and the analysis of immunostaining for EGFR, Ki67, p53, p16 ink4 and Collagen XVII proteins were carried out in digital whole slides. Statistical evaluation was carried out using Pearson's Chi-square test and Kaplan-Meier survival analysis. In the tested cohort, hypopharyngeal cancers had the least favorable, and glottic cancers had the most favorable prognosis. High Ki67 positive tumor cell fractions were associated with significantly worse prognosis and elevated rate of lymph node metastasis. Both Ki67 and EGFR expression correlated significantly with the tumor localization. Ki67 index was the highest in the hypopharyngeal region and it proved to be the lowest in the glottic region. EGFR expression was the highest in the oral cavity and the lowest in the glottic region. The survival rate of patients with p16 ink4

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Section: Discussionmentioning

confidence: 54%

Correlations Between Prognosis and Regional Biomarker Profiles in Head and Neck Squamous Cell Carcinomas

Szentkúti

Dános

Brauswetter³

et al. 2014

Pathol. Oncol. Res.

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“…The eight human HNSCC cell lines were chosen for this study because they (a) all express high level of EGFR, (b) have a wide range of sensitivity to the commonly used chemotherapy agent cisplatin, and (c) have known p53 and retinoblastoma status (25). 3 The cell lines were treated with retinoblastoma, which results in decreased retinoblastoma activity (27).…”

Section: Resultsmentioning

confidence: 99%

Potent Activity of a Novel Dimeric Heat Shock Protein 90 Inhibitor against Head and Neck Squamous Cell Carcinoma In vitro and In vivo

Yin

Zhang

Burrows

et al. 2005

Clinical Cancer Research

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Heat shock protein 90 (Hsp90) is a molecular chaperone that promotes the conformational maturation of numerous client proteins, many of which play critical roles in tumor cell growth and survival. The ansamycin-based Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) is currently in phase I/II clinical testing. However, 17-AAG is difficult to formulate and displays weak activity against some tumors. A novel dimeric ansamycin, EC5, was evaluated for antitumor activity in eight head and neck squamous cell carcinoma (HNSCC) cell lines. Both 17-AAG and EC5 inhibited tumor cell proliferation effectively, but EC5 was more potent, with IC 50 below 200 nmol/L in most cell lines tested, including several lines that were resistant to 17-AAG. The inability of 17-AAG to kill JHU12 cells was linked to a defect in retinoblastoma signaling and could be rescued by ectopic expression of p16 INK4a. EC5 induced G 1 growth arrest of tumor cells and apoptosis, with the degradation of client proteins including epidermal growth factor receptor, c-Raf-1, Akt, and Cdk4 and inhibition of Akt phosphorylation. In vivo, EC5 dramatically reduced the growth rate of established HNSCC xenografts in nude mice and decreased expression of epidermal growth factor receptor and Akt within the xenografts.These results suggest that this novel ansamycin-based Hsp90 inhibitor affects multiple pathways involved in tumor development and progression and may represent a new strategy for the treatment of HNSCC patients.

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“…Carey (University of Michigan, Ann Arbor, MI). These cell lines have been extensively characterized and exhibit alterations detected in the majority of HNSCC, including epidermal growth factor receptor activation (26), constitutive activation of NF-nB and target genes (10 -12) and either wild-type (UMSCC-1, UMSCC-6, UMSCC-9, and UMSCC-11A) or mutant (UMSCC-11B and UMSCC-38) p53 genotype (27). 3 UMSCC-11A and UMSCC-11B were used for molecular studies because they have been shown previously to form xenografts and differ in sensitivity to chemotherapy agents, with UMSCC-11A being relatively more resistant to bortezomib and other agents in vitro and in mice in vivo (16).…”

Section: Inhibitors and Antibodiesmentioning

confidence: 99%

Nuclear factor-κB p65 small interfering RNA or proteasome inhibitor bortezomib sensitizes head and neck squamous cell carcinomas to classic histone deacetylase inhibitors and novel histone deacetylase inhibitor PXD101

Duan

Friedman

Nottingham

et al. 2007

Molecular Cancer Therapeutics

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Histone deacetylase inhibitors (HDI) can inhibit proliferation and enhance apoptosis in a wide range of malignancies. However, HDIs show relatively modest activity in head and neck squamous cell carcinomas (HNSCC), in which we have shown the activation of nuclear factor-KB (NF-KB; NF-KB1/RelA or p50/p65), a transcription factor that promotes expression of proliferative and antiapoptotic genes. In this study, we examined if HDIs enhance activation of NF-KB and target genes and if genetic or pharmacologic inhibition of NF-KB can sensitize HNSCC to HDIs. Limited activity of classic HDIs trichostatin A and sodium butyrate was associated with enhanced activation of NF-KB reporter activity in a panel of six HNSCC cell lines. HDIs enhanced NF-KB p50/p65 DNA binding and acetylation of the RelA p65 subunit. Transfection of small interfering RNAs targeting p65 strongly inhibited NF-KB expression and activation, induced cell cycle arrest and cell death, and further sensitized HNSCC cells when combined with HDIs. The p65 small interfering RNA inhibited HDI-enhanced expression of several NF-KB -inducible genes implicated in oncogenesis of HNSCC, such as p21, cyclin D1, and BCL-XL. Bortezomib, an inhibitor of proteasome-dependent NF-KB activation, also increased sensitization to trichostatin A, sodium butyrate, and a novel HDI, PXD101, in vitro, and to the antitumor effects of PXD101 in bortezomib-resistant UMSCC-11A xenografts. However, gastrointestinal toxicity, weight loss, and mortality of the combination were dose limiting and required parenteral fluid administration. We conclude that HDI-enhanced NF-KB activation is one of the major mechanisms of resistance of HNSCC to HDIs.

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P53 mutation correlates with cisplatin sensitivity in head and neck squamous cell carcinoma lines

Abstract: These in vitro data support a role for mutation of the p53 tumor suppressor gene as a marker for response to cisplatin in HNSCC.

Cited by 144 publications

References 27 publications

Correlations Between Prognosis and Regional Biomarker Profiles in Head and Neck Squamous Cell Carcinomas

Correlations Between Prognosis and Regional Biomarker Profiles in Head and Neck Squamous Cell Carcinomas

Potent Activity of a Novel Dimeric Heat Shock Protein 90 Inhibitor against Head and Neck Squamous Cell Carcinoma In vitro and In vivo

Nuclear factor-κB p65 small interfering RNA or proteasome inhibitor bortezomib sensitizes head and neck squamous cell carcinomas to classic histone deacetylase inhibitors and novel histone deacetylase inhibitor PXD101

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