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Head and neck cancer (HNC) is a heterogenous and complex entity including diverse anatomical sites and a variety of tumor types displaying unique characteristics and different etilogies. Both environmental and genetic factors play a role in the development of the disease, but the underlying mechanism is still far from clear. Previous studies suggest that alterations in the genes acting in cellular signal pathways may contribute to head and neck carcinogenesis. In cancer, DNA methylation patterns display specific aberrations even in the early and precancerous stages and may confer susceptibility to further genetic or epigenetic changes. Silencing of the genes by hypermethylation or induction of oncogenes by promoter hypomethylation are frequent mechanisms in different types of cancer and achieve increasing diagnostic and therapeutic importance since the changes are reversible. Therefore, methylation analysis may provide promising clinical applications, including the development of new biomarkers and prediction of the therapeutic response or prognosis. In this review, we aimed to analyze the available information indicating a role for the epigenetic changes in HNC.  相似文献   

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Resistance to cisplatin-based chemotherapy is responsible for therapeutic failure of many common human cancers including cancer of head and neck (HNC). Mechanisms underlying cisplatin resistance remain unclear. In this study, we identified neurofilament light polypeptide (NEFL) as a novel hypermethylated gene associated with resistance to cisplatin-based chemotherapy in HNC. Analysis of 14 HNC cell lines revealed that downregulation of NEFL expression significantly correlated with increased resistance to cisplatin. Hypermethylation of NEFL promoter CpG islands was observed in cell lines as examined by bisulfite DNA sequencing and methylation-specific PCR (MSP) and tightly correlated with reduced NEFL mRNA and protein expression. Furthermore, in patient samples with HNC (n = 51) analyzed by quantitative MSP, NEFL promoter hypermethylation was associated with resistance to cisplatin-based chemotherapy [relative risk (RR), 3.045; 95% confidence interval (CI), 1.459-6.355; P = 0.007] and predicted diminished overall and disease-free survival for patients treated with cisplatin-based chemotherapy. Knockdown of NEFL by siRNA in the highly cisplatin-sensitive cell line PCI13 increased (P < 0.01) resistance to cisplatin. In cisplatin-resistant O11 and SCC25cp cells, restored expression of NEFL significantly increased sensitivity to the drug. Furthermore, NEFL physically associated with tuberous sclerosis complex 1 (TSC1), a known inhibitor of the mTOR pathway, and NEFL downregulation led to functional activation of mTOR pathway and consequentially conferred cisplatin resistance. This is the first study to show a role for NEFL in HNC chemoresistance. Our findings suggest that NEFL methylation is a novel mechanism for HNC chemoresistance and may represent a candidate biomarker predictive of chemotherapeutic response and survival in patients with HNC.  相似文献   

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Spinal stability is related to both the intrinsic stiffness of active muscle as well as neuromuscular reflex response. However, existing analyses of spinal stability ignore the role of the reflex response, focusing solely on the intrinsic muscle stiffness associated with voluntary activation patterns in the torso musculature. The goal of this study was to empirically characterize the role of reflex components of spinal stability during voluntary trunk extension exertions. Pseudorandom position perturbations of the torso and associated driving forces were recorded in 11 healthy adults. Nonlinear systems-identification analyses of the measured data provided an estimate of total systems dynamics that explained 81% of the movement variability. Proportional intrinsic response was less than zero in more than 60% of the trials, e.g. mean value of P(INT) during the 20% maximum voluntary exertion trunk extension exertions -415+/-354N/m. The negative value indicated that the intrinsic muscle stiffness was not sufficient to stabilize the spine without reflex response. Reflexes accounted for 42% of the total stabilizing trunk stiffness. Both intrinsic and reflex components of stiffness increased significantly with trunk extension effort. Results reveal that reflex dynamics are a necessary component in the stabilizing control of spinal stability.  相似文献   

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Lumbar spine stability has been extensively researched due to its necessity to facilitate load-bearing human movements and prevent structural injury. The nature of certain human movement tasks are such that they are not equivalent in levels of task-stability (i.e. the stability of the external environment). The goal of the current study was to compare the effects of dynamic lift instability, administered through both the load and base of support, on the dynamic stability (maximal Lyapunov exponents) and stiffness (EMG-driven model) of the lumbar spine during repeated sagittal lifts. Fifteen healthy males performed 23 repetitive lifts with varying conditions of instability at the loading and support interfaces. An increase in spine rotational stiffness occurred during unstable support scenarios resulting in an observed increase in mean and maximum Euclidean norm spine rotational stiffness (p=0.0011). Significant stiffening effects were observed in unstable support conditions about all lumbar spine axes with the exception of lateral bend. Relative to a stable control lifting trial, the addition of both an unstable load as well as an unstable support did not result in a significant change in the local dynamic stability of the lumbar spine (p=0.5592). The results suggest that local dynamic stability of the lumbar spine represents a conserved measure actively controlled, at least in part, by trunk muscle stiffening effects. It is evident therefore that local dynamic stability of the lumbar spine can be modulated effectively within a young-healthy population; however this may not be the case in a patient population.  相似文献   

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Epidermal growth factor receptor (EGFR) is highly expressed in head and neck cancer (HNC). Since EGFR has a large extracellular ligand binding as well as an intracellular tyrosine kinase domain, anti-EGFR therapy may involve anti-ligand binding domain antibody- or tyrosine kinase inhibitor therapies. Phase II-III studies confirmed the efficacy of anti-EGFR antibody therapy in case of squamous cell HNC. In combination with irradiation, anti-EGFR antibody therapy improved survival of locally advanced HNC patients. In case of recurrent or metastatic HNC, anti-EGFR antibody therapy in combination with chemotherapy significantly increased remission rate without increasing toxicity. Although studies on EGFR kinase inhibitors in HNC are in early phase, preliminary data are encouraging.  相似文献   

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DNA repair is critical for genotoxic susceptibility and cancer development. Forty-seven patients with head and neck squamous cell carcinoma (HNSCC) and 38 healthy controls were enrolled in this study. Among the patients, 16 subjects had metastasis of HNSCC. The extent of DNA damage, including oxidative lesions, and efficiency of repair after genotoxic treatment with hydrogen peroxide were examined using the alkaline comet assay. HNSCC cells were sensitive to genotoxic treatment and displayed impaired DNA repair. In particular, lesions caused by hydrogen peroxide were repaired less effectively in cancer cells from patients with metastasis than in cells from healthy controls. We suggest that impaired DNA repair might play a role in genotoxic susceptibility of patients with head and neck cancer. Finally, as a consequence of this finding we have shown that treatment with DNA-reactive drugs could be considered as an effective therapy strategy for head and neck cancer.  相似文献   

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In the non-surgical treatment of head and neck tumours, the "organ preserving" modalities have become more and more important. At present radiotherapy is the most important means of this kind of treatment. In the radiotherapy of head and neck cancer local dose escalation is an important factor in increasing local tumour control. However, with sole external beam irradiation it is difficult to spare adjacent normal tissues. Interstitial brachytherapy (BT) is ideally suited to deliver a high dose limited to the volume of the primary tumour, thus maximizing tumour control while minimizing complications. Low-dose-rate (LDR) BT, which has been applied for a long time in the treatment of these tumours, is now challenged by high-dose-rate (HDR) and pulsed-dose-rate (PDR) BT. The purpose of this work is to show the role and the indications of BT in tumours of the head and neck region and to offer general and site-specific recommendations based upon the available information from the literature.  相似文献   

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Head and neck cancer represents a challenging disease. Despite recent treatment advances, which have improved functional outcomes, the long-term survival of head and neck cancer patients has remained unchanged for the past 25 years. One of the goals of adjuvant cancer therapy is to eradicate local regional microscopic and micrometastatic disease with minimal toxicity to surrounding normal cells. In this respect, antigen-specific immunotherapy is an attractive therapeutic approach. With the advances in molecular genetics and fundamental immunology, antigen-specific immunotherapy is being actively explored using DNA, bacterial vector, viral vector, peptide, protein, dendritic cell, and tumor-cell based vaccines. Early phase clinical trials have demonstrated the safety and feasibility of these novel therapies and the emphasis is now shifting towards the development of strategies, which can increase the potency of these vaccines. As the field of immunotherapy matures and as our understanding of the complex interaction between tumor and host develops, we get closer to realizing the potential of immunotherapy as an adjunctive method to control head and neck cancer and improve long-term survival in this patient population.  相似文献   

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Cytokines in head and neck cancer   总被引:2,自引:0,他引:2  
Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers in the world. Standard treatment has only marginally improved the 5-year survival rate of patients with HNSCC in the last 40 years. Alterations in immune, inflammatory as well as angiogenetic responses within the HNSCC microenvironment play a critical role in tumor aggressiveness and its response to chemo- and radiation therapies as well as its influence on the immune system. Therefore, the better understanding of secretion and regulation pathways of immune suppressive and proangiogenic cytokines in HNSCC is essential to increase the clinical perspective of this tumor type with respect to an immunomodulatory intervention in patients with HNSCC.  相似文献   

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Advances in head and neck reconstruction   总被引:5,自引:0,他引:5  
Head and neck deformities, which can be caused by trauma, congenital defects, infections, or neoplasms, produce a stereotypical constellation of functional and aesthetic deficits, depending on the specific anatomic region. These deformities can be classified into six major anatomic categories: intraoral, mandibular, midfacial, cranial base, cutaneous, and scalp. This article presents a reliable approach to the reconstruction of these six areas that is used at the University of Texas M. D. Anderson Cancer Center. The emphasis is on an analysis of the unique functional and aesthetic problems presented by each of these specific anatomic lesions, and the reconstructive options are selected to maximize outcomes. The problems and limitations of current methods are discussed, and areas of potential development are explored.  相似文献   

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Molecular pathology of head and neck cancer   总被引:6,自引:0,他引:6  
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Cancers of the upper aerodigestive tract, collectively known as head and neck cancers, arise from a multiplicity of sites. In the West, excess tobacco and alcohol consumption are the most important of the known predisposing factors; elsewhere in the world, notably in India and China, the aetiology, pattern of primary sites, and clinical behaviour are different. Clinically these tumours pose exceptional problems in management, and skilled multidisciplinary teams are necessary in order to achieve the highest level of service and research. Historically, surgery and radiotherapy have been the most important treatment modalities; chemotherapy is now increasingly employed but not yet fully established. Successful rehabilitation of patients with head and neck cancers requires access to high quality speech therapists and other support staff with training in functional pharyngeal disorders. Current research efforts are largely directed towards defining the proper role of chemotherapy and assessing the possible advantage of unconventional radiation approaches. In recent years the roles of primary, reconstructive, and salvage surgery have also become better defined. Many patients are suitable for randomisation into ongoing prospective clinical trials which have been specifically designed to address these issues.  相似文献   

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Giant neurofibroma of the head and neck   总被引:1,自引:0,他引:1  
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