Molecular Diagnosis of Head and Neck Cancer

Houten, Viola M. M. van; Brekel, M.W.M. van den; Denkers, Fedor; Colnot, David R.; Westerga, Johan; Diest, P. J. van; Snow, Gordon B.; Brakenhoff, Ruud H.

doi:10.1007/978-3-642-57151-0_8

Cited by 12 publications

(10 citation statements)

References 45 publications

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“…Given identical conditions, DNA from control and treated samples amplify differently depending on the number of lesions present on the template by the time of the reaction. For example, DNA from cells exposed to UV amplifies less than DNA from the respective non-treated control [35]. The amount of damage can be expressed as number of lesions per 10 kb assuming a Poisson distribution of lesions on the template.…”

Section: Resultsmentioning

confidence: 99%

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Expression of NES-hTERT in Cancer Cells Delays Cell Cycle Progression and Increases Sensitivity to Genotoxic Stress

et al. 2010

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Telomerase is a reverse transcriptase associated with cellular immortality through telomere maintenance. This enzyme is activated in 90% of human cancers, and inhibitors of telomerase are currently in clinical trials to counteract tumor growth. Many aspects of telomerase biology have been investigated for therapy, particularly inhibition of the enzyme, but little was done regarding its subcellular shuttling. We have recently shown that mutations in the nuclear export signal of hTERT, the catalytic component of telomerase, led to a mutant (NES-hTERT) that failed to immortalize cells despite nuclear localization and catalytic activity. Expression of NES-hTERT in primary fibroblast resulted in telomere-based premature senescence and mitochondrial dysfunction. Here we show that expression of NES-hTERT in LNCaP, SQ20B and HeLa cells rapidly and significantly decreases their proliferation rate and ability to form colonies in soft agar while not interfering with endogenous telomerase activity. The cancer cells showed increased DNA damage at telomeric and extra-telomeric sites, and became sensitive to ionizing radiation and hydrogen peroxide exposures. Our data show that expression of NES-hTERT efficiently counteracts cancer cell growth in vitro in at least two different ways, and suggest manipulation with the NES of hTERT or its subcellular shuttling as a new strategy for cancer treatment.

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Section: Resultsmentioning

confidence: 99%

“…To monitor possible changes in mtDNA copy number, a short fragment of the mitochondrial genome is also amplified in order to normalize the data. Sensitivity limit of the technique is 1 lesion/10 5 bases (for more details on the assay, see references [25]–[27] and [35].…”

Section: Resultsmentioning

confidence: 99%

Expression of NES-hTERT in Cancer Cells Delays Cell Cycle Progression and Increases Sensitivity to Genotoxic Stress

et al. 2010

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“…17 Using the reverse transcriptase polymerase chain reaction (PCR) technique, one research group has been able to detect 1 tumor cell circulating in 7 mL of blood. 18 The potential for this strategy is tremendous. It is conceivable that the identification of a biomarker specific for head and neck tumors or of a panel of such biomarkers may allow the detection of microscopic distant disease.…”

mentioning

confidence: 99%

The Use of Genetic Markers in the Clinical Care of Patients With Head and Neck Cancer

Friedlander

2003

Arch Otolaryngol Head Neck Surg

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“…Over the past 30 years, patients with recurrent and/or metastatic HNSCC have had a poor prognosis [2, 3]. More than 50% of newly diagnosed patients do not achieve complete remission, and approximately 10% relapse with metastasis to distant organs [4]. Therefore, research focused on gaining a better understanding of this disease and on the development of novel treatment strategies is required.…”

Section: Introductionmentioning

confidence: 99%

Present and Future of EGFR Inhibitors for Head and Neck Squamous Cell Cancer

Baba

Fujisawa

Tokumaru

et al. 2012

Journal of Oncology

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Although EGFR is expressed at high levels in head and neck squamous cell carcinomas (HNSCCs) and mutations are extremely rare, monotherapy with EGFR inhibitors has shown limited success. The PI3kinase/Akt pathway is responsible for cellular survival, and inhibition of phosphatidylinositol (PI) synthesis has antiproliferative, anti-invasive, and antiangiogenesis effects on HNSCC. Molecular crosstalk has been observed between EGFR and IGF1R signaling through the PI3kinase/Akt pathway in HNSCC, as has molecular crosstalk between the NFκB and STAT3 signaling pathways. Therefore, the combination of an EGFR antagonist with an agent that inhibits the activation of both Akt and NFκB may overcome resistance to EGFR antagonists in HNSCC.

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Molecular Diagnosis of Head and Neck Cancer

Cited by 12 publications

References 45 publications

Expression of NES-hTERT in Cancer Cells Delays Cell Cycle Progression and Increases Sensitivity to Genotoxic Stress

Expression of NES-hTERT in Cancer Cells Delays Cell Cycle Progression and Increases Sensitivity to Genotoxic Stress

The Use of Genetic Markers in the Clinical Care of Patients With Head and Neck Cancer

Present and Future of EGFR Inhibitors for Head and Neck Squamous Cell Cancer

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