Laryngeal carcinoma and radioresistance

Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is an important hypoxic marker in malignant tumors, including laryngeal carcinoma. Apigenin is a natural phytoestrogen flavonoid that has potential anticancer effects. Various studies have reported that the effects of apigenin on lowering GLUT-1 expression were involved in downregulation of the PI3K/Akt pathway. Thus, apigenin may improve the radiosensitivity of laryngeal carcinoma by suppressing the expression of GLUT-1 via the PI3K/Akt pathway...

BACKGROUND: Increasing evidence indicates that dysregulation of microRNAs is involved in tumor progression and development. The aim of this study was to investigate the expression of microRNA-24 (miR-24) and its function in laryngeal squamous cell carcinoma (LSCC). METHODS: Quantitative RT-PCR (qRT-PCR) was used to detect miR-24 expression in LSCC cell lines and tissue samples. MTT, colony formation, and flow cytometry was performed to analyze the effects of miR-24 expression on growth, apoptosis, and radiosensitivity of LSCC cells...

Accumulating evidence suggests that changes in methylation patterns may help mediate the sensitivity or resistance of cancer cells to ionizing radiation. The present study provides evidence for the involvement of radioresistance-induced DNA methylation changes in tumor radioresistance. We established radioresistant laryngeal cancer cells via long-term fractionated irradiation, and examined differences in DNA methylation between control and radioresistant laryngeal cancer cells. Interestingly, we found that the promoter-CpG islands of 5 previously identified radioresistance-related genes (TOPO2A, PLXDC2, ETNK2, GFI1, and IL12B) were significantly altered in the radioresistant laryngeal cancer cells...

Radiotherapy is an important treatment modality for laryngeal carcinoma, however, some patients with early stage laryngeal carcinomas showed resistance to radiotherapy. Survivin overexpression is associated with radioresistance of laryngeal squamous cell carcinoma. We speculated that the inhibition of survivin expression might improve the radiosensitivity of laryngeal carcinoma. We assessed the effect of survivin expressions by shRNA on the radiosensitivity of laryngeal squamous cell carcinoma in vitro and in vivo...

PURPOSE: To assess clinical outcomes and patterns of loco-regional failure (LRF) in relation to clinical target volumes (CTV) in patients with locally advanced hypopharyngeal and laryngeal squamous cell carcinoma (HL-SCC) treated with definitive intensity modulated radiotherapy (IMRT) and concurrent systemic therapy. METHODS: Data from HL-SCC patients treated from 2007 to 2010 were retrospectively evaluated. Primary endpoint was loco-regional control (LRC). Secondary endpoints included local (LC) and regional (RC) controls, distant metastasis free survival (DMFS), laryngectomy free survival (LFS), overall survival (OS), and acute and late toxicities...

The aim of this systematic review was to determine the prognostic value of Bcl-2 immunostaining in patients affected by laryngeal squamous cell carcinoma. An appropriate search was conducted on PubMed to retrieve articles dealing with this topic. A double cross-check was performed on citations and full-text articles by 2 investigators independently to review all manuscripts and perform a comprehensive quality assessment. Of 115 abstracts identified, 15 articles were included. These studies reported on 1,150 patients with histologically confirmed diagnosis of laryngeal squamous cell carcinoma...

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PURPOSE: Laryngeal carcinomas always resist to radiotherapy. Hypoxia is an important factor in radioresistance of laryngeal carcinoma. Glucose transporter-1 (GLUT-1) is considered to be a possible intrinsic marker of hypoxia in malignant tumors. We speculated that the inhibition of GLUT-1 expression might improve the radiosensitivity of laryngeal carcinoma. METHODS: We assessed the effect of GLUT-1 expression on radioresistance of laryngeal carcinoma and the effect of GLUT-1 expressions by antisense oligodeoxynucleotides (AS-ODNs) on the radiosensitivity of laryngeal carcinoma in vitro and in vivo...

Accelerated radiotherapy (AR) improves the poor prognosis associated with epidermal growth factor receptor (EGFR) overexpression frequently seen in head and neck carcinomas. Combining AR with carbogen and nicotinamide (ARCON) counteracts enhanced tumour cell proliferation- and hypoxia-related radioresistance. The purpose of this study was to investigate if EGFR expression levels are associated with response to ARCON in patients with carcinoma of the larynx. Patients (N=272) with advanced stage larynx carcinoma were randomised between AR alone and ARCON...

The known functions of telomerase in tumor cells include replenishing telomeric DNA and maintaining cell immortality. We have previously shown the existence of a negative correlation between human telomerase reverse transcriptase (hTERT) and radiosensitivity in tumor cells. Here we set out to elucidate the molecular mechanisms underlying regulation by telomerase of radiosensitivity in MCF-7 cells. Toward this aim, yeast two-hybrid (Y2H) screening of a human laryngeal squamous cell carcinoma radioresistant (Hep2R) cDNA library was first performed to search for potential hTERT interacting proteins...

Hypoxia promotes the radioresistance of laryngeal carcinomas and CD133 is one of the markers expressed by tumor-initiating, human laryngeal carcinoma cells. In order to investigate whether CD133-positive Hep-2 cells exhibit a radioresistant phenotype and to determine whether hypoxia promotes this phenotype, we performed a series of experiments. Hep-2 cells, and Hep-2 cells stably expressing hypoxia-inducible factor (HIF)-targeted small interfering RNA (siRNA) were cultured under hypoxic and normoxic conditions and were treated with varying doses of γ-rays (0, 5, 10, 15 and 20 Gy)...

Laryngeal carcinoma, as a malignant tumor that occurs in the head and neck region, is widely treated by radiation, but in some cases, the cancer is radioresistant to the radiotherapy. The reason for the radioresistant response needs to be clinically understood. We designed our present study to identify the molecules that may be involved in this radioresistant response. In this study, we initially established the inherent radioresistant (Hep-2max) and radiosensitive (Hep-2min) cell lines from the parental laryngeal cancer cell line Hep-2...

BACKGROUND: Early-stage laryngeal squamous cell carcinoma is managed with radiotherapy or endoscopic surgery. Although cure rates are high, radiation failures often require total laryngectomy for salvage. Biomarkers that can predict tumour radioresistance may be useful in modifying the treatment approach for individual patients. METHODS: Retrospective patient chart review yielded 75 patients with T1-T2 glottic squamous cell carcinoma treated with radiation therapy at the London Health Sciences Centre...

OBJECTIVE: To study whether cancer stem cells promotes resistance of laryngeal squamous cancer to irradiation mediated by hypoxia. METHOD: Hep-2 cells were respectively cultured in hypoxia and normoxia environment, and the express of HIF-la was detected by western blot. Then they were radiated with different doses of gamma-rays. After that we detected growth inhibition ratio with MTT assay, cell circle and ratio of CD133+ cells with Flow cytometry at different times...

BACKGROUND: The aim of this study was to evaluate the significance of nuclear factor-kappa B (NF-kappaB) expression as a marker of radioresistance in early-stage laryngeal cancer. METHODS: Thirty-five patients with local recurrence and 70 case-matched patients without local recurrence were entered in this study. NF-kappaB expression was compared with Bcl-2 and epidermal growth factor (EGF) receptor expression by immunohistochemistry, using pretreatment biopsy specimens...

Targeting hypoxia-inducible factor-1 (HIF-1) active cells in tumors may be an excellent strategy to improve the outcome of radiation therapy. On the basis of the reported role of YC-1 as a HIF-1 inhibitor with anti-cancer activity, we tested the therapeutic efficacy of YC-1 against radioresistance in vitro. The AMC-HN3 cancer cell line, developed from squamous cell carcinoma of the larynx, was cultured under hypoxic conditions or in the presence of cobalt chloride. Both treatments induced nuclear accumulation of HIF-1alpha protein...

Telomere-associated proteins function as survival factors in telomere maintenance, which are major contributors to radiosensitivity in human cancers. The aim of this study was to investigate the association of telomere-associated gene expression and radiation resistance in human larynx squamous carcinoma. The changes of telomere-associated gene expressions and bionomical characteristics that occur in two human larynx squamous carcinoma cell lines (Hep-2 and Hep-2R), with different radiosensitivities in vitro were explored in the present study...

Radioresistant cells have been shown to correlate with poor outcome after radiotherapy. Here, we found that human telomerase reverse transcriptase promoter (hTERTp) had lower activity in laryngeal squamous carcinomas cells than in radioresistant variant cells. Combining radiotherapy with plasmid phTERTp-HRP, in which expression of enzyme horseradish peroxidase (HRP) controlled by hTERTp, resulted in increased apoptosis and necrosis of tumor cells after prodrug indole-3-acetic acid (IAA; converted by HRP into a cytotoxin) incubation...

OBJECTIVES/HYPOTHESIS: To find biomarkers associated with response to radiotherapy in laryngeal cancer that can be used together with clinical parameters to improve outcome prediction. METHODS: In this study, 26 patients irradiated for laryngeal carcinomas with a local recurrence within two years (cases) and 33 patients without recurrence (controls) were included. All pretreatment biopsies were arrayed onto a tissue array. Immunohistochemistry was performed for 13 biomarkers that were selected from the literature as potential predictors for radioresponse in head and neck (HN) cancer: Bcl-2, Bcl-xL, p16, p21, p27, p53, cyclin D1, HIF-1alpha, CA9, COX-2, EGFR, ki-67, and pRB...

TRAIL induces apoptosis in a variety of tumorigenic and transformed cell lines, but not in many normal cells. Recent studies have demonstrated that death receptor 5 (DR5), one of the two death receptors bound by TRAIL, showed expression in most malignantly transformed cells. This study evaluated effects of a monoclonal antibody (TRA-8) to human death receptor 5, combined with ionizing radiation, on radioresistant human larynx squamous carcinoma cell line (Hep-2R). Cells were treated with TRA-8 alone or in combination with radiation, cell viability inhibition was measured by MTT assay, and the induction of apoptosis was determined by Annexin V staining...