Taxanes as radiosensitizers for head and neck cancer

Herscher, Laurie L.; Cook, John

doi:10.1097/00001622-199905000-00008

Cited by 22 publications

(9 citation statements)

References 14 publications

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“…Inhibition of IkB-a phosphorylation, which blocks IkB-a disassociation from p65/ p50 complexes, downregulates NF-kB and sensitizes cells to DNA-damaging agents (Miyakoshi and Yagi, 2000). Many other results demonstrate that inhibition of NF-kB function increases cell radiosensitivity (Shao et al, 1997;Lee et al, 1998;Herscher et al, 1999;Yang et al, 1999;Kato et al, 2000). We have reported that NF-kB activity is induced by radiation in breast carcinoma MCF-7 cells ) and virus-transformed human keratinocytes (Chen et al, 2002).…”

Section: Introductionmentioning

confidence: 92%

Expression of ErbB2 enhances radiation-induced NF-κB activation

et al. 2004

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Her-2/neu (ErbB2) oncogene, the second member of the epidermal growth factor receptor (EGFR) family, encodes a transmembrane tyrosine kinase receptor in Her-2-positive tumors. Accumulating evidences demonstrate that signaling networks activated by EGFR and transcription factor NFjB are associated with cell response to ionizing radiation (IR). The present study shows that overexpression of ErbB2 enhanced NF-jB activation induced by IR in human breast carcinoma MCF-7 cells transfected with ErbB2 genes (MCF-7/ErbB2). Stable transfection of dominantnegative mutant IjB (MCF-7/ErbB2/mIjB) or treatment with anti-ErbB2 antibody, Herceptin, inhibited NF-jB activation and radiosensitized MCF-7/ErbB2 cells. Consistent with NF-jB regulation, basal and IR-induced Akt, a kinase downstream of ErbB2, was activated in MCF-7/ ErbB2 cells and inhibited by Herceptin. To identify specific genes affected by ErbB2-mediated NF-jB activation, a group of IR-responsive elements Cyclin B1, Cyclin D1, Bcl-2, Bcl/XL, BAD and BAX were evaluated. Basal levels of prosurvival elements Cyclin B1, Cyclin D1, Bcl-2 and Bcl/XL but not apoptotic BAD and BAX were upregulated in MCF-7/ErbB2 cells with striking enhancements in Bcl-2 and Bcl/XL. IR further induced Cyclin B1 and Cyclin D1 expression that was reduced by Herceptin. Bcl-2 kept a high steady level after Herceptin þ IR treatment and, in contrast to control MCF-7/Vector cells, Bcl/XL was inhibited in MCF-7/ErbB2 cells by Herceptin þ IR treatment. However, all four prosurvival proteins were downregulated by inhibition of NF-jB in MCF-7/ErbB2/mIjB cells. These results thus provide evidence suggesting that overexpression of ErbB2 is able to enhance NF-jB response to IR, and that a specific prosurvival network downstream of NF-jB is triggered by treatments using anti-ErbB2 antibody combined with radiation.

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Section: Introductionmentioning

confidence: 92%

Expression of ErbB2 enhances radiation-induced NF-κB activation

et al. 2004

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“…A reduction in CDK1/cyclin B1 kinase activity triggers G2/M cell cycle arrest (Cui et al, 2012;Khan et al, 2011). Accumulated evidence has suggested that a lot of radiosensitizing agents worked in different cancers such as taxol (Herscher et al, 1999), oxamate (Zhai et al, 2013) through inducing G2/M arrest via downregulation of cyclinB and CDK1. In the present study, a decrease in the protein levels of cyclin B1 and CDK1 were observed in the combined treatment of fenofibrate with irradiation group.…”

Section: Jia Liu Et Almentioning

confidence: 99%

Fenofibrate Increases Radiosensitivity in Head and Neck Squamous Cell Carcinoma via Inducing G2/M Arrest and Apoptosis

Liu¹,

Ge²,

Zhu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/ or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.

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“…The taxanes had been identified as potential radiosensitizers when preclinical data revealed their lethal effects of inhibiting mitosis, interfering with the cell cycle, and encouraging apoptosis (Herscher et al, 1999). Taxane was shown to have significant activity in patients with metastatic esophageal cancer in the early 1990s (Ajani et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Systematic Analysis of Pemetrexed-based Chemoradiotherapy for Patients with Locally Advanced or Metastatic Esophageal Cancer

Tian

Miu²,

Huang³

2014

Asian Pacific Journal of Cancer Prevention

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Purpose: This systematic analysis was conducted to evaluate the efficacy and safety of pemetrexed-based chemoradiotherapy in treating patients with locally advanced or metastatic esophageal cancer. Methods: Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for relevant patients were identified using a predefined search strategy. Pooled response rates (RRs) were calculated. Results: For pemetrexed-based regimens, 4 clinical studies including 47 patients with locally advanced or metastatic esophageal cancer were considered eligible for inclusion. Systematic analysis showed that, in all patients, the pooled RR was 51% (24/47) . Major adverse effects of grade III/IV were esophagitis, neutropenia, thrombocytopenia, anemia anorexia, fatigue, diarrhea, dysphagia and vomiting. No treatment related death occurred with pemetrexed-based treatment. Conclusion: This systematic analysis suggests that pemetrexed based radiotherapy is associated with reasonable activity and good tolerability in treating patients with locally advanced or metastatic esophageal cancer.

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Taxanes as radiosensitizers for head and neck cancer

Cited by 22 publications

References 14 publications

Expression of ErbB2 enhances radiation-induced NF-κB activation

Expression of ErbB2 enhances radiation-induced NF-κB activation

Fenofibrate Increases Radiosensitivity in Head and Neck Squamous Cell Carcinoma via Inducing G2/M Arrest and Apoptosis

Systematic Analysis of Pemetrexed-based Chemoradiotherapy for Patients with Locally Advanced or Metastatic Esophageal Cancer

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