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Sample records for nasopharyngeal carcinoma stenose

  1. Treatment for metastatic nasopharyngeal carcinoma.

    PubMed

    Bensouda, Y; Kaikani, W; Ahbeddou, N; Rahhali, R; Jabri, M; Mrabti, H; Boussen, H; Errihani, H

    2011-04-01

    Nasopharyngeal carcinoma (NPC) is a specific entity different from head and neck carcinoma. Incidence is higher in South-East Asia and North Africa. Prognosis, especially for locally advanced stages (IIB - IVB) and metastasis, remains poor: more than third of cases will present local and/or metastatic recurrence. Overall 5-year survival for all NPC stages ranges from 50% to 70%. The role of chemotherapy in metastasis is well established, and remains an important palliative treatment, although no randomized trial has been reported comparing the different chemotherapy regimens. As 1(st)-line treatment, platin-based regimens seems optimal; in 2(nd) line and after progression under platins, there is no consensus: monotherapy with drugs such as gemcitabine, capecitabine or taxanes has been the most widely tested, with acceptable results. Future trials should integrate targeted therapy, in the light of overexpression of EGFR1 and C-kit in NPC. The present study presents a review of the literature concerning the various studies of metastatic NPC. PMID:21177151

  2. A Review: Proteomics in Nasopharyngeal Carcinoma

    PubMed Central

    Chen, Ze-Tan; Liang, Zhong-Guo; Zhu, Xiao-Dong

    2015-01-01

    Although radiotherapy is generally effective in the treatment of major nasopharyngeal carcinoma (NPC), this treatment still makes approximately 20% of patients radioresistant. Therefore, the identification of blood or biopsy biomarkers that can predict the treatment response to radioresistance and that can diagnosis early stages of NPC would be highly useful to improve this situation. Proteomics is widely used in NPC for searching biomarkers and comparing differentially expressed proteins. In this review, an overview of proteomics with different samples related to NPC and common proteomics methods was made. In conclusion, identical proteins are sorted as follows: Keratin is ranked the highest followed by such proteins as annexin, heat shock protein, 14-3-3σ, nm-23 protein, cathepsin, heterogeneous nuclear ribonucleoproteins, enolase, triosephosphate isomerase, stathmin, prohibitin, and vimentin. This ranking indicates that these proteins may be NPC-related proteins and have potential value for further studies. PMID:26184160

  3. Therapeutic vaccination strategies to treat nasopharyngeal carcinoma.

    PubMed

    Taylor, Graham S; Steven, Neil M

    2016-04-01

    Epstein-Barr virus (EBV) infects most people worldwide. EBV has oncogenic potential and is strongly associated with several lymphomas and carcinomas, including nasopharyngeal carcinoma (NPC), that together total 200,000 cases of cancer each year. All EBV-associated cancers express viral proteins that allow highly selective immunotherapeutic targeting of the malignant cells. A number of therapeutic EBV vaccines have been tested in clinical trials with evidence of immune boosting and clinical responses in NPC patients. Therapeutic vaccination could be used after adoptive T-cell transfer to increase and sustain the number of infused T-cells or combined with immunotherapies acting at different stages of the cancer immunity cycle to increase efficacy. The therapeutic EBV vaccines tested to date have been well tolerated with minimal off-target toxicity. A safe therapeutic vaccine that was also able to be mass produced could, in principle, be used to vaccinate large numbers of patients after first line therapy to reduce recurrence. PMID:27121883

  4. Nasopharyngeal mucoepidermoid carcinoma - a common entity at an uncommon location.

    PubMed

    Hemalatha, A L; Kumar H K, Sharath; S, Geetanjali; M, Giripunja; S D, Shashikumar

    2014-01-01

    Mucoepidermoid carcinomas mostly occur in the major salivary glands, the minor salivary glands of oral cavity and in the lacrimal glands. These tumours rarely occur in the sino-nasal tract. When they occur in the sino-nasal tract, the most frequent site is the maxillary antrum, followed by the nasal cavity, the nasopharynx and the ethmoidal sinuses. As per review of literature, nasopharyngeal mucoepidermoid carcinomas account for 0.6% of salivary gland tumours and 4.8% of mucoepidermoid carcinomas. Extensive literature search revealed 21 cases of nasopharyngeal mucoepidermoid carcinomas reported till date. These cases showed an age incidence ranging from 20 to 60 years with a female preponderance. In contrast to nasopharyngeal carcinomas, these tumours show low positivity rates for Ebstein-Barr virus serological test. Histochemical positivity for mucin may be demonstrated in the glandular and mucinous components of these tumours. High grade mucoepidermoid carcinoma of nasopharynx is treated with surgical excision combined with radiotherapy and is associated with poor survival. Therefore, early diagnosis and prompt treatment are of utmost importance. This case report highlights the rare occurrence of a high grade nasopharyngeal muco-epidermoid carcinoma in a 70-year-old male and is presented for its unusual occurrence in the nasopharynx which is the most infrequent location for this lesion. PMID:24596757

  5. Salted fish and nasopharyngeal carcinoma in Malaysia.

    PubMed

    Armstrong, R W; Eng, A C

    1983-01-01

    The evidence for a hypothesis that eating salted fish is associated with nasopharyngeal carcinoma (NPC) is reviewed. The hypothesis was tested among Malaysian Chinese using a matched case-control design. The kinds of salted fish and patterns of use were also investigated in a control group comprising 100 Chinese, 50 Malay and 50 Indian households. During 1980, in Selangor, Malaysia, interviews with 100 Chinese cases of NPC and 100 non-disease controls indicated that salted fish consumption during childhood was a significant risk (relative risk = 3.0, P = 0.04), with an elevated risk for daily as opposed to less frequent consumption. Salted fish consumption during adolescence was a less significant risk, and current consumption not at all. There were 19 kinds of fishes reported as being eaten as salted fish by the 200 control households. There were marked differences between ethnic groups in preference for different kinds: Chinese preferred red snapper (74% of households), Malay jewfish (54%) and Indian red snapper (28%). Salted fish was hardly ever eaten daily by any household; weekly was a moderate frequency in all ethnic groups; less than weekly most common. There were no statistically significant differences between Chinese NPC case and non-disease control participants in kind of salted fish eaten. Results were the same when the data were analyzed by sex, subethnic group and income. PMID:6635717

  6. Advances in systemic treatment for nasopharyngeal carcinoma.

    PubMed

    Tan, Wan-Ling; Tan, Eng-Huat; Lim, Darren Wan-Teck; Ng, Quan-Sing; Tan, Daniel Shao-Weng; Jain, Amit; Ang, Mei-Kim

    2016-04-01

    Nasopharyngeal carcinoma (NPC) is a unique disease endemic in Asia. It is etiologically linked to the Epstein-Barr virus and is both radio- and chemo-sensitive. While radiotherapy (RT) remains the primary treatment modality with high cure rates for early stage disease, systemic treatment forms an important integral component in the treatment of NPC, both in the non-metastatic as well as palliative setting. Presently, standard therapy in locally advanced NPC comprises conventional cytotoxic chemotherapy administered concurrently during RT. The role of induction chemotherapy and adjuvant chemotherapy remain to be well-defined. Further research strategies in non-metastatic disease will require better identification of patients with high risk disease, and determining the optimal sequence and combination of chemotherapeutic regimens. In metastatic disease, whilst chemotherapy remains the mainstay of care, resistance inevitably develops. Development of molecularly targeted therapies has not yielded much success to date, and further research has been focused on development of EBV-targeted strategies such as vaccination or administration of cytotoxic T-cells directed towards EBV, as well as evaluation of immune checkpoint inhibition approaches. PMID:27121881

  7. Nasopharyngeal carcinoma with bone marrow metastasis.

    PubMed

    Zen, H G; Jame, J M; Chang, A Y; Li, W Y; Law, C K; Chen, K Y; Lin, C Z

    1991-02-01

    Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan. PMID:1987743

  8. MicroRNAs in nasopharyngeal carcinoma.

    PubMed

    Spence, Tara; Bruce, Jeff; Yip, Kenneth W; Liu, Fei-Fei

    2016-04-01

    It is becoming increasingly evident that aberrantly expressed microRNAs (miRNAs) are responsible for a number of disease processes, including cancer initiation and progression. miRNAs have been implicated as key players in numerous neoplasms, including nasopharyngeal carcinoma (NPC). Functionally, deregulation of miRNAs that act either as tumour suppressors or oncogenes results in numerous cancer-associated phenomena, including changes in proliferation, migration, and cell survival. Furthermore, miRNA expression has been associated with chemoresistant or radioresistant phenotypes; highlighting the importance of miRNAs in mediating oncogenic processes. Prognostic and predictive miRNA signatures have been defined for a variety of cancer types, including NPC, whereby these signatures offer a potentially important clinical tool for assessing the disease state, as well as predicting treatment response and clinical outcome. Therefore, further examination and validation of miRNAs that are deregulated in NPC will provide insight into the fundamental drivers of this disease, which will aid in the identification of novel targeted treatments. This review summarizes recent advances in the study of miRNAs in NPC, with specific discussion on the role of miRNAs in NPC pathogenesis and the potential utility of miRNAs as prognostic biomarkers. Our increasing understanding of the role of miRNAs in NPC tumorigenesis and their application as novel biomarkers will undoubtedly prove useful in the stratification of future patients into clinically relevant treatment classifications, thereby improving and personalizing disease management. PMID:27121877

  9. [Paraneoplastic dermatomyositis revealing an undifferentiated nasopharyngeal carcinoma: about a case].

    PubMed

    Ziani, Fatima Zahra; Brahmi, Sami Aziz; Najib, Rajae; Kanab, Rajae; Arifi, Samia; Mernissi, Fatima Zahra; Mellas, Nawfal

    2016-01-01

    Dermatomyositis (DM) is an inflammatory disease of unknown origin that manifests as a myopathy associated with typical skin lesions. Association between DM and cancer is frequent (from 18% to 32% according to case series). It was described for the first time by Stertz in 1916 in association with gastric cancer. All histological types and sites of cancer in the general population may be associated with DM. Its association with nasopharyngeal carcinoma (NPC) is rarely described and the incidence proportion is 1 case of nasopharyngeal carcinoma per 1.000 persons. PMID:27583093

  10. Incidence Trends and Geographical Distribution of Nasopharyngeal Carcinoma in Iran

    PubMed Central

    Safavi-Naini, Ali; Raad, Nasim; Ghorbani, Jahangir; Chaibakhsh, Samira; Ramezani-Daryasar, Rashid

    2015-01-01

    Background Nasopharyngeal carcinoma (NPC) has known as a highly distinct kind of head and neck cancer. This distinction has been due to its clinical presentation, epidemiology, outcome, and treatment. There have not been any reports of epidemiological analysis of NPC in Iran. This study has evaluated the incidence rates and trends of nasopharyngeal carcinoma in the Iranian population during 2004 to 2009. Methods The data have collected from the Iranian national cancer data system registry. All the cases of nasopharyngeal carcinoma (with the topography code 11 and histology of carcinoma) have retrieved and analyzed from an overall cancer database during a 6-year period. The data have analyzed by using the SPSS, version 16. Results To determine the current incidence of NPC in Iran, we have examined the NPC cases from 2004 to 2009. A total of 1431 cases (981 male and 450 female NPC patients) have analyzed epidemiologically in this study. The mean age of the patients was 47.1 years. The incidence was 0.33 per 100000 persons. The overall incidence rate have increased annually (p<0.05). The incidence of NPC gradually increased with age. Prefectures that bordering the Caspian Sea have proved to have a higher incidence than the other studied areas. Conclusion Our study has indicated an increasing trend in the incidence of nasopharyngeal carcinoma. Therefore; attempts should be precipitated for prevention. PMID:26396710

  11. Antinuclear antibodies in the sera of patients with nasopharyngeal carcinoma

    SciTech Connect

    Takimoto, T.; Ishikawa, S.; Masuda, K.; Tanaka, S.; Yoshizaki, T.; Umeda, R. )

    1989-11-01

    We studied the production of heterophile antinuclear antibodies (ANAs) in the sera of 50 patients, 20 with nasopharyngeal carcinoma (NPC) and 30 with other head and neck cancers (laryngeal cancer and maxillary cancer), before and after radiation therapy. A higher incidence of ANAs was found in the sera of patients with NPC and ANA production in these patients was higher after radiation therapy. We therefore performed in vitro experiments to explore the mechanisms of ANA production in the serum of postirradiated NPC patients. X-ray-irradiated NPC-derived cells (NPC-KT) produced a large amount of Epstein-Barr virus (NPC EBV) compared with non-irradiated NPC-KT cells. Nasopharyngeal carcinoma EBV-infected lymphocytes produced high levels of ANAs. These data suggest that lymphocytes infected by EBV from NPC cells may produce ANAs in the sera of NPC patients.

  12. Use Dose Bricks Concept to Implement Nasopharyngeal Carcinoma Treatment Planning

    PubMed Central

    Wu, Jia-Ming; Yu, Tsan-Jung; Yeh, Shyh-An; Chao, Pei-Ju; Huang, Chih-Jou

    2014-01-01

    Purpose. A “dose bricks” concept has been used to implement nasopharyngeal carcinoma treatment plan; this method specializes particularly in the case with bell shape nasopharyngeal carcinoma case. Materials and Methods. Five noncoplanar fields were used to accomplish the dose bricks technique treatment plan. These five fields include (a) right superior anterior oblique (RSAO), (b) left superior anterior oblique (LSAO), (c) right anterior oblique (RAO), (d) left anterior oblique (LAO), and (e) superior inferior vertex (SIV). Nondivergence collimator central axis planes were used to create different abutting field edge while normal organs were blocked by multileaf collimators in this technique. Results. The resulting 92% isodose curves encompassed the CTV, while maximum dose was about 115%. Approximately 50% volume of parotid glands obtained 10–15% of total dose and 50% volume of brain obtained less than 20% of total dose. Spinal cord receives only 5% from the scatter dose. Conclusions. Compared with IMRT, the expenditure of planning time and costing, “dose bricks” may after all be accepted as an optional implementation in nasopharyngeal carcinoma conformal treatment plan; furthermore, this method also fits the need of other nonhead and neck lesions if organ sparing and noncoplanar technique can be executed. PMID:24967395

  13. The diagnosis of nasopharyngeal carcinoma by optical coherence tomography (OCT)

    NASA Astrophysics Data System (ADS)

    Li, J. H.; Du, Y.

    2016-06-01

    We have attempted to explore the intrinsic differences in the optical properties of the nasopharyngeal carcinoma (NPC) and normal tissue by optical coherence tomography (OCT). OCT imaging of normal tissue provided three layers of epithelium, lamina propria, and the brighter interface of basement membrane; while carcinomas disrupted the layered construction embedded in signal-poor images. The morphologies were consistent with histological findings. Sensitivity and specificity were 90% and 100%, respectively. This pilot study demonstrates that NPC could be diagnosed by visualization, which implies that OCT might be potentially used to differentiate normal from NPC tissue in the early stage as an invasive biopsy.

  14. [Measurement of nasopharyngeal carcinoma tissue ex vivo by Raman spectroscopy].

    PubMed

    Huang, Wei; Pan, Jian-ji; Chen, Rong; Li, Yong-zeng; Feng, Shang-yuan; Xie, Shu-sen; Zeng, Hai-shan

    2009-05-01

    Raman spectroscopy has shown its potential and advantages in detecting molecular changes associated with tissue pathology, which makes it possible to diagnose with optical methods non-invasively and real-time. A compact and rapid near-infrared (NIR)Raman system was developed using 785 nm diode laser, volume phase technology (VPT)holographic grating system and NIR intensified charge-coupled device (CCD)with a specially designed Raman fibre probe which can effectively reduce the interference of fluorescence and Rayleigh scattering, maximize the ability of Raman collection as well as correct the image aberration of a planar grating diffraction. Adopting this method, signal-to-noise ratio has been greatly improved and human tissue signals can be acquired in a short time. Raman signals from fat and musculature of fresh pork were measured and referenced for further optimization, then Raman spectra of nasopharyngeal carcinoma in vitro and the effect of storage time on them were measured in 1-5 s and discussed. The sensitivities and performance of the system will be further enhanced and more Raman data will be acquired and compared between normal and cancerous nasopharyngeal tissue, expecting to discover the statistical characteristics, which will benefit the diagnosis and treatment of early nasopharyngeal carcinoma or other tumors. PMID:19650477

  15. Fine-needle aspiration cytology of metastatic nasopharyngeal carcinoma.

    PubMed

    Viguer, José M; Jiménez-Heffernan, José A; López-Ferrer, Pilar; Banaclocha, Marcos; Vicandi, Blanca

    2005-04-01

    Cytological features of nasopharyngeal carcinoma (NPC) were reviewed in an attempt to select cytological criteria that permit a specific recognition of metastases. For this purpose, 54 fine-needle aspiration (FNA) procedures from 43 patients with NPC were analyzed. Thirty-two (59.3%) procedures were performed before the histological diagnosis. In 25 (46.3%) procedures, smears showed many neoplastic single cells, clusters, and abundant lymphoid cells (mixed pattern). A dissociated (single cell) pattern consisting of individual neoplastic and lymphoid cells was seen in 18 (33.3%) cases. Finally, 11 (20.4%) cases showed cohesive epithelial clusters (cohesive pattern) without relevant cellular dissociation or lymphoid cells. Squamous-cell differentiation was seen in three of these cases. Most single neoplastic cells presented as large, pleomorphic naked nuclei. Other interesting findings were granulomas (n = 3), prominent eosinophilic infiltrates (n = 4), and suppurative changes (n = 5). In most smears with mixed and dissociated patterns, a nasopharyngeal origin could be suggested. On the contrary, those smears with a cohesive pattern were indistinguishable from other head and neck carcinomas. The presence (on cervical lymph nodes) of a dissociated or mixed (single cells and groups) architectural pattern of large, anaplastic cells and naked nuclei accompanied by an abundant lymphoid component is highly suggestive of undifferentiated NPC. Cytology offers a rapid diagnosis, establishes the necessity of a complete cavum examination, and helps in avoiding unnecessary and harmful biopsies. PMID:15754369

  16. Unusual coexistence of extramedullary plasmacytoma and nasopharyngeal carcinoma in nasopharynx.

    PubMed

    Du, Ri-Chang; Li, Hai-Nan; Huang, Wei; Tian, Xiao-Ying; Li, Zhi

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is an EBV-associated malignant tumor of nasopharynx. As extremely rare condition, the second primary cancer of nasopharynx can occur in NPC patients synchronously or subsequently. Extramedullary plasmacytoma (EMP) is a rare tumor and commonly originates in the head and neck region. However, there is no report to describe a collision tumor of NPC and EMP occurring in the same nasopharyngeal mass. We report here an unusual case of synchronous coexistence of NPC and EMP occurring in the nasopharynx of an old male patient. A 63-year-old male patient presented with a 3-month history of right-sided nasal obstruction and recently intermittent epistaxis without enlargement of cervical lymph nodes. The solitary mass of nasopharynx was found by radiological and nasopharyngeal examination. Histologically, the mass contained two separated portions and displayed typically histological features of NPC and EMP, respectively. In EMP portion, the tumor was composed of monomorphic plasmacytoid-appearing cells with immuno-positive to CD79a, CD138, CD38, MUM-1 and CD56, but lack immunoreactivity to pan-CK (AE1/AE3), CD20, CD21 and EBERs. In NPC portion, the tumor cells formed irregular-shaped islands with diffusely immuno-positive to pan-CK (AE1/AE3), EMA and EBERs, but lack expressions of lymphoplasmacytic markers. A diagnosis of simultaneous occurrence of EMP and NPC in nasopharynx was made. There was no evidence of tumor recurrence or metastasis 18-month follow-up after radiotherapy. To our knowledge, it may be the first case of coexistence of EMP and NPC synchronously. In addition, the histological differential diagnosis and relevant potential mechanism of this unusual collision tumor were also discussed. PMID:26376733

  17. Mathematical modeling of the cells repair regulations in Nasopharyngeal carcinoma.

    PubMed

    Adi-Kusumo, Fajar; Wiraya, Ario

    2016-07-01

    Nasopharyngeal Carcinoma (NPC) is a malignant cancer which is caused by the activation of Epstein-Barr Virus (EBV) via some external factors. In the cells repair regulations, the p53 gene mutation can be used as the early indication of the NPC growth. The NPC growth is due to the DNA damage accumulation caused by the EBV infection. In this paper we construct the cells repair regulations model to characterize the NPC growth. The model is a 15 dimensional of first order ODE system and consists the proteins and enzymes reactions. We do some numerical simulations to show the inactivation of the phosphorylated and acetylated p53, and the chromosomal instability of p53 gene, which can be used as the earlier stage detection of NPC. PMID:27140528

  18. Omics-Based Identification of Biomarkers for Nasopharyngeal Carcinoma

    PubMed Central

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is a head and neck cancer that is highly found in distinct geographic areas, such as Southeast Asia. The management of NPC remains burdensome as the prognosis is poor due to the late presentation of the disease and the complex nature of NPC pathogenesis. Therefore, it is necessary to find effective molecular markers for early detection and therapeutic measure of NPC. In this paper, the discovery of molecular biomarker for NPC through the emerging omics technologies including genomics, miRNA-omics, transcriptomics, proteomics, and metabolomics will be extensively reviewed. These markers have been shown to play roles in various cellular pathways in NPC progression. The knowledge on their function will help us understand in more detail the complexity in tumor biology, leading to the better strategies for early detection, outcome prediction, detection of disease recurrence, and therapeutic approach. PMID:25999660

  19. Nasopharyngeal carcinoma in children: review of 16 cases

    SciTech Connect

    Jereb, B.; Huvos, A.G.; Steinherz, P.; Unal, A.

    1980-04-01

    Of fifty two children with nasopharyngeal tumors who were registered and treated a Memorial Sloan-Kettering Cancer Center (MSKCC), from 1961 through 1977, 16 had carcinoma. The results of retrospective analysis of these patients are presented here. There were 7 girls and 9 boys between 12 and 16 years of age. One patient had a Stage I tumor; one had a Stage II tumor and 14 had Stage IV tumors. The histology was poorly differentiated epidermoid carcinoma in all patients. All patients had radiotherapy to the primary site. Six patients received chemotherapy for distant metastases, and 2 had adjuvant chemotherapy. Of the 13 patients who were treated initially with radiation alone, 2 were alive and free of disease at 12 and 14 years respectively. Of the 3 patients who had chemotherapy at initial treatment, one was alive and free of disease 18 months from diagnosis and one patient died of treatment without tumor. Bone was the common site of distant metastases. While radiation therapy alone appears to be adequate treatment for early tumors, adjuvant chemotherapy should be tried to improve results in advanced tumors.

  20. Stenosing tenosynovitis

    PubMed Central

    Vuillemin, V.; Guerini, H.; Bard, H.; Morvan, G.

    2012-01-01

    Tenosynovitis refers to an inflammatory condition involving the synovial sheath of a tendon. Stenosing tenosynovitis is a peculiar entity caused by multiple factors, including local anatomy, mechanical factors, and hormonal factors. The main forms include de Quervain tendinopathy; trigger finger (stenosing tenosynovitis involving the flexor digitorum tendons); stenosing tenosynovitis of the extensor carpi ulnaris, extensor carpi radialis, or extensor comunis tendons; stenosing tenosynovitis of the flexor hallucis tendon; and stenosing tenosynovitis of the peroneal tendons. The cardinal finding on ultrasonography is the presence of a thickened retinaculum or pulley that constricts the osseofibrous tunnel through which the tendon runs. PMID:23396894

  1. Genomic alterations in nasopharyngeal carcinoma: loss of heterozygosity and Epstein-Barr virus infection.

    PubMed Central

    Mutirangura, A.; Tanunyutthawongese, C.; Pornthanakasem, W.; Kerekhanjanarong, V.; Sriuranpong, V.; Yenrudi, S.; Supiyaphun, P.; Voravud, N.

    1997-01-01

    Nasopharyngeal carcinoma is a subset of head and neck squamous cell cancers with unique endemic distribution and aetiological co-factors. Epstein-Barr virus has been revealed to be an important aetiological factor for most nasopharyngeal carcinomas. Nevertheless, additional genetic alterations may be involved in their development and progression. The aim of this study was to determine the likely chromosomal locations of tumour-suppressor genes related to Epstein-Barr virus-associated nasopharyngeal carcinoma. Fifty-six microsatellite polymorphic markers located on every autosomal arm were used to estimate the incidence of loss of heterozygosity in 27 Epstein-Barr virus-associated nasopharyngeal carcinomas. High frequencies of allelic loss were observed on chromosome 3p (75.0%) and 9p (87.0%). Chromosome 9q, 11q, 13q and 14q displayed loss in over 50%, while chromosome 3q, 6p, 16q, 19q and 22q exhibited loss in 35-50%. Furthermore, several other chromosomal arms demonstrated allelic loss in 20-35%. Additionally, 1 of the 27 cases showed microsatellite instability at multiple loci. These findings provide evidence of multiple genetic alterations during cancer development and clues for further studies of tumour-suppressor genes in Epstein-Barr virus-associated nasopharyngeal carcinoma. Images Figure 1 Figure 2 Figure 4 PMID:9310244

  2. Segmentation of nasopharyngeal carcinoma (NPC) lesions in MR images

    SciTech Connect

    Lee, Francis K.H. . E-mail: fkhlee@cuhk.edu.hk; Yeung, David K.W.; King, Ann D.; Leung, S.F.; Ahuja, Anil

    2005-02-01

    Purpose: An accurate and reproducible method to delineate tumor margins from uninvolved tissues is of vital importance in guiding radiation therapy (RT). In nasopharyngeal carcinoma (NPC), tumor margin may be difficult to identify in magnetic resonance (MR) images, making the task of optimizing RT treatment more difficult. Our aim in this study is to develop a semiautomatic image segmentation method for NPC that requires minimal human intervention and is capable of delineating tumor margins with good accuracy and reproducibility. Methods and materials: The segmentation algorithm includes 5 stages: masking, Bayesian probability calculation, smoothing, thresholding and seed growing, and finally dilation and overlaying of results with different thresholds. The algorithm is based on information obtained from the contrast enhancement ratio of T1-weighted images and signal intensity of T2-weighted images. The algorithm is initiated by the selection of a valid anatomical seed point within the tumor by the user. The algorithm was evaluated on MR images from 7 NPC patients and was compared against the radiologist's reference outline. Results: The algorithm was successfully implemented on all 7 subjects. With a threshold of 1, the average percent match is 78.5 {+-} 3.86 (standard deviation) %, and the correspondence ratio is 66.5 {+-} 7%. Discussion: The segmentation algorithm presented here may be useful for diagnosing NPC and may guide RT treatment planning. Further improvement will be desirable to improve the accuracy and versatility of the method.

  3. Metabolic reprogramming orchestrates cancer stem cell properties in nasopharyngeal carcinoma

    PubMed Central

    Shen, Yao-An; Wang, Chia-Yu; Hsieh, Yi-Tao; Chen, Yann-Jang; Wei, Yau-Huei

    2015-01-01

    Cancer stem cells (CSCs) represent a subpopulation of tumor cells endowed with self-renewal capacity and are considered as an underlying cause of tumor recurrence and metastasis. The metabolic signatures of CSCs and the mechanisms involved in the regulation of their stem cell-like properties still remain elusive. We utilized nasopharyngeal carcinoma (NPC) CSCs as a model to dissect their metabolic signatures and found that CSCs underwent metabolic shift and mitochondrial resetting distinguished from their differentiated counterparts. In metabolic shift, CSCs showed a greater reliance on glycolysis for energy supply compared with the parental cells. In mitochondrial resetting, the quantity and function of mitochondria of CSCs were modulated by the biogenesis of the organelles, and the round-shaped mitochondria were distributed in a peri-nuclear manner similar to those seen in the stem cells. In addition, we blocked the glycolytic pathway, increased the ROS levels, and depolarized mitochondrial membranes of CSCs, respectively, and examined the effects of these metabolic factors on CSC properties. Intriguingly, the properties of CSCs were curbed when we redirected the quintessential metabolic reprogramming, which indicates that the plasticity of energy metabolism regulated the balance between acquisition and loss of the stemness status. Taken together, we suggest that metabolic reprogramming is critical for CSCs to sustain self-renewal, deter from differentiation and enhance the antioxidant defense mechanism. Characterization of metabolic reprogramming governing CSC properties is paramount to the design of novel therapeutic strategies through metabolic intervention of CSCs. PMID:25483072

  4. Improved outcome of nasopharyngeal carcinoma treated with conventional radiotherapy

    SciTech Connect

    Palazzi, Mauro . E-mail: mauro.palazzi@istitutotumori.mi.it; Guzzo, Marco; Tomatis, Stefano Ph.D.; Cerrotta, Annamaria; Potepan, Paolo; Quattrone, Pasquale; Cantu, Giulio

    2004-12-01

    Purpose: To describe the outcome of patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with conventional radiotherapy at a single institution. Methods and materials: From 1990 to 1999, 171 consecutive patients with NPC were treated with conventional (two-dimensional) radiotherapy. Tumor histology was undifferentiated in 82% of cases. Tumor-node-metastasis Stage (American Joint Committee on Cancer/International Union Against Cancer 1997 system) was I in 6%, II in 36%, III in 22%, and IV in 36% of patients. Mean total radiation dose was 68.4 Gy. Chemotherapy was given to 62% of the patients. The median follow-up for surviving patients was 6.3 years (range, 3.1-13.1 years). Results: The 5-year overall survival, disease-specific survival, and disease-free survival rates were 72%, 74%, and 62%, respectively. The 5-year local, regional, and distant control rates were 84%, 80%, and 83% respectively. Late effects of radiotherapy were prospectively recorded in 100 patients surviving without relapse; 44% of these patients had Grade 3 xerostomia, 33% had Grade 3 dental damage, and 11% had Grade 3 hearing loss. Conclusions: This analysis shows an improved outcome for patients treated from 1990 to 1999 compared with earlier retrospective series, despite the use of two-dimensional radiotherapy. Late toxicity, however, was substantial with conventional radiotherapy.

  5. Nasopharyngeal carcinoma--a review of radiotherapy techniques.

    PubMed

    Tsao, S Y

    1993-07-01

    With modern megavoltage external X-ray treatment for nasopharyngeal carcinoma, results have improved but late sequelae, which are more often associated with the treatment of advanced tumours or multiple courses of external treatment, have also surfaced. Life-threatening complications include temporal lobe necrosis and hypothalamic-pituitary dysfunction. As CT scanning is superior to conventional radiography in tumour mapping, a new dedicated working staging system, catering for cross-sectional imaging parameters, is proposed for a prospective, multi-centre exercise to finalise on a badly needed common system. With it, case selection for more conservative (to minimise complications) or intensified treatments is facilitated. Intracavitary radiation has now been developed well enough for the nasopharynx. For earlier cases, based on the new staging system, this method has the potential to complement a "sub-radical" external treatment dose designed to minimise complications. A multi-centre trial is indicated. To reach cancericidal doses for the more advanced tumours coming very close to vital structures, extra machine time, though precious, is fully justified so that smaller treatment fractions delivered with facial shells for accurate reproduction of precise machine geometry and field geography can be implemented. Otherwise, subsequent management of possible serious treatment complications may cost more than the treatment itself. Various possible complications of radiotherapy and avoidance and management are outlined. PMID:8257075

  6. Deregulation of lipid metabolism pathway genes in nasopharyngeal carcinoma cells.

    PubMed

    Daker, Maelinda; Bhuvanendran, Saatheeyavaane; Ahmad, Munirah; Takada, Kenzo; Khoo, Alan Soo-Beng

    2013-03-01

    Nasopharyngeal carcinoma (NPC) is a unique tumour of epithelial origin with a distinct geographical distribution, closely associated with the Epstein‑Barr virus (EBV). EBV‑encoded RNAs (EBERs) are small non‑polyadenylated RNAs that are abundantly expressed in latent EBV‑infected NPC cells. To study the role of EBERs in NPC, we established stable expression of EBERs in HK1, an EBV‑negative NPC cell line. Cells expressing EBERs consistently exhibited an increased growth rate. However, EBERs did not confer resistance towards cisplatin‑induced apoptosis or promote migration or invasion ability in the cells tested. Using microarray gene expression profiling, we identified potential candidate genes that were deregulated in NPC cells expressing EBERs. Gene Ontology analysis of the data set revealed that EBERs upregulate the cellular lipid metabolic process. Upregulation of low‑density lipoprotein receptor (LDLR) and fatty acid synthase (FASN) was observed in EBER‑expressing cells. NPC cells exhibited LDL‑dependent cell proliferation. In addition, a polyphenolic flavonoid compound, quercetin, known to inhibit FASN, was found to inhibit proliferation of NPC cells. PMID:23292678

  7. Transcriptome meta-analysis reveals dysregulated pathways in nasopharyngeal carcinoma.

    PubMed

    Tulalamba, Warut; Larbcharoensub, Noppadol; Sirachainan, Ekaphop; Tantiwetrueangdet, Aunchalee; Janvilisri, Tavan

    2015-08-01

    Nasopharyngeal carcinoma (NPC) is a malignant cancer arising from the epithelial surface of the nasopharynx that mostly appears in advanced stages of the disease, leading to a poor prognosis. To date, a number of mRNA profiling investigations on NPC have been reported in order to identify suitable biomarkers for early detection. However, the results may be specific to each study with distinct sample types. In this study, an integrative meta-analysis of NPC transcriptome data was performed to determine dysregulated pathways, potentially leading to identification of molecular markers. Ten independent NPC gene expression profiling microarray datasets, including 135 samples from NPC cell lines, primary cell lines, and tissues were assimilated into a meta-analysis and cross-validation to identify a cohort of genes that were significantly dysregulated in NPC. Bioinformatics analyses of these genes revealed the significant pathways and individual players involving in cellular metabolism, cell cycle regulation, DNA repair, as well as ErbB pathway. Altogether, we propose that dysregulation of these molecular pathways in NPC might play a role in the NPC pathogenesis, providing clues, which could eventually translate into diagnostic and therapeutic approaches. PMID:25724187

  8. Nasopharyngeal Carcinoma in Oman: 
A Descriptive Analysis

    PubMed Central

    Al-Azri, AbdulAziz; Al-Sheibani, Salma

    2015-01-01

    Objectives We sought to analyze all cases of nasopharyngeal carcinomas (NPC) in Oman to determine the most common clinical presentation, whether it is associated with certain tribes in Oman, and its distribution in different regions of the country. We also looked at the histopathological diagnosis, treatment modality, recurrence, and metastasis. Methods This retrospective chart analysis was performed using the data of all patients with NPC who presented to the Al Nahdha Hospital (the main tertiary hospital of head and neck surgery in Oman) from January 2003 until August 2011. Results Twenty-six cases of NPC were included in the final study population. Muscat (the capital city of Oman) had the highest number of cases followed by the Ash Sharqiyah, Al-Batinah, and Dhofar regions. The largest number of cases were found in the Al-Balushi tribe. Cases had a bimodal distribution within two age groups (20–30 years and 50–60 years). Follow-up ranged between six months and seven years. Conclusion Neck mass and nasal symptoms were the most common presentations of NPC in Oman. Further studies, with a larger sample size are required in order to support our results. PMID:26171122

  9. Metabolic reprogramming orchestrates cancer stem cell properties in nasopharyngeal carcinoma.

    PubMed

    Shen, Yao-An; Wang, Chia-Yu; Hsieh, Yi-Tao; Chen, Yann-Jang; Wei, Yau-Huei

    2015-01-01

    Cancer stem cells (CSCs) represent a subpopulation of tumor cells endowed with self-renewal capacity and are considered as an underlying cause of tumor recurrence and metastasis. The metabolic signatures of CSCs and the mechanisms involved in the regulation of their stem cell-like properties still remain elusive. We utilized nasopharyngeal carcinoma (NPC) CSCs as a model to dissect their metabolic signatures and found that CSCs underwent metabolic shift and mitochondrial resetting distinguished from their differentiated counterparts. In metabolic shift, CSCs showed a greater reliance on glycolysis for energy supply compared with the parental cells. In mitochondrial resetting, the quantity and function of mitochondria of CSCs were modulated by the biogenesis of the organelles, and the round-shaped mitochondria were distributed in a peri-nuclear manner similar to those seen in the stem cells. In addition, we blocked the glycolytic pathway, increased the ROS levels, and depolarized mitochondrial membranes of CSCs, respectively, and examined the effects of these metabolic factors on CSC properties. Intriguingly, the properties of CSCs were curbed when we redirected the quintessential metabolic reprogramming, which indicates that the plasticity of energy metabolism regulated the balance between acquisition and loss of the stemness status. Taken together, we suggest that metabolic reprogramming is critical for CSCs to sustain self-renewal, deter from differentiation and enhance the antioxidant defense mechanism. Characterization of metabolic reprogramming governing CSC properties is paramount to the design of novel therapeutic strategies through metabolic intervention of CSCs. PMID:25483072

  10. Challenges of managing nasopharyngeal carcinoma in a developing country.

    PubMed Central

    Fatusi, Olawunmi; Akinpelu, Olubunmi; Amusa, Yemisi

    2006-01-01

    The maxillofacial unit is an uncommon entry point for cases of nasopharyngeal carcinoma (NPC). This report documents involvement of the maxillofacial unit in the management of NPC in Obafemi Awolowo University Teaching Hospitals Complex, Ile-lfe, Nigeria, with the aim of highlighting the challenges associated with recognition and management of the disease. Almost all cases (86.7%) were recorded in the low socioeconomic group, and males constituted 66.7%. The median age of our patients was 38 years, with an earlier cluster in females. Most of our patients (86.7%) presented with late stages of the disease. The challenges posed to surgeons in the management of NPC in the tropics include limited availability of diagnostic and treatment facilities. The inability of patients to afford the cost of relevant healthcare services due to high poverty level and absence of effective social support system also limits their access and utilization of available clinical facilities. These issues need to be addressed to facilitate early diagnosis and improved management that would ensure better prognosis for Nigerian patients with NPC. Education targeted at community members as well as healthcare service providers, including maxillofacial surgeons, would be important to enhance the possibility of detecting the cases at an earlier stage. Images Figure 1 PMID:16749652

  11. CXCL12 genetic variants as prognostic markers in nasopharyngeal carcinoma

    PubMed Central

    Chen, Ruiwan; Xu, Yafei; Du, Xiaojing; Liu, Na; Li, Yingqin; He, Qingmei; Tang, Linglong; Mao, Yanping; Sun, Ying; Chen, Lei; Ma, Jun

    2015-01-01

    The chemokine receptor 4/chemokine ligand 12 (CXCR4/CXCL12) axis plays an important role in tumorigenesis, metastasis, and recurrence of tumors. Its single nucleotide polymorphisms (SNPs) are associated with patient survival in several types of cancer. However, the prognostic value of SNPs in nasopharyngeal carcinoma (NPC) has not been fully investigated. This retrospective study assessed the relationships between CXCR4 rs2228014 and CXCL12 rs1801157 polymorphisms and patient outcome in 222 patients newly diagnosed with NPC. The analysis found no significant correlation between the presence of both SNPs and clinicopathological factors. However, univariate analysis showed that N classification, clinical stage, and the CXCL12 rs1801157 polymorphism were significantly associated with distant metastasis-free survival (P=0.018, 0.028, and 0.013, respectively) and progression-free survival (P=0.007, 0.046, and 0.021, respectively). After adjusting clinicopathological factors, multivariate analysis identified CXCL12 rs1801157 as an independent prognostic factor for distant metastasis-free survival and progression-free survival (hazard ratio: 3.332; 95% confidence interval: 1.597–6.949; P=0.001 and hazard ratio: 2.665 95% confidence interval: 1.387–5.119; P=0.003, respectively). Our results suggest that CXCL12 rs1801157 AA genotype might serve as a potential prognostic factor in patients with NPC. PMID:26504400

  12. Pregnancy and nasopharyngeal carcinoma: a prognostic evaluation of 27 patients

    SciTech Connect

    Jie-Hua, Y.; Caisen, L.; Yuhua, H.

    1984-06-01

    In order to study the influence of pregnancy on the prognosis of nasopharyngeal carcinoma (NPC), the authors have retrospectively studied 27 patients who either were discovered to be pregnant during radiotherapy (9 patients, herein abbreviated as concurrent group) or became pregnant after treatment (18 patients, herein abbreviated as subsequent group). This material was collected from 811 NPC patients treated in their hospital from March 1958 to 1972. The results obtained are presented as follows: Concurrent pregnancy had a disastrous effect on the prognosis of NPC patients giving a five year survival of only 11% (1/9). This adverse influence was not observed in the subsequent group, yet the time of gestation seemed to be relevant to the prognosis. Two of the three patients who became pregnant within one year of the treatment died of disease, those who became pregnant beyond the second year after irradiation had the best prognosis. All seven patients who became pregnant after the second year of treatment survived. A total of 21 children were born to the patients of these two groups. They have been followed regularly for 10 to 20 years. No deformity, or retardation in growth or mentality was discovered, nor was there any evidence of radiation tumor or leukemia observed.

  13. Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance

    PubMed Central

    Liu, Shu-Chen; Tsang, Ngan-Ming; Chiang, Wen-Che; Chang, Kai-Ping; Hsueh, Chuen; Liang, Ying; Juang, Jyh-Lyh; Chow, Kai-Ping N.; Chang, Yu-Sun

    2013-01-01

    Radioresistance of EBV-associated nasopharyngeal carcinoma (NPC) is associated with poor prognosis for patients with this form of cancer. Here, we found that NPC patients had increased serum levels of leukemia inhibitory factor (LIF) and that higher LIF levels correlated with local tumor recurrence. Furthermore, in vitro studies with NPC cells and in vivo xenograft mouse studies demonstrated that LIF critically contributes to NPC tumor growth and radioresistance. Using these model systems, we found that LIF treatment activated the mTORC1/p70S6K signaling pathway, enhanced tumor growth, inhibited DNA damage responses, and enhanced radioresistance. Treatment with either soluble LIF receptor (sLIFR), a LIF antagonist, or the mTOR inhibitor rapamycin reversed LIF-mediated effects, resulting in growth arrest and increased sensitivity to γ irradiation. Immunohistochemical (IHC) analyses of human NPC biopsies revealed that LIF and LIFR were overexpressed in tumor cells and that LIF expression correlated with the presence of the activated p-p70S6K. Finally, we found that the EBV-encoded protein latent membrane protein 1 (LMP1) enhances LIF production. Together, our findings indicate that LIF promotes NPC tumorigenesis and suggest that serum LIF levels may predict local recurrence and radiosensitivity in NPC patients. PMID:24270418

  14. Mesenchymal stem cell-derived exosomes facilitate nasopharyngeal carcinoma progression

    PubMed Central

    Shi, Si; Zhang, Qicheng; Xia, Yunfei; You, Bo; Shan, Ying; Bao, Lili; Li, Li; You, Yiwen; Gu, Zhifeng

    2016-01-01

    Mesenchymal stem cells (MSCs), which are capable of differentiating into multiple cell types, are reported to exert multiple effects on tumor development. However, the relationship between MSCs and nasopharyngeal carcinoma (NPC) cells remains unclear. Exosomes are small membrane vesicles that can be released by several cell types, including MSCs. Exosomes, which can carry membrane and cytoplasmic constituents, have been described as participants in a novel mechanism of cell-to-cell communication. In the present study, we investigated the mechanisms underlying the interaction between MSCs and NPC cells. The data showed that MSCs secreted 40-100 nm heterogeneous small vesicles, which were defined as exosomes. Incubation of NPC cells with MSC-derived exosomes resulted in the uptake of exosomes by the cells, which promoted their proliferation, migration and tumorigenesis. After an extended treatment duration, the tumor cells showed morphological changes and significant changes in the expression of epithelial-mesenchymal transition (EMT) markers. Moreover, we found that FGF19 was highly expressed in MSC-exosomes and that exosomes stimulated NPC progression by activating the FGF19-FGFR4-dependent ERK signaling cascade and by modulating the EMT. All of these data indicated that exosomes participate in a novel mechanism by which MSCs influence NPC progression. PMID:27186416

  15. iTRAQ-Based Quantitative Proteomic Analysis of Nasopharyngeal Carcinoma.

    PubMed

    Cai, Xin-Zhang; Zeng, Wei-Qun; Xiang, Yi; Liu, Yi; Zhang, Hong-Min; Li, Hong; She, Sha; Yang, Min; Xia, Kun; Peng, Shi-Fang

    2015-07-01

    Nasopharyngeal carcinoma (NPC) is a common disease in the southern provinces of China with a poor prognosis. To better understand the pathogenesis of NPC and identify proteins involved in NPC carcinogenesis, we applied iTRAQ coupled with two-dimensional LC-MS/MS to compare the proteome profiles of NPC tissues and the adjacent non-tumor tissues. We identified 54 proteins with differential expression in NPC and the adjacent non-tumor tissues. The differentially expressed proteins were further determined by RT-PCR and Western blot analysis. In addition, the up-regulation of HSPB1, NPM1 and NCL were determined by immunohistochemistry using tissue microarray. Functionally, we found that siRNA mediated knockdown of NPM1 inhibited the migration and invasion of human NPC CNE1 cell line. In summary, this is the first study on proteome analysis of NPC tissues using an iTRAQ method, and we identified many new differentially expressed proteins which are potential targets for the diagnosis and therapy of NPC. PMID:25648846

  16. The prevalence and prevention of nasopharyngeal carcinoma in China

    PubMed Central

    Cao, Su-Mei; Simons, Malcolm J.; Qian, Chao-Nan

    2011-01-01

    Nasopharyngeal carcinoma (NPC) has remarkable epidemiological features, including regional, racial, and familial aggregations. The aim of this review is to describe the epidemiological characteristics of NPC and to propose possible causes for the high incidence patterns in southern China. Since the etiology of NPC is not completely understood, approaches to primary prevention of NPC remain under consideration. This situation highlights the need to conduct secondary prevention, including improving rates of early detection, early diagnosis, and early treatment in NPC patients. Since the 1970's, high-risk populations in southern China have been screened extensively for early detection of NPC using anti–Epstein-Barr virus (EBV) serum biomarkers. This review summarizes several large screening studies that have been conducted in the high-incidence areas of China. Screening markers, high-risk age range for screening, time intervals for blood re-examination, and the effectiveness of these screening studies will be discussed. Conduction of prospective randomized controlled screening trials in southern China can be expected to maximize the cost-effectiveness of early NPC detection screening. PMID:21272443

  17. Incidence of nasopharyngeal carcinoma in Malaysia, 1968--1977.

    PubMed Central

    Armstrong, R. W.; Kannan Kutty, M.; Dharmalingam, S. K.; Ponnudurai, J. R.

    1979-01-01

    A record of all known cases of nasopharyngeal carcinoma in Malaysia is complete for 10 years from 1968 to 1977. Special efforts in case-finding were made in the State of Selangor where conditions are optimal. Age-adjusted incidence rates among Chinese males and females were 16.5 and 7.2 per 100,000, among Malay males and females 2.3 and 0.7 and among Indian males, 1.0. There were no significant changes in incidence rates over the 10-year period for sex and ethnic groups, or for Chinese subethnic groups. In Chinese subethnic groups, rates were highest among Cantonese, moderate among Khek and lowest among Hokkien and Teochiu. Standardized incidence ratios using Selangor as the standard population indicate considerable under-reporting in the less urban states of Malaysia, particularly among females. In Selangor, incidence rates were similar for urban and rural residents, but the frequency of cases was higher among Chinese working in industry and living in poor neighbourhoods. PMID:497106

  18. [MRI findings delay the diagnosis of nasopharyngeal carcinoma].

    PubMed

    Becker, H

    2011-09-01

    This report concerns a 55-year-old female patient who presented with headache, dry right eye and dry nose on the right side. After 5 months magnetic resonance imaging (MRI) was carried out but no pathological findings were diagnosed. Right-sided facial pain appeared 6 months later and a second MRI was carried out but only fluid retention in the right mastoid was diagnosed. After a further 8 months paresis of the right abducent nerve occurred and a computed tomography (CT) scan of the petrous bone showed extensive destruction of the apex of the petrous pyramid. Subsequently a third MRI revealed a tumor of about 5 cm in diameter in the right pterygopalatine fossa which was also retrospectively visible in the first MRI with a size of approximately 3 cm and in the second MRI with 4 cm in diameter. The histological examination after biopsy resulted in the diagnosis of a nasopharyngeal carcinoma and radiochemotherapy was initiated. The patient died 9 months later. The relatives of the patient applied to the arbitration board for medical liability which requested expert opinions in neuroradiology and otorhinolaryngology. The board came to the conclusion that the claims for damages against the radiologist who had made the three MRIs were well-founded and recommended an extrajudicial settlement. PMID:21717162

  19. Pregnancy Incidence in Female Nasopharyngeal Carcinoma Survivors of Reproductive Age

    PubMed Central

    Lee, Bo-Ching; Yen, Ruoh-Fang; Lin, Cheng-Li; Liang, Ji-An; Lin, Ming-Chia; Kao, Chia-Hung

    2016-01-01

    Abstract This study evaluated the pregnancy incidence in female nasopharyngeal carcinoma (NPC) survivors of reproductive age. In a nationwide cohort, 2816 female patients 15 to 50 years of age from 1998 to 2010 were identified from the Taiwan National Health Insurance Research database. Comorbidities, complications during pregnancy, and delivery status were recorded. All patients were followed up until a diagnosis of pregnancy, withdrawal from the National Health Insurance system, or December 31, 2011. Overall, 155 patients (incidence rate [IR] = 9.50) were pregnant in the NPC group, whereas 251 patients (IR = 12.80) were pregnant in the non-NPC group. The cumulative incidence of pregnancy in the NPC group was lower than that in the non-NPC group (incidence rate ratio = 0.74, 95% CI = 0.61–0.91). The adjusted hazard ratio of pregnancy in the NPC group was 0.79 with 95% CI = 0.61–0.96, compared with the non-NPC group. The incidence of pregnancy is significantly lower among female NPC survivors of reproductive age than among those without NPC. PMID:27196495

  20. Effectiveness of a multicentre nasopharyngeal carcinoma awareness programme in Indonesia

    PubMed Central

    Fles, Renske; Indrasari, Sagung R; Herdini, Camelia; Martini, Santi; Isfandiari, Atoillah; Romdhoni, Achmad C; Adham, Marlinda; Mayangsari, Ika D; van Werkhoven, Erik; Wildeman, Maarten A; Hariwiyanto, Bambang; Hermani, Bambang; Kentjono, Widodo A; Haryana, Sofia M; Schmidt, Marjanka K; Tan, I Bing

    2016-01-01

    Objective To evaluate the effectiveness of a nasopharyngeal carcinoma (NPC) awareness programme on the short-term and long-term improvement of knowledge and referral of patients with NPC by primary healthcare centres (PHCCs) staff in Indonesia. Design The NPC awareness programme consisted of 12 symposia including a Train-The-Trainer component, containing lectures about early symptoms and risk factors of NPC, practical examination and the referral system for NPC suspects. Before and after training participants completed a questionnaire. The Indonesian Doctors Association accredited all activities. Participants 1 representative general practitioner (GP) from each PHCC attended an NPC awareness symposium. On the basis of the Train-The-Trainer principle, GPs received training material and were obligated to train their colleagues in the PHCC. Results 703 GPs attended the symposia and trained 1349 staff members: 314 other GPs, 685 nurses and 350 midwives. After the training, respondents’ average score regarding the knowledge of NPC symptoms increased from 47 points (of the 100) to 74 points (p<0.001); this increase was similar between symposium and Train-The-Trainer component (p=0.88). At 1½ years after the training, this knowledge remained significantly increased at 59 points (p<0.001). Conclusions The initial results of this NPC awareness programme indicate that the programme effectively increases NPC knowledge in the short and long term and therefore should be continued. Effects of the improved knowledge on the stage at diagnoses of the patients with NPC will still need to be scrutinised. This awareness programme can serve as a blueprint for other cancer types in Indonesia and for other developing countries. PMID:26932137

  1. A novel curcuminoid exhibits enhanced antitumor activity in nasopharyngeal carcinoma.

    PubMed

    Pan, Yunbao; Liu, Guohong; Xiao, Jian; Su, Bojin; Zhou, Fuling; Wei, Yongchang

    2016-05-01

    Curcumin shows growth-inhibition against tumor cells through multi-target mechanisms. Nevertheless, the poor stability and pharmacokinetics considerably limit its clinical functions. Increased effort has been put into the chemical alteration of curcumin to find potential analogues with improved bioavailability and antitumor activities. In this study, the antitumor activity of a novel curcuminoid (B63) in nasopharyngeal carcinoma (NPC) was examined. The MTT and colony formation assays were used to detect NPC cell viability and proliferation. Flow cytometry was used to detect cell cycle distribution. The Annexin V/PI staining assay and cleavage PARP and cleavage caspase-3 expression were used to examine apoptosis. Western blotting was used to examine the protein expression of endoplasmic reticulum (ER) stress pathway markers, XBP-1, ATF-4 and CHOP. The suppressive effect of B63 on tumor growth was examined in vivo by subcutaneously inoculated NPC in a tumor model using nude mice. Treatment with B63 potentially caused growth inhibition and apoptosis in NPC cells in a dose- and time-responsive manner. Its antitumor effect was associated with the ER stress activation. Nevertheless, the same dose of curcumin did not activate ER stress. In addition, knockdown of Chop attenuated B63-induced cell viability inhibition, suggesting that the apoptotic pathway is ER stress-dependent. The tumor volume and weight were significantly reduced by pretreating the NPC cells with B63 before implantation in the in vivo mouse model. B63 exhibited a more potent antitumor action than curcumin in NPC. These observations on the novel compound B63 indicate a novel candidate for NPC therapy. PMID:26983360

  2. Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

    SciTech Connect

    Lee, Ching-Chih; Su, Yu-Chieh; Ho, Hsu-Chueh; Hung, Shih-Kai; Lee, Moon-Sing; Chiou, Wen-Yen; Chou, Pesus; Huang, Yung-Sung

    2011-12-01

    Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival rate between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35-54 had a 1.66 times (95% CI, 1.16-2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55-64 years (hazard ratio = 0.87; 95% CI, 0.56-1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.

  3. Patterns of Retropharyngeal Node Metastasis in Nasopharyngeal Carcinoma

    SciTech Connect

    Wang Xiaoshen; Hu Chaosu Ying Hongmei; Zhou Zhengrong; Ding Jianhui; Feng Yan

    2009-01-01

    Purpose: To explore the pattern of metastasis to retropharyngeal lymph nodes (RLN) and its relationship with tumor range in nasopharyngeal carcinoma (NPC) patients by using magnetic resonance imaging. Methods and Materials: Magnetic resonance images of 618 NPC patients were reviewed. Nodes were classified as metastatic on the basis of size criteria, the presence of nodal necrosis, and extracapsular spread. Results: A total of 597 involved RLN were detected in 392 patients (63.4%). The sites of RLN metastasis included occipital bone, 37 (6.2%); first cervical vertebra (C1), 453 (75.9%); second cervical vertebra (C2), 104 (17.4%); and third cervical vertebra (C3), 3 (0.5%). The incidence of RLN involvement was less than that of Level IIb node involvement (72.2% vs. 86.5%) in 543 patients with lymphadenopathy. The incidence of RLN metastasis was significantly higher in cases of parapharyngeal space invasion or involvement of Level II, Level III, Level IV, and/or Level V nodes and significantly lower in N0 and Stage I disease. Conversely, the incidence of RLN metastasis did not differ significantly among T1, 2, 3, and 4 disease or among Stage II, III, and IV disease. Conclusions: Level IIb nodes, rather than RLN, seem to be the first-echelon nodes in NPC. The incidence of RLN metastasis decreases steadily from level C1 to level C3. Retropharyngeal lymph node metastasis correlates well with involvement of the parapharyngeal space and metastases to Level II, III, IV, and/or V nodes but not with T stage.

  4. Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells.

    PubMed

    Zou, Xue; Zhang, Mengxiao; Sun, Yiming; Zhao, Surong; Wei, Yingmei; Zhang, Xudong; Jiang, Chenchen; Liu, Hao

    2015-10-01

    Tumor cells depend on aerobic glycolysis for adenosine triphosphate (ATP) production, which is therefore targeted by therapeutic agents. The compound 3-bromopyruvate (3-BrPA), a strong alkylating agent and hexokinase inhibitor, inhibits tumor cell glycolysis and the production of ATP, causing apoptosis. 3-BrPA induces apoptosis of nasopharyngeal carcinoma (NPC) cell lines HNE1 and CNE-2Z, which may be related to its molecular mechanisms. In the present study, we investigated the effects of 3-BrPA on the viability, reactive oxygen species (ROS), apoptosis and other types of programmed cell death in NPC cells in vitro and in vivo. PI staining showed significant apoptosis in NPC cells accompanied by the overproduction of ROS and downregulation of mitochondrial membrane potential (MMP, ΔΨm) by 3-BrPA. However, the ROS scavenger N-acetyl-L-cysteine (NAC) significantly reduced 3-BrPA-induced apoptosis by decreasing ROS and facilitating the recovery of MMP. We elucidated the molecular mechanisms underlying 3-BrPA activity and found that it caused mitochondrial dysfunction and ROS production, leading to necroptosis of NPC cells. We investigated the effects of the caspase inhibitor z-VAD-fmk, which inhibits apoptosis but promotes death domain receptor (DR)-induced NPC cell necrosis. Necrostatin-1 (Nec-1) inhibits necroptosis, apparently via a DR signaling pathway and thus abrogates the effects of z-VAD‑fmk. In addition, we demonstrated the effective attenuation of 3-BrPA-induced necrotic cell death by Nec-1. Finally, animal studies proved that 3-BrPA exhibited significant antitumor activity in nude mice. The present study is the first demonstration of 3-BrPA-induced non-apoptotic necroptosis and ROS generation in NPC cells and provides potential strategies for developing agents against apoptosis‑resistant cancers. PMID:26239511

  5. Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis

    SciTech Connect

    Stenmark, Matthew H.; McHugh, Jonathan B.; Schipper, Matthew; Walline, Heather M.; Komarck, Christine; Feng, Felix Y.; Worden, Francis P.; Wolf, Gregory T.; Chepeha, Douglas B.; Prince, Mark E.; Bradford, Carol R.; Mukherji, Suresh K.; Eisbruch, Avraham; Carey, Thomas E.

    2014-03-01

    Purpose: To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials: Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results: Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001). Conclusion: In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings.

  6. Cytotoxic T Cell Adoptive Immunotherapy as a Treatment for Nasopharyngeal Carcinoma

    PubMed Central

    Crooks, Pauline; Morrison, Leanne; Stevens, Natasha; Davis, Joanne E.; Corban, Monika; Hall, David; Panizza, Benedict; Coman, William B.; Coman, Scott; Moss, Denis J.

    2014-01-01

    Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). We assess the safety and tolerability of adoptive transfer of autologous cytotoxic T lymphocytes (CTLs) specific for the EBV latent membrane protein (LMP) in a patient with recurrent NPC. After infusion, the majority of pulmonary lesions were no longer evident, although the primary tumor did not regress. PMID:24351754

  7. The HLA-DRB1 allele polymorphisms and nasopharyngeal carcinoma.

    PubMed

    Yang, Huimin; Yu, Kaihui; Zhang, Ruoheng; Li, Jiatong; Wei, Xiaomou; Zhang, Yuening; Zhang, Chengdong; Xiao, Feifan; Zhao, Dong; Lin, Xuandong; Wu, Huayu; Yang, Xiaoli

    2016-06-01

    Human leukocyte antigen (HLA)-DRB1 has been reported to influence individual's susceptibility to nasopharyngeal carcinoma (NPC) by many studies in recent years; however, these studies provided controversial results. The meta-analysis was thus conducted here to estimate the relationship between HLA-DRB1 polymorphisms and NPC. After an extensive review of journals from various databases (PubMed, the Web of Science, Embase, China National Knowledge Internet (CNKI), and Wanfang Database), 8 out of 69 case-control studies, including 778 cases and 1148 controls, were extracted. The results showed that 4 of 13 polymorphisms allele are statistically significantly associated with NPC, among them, HLA-DRB1*3, HLA-DRB1*9, and HLA-DRB1*10 may increase the risk of NPC while HLA-DRB1*01 has the opposite effect. The pooled odds ratio and 95 % confidence interval (CI) were 1.702 [95 % CI (1.047, 2.765)], 1.363 [95 % CI (1.029, 1.806)], 1.989 [95 % CI (1.042, 3.799)], and 0.461 [95 % CI (0.315, 0.676)], respectively. In a further ethnicity-based subgroup analysis, HLA-DRB1*08, HLA-DRB1*11, and HLA-DRB1*16 were found to be linked with NPC in Asian, Tunisian, and Caucasian, respectively. In Asian, HLA-DRB1*03, 08, and 10 may elevate the risk whereas HLA-DRB1*09 could lower it. In Tunisian, HLA-DRB1*01 and 11 are the protective factors while HLA-DRB1*03 is the only risk factor. In Caucasian, HLA-DRB1*01 and 03 increase the risk and HLA-DRB1*16 lowers it. The most frequent statistically associated gene is found to be HLA-DRB1*03 which has protective influence on Asian and Tunisian. In conclusion, HLA-DRB1*01, DRB1*03, DRB1*09, and DRB1*10 are related with NPC susceptibility, and the association of HLA-DRB1*08, DRB1*11, and DRB1*16 with NPC risk are significantly different in different ethnicities. PMID:27059731

  8. Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis

    PubMed Central

    Stenmark, Matthew H.; McHugh, Jonathan B.; Schipper, Matthew; Walline, Heather M.; Komarck, Christine; Feng, Felix Y.; Worden, Francis P.; Wolf, Gregory T.; Chepeha, Douglas B.; Prince, Mark E.; Bradford, Carol R.; Mukherji, Suresh K.; Eisbruch, Avraham; Carey, Thomas E.

    2014-01-01

    Purpose To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in non-endemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined using in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex PCR-MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV-positivity was significantly correlated with WHO grade II tumors, older age, and smoking (all p <0.001). The racial distribution of the study population was 74% Caucasian, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were Caucasian. At a median follow-up of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes as compared to EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, p=0.01 and HR 3.89, p=0.002], progression-free survival (HR 2.55, p=0.02 and HR 4.04, p <0.001], and locoregional control (HR 4.01, p=0.03 and HR 6.87, p=0.001). Conclusion In our Midwestern population high-risk HPV infection may play an etiologic role in the development of non-endemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings. PMID:24521676

  9. Identification of miRNA/mRNA-Negative Regulation Pairs in Nasopharyngeal Carcinoma

    PubMed Central

    Liu, Minglei; Zhu, Kangru; Qian, Xinmei; Li, Wei

    2016-01-01

    Background Nasopharyngeal carcinoma (NPC) is a common malignancy in South-East Asia. NPC is characterized by distant metastasis and poor prognosis. The pathophysiological mechanism of nasopharyngeal carcinoma is unknown. This study aimed to identify the crucial miRNAs in nasopharyngeal carcinoma and their target genes, and to discover the potential mechanism of nasopharyngeal carcinoma development. Material/Methods Microarray expression profiling of miRNA and mRNA from the Gene Expression Omnibus database was downloaded, and we performed a significance analysis of differential expression. An interaction network of miRNAs and target genes was constructed. The underlying function of differentially expressed genes was predicted through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. To validate the microarray analysis data, significantly different expression levels of miRNAs and target genes were validated by quantitative real-time polymerase chain reaction. Results We identified 27 differentially expressed miRNAs and 982 differentially expressed mRNAs between NPC and normal control tissues. 12 miRNAs and 547 mRNAs were up-regulated and 15 miRNAs and 435 mRNAs were down-regulated in NPC samples. We found a total of 1185 negative correlation pairs between miRNA and mRNA. Differentially expressed target genes were significantly enriched in pathways in cancer, cell cycle, and cytokine-cytokine receptor interaction signaling pathways. Significantly differentially expressed miRNAs and genes, such as hsa-miR-205, hsa-miR-18b, hsa-miR-632, hsa-miR-130a, hsa-miR-34b, PIGR, SMPD3, CD22, DTX4, and CDC6, may play essential roles in the development of nasopharyngeal carcinoma. Conclusions hsa-miR-205, hsa-miR-18b, hsa-miR-632, hsa-miR-130a, and hsa-miR-34b may be related to the development of nasopharyngeal carcinoma by regulating the genes involved in pathways in cancer and cell cycle signaling pathways. PMID:27350400

  10. Prognostic value of cystatin C in patients with nasopharyngeal carcinoma: a retrospective study of 1063 patients

    PubMed Central

    Yuan, Jing; Xu, Miao; Li, Jing; Li, Ning; Chen, Li-Zhen; Feng, Qi-Sheng; Zeng, Yi-Xin

    2016-01-01

    OBJECTIVE: Patients with nasopharyngeal carcinoma experience highly variable outcomes despite receiving similar therapeutic regimens. Identifying biomarkers that predict survival and guide individualized therapy is urgently needed. Cystatin C has been explored as a valuable prognostic marker in several malignancies. We retrospectively assessed the relationship between serum cystatin C levels and nasopharyngeal carcinoma prognosis in a large cohort of nasopharyngeal carcinoma patients receiving long-term follow-up. METHODS: A total of 1063 consecutive patients diagnosed with nasopharyngeal carcinoma from June 2006 to December 2010 were retrospectively analyzed. The serum levels of cystatin C at the time of diagnosis were collected. Receiver operating characteristic curve analysis, the Kaplan-Meier method and multivariate analyses using a Cox regression model were performed to assess the correlation of cystatin C levels with overall survival, progression-free survival, distant metastasis-free survival and loco-regional recurrence-free survival. RESULTS: The median follow-up duration was 68.3 months. The optimal cut-off value of cystatin C levels for predicting death was 0.945 mg/L. Compared with the low cystatin C group, the high cystatin C group experienced significantly shorter overall survival (hazard ratio=1.47, p=0.050), progression-free survival (hazard ratio=1.65, p=0.004), distant metastasis-free survival (hazard ratio=2.37, p<0.001) and loco-regional recurrence-free survival (hazard ratio=2.40, p=0.002). Based on multivariate analysis, a high cystatin C level was identified as a significant and independent negative predictor of overall survival (hazard ratio=1.47, p=0.050), progression-free survival (hazard ratio=1.65, p=0.004), distant metastasis-free survival (hazard ratio=2.37, p<0.001), and loco-regional recurrence-free survival (hazard ratio=2.40, p=0.002). CONCLUSION: Cystatin C levels are associated with the prognosis of nasopharyngeal carcinoma

  11. Nasopharyngeal carcinoma as a paradigm of cancer genetics.

    PubMed

    Simons, Malcolm J

    2011-02-01

    The unusual incidence patterns for nasopharyngeal carcinoma (NPC) in China, Northeast India, Arctic Inuit, Peninsular and island Southeast Asia, Polynesian Islanders, and North Africans indicate a role for NPC risk genes in Chinese, Chinese-related, and not-obviously Chinese-related populations. Renewed interest in NPC genetic risk has been stimulated by a hypothesis that NPC population patterns originated in Bai-Yue / pre-Austronesian-speaking aborigines and were dispersed during the last glacial maximum by Sundaland submersion. Five articles in this issue of the Chinese Journal of Cancer, first presented at a meeting on genetic aspects of NPC [National Cancer Center of Singapore (NCCS), February 20-21, 2010], are directed towards incidence patterns, to early detection of affected individuals within risk populations, and to the application of genetic technology advances to understanding the nature of high risk. Turnbull presents a general framework for understanding population migrations that underlie NPC and similar complex diseases, including other viral cancers. Trejaut et al. apply genetic markers to detail migration from East Asia through Taiwan to the populating of Island Polynesia. Migration dispersal in a westward direction took mongoloid peoples to modern day Northeast India adjacent to Western China (Xinjiang). NPC incidence in mongoloid Nagas ranks amongst the highest in the world, whereas elsewhere in India NPC is uncommon. Cao et al. detail incidence patterns in Southeast China that have occurred over recent decades. Finally, Ji et al. describe the utility of Epstein-Barr virus serostatus in early NPC detection. While genetic risk factors still remain largely unknown, human leukocyte antigen (HLA) genes have been a focus of attention since the discovery of an HLA association with NPC in 1973 and, two years later, that NPC susceptibility in highest-risk Cantonese involved the co-occurrence of multi-HLA locus combinations of HLA genes as chromosome

  12. Andrographolide Suppresses Proliferation of Nasopharyngeal Carcinoma Cells via Attenuating NF-κB Pathway

    PubMed Central

    Peng, Tao; Hu, Min; Wu, Ting-Ting; Zhang, Cen; Chen, Zhe; Huang, Shuo; Zhou, Xu-Hong

    2015-01-01

    Andrographolide (Andro) has been reported to have anticancer activity in multiple types of cancer due to its capacity to inactivate NF-κB pathway. Previous studies showed the therapeutic potential of targeting NF-κB pathway in nasopharyngeal carcinoma (NPC). However, the anticancer activity of Andro in NPC has not been reported. In this study, we defined the anticancer effects of Andro in NPC and elucidated its potential mechanisms of action. Our results showed that Andro significantly inhibited the proliferation and invasion of NPC cells (P < 0.05, resp.). These anticancer activities were associated with cell apoptosis, cell death and induction of cell cycle arrest, and the downregulation of NF-κB target genes. This work provides evidence that NF-κB pathway is a potential therapeutic target and may also be indispensable in the Andro-mediated anticancer activities in nasopharyngeal carcinoma. PMID:25861643

  13. Automated Ki-67 Quantification of Immunohistochemical Staining Image of Human Nasopharyngeal Carcinoma Xenografts

    PubMed Central

    Shi, Peng; Zhong, Jing; Hong, Jinsheng; Huang, Rongfang; Wang, Kaijun; Chen, Yunbin

    2016-01-01

    Nasopharyngeal carcinoma is one of the malignant neoplasm with high incidence in China and south-east Asia. Ki-67 protein is strictly associated with cell proliferation and malignant degree. Cells with higher Ki-67 expression are always sensitive to chemotherapy and radiotherapy, the assessment of which is beneficial to NPC treatment. It is still challenging to automatically analyze immunohistochemical Ki-67 staining nasopharyngeal carcinoma images due to the uneven color distributions in different cell types. In order to solve the problem, an automated image processing pipeline based on clustering of local correlation features is proposed in this paper. Unlike traditional morphology-based methods, our algorithm segments cells by classifying image pixels on the basis of local pixel correlations from particularly selected color spaces, then characterizes cells with a set of grading criteria for the reference of pathological analysis. Experimental results showed high accuracy and robustness in nucleus segmentation despite image data variance. Quantitative indicators obtained in this essay provide a reliable evidence for the analysis of Ki-67 staining nasopharyngeal carcinoma microscopic images, which would be helpful in relevant histopathological researches. PMID:27562647

  14. Automated Ki-67 Quantification of Immunohistochemical Staining Image of Human Nasopharyngeal Carcinoma Xenografts.

    PubMed

    Shi, Peng; Zhong, Jing; Hong, Jinsheng; Huang, Rongfang; Wang, Kaijun; Chen, Yunbin

    2016-01-01

    Nasopharyngeal carcinoma is one of the malignant neoplasm with high incidence in China and south-east Asia. Ki-67 protein is strictly associated with cell proliferation and malignant degree. Cells with higher Ki-67 expression are always sensitive to chemotherapy and radiotherapy, the assessment of which is beneficial to NPC treatment. It is still challenging to automatically analyze immunohistochemical Ki-67 staining nasopharyngeal carcinoma images due to the uneven color distributions in different cell types. In order to solve the problem, an automated image processing pipeline based on clustering of local correlation features is proposed in this paper. Unlike traditional morphology-based methods, our algorithm segments cells by classifying image pixels on the basis of local pixel correlations from particularly selected color spaces, then characterizes cells with a set of grading criteria for the reference of pathological analysis. Experimental results showed high accuracy and robustness in nucleus segmentation despite image data variance. Quantitative indicators obtained in this essay provide a reliable evidence for the analysis of Ki-67 staining nasopharyngeal carcinoma microscopic images, which would be helpful in relevant histopathological researches. PMID:27562647

  15. Osteosarcoma of the maxilla in Hong Kong Chinese postirradiation for nasopharyngeal carcinoma. A report of four cases

    SciTech Connect

    Dickens, P.; Wei, W.I.; Sham, J.S. )

    1990-11-01

    Postirradiation osteosarcoma of the maxilla was seen in four Hong Kong Chinese patients treated for nasopharyngeal carcinoma. These cases represent four of 42 (9%) cases of osteosarcoma at all sites in this institution during the period 1979 to 1989, when more than 1000 patients were treated with radiotherapy for nasopharyngeal carcinoma. The latent periods varied from 8 to 11 years from completion of radiotherapy treatment to development of osteosarcoma. The radiation dosage varied from 6000 to 6280 cGy in three of the patients. These cases fit the criteria for diagnosis of postirradiation sarcomas. Maxillary osteosarcomas after irradiation for nasopharyngeal carcinoma do not appear to have been described. The very high incidence of nasopharyngeal carcinoma (for which radiotherapy is the treatment of choice) in Hong Kong Chinese would make the occurrence of such tumors more likely in Hong Kong, although the small risk does not contraindicate the use of radiation in the treatment of nasopharyngeal carcinoma in view of its well-documented efficacy.

  16. Expression levels of JNK associated with polymorphic lactotransferrin haplotypes in human nasopharyngeal carcinoma

    PubMed Central

    Luo, Gengqiu; Zhou, Yanhong; Yi, Wei; Yi, Hong

    2016-01-01

    Lactotransferrin (LTF), a member of the transferrin family, serves a role in the innate immune response and is involved in anti-inflammatory, anti-microbial and anti-tumor activity. Alterations in the LTF gene are associated with an increased incidence of cancer. The LTF gene is polymorphic, and several common alleles may be observed in the general population. Our previous study identified a lower rate of occurrence of the ‘A-G-G-T’ haplotype (constructed with rs1126477, rs1126478, rs2073495 and rs9110) in nasopharyngeal carcinoma (NPC) patients compared with controls. In the present study, in order to elucidate a possible mechanism of LTF-mediated anti-tumor activity in NPC, the protein profiles of NPC and non-tumorous nasopharyngeal epithelium tissues with/without the ‘A-G-G-T’ haplotype were constructed using LTQ Orbitrap technology. The results revealed that c-Jun N-terminal kinase 2 (JNK2) was highly expressed in NPC tissues and non-tumor nasopharyngeal epithelium tissues without the ‘A-G-G-T’ haplotype. These results were confirmed by western blot analysis. Furthermore, microRNA (miRNA) microarray analysis was conducted to investigate the differential miRNA profiles of NPC and non-tumor nasopharyngeal epithelium tissues with/without the ‘A-G-G-T’ haplotype. It was observed that hsa-miR-1256 and hsa-miR-659, which are potentially targeted to the JNK2 gene, were downregulated in NPC tissues without the ‘A-G-G-T’ haplotype. Hsa-miR-298, another miRNA potentially targeted to the JNK2 gene, was downregulated in non-tumor nasopharyngeal epithelium tissues without the ‘A-G-G-T’ haplotype. In summary, these results suggested that the expression levels of JNK2 may be associated with polymorphic LTF haplotypes in human NPC. PMID:27446399

  17. Optimal multivariate method for Raman spectroscopy based diagnosis of nasopharyngeal carcinoma

    NASA Astrophysics Data System (ADS)

    Chen, Bingling; Li, Shaoxin; Li, Jianghua; Guo, Zhouyi; Chen, Qiuyan; Mai, Haiqiang

    2013-12-01

    In this paper, we evaluated four kinds of classification algorithms on Raman spectra for nasopharyngeal carcinoma (NPC) diagnosis: Bayesian classification (BC), Linear discriminate analysis (LDA), Mahalanobis distance after the principal component analysis (PCA); as well the Genetic algorithm-LDA. A total of 225 Raman spectra were acquired from 120 tissue sites of 63 patients, in which 56 Raman spectra were from normal tissue, whereas 171 Raman spectra were from cancer nasopharyngeal tissue. The averaged Raman spectrum of NPC could be distinguished from that of the control group by the above multivariate analysis. Discrimination analysis of PCA-BC revealed that the highest sensitivity, specificity and overall accuracy of cancer diagnosis were 98% (1/56), 99% (1/171), and 99%, respectively. The results showed that Raman spectroscopy in combination with Bayesian classification had high enough sensitivity and specificity to accurately detect and diagnose NPC.

  18. Habitual Consumption of Soy Products and Risk of Nasopharyngeal Carcinoma in Chinese Adults: A Case-Control Study

    PubMed Central

    Liu, Yuan-ting; Fan, Yu-ying; Xu, Chun-hua; Lin, Xiao-ling; Lu, Yun-kai; Zhang, Xing-lan; Zhang, Cai-xia; Chen, Yu-ming

    2013-01-01

    Background and Objectives Many studies have shown a negative association between the consumption of soy products and the risk of some cancers, but little is known about the effect of soy consumption on nasopharyngeal carcinoma. We assessed the association between the consumption of soy products on nasopharyngeal carcinoma risk in Chinese individuals. Methods This case-control study included 600 (448 males and 152 females) incident cases of nasopharyngeal carcinoma, and an equal number of controls, matched according to gender, age (± 3 y) and household type to the nasopharyngeal carcinoma cases. All subjects were recruited from hospitals in Guangzhou, China. A face-to-face interview was conducted with each study individual to collect general information and habitual dietary intake using a 78-item quantitative food-frequency questionnaire. Odds ratios and their 95% confidence intervals were estimated using conditional logistic regression analyses. Results The median intakes of soy foods (in protein) were 0.5/0.5, 1.4/1.7, 2.7/3.3 and 6.1/7.7 (male/female) g/d in the quartiles 1 to 4. Both univariate and multivariate analyses showed no significant association between the consumption of soy proteins or soy isoflavones and the risk of nasopharyngeal carcinoma. The adjusted odds ratios (95% confidence intervals) between extreme quartiles were 0.97 (0.66-1.45) for soy proteins and 0.97 (0.66-1.42) for total isoflavones. Null associations were also observed between intake of the individual isoflavones daidzein, genistein and glycitein and NPC risk, with adjusted odds ratios for the extreme quartiles ranging between 0.73 and 1.23. Conclusion Habitual consumption of soy products had no significant effect on the risk of nasopharyngeal carcinoma in Chinese adults with a relatively low intake. PMID:24155974

  19. Sphenoid sinus mucocoele and cranial nerve palsies in a patient with a history of nasopharyngeal carcinoma: may mimic local recurrence.

    PubMed

    Wong, C S; Luk, S H; Leung, T W; Yuen, K K; Sze, W K; Tung, S Y

    2001-01-01

    We report the case history of a patient with a sphenoid sinus mucocoele detected by computed tomography and medical resonance imaging. The patient had a history of nasopharyngeal carcinoma, which was treated by radiotherapy more than 10 years previously. He presented with bilateral twelfth and sixth cranial nerve palsies. Local tumour recurrence was suspected. Further investigations showed that the cranial nerve palsies were caused by radiation damage and the sphenoid sinus mucocoele was an incidental finding. Sphenoid sinus mucocoele is a possible rare late complication of radiotherapy in patients with nasopharyngeal carcinoma. PMID:11716228

  20. Pediatric and Young Adult Nasopharyngeal Carcinoma Patients Treated With Preradiation Cisplatin and Docetaxel Chemotherapy

    SciTech Connect

    Varan, Ali Ozyar, Enis; Corapcioglu, Funda; Koeksal, Yavuz; Aydin, Burca; Yazici, Nalan; Akyuez, Canan; Bueyuekpamukcu, Muenevver

    2009-03-15

    Purpose: To evaluate treatment results for pediatric and young adult (aged <21 years) patients with nonmetastatic nasopharyngeal carcinoma treated with neoadjuvant cisplatin + docetaxel and radiotherapy. Methods and Materials: Ten patients with nasopharyngeal carcinoma who received diagnoses between 2004 and 2007 were treated with four cycles of cisplatin 100 mg/m{sup 2} + docetaxel 75 mg/m{sup 2} on Day 1 with premedication every 3 weeks. All patients were treated with fractionated external beam radiotherapy after chemotherapy to a median dose of 59.4 Gy (range, 54-59.4 Gy) to the primary disease and 40 Gy to the supraclavicular field with the clavicles shielded. Five children were monitored with serum EBV DNA quantification at diagnosis, after each cycle of chemotherapy, before radiotherapy, and at follow-up. Results: The median age of the patients was 14 years (range, 9-20 years), with a male:female ratio of 6:4. Stage distribution was as follows: 2 patients had Stage IIb disease, 2 had Stage III, 4 had Stage IVa, and 2 had Stage IVb disease. After cisplatin+docetaxel chemotherapy 1 patient had a complete response, 5 had a partial response, 3 had stable disease, and 1 had disease progression. The 2-year overall survival rate in our series was 90% and the event-free survival rate was 70%. No major chemotherapy toxicity was observed. The EBV DNA titers were higher in 2 of the 5 monitored patients at the time of diagnosis. Conclusion: As neoadjuvant chemotherapy before radiotherapy, the cisplatin+docetaxel combination is safe for use in the treatment of childhood nasopharyngeal carcinoma.

  1. Is Elective Irradiation to the Lower Neck Necessary for N0 Nasopharyngeal Carcinoma?

    SciTech Connect

    Gao Yunsheng; Zhu Guopei; Lu Jiade; Ying Hongmei; Kong Ling; Wu Yongru; Hu Chaosu

    2010-08-01

    Purpose: To summarize our experience and treatment results in lymph node-negative nasopharyngeal carcinoma treated in a single institution. Methods and Materials: From January 2000 to December 2003, 410 patients with lymph node-negative nasopharyngeal carcinoma were retrospectively analyzed. The T-stage distribution was 18.8% in T1, 54.6% in T2 (T2a, 41 patients; T2b, 183 patients), 13.2% in T3, and 13.4% in T4. All patients received radiotherapy to the nasopharynx, skull base, and upper neck drainage areas, including levels II, III, and VA. The dose was 64-74 Gy, 1. 8-2.0 Gy per fraction over 6.5-7.5 weeks to the primary tumor with {sup 60}Co or 6-MV X-rays, and 50-56 Gy to levels II, III, and VA. Residual disease was boosted with either {sup 192}Ir afterloading brachytherapy or small external beam fields. Results: The median follow-up time was 54 months (range, 3-90 months). Four patients developed neck recurrence, and only 1 patient (0.2%) experienced relapse outside the irradiation fields. The 5-year overall survival rate was 84.2%. The 5-year relapse-free survival rate, distant metastasis-free survival rate, and disease-free survival rate were 88.6%, 90.6% and 80.1%, respectively. Both univariate and multivariate analyses demonstrated that T classification was the only significant prognostic factor for predicting overall survival. The observed serious late toxicities were radiation-induced brain damage (7 cases), cranial nerve palsy (16 cases), and severe trismus (13 cases; the distance between the incisors was {<=}1 cm). Conclusion: Elective levels II, III, and VA irradiation is suitable for nasopharyngeal carcinoma without neck lymph node metastasis.

  2. Association between PIN1 promoter polymorphisms and risk of nasopharyngeal carcinoma.

    PubMed

    Lu, Yan; Huang, Guo-Liang; Pu, Xing-Xiang; He, Yu-Xiang; Li, Bin-Bin; Liu, Xing-Yan; Dong, Zigang; He, Zhiwei

    2013-05-01

    Peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (PIN1) plays an important role in cell transformation and oncogenesis. Association between PIN1 promoter polymorphisms and cancer risk was reported in several cancers. This study aimed to evaluate the association between two single nucleotide polymorphisms (SNPs, -667T>C, rs2233679 and -842G>C, rs2233678) on PIN1 promoter and risk of nasopharyngeal carcinoma (NPC). The two SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism in a total of 334 native Chinese subjects consisting of 178 cases and 156 controls. The results indicated that the -667CT heterozygote and -667CC homozygote exhibited a significantly decreased risk of nasopharyngeal carcinoma when compared with -667TT homozygote (OR = 0.639, 95% CI = 0.452-0.903, p = 0.011 for -667CT; and OR = 0.441, 95% CI = 0.213-0.915, p = 0.038 for -667CC, respectively). In the -842G>C polymorphism, compared with -842GG homozygote, only -842CG heterozygote but not -842CC homozygote had a significantly decreased risk of nasopharyngeal carcinoma (OR = 0.465, 95% CI = 0.249-0.871, p = 0.010). Genotype in the two SNPs in patients showed no significant associations with the clinicopathologic features examined. Our study showed that the minor genotypes of PIN1 promoter (-667CT, -667CC and -842CG) were associated with decreased risk of NPC in a Chinese population, suggested that PIN1 promoter polymorphisms might play an important role in NPC carcinogenesis. PMID:23269625

  3. Unidimensional Measurement May Evaluate Target Lymph Nodal Response After Induction Chemotherapy for Nasopharyngeal Carcinoma

    PubMed Central

    Chen, Chuanben; Zhang, Mingwei; Xu, Yuanji; Yue, Qiuyuan; Bai, Penggang; Zhou, Lin; Xiao, Youping; Zheng, Dechun; Lin, Kongqi; Qiu, Sufang; Chen, Yunbin; Pan, Jianji

    2016-01-01

    Abstract The aim of the study was to evaluate whether short axis and long axis on axial and coronal magnetic resonance imaging planes would reflect the tumor burden or alteration in size after induction chemotherapy in nasopharyngeal carcinoma. Patients with pathologically confirmed nasopharyngeal carcinoma (n = 37) with at least 1 positive cervical lymph node (axial short axis ≥15 mm) were consecutively enrolled in this prospective study. Lymph nodal measurements were performed along its short axis and long axis in both axial and coronal magnetic resonance imaging planes at diagnosis and after 2 cycles of induction chemotherapy. In addition, lymph nodal volumes were automatically calculated in 3D treatment-planning system, which were used as reference standard. Student's t test or nonparametric Mann–Whitney U test was used to compare the continuous quantitative variables. Meanwhile, the κ statistic and McNemar's test were used to evaluate the degree of agreement and discordance in response categorization among different measurements. Axial short axis was significantly associated with volumes at diagnosis (P < 0.001). A good agreement (κ=0.583) was found between axial short axis and volumetric criteria. However, the inconsistent lymph nodal shrinkage in 4 directions was observed. Axial short-axis shrinking was more rapid than the other 3 parameters. Interestingly, when utilizing the alternative planes for unidimensional measurements to assess tumor response, coronal short-axis showed the best concordance (κ=0.792) to the volumes. Axial short axis may effectively reflect tumor burden or change in tumor size in the assessment of target lymph nodal response after induction chemotherapy for nasopharyngeal carcinoma. However, it should be noted that axial short axis may amplify the therapeutic response. In addition, the role of coronal short axis in the assessment of tumor response needs further evaluation. PMID:26945354

  4. Clinical evaluation of the diagnosis of nasopharyngeal carcinoma using teleconsultation system

    NASA Astrophysics Data System (ADS)

    Zhang, Hong; Hu, Dake; Zhou, Shengmin; Tian, Peilin

    1997-05-01

    Diagnosing nasopharyngeal carcinoma in its early stage plays an important role in the treatment of this disease. We have developed a teleconsultation system to assist rural clinician diagnose the carcinoma under the help of radiologist at metropolitan hospital. In November 1996, we put the system into clinical environment for trial. The purpose is, from the radiologist and physician's points of view, to compare our teleconsultation system to the traditional travel-based consultation. Two hospitals were involved in the trial. We deployed a teleconsultation expert center (TEC) and remote clinician's workstation connected to TEC through publish telephone networks. Three radiologists and one clinician were involved in the three-week trial collecting 35 cases. For each case in our trial, two kinds of consultation were performed: the teleconsultation and then the travel-based one. We, for both ways of consultation, (1) collected all pairs of reports, (2) calculated financial expenditure, and (3) recorded time involved. We also asked the professionals involved for their impression of the system. Data collected from the evaluation has indicated a sanguine feature for diagnosing nasopharyngeal carcinoma using teleconsultation system: the diagnosis accuracy is excellent, the cost and the consultation delay were significantly reduced.

  5. Pharmacological inactivation of CHK1 and WEE1 induces mitotic catastrophe in nasopharyngeal carcinoma cells.

    PubMed

    Mak, Joyce P Y; Man, Wing Yu; Chow, Jeremy P H; Ma, Hoi Tang; Poon, Randy Y C

    2015-08-28

    Nasopharyngeal carcinoma (NPC) is a rare but highly invasive cancer. As radiotherapy is the primary treatment for NPC, this offers a rationale to investigate if uncoupling the DNA damage responses can sensitize this cancer type. The G2 DNA damage checkpoint is controlled by a cascade of protein kinases: ATM/ATR, which phosphorylates CHK1/CHK2, which in turn phosphorylates WEE1. A number of small molecule inhibitors have been developed against these kinases as potential therapeutic agents. Here we demonstrated that compare to that in immortalized nasopharyngeal epithelial cells, ATR, CHK1, and WEE1 were overexpressed in NPC cell lines. Inhibitors of these kinases were unable to promote extensive mitotic catastrophe in ionizing radiation-treated NPC cells, indicating that they are not very effective radiosensitizer for this cancer. In the absence of prior irradiation, however, mitotic catastrophe could be induced with inhibitors against CHK1 (AZD7762) or WEE1 (MK-1775). NPC cells were more sensitive to WEE1 inactivation than nasopharyngeal epithelial cells. Targeting CHK1 and WEE1 together induced more extensive mitotic catastrophe than the individual components alone. Taken together, our results show that NPC cells depend on CHK1 and WEE1 activity for growth and that inhibitors of these kinases may serve as potential therapeutics for NPC. PMID:26025928

  6. Pharmacological inactivation of CHK1 and WEE1 induces mitotic catastrophe in nasopharyngeal carcinoma cells

    PubMed Central

    Mak, Joyce P.Y.; Man, Wing Yu; Chow, Jeremy P.H.; Ma, Hoi Tang; Poon, Randy Y.C.

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is a rare but highly invasive cancer. As radiotherapy is the primary treatment for NPC, this offers a rationale to investigate if uncoupling the DNA damage responses can sensitize this cancer type. The G2 DNA damage checkpoint is controlled by a cascade of protein kinases: ATM/ATR, which phosphorylates CHK1/CHK2, which in turn phosphorylates WEE1. A number of small molecule inhibitors have been developed against these kinases as potential therapeutic agents. Here we demonstrated that compare to that in immortalized nasopharyngeal epithelial cells, ATR, CHK1, and WEE1 were overexpressed in NPC cell lines. Inhibitors of these kinases were unable to promote extensive mitotic catastrophe in ionizing radiation-treated NPC cells, indicating that they are not very effective radiosensitizer for this cancer. In the absence of prior irradiation, however, mitotic catastrophe could be induced with inhibitors against CHK1 (AZD7762) or WEE1 (MK-1775). NPC cells were more sensitive to WEE1 inactivation than nasopharyngeal epithelial cells. Targeting CHK1 and WEE1 together induced more extensive mitotic catastrophe than the individual components alone. Taken together, our results show that NPC cells depend on CHK1 and WEE1 activity for growth and that inhibitors of these kinases may serve as potential therapeutics for NPC. PMID:26025928

  7. Nasopharyngeal carcinomas frequently lack the p16/MTS1 tumor suppressor protein but consistently express the retinoblastoma gene product.

    PubMed Central

    Gulley, M. L.; Nicholls, J. M.; Schneider, B. G.; Amin, M. B.; Ro, J. Y.; Geradts, J.

    1998-01-01

    The p16/MTS1 gene is altered by deletion, mutation, or hypermethylation in a wide variety of human cancers. As a result of deficient p16 protein, these cancers lack a critical mechanism for halting G1/S cell cycle progression. In the current study, 59 cases of nasopharyngeal carcinoma were evaluated for expression of the p16 tumor suppressor protein by immunohistochemical analysis of paraffin-embedded tissue. There was no detectable p16 in 38/59 cases (64%), which implies a very high rate of p16 inactivation in this type of cancer. On the other hand, the retinoblastoma gene product, which also regulates the G1 to S phase transition of the cell cycle, was consistently expressed in nasopharyngeal carcinomas by immunohistochemical analysis. These results implicate p16 inactivation but not Rb alteration in the stepwise progression of nasopharyngeal carcinogenesis. Images Figure 1 Figure 2 PMID:9546345

  8. Role of plasma EBV DNA levels in predicting recurrence of nasopharyngeal carcinoma in a western population

    PubMed Central

    2012-01-01

    Background Loco-regionally advanced nasopharyngeal carcinomas can be cured by the combination of chemotherapy and radiotherapy. In Eastern countries, plasma levels of viral Epstein-Barr deoxyribonucleic acid (DNA) are accurate in predicting recurrence, but few data are available in Western populations. The aim of this prospective study was to evaluate the relationship between viral Epstein-Barr DNA copy numbers in plasma and the response rate, progression-free survival and overall survival in a cohort of Western patients with stage IIb-IVb nasopharyngeal cancer. Methods We evaluated plasma samples from 36 consecutive patients treated with induction chemotherapy followed by chemoradiation. EBV copy numbers were determined after DNA extraction using real-time quantitative polymerase chain reaction. Survival curves were estimated using the Kaplan–Meier method. Results Circulating Epstein-Barr virus DNA levels were measured before treatment, at the end of concomitant chemo- and radiotherapy, and during the follow-up period. Pre-treatment levels significantly correlated with the initial stage and probability of relapse. Their increase was 100% specific and 71.3% sensitive in detecting loco-regional or metastatic recurrence (an overall accuracy of 94.4%). Three-year progression-free and overall survival were respectively 78.2% and 97.1%. Conclusions The results of this study confirm that patients from a Western country affected by loco-regionally advanced nasopharyngeal carcinoma have high plasma Epstein-Barr virus DNA levels at diagnosis. The monitoring of plasma levels is sensitive and highly specific in detecting disease recurrence and metastases. PMID:22646734

  9. Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma

    ClinicalTrials.gov

    2016-07-20

    Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Nasopharyngeal Undifferentiated Carcinoma; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IV Nasopharyngeal Undifferentiated Carcinoma

  10. LOX expression in primary nasopharyngeal carcinoma: correlation with prognostic parameters and outcome

    PubMed Central

    Tang, Ling-Quan; Chen, Qiu-Yan; Shao, Jian-Yong; Mai, Hai-Qiang

    2016-01-01

    Lysyl oxidase (LOX) is an extracellular matrix-remodeling enzyme that plays important roles in tumor development and progression. To evaluate the prognostic value of LOX levels in primary nasopharyngeal carcinoma, we performed an immunohistochemical analysis using 233 tissue biopsy specimens from as many patients. We found that the extent of immunohistochemical LOX staining correlated inversely with the clinicopathological features and survival. High LOX expression correlated with decreases in 5-year survival, overall survival, distant metastasis-free survival and disease-free survival (p < 0.05). Cox regression analysis confirmed that LOX was a significant prognostic indicator of increased risk of 5-year mortality for all patients (hazard ratio [HR], 1.670; 95% confidence interval [95% CI], 1.033–2.701 [p < .005]). Higher LOX expression was also an independent predictor of poor prognosis in patients with nasopharyngeal carcinoma. These findings suggest LOX may be a new biomarker predictive of NPC prognosis and may also be a useful treatment target. PMID:26882568

  11. miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4

    SciTech Connect

    Chen, Liang; Tang, Yanping; Wang, Jian; Yan, Zhongjie; Xu, Ruxiang

    2013-06-14

    Highlights: •miR-421 is upregulated in nasopharyngeal carcinoma. •miR-421 induces cell proliferation and apoptosis resistance. •FOXO4 is a direct and functional target of miR-421. -- Abstract: microRNAs have been demonstrated to play important roles in cancer development and progression. Hence, identifying functional microRNAs and better understanding of the underlying molecular mechanisms would provide new clues for the development of targeted cancer therapies. Herein, we reported that a microRNA, miR-421 played an oncogenic role in nasopharyngeal carcinoma. Upregulation of miR-421 induced, whereas inhibition of miR-421 repressed cell proliferation and apoptosis resistance. Furthermore, we found that upregulation of miR-421 inhibited forkhead box protein O4 (FOXO4) signaling pathway following downregulation of p21, p27, Bim and FASL expression by directly targeting FOXO4 3′UTR. Additionally, we demonstrated that FOXO4 expression is critical for miR-421-induced cell growth and apoptosis resistance. Taken together, our findings not only suggest that miR-421 promotes nasopharyngeal carcinoma cell proliferation and anti-apoptosis, but also uncover a novel regulatory mechanism for inactivation of FOXO4 in nasopharyngeal carcinoma.

  12. Nasopharyngeal Carcinoma in Children: Comparison of Conventional and Intensity-Modulated Radiotherapy

    SciTech Connect

    Laskar, Siddhartha Bahl, Gaurav; Muckaden, MaryAnn; Pai, Suresh K.; Gupta, Tejpal; Banavali, Shripad; Arora, Brijesh; Sharma, Dayanand; Kurkure, Purna A.; Ramadwar, Mukta; Viswanathan, Seethalaxhmi; Rangarajan, Venkatesh; Qureshi, Sajid; Deshpande, Deepak D.; Shrivastava, Shyam K.; Dinshaw, Ketayun A.

    2008-11-01

    Purpose: To evaluate the efficacy of intensity-modulated radiotherapy (IMRT) in reducing the acute toxicities associated with conventional RT (CRT) in children with nasopharyngeal carcinoma. Patients and Methods: A total of 36 children with nonmetastatic nasopharyngeal carcinoma, treated at the Tata Memorial Hospital between June 2003 and December 2006, were included in this study. Of the 36 patients, 28 were boys and 8 were girls, with a median age of 14 years; 4 (11%) had Stage II and 10 (28%) Stage III disease at presentation. All patients had undifferentiated carcinoma and were treated with a combination of chemotherapy and RT. Of the 36 patients, 19 underwent IMRT and 17 underwent CRT. Results: After a median follow-up of 27 months, the 2-year locoregional control, disease-free, and overall survival rate was 76.5%, 60.6%, and 71.3%, respectively. A significant reduction in acute Grade 3 toxicities of the skin (p = 0.006), mucous membrane (p = 0.033), and pharynx (p = 0.035) was noted with the use of IMRT. The median time to the development of Grade 2 toxicity was delayed with IMRT (skin, 35 vs. 25 days, p = 0.016; mucous-membrane, 39 vs. 27 days, p = 0.002; and larynx, 50 vs. 28 days, p = 0.009). The duration of RT significantly influenced disease-free survival on multivariate analysis (RT duration >52 days, hazard ratio = 5.49, 95% confidence interval, 1.14-26.45, p = 0.034). The average mean dose to the first and second planning target volume was 71.8 Gy and 62.5 Gy with IMRT compared with 66.3 Gy (p = 0.001) and 64.4 Gy (p = 0.046) with CRT, respectively. Conclusion: The results of our study have shown that IMRT significantly reduces and delays the onset of acute toxicity, resulting in improved tolerance and treatment compliance for children with nasopharyngeal carcinoma. Also, IMRT provided superior target coverage and normal tissue sparing compared with CRT.

  13. [Contribution of serum Cyfra 21-1 in nasopharyngeal carcinoma in Tunisia].

    PubMed

    Jmal, Aouatef; Boussen, Hamouda; Abdennebi, Monia; Gara, Sonia; Harzallah, Latifa; Gritli, Saïd; Ladgham, Abderrahmen; Guemira, Fethi; Ghanem, Abderraouf

    2004-04-01

    Cyfra 21-1 is a recognised marker for epidermoid lung and head and neck carcinomas oriented to the cytokeratin 19 that is expressed particularly in malignant epithelial cells. The aims of this study were to evaluate the importance of the use of this marker in nasopharyngeal carcinoma (NPC). Our prospective study interested 41 patients (33M/8F) with a mean age of 44 years (13 to 70) with 8 of them aged less than 30 years, presenting a nasopharyngeal carcinoma histologically confirmed from September 1999 to March 2000 and 45 healthy controls without evidence neoplasm. Undifferentiated forms represent 90.2% of cases and lesions are staged T2, T3 and T4 in 2.4%, 36.6% and 61% of cases, while N1, N2 and N3 represent 9.8%, 26.8% and 41.5% of cases. A blood sample was collected from each patient and control before any treatment, as well as controls to measure Cyfra 21-1 by immunoenzymatic assay, 2 groups of patients were selected after a period varying from 4 to 37 months with a median of 29 months: 27 patients with favourable evolution (without evidence of disease after initial treatment), 12 patients with non favourable evolution (1 death, 2 cases of loco-regional relapse and 9 patients with metastatic disease). 2 patients were lost to follow-up. The results showed that the mean serum Cyfra 21-1 values were significantly higher in patients with NPC than those in controls (p = 0.001). A significant correlation was found between the serum Cyfra 21-1 level before treatment and the clinical outcome of patients (p = 0.0009). Patients having a favourable evolution have the lowest level. Seric level of Cyfra 21-1 at diagnosis of NPC may play a predictive role to evaluate the risk of metastatic disease and prognosis. PMID:15242321

  14. Expression of the Pokemon proto-oncogene in nasopharyngeal carcinoma cell lines and tissues.

    PubMed

    Jiao, Wei; Liu, Fei; Tang, Feng-Zhu; Lan, Jiao; Xiao, Rui-Ping; Chen, Xing-Zhou; Ye, Hui-Lan; Cai, Yong-Lin

    2013-01-01

    To study the differentiated expression of the proto-oncogene Pokemon in nasopharyngeal carcinoma (NPC) cell lines and tissues, mRNA and protein expression levels of CNE1, CNE2, CNE3 and C666-1 were detected separately by reverse transcription polymerase chain reaction (RT-PCR), real-time PCR and Western-blotting. The immortalized nasopharyngeal epithelial cell line NP69 was used as a control. The Pokemon protein expression level in biopsy specimens from chronic rhinitis patients and undifferentiated non keratinizing NPC patients was determined by Western-blotting and arranged from high to low: C666-1>CNE1>CNE2> CNE3>NP69. The Pokemon mRNA expression level was also arranged from high to low: CNE1>CNE2>NP69>C666-1>CNE3. Pokemon expression of NP69 and C666-1 obviously varied from mRNA to protein. The Pokemon protein level of NPC biopsy specimens was obviously higher than in chronic rhinitis. The data suggest that high Pokemon protein expression is closely associated with undifferentiated non-keratinizing NPC and may provide useful information for NPC molecular target therapy. PMID:24377524

  15. Label-free discrimination of different stage nasopharyngeal carcinoma tissue based on Raman spectroscopy

    PubMed Central

    QIU, SUFANG; HUANG, QINGTING; HUANG, LINGLING; LIN, JINYONG; LU, JUN; LIN, DUO; CAO, GANG; CHEN, CHAO; PAN, JIANJI; CHEN, RONG

    2016-01-01

    The present study aimed to evaluate a label-free tissue test for the detection of nasopharyngeal carcinoma (NPC) at early and advanced stages using Raman spectroscopy (RS). RS measurements were performed to acquire high quality Raman spectra on two groups of tissue samples: One group consists of 30 NPC patients at the early stages (I–II), and the other group is 46 NPC patients at the advanced stages (III–IV). Tentative assignment of Raman bands showed specific biomolecular changes associated with cancer development. Furthermore, effective diagnostic algorithms based on principal components analysis (PCA) and linear discriminant analysis (LDA) were applied for distinguishing Raman spectra of nasopharyngeal tissues from different stages, yielding a diagnostic sensitivity of 70% and a specificity of 78%. This exploratory work suggests that RS in conjunction with the PCA-LDA algorithms provides good diagnostic ability for the early and the advanced staged NPC tissues, and RS has enormous potential for the non-invasive detection of early and advanced stage NPC. PMID:27073522

  16. Identification of a Novel Methylated Gene in Nasopharyngeal Carcinoma: TTC40

    PubMed Central

    Ayadi, Wajdi; Allaya, Nesrine; Frikha, Hanèn; Trigui, Emna; Khabir, Abdelmajid; Ghorbel, Abdelmonem; Daoud, Jamel; Frikha, Mounir; Mokdad-Gargouri, Raja

    2014-01-01

    To further explore the epigenetic changes in nasopharyngeal carcinoma (NPC), methylation-sensitive arbitrarily primed PCR was performed on NPC biopsies and nontumor nasopharyngeal samples. We have shown mainly two DNA fragments that appeared to be differentially methylated in NPCs versus nontumors. The first, defined as hypermethylated, corresponds to a CpG island at the 5′-end of the tetratricopeptide repeat domain 40 (TTC40) gene, whereas the second, defined as hypo-methylated, is located on repetitive sequences at chromosomes 16p11.1 and 13.1. Thereafter, the epigenetic alteration on the 5′-TTC40 gene was confirmed by methylation-specific PCR, showing a significant aberrant methylation in NPCs, compared to nontumors. In addition, the bisulfite sequencing analysis has shown a very high density of methylated cytosines in C15, C17, and X666 NPC xenografts. To assess whether TTC40 gene is silenced by aberrant methylation, we examined the gene expression by reverse transcription-PCR. Our analysis showed that the mRNA expression was significantly lower in tumors than in nontumors, which is associated with 5′-TTC40 gene hypermethylation. In conclusion, we found that the 5′-TTC40 gene is frequently methylated and is associated with the loss of mRNA expression in NPCs. Hypermethylation of 5′-TTC40 gene might play a role in NPC development; nevertheless, other studies are needed. PMID:25101295

  17. Urokinase-type plasminogen activator receptor signaling is critical in nasopharyngeal carcinoma cell growth and metastasis.

    PubMed

    Bao, Ying-Na; Cao, Xue; Luo, Dong-Hua; Sun, Rui; Peng, Li-Xia; Wang, Lin; Yan, Yong-Pan; Zheng, Li-Sheng; Xie, Ping; Cao, Yun; Liang, Ying-Ying; Zheng, Fang-Jing; Huang, Bi-Jun; Xiang, Yan-Qun; Lv, Xing; Chen, Qiu-Yan; Chen, Ming-Yuan; Huang, Pei-Yu; Guo, Ling; Mai, Hai-Qiang; Guo, Xiang; Zeng, Yi-Xin; Qian, Chao-Nan

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in southern China and Southeast Asia, with the highest metastasis rate among head and neck cancers. The mechanisms underlying NPC progression remain poorly understood. Genome-wide expression profiling on 18 NPC vs. 18 noncancerous nasopharyngeal tissues together with GeneGo pathway analysis and expression verification in NPC cells and tissues revealed a potential role of urokinase-type plasminogen activator receptor (uPAR) in NPC progression, which has not been investigated in NPC. We then observed that uPAR expression is increased in poorly differentiated, highly metastatic NPC cells compared with lowly metastatic cells or differentiated NPC cells. In vitro studies demonstrated that uPAR regulates NPC cell growth, colony formation, migration, and invasion and promotes the epithelial-mesenchymal transition (EMT). Additional tumor xenograft and spontaneous metastasis experiments revealed that uPAR promotes NPC cell growth and metastasis in vivo. The JAK-STAT pathway is involved in uPAR-regulated signaling in NPC cells as determined by immunoblotting. Moreover, uPAR-mediated growth and motility is partially abolished upon treatment with the Jak1/Jak2 inhibitor INCB018424. We suppressed uPA expression in uPAR-overexpressing NPC cells and found that uPAR-mediated cellular growth and motility is not exclusively dependent on uPA. In summary, uPAR is a significant regulator of NPC progression and could serve as a promising therapeutic target. PMID:24763226

  18. Long noncoding RNA hotair mediated angiogenesis in nasopharyngeal carcinoma by direct and indirect signaling pathways

    PubMed Central

    Hu, Bao-guang; Liang, Wei-cheng; Zhu, Xiao; Yang, Hai-di; Li, Gang; Zhang, Jin-fang

    2016-01-01

    Nasopharyngeal carcinoma (NPC), as a unique head and neck cancer type, is particularly prevalent in certain geographic areas such as eastern Asia. Until now, the therapeutic options have been restricted mainly to radiotherapy or chemotherapy. However, the clinical treatment effect remains unsatisfactory even if the combined radio-chemotherapies. Therefore, it is urgently needed to develop effective novel therapies against NPC. In this study, we discovered that lncRNA Hotair was extremely abundant in NPC cells and clinical NPC samples. Further studies showed that Hotair knockdown significantly attenuated both in vitro and in vivo tumor cell growth and angiogenesis. Our study also demonstrated that Hotair promoted angiogenesis through directly activating the transcription of angiogenic factor VEGFA as well as through GRP78-mediated upregulation of VEGFA and Ang2 expression. Therefore, Hotair may serve as a promising diagnostic marker and therapeutic target for NPC patients. PMID:26717040

  19. Incidence of Nasopharyngeal Carcinoma in Malaysia, with Special Reference to the State of Selangor

    PubMed Central

    Armstrong, R. W.; Kutty, M.; Dharmalingam, S. K.

    1974-01-01

    A “registry” of all known cases of nasopharyngeal carcinoma in Malaysia, 1968-72, was established. Attention was focused on the State of Selangor where conditions are best for case finding. Age-adjusted incidence rates among Chinese males and females were 17·3 and 7·3 per 100,000; among Malay males and females, the rates were 2·5 and 0·3 and among Indian males, 1·1. The detailed ethnicity of 192 cases in Selangor was established. Estimated incidence rates for the Chinese sub-groups agreed with the pattern observed elsewhere: highest among the Cantonese, lowest among the Hokkien/Teochiu, with the Khek in between. There was no correlation between histological type and sub-ethnic group among the Chinese cases. PMID:4413823

  20. ISG15 predicts poor prognosis and promotes cancer stem cell phenotype in nasopharyngeal carcinoma

    PubMed Central

    Han, Ping; Wang, Hong-Bo; Liang, Fa-Ya; Feng, Guo-Kai; Zhou, Ai-Jun; Cai, Mu-Yan; Zhong, Qian; Zeng, Mu-Sheng; Huang, Xiao-Ming

    2016-01-01

    Interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, is known for its anti-viral capacity. However, its role in tumorigenesis remains controversial. Here, using RNA-seq profiling analysis, we identified ISG15 as a differentially expressed gene in nasopharyngeal carcinoma (NPC) and validated its overexpression in NPC samples and cells. High ISG15 levels in NPC tissues were correlated with more frequent local recurrence and shorter overall survival and disease-free survival. ISG15 overexpression promoted a cancer stem cell phenotype in NPC cells, including increased colony and tumorsphere formation abilities, pluripotency-associated genes expression, and in vivo tumorigenicity. By contrast, knockdown of ISG15 attenuated stemness characteristics in NPC cells. Furthermore, overexpression of ISG15 increased NPC cell resistance to radiation and cisplatin (DDP) treatment. Our study demonstrates a protumor role of ISG15, and suggests that ISG15 is a prognostic predictor and a potential therapeutic target for NPC. PMID:26919245

  1. Anti-cancer effects of celecoxib on nasopharyngeal carcinoma HNE-1 cells expressing COX-2 oncoprotein

    PubMed Central

    Chen, Jiongyu; Ran, Yonggang; Hong, Chaoqun; Chen, Zhijian

    2010-01-01

    Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor with antitumor and antiangiogenic activities. To investigate the effects of celecoxib on nasopharyngeal carcinoma (NPC), HNE-1 cells were treated with celecoxib at various concentrations. MTT assay, migration assay and invasion assay were performed to observe the inhibitory activity of celecoxib on HNE-1 cells. Additionally, VEGF-A expression and radiation survival of NPC cell were also examined after treatment with celecoxib. Celecoxib treatment presented an anti-proliferation function in a time and dose-dependent manner on HNE-1 cells which highly express COX-2 protein. Celecoxib also displayed an obvious inhibitory activity on invasive capacity of NPC cells. Moreover, the celecoxib’s effects to suppress VEGF-A expression and enhance radiosensitivity were detected in HNE-1 cells. These findings implicate that application of celecoxib may be an effective strategy for NPC therapy. PMID:20809260

  2. A Rare Case of Zosteriform Cutaneous Metastases from a Nasopharyngeal Carcinoma

    PubMed Central

    González García, Andrés; Fernández, Emiliano Grillo; Barbolla Díaz, Ignacio; Ballester, Asunción; Pian, Héctor; Fraile, Guadalupe

    2015-01-01

    From a clinical point of view, the most common presentations of cutaneous metastatic disease are papules and nodules. However, a wide morphological spectrum of lesions has been described, including erythematous patches or plaques, inflammatory erysipelas-like lesions, diffuse sclerodermiform lesions with induration of the skin, telangiectatic papulovesicles, purpuric plaques mimicking vasculitis, and alopecia areata like scalp lesions. The so-called zosteriform pattern has been described to be in few cases and to the best of our knowledge has never been described associated with a metastasis of a nasopharyngeal carcinoma. This case highlights the relevance of including cutaneous metastases in the differential diagnosis of patients with nonhealing herpes zoster-like lesions, especially in those with underlying neoplasm recently diagnosed. PMID:26697235

  3. Knockdown of miR-214 promotes apoptosis and inhibits cell proliferation in nasopharyngeal carcinoma.

    PubMed

    Zhang, Zi-Chen; Li, Yang-Yang; Wang, Hai-Yun; Fu, Sha; Wang, Xiao-Pai; Zeng, Mu-Sheng; Zeng, Yi-Xin; Shao, Jian-Yong

    2014-01-01

    MicroRNA-214 (MiR-214) is aberrantly expressed in several human tumors such as ovarian cancer and breast cancer. However, the role of miR-214 in nasopharyngeal carcinoma (NPC) is still unknown. In this study, we report that miR-214 was overexpressed in NPC cell lines and tissues. Silencing of miR-214 by LNA-antimiR-214 in NPC cells resulted in promoting apoptosis and suppressing cell proliferation in vitro, and suppressed tumor growth in nude mice in vivo. Luciferase reporter assay was performed to identify Bim as a direct target of miR-214. Furthermore, this study showed that low Bim expression in NPC tissues correlated with poor survival of NPC patients. Taken together, our findings suggest that miR-214 plays an important role in NPC carcinogenesis. PMID:24465927

  4. Characterization of the Variability of Epstein-Barr Virus Genes in Nasopharyngeal Biopsies: Potential Predictors for Carcinoma Progression

    PubMed Central

    Banko, Ana V.; Lazarevic, Ivana B.; Folic, Miljan M.; Djukic, Vojko B.; Cirkovic, Andja M.; Karalic, Danijela Z.; Cupic, Maja D.; Jovanovic, Tanja P.

    2016-01-01

    Epstein-Barr virus (EBV) infection is a significant factor in the pathogenesis of nasopharyngeal carcinoma, especially in the undifferentiated carcinoma of nasopharyngeal type (UCNT, World Health Organization type III), which is the dominant histopathological type in high-risk areas. The major EBV oncogene is latent membrane protein 1 (LMP1). LMP1 gene shows variability with different tumorigenic and immunogenic potentials. EBV nuclear antigen 1 (EBNA1) regulates progression of EBV-related tumors; however, the influence of EBNA1 sequence variability on tumor pathogenesis is controversial. The aims of this study were to characterize polymorphisms of EBV genes in non-endemic nasopharyngeal carcinoma biopsies and to investigate potential sequence patterns that correlate with the clinical presentation of nasopharyngeal carcinoma. In total, 116 tumor biopsies of undifferentiated carcinoma of nasopharyngeal type (UCNT), collected from 2008 to 2014, were evaluated in this study. The genes EBNA2, LMP1, and EBNA1 were amplified using nested-PCR. EBNA2 genotyping was performed by visualization of PCR products using gel electrophoresis. Investigation of LMP1 and EBNA1 included sequence, phylogenetic, and statistical analyses. The presence of EBV DNA was significantly distributed between TNM stages. LMP1 variability showed six variants, with the detection of the first China1 and North Carolina variants in European nasopharyngeal carcinoma biopsies. Newly discovered variants Srb1 and Srb2 were UCNT-specific LMP1 polymorphisms. The B95-8 and North Carolina variants are possible predictors for favorable TNM stages. In contrast, deletions in LMP1 are possible risk factors for the most disfavorable TNM stage, independent of EBNA2 or EBNA1 variability. A newly discovered EBNA1 subvariant, P-thr-sv-5, could be a potential diagnostic marker, as it represented a UCNT-specific EBNA1 subvariant. A particular combination of EBNA2, LMP1, and EBNA1 polymorphisms, type 1/Med/P-thr was

  5. A nomogram for predicting survival of nasopharyngeal carcinoma patients with metachronous metastasis.

    PubMed

    Zeng, Zixun; Shen, Lujun; Wang, Yue; Shi, Feng; Chen, Chen; Wu, Ming; Bai, Yutong; Pan, Changchuan; Xia, Yunfei; Wu, Peihong; Li, Wang

    2016-07-01

    Patients with metachronous metastatic nasopharyngeal carcinoma (NPC) differ significantly in survival outcomes. The aim of this study is to build a clinically practical nomogram incorporating known tumor prognostic factors to predict survival for metastatic NPC patients in epidemic areas.A total of 860 patients with metachronous metastatic nasopharyngeal carcinoma were analyzed retrospectively. Variables assessed were age, gender, body mass index, Karnofsky Performance Status (KPS), Union for International Cancer Control (UICC) T and N stages, World Health Organization (WHO) histology type, serum lactate dehydrogenase (sLDH) level, serum Epstein-Barr virus (EBV) level, treatment modality, specific metastatic location (lung/liver/bone), number of metastatic location(s) (isolated vs multiple), and number of metastatic lesion(s) in metastatic location(s) (single vs multiple). The independent prognostic factors for overall survival (OS) by Cox-regression model were utilized to build the nomogram.Independent prognostic factors for OS of metastatic NPC patients included age, UICC N stage, KPS, sLDH, number of metastatic locations, number of metastatic lesions, involvement of liver metastasis, and involvement of bone metastasis. Calibration of the final model suggested a c-index of 0.68 (95% confidence interval [CI], 0.65-0.69). Based on the total point (TP) by nomogram, we further subdivided the study cohort into 4 groups. Group 1 (TP < 320, 208 patients) had the lowest risk of dying. Discrimination was visualized by the differences in survival between these 4 groups (group 2/group 1: hazard ratio [HR] = 1.61, 95%CI: 1.24-2.09; group 3/group 1: HR = 2.20, 95%CI: 1.69-2.86; and group 4/group 1: HR = 3.66, 95%CI: 2.82-4.75).The developed nomogram can help guide the prognostication of patients with metachronous metastatic NPC in epidemic areas. PMID:27399084

  6. Investigation of salivary function and oral microbiota of radiation caries-free people with nasopharyngeal carcinoma.

    PubMed

    Zhang, Jingyang; Liu, Hongling; Liang, Xue; Zhang, Min; Wang, Renke; Peng, Guang; Li, Jiyao

    2015-01-01

    Radiation caries have been reported to be correlated with radiotherapy-induced destruction of salivary function and changes in oral microbiota. There have been no published reports detailing patients who have remained radiation caries-free following radiotherapy for nasopharyngeal carcinoma. The aim of this study was to investigate the relationship between salivary function, oral microbiota and the absence of radiation caries. Twelve radiation caries-free patients and nine patients exhibiting radiation caries following irradiated nasopharyngeal carcinoma were selected. V40, the dose at which the volume of the contralateral parotid gland receives more than 40 Gy, was recorded. Stimulated saliva flow rate, pH values and buffering capacity were examined to assess salivary function. Stimulated saliva was used for molecular profiling by Denaturing Gradient Gel Electrophoresis. Mutans streptococci and Lactobacilli in saliva were also cultivated. There were no significant differences in V40 between radiation caries-free individuals and those with radiation caries. Compared with normal values, the radiation caries-free group had significantly decreased simulated saliva flow rate, while there were no significant differences in the saliva pH value and buffering capacity. Similar results were observed in the radiation caries group. There was no statistical difference in microbial diversity, composition and log CFU counts in cultivation from the radiation caries-free group and the radiation caries group. Eleven genera were detected in these two groups, among which Streptococcus spp. and Neisseria spp. had the highest distribution. Our results suggest that changes in salivary function and in salivary microbiota do not explain the absence of radiation caries in radiation caries-free individuals. PMID:25860481

  7. Investigation of Salivary Function and Oral Microbiota of Radiation Caries-Free People with Nasopharyngeal Carcinoma

    PubMed Central

    Zhang, Jingyang; Liu, Hongling; Liang, Xue; Zhang, Min; Wang, Renke; Peng, Guang; Li, Jiyao

    2015-01-01

    Radiation caries have been reported to be correlated with radiotherapy-induced destruction of salivary function and changes in oral microbiota. There have been no published reports detailing patients who have remained radiation caries-free following radiotherapy for nasopharyngeal carcinoma. The aim of this study was to investigate the relationship between salivary function, oral microbiota and the absence of radiation caries. Twelve radiation caries-free patients and nine patients exhibiting radiation caries following irradiated nasopharyngeal carcinoma were selected. V40, the dose at which the volume of the contralateral parotid gland receives more than 40 Gy, was recorded. Stimulated saliva flow rate, pH values and buffering capacity were examined to assess salivary function. Stimulated saliva was used for molecular profiling by Denaturing Gradient Gel Electrophoresis. Mutans streptococci and Lactobacilli in saliva were also cultivated. There were no significant differences in V40 between radiation caries-free individuals and those with radiation caries. Compared with normal values, the radiation caries-free group had significantly decreased simulated saliva flow rate, while there were no significant differences in the saliva pH value and buffering capacity. Similar results were observed in the radiation caries group. There was no statistical difference in microbial diversity, composition and log CFU counts in cultivation from the radiation caries-free group and the radiation caries group. Eleven genera were detected in these two groups, among which Streptococcus spp. and Neisseria spp. had the highest distribution. Our results suggest that changes in salivary function and in salivary microbiota do not explain the absence of radiation caries in radiation caries-free individuals. PMID:25860481

  8. Sensorineural Hearing Loss After Treatment of Nasopharyngeal Carcinoma: A Longitudinal Analysis

    SciTech Connect

    Chan, S.H. Ng, W.T.; Kam, K.L.; Lee, Michael C.H.; Choi, C.W.; Yau, T.K.; Lee, Anne W.M.; Chow, S.K.

    2009-04-01

    Purpose: To analyze the effects of radiotherapy (RT) and chemotherapy in relation to sensorineural hearing loss (SNHL) after contemporary treatment of nasopharyngeal carcinoma. Methods and Materials: A total of 87 nasopharyngeal carcinoma patients were treated with RT or chemoradiotherapy using either three-dimensional conformal RT or intensity-modulated RT between 2004 and 2005. Tympanometry and pure-tone audiogram assessments were performed before treatment and then serially at 6-month intervals. The dose-volume data of the cochlea were analyzed. The effects of cisplatin administered in concurrent and nonconcurrent phases was explored. Results: Of the 170 eligible ears, RT (n = 30) and chemoradiotherapy (n = 140) resulted in 40% (n = 12) and 56.4% (n = 79) persistent SNHL ({>=}15 dB loss), respectively, after a median follow-up of 2 years. SNHL at a high frequency was more frequent statistically in the chemoradiotherapy group than in the RT-alone group (55% vs. 33.3%, p < 0.01), but not at a low frequency (7.9% vs. 16.7%, p = 0.14). Within the chemoradiotherapy group, the mean cochlea dose and concurrent cisplatin dose were important determinants of high-frequency SNHL, with an odds ratio of 1.07/Gy increase (p = 0.01) and an odds ratio of 1.008/mg/m{sup 2} increase (p < 0.01), respectively. Age, gender, and nonconcurrent cisplatin dose were not statistically significant factors. A mean radiation dose to the cochlea of <47 Gy would result in <15% of patients developing severe ({>=}30 dB) high-frequency SNHL. Conclusion: The results of our study have shown that high-frequency SNHL is significantly related to the mean cochlea dose and the concurrent cisplatin dose. A mean dose constraint of 47 Gy to the cochlea is recommended to minimize SNHL after chemoradiotherapy.

  9. Helical Tomotherapy of Nasopharyngeal Carcinoma-Any Advantages Over Conventional Intensity-Modulated Radiotherapy?

    SciTech Connect

    Wu, W.C. Vincent Mui, Wing-lun A.; Fung, Wing-ki W.

    2010-07-01

    Helical tomotherapy uses different planning algorithm and dose delivery method from the linear accelerator (linac)-based intensity-modulated radiotherapy (IMRT). This study compared the dosimetric outcomes between the tomotherapy plans and conventional linac-based IMRT plans in the treatment of nasopharyngeal carcinoma (NPC). Fifteen stage II-III cancer (American Joint Committee on Cancer) NPC patients treated by tomotherapy were conveniently recruited. Apart from the tomotherapy plans, a 7-field 6-MV photon conventional IMRT plan was computed for each patient with the same CT dataset and reference from the dose constraints and target dose prescriptions of the tomotherapy plans using the XiO treatment planning system. Average values of the dose parameters including the conformity index (CI), homogeneity index (HI), maximum and minimum doses of the target volumes, and the maximum and mean doses of the organs at risk (OAR) were compared between the two treatment methods. Better dose coverage of the planning target volume (PTV) was demonstrated in the tomotherapy plans, in which the differences in the maximum and mean doses reached statistical significance (p < 0.05). Besides, the CI of the tomotherapy plans were significantly higher than the conventional linac-based plans for the nasopharynx PTV (NP-PTV) and neck lymphatics PTV (LN-PTV) (p = 0.017 and 0.010, respectively). The HI was significantly smaller in both NP-PTV and LN-PTV (p = 0.024 and < 0.001, respectively). Among the OAR, the brain stem and spinal cord doses in the tomotherapy plans were lower than that of the conventional IMRT plans. However, the doses to the other OAR did not show significant dosimetric differences. In the treatment of nasopharyngeal carcinoma, tomotherapy plans were superior to the 7-field conventional IMRT plans in PTV dose conformity and homogeneity and the sparing of the brain stem and spinal cord. However, no significant advantages were observed for the rest of the OAR.

  10. A Survey of Methylated Candidate Tumor Suppressor Genes in Nasopharyngeal Carcinoma

    PubMed Central

    Loyo, Myriam; Brait, Mariana; Kim, Myoung S; Ostrow, Kimberly L.; Jie, Chunfa C; Chuang, Alice Y; Califano, Joseph A.; Liégeois, Nanette J; Begum, Shahnaz; Westra, William H; Hoque, Mohammad O; Tao, Qian; Sidransky, David

    2010-01-01

    Nasopharyngeal carcinoma (NPC) is a rare malignancy with unique genetic, viral and environmental characteristic that distinguishes it from other head and neck carcinomas. The clinical management of NPC remains challenging largely due to the lack of early detection strategies for this tumor. In the present study we have sought to identify novel genes involved in the pathogenesis of NPC that might provide insight into this tumor's biology and could potentially be used as biomarkers. To identify these genes, we studied the epigenetics of NPC by characterizing a panel of methylation markers. Eighteen genes were evaluated by quantitative methylation-specific PCR in cell lines as well as in tissue samples including 50 NPC tumors and 28 benign nasopharyngeal biopsies. Significance was evaluated using Fisher's exact test and quantitative values were optimized using cut off values derived from receiver-operator characteristic curves. The methylation status of AIM1, APC, CALCA, DCC, DLEC, DLC1, ESR, FHIT, KIF1A, and PGP9.5 was significantly associated with NPC compared to controls. The sensitivity of the individual genes ranged from 26 to 66% and the specificity was above 92% for all genes except FHIT. The combination of PGP9.5, KIF1A, and DLEC had a sensitivity of 84% and a specificity of 92%. Ectopic expression of DCC and DLC1 lead to decrease in colony formation and invasion properties. Our results indicate that methylation of novel biomarkers in NPC could be used to enhance early detection approaches. Additionally, our functional studies reveal previously unknown tumor suppressor roles in NPC. PMID:20473931

  11. The incidence of Epstein-Barr virus in nasopharyngeal carcinoma of Jordanian patients.

    PubMed

    Matalka, Ismail; Al Hamad, Mohammad; Al-Hussaini, Maysa; Alzoubi, Firas Q

    2012-01-01

    Aim of this study was to investigate the incidence of Epstein-Barr virus (EBV) in patients diagnosed with undifferentiated nasopharyngeal carcinoma (UNPC) from the Northern Province of Jordan. All cases diagnosed with UNPC at King Abdullah University Hospital, Irbid, Jordan, between the years 1991 and 2009 inclusive were examined. Clinical data including age, gender, mode of presentation, site of biopsy were retrieved from pathology reports. In situ hybridization for (EBV)--EBERs was performed on cases with available paraffin blocks. Correlation between the different clinical variables and results of in situ hybridization was performed. There were 49 cases diagnosed with UNPC, only 39 specimens were available and studied. The median age of presentation was 41 years (range 9-70 years). Bimodal age distribution was noted, the first peak between 15 and 19 years of age and second between 60 and 64 years of age. Males were slightly more commonly affected than females. Cervical lymph node enlargement was the most common mode of presentation, followed by nasal obstruction. Biopsies were obtained primarily from the posterior nasal space, followed by cervical lymph node. Positive staining for EBERs by in situ hybridization was seen in 92.3% of the cases examined. There was no difference in detection rate between males and females or adults and pediatrics. All cases obtained from posterior nasal space were positive. The three negative cases were from biopsies obtained from cervical lymph nodes, which was statistically significant (P value <0.05). Nasopharyngeal carcinoma in Jordan is seen in both children and adults. It is associated with EBV infection in most, but not all cases. Posterior nasal space shows a more consistent staining for EBERs than cervical lymph nodes. The presence of other association with UNPC including cigarette smoking could possibly explain the cases with negative association. PMID:21409390

  12. Symptomatic hypothalamic-pituitary dysfunction in nasopharyngeal carcinoma patients following radiation therapy: a retrospective study

    SciTech Connect

    Lam, K.S.; Ho, J.H.; Lee, A.W.; Tse, V.K.; Chan, P.K.; Wang, C.; Ma, J.T.; Yeung, R.T.

    1987-09-01

    Endocrine assessment was performed in 32 relapse-free southern Chinese patients 5-17 years following radiation therapy (RT) alone for early nasopharyngeal carcinoma (NPC). Initial screening was done using questionnaires emphasizing impaired sexual function and menstrual disturbance plus measurement of serum levels of thyroxine, free thyroxine index, thyrotropic hormone, prolactin, and additionally testosterone for males only. Those showing abnormalities were subjected to detailed pituitary function tests. Hypothalamic-pituitary dysfunction was found in 7 female patients and only 1 male patient. A delayed TSH response to thyrotropin releasing hormone suggesting a hypothalamic disorder was seen in 6 of the affected female patients, and hyperprolactinaemia in also 6. None of the patients had evidence of diabetes insipidus. Hypopituitarism became symptomatic 2-5 years after RT with a mean latent interval of 3.8 years. A practical protocol for regular endocrine assessment for NPC patients after RT has been proposed. Multiple linear regression analysis of the radiotherapeutic data from the 11 female patients indicates that the likelihood of late occurrence of symptomatic hypothalamic-pituitary dysfunction following RT is dependent on the TDF of the target dose to the nasopharyngeal region and the height of the upper margin of the opposed lateral facial fields above the diaphragma sellae (coefficient of multiple correlation = 0.9025). Except when the sphenoid sinus or the middle cranial fossa is involved, it is advisable to set the height of the upper margin of the lateral facial field at a level no higher than the diaphragma sellae. The hypothalamus and possibly the pituitary stalk as well may sustain permanent damage by doses of radiation within the conventional radiotherapeutic range for carcinomas.

  13. Adenovirus-mediated delivery of interferon-γ gene inhibits the growth of nasopharyngeal carcinoma

    PubMed Central

    2012-01-01

    Background Interferon-γ (IFN-γ) is regarded as a potent antitumor agent, but its clinical application is limited by its short half-life and significant side effects. In this paper, we tried to develop IFN-γ gene therapy by a replication defective adenovirus encoding the human IFN-γ (Ad-IFNγ), and evaluate the antitumoral effects of Ad-IFNγ on nasopharyngeal carcinoma (NPC) cell lines in vitro and in xenografts model. Methods The mRNA levels of human IFN-γ in Ad-IFNγ-infected NPC cells were detected by reverse transcription-polymerase chain reaction (RT-PCR), and IFN-γ protein concentrations were measured by enzyme-linked immunosorbent assay (ELISA) in the culture supernatants of NPC cells and tumor tissues and bloods of nude mice treated with Ad-IFNγ. The effects of Ad-IFNγ on NPC cell proliferation was determined using MTT assay, cell cycle distribution was determined by flow cytometry analysis for DNA content, and cells apoptosis were analyzed by Annexin V-FITC/7-AAD binding assay and hoechst 33342/PI double staining. The anti-tumor effects and toxicity of Ad-IFNγ were evaluated in BALB/c nude mice carrying NPC xenografts. Results The results demonstrated that Ad-IFNγ efficiently expressed human IFN-γ protein in NPC cell lines in vitro and in vivo. Ad-IFNγ infection resulted in antiproliferative effects on NPC cells by inducing G1 phase arrest and cell apoptosis. Intratumoral administration of Ad-IFNγ significantly inhibited the growth of CNE-2 and C666-1 cell xenografts in nude mice, while no significant toxicity was observed. Conclusions These findings indicate IFN-γ gene therapy mediated by replication defective adenoviral vector is likely a promising approach in the treatment of nasopharyngeal carcinoma. PMID:23272637

  14. Thyroid adenoma and nasopharyngeal carcinoma with metastasis to cervical lymph nodes is misdiagnosed and treated for thyroid carcinoma: A case report

    PubMed Central

    ZHANG, MIAO; WANG, HENG; PAN, XUEFENG; WU, WENBIN; ZHANG, HUI

    2016-01-01

    Lymph node metastasis of nasopharyngeal carcinoma follows an orderly pattern, and diagnosis of nasopharyngeal carcinoma is often made by lymph node biopsy. In the present study, following neck palpation, ultrasonography and cervical computer tomography, a 52-year-old female patient with thyroid adenoma and enlarged cervical lymph nodes was misdiagnosed as thyroid carcinoma without undergoing preoperative biopsy, followed by unnecessary total thyroidectomy. Systematic CT scan and nasal endoscopic biopsy confirmed the correct diagnosis of primary NPC concurrent with thyroid adenoma. The patient received palliative radiotherapy and L-thyroxine substitution therapy, and was followed up closely via internet-based approaches with life-style intervention, medication consultation and psychological support for improvement of life quality after radiotherapy. In conclusion, primary malignancies with thyroid metastasis must be considered in the differential diagnosis of thyroid tumors with enlarged cervical lymph nodes. PMID:27347179

  15. Decreased EBNA-1-specific CD8+ T cells in patients with Epstein–Barr virus-associated nasopharyngeal carcinoma

    PubMed Central

    Fogg, Mark H.; Wirth, Lori J.; Posner, Marshall; Wang, Fred

    2009-01-01

    The Epstein–Barr virus (EBV) nuclear antigen-1 (EBNA-1) is potentially a universal target for immune recognition of EBV-infected normal or malignant cells. EBNA-1-specific CD8+ T-cell responses have been assessed against a few epitopes presented on a limited number of HLA class I alleles. We now assess CD8+ T-cell responses to a complete panel of EBNA-1 peptides in an HLA-characterized population. We detected EBNA-1-specific CD8+ T cells in 10 of 14 healthy donors by analysis of peripheral blood mononuclear cells and EBV-specific T-cell lines. The frequent detection of CD8+ T-cell responses was confirmed by mapping EBNA-1 epitopes and demonstrating HLA class I presentation to CD8+ T cells in 6 of 6 donors, including 2 new EBNA-1 epitopes presented by HLA A0206 and A6802. Importantly, EBNA-1-specific CD8+ T cells were significantly less frequent in EBV-specific T-cell lines from patients with EBV-associated nasopharyngeal carcinoma (3 out of 22, P = 0.0003), whereas the frequency of LMP2-specific responses (14 out of 22) was not significantly different from healthy donors (11 out of 14). EBNA-1-specific CD8+ T-cell responses were rescued in approximately half of nasopharyngeal carcinoma patients by peptide and cytokine stimulation of peripheral blood mononuclear cells, suggesting these EBNA-1-specific CD8+ T cells were functionally defective in their response to EBV-infected cells. These results indicate that humans normally mount a significant EBNA-1-specific CD8+ T-cell response to EBV infection, but the immune response to this tumor antigen has been significantly altered in nasopharyngeal carcinoma patients. Overcoming this defect in EBV-specific immunity may prevent or enhance treatment of EBV-associated nasopharyngeal carcinoma. PMID:19211798

  16. Correlation Analysis of Nasopharyngeal Carcinoma TNM Staging with Serum EA IgA and VCA IgA in EBV and VEGF-C and -D

    PubMed Central

    Sun, Ruimei; Wang, Xiaoli; Li, Xiaojiang

    2015-01-01

    Background Nasopharyngeal carcinoma often occurs in humans in the nasopharyngeal epithelium area. Ebstein-Barr (EB) virus plays a key role in the process of nasopharyngeal carcinoma lesions. Early antigen antibody (EA-IgA) and viral capsid antigen IgA (VCA-IgA) of EB virus detection in serum can effectively monitor the process of nasopharyngeal carcinoma lesions. Serum vascular endothelial growth factor (VEGF) -C and VEGF-D expression detection can reflect the distant metastases ability of human tumor cells. Material/Methods 153 cases of nasopharyngeal carcinoma patients in our hospital were enrolled, while 148 cases of healthy adults were selected as control. ELISA was used to detect serum EA-IgA, VCA-IgA, VEGF-C and -D expression levels. Spearman rank correlation analysis was applied to test the correlation of nasopharyngeal carcinoma TNM clinical stage and different indexes. Results Serum EA-IgA, VCA-IgA, VEGF-C and -D expression in nasopharyngeal carcinoma patients was 43.74±2.6 U·mL−1, 62.5±2.7 U·mL−1, 473.25±3.4 pg·mL−1, and 498.36±2.3 pg·mL−1, respectively, which was significantly higher than in the control group as 18.65±3.7 U·mL−1, 23.74±1.5 U·mL−1, 225.42±2.3 pg·mL−1, and 257.24±3.5 pg·mL−1 (P<0.05). Nasopharyngeal carcinoma TNM clinical staging was obviously correlated with serum EA-IgA, VCA-IgA, and VEGF-C (P<0.05), but not VEGF-D (P>0.05). Conclusions Nasopharyngeal carcinoma patient serum EA-IgA and VCA-IgA expression levels were significantly correlated with TNM staging. The high levels of these 3 indicators suggest advanced nasopharyngeal carcinoma TNM staging and serious lesions. PMID:26191775

  17. Can Intensity-Modulated Radiotherapy Preserve Oral Health-Related Quality of Life of Nasopharyngeal Carcinoma Patients?

    SciTech Connect

    Pow, Edmond H.N.; Kwong, Dora L.W.; Sham, Jonathan S.T.; Lee, Victor H.F.; Ng, Sherry C.Y.

    2012-06-01

    Purpose: To investigate the changes in salivary function and oral health-related quality of life for patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy (IMRT). Methods and Materials: A total of 57 patients with early-stage nasopharyngeal carcinoma received IMRT. The parotid and whole saliva flow was measured, and the Medical Outcomes Study 36-item short form, European Organization for Research and Treatment of Cancer Quality of Life questionnaire-C30, European Organization for Research and Treatment of Cancer Quality of Life questionnaire 35-item head-and-neck module, and Oral Health Impact Profile questionnaires were completed at baseline and 2, 6, 12, 18, and 24 months after IMRT. Results: Parotid saliva flow recovered fully after 1 year and maintained. Whole saliva flow recovered partially to 40% of baseline. A general trend of deterioration in most quality of life scales was observed after IMRT, followed by gradual recovery. Persistent oral-related symptoms were found 2 years after treatment. Conclusion: IMRT for early-stage nasopharyngeal carcinoma could only partially preserve the whole salivary function and oral health-related quality of life.

  18. Embelin prevents LMP1-induced TRAIL resistance via inhibition of XIAP in nasopharyngeal carcinoma cells

    PubMed Central

    YANG, SHU; LI, SHI-SHENG; YANG, XIN-MING; YIN, DAN-HUI; WANG, LIN

    2016-01-01

    The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in the majority of tumor cells, whilst sparing normal cells. However, the potential use of TRAIL in the treatment of cancer is limited by the inevitable emergence of drug resistance. The present study reports the upregulation of latent membrane protein 1 (LMP1)-induced TRAIL resistance via the enhanced expression of X-linked inhibitor of apoptosis protein (XIAP) in nasopharyngeal carcinoma (NPC) cells. LMP1-positive NPC cells were indicated to be more sensitive to TRAIL compared with LMP1-negative NPC cells in three NPC cell lines. CNE-1 is a LMP1-negative NPC cell line that was transfected with pGL6-LMP1; following which, sensitivity to TRAIL decreased. LMP1-induced TRAIL resistance was associated with the decreased cleavage of caspase-8,-3 and −9, BH3 interacting domain death agonist (Bid) and mitochondrial depolarization, without any effects on the expression of the death receptors, B-cell lymphoma (Bcl)-2 and Bcl-extra long. Knockdown of XIAP with small interfering RNA increased caspase-3 and −9 and Bid cleavage, and prevented LMP1-induced TRAIL resistance. Furthermore, embelin, the inhibitor of XIAP, prevented LMP1-induced TRAIL resistance in the Epstein-Barr virus (EBV)-positive CNE-1-LMP1 and C666-1 NPC cell lines. However, embelin did not enhance TRAIL-induced apoptosis in NP-69, which was used as a benign nasopharyngeal epithelial cell line. These data show that LMP1 inhibits TRAIL-mediated apoptosis by upregulation of XIAP. Embelin may be used in an efficacious and safe manner to prevent LMP1-induced TRAIL resistance. The present study may have implications for the development and validation of novel strategies to prevent TRAIL resistance in EBV-positive NPC. PMID:27313761

  19. A Case Report on the Effect of Fan Beam Thickness in Helical Tomotherapy of Nasopharyngeal Carcinoma

    SciTech Connect

    Wu, W.C. Vincent; Mui, Wing Lun A.

    2011-04-01

    The fan beam thickness (FBT) in helical tomotherapy is defined by a pair of collimators parallel to the rotational orbit of the radiation beam and is fixed for a specific patient treatment. The aim of this case study is to evaluate the dosimetric influence of changing the FBT in the treatment of a nasopharyngeal carcinoma (NPC) patient. The subject was a T2N1M0 stage NPC patient. The planning target volumes (PTVs) of the primary nasopharyngeal tumor and the left and right cervical lymphatics were delineated along with the organs at risk (OARs) in the corresponding computed tomography slices. Three treatment plans with FBT of 1.0 cm, 2.5 cm, and 5.0 cm (FBT-10, FBT-25, and FBT-50) were generated separately based on similar dose constraints and planning parameters. The dosimetric results of the PTV and OARs were collected and compared among the 3 treatment plans. The differences in the dose parameters of the PTVs were small among the 3 plans. The FBT-10 plan demonstrated the most homogeneous PTV doses with the smallest homogeneity indices (HIs). The FBT-50 plan delivered the highest dose to the OARs and the FBT-10 plan delivered the lowest. The differences between the 2 plans were more significant in the spinal cord, optic chiasm, optic nerves, and lens. This case study demonstrated that the variation of FBT in tomotherapy affected the quality of the treatment plan mainly in the OAR doses, but not so much in the PTV. Increasing the FBT reduced the effectiveness in the sparing of OARs.

  20. Upregulation of KLHDC4 Predicts a Poor Prognosis in Human Nasopharyngeal Carcinoma.

    PubMed

    Lian, Yi-Fan; Yuan, Jing; Cui, Qian; Feng, Qi-Sheng; Xu, Miao; Bei, Jin-Xin; Zeng, Yi-Xin; Feng, Lin

    2016-01-01

    Kelch proteins are implicated in the pathogenesis of many human diseases, including cancer. Nasopharyngeal carcinoma (NPC) is a rare malignancy in most countries, but prevalent in southern China and certain areas of Southeast Asia. In this study, we identified Kelch Domain Containing 4 (KLHDC4), an orphan member of the kelch repeat superfamily, as a prognosis marker for NPC. We examined the expression of KLHDC4 in 168 NPC cases by immunohistochemical staining and found a substantially higher level of KLHDC4 in NPC biopsies compared to adjacent normal nasopharyngeal mucosa. KLHDC4 expression was significantly related to the T classification (P <0.05), N classification (P <0.05) and total staging (P <0.01) in NPC, and patients with higher KLHDC4 expression had poorer overall (P <0.01) and metastasis-free survival (P <0.05) rates. Knockout (KO) of KLHDC4 via CRISPR/Cas9-mediated gene editing in NPC cell line dramatically inhibited cell proliferation, colony formation in soft agar and tumor formation in nude mice. In addition, cell migration and invasion were also impaired by KLHDC4 depletion as revealed by wound healing and Transwell assay. Mechanically, loss of KLHDC4 markedly induced spontaneous apoptosis in NPC cells, as evidenced by increased levels of cleaved caspase-3 and cleaved PARP. Consistently, KLHDC4 knockout cell-derived xenografts also showed elevated cleaved caspase-3 and PARP but reduced Ki-67 staining. In conclusion, our results suggest that KLHDC4 promotes NPC oncogenesis by suppressing cellular apoptosis. Thus, KLHDC4 may serve as a prognosis biomarker and a potential therapeutic target for NPC. PMID:27030985

  1. Integrated miRNA-mRNA analysis of Epstein-Barr virus-positive nasopharyngeal carcinoma.

    PubMed

    Zhu, L H; Miao, X T; Wang, N Y

    2015-01-01

    This study aims to identify the crucial miRNAs in Epstein-Barr virus-positive nasopharyngeal carcinoma (NPC) and their target genes. Gene expression profile data (GSE12452) that included 31 NPC and 10 normal nasopharyngeal tissue specimens were downloaded. Differentially expressed genes (DEGs) were identified using significance analysis of microarrays. The underlying function of DEGs was predicted via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The miRNA sequencing dataset GSE14738 was also downloaded, and expression levels of miRNA were calculated by the number of reads mapped to each miRNA. The selected miRNAs were integrated into the miRecords database to obtain their target genes. Target genes associated with DEGs were used to construct the interaction network via Cytoscape. A total of 1437 DEGs between NPC and control were identified, most of which were enriched in cell cycle and extracellular matrix-receptor interaction signaling pathways. Furthermore, 112 miRNAs were considered upregulated in NPC samples. A total of 2228 relationships between 39 miRNAs and 1247 target genes were obtained, of which 182 relationships between 32 miRNAs and 97 target genes were chosen to construct an interaction network. The interactions between DEGs and the let-7 or miR-29 families appeared strongest in this network, where CDC25A, COL3A1, and COL1A1 were regulated by several let-7 family members, while COL4A1 and COL5A2 were regulated by several miR-29 family members. The let-7 and miR-29 families may be related to the development of NPC by regulating the genes involved in cell cycle and ECM-receptor interaction. PMID:26125802

  2. Upregulation of KLHDC4 Predicts a Poor Prognosis in Human Nasopharyngeal Carcinoma

    PubMed Central

    Feng, Qi-Sheng; Xu, Miao; Bei, Jin-Xin; Zeng, Yi-Xin; Feng, Lin

    2016-01-01

    Kelch proteins are implicated in the pathogenesis of many human diseases, including cancer. Nasopharyngeal carcinoma (NPC) is a rare malignancy in most countries, but prevalent in southern China and certain areas of Southeast Asia. In this study, we identified Kelch Domain Containing 4 (KLHDC4), an orphan member of the kelch repeat superfamily, as a prognosis marker for NPC. We examined the expression of KLHDC4 in 168 NPC cases by immunohistochemical staining and found a substantially higher level of KLHDC4 in NPC biopsies compared to adjacent normal nasopharyngeal mucosa. KLHDC4 expression was significantly related to the T classification (P <0.05), N classification (P <0.05) and total staging (P <0.01) in NPC, and patients with higher KLHDC4 expression had poorer overall (P <0.01) and metastasis-free survival (P <0.05) rates. Knockout (KO) of KLHDC4 via CRISPR/Cas9-mediated gene editing in NPC cell line dramatically inhibited cell proliferation, colony formation in soft agar and tumor formation in nude mice. In addition, cell migration and invasion were also impaired by KLHDC4 depletion as revealed by wound healing and Transwell assay. Mechanically, loss of KLHDC4 markedly induced spontaneous apoptosis in NPC cells, as evidenced by increased levels of cleaved caspase-3 and cleaved PARP. Consistently, KLHDC4 knockout cell-derived xenografts also showed elevated cleaved caspase-3 and PARP but reduced Ki-67 staining. In conclusion, our results suggest that KLHDC4 promotes NPC oncogenesis by suppressing cellular apoptosis. Thus, KLHDC4 may serve as a prognosis biomarker and a potential therapeutic target for NPC. PMID:27030985

  3. Whole-exome sequencing identifies MST1R as a genetic susceptibility gene in nasopharyngeal carcinoma.

    PubMed

    Dai, Wei; Zheng, Hong; Cheung, Arthur Kwok Leung; Tang, Clara Sze-Man; Ko, Josephine Mun Yee; Wong, Bonnie Wing Yan; Leong, Merrin Man Long; Sham, Pak Chung; Cheung, Florence; Kwong, Dora Lai-Wan; Ngan, Roger Kai Cheong; Ng, Wai Tong; Yau, Chun Chung; Pan, Jianji; Peng, Xun; Tung, Stewart; Zhang, Zengfeng; Ji, Mingfang; Chiang, Alan Kwok-Shing; Lee, Anne Wing-Mui; Lee, Victor Ho-Fun; Lam, Ka-On; Au, Kwok Hung; Cheng, Hoi Ching; Yiu, Harry Ho-Yin; Lung, Maria Li

    2016-03-22

    Multiple factors, including host genetics, environmental factors, and Epstein-Barr virus (EBV) infection, contribute to nasopharyngeal carcinoma (NPC) development. To identify genetic susceptibility genes for NPC, a whole-exome sequencing (WES) study was performed in 161 NPC cases and 895 controls of Southern Chinese descent. The gene-based burden test discovered an association between macrophage-stimulating 1 receptor (MST1R) and NPC. We identified 13 independent cases carrying theMST1Rpathogenic heterozygous germ-line variants, and 53.8% of these cases were diagnosed with NPC aged at or even younger than 20 y, indicating thatMST1Rgerm-line variants are relevant to disease early-age onset (EAO) (age of ≤20 y). In total, fiveMST1Rmissense variants were found in EAO cases but were rare in controls (EAO vs. control, 17.9% vs. 1.2%,P= 7.94 × 10(-12)). The validation study, including 2,160 cases and 2,433 controls, showed that theMST1Rvariant c.G917A:p.R306H is highly associated with NPC (odds ratio of 9.0).MST1Ris predominantly expressed in the tissue-resident macrophages and is critical for innate immunity that protects organs from tissue damage and inflammation. Importantly, MST1R expression is detected in the ciliated epithelial cells in normal nasopharyngeal mucosa and plays a role in the cilia motility important for host defense. Although no somatic mutation ofMST1Rwas identified in the sporadic NPC tumors, copy number alterations and promoter hypermethylation atMST1Rwere often observed. Our findings provide new insights into the pathogenesis of NPC by highlighting the involvement of the MST1R-mediated signaling pathways. PMID:26951679

  4. Overexpression of the PSAT1 Gene in Nasopharyngeal Carcinoma Is an Indicator of Poor Prognosis

    PubMed Central

    Liao, Kuang-Ming; Chao, Tung-Bo; Tian, Yu-Feng; Lin, Ching-Yih; Lee, Sung-Wei; Chuang, Hua-Ying; Chan, Ti-Chun; Chen, Tzu-Ju; Hsing, Chung-Hsi; Sheu, Ming-Jen; Li, Chien-Feng

    2016-01-01

    Purpose: Nasopharyngeal carcinoma (NPC) is a common cancer in southern China and Southeast Asia, but risk stratification and treatment outcome in NPC patients remain suboptimal. Our study identified and validated metabolic drivers that are relevant to the pathogenesis of NPC using a published transcriptome. Phosphoserine aminotransferase 1 (PSAT1) is an enzyme that is involved in serine biosynthesis, and its overexpression is associated with colon cancer, non-small cell lung cancer and breast cancer. However, its expression has not been systemically evaluated in patients with NPC. Materials and Methods: We evaluated two public transcriptomes of NPC tissues and benign nasopharyngeal mucosal epithelial tissues that deposited in the NIH Gene Expression Omnibus database under accession number GSE34574 and GSE12452. We also performed immunohistochemical staining and assessment of PSAT1 in a total of 124 NPC patients received radiotherapy and were regularly followed-up until death or loss. The endpoints analyzed were local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS). Results: We retrospectively evaluated 124 patients with NPC and found that high PSAT1 expression was associated with poor prognosis of NPC and indicator of advanced tumor stage. High PSAT1 expression also correlated with an aggressive clinical course, with significantly shorter DSS (HR= 2.856, 95% CI 1.599 to 5.101), DMFS (HR= 3.305, 95% CI 1.720 to 6.347), LRFS (HR= 2.834, 95% CI 1.376 to 5.835), and OS HR= 2.935, 95% CI 1.646-5.234) in multivariate analyses. Conclusions: Our study showed that PSAT1 is a potential prognostic biomarker and higher expression of PSAT1 is associated with a poor prognosis in NPC. PMID:27326252

  5. Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins.

    PubMed

    Chan, Yuk-Kit; Zhang, Huoming; Liu, Pei; Tsao, Sai-Wah; Lung, Maria Li; Mak, Nai-Ki; Ngok-Shun Wong, Ricky; Ying-Kit Yue, Patrick

    2015-10-15

    Exosomes, a group of secreted extracellular nanovesicles containing genetic materials and signaling molecules, play a critical role in intercellular communication. During tumorigenesis, exosomes have been demonstrated to promote tumor angiogenesis and metastasis while their biological functions in nasopharyngeal carcinoma (NPC) are poorly understood. In this study, we focused on the role of NPC-derived exosomes on angiogenesis. Exosomes derived from the NPC C666-1 cells and immortalized nasopharyngeal epithelial cells (NP69 and NP460) were isolated using ultracentrifugation. The molecular profile and biophysical characteristics of exosomes were verified by Western blotting, sucrose density gradient and electron microscopy. We showed that the C666-1 exosomes (10 and 20 μg/ml) could significantly increase the tubulogenesis, migration and invasion of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Subsequently, an iTRAQ-based quantitative proteomics was used to identify the differentially expressed proteins in C666-1 exosomes. Among the 640 identified proteins, 51 and 89 proteins were considered as up- and down-regulated (≥ 1.5-fold variations) in C666-1 exosomes compared to the normal counterparts, respectively. As expected, pro-angiogenic proteins including intercellular adhesion molecule-1 (ICAM-1) and CD44 variant isoform 5 (CD44v5) are among the up-regulated proteins, whereas angio-suppressive protein, thrombospondin-1 (TSP-1) was down-regulated in C666-1 exosomes. Further confocal microscopic study and Western blotting clearly demonstrated that the alteration of ICAM-1 and TSP-1 expressions in recipient HUVECs are due to internalization of exosomes. Taken together, these data strongly indicated the critical roles of identified angiogenic proteins in the involvement of exosomes-induced angiogenesis, which could potentially be developed as therapeutic targets in future. PMID:25857718

  6. Far upstream element-binding protein 1 is a prognostic biomarker and promotes nasopharyngeal carcinoma progression

    PubMed Central

    Liu, Z-H; Hu, J-L; Liang, J-Z; Zhou, A-J; Li, M-Z; Yan, S-M; Zhang, X; Gao, S; Chen, L; Zhong, Q; Zeng, M-S

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor with tremendous invasion and metastasis capacities, and it has a high incidence in southeast Asia and southern China. Previous studies identified that far upstream element-binding protein 1 (FBP1), a transcriptional regulator of c-Myc that is one of the most frequently aberrantly expressed oncogenes in various human cancers, including NPC, is an important biomarker for many cancers. Our study aimed to investigate the expression and function of FBP1 in human NPC. Quantitative real-time RT-PCR (qRT-PCR), western blot and immunohistochemical staining (IHC) were performed in NPC cells and biopsies. Furthermore, the effect of FBP1 knockdown on cell proliferation, colony formation, side population tests and tumorigenesis in nude mice were measured by MTT, clonogenicity analysis, flow cytometry and a xenograft model, respectively. The results showed that the mRNA and protein levels of FBP1, which are positively correlated with c-Myc expression, were substantially higher in NPC than that in nasopharyngeal epithelial cells. IHC revealed that the patients with high FBP1 expression had a significantly poorer prognosis compared with the patients with low expression (P=0.020). In univariate analysis, high FBP1 and c-Myc expression predicted poorer overall survival (OS) and poorer progression-free survival. Multivariate analysis indicated that high FBP1 and c-Myc expression were independent prognostic markers. Knockdown of FBP1 reduced cell proliferation, clonogenicity and the ratio of side populations, as well as tumorigenesis in nude mice. These data indicate that FBP1 expression, which is closely correlated with c-Myc expression, is an independent prognostic factor and promotes NPC progression. Our results suggest that FBP1 can not only serve as a useful prognostic biomarker for NPC but also as a potential therapeutic target for NPC patients. PMID:26469968

  7. Aberrant SATB1 expression is associated with Epstein-Barr virus infection, metastasis and survival in human nasopharyngeal cells and endemic nasopharyngeal carcinoma.

    PubMed

    Deng, Yan-Fei; Zhou, Dong-Ni; Pan, Zhi-Yong; Yin, Ping

    2014-01-01

    Special AT-rich sequence-binding protein 1 (SATB1) has been identified as a key factor in the progression of some cancers, functioning as a global genome organizer and chromatin regulator. We examined the levels of SATB1 mRNA expression in NPC cell lines 5-8F (high metastasis) and 6-10B (low metastasis) and immortalized human nasopharyngeal epithelial cells NP69-SV40T by quantitative real-time PCR. We also examined the protein expression levels of SATB1 in 72 cases of nasopharyngeal carcinoma (NPC) tissues and 30 cases of normal nasopharyngeal (NNP) tissues by immunohistochemistry, and then assessed the correlations between SATB1 expression and clinicopathological factors. The expression level of SATB1 mRNA in 5-8F was much higher than those in 6-10B and NP69-SV40T (P<0.05). The expression level of SATB1 mRNA in 6-10B was higher than in NP69-SV40T, but the difference was not statistically significant (P>0.05). The positive expression rates of SATB1 protein in NPC (38/72, 52.8%) were significantly higher than in NNP (4/30, 13.3%) (P<0.05). SATB1 protein levels in NPC were not associated with gender, age, and T stage (P>0.05), but positively correlated with the titers of EBVCA-IgA, metastasis (N and M stage), recurrence, and survival (P<0.05). Multivariate analysis showed that the overexpression of SATB1 protein is an independent prognostic factor for NPC. The expression levels of SATB1 were obviously upregulated in primary NPC tissues and human NPC cell lines. Therefore, SATB1 may be a valuable predictor in assessing the metastasis, recurrence, and prognosis of NPC. PMID:24966956

  8. Epstein-Barr virus mir-bart1-5p detection via nasopharyngeal brush sampling is effective for diagnosing nasopharyngeal carcinoma

    PubMed Central

    Chen, Ming-Yuan; Li, Xi-Zhao; Jia, Wei-Hua

    2016-01-01

    Epstein-Barr virus (EBV)-encoded microRNAs (miRNAs) are highly expressed in nasopharyngeal carcinoma (NPC) cases in high-risk areas, and may be involved in tumorigenesis. Using quantitative RT-PCR, we detected four EBV-encoded BamHI A rightward transcript (BART) miRNAs (mir-bart1-5p, mir-bart5, mir-bart6-5p and mir-bart17-5p) exclusively in 53 NPC biopsies as compared to 69 controls. In a larger patient group, that included 215 NPC cases and 209 controls, significantly higher levels of all four EBV miRNAs were detected in tumor cells harvested directly from the nasopharynx using a less invasive nasopharyngeal (NP) brush than in the controls (p < 0.001). One EBV miRNA, mir-bart1-5p, holds particular promise for use as a diagnostic indicator of NPC (with 93.5% sensitivity and 100% specificity), and its relative expression level was reflective of disease progression. Detection of this miRNA was effective for diagnosing early-stage NPC, even in cases that were falsely diagnosed as negative based on histopathological analysis, plasma EBV DNA load, and VCA-IgA and EA-IgA titers. EBV-encoded mir-bart1-5p detection via NP brush sampling could act as an efficient and less invasive method assisting clinical diagnosis of NPC. PMID:26701721

  9. A feedback constraint optimization method for intensity-modulated radiation therapy of nasopharyngeal carcinoma

    PubMed Central

    LI, YONGWU; SUN, XIAONAN; WANG, QI; ZHOU, QINXUAN; GU, BENXING; SHI, GUOZHI; JIANG, DONGLIANG

    2015-01-01

    Intensity-modulated radiation therapy (IMRT) is able to achieve good target conformance with a limited dose to organs at risk (OARs); however, IMRT increases the irradiation volume and monitor units (MUs) required. The present study aimed to evaluate the use of an IMRT plan with fewer segments and MUs, while maintaining quality in the treatment of nasopharyngeal carcinoma. In the present study, two types of IMRT plan were therefore compared: The direct machine parameter optimization (DMPO)-RT method and the feedback constraint DMPO-RT (fc_DMPO-RT) method, which utilizes compensative feedback constraint in DMPO-RT and maintains optimization. Plans for 23 patients were developed with identical dose prescriptions. Each plan involved synchronous delivery to various targets, with identical OAR constraints, by means of 7 coplanar fields. The average dose, maximum dose, dose-volume histograms of targets and the OAR, MUs of the plan, the number of segments, delivery time and accuracy were subsequently compared. The fc_DMPO-RT exhibited superior dose distribution in terms of the average, maximum and minimum doses to the gross tumor volume compared with that of DMPO-RT (t=62.7, 20.5 and 22.0, respectively; P<0.05). The fc_DMPO-RT also resulted in a smaller maximum dose to the spinal cord (t=7.3; P<0.05), as well as fewer MUs, fewer segments and decreased treatment times than that of the DMPO-RT (t=6.2, 393.4 and 244.3, respectively; P<0.05). The fc_DMPO-RT maintained plan quality with fewer segments and MUs, and the treatment time was significantly reduced, thereby resulting in reduced radiation leakage and an enhanced curative effect. Therefore, introducing feedback constraint into DMPO may result in improved IMRT planning. In nasopharyngeal carcinoma specifically, feedback constraint resulted in the improved protection of OARs in proximity of targets (such as the brainstem and parotid) due to sharp dose distribution and reduced MUs. PMID:26622793

  10. Cripto-1 overexpression is involved in the tumorigenesis of nasopharyngeal carcinoma

    PubMed Central

    2009-01-01

    Background Human Cripto-1, a member of the EGF-CFC family, is indispensable for early embryonic development. Cripto-1 plays an important oncogenic role during tumorigenesis and is overexpressed in a wide range of epithelial carcinomas, yet little is known about Cripto-1 in nasopharyngeal carcinoma (NPC). The aim of this study was to analyze the roles of Cripto-1 in the progression and clinical characteristics in NPC clinical samples and cell lines. Methods The expression of Cripto-1 at mRNA level was detected by the reverse transcription-polymerase chain reaction (RT-PCR) and real time RT-PCR, and western blot was used to examine the protein expression. Cripto-1 expression and its clinical characteristics were investigated by performing immunohistochemical analysis on a total of 37 NPC clinical tissue samples. Lentiviral vectors were constructed to get an efficient expression of anti-Cripto-1 siRNA in CNE-2 and C666-1 cells, with invalid RNAi sequence as control. After the inhibition of the endogenous Cripto-1, the growth, cell cycle and invasion of cells were detected by MTT, FACS and Boyden chamber assay respectively. Moreover, in vivo, the proliferation of the tumor cells was evaluated in xenotransplant nude mice model with whole-body visualizing instrument. Results The results of real-time RT-PCR and western blot showed that the expression level of Cripto-1 was markedly higher in NPC cell lines than that in the immortalized nasopharyngeal epithelial cell at both mRNA and protein levels. RT-PCR of 17 NPC tissues showed a high expression rate in 76.5% (13/17) cases. In an immunohistochemical study, Cripto-1 was found to express in 54.1% (20/37) cases of NPC. In addition, Cripto-1 overexpression was significantly associated with N classification (p = 0.034), distant metastasis (p = 0.036), and clinical stage (p = 0.007). Inhibition of endogenous Cripto-1 by lentivirus-mediated RNAi silencing technique suppressed NPC cell growth and invasion in vitro. In vivo, the

  11. Prognostic significance of pretreated serum lactate dehydrogenase level in nasopharyngeal carcinoma among Chinese population

    PubMed Central

    Zhang, Mingwei; Wei, Shushan; Su, Li; Lv, Wenlong; Hong, Jinsheng

    2016-01-01

    Abstract Background: A large number of studies have investigated the prognostic value of pretreated lactate dehydrogenase (LDH) level in nasopharyngeal carcinoma (NPC) patients while the role of it was inconsistent and inconclusive. Hence, the aim of the current study was to conduct a meta-analysis of all published studies to quantify the prognostic impact of pretreated serum LDH in NPC for Chinese population. Objectives: The aim of the current study was to conduct a meta-analysis of all published studies to quantify the prognostic impact of pretreated serum lactate dehydrogenase (LDH) in nasopharyngeal carcinoma (NPC) for Chinese population. Methods: The PubMed, Medline, Embase, and Web of Science databases were searched for studies that assessed survival outcome and LDH in NPC. Overall survival (OS) was the primary survival outcome. Distant metastasis-free survival (DMFS) and disease-free survival (DFS) were secondary outcomes. The pooled hazard ratios (HRs), associated with 95% confidence intervals (95% CIs), were combined to calculate overall effects. The Cochran Q and I2 statistics were used to assess heterogeneity. When apparent heterogeneity was observed, sensitivity and meta-regression analyses were performed to explore its origin. Results: Sixteen studies, which included 14,803 patients, were enrolled in the current meta-analysis to yield statistics. Overall, the pooled HR for OS in 11 eligible studies with high LDH level was 1.79 (95% CI = 1.47–2.12), and the pooled HR for DMFS in 9 eligible studies with high LDH level was 1.85 (95% CI = 1.48–2.22). Meanwhile, the pooled HR for DFS in 5 eligible studies with high LDH level was 1.63 (95% CI = 1.34–1.91). Egger test and funnel plots revealed that the publication bias in the current meta-analysis was insignificant. Conclusions: The present meta-analysis demonstrated that high pretreated LDH level is significantly associated with poorer OS, DMFS, and DFS, suggesting that pretreated LDH could

  12. Rad51 Expression in Nasopharyngeal Carcinoma and Its Association with Tumor Reduction: A Preliminary Study in Indonesia

    PubMed Central

    Cahyanti, Dian; Rachmadi, Lisnawati; Wulani, Vally; Adham, Marlinda

    2016-01-01

    Background: Overexpression of Rad51 protein in many tumor cells has been proven to increase radioresistance and can be related to the resistance of chemosensitivity of tumor cells. This preliminary study was conducted to determine the relationship between the Rad51 expression level in nasopharyngeal carcinoma and the response of the treatment based on the measurement of the tumor reduction. Methods: Thirteen cases of the NPCs were analyzed. The expression levels of the Rad51 were examined from the pretreatment biopsies. Furthermore, tumor reductions were determined based on the change in sum longest diameter of the nasopharyngeal CT-scan before and after therapy. Results: The expression level of the Rad51 was associated with the reduction of tumor mass. The P value was 0.049 and the correlation coefficient was 0.479. Conclusion: The tumor cells Rad51 expression levels may affect the tumor reduction of NPC after the therapy. PMID:27499778

  13. Therapeutic effect of TMZ-POH on human nasopharyngeal carcinoma depends on reactive oxygen species accumulation

    PubMed Central

    Guo, Wei; Wang, Xingwu; Wei, Ling; Li, Yang; Lv, Liyan; Wang, Weijun; Chen, Thomas C.; Song, Xianrang

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy without efficient chemotherapeutic agents for it. In our current study, we demonstrated the cytotoxicity effects of a newly patented compound temozolomide–perillyl alcohol (TMZ-POH) on NPC in vitro and in vivo, and the possible mechanisms involved. Human NPC cell lines CNE1, CNE2, HNE2, and SUME-α were treated with control (DMSO), TMZ, POH, TMZ plus POH, and TMZ-POH. Our data indicated that TMZ-POH could inhibit NPC cell proliferation, cause G2/M arrest and DNA damage. TMZ-POH triggered apoptosis in NPC cells via significant activation of caspase-3 and poly(ADP-ribose) polymerase (PARP). Importantly, TMZ-POH-induced cell death was found to be associated with (i) the loss of inner mitochondrial membrane potential (ΔΨm) and release of mitochondrial Cytochrome c, (ii) the increase in ROS generation, and (iii) the activation of stress-activated protein kinases (SAPK)/c-Jun N-terminal kinases (JNK) signaling pathway. The generation of ROS in response to TMZ-POH seems to play a crucial role in the cell death process since the blockage of ROS production using the antioxidant N-acetyl-L-cysteine or catalase reversed the TMZ-POH-induced JNK activation, DNA damage, and cancer cell apoptosis. These results provide the rationale for further research and preclinical investigation of the antitumor effect of TMZ-POH against human NPC. PMID:26625208

  14. Alcohol drinking as an unfavorable prognostic factor for male patients with nasopharyngeal carcinoma

    PubMed Central

    Chen, Yu-Pei; Zhao, Bing-Cheng; Chen, Chen; Lei, Xin-Xing; Shen, Lu-Jun; Chen, Gang; Yan, Fang; Wang, Guan-Nan; Chen, Han; Jiang, Yi-Quan; Xia, Yun-Fei

    2016-01-01

    The relationship between alcohol drinking and the prognosis of nasopharyngeal carcinoma (NPC) is unknown. To investigate the prognostic value of alcohol drinking on NPC, this retrospective study was conducted on 1923 male NPC patients. Patients were classified as current, former and non-drinkers according to their drinking status. Furthermore, they were categorized as heavy drinkers and mild/none drinkers based on the intensity and duration of alcohol drinking. Survival outcomes were compared using Kaplan–Meier analysis and Cox proportional hazards model. We found that current drinkers had significantly lower overall survival (OS) rate (5-year OS: 70.2% vs. 76.4%, P < 0.001) and locoregional recurrence-free survival (LRFS) rate (5-year LRFS: 69.3% vs. 77.5%, P < 0.001) compared with non-drinkers. Drinking ≥14 drinks/week, and drinking ≥20 years were both independent unfavorable prognostic factors for OS (hazard ratio [HR] = 1.38, 95% confidence interval [CI] 1.05–1.81, P = 0.022; HR = 1.38, 95% CI 1.09–1.75, P = 0.007). Stratified analyses further revealed that the negative impacts of alcohol were manifested mainly among older patients and among smokers. In conclusion, alcohol drinking is a useful predictor of prognosis in male NPC patients; drinkers, especially heavy drinkers have poorer prognosis. PMID:26776301

  15. High expression of Sox10 correlates with tumor aggressiveness and poor prognosis in human nasopharyngeal carcinoma

    PubMed Central

    Zhao, Yu; Liu, Zhi-gang; Tang, Jiao; Zou, Ren-fang; Chen, Xiao-yan; Jiang, Guan-min; Qiu, Yan-fang; Wang, Hui

    2016-01-01

    Purpose The aim of the study was to detect the expression of Sox10 in human nasopharyngeal carcinoma (NPC) and investigate the relationship between its expression and the clinicopathological characteristics of NPC patients. Patients and methods Tumor specimens (n=105) were retrospectively collected from patients with NPC diagnosed between 2004 and 2005 who presented at Hunan Cancer Hospital. Immunohistochemistry analyses were performed to characterize the expression of Sox10 in NPC. Kaplan–Meier survival and Cox regression analyses were employed to evaluate the prognosis of 105 NPC patients. Results The results showed that Sox10 was markedly overexpressed in human NPC tissues. Analysis of clinicopathological parameters showed that high Sox10 expression was significantly correlated with the clinical stage (P=0.032), T classification (P=0.034), and lymph node metastasis (P=0.03). Cox regression analyses further showed that Sox10 expression was an independent prognostic factor for overall survival (P=0.005). This is the first time Sox10 has shown its importance in predicting NPC progressiveness and survival outcomes. Conclusion Sox10 serves as a potential biomarker for NPC patients. It may hopefully become a novel therapeutic target for NPC patients. PMID:27051302

  16. Application of a patient-derived xenograft model in cytolytic viral activation therapy for nasopharyngeal carcinoma

    PubMed Central

    Hsu, Cheng-Lung; Kuo, Yung-Chia; Huang, Yenlin; Huang, Yin-Cheng; Lui, Kar-Wai; Chang, Kai-Ping; Lin, Tung-Liang; Fan, Hsien-Chi; Lin, An-Chi; Hsieh, Chia-Hsun; Lee, Li-Yu; Wang, Hung-Ming; Li, Hsin-Pai; Chang, Yu-Sun

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is an Epstein Barr virus (EBV)-related malignancy in which the tumor microenvironment plays a pivotal role in tumor progression. Here, we developed two patient-derived xenograft (PDX) mouse lines from engrafted NPC metastatic tumors. Positive staining for EBV-encoded small RNAs confirmed that these tumors harbored EBV, and gene expression profile analyses further showed that the PDX was highly similar to the primary parent tumor. In vivo drug screening using the PDX system demonstrated that gemcitabine had the best antitumor effect among the tested drugs. The donor of this PDX also showed excellent responsiveness to gemcitabine treatment. The combination of gemcitabine and valproic acid exerted synergistic antitumor effects. Further addition of ganciclovir to this two-drug combination regimen enhanced cytolytic viral activation, yielding the best antitumor response among tested regimens. Treatment with this three-drug combination regimen decreased plasma EBV-DNA load, tumor viral concentration, and the number of viable tumor cells to a greater extent than the two-drug gemcitabine and valproic acid combination. These results highlight the value of PDX models in the development of EBV-targeted strategies to treat NPC. PMID:26416517

  17. Sensori-neural hearing loss in patients treated with irradiation for nasopharyngeal carcinoma

    SciTech Connect

    Grau, C.; Moller, K.; Overgaard, M.; Overgaard, J.; Elbrond, O. )

    1991-08-01

    The present investigation has been carried out to evaluate the sensitivity of the inner ear to irradiation. Cochlear function was tested in a cohort of 22 patients before and 7-84 months after receiving external irradiation for nasopharyngeal carcinoma. The pre-irradiation sensori-neural hearing threshold at 500, 1000, 2000, and 4000 Hz was used as a baseline for the individual patient, and the observed sensori-neural hearing loss (SNHL) was calculated as the difference between pre- and post-irradiation values. The pre-irradiation hearing level or patient age was not correlated with the actual SNHL. In contrast, there was a significant correlation between the total radiation dose to the inner ear and the observed hearing impairment. SNHL was most pronounced in the high frequencies, with values up to 35 dB (4000 Hz) and 25 dB (2000 Hz) in some patients. The latent period for the complication appeared to be 12 months or more. The deleterious effect of irradiation on the hearing should be kept in mind both in treatment planning and in the follow-up after radiotherapy.

  18. Long-term maxillofacial effects of radiotherapy in young nasopharyngeal carcinoma patients: report of 3 cases.

    PubMed

    Bektaş-Kayhan, K; Ozbek, C D; Yazicioğlu, O; Karagöz, G; Altun, M; Meral, R; Unür, M

    2013-01-01

    Nasopharyngeal carcinoma (NPC) is a rare and distinct malignancy that arises from the epithelium of the nasopharynx. It accounts almost 1% of all pediatric malignancies. Oral complications of radiotherapy in the head and neck region are the result of the deleterious effects of radiation on salivary glands, oral mucosa, bone, dentition, masticatory musculature, and temporomandibular joints. Here we present 3 male NPC patients 13, 14 and 15 years old. One of them had stage III and the others stage IV diseases. Administered dose of radiation was 66 Gy for case I, 70 Gy for case II and 68 Gy for case III. The follow-up period was more than 12 months except for case III and all of them were disease free in their last visit. All attended dental clinics for dental and TMJ problems. Dentitions were severely affected, trismus and severe xerostomia. Long-term effects of radiotherapy which has a great impact on patients' quality of life and the role of supportive care and minimizing the late effects of ionizing radiation are discussed. PMID:24046991

  19. Diabetes, Prediabetes and the Survival of Nasopharyngeal Carcinoma: A Study of 5,860 Patients

    PubMed Central

    OuYang, Pu-Yun; Su, Zhen; Tang, Jie; Lan, Xiao-Wen; Mao, Yan-Ping

    2014-01-01

    Background The incidence of diabetes is increasing. But the impact of diabetes and prediabetes on survival of patients with nasopharyngeal carcinoma (NPC) has received little evaluation. Methods In a cohort of 5,860 patients, we compared the disease specific survival (DSS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) of patients with diabetes, prediabetes and normoglycemia defined by pretreatment fasting plasma glucose (FPG) using Kaplan–Meier method, log-rank test and Cox proportional hazards model. Results Comparing to normoglycemic patients, the diabetic and the prediabetic were generally older, fatter, had hypertension, heart diseases and hyperlipaemia and usually received radiotherapy alone. But both the diabetic and the prediabetic had similar DSS, LRFS and DMFS to normoglycemic patients, even adjusting for such important factors as age, gender, smoking, drinking, hypertension, heart diseases, body mass index, hyperlipaemia, titer of VCA-IgA and EA-IgA, pathology, T-stage, N-stage, chemotherapy and radiotherapy (P>0.05 for all). Additionally, the findings remained unchanged in sensitivity analysis by excluding patients with known diabetes history and in subgroups of the various factors. Conclusions The diabetic and prediabetic NPC patients had similar survival to normoglycemic NPC patients. These data, in the largest reported cohort, are the first to evaluate the association between diabetes, prediabetes and the survival in NPC. The findings are relevant to patient management and provided evidence of the effect on this disease exerted by comorbidities. PMID:25350747

  20. Pregnancy Incidence in Female Nasopharyngeal Carcinoma Survivors of Reproductive Age: A Population-Based Study.

    PubMed

    Lee, Bo-Ching; Yen, Ruoh-Fang; Lin, Cheng-Li; Liang, Ji-An; Lin, Ming-Chia; Kao, Chia-Hung

    2016-05-01

    This study evaluated the pregnancy incidence in female nasopharyngeal carcinoma (NPC) survivors of reproductive age.In a nationwide cohort, 2816 female patients 15 to 50 years of age from 1998 to 2010 were identified from the Taiwan National Health Insurance Research database. Comorbidities, complications during pregnancy, and delivery status were recorded. All patients were followed up until a diagnosis of pregnancy, withdrawal from the National Health Insurance system, or December 31, 2011.Overall, 155 patients (incidence rate [IR] = 9.50) were pregnant in the NPC group, whereas 251 patients (IR = 12.80) were pregnant in the non-NPC group. The cumulative incidence of pregnancy in the NPC group was lower than that in the non-NPC group (incidence rate ratio = 0.74, 95% CI = 0.61-0.91). The adjusted hazard ratio of pregnancy in the NPC group was 0.79 with 95% CI = 0.61-0.96, compared with the non-NPC group.The incidence of pregnancy is significantly lower among female NPC survivors of reproductive age than among those without NPC. PMID:27196495

  1. Epigenetic inactivation of follistatin-like 1 mediates tumor immune evasion in nasopharyngeal carcinoma

    PubMed Central

    Huang, Tingting; Du, Chunping; Wang, Shumin; Mo, Yingxi; Ma, Ning; Murata, Mariko; Li, Bo; Wen, Wensheng; Huang, Guangwu; Zeng, Xianjie; Zhang, Zhe

    2016-01-01

    Follistatin like-1 (FSTL1) is a secreted glycoprotein involved in a series of physiological and pathological processes. However, its contribution to the development of cancer, especially the pathogenesis of nasopharyngeal carcinoma (NPC), remains to be elucidated. We aimed to investigate the dysregulation of FSTL1 and its possible function in NPC. FSTL1 was frequently downregulated in NPC cell lines and primary tumor biopsies by promoter hypermethylation. Ectopic expression of FSTL1 significantly suppressed the colony formation, proliferation, migration and invasion ability of NPC cells and induced cell apoptosis. Overexpression of FSTL1 decreased the tumorigenicity of NPC cells in vivo. In addition, the proliferation of NPC cells in vitro was inhibited by treatment with soluble recombinant FSTL1 protein. The protein level of FSTL1 was decreased in primary NPC tumors and was associated with downregulated interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α). Furthermore, recombinant human FSTL1 protein induced secretion of IL-1β and TNF-α in macrophage cultures, therefore FSTL1 might activate macrophages and attenuate the immune evasion of NPC cells. In conclusion, the epigenetic downregulation of FSTL1 may suppress the proliferation and migration of NPC cells, leading to dysfunctional innate responses in surrounding macrophages. PMID:26918942

  2. Elevated expression of CD93 promotes angiogenesis and tumor growth in nasopharyngeal carcinoma.

    PubMed

    Bao, Lili; Tang, Mingming; Zhang, Qicheng; You, Bo; Shan, Ying; Shi, Si; Li, Li; Hu, Songqun; You, Yiwen

    2016-08-01

    CD93, also known as the complement component C1q receptor (C1qRp), has been reported to promote the progression of some cancer types. However, the expression and physiological significance of CD93 in nasopharyngeal carcinoma (NPC) remain largely elusive. In this study, we first examined the expression of CD93 in NPC and experimentally manipulated its expression. We observed that vascular CD93 expression is elevated in NPC and is correlated with T classification, N classification, distant metastasis, clinical stage and poor prognosis (all P < 0.05). In addition, overexpression of CD93 promoted angiogenesis in vitro. What's more, we found that CD93 was highly expressed in NPC tissues and cells, and the regulation of CD93 on cell proliferation was determined by cell counting kit (CCK)-8 assay and cell cycle analyses. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as CD93 to improve NPC treatment. PMID:27255994

  3. Treatment of Nasopharyngeal Carcinoma Using Intensity-Modulated Radiotherapy-The National Cancer Centre Singapore Experience

    SciTech Connect

    Tham, Ivan Weng-Keong; Hee, Siew Wan; Yeo, Richard Ming-Chert; Salleh, Patemah; Lee, James; Tan, Terence Wee-Kiat; Fong, Kam Weng; Chua, Eu Tiong; Wee, Joseph Tien-Seng

    2009-12-01

    Purpose: The aim of this study was to determine the efficacy and acute toxicity of our early experience with treating nasopharyngeal carcinoma (NPC) patients with intensity-modulated radiotherapy (IMRT). Methods and materials: A review was conducted on case records of 195 patients with histologically proven, nonmetastatic NPC treated with IMRT between 2002 and 2005. MRI of the head and neck was fused with CT simulation images. All plans had target volumes at three dose levels, with a prescribed dose of 70 Gy to the gross disease, in 2.0-2.12 Gy/fraction over 33-35 fractions. Cisplatin-based chemotherapy was offered to Stage III/IV patients. Results: Median patient age was 52 years, and 69% were male. Median follow-up was 36.5 months. One hundred and twenty-three patients had Stage III/IV disease (63%); 50 (26%) had T4 disease. One hundred and eighty-eight (96%) had complete response; 7 (4%) had partial response. Of the complete responders, 10 (5.3%) had local recurrence, giving a 3-year local recurrence-free survival estimate of 93.1% and a 3-year disease-free survival of 82.1%. Fifty-one patients (26%) had at least one Grade 3 toxicity. Conclusions: Results from our series are comparable to those reported by other centers. Acute toxicity is common. Local failure or persistent disease, especially in patients with bulky T4 disease, are issues that must be addressed in future trials.

  4. Non-invasive detection of nasopharyngeal carcinoma using saliva surface-enhanced Raman spectroscopy

    PubMed Central

    QIU, SUFANG; XU, YUANJI; HUANG, LINGLING; ZHENG, WEI; HUANG, CHAOBIN; HUANG, SHAOHUA; LIN, JINYONG; LIN, DUO; FENG, SHANGYUAN; CHEN, RONG; PAN, JIANJI

    2016-01-01

    The present study evaluated the use of saliva surface-enhanced Raman spectroscopy (SERS) for the detection of non-invasive nasopharyngeal carcinoma (NPC). SERS measurements were taken from 62 saliva samples, of which 32 were from NPC patients and 30 from healthy volunteers. Notable biochemical Raman bands in the SERS spectra were tentatively assigned to various saliva components. The saliva SERS spectra obtained from the NPC patients and the healthy volunteers were also analyzed by multivariate statistical techniques based on principal component analysis and linear discriminant analysis (PCA-LDA). Significant differences were observed between the saliva SERS spectral intensities for NPC patients and healthy volunteers, particularly at 447, 496, 635, 729, 1134, 1270 and 1448 cm−1, which primarily contained signals associated with proteins, nucleic acids, fatty acids, glycogen and collagen. The classification results based on the PCA-LDA method provided a relatively high diagnostic sensitivity of 86.7%, specificity of 81.3% and diagnostic accuracy of 83.9% for NPC identification. The results from the present study demonstrate that saliva SERS analysis used in conjunction with PCA-LDA diagnostic algorithms possesses a promising clinical application for the non-invasive detection of NPC. PMID:26870300

  5. TEL2 suppresses metastasis by down-regulating SERPINE1 in nasopharyngeal carcinoma

    PubMed Central

    Zhang, Ru-Hua; Wang, Li; Li, Mei; Luo, Rongzhen; Qian, Chao-Nan; Shao, Jian-Yong; Zeng, Yi-Xin; Kang, Tiebang

    2015-01-01

    Metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). However, the molecular mechanisms of NPC metastasis are poorly understood. Here, using our customized gene microarray containing all of the known human transcription factors and the current markers for epithelial-mesenchymal transition, we report that TEL2 was down-regulated in highly metastatic NPC cells and the metastatic tissues in lymph node. Mechanistically, TEL2 inhibits the cell migration and invasion in vitro and metastasis in vivo by releasing its direct suppression on the SERPINE1 promoter in NPC. Consistently, an inverse correlation was observed between the protein levels of TEL2 and SERPINE1 using clinical NPC samples. Collectively, we have provided the first evidence that TEL2 plays a key role in NPC metastasis by directly down-regulating SERPINE1, and that this novel axis of TEL2 / SERPINE1 may be valuable to develop new strategies for treating NPC patients with metastasis. PMID:26335051

  6. Reduced RKIP enhances nasopharyngeal carcinoma radioresistance by increasing ERK and AKT activity

    PubMed Central

    Yuan, Li; Yi, Hong-Mei; Yi, Hong; Qu, Jia-Quan; Zhu, Jin-Feng; Li, Li-Na; Xiao, Ta; Zheng, Zhen; Lu, Shan-Shan; Xiao, Zhi-Qiang

    2016-01-01

    Raf kinase inhibitory protein (RKIP) functions as a chemo-immunotherapeutic sensitizer of cancers, but regulation of RKIP on tumor radiosensitivity remains largely unexplored. In this study, we investigate the role and mechanism of RKIP in nasopharyngeal carcinoma (NPC) radioresistance. The results showed that RKIP was frequently downregulated in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and its reduction correlated with NPC radioresistance and poor patient survival, and was an independent prognostic factor. In vitro radioresponse assay showed that RKIP overexpression decreased while RKIP knockdown increased NPC cell radioresistance. In the NPC xenografts, RKIP overexpression decreased while RKIP knockdown increased tumor radioresistance. Mechanistically, RKIP reduction promoted NPC cell radioresistance by increasing ERK and AKT activity, and AKT may be a downstream transducer of ERK signaling. Moreover, the levels of phospho-ERK−1/2 and phospho-AKT were increased in the radioresistant NPC tissues compared with radiosensitive ones, and negatively associated with RKIP expression, indicating that RKIP-regulated NPC radioresponse is mediated by ERK and AKT signaling in the clinical samples. Our data demonstrate that RKIP is a critical determinant of NPC radioresponse, and its reduction enhances NPC radioresistance through increasing ERK and AKT signaling activity, highlighting the therapeutic potential of RKIP-ERK-AKT signaling axis in NPC radiosensitization. PMID:26862850

  7. Functional Inactivation of EBV-Specific T-Lymphocytes in Nasopharyngeal Carcinoma: Implications for Tumor Immunotherapy

    PubMed Central

    Li, Jiang; Zeng, Xue-hui; Mo, Hao-yuan; Rolén, Ulrika; Gao, Yan-fang; Zhang, Xiao-shi; Chen, Qiu-yan; Zhang, Li; Zeng, Mu-sheng; Li, Man-zhi; Huang, Wen-lin; Wang, Xiao-ning; Zeng, Yi-Xin; Masucci, Maria G.

    2007-01-01

    Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated malignancy with high prevalence in Southern Chinese. In order to assess whether defects of EBV-specific immunity may contribute to the tumor, the phenotype and function of circulating T-cells and tumor infiltrating lymphocytes (TILs) were investigated in untreated NPC patients. Circulating naïve CD3+CD45RA+ and CD4+CD25− cells were decreased, while activated CD4+CD25+ T-cells and CD3−CD16+ NK-cells were increased in patients compared to healthy donors. The frequency of T-cells recognizing seven HLA-A2 restricted epitopes in LMP1 and LMP2 was lower in the patients and remained low after stimulation with autologous EBV-carrying cells. TILs expanded in low doses of IL-2 exhibited an increase of CD3+CD4+, CD3+CD45RO+ and CD4+CD25+ cells and 2 to 5 fold higher frequency of LMP1 and LMP2 tetramer positive cells compared to peripheral blood. EBV-specific cytotoxicity could be reactivated from the blood of most patients, whereas the TILs lacked cytotoxic activity and failed to produce IFNγ upon specific stimulation. Thus, EBV-specific rejection responses appear to be functionally inactivated at the tumor site in NPC. PMID:17987110

  8. EBV-encoded RNA via TLR3 induces inflammation in nasopharyngeal carcinoma.

    PubMed

    Li, Zhi; Duan, Yumei; Cheng, Shiyue; Chen, Yan; Hu, Yanxin; Zhang, Lu; He, Jiang; Liao, Qiong; Yang, Lifang; Sun, Lun-Quan

    2015-09-15

    Pathogen-induced inflammation has been one of the intensive research areas in carcinogenesis. EBV encoded RNAs (EBERs) have been suggested to play roles in anti-apoptosis and growth-promotion in lymphoid and immune disorders. However, pathological roles of EBERs in solid tumors of epithelia origin remain to be elucidated. Given their characteristic dsRNA structures, recent studies provided evidences for the activation of some pattern recognition receptors (PRR) by EBERs, which is fundamental in the process of pathogenesis. Here, we show that EBERs induce inflammatory response in nasopharyngeal carcinoma (NPC) cells through Toll-like receptor 3 (TLR3), mainly featured by high level of TNFα production. Interestingly, EBERs and EBV latent membrane protein 1 (LMP1) form a positive regulatory loop with NF-κB as a key node that amplifies the inflammatory signals in EBV infected epithelial cells. We demonstrate in vivo that EBERs can interact with TLR3 and induce tumor cells to produce cytokines in B16 synergetic tumor and human NPC xenograft models, in which macrophages are recruited and activated, leading to a favorable microenvironment for solid tumor growth. Lastly, we verify a positive association between EBER and TNFα levels in NPC clinical samples and the combination of EBER and TNFα expressions provides a predictor of poor survival of NPC patients. In conclusion, EBERs play a pivotal role in inflammation-to-oncogenesis transition in NPC development. PMID:26172457

  9. MicroRNAs serving as potential biomarkers and therapeutic targets in nasopharyngeal carcinoma: A critical review.

    PubMed

    Lee, Katherine Ting-Wei; Tan, Juan-King; Lam, Alfred King-Yin; Gan, Sook-Yee

    2016-07-01

    Despite significant medical advancement, nasopharyngeal carcinoma (NPC) remains one of the most difficult cancers to detect and treat where it continues to prevail especially among the Asian population. miRNAs could act as tumour suppressor genes or oncogenes in NPC. They play important roles in the pathogenesis of NPC by regulating specific target genes which are involved in various cellular processes and pathways. In particular, studies on miRNAs related to the Epstein Barr virus (EBV)-encoded latent membrane protein one (LMP1) and EBVmiRNA- BART miRNA confirmed the link between EBV and NPC. Both miRNA and its target genes could potentially be exploited for prognostic and therapeutic strategies. They are also important in predicting the sensitivity of NPC to radiotherapy and chemotherapy. The detection of stable circulating miRNAs in plasma of NPC patients has raised the potential of miRNAs as novel diagnostic markers. To conclude, understanding the roles of miRNA in NPC will identify ways to improve the management of patients with NPC. PMID:27179594

  10. Clinical Study of Nasopharyngeal Carcinoma Treated by Helical Tomotherapy in China: 5-Year Outcomes

    PubMed Central

    Du, Lei; Zhang, Xin-Xin; Ma, Lin; Feng, Lin-Chun; Li, Fang; Zhou, Gui-Xia; Qu, Bao-Lin; Xu, Shou-Ping; Xie, Chuan-Bin; Yang, Jack

    2014-01-01

    Background. To evaluate the outcomes of nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT). Methods. Between September 2007 and August 2012, 190 newly diagnosed NPC patients were treated with HT. Thirty-one patients were treated with radiation therapy as single modality, 129 with additional cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody therapy, and 30 with concurrent anti-EGFR monoclonal antibody therapy. Results. Acute radiation related side effects were mainly grade 1 or 2. Grade 3 and greater toxicities were rarely noted. The median followup was 32 (3–38) months. The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 96.1%, 98.2%, 92.0%, and 86.3%, respectively, at 3 years. Cox multivariate regression analysis showed that age and T stage were independent predictors for 3-year OS. Conclusions. Helical tomotherapy for NPC patients achieved excellent 3-year locoregional control, distant metastasis-free survival, and overall survival, with relatively minor acute and late toxicities. Age and T stage were the main prognosis factors. PMID:25114932

  11. MiR-593 mediates curcumin-induced radiosensitization of nasopharyngeal carcinoma cells via MDR1

    PubMed Central

    FAN, HAONING; SHAO, MENG; HUANG, SHAOHUI; LIU, YING; LIU, JIE; WANG, ZHIYUAN; DIAO, JIANXIN; LIU, YUANLIANG; TONG, LI; FAN, QIN

    2016-01-01

    Curcumin (Cur) exhibits radiosensitization effects to a variety of malignant tumors. The present study investigates the radiosensitizing effect of Cur on nasopharyngeal carcinoma (NPC) cells and whether its mechanism is associated with microRNA-593 (miR-593) and multidrug resistance gene 1 (MDR1). A clonogenic assay was performed to measure the radiosensitizing effect. The expression of miR-593 and MDR1 was analyzed by quantitative polymerase chain reaction (qPCR) or western blot assay. A transplanted tumor model was established to identify the radiosensitizing effect in vivo. A luciferase-based reporter was constructed to evaluate the effect of direct binding of miR-593 to the putative target site on the 3′ UTR of MDR1. The clonogenic assay showed that Cur enhanced the radiosensitivity of cells. Cur (100 mg/kg) combined with 4 Gy irradiation inhibited the growth of a transplanted tumor model in vivo, resulting in the higher inhibition ratio compared with the radiotherapy-alone group. These results demonstrated that Cur had a radiosensitizing effect on NPC cells in vivo and in vitro; Cur-mediated upregulation of miR-593 resulted in reduced MDR1 expression, which may promote radiosensitivity of NPC cells. PMID:27313684

  12. Association study between miR-149 gene polymorphism and nasopharyngeal carcinoma.

    PubMed

    Huang, Guo-Liang; Lu, Yan; Pu, Xing-Xiang; He, Yu-Xiang; Chen, Mei-Ling; Li, Ya-Zhen; Tang, Shu-Yin; Che, Hua; He, Zhiwei

    2013-07-01

    Association studies between single-nucleotide polymorphism (SNP) rs2292832 on miR-149 gene and cancer risk have been previously analyzed in several types of cancer. The aim of this study was to evaluate the association between miR-149 polymorphism and risk of nasopharyngeal carcinoma (NPC). miR-149 gene polymorphism was genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 158 patients with NPC and 242 healthy individuals. Associations with cancer risk and clinicopathological characteristics were analyzed by χ(2) test. No significant difference was observed for miR-149 gene polymorphism in NPC patients and healthy controls in either genotype (P=0.427 for CC vs. CT vs. TT, P=0.247 for CT vs. TT and P=0.323 for CC vs. TT, respectively) or allelic analysis (P=0.216). No significant difference was noted between the genotypes and the clinicopathological parameters examined with the exception of clinical stage. A significantly higher CC distribution in clinical stage I-II compared with III-IV was observed under the dominant model (CC vs. CT vs. TT, P=0.026) and the co-dominant model (CC vs. TT, P=0.030). The results of this study suggested that the CC genotype of miR-149 contributes to the progression and development, rather than the initiation of NPC. PMID:24648993

  13. Chick Chorioallantoic Membrane Assay: A 3D Animal Model for Study of Human Nasopharyngeal Carcinoma

    PubMed Central

    Ming, Huixin; Zhang, Jinyan; Huang, Guangwu; Zhang, Zhe; Li, Ping

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is a highly invasive and metastatic head and neck cancer. However, mechanistic study of the invasion and metastasis of NPC has been hampered by the lack of proper in vivo models. We established an in vivo chick embryo chorioallantoic membrane (CAM) model to study NPC tumor biology. We found 100% micro-tumor formation 3 days after inoculation with NPC cell lines (4/4) or primary tumor biopsy tissue (35/35). The transplanted NPC micro-tumors grew on CAMs with extracellular matrix interaction and induced angiogenesis. In addition, the CAM model could be used to study the growth of transplanted NPC tumors and also several important steps of metastasis, including tumor invasion by detecting the extent of basement membrane penetration, tumor angiogenesis by analyzing the area of neo-vessels, and tumor metastasis by quantifying tumor cells in distant organs. We established and described a feasible, easy-to-manipulate and reliable CAM model for in vivo study of NPC tumor biology. This model closely simulates the clinical features of NPC growth, progression and metastasis and could help elucidate the biological mechanisms of the growth pattern and invasion of NPC cells and in quantitative assessment of angiogenesis and cell intravasation. PMID:26107941

  14. Houttuynia cordata Thunb extract induces cytotoxicity in human nasopharyngeal carcinoma cells: Raman spectroscopic studies

    NASA Astrophysics Data System (ADS)

    Chen, Weiwei; Li, Zuanfang; Yu, Yun; Lin, Duo; Huang, Hao; Shi, Hong

    2016-01-01

    The molecular mechanisms of cytotoxicity induced by Houttuynia cordata Thunb (HCT) in nasopharyngeal carcinoma (NPC) cells was investigated by Raman spectroscopy (RS). The average Raman spectra of cell groups treated with HCT (0, 62.5, 125, 250, and 500 μg ml-1) for 24 h were measured separately. Compared to the control group, the intensities of the selected bands (1002, 1338, and 1448 cm-1) related to protein, DNA, and lipid in the treatment groups decreased obviously as the concentration of HCT increased. Both cell groups treated with 250 and 500 μg ml-1 of HCT could be differentiated from the control group by principal component analysis (PCA) combined with linear discriminate analysis (LDA) with a diagnostic accuracy of 100%, suggesting that cytotoxicity occurred and that 250 μg ml-1 was the proper dose for treatment. Simultaneously, the Raman spectra of cells treated with different treatment times with 250 μg ml-1 of HCT were obtained. We can get that treatment with HCT decreased cell viability in a dose and time-dependent fashion. The results indicated that the RS combined with PCA-LDA can be used for pharmacokinetics studies of HCT in NPC cells, which could also provide useful data for clinical dosage optimization for HCT.

  15. MiR-34c suppresses tumor growth and metastasis in nasopharyngeal carcinoma by targeting MET

    PubMed Central

    Li, Y-Q; Ren, X-Y; He, Q-M; Xu, Y-F; Tang, X-R; Sun, Y; Zeng, M-S; Kang, T-B; Liu, N; Ma, J

    2015-01-01

    Our previous microarray analysis indicated that miR-34c was downregulated in nasopharyngeal carcinoma (NPC). However, little is known about the function and molecular mechanism of miR-34c in NPC. In this study, miR-34c was found to be significantly downregulated in NPC cell lines and clinical tissues. Ectopic expression of miR-34c suppressed NPC cell viability, colony formation, anchorage-independent growth, cell migration and invasion in vitro, and inhibited xenograft tumor growth and lung metastasis in vivo. MET proto-oncogene (MET) was identified as a direct target of miR-34c using luciferase reporter assays, quantitative RT-PCR, western blotting and immunofluorescent staining. Overexpression of miR-34c markedly reduced MET expression at both the mRNA and protein levels. Knockdown of MET suppressed NPC cell proliferation, migration and invasion, whereas the restoration of MET rescued the suppressive effects of miR-34c. The demethylation agent 5-aza-2′-deoxycytidine (DAC) restored the expression of miR-34c in NPC cell lines. The promoter region of miR-34c was hypermethylated in NPC cells. In conclusion, miR-34c suppresses tumor growth and metastasis in NPC by targeting MET. The newly identified miR-34c/MET pathway provides further insights into the development and progression of NPC, and may represent a novel therapeutic target for NPC treatment. PMID:25611392

  16. Matrine inhibits the migratory and invasive properties of nasopharyngeal carcinoma cells

    PubMed Central

    SUN, BIN; XU, MIN

    2015-01-01

    Matrine is a widely used Chinese herbal medicine that has historically been used in the treatment of inflammation and cancer. However, the antimetastatic effects and associated molecular mechanisms of matrine on nasopharyngeal carcinoma (NPC) remain to be elucidated. Therefore, the aims of the present study were to assess the antimetastatic effects of matrine on NPC, and identify the underlying mechanisms. Matrine inhibited the proliferation of NPC cells in vitro and in vivo. Furthermore, matrine inhibited the migration and invasion of NPC tumor cells at doses below the toxic range. Following treatment with matrine for 24 h, there was a decrease in the protein expression levels and activities of matrix metal-loproteinase (MMP)-2 and MMP-9 in NPC-039 cells. In addition, matrine markedly reduced the expression levels of p65 and p50 in the nuclei. Combined treatment of matrine with helenalin, a nuclear factor-κB (NF-κB) inhibitor resulted in a synergistic reduction in MMP-2 and MMP-9 expression levels, and the invasive capabilities of the NPC-039 cells were also reduced. In conclusion, matrine inhibits NPC cell migration and invasion by suppressing the NF-κB pathway. These results suggest that matrine may be a potential therapeutic agent for NPC. PMID:25633440

  17. RASSF1A gene methylation is associated with nasopharyngeal carcinoma risk in Chinese.

    PubMed

    Wu, Kun; Xu, Xiao-Ning; Chen, Yu; Pu, Xiao-Lin; Wang, Bo-Yuan; Tang, Xiao-Dan

    2015-01-01

    In order to explore the association between RASSF1A methylation and nasopharyngeal carcinoma (NPC) risk of Chinese, we carried out a meta-analysis with searches of PubMed, Web of Science, ProQest and Medline databases. Ultimately, 14 articles were identified and analysised using R Software (R version 3.1.2) including meta packages. Overall, we found a significant relationship between RASSF1A methylation and NPC risk (OR 30.7; 95 % CI, 16.71~56.23; z=11.0591; p<0.0001) in a fixed effects model and (OR 32.1; 95% CI, 14.27~72.01; z=8.3984; p<0.0001) in a random effects model pooled. In tissue and NP brushings groups , similar results were found. Hence, our study identified a strong association between RASSF1A methylation and NPC and highlighted a promising potential for RASSF1A methylation in NPC risk prediction of Chinese. PMID:25824751

  18. Reversing effect of sorcin in the drug resistance of human nasopharyngeal carcinoma.

    PubMed

    Liu, Xuebing; Chen, Lei; Feng, Bin; Liu, Gang

    2014-02-01

    Nasopharyngeal carcinoma (NPC) is one of the most common cancers originating in the nasopharynx, and chemoresistance is an essential aspect of NPC chemotherapy failure. Sorcin has been implicated in multidrug resistance (MDR) of many types of human tumor. However, the effect and mechanism of Sorcin in MDR of human NPC is not fully clear. In this report, we silenced Sorcin in human NPC CNE2/DDP cells, and explored the role of Sorcin in MDR reversal. The results showed an increased cytotoxicity of cisplatin and intracellular accumulation of Rhodamine-123 and glutathione depletion in Sorcin silencing CNE2/DDP cells. We also found a decreased messenger RNA and protein expression of multidrug resistance gene (MDR1), multidrug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase-π (GST-n), RhoE, Bcl-2, and Survivin in Sorcin silencing CNE2/DDP cells. The increased expression of PTEN and decreased expression of p-Akt and NF-κB suggested that the key cellular signaling pathways were triggered by Sorcin silencing. We concluded that Sorcin silencing would contribute to establish a potent target point for MDR reversal. PMID:24376145

  19. Comprehensive profiling of EBV gene expression in nasopharyngeal carcinoma through paired-end transcriptome sequencing.

    PubMed

    Hu, Lijuan; Lin, Zhirui; Wu, Yanheng; Dong, Juqin; Zhao, Bo; Cheng, Yanbing; Huang, Peiyu; Xu, Lihua; Xia, Tianliang; Xiong, Dan; Wang, Hongbo; Li, Manzhi; Guo, Ling; Kieff, Elliott; Zeng, Yixin; Zhong, Qian; Zeng, Musheng

    2016-03-01

    The latent expression pattern of Epstein-Barr Virus (EBV) genes in nasopharyngeal carcinoma (NPC) has been extensively investigated, and the expression of several lytic genes in NPC has been reported. However, comprehensive information through EBV transcriptome analysis in NPC is limited. We performed paired-end RNA-seq to systematically and comprehensively characterize the expression of EBV genes in NPC tissue and C666-1 NPC cell line, which consistently carries EBV. In addition to the transcripts restricted to type II latency infection, the type III latency EBNA3s genes and a substantial number of lytic genes, such as BZLF1, BRLF1, and BMRF1, were detected through RNA-seq and were further verified in C666-1 cells and NPC tissue through realtime PCR.We also performed clustering analysis to classify NPC patient groups in terms of EBV gene expression, which presented two subtypes of NPC samples. Results revealed interesting patterns of EBV gene expression in NPC patients. This clustering was correlated with many signaling pathways, such as those related to heterotrimeric G-protein signaling, inflammation mediated by chemokine and cytokine signaling, ribosomes, protein metabolism, influenza infection, and ECM-receptor interaction. Our combined findings suggested that the expression of EBV genes in NPC is restricted not only to type II latency genes but also to type III latency and lytic genes. This study provided further insights into the potential role of EBV in the development of NPC. PMID:26969667

  20. Stereotactic Radiosurgery Versus Gold Grain Implantation in Salvaging Local Failures of Nasopharyngeal Carcinoma

    SciTech Connect

    Chua, Daniel Wei, William I.; Sham, Jonathan S.T.; Hung, Kwan Ngai; Au, Gordon K.H.

    2007-10-01

    Background: Limited local failure of nasopharyngeal carcinoma (NPC) can often be salvaged by reirradiation using different techniques. Both gold grain implantation (GGI) and stereotactic radiosurgery (SRS) have been used as salvage treatment of NPC but the relative efficacy of these two treatments is not known. Methods and Materials: A total of 74 patients with local NPC failure were included in this retrospective analysis. Of these patients, 37 underwent SRS (median dose, 12.5 Gy) and 37 split-palatal GGI at a dose of 60 Gy. The two groups were individually matched for prognostic factors, except for tumor volume. The median follow-up was 42 months. Results: Local control was better in the GGI group. The 3-year local failure-free rate was 77.9% for the GGI group compared with 68.3% for the SRS group. However, the difference was not statistically significant (p = 0.098). In the subgroup with a tumor volume of {<=}5 cm{sup 3}, the 3-year local failure-free rates were similar, with 79.3% in the GGI group and 72.4% in the SRS group. Neuroendocrine complications were more common in the SRS group, and headache and fistula were more common in the GGI group. Conclusion: Stereotactic radiosurgery and GGI are both effective salvage treatment for NPC. In patients with limited local failure, both yielded comparable high tumor control rates.

  1. Salivary Anionic Changes after Radiotherapy for Nasopharyngeal Carcinoma: A 1-Year Prospective Study

    PubMed Central

    Pow, Edmond H. N.; Chen, Zhuofan; Kwong, Dora L. W.; Lam, Otto L. T.

    2016-01-01

    Objectives To investigate the salivary anionic changes of patients with nasopharyngeal carcinoma (NPC) treated by radiotherapy. Material and Methods Thirty-eight patients with T1-4, N0-2, M0 NPC received conventional radiotherapy. Stimulated whole saliva was collected at baseline and 2, 6 and 12 months after radiotherapy. Salivary anions levels were measured using ion chromatography. Results A reduction in stimulated saliva flow and salivary pH was accompanied by sustained changes in anionic composition. At 2 months following radiotherapy, there was a significant increase in chloride, sulphate, lactate and formate levels while significant reductions in nitrate and thiocyanate levels were found. No further changes in these anion levels were observed at 6 and 12 months. No significant changes were found in phosphate, acetate, or propionate levels throughout the study period. Conclusions Conventional radiotherapy has a significant and prolonged impact on certain anionic species, likely contributing to increased cariogenic properties and reduced antimicrobial capacities of saliva in NPC patients post-radiotherapy. PMID:27031997

  2. HGF stimulates proliferation through the HGF/c-Met pathway in nasopharyngeal carcinoma cells

    PubMed Central

    SUN, RUI; ZHANG, QING; GUO, LING; CHEN, MING-YUAN; SUN, YING; CAO, BRIAN; SUN, JIAN

    2012-01-01

    Hepatocyte growth factor (HGF) and its receptor c-Met are important in the development and homeostasis of a variety of human malignancies. However, the role of the HGF/c-Met signaling pathway in nasopharyngeal carcinoma (NPC) has not been clearly elucidated. This study examined the effect of HGF/c-Met on proliferation and migration in several NPC cell lines. RT-PCR was used to detect the HGF gene in CNE-1, CNE-2, HK-1, HONE-1 and SUNE-1 NPC cells. However, HGF gene expression was not detected in any of these cells. Using immunoblotting analysis, the Met25 protein was identified in HONE-1, HK-1 and CNE-1 cells. Results from fluorescence-activated cell sorting (FACS) analysis revealed that anti-Met25 mAb specifically bound Met-expressing HONE-1, HK-1 and CNE-1 cells. It was further demonstrated that exogenous HGF was able to stimulate the proliferation of HONE-1 and HK-1 cells and the healing of scrape wounds in HONE-1 NPC cells. Our results reveal the potential therapeutic applications of combination therapy with antibodies targeting HGF in NPC patients. PMID:22783404

  3. Multi-modality imaging to determine the cellular heterogeneity of nasopharyngeal carcinoma components

    PubMed Central

    Ke, Shi; Yang, Guang; Zhang, Tao; Han, Jianjun; Liu, Zhenyin; Wang, Wei; Ran, Henry; Zou, Chaoxia; Hu, Shaofan; Lei, Guangtao; Li, Chuanxing; Zhang, Fujun

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is an endemic public health problem in South and Southeast Asian countries. The disease components at the molecular level are unclear and need exploration for the development of future individualized molecular medicine. The purpose of this study was to test the feasibility of target-specific agents to detect different components of NPC. The binding capability of human NPC cell lines was determined by incubation with either agents that specifically target the metabolic status, host cytokines, and stroma. Mice bearing human NPC xenografts were injected with the same test agents plus a clinical molecular imaging agent (18F-fluorodeoxyglucose) and computer tomography (CT) contrast agent. In vitro cell studies have demonstrated that target-specific agents bind to NPC cells with significantly higher signal intensities. Those agents not only bound to the cell membrane but also penetrated into the cytosol and cell nuclei. In vivo imaging demonstrated that the human NPC xenografts revealed high glucose uptake and a profound vasculature in the tumor. All agents were bound to the tumor regions with a high tumor-to-muscle ratio. Finally, all imaging data were validated by histopathological results. Multiple, target-specific agents determine the dynamic and heterogeneous components of NPC at the molecular level. PMID:24809847

  4. Clinical and biological significance of HAX-1 overexpression in nasopharyngeal carcinoma

    PubMed Central

    Shao, Xiaoyi; Ni, Haosheng; Shi, Si; Shan, Ying; Gu, Zhifeng; You, Yiwen

    2016-01-01

    HS1-associated protein X-1 (HAX-1) is an important marker in many types of cancers and contributes to cancer progression and metastasis. We examined the expression of HAX-1 in nasopharyngeal carcinoma (NPC) and experimentally manipulated its expression. We observed that HAX-1 expression is elevated in NPC and is correlated with lymph node metastasis, M classification, clinical stage, and poor prognosis. In addition, overexpression of HAX-1 promoted NPC proliferation both in vitro and in vivo. Exosomes are potential carriers of pro-tumorigenic factors that participate in oncogenesis. We found that NPC-derived exosomes are enriched in HAX-1 and accelerate NPC tumor growth and angiogenesis in vitro and in vivo. Furthermore, we demonstrated that oncogenic HAX-1 facilitates the growth of NPC when it is transferred via exosomes to recipient human umbilical vein endothelial cells (HUVECs). Oncogenic HAX-1 also increases the proliferation, migration, and angiogenic activity of HUVECs. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as HAX-1 to improve NPC treatment. PMID:26871467

  5. Long Noncoding RNA Expression Signatures of Metastatic Nasopharyngeal Carcinoma and Their Prognostic Value

    PubMed Central

    Zhang, Wei; Wang, Lin; Zheng, Fang; Zou, Ruhai; Xie, Changqing; Guo, Qiannan; Hu, Qian; Chen, Jianing; Yang, Xing; Yao, Herui; Song, Erwei; Xiang, Yanqun

    2015-01-01

    Long noncoding RNAs (lncRNAs) have recently been found to play important roles in various cancer types. The elucidation of genome-wide lncRNA expression patterns in metastatic nasopharyngeal carcinoma (NPC) could reveal novel mechanisms underlying NPC carcinogenesis and progression. In this study, lncRNA expression profiling was performed on metastatic and primary NPC tumors, and the differentially expressed lncRNAs between these samples were identified. A total of 33,045 lncRNA probes were generated for our microarray based on authoritative data sources, including RefSeq, UCSC Knowngenes, Ensembl, and related literature. Using these probes, 8,088 lncRNAs were found to be significantly differentially expressed (≥2-fold). To identify the prognostic value of these differentially expressed lncRNAs, four lncRNAs (LOC84740, ENST00000498296, AL359062, and ENST00000438550) were selected; their expression levels were measured in an independent panel of 106 primary NPC samples via QPCR. Among these lncRNAs, ENST00000438550 expression was demonstrated to be significantly correlated with NPC disease progression. A survival analysis showed that a high expression level of ENST00000438550 was an independent indicator of disease progression in NPC patients (P = 0.01). In summary, this study may provide novel diagnostic and prognostic biomarkers for NPC, as well as a novel understanding of the mechanism underlying NPC metastasis and potential targets for future treatment. PMID:26448942

  6. Predictors of Mastoiditis after Intensity-Modulated Radiotherapy in Nasopharyngeal Carcinoma: A Dose-Volume Analysis

    PubMed Central

    Yao, Ji-Jin; Zhou, Guan-Qun; Jin, Ya-Nan; Zhang, Wang-Jian; Lin, Li; Yu, Xiao-Li; Shao, Jian-Yong; Ma, Jun; Sun, Ying

    2016-01-01

    Background: To identify predictors for development of mastoiditis after intensity-modulated radiation therapy (IMRT) in nasopharyngeal carcinoma (NPC). Methods: Data for 146 NPC patients treated with IMRT was retrospectively reviewed under institutional ethics committee approval. Clinical factors associated with mastoiditis were analyzed. Dose-volume histogram analysis was performed for the Eustachian tube, tympanic cavity, mastoid air cells, cochlea, internal auditory canal and vestibular apparatus to relate doses to radiographic changes in the mastoid. Mastoiditis was assessed using magnetic resonance imaging and was classified as Grade 0 (none), 1 (mild), 2 (moderate) or 3 (severe); Grade 3 mastoiditis was the study end-point. Results: Eighty-eight ears (36%) had radiation-induced mastoiditis: 38/244 (15.6%) mastoid complexes had Grade 1-2 mastoiditis and 50/244 (20.5%) mastoid complexes had Grade 3 mastoiditis. Multivariate analysis revealed a mastoid mean dose > 35.93 Gy (odds ratio [OR]=4.22, P=.003), Eustachian tube mean dose > 53.43 Gy (OR=2.16, P=.034) and advanced T category (T3 and T4; OR=10.33, P=.032) were negative prognostic factors for Grade 3 mastoiditis. Conclusions: Radiation-induced mastoiditis remains a common late toxicity in NPC after radiotherapy. The mean dose to the mastoid air cells and Eustachian tube should be limited to reduce the risk of radiation-induced mastoiditis. PMID:26918040

  7. Cetuximab in combination with chemoradiotherapy in the treatment of recurrent and/or metastatic nasopharyngeal carcinoma.

    PubMed

    Xu, Tingting; Ou, Xiaomin; Shen, Chunying; Hu, Chaosu

    2016-01-01

    The aim of the study was to assess the efficacy and toxicity of cetuximab in the combined treatment for patients with recurrent and/or metastatic nasopharyngeal carcinoma (R/M NPC). Between March 2007 and November 2011, a total of 30 R/M NPC patients treated with comprehensive therapy including cetuximab were retrospectively enrolled. Intensity-modulated radiation therapy was delivered in recurrent disease with a median dose of 60 Gy. Chemotherapy regimens included TP/TPF (docetaxel 60-75 mg/m d1+DDP 25 mg/m d1-3±5-FU 500 mg/m/day with 120-h infusion), GP (gemcitabine 1.0 g/m d1, d8+DDP 25 mg/m d1-3), and PC (paclitaxel 60 mg/m/week d1+carboplatin AUC 2/week d1). Acute and late toxicities were documented by the radiation oncologists. The median age of the patients was 44 years (range 26-62). A total of 21 patients (70%) achieved response (CR+PR). The median survival time, time to progression, and 2-year overall survival were 23.6, 12.2 months, and 53.3%, respectively. Cetuximab appears to be effective and well tolerated when combined with chemoradiation therapy for the treatment of R/M NPC. PMID:26352217

  8. IKBB tumor suppressive role in nasopharyngeal carcinoma via NF-κB-mediated signalling.

    PubMed

    Phoon, Yee Peng; Cheung, Arthur Kwok Leung; Cheung, Florence Man Fung; Chan, Kui Fat; Wong, Shun; Wong, Bonnie Wing Yan; Tung, Stewart Yuk; Yau, Chun Chung; Ng, Wai Tong; Lung, Maria Li

    2016-01-01

    Tumor suppressor genes (TSGs) play a prominent role in cancer and are important in the development of nasopharyngeal carcinoma (NPC), which is endemic in Southern China as well as Southeast Asia. Apart from TSGs, aberrant signalling pathways are also commonly associated with tumor progression. Unsurprisingly, the NF-κB pathway is frequently associated with angiogenesis and promoting tumor growth and development. Functional complementation studies using microcell-mediated chromosome transfer helped to identify IKBB as a putative TSG in NPC. IKBB, an inhibitor of NF-κB, has recently been shown to be inversely associated with tumor growth and metastasis via inactivation of the NF-κB pathway, but its suppressive role is still only poorly understood. This study takes the lead in revealing the suppressive role of IKBB in NPC. IKBB is silenced in the majority of NPC tumor tissues in all stages. Its suppressive role is substantiated by perturbation in tumor formation, cell migration and angiogenesis. Interestingly, IKBB not only affects the 'seed', but also influences the 'soil' by downregulating the transcriptional level of proangiogenic factors Rantes, Upar, IL6, and IL8. For the first time, our data establish the importance of a novel tumor suppressive IKBB gene in abrogating angiogenesis in NPC via the NF-κB signalling pathway, which is likely mediated by crosstalk with the Akt/Gsk3β signalling pathway. PMID:26227166

  9. Network analysis of microRNAs, transcription factors, target genes and host genes in nasopharyngeal carcinoma

    PubMed Central

    WANG, HAO; XU, ZHIWEN; MA, MENGYAO; WANG, NING; WANG, KUNHAO

    2016-01-01

    Numerous studies on the morbidity of nasopharyngeal carcinoma (NPC) have identified several genes, microRNAs (miRNAs or miRs) and transcription factors (TFs) that influence the pathogenesis of NPC. However, summarizing all the regulatory networks involved in NPC is challenging. In the present study, the genes, miRNAs and TFs involved in NPC were considered as the nodes of the so-called regulatory network, and the associations between them were investigated. To clearly represent these associations, three regulatory networks were built seperately, namely, the differentially expressed network, the associated network and the global network. The differentially expressed network is the most important one of these three networks, since its nodes are differentially expressed genes whose mutations may lead to the development of NPC. Therefore, by modifying the aberrant expression of those genes that are differentially expressed in this network, their dysregulation may be corrected and the tumorigenesis of NPC may thus be prevented. Analysis of the aforementioned three networks highlighted the importance of certain pathways, such as self-adaptation pathways, in the development of NPC. For example, cyclin D1 (CCND1) was observed to regulate Homo sapiens-miR-20a, which in turn targeted CCND1. The present study conducted a systematic analysis of the pathogenesis of NPC through the three aforementioned regulatory networks, and provided a theoretical model for biologists. Future studies are required to evaluate the influence of the highlighted pathways in NPC. PMID:27313701

  10. Prognostic Evaluation of Nasopharyngeal Carcinoma with Bone-Only Metastasis after Therapy

    PubMed Central

    Lu, Tianzhu; Guo, Qiaojuan; Cui, Xiaofei; Chen, Zhuhong; Lin, Shaojun; Xu, Luying; Lin, Jin; Zong, Jingfeng

    2016-01-01

    Purpose To evaluate the prognosis of nasopharyngeal carcinoma (NPC) patients who developed bone-only metastasis after primary treatment and the stratification of these patients into different risk groups based on independent prognostic factors. Materials and Methods Eighty NPC patients who developed bone-only metastasis after definitive radiotherapy from October 2005 to December 2010 were enrolled. All these patients received palliative treatment for bone metastasis, including chemotherapy and/or radiotherapy. Clinical features, treatment modality, and laboratory parameters were examined with univariate and multivariate analyses. Results The median follow-up time was 15.5 months (range, 2–67 months) for the whole cohort. The median overall metastatic survival (OMS) time and the 2-year estimate OMS rate were 26.5 months and 52%, respectively. Multivariate analysis indicated that patients with short metastases-free interval, multiple bone metastases sites, high serum lactic dehydrogenase levels, and treated with radiotherapy or chemotherapy alone had significantly worse outcomes. Patients were stratified into three different risk groups based on the number of adverse factors present. The OMS curves of the three groups were all significantly different (p<0.001). Conclusion Severl prognostic factors were found to be associated with worse outcomes. According to the number of adverse factors present, bone-only metastasis patients can be stratified into three risk groups with significantly different prognoses. Such grouping may help in improving the design of clinical trials and in guiding individualized treatment for NPC patients with bone-only metastasis. PMID:27189275

  11. Clusterin induced by N,N′-Dinitrosopiperazine is involved in nasopharyngeal carcinoma metastasis

    PubMed Central

    Wang, Weiwei; Tan, Gongjun; Zhang, Zhenlin; Dong, Zigang; Kang, Tiebang; Tang, Faqing

    2016-01-01

    Nasopharyngeal carcinoma (NPC) has a high metastatic clinicopathological feature. As a carcinogen factor, N,N′-Dinitrosopiperazine (DNP) is involved in NPC metastasis, but its precise mechanism has not been fully elucidated. Herein, we showed that DNP promotes NPC metastasis through up-regulating anterior clusterin (CLU). DNP was found to increase CLU, matrix metalloproteinases (MMP) 9 and vascular endothelial growth factor (VEGF) expression and activity, further DNP-increased MMP-9 and VEGF expression was through up-regulating CLU. We also found that DNP increased the binding of CLU with MMP-9 or VEGF. DNP induced the motility and invasion of NPC cell, which was inhibited by siRNA-CLU. The clinical investigation showed that CLU, MMP-9 and VEGF were positively correlated with the tumor-node -metastasis (TNM) classification. These results indicate that DNP may promote NPC tumor metastasis through up-regulating CLU, MMP-9 and VEGF expression. Therefore, DNP-increased CLU expression may be an important factor of NPC-high metastasis, and CLU may serve as a biomarker for NPC metastasis. PMID:26716898

  12. Dose-volume factors associated with ear disorders following intensity modulated radiotherapy in nasopharyngeal carcinoma

    PubMed Central

    Yao, Ji-Jin; Zhou, Guan-Qun; Lin, Li; Zhang, Wang-Jian; Peng, Ying-Lin; Chen, Lei; Tang, Ling-Long; Mao, Yan-Ping; Ma, Jun; Sun, Ying

    2015-01-01

    This study is to identify significant dosimetric parameters for ear disorders in nasopharyngeal carcinoma (NPC) patients treated with intensity modulated therapy only. Ninety-seven patients with NPC were retrospectively reviewed. Organs at risk (OARs) in the auditory apparatus were contoured. Dose–volume histogram parameters were generated for the Eustachian tube (ET), tympanic cavity (TC), mastoid air cells, vestibular apparatus, cochlea and internal auditory canal (IAC). Ear disorders were rated 0 (none), 1 (mild) or 2 (severe) by a clinician blinded to radiation doses; Grade 2 ear disorders was the study end-point. Multivariate analysis revealed ET.D30 (dose to 30% of ET volume) >52.75 Gy and M.D0.5CC (dose to 0.5 ml of mastoid volume) >41.04 Gy (OR = 3.77, P = 0.012 and OR = 1.27, P = 0.033, respectively) were associated with Grade 2 ear disorders. Our results demonstrated that post-irradiation ear disorders remain a common late toxicity in NPC after IMRT. ET.D30 and M.D0.5CC should be considered during IMRT treatment plan optimization, review and approval. PMID:26323586

  13. Partial Least Square Discriminant Analysis Discovered a Dietary Pattern Inversely Associated with Nasopharyngeal Carcinoma Risk

    PubMed Central

    Lo, Yen-Li; Pan, Wen-Harn; Hsu, Wan-Lun; Chien, Yin-Chu; Chen, Jen-Yang; Hsu, Mow-Ming; Lou, Pei-Jen; Chen, I-How; Hildesheim, Allan; Chen, Chien-Jen

    2016-01-01

    Evidence on the association between dietary component, dietary pattern and nasopharyngeal carcinoma (NPC) is scarce. A major challenge is the high degree of correlation among dietary constituents. We aimed to identify dietary pattern associated with NPC and to illustrate the dose-response relationship between the identified dietary pattern scores and the risk of NPC. Taking advantage of a matched NPC case–control study, data from a total of 319 incident cases and 319 matched controls were analyzed. Dietary pattern was derived employing partial least square discriminant analysis (PLS-DA) performed on energy-adjusted food frequencies derived from a 66-item food-frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with multiple conditional logistic regression models, linking pattern scores and NPC risk. A high score of the PLS-DA derived pattern was characterized by high intakes of fruits, milk, fresh fish, vegetables, tea, and eggs ordered by loading values. We observed that one unit increase in the scores was associated with a significantly lower risk of NPC (ORadj = 0.73, 95% CI = 0.60–0.88) after controlling for potential confounders. Similar results were observed among Epstein-Barr virus seropositive subjects. An NPC protective diet is indicated with more phytonutrient-rich plant foods (fruits, vegetables), milk, other protein-rich foods (in particular fresh fish and eggs), and tea. This information may be used to design potential dietary regimen for NPC prevention. PMID:27249558

  14. Photodynamic effects on nasopharyngeal carcinoma (NPC) cells with 5-aminolevulinic acid or its hexyl ester.

    PubMed

    Wu, R W K; Chu, E S M; Yow, C M N; Chen, J Y

    2006-10-01

    Nasopharyngeal carcinoma (NPC) is a prevalent cancer in Hong Kong and southern China. To explore a new modality of NPC treatment, 5-aminolevulinic acid (ALA) or its hexyl ester (ALA-H) mediated photodynamic therapy (PDT) was studied in vitro. The results show that NPC cells are sensitive to both ALA and ALA-H mediated PDT. However, ALA-H PDT is much more effective at cell inactivation than ALA-PDT, due to a higher efficiency of ALA-H on producing endogenous protoporphyrin (PpIX) in cells. Both apoptosis and necrosis are involved in cell death, but apoptosis plays a major role under the short time incubation of drugs. ALA and ALA-H mediated PDT not only destroy the cells directly, but also inhibit the expression of matrix metalloproteinase-2 (MMP2) in cells, a maker for tumor metastasis. The ALA-H shows promising PDT results on NPC in vitro; therefore it is worth investigating further in vivo for NPC treatment. PMID:16442708

  15. Replanning Criteria and Timing Definition for Parotid Protection-Based Adaptive Radiation Therapy in Nasopharyngeal Carcinoma

    PubMed Central

    Yao, Wei-Rong; Xu, Shou-Ping; Liu, Bo; Cao, Xiu-Tang; Ren, Gang; Du, Lei; Zhou, Fu-Gen; Feng, Lin-Chun; Qu, Bao-Lin; Xie, Chuan-Bin; Ma, Lin

    2015-01-01

    The goal of this study was to evaluate real-time volumetric and dosimetric changes of the parotid gland so as to determine replanning criteria and timing for parotid protection-based adaptive radiation therapy in nasopharyngeal carcinoma. Fifty NPC patients were treated with helical tomotherapy; volumetric and dosimetric (Dmean, V1, and D50) changes of the parotid gland at the 1st, 6th, 11th, 16th, 21st, 26th, 31st, and 33rd fractions were evaluated. The clinical parameters affecting these changes were studied by analyses of variance methods for repeated measures. Factors influencing the actual parotid dose were analyzed by a multivariate logistic regression model. The cut-off values predicting parotid overdose were developed from receiver operating characteristic curves and judged by combining them with a diagnostic test consistency check. The median absolute value and percentage of parotid volume reduction were 19.51 cm3 and 35%, respectively. The interweekly parotid volume varied significantly (p < 0.05). The parotid Dmean, V1, and D50 increased by 22.13%, 39.42%, and 48.45%, respectively. The actual parotid dose increased by an average of 11.38% at the end of radiation therapy. Initial parotid volume, initial parotid Dmean, and weight loss rate are valuable indicators for parotid protection-based replanning. PMID:26793717

  16. Nuclear magnetic resonance-based study reveals the metabolomics profile of nasopharyngeal carcinoma.

    PubMed

    Wang, Y; Luo, X; Zhang, G H; Li, S L

    2016-01-01

    Proton nuclear magnetic resonance ([(1)H]-NMR) spectroscopy has been used to investigate metabolites in serum and several types of tissue. We used NMR spectroscopy to explore the differential metabolic profiles in serum from nasopharyngeal carcinoma (NPC) patients. Moreover, metabolites with potential as biomarkers for identifying NPC patients were primarily identified. Serum samples were collected from 40 enrolled participants comprising 20 healthy subjects and 20 NPC patients. Samples were analyzed using a 600-MHz NMR spectrometer. The [(1)H]-NMR spectra were further analyzed with partial least squares-discriminant analysis for screening differential metabolites. NMR spectroscopy identified a total of eight metabolites that were present at different levels when the sera of NPC patients were compared with those of healthy individuals. Methionine, taurine (P < 0.05), and choline-like metabolites (P < 0.05) were mostly elevated in the sera of NPC patients. In contrast, the levels of lipids (P < 0.01), isoleucine (P < 0.05), unsaturated lipids (P < 0.01), trimethylamine oxidase (P < 0.05), and carbohydrates (P < 0.05) were lower in the sera of the NPC patients than in the healthy controls. We explored the differential metabolic profiles in sera from NPC patients. [(1)H]-NMR spectroscopy can be used to identify specific metabolites, and is capable of distinguishing between NPC patients and healthy individuals. PMID:27323073

  17. Tumor CTLA-4 overexpression predicts poor survival in patients with nasopharyngeal carcinoma

    PubMed Central

    Lu, Jia-Bin; Chen, Qiu-Yan; Tang, Lin-Quan; Zhang, Lu; Liu, Li-Ting; Zhang, Li; Mai, Hai-Qiang

    2016-01-01

    The expression levels of CTLA-4 and CD28 were analyzed in 191 nasopharyngeal carcinoma (NPC) patients diagnosed and treated at our hospital between January 2010 and November 2011. The 3-year overall survival (OS) rate (91.4% vs. 81.2%,p = 0.043), failure-free survival (FFS) rate (82.8% vs. 68.0%, p = 0.009) and distant failure-free survival (D-FFS) rate (85.8% vs. 72.3%, p = 0.006) in the low tumor CTLA-4 expression group was higher than in the high tumor CTLA-4 group. There were no differences between the locoregional failure-free survival (LR-FFS) rates in the high and low tumor CTLA-4 expression groups. Moreover, no differences in the OS, FFS, D-FFS, or LR-FFS were observed between the groups with high and low lymphocyte CTLA-4 levels, high and low tumor CD28 levels, or high and low lymphocyte CD28 levels. Cox regression analysis confirmed the prognostic value of tumor CTLA-4 expression, particularly for D-FFS, in NPC patients (p = 0.044). NPC patients with high tumor CTLA-4 expression had a poorer prognosis than those with low expression. PMID:26918337

  18. WNT5A promotes stemness characteristics in nasopharyngeal carcinoma cells leading to metastasis and tumorigenesis.

    PubMed

    Qin, Li; Yin, Yan-Tao; Zheng, Fang-Jing; Peng, Li-Xia; Yang, Chang-Fu; Bao, Ying-Na; Liang, Ying-Ying; Li, Xin-Jian; Xiang, Yan-Qun; Sun, Rui; Li, An-Hua; Zou, Ru-Hai; Pei, Xiao-Qing; Huang, Bi-Jun; Kang, Tie-Bang; Liao, Duan-Fang; Zeng, Yi-Xin; Williams, Bart O; Qian, Chao-Nan

    2015-04-30

    Nasopharyngeal carcinoma (NPC) has the highest metastasis rate among head and neck cancers with unclear mechanism. WNT5A belongs to the WNT family of cysteine-rich secreted glycoproteins. Our previous high-throughput gene expression profiling revealed that WNT5A was up-regulated in highly metastatic cells. In the present study, we first confirmed the elevated expression of WNT5A in metastatic NPC tissues at both the mRNA and protein levels. We then found that WNT5A promoted epithelial-mesenchymal transition (EMT) in NPC cells, induced the accumulation of CD24-CD44+ cells and side population, which are believed to be cancer stem cell characteristics. Moreover, WNT5A promoted the migration and invasion of NPC cells in vitro, while in vivo treatment with recombinant WNT5A promoted lung metastasis. Knocking down WNT5A diminished NPC tumorigenesis in vivo. When elevated expression of WNT5A coincided with the elevated expression of vimentin in the primary NPC, the patients had a poorer prognosis. Among major signaling pathways, protein kinase C (PKC) signaling was activated by WNT5A in NPC cells. A positive feedback loop between WNT5A and phospho-PKC to promote EMT was also revealed. Taken together, these data suggest that WNT5A is an important molecule in promoting stem cell characteristics in NPC, leading to tumorigenesis and metastasis. PMID:25823923

  19. Effects of ADAM10 upregulation on progression, migration, and prognosis of nasopharyngeal carcinoma.

    PubMed

    You, Bo; Shan, Ying; Shi, Si; Li, Xingyu; You, Yiwen

    2015-11-01

    A disintegrin and metalloprotease 10 (ADAM10) is a typical member of the ADAMs family, which has been reported to be upregulated in various types of cancers and contribute to cancer progression and metastasis. However, little is known about the role of ADAM10 in nasopharyngeal carcinoma (NPC). The purpose of this study is to explore ADAM10 expression status and its biological functions in NPC. We first examined the expression of ADAM10 in NPC tissues and cell lines by immunohistochemistry, Western blotting, PCR, and immunofluorescence analysis. We observed that ADAM10 was significantly elevated in NPC and its expression level was correlated with T classification (P = 0.044), distant metastasis (P = 0.016), TNM clinical stage (P = 0.013), and proliferation marker Ki-67 expression (P = 0.001). Patients with NPC with high expression of ADAM10 had shorter overall survival rates. In addition, knockdown of ADAM10 by RNAi was found to inhibit the CNE-2 cell proliferation and migration. Our findings hinted that overexpression of ADAM10 promotes the progression and migration of NPC, which makes it a potential therapeutic target for the treatment of tumor metastases in NPC. PMID:26310711

  20. Diet Quality Scores and Risk of Nasopharyngeal Carcinoma in Chinese Adults: A Case-Control Study.

    PubMed

    Wang, Cheng; Lin, Xiao-Ling; Fan, Yu-Ying; Liu, Yuan-Ting; Zhang, Xing-Lan; Lu, Yun-Kai; Xu, Chun-Hua; Chen, Yu-Ming

    2016-03-01

    Many studies show that dietary factors may affect the risk of nasopharyngeal carcinoma (NPC). We examined the association between overall diet quality and NPC risk in a Chinese population. This case-control study included 600 NPC patients and 600 matched controls between 2009 and 2011 in Guangzhou, China. Habitual dietary intake and various covariates were assessed via face-to-face interviews. Diet quality scores were calculated according to the Healthy Eating Index-2005 (HEI-2005), the alternate Healthy Eating Index (aHEI), the Diet Quality Index-International (DQI-I), and the alternate Mediterranean Diet Score (aMed). After adjustment for various lifestyle and dietary factors, greater diet quality scores on the HEI-2005, aHEI, and DQI-I-but not on the aMed-showed a significant association with a lower risk of NPC (p-trends, <0.001-0.001). The odds ratios (95% confidence interval) comparing the extreme quartiles of the three significant scores were 0.47 (0.32-0.68) (HEI-2005), 0.48 (0.33-0.70) (aHEI), and 0.43 (0.30-0.62) (DQI-I). In gender-stratified analyses, the favorable association remained significant in men but not in women. We found that adherence to the predefined dietary patterns represented by the HEI-2005, aHEI, and DQI-I scales predicted a lower risk of NPC in adults from south China, especially in men. PMID:26927167

  1. Trismus, xerostomia and nutrition status in nasopharyngeal carcinoma survivors treated with radiation.

    PubMed

    Chen, Y-J; Chen, S-C; Wang, C-P; Fang, Y-Y; Lee, Y-H; Lou, P-J; Ko, J-Y; Chiang, C-C; Lai, Y-H

    2016-05-01

    The aims of the study were to: (1) examine levels of trismus, xerostomia and nutritional status; (2) compare levels of trismus, xerostomia and nutritional status in patients with nasopharyngeal carcinoma (NPC) receiving different types of radiation modalities; and (3) identify factors related to NPC survivors' risk status for malnutrition and existing malnutrition. A cross-sectional study with consecutive sampling was conducted. NPC survivors were recruited from otolaryngology/oncology outpatient clinics in a medical centre in Northern Taiwan. Study measures included (1) Mandibular Function Impairment Questionnaire, (2) Xerostomia Questionnaire, (3) Mini Nutrition Assessment, (4) Hospital Anxiety and Depression Scale - Depression subscale, and (5) Symptom Severity Scale. A total of 110 subjects were recruited. Those receiving intensity-modulated radiation therapy had less trismus and xerostomia than patients receiving two-dimensional radiation therapy. Patients with female gender, advanced stage, completion of treatments within 1 year, higher levels of depression, more severe trismus and higher symptom severity tended to have malnutrition or were at risk of malnutrition. Trismus and xerostomia are long-term problems in some NPC survivors and may contribute to malnutrition. To better manage a patient's trismus and xerostomia and to enhance nutritional status, clinicians should develop a patient-specific care programme based on careful assessment and targeted measures to improve oral function and insure adequate nutritional intake. PMID:25495287

  2. Epigenetic inactivation of follistatin-like 1 mediates tumor immune evasion in nasopharyngeal carcinoma.

    PubMed

    Zhou, Xiaoying; Xiao, Xue; Huang, Tingting; Du, Chunping; Wang, Shumin; Mo, Yingxi; Ma, Ning; Murata, Mariko; Li, Bo; Wen, Wensheng; Huang, Guangwu; Zeng, Xianjie; Zhang, Zhe

    2016-03-29

    Follistatin like-1 (FSTL1) is a secreted glycoprotein involved in a series of physiological and pathological processes. However, its contribution to the development of cancer, especially the pathogenesis of nasopharyngeal carcinoma (NPC), remains to be elucidated. We aimed to investigate the dysregulation of FSTL1 and its possible function in NPC. FSTL1 was frequently downregulated in NPC cell lines and primary tumor biopsies by promoter hypermethylation. Ectopic expression of FSTL1 significantly suppressed the colony formation, proliferation, migration and invasion ability of NPC cells and induced cell apoptosis. Overexpression of FSTL1 decreased the tumorigenicity of NPC cells in vivo. In addition, the proliferation of NPC cells in vitro was inhibited by treatment with soluble recombinant FSTL1 protein. The protein level of FSTL1 was decreased in primary NPC tumors and was associated with downregulated interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α). Furthermore, recombinant human FSTL1 protein induced secretion of IL-1β and TNF-α in macrophage cultures, therefore FSTL1 might activate macrophages and attenuate the immune evasion of NPC cells. In conclusion, the epigenetic downregulation of FSTL1 may suppress the proliferation and migration of NPC cells, leading to dysfunctional innate responses in surrounding macrophages. PMID:26918942

  3. Integrated pathway analysis of nasopharyngeal carcinoma implicates the axonemal dynein complex in the Malaysian cohort.

    PubMed

    Chin, Yoon-Ming; Tan, Lu Ping; Abdul Aziz, Norazlin; Mushiroda, Taisei; Kubo, Michiaki; Mohd Kornain, Noor Kaslina; Tan, Geok Wee; Khoo, Alan Soo-Beng; Krishnan, Gopala; Pua, Kin-Choo; Yap, Yoke-Yeow; Teo, Soo-Hwang; Lim, Paul Vey-Hong; Nakamura, Yusuke; Lum, Chee Lun; Ng, Ching-Ching

    2016-10-15

    Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma on the mucosal lining of the nasopharynx. The etiology of NPC remains elusive despite many reported studies. Most studies employ a single platform approach, neglecting the cumulative influence of both the genome and transcriptome toward NPC development. We aim to employ an integrated pathway approach to identify dysregulated pathways linked to NPC. Our approach combines imputation NPC GWAS data from a Malaysian cohort as well as published expression data GSE12452 from both NPC and non-NPC nasopharynx tissues. Pathway association for GWAS data was performed using MAGENTA while for expression data, GSA-SNP was used with gene p values derived from differential expression values from GEO2R. Our study identified NPC association in the gene ontology (GO) axonemal dynein complex pathway (pGWAS-GSEA  = 1.98 × 10(-2) ; pExpr-GSEA  = 1.27 × 10(-24) ; pBonf-Combined  = 4.15 × 10(-21) ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (pAmpliSeq-GSEA  = 6.56 × 10(-4) ). Loss of function in the axonemal dynein complex causes impaired cilia function, leading to poor mucociliary clearance and subsequently upper or lower respiratory tract infection, the former of which includes the nasopharynx. Our approach illustrates the potential use of integrated pathway analysis in detecting gene sets involved in the development of NPC in the Malaysian cohort. PMID:27236004

  4. GADD45γ induces G2/M arrest in human pharynx and nasopharyngeal carcinoma cells by cucurbitacin E

    PubMed Central

    Hung, Chao-Ming; Chang, Chi-Chang; Lin, Chen-Wei; Chen, Chih-Chen; Hsu, Yi-Chiang

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is a common form of malignant cancer, for which radiotherapy or chemotherapy are the main treatment methods. Cucurbitacin E (CuE) is a natural compound-based drug which from the climbing stem of Cucumic melo L (Guadi). Previously shown to be an antifeedant as well as a potent chemopreventive agent against several types of cancer. The present study, investigated anti-proliferation and cell cycle G2/M arrest induced by CuE in Detroit 562 cells (pharynx carcinoma) and HONE-1 (nasopharyngeal carcinoma) cells. Results indicate that the cytotoxicity is associated with accumulation in G2/M cell-cycle phases. CuE produced cell cycle arrest as well as the downregulation of cyclin B1 and CDC2 expression. In addition, treated cells with CuE and GADD45γ SiRNA that also coincided with GADD45γ gene activation in cell cycle arrest. Both effects increased proportionally with the dose of CuE; however, proliferation inhibition and mitosis delay was dependant on the amount of CuE treatment in the cancer cells. PMID:25245461

  5. Effect of beam arrangement on oral cavity dose in external beam radiotherapy of nasopharyngeal carcinoma

    SciTech Connect

    Wu, Vincent W.C.; Yang Zhining; Zhang Wuzhe; Wu Lili; Lin Zhixiong

    2012-07-01

    This study compared the oral cavity dose between the routine 7-beam intensity-modulated radiotherapy (IMRT) beam arrangement and 2 other 7-beam IMRT with the conventional radiotherapy beam arrangements in the treatment of nasopharyngeal carcinoma (NPC). Ten NPC patients treated by the 7-beam routine IMRT technique (IMRT-7R) between April 2009 and June 2009 were recruited. Using the same computed tomography data, target information, and dose constraints for all the contoured structures, 2 IMRT plans with alternative beam arrangements (IMRT-7M and IMRT-7P) by avoiding the anterior facial beam and 1 conventional radiotherapy plan (CONRT) were computed using the Pinnacle treatment planning system. Dose-volume histograms were generated for the planning target volumes (PTVs) and oral cavity from which the dose parameters and the conformity index of the PTV were recorded for dosimetric comparisons among the plans with different beam arrangements. The dose distributions to the PTVs were similar among the 3 IMRT beam arrangements, whereas the differences were significant between IMRT-7R and CONRT plans. For the oral cavity dose, the 3 IMRT beam arrangements did not show significant difference. Compared with IMRT-7R, CONRT plan showed a significantly lower mean dose, V30 and V-40, whereas the V-60 was significantly higher. The 2 suggested alternative beam arrangements did not significantly reduce the oral cavity dose. The impact of varying the beam angles in IMRT of NPC did not give noticeable effect on the target and oral cavity. Compared with IMRT, the 2-D conventional radiotherapy irradiated a greater high-dose volume in the oral cavity.

  6. Replanning During Intensity Modulated Radiation Therapy Improved Quality of Life in Patients With Nasopharyngeal Carcinoma

    SciTech Connect

    Yang Haihua; Hu Wei; Wang Wei; Chen Peifang; Ding Weijun; Luo Wei

    2013-01-01

    Purpose: Anatomic and dosimetric changes have been reported during intensity modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the effects of replanning on quality of life (QoL) and clinical outcomes during the course of IMRT for NPC patients. Methods and Materials: Between June 2007 and August 2011, 129 patients with NPC were enrolled. Forty-three patients received IMRT without replanning, while 86 patients received IMRT replanning after computed tomography (CT) images were retaken part way through therapy. Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Head and Neck Quality of Life Questionnaire 35 were completed before treatment began and at the end of treatment and at 1, 3, 6, and 12 months after the completion of treatment. Overall survival (OS) data were compared using the Kaplan-Meier method. Results: IMRT replanning had a profound impact on the QoL of NPC patients, as determined by statistically significant changes in global QoL and other QoL scales. Additionally, the clinical outcome comparison indicates that replanning during IMRT for NPC significantly improved 2-year local regional control (97.2% vs 92.4%, respectively, P=.040) but did not improve 2-year OS (89.8% vs 82.2%, respectively, P=.475). Conclusions: IMRT replanning improves QoL as well as local regional control in patients with NPC. Future research is needed to determine the criteria for replanning for NPC patients undergoing IMRT.

  7. Prognostic Value of Prevertebral Space Involvement in Nasopharyngeal Carcinoma Based on Intensity-Modulated Radiotherapy

    SciTech Connect

    Zhou Guanqun; Mao YanPing; Chen Lei; Li Wenfei; Liu Lizhi; Sun Ying; Chen Yong; Tian Li; Lin Aihua; Li Li; and others

    2012-03-01

    Purpose: To investigate the prognostic significance of prevertebral space involvement (PSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: A retrospective review of data from 506 biopsy-proven, nonmetastatic NPCs was performed. Patients underwent magnetic resonance imaging examinations and received IMRT as their primary treatment. Results: In this series, 161 NPC patients (31.8%) had PSI. Parapharyngeal space (p < 0.001), skull base (p < 0.001), and paranasal sinuses (p = 0.009) were associated with PSI after multivariate analysis. The 4-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis-free survival (DMFS) for NPC patients with and without PSI was 69.1% and 89.2% (p < 0.0001), 83.9% and 96.4% (p < 0.0001), and 71.6% and 89.6% (p < 0.0001), respectively. Multivariate analysis identified PSI as an independent negative prognostic factor for both OS (HR = 1.478-4.380; p = 0.001) and DMFS (HR = 1.389-4.174; p = 0.002). Patients with PSI had similar survival rates in OS and DMFS (p = 0.241 and p = 0.493, respectively) to that of T4 disease, while the differences between PSI and T3 disease in both OS and DMFS were distinctly significant (p = 0.029 and p = 0.029, respectively). Conclusions: For NPC patients treated with IMRT, PSI was found to be an independent prognostic factor for both OS and DMFS. It seems reasonable that PSI should be classified as a T4 disease on the basis of the current American Joint Committee on Cancer staging classification criteria.

  8. Primary tumor inflammation in gross tumor volume as a prognostic factor for nasopharyngeal carcinoma patients

    PubMed Central

    Peng, Hao; Chen, Lei; Tang, Ling-Long; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    Purpose The objective of this study is to investigate the prognostic value of primary tumor inflammation (PTI) in nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiation therapy (IMRT). Results PTI was observed in 376/1708 (22.0%) patients, and was present in the sphenoid sinus in 289/376 (76.9%), in the nasal cavity in 27 (7.2%), and in both places in 60 (15.9%). The estimated 4-year local relapse-free survival (LRFS), disease-free survival (DFS), overall survival (OS) and distant metastasis-free survival (DMFS) rates for PTI vs. non-PTI group were 89.2% vs. 96.1% (P < 0.001), 73.4% vs. 85.1% (P < 0.001), 85.0% vs. 92.1% (P < 0.001) and 83.6% vs. 91.4% (P < 0.001), respectively. After adjustment for these known prognostic factors, PTI was confirmed as an independent prognostic factor for LRFS (HR 2.152, 95% CI 1.318–3.516, P = 0.002), DFS (HR 1.581, 95% CI 1.204–2.077, P = 0.001) and DMFS (HR 1.682, 95% CI 1.177–2.402, P = 0.004). Conclusions Primary tumor inflammation was identified as a strong prognostic factor for patients with NPC in the era of IMRT and should be considered when devising future treatment strategies aimed at improving survival in NPC patients. Materials and Methods Data on 1708 patients with nonmetastatic, histologically-confirmed NPC treated with IMRT between November 2009 and February 2012 at Sun Yat-Sen University Cancer Center were retrospectively reviewed. Patient survival between PTI and non-PTI groups were compared. PMID:26934649

  9. Picropodophyllin inhibits tumor growth of human nasopharyngeal carcinoma in a mouse model

    SciTech Connect

    Yin, Shu-Cheng; Guo, Wei; Tao, Ze-Zhang

    2013-09-13

    Highlights: •We identified that PPP inhibits IGF-1R/Akt pathway in NPC cells. •PPP dose-dependently inhibits NPC cell proliferation in vitro. •PPP suppresses tumor growth of NPC in nude mice. •PPP have little effect on microtubule assembly. -- Abstract: Insulin-like growth factor-1 receptor (IGF-1R) is a cell membrane receptor with tyrosine kinase activity and plays important roles in cell transformation, tumor growth, tumor invasion, and metastasis. Picropodophyllin (PPP) is a selective IGF-1R inhibitor and shows promising antitumor effects for several human cancers. However, its antitumor effects in nasopharyngeal carcinoma (NPC) remain unclear. The purpose of this study is to investigate the antitumor activity of PPP in NPC using in vitro cell culture and in vivo animal model. We found that PPP dose-dependently decreased the IGF-induced phosphorylation and activity of IGF-1R and consequently reduced the phosphorylation of Akt, one downstream target of IGF-1R. In addition, PPP inhibited NPC cell proliferation in vitro. The half maximal inhibitory concentration (IC50) of PPP for NPC cell line CNE-2 was ⩽1 μM at 24 h after treatment and ⩽0.5 μM at 48 h after treatment, respectively. Moreover, administration of PPP by intraperitoneal injection significantly suppressed the tumor growth of xenografted NPC in nude mice. Taken together, these results suggest targeting IGF-1R by PPP may represent a new strategy for treatment of NPCs with positive IGF-1R expression.

  10. Proteomics analysis of nasopharyngeal carcinoma cell secretome using a hollow fiber culture system and mass spectrometry.

    PubMed

    Wu, Hsin-Yi; Chang, Ying-Hwa; Chang, Yu-Chen; Liao, Pao-Chi

    2009-01-01

    Secreted proteins, referred to as the secretome, are known to regulate a variety of biological functions and are involved in a multitude of pathological processes. However, some secreted proteins from cell cultures are difficult to detect because of their intrinsic low abundance. They are frequently masked by proteins shed from lysed cells and the substantial amounts of serum proteins used in culture medium. We have proposed an analytical platform for sensitive detection of secreted proteins by utilizing a hollow fiber culture (HFC) system coupled with proteomic approaches. The HFC system enables culture of high-density cells in a small volume where secreted proteins can be accumulated. In addition, cell lysis rates can be greatly reduced, which alleviates the contamination from lysed cells. In this study, nasopharyngeal carcinoma (NPC) cells were utilized to evaluate the efficiency of this system in the collection and analysis of the cell secretome. Cells were adapted to serum-free medium and inoculated into the HFC system. The cell lysis rate in the culture system was estimated to be 0.001-0.022%, as determined by probing four intracellular proteins in the conditioned medium (CM), while a cell lysis rate of 0.32-1.84% was observed in dish cultures. Proteins in the CM were analyzed using SDS-PAGE and liquid chromatography tandem mass spectrometry (LC-MS/MS). A total of 134 proteins were identified in 62 gel bands, of which 61% possess a signal peptide and/or a transmembrane domain. In addition, 37% of the identified secretome were classified as extracellular or membrane proteins, whereas 98% of the lysate proteins were identified as intracellular proteins. We suggest that the HFC system may be used to collect secreted proteins efficiently and facilitate comprehensive characterization of cell secretome. PMID:19012429

  11. Hypofractionated Dose-Painting Intensity Modulated Radiation Therapy With Chemotherapy for Nasopharyngeal Carcinoma: A Prospective Trial

    SciTech Connect

    Bakst, Richard L.; Lee, Nancy; Pfister, David G.; Zelefsky, Michael J.; Hunt, Margie A.; Kraus, Dennis H.; Wolden, Suzanne L.

    2011-05-01

    Purpose: To evaluate the feasibility of dose-painting intensity-modulated radiation therapy (DP-IMRT) with a hypofractionated regimen to treat nasopharyngeal carcinoma (NPC) with concomitant toxicity reduction. Methods and Materials: From October 2002 through April 2007, 25 newly diagnosed NPC patients were enrolled in a prospective trial. DP-IMRT was prescribed to deliver 70.2 Gy using 2.34-Gy fractions to the gross tumor volume for the primary and nodal sites while simultaneously delivering 54 Gy in 1.8-Gy fractions to regions at risk of microscopic disease. Patients received concurrent and adjuvant platin-based chemotherapy similar to the Intergroup 0099 trial. Results: Patient and disease characteristics are as follows: median age, 46; 44% Asian; 68% male; 76% World Health Organization III; 20% T1, 52% T2, 16% T3, 12% T4; 20% N0, 36% N1, 36% N2, 8% N3. With median follow-up of 33 months, 3-year local control was 91%, regional control was 91%, freedom from distant metastases was 91%, and overall survival was 89%. The average mean dose to each cochlea was 43 Gy. With median audiogram follow-up of 14 months, only one patient had clinically significant (Grade 3) hearing loss. Twelve percent of patients developed temporal lobe necrosis; one patient required surgical resection. Conclusions: Preliminary findings using a hypofractionated DP-IMRT regimen demonstrated that local control, freedom from distant metastases, and overall survival compared favorably with other series of IMRT and chemotherapy. The highly conformal boost to the tumor bed resulted low rates of severe ototoxicity (Grade 3-4). However, the incidence of in-field brain radiation necrosis indicates that 2.34 Gy per fraction is not safe in this setting.

  12. Protein N-arginine methyltransferase 5 promotes the tumor progression and radioresistance of nasopharyngeal carcinoma.

    PubMed

    Yang, Daoke; Liang, Tiansong; Gu, Yue; Zhao, Yulin; Shi, Yonggang; Zuo, Xiaoxiao; Cao, Qinchen; Yang, Ya; Kan, Quancheng

    2016-03-01

    Radiotherapy resistance is the main cause of the the poor prognosis of some nasopharyngeal carcinoma (NPC) patients. Yet, the exact mechanism is still elusive. In the present study, we explored the clinical and biological role of protein arginine methyltransferase 5 (PRMT5) in NPC. Our results revealed that PRMT5 was overexpressed in NPC tissues when compared with that in adjacent non-tumor tissues by quantitative RT-PCR and immunoblotting. High expression of PRMT5 was correlated with adverse outcomes of NPC patients as determined by the scoring of a tissue microarray. Silencing of PRMT5 promoted the radiosensitivity of 5-8F and CNE2 cells as determined by cell proliferation and colony formation assays. Furthermore, fibroblast growth factor receptor 3 (FGFR3) was identified as one of the downstream targets of PRMT5, and the silencing of PRMT5 decreased the mRNA and protein levels of FGFR3 in the 5-8F and CNE2 cells. Silencing of FGFR3 induced similar phenotypes as the inhibition of PRMT5, and re-expression of FGFR3 in 5-8F/shPRMT5 and CNE2/shPRMT5 cells restored the proliferation and colony formation ability induced by irradiation exposure. Our results indicate that PRMT5 is a marker of poor prognosis in NPC patients. PRMT5 promoted the radioresistance of NPC cells via targeting FGFR3, at least partly if not totally. PRMT5 and its downstream effector FGFR3 may be potential targets for anticancer strategy. PMID:26708443

  13. Excellent Local Control With Stereotactic Radiotherapy Boost After External Beam Radiotherapy in Patients With Nasopharyngeal Carcinoma

    SciTech Connect

    Hara, Wendy; Loo, Billy W.; Goffinet, Don R.; Chang, Steven D.; Adler, John R.; Pinto, Harlan A.; Fee, Willard E.; Kaplan, Michael J.; Fischbein, Nancy J.; Le, Quynh-Thu

    2008-06-01

    Purpose: To determine long-term outcomes in patients receiving stereotactic radiotherapy (SRT) as a boost after external beam radiotherapy (EBRT) for locally advanced nasopharyngeal carcinoma (NPC). Methods and Materials: Eight-two patients received an SRT boost after EBRT between September 1992 and July 2006. Nine patients had T1, 30 had T2, 12 had T3, and 31 had T4 tumors. Sixteen patients had Stage II, 19 had Stage III, and 47 had Stage IV disease. Patients received 66 Gy of EBRT followed by a single-fraction SRT boost of 7-15 Gy, delivered 2-6 weeks after EBRT. Seventy patients also received cisplatin-based chemotherapy delivered concurrently with and adjuvant to radiotherapy. Results: At a median follow-up of 40.7 months (range, 6.5-144.2 months) for living patients, there was only 1 local failure in a patient with a T4 tumor. At 5 years, the freedom from local relapse rate was 98%, freedom from nodal relapse 83%, freedom from distant metastasis 68%, freedom from any relapse 67%, and overall survival 69%. Late toxicity included radiation-related retinopathy in 3, carotid aneurysm in 1, and radiographic temporal lobe necrosis in 10 patients, of whom 2 patients were symptomatic with seizures. Of 10 patients with temporal lobe necrosis, 9 had T4 tumors. Conclusion: Stereotactic radiotherapy boost after EBRT provides excellent local control for patients with NPC. Improved target delineation and dose homogeneity of radiation delivery for both EBRT and SRT is important to avoid long-term complications. Better systemic therapies for distant control are needed.

  14. Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma.

    PubMed

    Fåhraeus, R; Fu, H L; Ernberg, I; Finke, J; Rowe, M; Klein, G; Falk, K; Nilsson, E; Yadav, M; Busson, P

    1988-09-15

    Expression of the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNA 1 to 6) and membrane-associated protein (LMP) was investigated by immunoblotting in 83 nasopharyngeal carcinoma (NPC) biopsies and 25 other tumor and normal tissue specimens from the head and neck region. Fifty-eight of the 83 NPC biopsies were large enough to yield parallel data on virus DNA and viral expression. All 16 cases of clinically diagnosed and histologically confirmed NPCs from North Africa contained EBV DNA and expressed EBNA-1. Of 31 clinically diagnosed NPCs from China, 29 contained EBV DNA and 25 of these expressed EBNA-1. One control tissue biopsy from the oropharynx of NPC patients contained EBV DNA, but none expressed EBNA-1. The latent membrane protein (LMP) was detected in 22/31 of the Chinese and in 10/16 of the North African NPC biopsies. None of the NPC biopsies or control tissues expressed detectable amounts of EBNA 2 or any of the other 4 nuclear antigens which are invariably expressed in EBV-transformed B cells. A smaller number of tumors from Malaysia and East Africa exhibited a similar pattern of expression. EBV was rescued from a nude-mouse-passaged North African NPC tumor by co-cultivation of the tumor cells with umbilical cord blood lymphocytes. The tumor expressed EBNA 1 and LMP, but not EBNA 2 or the other 4 EBNAs. The resulting LCLs expressed all 6 nuclear antigens, EBNA 1 to 6 and LMP. Our data suggest that expression of the EBV genome is regulated in a tissue-specific fashion. PMID:2843473

  15. Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

    PubMed Central

    Dai, Wei; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Cheng, Yue; Zheng, Hong; Ngan, Roger Kai Cheong; Ng, Wai Tong; Lee, Anne Wing Mui; Yau, Chun Chung; Lee, Victor Ho Fu; Lung, Maria Li

    2015-01-01

    Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10−9), but was less obvious in other types of solid tumors except for prostate and Epstein–Barr virus (EBV)-positive gastric cancer (FDR<10−3). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection. PMID:25924914

  16. Radiation-induced functional connectivity alterations in nasopharyngeal carcinoma patients with radiotherapy.

    PubMed

    Ma, Qiongmin; Wu, Donglin; Zeng, Ling-Li; Shen, Hui; Hu, Dewen; Qiu, Shijun

    2016-07-01

    The study aims to investigate the radiation-induced brain functional alterations in nasopharyngeal carcinoma (NPC) patients who received radiotherapy (RT) using functional magnetic resonance imaging (fMRI) and statistic scale.The fMRI data of 35 NPC patients with RT and 24 demographically matched untreated NPC patients were acquired. Montreal Cognitive Assessment (MoCA) was also measured to evaluate their global cognition performance. Multivariate pattern analysis was performed to find the significantly altered functional connections between these 2 groups, while the linear correlation level was detected between the altered functional connections and the MoCA scores.Forty-five notably altered functional connections were found, which were mainly located between 3 brain networks, the cerebellum, sensorimotor, and cingulo-opercular. With strictly false discovery rate correction, 5 altered functional connections were shown to have significant linear correlations with the MoCA scores, that is, the connections between the vermis and hippocampus, cerebellum lobule VI and dorsolateral prefrontal cortex, precuneus and dorsal frontal cortex, cuneus and middle occipital lobe, and insula and cuneus. Besides, the connectivity between the vermis and hippocampus was also significantly correlated with the attention score, 1 of the 7 subscores of the MoCA.The present study provides new insights into the radiation-induced functional connectivity impairments in NPC patients. The results showed that the RT may induce the cognitive impairments, especially the attention alterations. The 45 altered functional connections, especially the 5 altered functional connections that were significantly correlated to the MoCA scores, may serve as the potential biomarkers of the RT-induced brain functional impairments and provide valuable targets for further functional recovery treatment. PMID:27442663

  17. Identification of a functional variant in SPLUNC1 associated with nasopharyngeal carcinoma susceptibility among Malaysian Chinese.

    PubMed

    Yew, Poh-Yin; Mushiroda, Taisei; Kiyotani, Kazuma; Govindasamy, Gopala Krishnan; Yap, Lee-Fah; Teo, Soo-Hwang; Lim, Paul Vey-Hong; Govindaraju, Selvaratnam; Ratnavelu, Kananathan; Sam, Choon-Kook; Yap, Yoke-Yeow; Khoo, Alan Soo-Beng; Pua, Kin-Choo; Nakamura, Yusuke; Ng, Ching-Ching

    2012-10-01

    Nasopharyngeal carcinoma (NPC) is a multifactorial and polygenic disease with high incidence in Asian countries. Epstein-Barr virus infection, environmental and genetic factors are believed to be involved in the tumorigenesis of NPC. The association of single nucleotide polymorphisms (SNPs) in LPLUNC1 and SPLUNC1 genes with NPC was investigated by performing a two-stage case control association study in a Malaysian Chinese population. The initial screening consisted of 81 NPC patients and 147 healthy controls while the replication study consisted of 366 NPC patients and 340 healthy controls. The combined analysis showed that a SNP (rs2752903) of SPLUNC1 was significantly associated with the risk of NPC (combined P = 0.00032, odds ratio = 1.62, 95% confidence interval = 1.25-2.11). In the subsequent dense fine mapping of SPLUNC1 locus, 36 SNPs in strong linkage disequilibrium with rs2752903 (r(2) ≥ 0.85) were associated with NPC susceptibility. Screening of these variants by electrophoretic mobility shift and luciferase reporter assays showed that rs1407019 located in intron 3 (r(2)  = 0.994 with rs2752903) caused allelic difference in the binding of specificity protein 1 (Sp1) transcription factor and affected luciferase activity. This SNP may consequently alter the expression of SPLUNC1 in the epithelial cells. In summary, our study suggested that rs1407019 in intronic enhancer of SPLUNC1 is associated with NPC susceptibility in which its A allele confers an increased risk of NPC in the Malaysian Chinese population. PMID:22213098

  18. Upregulation of metastasis-associated gene 2 promotes cell proliferation and invasion in nasopharyngeal carcinoma

    PubMed Central

    Wu, Minhua; Ye, Xiaoxia; Deng, Xubin; Wu, Yanxia; Li, Xiaofang; Zhang, Lin

    2016-01-01

    Aims Metastasis-associated gene 2 (MTA2) is reported to play an important role in tumor progression, but little is known about the role of MTA2 in nasopharyngeal carcinoma (NPC). The aim of the study was to explore the expression and function of MTA2 in NPC. Methods Expression of MTA2 in NPC tissues and cell lines was detected by immunohistochemistry and Western blotting. Relationship between MTA2 expression and clinicopathological features was analyzed. Stable MTA2-overexpressing and MTA2-siliencing NPC cells were established by transfection with plasmids encoding MTA2 cDNA and lentivirus-mediated short hairpin RNA, respectively. Cell viability was determined by Cell Counting Kit-8 and colony formation assay. Cell migration ability was evaluated by wound healing and transwell invasion assay. The impact of MTA2 knockdown on growth and metastasis of CNE2 cells in vivo was determined by nude mouse xenograft models. Expression of several Akt pathway proteins was detected by Western blotting. Results MTA2 was upregulated in NPC tissues and three NPC cell lines detected (CNE1, CNE2, and HNE1). MTA2 expression was related to clinical stage and lymph node metastasis of patients with NPC. MTA2 upregulation promoted proliferation and invasion of CNE1 cells, while MTA2 depletion had opposite effects on CNE2 cells. Moreover, MTA2 depletion suppressed growth and metastasis of CNE2 cells in vivo. MTA2 overexpression activated Akt and upregulated the expression of matrix metalloproteinase 7 and cyclin D1. Conclusion We conclude that MTA2 acts as an oncogene in tumorigenesis of NPC. MTA2 may be a potential target for gene therapy in NPC. PMID:27051300

  19. Deuterium-depleted water (DDW) inhibits the proliferation and migration of nasopharyngeal carcinoma cells in vitro.

    PubMed

    Wang, Hongqiang; Zhu, Baohua; He, Zhiwei; Fu, Hui; Dai, Zhong; Huang, Guoliang; Li, Binbin; Qin, Dongyun; Zhang, Xiaoyan; Tian, Lu; Fang, Weiyi; Yang, Huiling

    2013-07-01

    Recent studies have demonstrated that natural water that has 65% of the deuterium concentration depleted, can exhibit anti-tumor properties. However, the anti-tumor effects of DDW on various nasopharyngeal carcinoma (NPC) cells have not previously been reported. In the present study, NPC cell lines and normal preosteoblast MC3T3-E1 cells were grown in RPMI1640 media containing different deuterium concentrations (50-150 ppm). The effects of DDW on the proliferation and migration of NPC and MC3T3-E1 cells were investigated using the MTT, plate colony formation, and Transwell assays, as well as Boyden chamber arrays, flow cytometry (FCM), western blot and immunofluorescence. We found that DDW was an effective inhibitor of NPC cell proliferation, plated colony formation, migration and invasion. In contrast, the growth of normal preosteoblast MC3T3-E1 cells was promoted when they were cultured in the presence of DDW. Cell cycle analysis revealed that DDW caused cell cycle arrest in the G1/S transition, reduced the number of cells in the S phase and significantly increased the population of cells in the G1 phase in NPC cells. Western blot analysis revealed that treatment with DDW significantly increased the expression of NADPH:quinone oxidoreductase-1 (NQO1), while immunofluorescence assay analysis revealed that treatment with DDW decreased the expression of PCNA and matrix metalloproteinase 9 (MMP9) in NPC cells. These results demonstrated that DDW is a novel, non-toxic adjuvant therapeutic agent that suppresses NPC cell proliferation, migration, and invasion by inducing the expression of NQO1 and causing cell cycle arrest, as well as decreasing PCNA and MMP9 expression. PMID:23773852

  20. Intensity-Modulated Radiation Therapy in the Salvage of Locally Recurrent Nasopharyngeal Carcinoma

    SciTech Connect

    Qiu Sufang; Lin Shaojun; Tham, Ivan W.K.; Pan Jianji; Lu Jun; Lu, Jiade J.

    2012-06-01

    Purpose: Local recurrences of nasopharyngeal carcinoma (NPC) may be salvaged by reirradiation with conventional techniques, but with significant morbidity. Intensity-modulated radiation therapy (IMRT) may improve the therapeutic ratio by reducing doses to normal tissue. The aim of this study was to address the efficacy and toxicity profile of IMRT for a cohort of patients with locally recurrent NPC. Methods and Materials: Between August 2003 and June 2009, 70 patients with radiologic or pathologically proven locally recurrent NPC were treated with IMRT. The median time to recurrence was 30 months after the completion of conventional radiation to definitive dose. Fifty-seven percent of the tumors were classified asrT3-4. The minimum planned doses were 59.4 to 60 Gy in 1.8- to 2-Gy fractions per day to the gross disease with margins, with or without chemotherapy. Results: The median dose to the recurrent tumor was 70 Gy (range, 50-77.4 Gy). Sixty-five patients received the planned radiation therapy; 5 patients received between 50 and 60 Gy because of acute side effects. With a median follow-up time of 25 months, the rates of 2-year locoregional recurrence-free survival, disease-free survival, and overall survival were 65.8%, 65.8%, and 67.4%, respectively. Moderate to severe late toxicities were noted in 25 patients (35.7%). Eleven patients (15.7%) had posterior nasal space ulceration, 17 (24.3%) experienced cranial nerve palsies, 12 (17.1%) had trismus, and 12 (17.1%) experienced deafness. Extended disease-free interval (relative risk 2.049) and advanced T classification (relative risk 3.895) at presentation were adverse prognostic factors. Conclusion: Reirradiation with IMRT provides reasonable long-term control in patients with locally recurrent NPC.

  1. Pharmacokinetic and pharmacodynamic studies with 4'-epi-doxorubicin in nasopharyngeal carcinoma patients.

    PubMed

    Hu, O Y; Chang, S P; Jame, J M; Chen, K Y

    1989-01-01

    The plasma pharmacokinetic profile of 4'-epidoxorubicin (epirubicin) was investigated in 28 patients with nasopharyngeal carcinoma (NPC) after single i.v. rapid infusions. All patients had normal liver and renal functions. Plasma concentrations of the parent compound were specifically determined by a high-performance liquid chromatographic (HPLC) method, with UV detection at 254 nm. Plasma levels of the compound were fitted to a three-compartment open model; a triexponential decrease in plasma concentrations with a long terminal plasma half-life (44.8 +/- 21.2 h) was observed in 27 patients. The respective mean (+/- SD) serum concentration at 72 h and the AUC, plasma clearance, and terminal elimination rate constant in complete responders were 7.67 +/- 1.98 ng/ml, 4,002 +/- 3,080 ng.h/ml, 26.6 +/- 12.9 l/h.m2, and 0.009 +/- 0.007 l/h, whereas those in nonresponders were 4.96 +/- 1.8 ng/ml, 1.88 +/- 652.8 ng.h/ml, 44.4 +/- 15 l/h.m2, and 0.017 +/- 0.006 l/h, respectively; these differences were significant (P less than 0.05). Epirubicin produced a 52% response rate, including 6 patients with a complete response, 8 with a partial response, 11 with no change, and 2 with progressive disease. No relationship could be found between the various pharmacokinetic parameters and either leukopenia, age, or sex. These observations strongly suggest that plasma clearance may be one of the determining factors affecting the response or nonresponse of NPC patients to epirubicin, and a dose adjustment according to plasma clearance would probably increase the response rate. PMID:2758564

  2. Prognostic value of wait time in nasopharyngeal carcinoma treated with intensity modulated radiotherapy: a propensitymatched analysis

    PubMed Central

    Chen, Lei; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Zhou, Guan-Qun; Guo, Rui; Sun, Ying; Kang, Tie-Bang; Zeng, Mu-Sheng; Ma, Jun

    2016-01-01

    The aim of this study was to determine the prognostic value of wait time from histological diagnosis to primary treatmen for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Between October 2009 and February 2012, a total of 1672 NPC patients were retrospectively analyzed. A cutoff value of > 4 weeks was used to define prolonged wait time. Matched patients according to the wait time were identified using propensity score matching (PSM), which was also used to identify matched patients for subsequent stratified analyses. Differences in progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) were estimated using the Kaplan–Meier method and Cox proportional hazards models. In total, 407 pairs of NPC patients were selected by PSM. The 3-year PFS rate was significantly lower for patients with a prolonged wait time (> 4 weeks) than for those with an acceptable wait time (P = 0.035). Stratified analyses revealed that the negative effects of a prolonged wait time occurred primarily in patients with advanced NPC without neoadjuvant chemotherapy (NACT; PFS:P = 0.040; DMFS:P = 0.028). In multivariate analysis, a prolonged wait time was found to be an independent unfavorable prognostic factor for PFS and DMFS in advanced-staged patients without NACT. These results suggest that a prolonged time (> 4 weeks) between diagnosis and primary radical radiotherapy is a disadvantage for NPC patients, particularly those with advanced disease receiving no NACT. Thus, it is necessary to optimize resources for decreasing this wait time, although additional studies are warranted to further clarify our findings. PMID:26942870

  3. Radiation-induced brachial plexopathy in patients with nasopharyngeal carcinoma: a retrospective study

    PubMed Central

    Fu, Ruying; Rong, Xiaoming; Wu, Rong; Cheng, Jinping; Huang, Xiaolong; Luo, Jinjun; Tang, Yamei

    2016-01-01

    Radiation-induced brachial plexopathy (RIBP) is one of the late complications in nasopharyngeal carcinoma (NPC) patients who received radiotherapy. We conducted a retrospective study to investigate its clinical characteristics and risk factors. Thirty-onepatients with RIBP after radiotherapy for NPC were enrolled. Clinical manifestations of RIBP, electrophysiologic data, magnetic resonance imaging (MRI), and the correlation between irradiation strategy and incidence of RIBP were evaluated. The mean latency at the onset of RIBP was 4.26 years. Of the symptoms, paraesthesia usually presented first (51.6%), followed by pain (22.6%) and weakness (22.6%). The major symptoms included paraesthesia (90.3%), pain (54.8%), weakness (48.4%), fasciculation (19.3%) and muscle atrophy (9.7%). Nerve conduction velocity (NCV) and electromyography (EMG) disclosed that pathological changes of brachial plexus involved predominantly in the upper and middle trunks in distribution. MRI of the brachial plexus showed hyper-intensity on T1, T2, post-contrast T1 and diffusion weighted whole body imaging with background body signal suppression (DWIBS) images in lower cervical nerves. Radiotherapy with Gross Tumor volume (GTVnd) and therapeutic dose (mean 66.8±2.8Gy) for patients with lower cervical lymph node metastasis was related to a significantly higher incidence of RIBP (P<0.001). Thus, RIBP is a severe and progressive complication of NPC after radiotherapy. The clinical symptoms are predominantly involved in upper and middle trunk of the brachial plexus in distribution. Lower cervical lymph node metastasis and corresponding radiotherapy might cause a significant increase of the RIBP incidence. PMID:26934119

  4. Grape seed proanthocyanidins induce apoptosis through the mitochondrial pathway in nasopharyngeal carcinoma CNE-2 cells.

    PubMed

    Yao, Kai; Shao, Jingjing; Zhou, Keyuan; Qiu, Haitao; Cao, Fengxiang; Li, Caihong; Dai, De

    2016-08-01

    Although modern radiotherapy offers excellent local control in the treatment of nasopharyngeal carcinoma (NPC), current therapeutic decisions remain burdensome due to the frequency of local recurrence and treatment failure at distant sites. One potential and promising strategy for the prevention or treatment of cancers is the use of bioactive components of plant origin, including dietary plant products. Herein, we studied one class of these bioactive compounds, grape seed proanthocyanidins (GSPs), and explored their effect on NPC CNE-2 cells, as well as the primary mechanism underlying this effect. Our results revealed that treatment of human NPC CNE-2 cells with GSPs reduced cell viability in a dose- and time-dependent manner, and moreover, markedly induced cell cycle arrest at the G2/M phase, leading to induction of apoptosis. In addition, we found that the underlying mechanism was associated with increased expression of the pro-apoptotic protein Bax, decreased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, upregulation of cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PRAP) protein, and the loss of mitochondrial membrane potential (MMP) (Δψm). Furthermore, GSPs upregulated the Bcl-2 homology 3 (BH3)-only proteins, Bim and Bad, in a concentration-dependent manner. Taken together, these data supported our hypothesis that, in human NPC CNE-2 cells, GSPs could induce apoptosis through the mitochondrial pathway and ultimately reduce cell viability. Collectively, the results discussed above provide substantive evidence for the potential of GSPs as an effective bioactive phytochemical for the treatment of NPC. PMID:27277418

  5. Transient overexpression of TGFBR3 induces apoptosis in human nasopharyngeal carcinoma CNE-2Z cells

    PubMed Central

    Zheng, Fangfang; He, Kaiwen; Li, Xin; Zhao, Dan; Sun, Fei; Zhang, Yu; Nie, Dan; Li, Xingda; Chu, Wenfeng; Sun, Yan; Lu, Yanjie

    2013-01-01

    NPC (nasopharyngeal carcinoma) is a common malignancy in southern China without defined aetiology. Recent studies have shown that TGFBR3 (transforming growth factor type III receptor, also known as betaglycan), exhibits anticancer activities. This study was to investigate the effects of TGFBR3 on NPC growth and the mechanisms for its actions. Effects of TGFBR3 overexpression on cell viability and apoptosis were measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide], AO/EB (acridine orange/ethidium bromide) staining and electron microscopy in human NPC CNE-2Z cells. The expression of apoptosis-related proteins, p-Bad, Bad, XIAP (X-linked inhibitor of apoptosis), AIF (apoptosis-inducing factor), Bax and Bcl-2, was determined by Western blot or immunofluorescence analysis. Caspase 3 activity was measured by caspase 3 activity kit and [Ca2+]i (intracellular Ca2+ concentration) was detected by confocal microscopy. Transfection of TGFBR3 containing plasmid DNA at concentrations of 0.5 and 1 μg/ml reduced viability and induced apoptosis in CNE-2Z in concentration- and time-dependent manners. Forced expression of TGFBR3 up-regulated pro-apoptotic Bad and Bax protein, and down-regulated anti-apoptotic p-Bad, Bcl-2 and XIAP protein. Furthermore, transient overexpression of TGFBR3 also enhanced caspase 3 activity, increased [Ca2+]i and facilitated AIF redistribution from the mitochondria to the nucleus in CNE-2Z cells, which is independent of the caspase 3 pathway. These events were associated with TGFBR3-regulated multiple targets involved in CNE-2Z proliferation. Therefore transient overexpression of TGFBR3 may be a novel strategy for NPC prevention and therapy. PMID:23387308

  6. Incidence of and Risk Factors for Mastoiditis after Intensity Modulated Radiotherapy in Nasopharyngeal Carcinoma

    PubMed Central

    Yu, Xiao-Li; Tang, Ling-Long; Chen, Lei; Mao, Yan-Ping; Lin, Li; Zhang, Lu-Lu; Shao, Jian-Yong; Guo, Ying; Ma, Jun; Sun, Ying

    2015-01-01

    Purpose To report the incidence of and risk factors for mastoiditis after intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). Patients and Methods Retrospective analysis of pretreatment and follow-up magnetic resonance imaging (MRI) data for 451 patients with NPC treated with IMRT at a single institution. The diagnosis of mastoiditis was based on MRI; otomastoid opacification was rated as Grade 0 (none), 1 (mild), 2 (moderate) or 3 (severe) by radiologists blinded to clinical outcome. This study mainly focused on severe mastoiditis; patients were divided into three groups: the G0M (Grade 0 mastoiditis before treatment) group, G1-2M (Grade 1 to 2 mastoiditis before treatment) group and G3M (Grade 3 mastoiditis before treatment) group. The software SAS9.3 program was used to analyze the data. Results For the entire cohort, the incidence of Grade 3 mastoiditis was 20% before treatment and 31%, 19% and 17% at 3, 12 and 24 months after radiotherapy, respectively. In the G0M group, the incidence of severe mastoiditis was 0% before treatment and 23%, 15% and 13% at 3, 12 and 24 months after radiotherapy, respectively. Multivariate analysis revealed T category (OR=0.68, 95% CI = 0.469 to 0.984), time (OR=0.668, 95% CI = 0.59 to 0.757) and chemotherapy (OR=0.598, 95% CI = 0.343 to 0.934) were independent factors associated with severe mastoiditis in the G0M group after treatment. Conclusions Mastoiditis, as diagnosed by MRI, occurs as a progressive process that regresses and resolves over time in patients with NPC treated using IMRT. PMID:26114761

  7. Clinical Outcome and Prognostic Factors of Intensity-Modulated Radiotherapy for T4 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Luo, Yangkun; Gao, Yang; Yang, Guangquan; Lang, Jinyi

    2016-01-01

    Objective. To analyze the clinical outcomes and prognostic factors of intensity-modulated radiotherapy (IMRT) for T4 stage nasopharyngeal carcinoma (NPC). Methods. Between March 2005 and March 2010, 110 patients with T4 stage NPC without distant metastases were treated. All patients received IMRT. Induction and/or concurrent chemotherapy were given. 47 (42.7%) patients received IMRT replanning. Results. The 5-year local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were 90.1%, 97.0%, 67.5%, 63.9%, and 64.5%, respectively. Eleven patients experienced local-regional failure and total distant metastasis occurred in 34 patients. 45 patients died and 26 patients died of distant metastasis alone. The 5-year LRFS rates were 97.7% and 83.8% for the patients that received and did not receive IMRT replanning, respectively (P = 0.023). Metastasis to the retropharyngeal lymph nodes (RLN) was associated with inferior 5-year OS rate (61.0% versus 91.7%, P = 0.034). The gross tumor volume of the right/left lymph nodes (GTVln) was an independent prognostic factor for DMFS (P = 0.006) and PFS (P = 0.018). GTVln was with marginal significance as the prognostic factor for OS (P = 0.050). Conclusion. IMRT provides excellent local-regional control for T4 stage NPC. Benefit of IMRT replanning may be associated with improvement in local control. Incorporating GTVln into the N staging system may provide better prognostic information. PMID:27195286

  8. Impact of Prolonged Fraction Delivery Times Simulating IMRT on Cultured Nasopharyngeal Carcinoma Cell Killing

    SciTech Connect

    Zheng Xiaokang; Chen Longhua; Wang Wenjun; Ye Feng; Liu Jiabing; Li Qisheng; Sun Henwen

    2010-12-01

    Purpose: To determine the impact of prolonged fraction delivery times (FDTs) simulating intensity-modulated radiotherapy (IMRT) on cultured nasopharyngeal carcinoma (NPC) cell killing. Methods and Material: Cultured NPC cell lines CNE1 and CNE2 were used in this study. The biological effectiveness of fractionated irradiation protocols simulating conventional external beam radiotherapy and IMRT (FDT of 15, 36, and 50 minutes) was estimated with standard colony assay, and the differences in cell surviving fractions after irradiation with different protocols were tested by use of the paired t test. The impact degree of prolonged FDTs (from 8 to 50 minutes) on cell killing was also assessed by the dose-modifying factors, which were estimated by comparing the effectiveness of intermittently delivered 2 Gy with that of continuously delivered 1.5 to 2 Gy. Results: The cell surviving fractions of both CNE1 and CNE2 after fractionated irradiation simulating IMRT were higher than those simulating conventional external beam radiotherapy (p < 0.05). The dose-modifying factors for a fraction dose of 2 Gy increased from 1.05 to 1.18 for CNE1 and from 1.05 to 1.11 for CNE2 with the FDT being prolonged from 15 to 50 minutes. Conclusions: This study showed that the prolonged FDTs simulating IMRT significantly decreased the cell killing in both CNE1 and CNE2 cell lines, and these negative effects increased with the FDT being prolonged from 15 to 50 minutes. These effects, if confirmed by in vivo and clinical studies, need to be considered in designing IMRT treatments for NPC.

  9. Diet Quality Scores and Risk of Nasopharyngeal Carcinoma in Chinese Adults: A Case-Control Study

    PubMed Central

    Wang, Cheng; Lin, Xiao-Ling; Fan, Yu-Ying; Liu, Yuan-Ting; Zhang, Xing-Lan; Lu, Yun-Kai; Xu, Chun-Hua; Chen, Yu-Ming

    2016-01-01

    Many studies show that dietary factors may affect the risk of nasopharyngeal carcinoma (NPC). We examined the association between overall diet quality and NPC risk in a Chinese population. This case-control study included 600 NPC patients and 600 matched controls between 2009 and 2011 in Guangzhou, China. Habitual dietary intake and various covariates were assessed via face-to-face interviews. Diet quality scores were calculated according to the Healthy Eating Index-2005 (HEI-2005), the alternate Healthy Eating Index (aHEI), the Diet Quality Index-International (DQI-I), and the alternate Mediterranean Diet Score (aMed). After adjustment for various lifestyle and dietary factors, greater diet quality scores on the HEI-2005, aHEI, and DQI-I—but not on the aMed—showed a significant association with a lower risk of NPC (p-trends, <0.001–0.001). The odds ratios (95% confidence interval) comparing the extreme quartiles of the three significant scores were 0.47 (0.32–0.68) (HEI-2005), 0.48 (0.33–0.70) (aHEI), and 0.43 (0.30–0.62) (DQI-I). In gender-stratified analyses, the favorable association remained significant in men but not in women. We found that adherence to the predefined dietary patterns represented by the HEI-2005, aHEI, and DQI-I scales predicted a lower risk of NPC in adults from south China, especially in men. PMID:26927167

  10. Prognostic value of Diabetes in Patients with Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiation Therapy

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    The prognostic value of diabetes remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). We retrospectively reviewed medical records of 1489 patients with non-metastatic, histologically-proven NPC treated using IMRT. 81/1489 (5.4%) patients were diabetic, 168/1489 (11.3%) were prediabetic, and 1240/1489 (83.3%) were normoglycemic. The 4-year disease-free survival (DFS), overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) rates were 77.1% vs. 82.4% (P = 0.358), 85.8% vs. 91.0% (P = 0.123), 90.9% vs. 91.7% (P = 0.884), and 85.5% vs. 89.2% (P = 0.445) for diabetic vs. normoglycemic patients, and 82.4% vs. 82.4% (P = 0.993), 88.7% vs. 91.0% (P = 0.285), 90.6% vs. 91.7% (P = 0.832) and 91.5% vs. 89.2% (P = 0.594) for preidabetic vs. normoglycemic patients. Multivariate analysis did not established diabetes as poor prognostic factors in NPC patients treated with IMRT (P = 0.332 for DFS, P = 0.944 for OS, P = 0.977 for LRRFS, P = 0.157 for DMFS), however, triglycerides and low density lipoprotein cholesterol were independent prognostic factors. In conclusion, diabetes does not appear to be a prognostic factor in NPC patients treated with IMRT, and attention should be paid to hyperglycemia-associated hyperlipaemia. PMID:26927312

  11. Correlation between pretreatment serum LDL-cholesterol levels and prognosis in nasopharyngeal carcinoma patients

    PubMed Central

    Tang, Qiu; Hu, Qiao-Ying; Piao, Yong-feng; Hua, Yong-Hong

    2016-01-01

    Purpose To investigate the correlations between long-term survival outcomes in patients with nasopharyngeal carcinoma (NPC) and pretreatment serum low-density lipoprotein cholesterol (LDL-C) levels. Patients and methods Between January 2008 and December 2011, 935 patients with newly diagnosed NPC who were treated with intensity-modulated radiation therapy were included in this retrospective clinical analysis. Patients were divided into two groups based on pretreatment LDL-C levels: normal LDL-C (≤3.64 mmol/L; n=816) and elevated LDL-C (>3.64 mmol/L; n=119). Associations between pretreatment LDL-C levels and treatment outcome were analyzed by univariate and multivariate analyses. Results The overall patient follow-up rate was 95.1%, and 726 patients received more than 5 years of follow-up. Five-year overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) rates of the entire patient population were 87.1%, 91.1%, and 87.2%, respectively. Rates of 5-year OS, LC, and DMFS for the elevated versus normal LDL-C groups were 77.0% vs 89.1% (P<0.001), 85.8% vs 91.9% (P=0.041), and 81.1% vs 88.1% (P=0.038), respectively. Compared with normal LDL-C levels, elevated LDL-C levels were identified as an independent prognostic factor of a poorer OS (hazard ratio [HR] =2.171; 95% confidence interval [CI] =1.424–3.309), LC rate (HR =1.762; 95% CI =1.021–3.942), and DMFS (HR =1.594; 95% CI =1.003–2.532). Conclusion This study found that elevated pretreatment LDL-C levels are negative prognostic indicators of NPC. Elevated LDL-C levels may be useful indicators of locoregional control and distant metastasis in NPC patients. PMID:27217776

  12. A clinical staging system and treatment guidelines for maxillary osteoradionecrosis in irradiated nasopharyngeal carcinoma patients

    SciTech Connect

    Cheng, S.-J.; Lee, J.-J.; Ting, L.-L.; Tseng, I.-Y.; Chang, H.-H.; Chen, H.-M.; Kuo, Y.-S.; Hahn, L.-J.; Kok, S.-H. . E-mail: kok@ha.mc.ntu.edu.tw

    2006-01-01

    Purpose: To develop a clinical staging system for maxillary osteoradionecrosis (ORN) in irradiated nasopharyngeal carcinoma (NPC) patients. Methods and Materials: The data of maxillary ORN cases among 1,758 irradiated NPC patients were analyzed. A staging system based on the degrees of bone exposure (E), infection (I), and bleeding (B) was developed. Correlations between various clinical parameters and stages of maxillary ORN and relationships between treatment modalities and outcomes at each stage were evaluated. Cumulative success of treatment and risk factors that affect treatment outcomes were analyzed. Results: The incidence of maxillary ORN was 2.7% (48/1,758). TNM stage of NPC (p < 0.001), radiation dose (p = 0.029), and tooth extraction (p < 0.001) appeared to have significant influences on disease severity. Success rates between conservative therapy and surgical treatment were not significantly different for Stage I ORN but differed significantly for Stage II (p = 0.013) and Stage III (p = 0.008) lesions. Grade 3 infection and bleeding significantly jeopardized treatment success (p = 0.043 and 0.015, respectively). The risk ratios of treatment failure for Grade 3 infection and bleeding were 2.523 (p = 0.034) and 3.141 (p = 0.027), respectively. Conclusions: More serious maxillary ORN tended to occur in cases with more advanced NPC, higher radiation dose, and history of tooth extraction. Surgical treatment was usually required in Stage II and III ORN. The grades of infection and bleeding are important factors in guidance of treatment and prediction of outcomes.

  13. Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma

    PubMed Central

    Chai, San Jiun; Yap, Yoke Yeow; Foo, Yoke Ching; Yap, Lee Fah; Ponniah, Sathibalan; Teo, Soo Hwang; Cheong, Sok Ching; Patel, Vyomesh; Lim, Kue Peng

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is highly prevalent in South East Asia and China. The poor outcome is due to late presentation, recurrence, distant metastasis and limited therapeutic options. For improved treatment outcome, immunotherapeutic approaches focusing on dendritic and autologous cytotoxic T-cell based therapies have been developed, but cost and infrastructure remain barriers for implementing these in low-resource settings. As our prior observations had found that four-jointed box 1 (FJX1), a tumor antigen, is overexpressed in NPCs, we investigated if short 9–20 amino acid sequence specific peptides matching to FJX1 requiring only intramuscular immunization to train host immune systems would be a better treatment option for this disease. Thus, we designed 8 FJX1-specific peptides and implemented an assay system to first, assess the binding of these peptides to HLA-A2 molecules on T2 cells. After, ELISPOT assays were used to determine the peptides immunogenicity and ability to induce potential cytotoxicity activity towards cancer cells. Also, T-cell proliferation assay was used to evaluate the potential of MHC class II peptides to stimulate the expansion of isolated T-cells. Our results demonstrate that these peptides are immunogenic and peptide stimulated T-cells were able to induce peptide-specific cytolytic activity specifically against FJX1-expressing cancer cells. In addition, we demonstrated that the MHC class II peptides were capable of inducing T-cell proliferation. Our results suggest that these peptides are capable of inducing specific cytotoxic cytokines secretion against FJX1-expressing cancer cells and serve as a potential vaccine-based therapy for NPC patients. PMID:26536470

  14. Prognostic value of Diabetes in Patients with Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiation Therapy.

    PubMed

    Peng, Hao; Chen, Lei; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Fan; Guo, Rui; Liu, Li-Zhi; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    The prognostic value of diabetes remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). We retrospectively reviewed medical records of 1489 patients with non-metastatic, histologically-proven NPC treated using IMRT. 81/1489 (5.4%) patients were diabetic, 168/1489 (11.3%) were prediabetic, and 1240/1489 (83.3%) were normoglycemic. The 4-year disease-free survival (DFS), overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) rates were 77.1% vs. 82.4% (P = 0.358), 85.8% vs. 91.0% (P = 0.123), 90.9% vs. 91.7% (P = 0.884), and 85.5% vs. 89.2% (P = 0.445) for diabetic vs. normoglycemic patients, and 82.4% vs. 82.4% (P = 0.993), 88.7% vs. 91.0% (P = 0.285), 90.6% vs. 91.7% (P = 0.832) and 91.5% vs. 89.2% (P = 0.594) for preidabetic vs. normoglycemic patients. Multivariate analysis did not established diabetes as poor prognostic factors in NPC patients treated with IMRT (P = 0.332 for DFS, P = 0.944 for OS, P = 0.977 for LRRFS, P = 0.157 for DMFS), however, triglycerides and low density lipoprotein cholesterol were independent prognostic factors. In conclusion, diabetes does not appear to be a prognostic factor in NPC patients treated with IMRT, and attention should be paid to hyperglycemia-associated hyperlipaemia. PMID:26927312

  15. Patterns of failure after the reduced volume approach for elective nodal irradiation in nasopharyngeal carcinoma

    PubMed Central

    Seol, Ki Ho

    2016-01-01

    Purpose To evaluate the patterns of nodal failure after radiotherapy (RT) with the reduced volume approach for elective neck nodal irradiation (ENI) in nasopharyngeal carcinoma (NPC). Materials and Methods Fifty-six NPC patients who underwent definitive chemoradiotherapy with the reduced volume approach for ENI were reviewed. The ENI included retropharyngeal and level II lymph nodes, and only encompassed the echelon inferior to the involved level to eliminate the entire neck irradiation. Patients received either moderate hypofractionated intensity-modulated RT for a total of 72.6 Gy (49.5 Gy to elective nodal areas) or a conventional fractionated three-dimensional conformal RT for a total of 68.4–72 Gy (39.6–45 Gy to elective nodal areas). Patterns of failure, locoregional control, and survival were analyzed. Results The median follow-up was 38 months (range, 3 to 80 months). The out-of-field nodal failure when omitting ENI was none. Three patients developed neck recurrences (one in-field recurrence in the 72.6 Gy irradiated nodal area and two in the elective irradiated region of 39.6 Gy). Overall disease failure at any site developed in 11 patients (19.6%). Among these, there were six local failures (10.7%), three regional failures (5.4%), and five distant metastases (8.9%). The 3-year locoregional control rate was 87.1%, and the distant failure-free rate was 90.4%; disease-free survival and overall survival at 3 years was 80% and 86.8%, respectively. Conclusion No patient developed nodal failure in the omitted ENI site. Our investigation has demonstrated that the reduced volume approach for ENI appears to be a safe treatment approach in NPC. PMID:27104162

  16. Long-Term Outcomes of Nasopharyngeal Carcinoma in 148 Children and Adolescents

    PubMed Central

    Lu, Suying; Chang, Hui; Sun, Xiaofei; Zhen, Zijun; Sun, Feifei; Zhu, Jia; Wang, Juan; Huang, Junting; Liao, Ru; Guo, Xiaofang; Lu, Lixia; Gao, Yuanhong

    2016-01-01

    Abstract The aim of this study was to investigate the survival and long-term morbidities of nasopharyngeal carcinoma (NPC) in children and adolescents. We retrospectively reviewed children and adolescents with NPC treated at Sun Yat-sen University Cancer Center from February 1991 to October 2010, where the prognostic factors and long-term effects of therapy were analyzed. A total of 148 patients were identified. The median age was 15 years old (range, 5–18 years) and the male to female ratio was 3.6:1. Most of the tumor histopathology was undifferentiated nonkeratinizing carcinoma (97.3%). The number of patients staged with IVa, IVb, IVc, III, and II were 45 (30.4%), 12 (8.1%), 5 (3.4%), 70 (47.3%), and 16 (10.8%), respectively. For the whole series with a median follow-up of 81 months (range, 6–282 months), the 5-year overall survival (OS) and disease-free survival (DFS) ratios were 79.3% and 69.7%, respectively. We observed significant differences in the 5-year OS (81.1% vs 25.0%, P = 0.002) and the DFS rates (72.2% vs 0.0%, P = 0.000) between patients with stage II to IVb disease and stage IVc disease. For patients with stage II, III, IVa, and IVb disease, we found a high radiation dose (dose > 66 Gy to the primary lesion) would not significantly improve the survival compared to the sub-high radiation dose group (dose = 60–66 Gy to the primary lesion), even considering the type of radiation therapy technologies. However, the incidences of sequelae (grades I–IV) in patients with high radiation dose were apparently higher than those in patients with low radiation dose. Considering the late sequelae, a dose of 60 to 66 Gy to the primary lesions seems to be enough for children and adolescents with NPC. PMID:27124036

  17. Apoptosis-inducing effects of cetuximab combined with radiotherapy and hypothermia on human nasopharyngeal carcinoma CNE cells

    PubMed Central

    Liu, Wenqi; Kang, Min; Qin, Yutao; Wei, Zhuxin; Wang, Rensheng

    2015-01-01

    To investigate the apoptosis-inducing effects of cetuximab combined with radiotherapy and hypothermia in human nasopharyngeal carcinoma CNE cells. CNE cells were treated with the radiation monotherapy, the radiation and hypothermia, the cetuximab and radiation, and the triple-combination treatment, respectively. MTT assay was performed to assess cell proliferation following treatments. Hoechst 33258 staining and flow cytometry analyses were used to detect apoptotic process. Western blot analysis was performed to determine the protein expression levels. Cetuximab monotherapy inhibited the proliferation of CNE cells. Hyperthermia alone inhibited EGFR expression, and prolonged hypothermia treatment resulted in declining EGFR expression levels in these cells. Moreover, Hoechst 33258 staining showed obvious apoptotic morphologies in the treatment groups. Flow cytometry analysis showed that the interventions dramatically increased the apoptosis rates in CNE cells, with the most potent effect for the triple-combination treatment. Western blot analysis showed that, in the treatment groups, the expression levels of Bax were increased, while the expression levels of Bcl-2 were decreased, leading to significantly elevated Bax/Bcl-2 ratios in these groups, with the highest ratio for the triple-combination treatment. Cetuximab combined with radiotherapy and hypothermia treatments could efficiently inhibit the proliferation of CNE cells, and enhance the cellular apoptotic processes via regulating the expression levels of Bax and Bcl-2. Our findings provide experimental evidence for the application of the combination therapy in clinical treatment of nasopharyngeal carcinoma. PMID:25932149

  18. Salinomycin inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cell in vitro and suppresses tumor growth in vivo

    SciTech Connect

    Wu, Danxin; Zhang, Yu; Huang, Jie; Fan, Zirong; Shi, Fengrong; Wang, Senming

    2014-01-10

    Highlight: •We first evaluated the effect of salinomycin on nasopharyngeal carcinoma (NPC). •Salinomycin could inhibit Wnt/β-catenin signaling and induce apoptosis in NPC. •So salinomycin may be a good potential candidate for the chemotherapy of NPC. -- Abstract: Salinomycin (Sal) is a polyether ionophore antibiotic that has recently been shown to induce cell death in various human cancer cells. However, whether salinomycin plays a functional role in nasopharyngeal carcinoma (NPC) has not been determined to date. The present study investigated the chemotherapeutic efficacy of salinomycin and its molecular mechanisms of action in NPC cells. Salinomycin efficiently inhibited proliferation and invasion of 3 NPC cell lines (CNE-1, CNE-2, and CNE-2/DDP) and activated a extensive apoptotic process that is accompanied by activation of caspase-3 and caspase-9, and decreased mitochondrial membrane potential. Meanwhile, the protein expression level of the Wnt coreceptor lipoprotein receptor related protein 6 (LRP6) and β-catenin was down-regulated, which showed that the Wnt/β-catenin signaling was involved in salinomycin-induced apoptosis of NPC cells. In a nude mouse NPC xenograft model, the anti-tumor effect of salinomycin was associated with the downregulation of β-catenin expression. The present study demonstrated that salinomycin can effectively inhibit proliferation and invasion, and induce apoptosis of NPC cells in vitro and inhibit tumor growth in vivo, probably via the inhibition of Wnt/β-catenin signaling, suggesting salinomycin as a potential candidate for the chemotherapy of NPC.

  19. MWCNT-Fe3O4-based immuno-PCR for the early screening of nasopharyngeal carcinoma.

    PubMed

    Chia-Ching, Liu; Subramaniam, Sadhasivam; Sivasubramanian, Savitha; Feng-Huei, Lin

    2016-04-01

    Nasopharyngeal carcinoma (NPC) is the most prevalent form of malignancy in southeast China and its development is meticulously related to EBV pathogenesis. The current screening techniques are unsatisfactory in terms of the sensitivity and hence most of the NPC patients are diagnosed at an advanced stage. Herein, we report the multi-walled carbon nanotubes (MWCNTs) combined with iron oxide nanoparticles as a sensing surface for the early screening of nasopharyngeal carcinoma (NPC) by immuno-PCR (iPCR). The MWCNT-Fe3O4 nanocomposite was characterized by Fourier transform infrared spectra (FTIR), Raman spectra, X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM). The characterization techniques had confirmed the successful formation of MWCNT-Fe3O4 nanocomposites. The MWCNT-Fe3O4-based iPCR was effectively tested for the quantification of anti-EBV antibodies in human serum and the limit of detection (LOD) was compared with ELISA. The limit of detection by iPCR was valid until 1:10,000,000 fold dilution of NPC(+ve) human serum, whereas ELISA can detect the anti-EBV antibodies in human serum up to 1:100,000 fold dilution. The MWCNT-Fe3O4 offers an excellent surface area for the antigen-antibody binding and hence greater sensitivity was achieved. PMID:26838868

  20. Intravoxel Incoherent Motion Diffusion Weighted Magnetic Resonance Imaging for Differentiation Between Nasopharyngeal Carcinoma and Lymphoma at the Primary Site

    PubMed Central

    Yu, Xiao-Ping; Hou, Jing; Li, Fei-Ping; Wang, Hui; Hu, Ping-Sheng; Bi, Feng; Wang, Wei

    2016-01-01

    Objective The aim of the study was to investigate the utility of intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (DWI) for differentiating nasopharyngeal carcinoma (NPC) from lymphoma. Methods Intravoxel incoherent motion–based parameters including the apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudodiffusion coefficient (D*), perfusion fraction (f), and fD* (the product of D* and f) were retrospectively compared between 102 patients (82 with NPC, 20 with lymphoma) who received pretreatment IVIM DWI. Results Compared with lymphoma, NPC exhibited higher ADC, D, D*, fD* values (P < 0.001) and f value (P = 0.047). The optimal cutoff values (area under the curve, sensitivity, and specificity, respectively) for distinguishing the 2 tumors were as follows: ADC value of 0.761 × 10−3 mm2/s (0.781, 93.90%, 55.00%); D, 0.66 × 10−3 mm2/s (0.802, 54.88%, 100.00%); D*, 7.89 × 10−3 mm2/s (0.898, 82.93%, 85.00%); f, 0.29 (0.644, 41.46%, 95.00%); and fD*, 1.99 × 10−3 mm2/s (0.960, 85.37%, 100.00%). Conclusions Nasopharyngeal carcinoma exhibits different IVIM-based imaging features from lymphoma. Intravoxel incoherent motion DWI is useful for differentiating lymphoma from NPC. PMID:26953769

  1. Expression of the DNase encoded by the BGLF5 gene of Epstein-Barr virus in nasopharyngeal carcinoma epithelial cells.

    PubMed

    Sbih-Lammali, F; Berger, F; Busson, P; Ooka, T

    1996-08-01

    In contrast with most Epstein-Barr virus (EBV)-infected healthy carriers, nasopharyngeal carcinoma patients frequently have increased serum levels of antibodies directed against EBV-DNase. These antibodies are potentially interesting serological markers for the diagnosis and the follow-up of nasopharyngeal carcinoma (NPC). In this context, it is important to determine whether malignant EBV-infected cells are the source of significant amounts of EBV-DNase contributing to antigenic stimulation. Therefore EBV-DNase expression has been investigated in several NPC specimens. A significant expression of this viral enzyme was demonstrated in both fresh biopsies and transplanted tumor lines. The DNase isolated from tumor has a molecular weight varying between 52 and 60 kDa and its activity eluted from a single-stranded DNA affinity column was specifically inhibited by both NPC sera and the rabbit polyclonal antibody against EBV-DNase. The enzyme activity was functional in the presence of 300 mM KCl, with which cellular DNases are completely inhibited. The DNase was mainly localized in epithelial tumor cells of both NPC biopsies and nude mice-derived NPC cells. PMID:8806488

  2. Fatal Fast-Evolution of Nasopharyngeal Squamous Cell Carcinoma in an HIV Patient with EBV and HPV (-16 AND -33) in Blood Serum

    PubMed Central

    Sirera, Guillem; Videla, Sebastià; Romeu, Joan; Cañadas, MariPaz; Fernández, Maria-Teresa; Balo, Susana; Cirauqui, Beatriz; Darwich, Laila; Rey-Joly, Celestino; Clotet, Bonaventura

    2008-01-01

    Our case illustrates the first report of an HIV-infected patient with a nasopharyngeal squamous cell carcinoma with viremia by one Epstein-Barr virus (EBV) and seropositivity by two high risk oncogenic human papilloma viruses (HPV)-types (HPV-16 and HPV-33), previous to his death. This patient presented a fatal fast-evolution. PMID:18923693

  3. Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptor-mediated endocytosis by molecular targeted nanomedicine

    PubMed Central

    Xie, M; Zhang, H; Xu, Y; Liu, T; Chen, S; Wang, J; Zhang, T

    2013-01-01

    Immunohistochemistry and an immunofluorescence technique was used to detect folate receptor expression in tissue samples and cell lines of head and neck squamous carcinoma, including 20 tissue samples of nasopharyngeal carcinoma, 16 tissue samples of laryngeal carcinoma, and HNE-1, HNE-2, CNE-1, CNE-2, SUNE-1, 5–8F, and Hep-2 cell lines. Iron staining, electron microscopy, and magnetic resonance imaging were used to observe endocytosis of folate-conjugated cisplatin-loaded magnetic nanoparticles (CDDP-FA-ASA-MNP) in cultured cells and transplanted tumors. As shown by immunohistochemistry, 83.3% (30/36) of the head and neck squamous carcinomas expressed the folate receptor versus none in the control group (0/24). Only the HNE-1 and Hep-2 cell lines expressed the folate receptor, and the other five cell lines did not. Endocytosis of CDDP-FA-ASA-MNP was seen in HNE-1 and Hep-2 cells by iron staining and electron microscopy. A similar result was seen in transplanted tumors in nude mice. Magnetic resonance imaging showed low signal intensity of HNE-1 cells and HNE-1 transplanted tumors on T2-weighted images after uptake of CDDP-FA-ASA-MNP, and this was not seen in CNE-2 transplanted tumors. In conclusion, head and neck squamous carcinoma cell strongly expressed the folate receptor, while normal tissue did not. The folate receptor can mediate endocytosis of folate-conjugated anticancer nanomedicines, and lays the foundation for molecular targeted treatment of cancer. PMID:23874095

  4. Pretreatment platelet count as a predictor for survival and distant metastasis in nasopharyngeal carcinoma patients

    PubMed Central

    CHEN, YU-PEI; CHEN, CHEN; MAI, ZHUO-YAO; GAO, JIN; SHEN, LU-JUN; ZHAO, BING-CHENG; CHEN, MENG-KUN; CHEN, GANG; YAN, FANG; HUANG, TONG-YI; XIA, YUN-FEI

    2015-01-01

    The aim of the present study was to investigate the prognostic value of different pretreatment platelet (PLT) counts on the treatment outcome in nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone. A total of 1,501 NPC patients, including 412 receiving CCRT and 1,089 receiving RT, were enrolled in the present study. The PLT count cut-off points for the CCRT and RT groups were 150 and 300×109/l, respectively, and the PLT counts were categorized it into three groups: Low (PLT≤150×109/l), moderate (150×109/l300×109/l). To identify independent predictors of overall survival (OS), the Cox proportional hazards model was used to determine local-regional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates in the CCRT and RT patients. Furthermore, univariate and multivariate analysis indicated that compared with a moderate PLT count, a low PLT count was an independent unfavorable prognostic factor for OS rate in CCRT patients [hazard ratio (HR), 2.024; 95% confidence interval (CI), 1.165–3.516], and a high PLT count was an independent unfavorable prognostic factor for OS and DMFS rates in CCRT (OS: HR, 1.742; 95% CI, 1.090–2.786; DFMS: HR, 2.110; 95%CI, 1.084–4.108) and RT (OS: HR, 1.740; 95%CI, 1.283–2.362; DMFS: HR, 2.819; 95% CI, 1.766–4.497) patients. Compared with a low PLT count, a high PLT count was significantly and independently associated with a poor DMFS rate in the RT patients (P=0.025; HR, 2.454; 95% CI, 1.121–5.372). Therefore, the present study indicates that low and high PLT counts may be useful indicators of survival and distant metastasis in NPC patients who have undergone radiation treatment. PMID:25663931

  5. Primary tumor regression speed after radiotherapy and its prognostic significance in nasopharyngeal carcinoma: a retrospective study

    PubMed Central

    2014-01-01

    Background To observe the primary tumor (PT) regression speed after radiotherapy (RT) in nasopharyngeal carcinoma (NPC) and evaluate its prognostic significance. Methods One hundred and eighty-eight consecutive newly diagnosed NPC patients were reviewed retrospectively. All patients underwent magnetic resonance imaging and fiberscope examination of the nasopharynx before RT, during RT when the accumulated dose was 46–50 Gy, at the end of RT, and 3–4 months after RT. Results Of 188 patients, 40.4% had complete response of PT (CRPT), 44.7% had partial response of PT (PRPT), and 14.9% had stable disease of PT (SDPT) at the end of RT. The 5-year overall survival (OS) rates for patients with CRPT, PRPT, and SDPT at the end of RT were 84.0%, 70.7%, and 44.3%, respectively (P < 0.001, hazard ratio [HR] = 2.177, 95% confidence interval [CI] = 1.480-3.202). The 5-year failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates also differed significantly (87.8% vs. 74.3% vs. 52.7%, P = 0.001, HR = 2.148, 95% CI, 1.384-3.333; 91.7% vs. 84.7% vs. 66.1%, P = 0.004, HR = 2.252, 95% CI = 1.296-3.912). The 5-year local relapse–free survival (LRFS) rates were not significantly different (95.8% vs. 86.0% vs. 81.8%, P = 0.137, HR = 1.975, 95% CI, 0.976-3.995). By multivariate analyses, the PT regression speed at the end of RT was the only independent prognostic factor of OS, FFS, and DMFS (P < 0.001, P = 0.001, and P = 0.004, respectively). The 5-year FFS rates for patients with CRPT during RT and CRPT only at the end of RT were 80.2% and 97.1%, respectively (P = 0.033). For patients with persistent PT at the end of RT, the 5-year LRFS rates of patients without and with boost irradiation were 87.1% and 84.6%, respectively (P = 0.812). Conclusions PT regression speed at the end of RT was an independent prognostic factor of OS, FFS, and DMFS in NPC patients. Immediate strengthening treatment may be provided to patients with poor

  6. Clinical Outcomes of 174 Nasopharyngeal Carcinoma Patients With Radiation-Induced Temporal Lobe Necrosis

    SciTech Connect

    Lam, Tai-Chung; Wong, Frank C.S.; Leung, To-Wai; Ng, S.H.; Tung, Stewart Y.

    2012-01-01

    Purpose: To retrospectively study the clinical outcomes of nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis (TLN) treated with steroids, surgery, or observation only. Methods and Patients: We performed a retrospective analysis of 174 consecutive patients diagnosed with TLN between 1990 and 2008. Before 1998, symptomatic patients were treated with oral steroids, while asymptomatic patients were treated conservatively. After 1998, most symptomatic and asymptomatic patients with a large volume of necrosis were treated by intravenously pulsed-steroid therapy with a standardized protocol. We examined factors affecting grade 4 complication-free survival and overall survival. Outcomes of the three treatment groups, those receiving conservative treatment, those receiving oral steroid, and those receiving intravenous pulse steroid, were compared. Results: The mean follow-up time was 115 months. Rates of grade 4 complication-free survival at 2 years and at 5 years after diagnosis of TLN were 72.2% and 54.1%, respectively. The 2-year and 5-year overall survival rates were 57.5% and 35.4%, respectively. Multivariate analysis revealed that being symptomatic at diagnosis (relative risk [RR], 4.5; p = 0.0001), re-irradiation of the nasopharynx (NP) (RR, 1.56; p = 0.008), salvage brachytherapy to the NP (RR, 1.75; p = 0.012), and a short latency period before the diagnosis of TLN (RR, 0.96, p < 0.0001) were independent prognosticators of poor grade 4 complication-free survival. Patients with all four factors had a 100% risk of developing grade 4 complications within 5 years; whereas if no factor was present, the risk was 12.5%. Intravenous pulse steroid therapy was associated with a higher clinical response rate compared with conventional steroid therapy (p < 0.0001); however, it did not affect complication-free survival in multivariate analysis. Conclusions: TLN patients with good prognosticators could be observed without active treatment. Although

  7. Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Wang, Xue; Chen, Meng; Wu, Jing; Xu, Jian-Hua; Qian, Pu-Dong; Guo, Wen-Jie; Jiang, Xue-Song; Zhu, Huan-Feng; Gu, Jia-Jia; Wu, Jian-Feng; Zhang, Ye-wei; He, Xia

    2015-01-01

    Background N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Patients and Methods Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. Results With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. Conclusion IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute

  8. Dosimetric evaluation of a three-phase adaptive radiotherapy for nasopharyngeal carcinoma using helical tomotherapy

    SciTech Connect

    Fung, Winky Wing Ki; Wu, Vincent Wing Cheung; Teo, Peter Man Lung

    2012-04-01

    Adaptive radiotherapy (ART) has been introduced to correct the radiation-induced anatomic changes in head and neck cases during a treatment course. This study evaluated the potential dosimetric benefits of applying a 3-phase adaptive radiotherapy protocol in nasopharyngeal carcinoma (NPC) patients compared with the nonadaptive single-phase treatment protocol. Ten NPC patients previously treated with this 3-phase radiation protocol using Hi-Art Tomotherapy were recruited. Two new plans, PII-ART and PIII-ART, were generated based on the up-to-date computed tomography (CT) images and contours and were used for treatment in phase two (PII; after 25th fraction) and phase three (PIII; after 35th fraction), respectively. To simulate the situation of no replanning, 2 hybrid plans denoted as PII-NART and PIII-NART were generated using the original contours pasted on the PII- and PIII-CT sets by CT-CT fusion. Dosimetric comparisons were made between the NART plans and the corresponding ART plans. In both PII- and PIII-NART plans, the doses to 95% of all the target volumes (D{sub 95}) were increased with better dose uniformity, whereas the organs at risk (OARs) received higher doses compared with the corresponding ART plans. Without replanning, the total dose to 1% of brainstem and spinal cord (D{sub 1}) significantly increased 7.87 {+-} 7.26% and 10.69 {+-} 6.72%, respectively (P = 0.011 and 0.001, respectively), in which 3 patients would have these structures overdosed when compared with those with two replannings. The total maximum doses to the optic chiasm and pituitary gland and the mean doses to the left and right parotid glands were increased by 10.50 {+-} 10.51%, 8.59 {+-} 6.10%, 3.03 {+-} 4.48%, and 2.24 {+-} 3.11%, respectively (P = 0.014, 0.003, 0.053, and 0.046, respectively). The 3-phase radiotherapy protocol showed improved dosimetric results to the critical structures while keeping satisfactory target dose coverage, which demonstrated the advantages of ART in

  9. Retrospective Analysis of the Survival Benefit of Induction Chemotherapy in Stage IVa-b Nasopharyngeal Carcinoma

    PubMed Central

    Xiao, Yao; Tang, Jie; OuYang, Pu-Yun; Su, Zhen; Xie, Fang-Yun

    2016-01-01

    Purpose The value of adding induction chemotherapy to chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains controversial, yet high-risk patients with LA-NPC have poor outcomes after chemoradiotherapy. We aimed to assess the survival benefits of induction chemotherapy in stage IVa-b NPC. Patients and Methods A total of 602 patients with stage IVa-b NPC treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with or without induction chemotherapy were retrospectively analyzed. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, log-rank test and Cox regression analysis. Results In univariate analysis, 5-year OS was 83.2% for induction chemotherapy plus concurrent chemotherapy and 74.8% for concurrent chemotherapy alone, corresponding to an absolute risk reduction of 8.4% (P = 0.022). Compared to concurrent chemotherapy alone, addition of induction chemotherapy improved 5-year DMFS (83.2% vs. 74.4%, P = 0.018) but not 5-year LRFS (83.7% vs. 83.0%, P = 0.848) or PFS (71.9% vs. 66.0%, P = 0.12). Age, T category, N category, chemotherapy strategy and clinical stage were associated with 5-year OS (P = 0.017, P = 0.031, P = 0.007, P = 0.022, P = 0.001, respectively). In multivariate analysis, induction chemotherapy plus concurrent chemotherapy was an independent favorable prognostic factor for OS (HR, 0.62; 95% CI, 0.43–0.90, P = 0.012) and DMFS (HR, 0.57; 95% CI, 0.38–0.83, P = 0.004). In subgroup analysis, induction chemotherapy significantly improved 5-year DMFS in stage IVa (86.8% vs. 77.3%, P = 0.008), but provided no significant benefit in stage IVb. Conclusions In patients with stage IVa-b NPC treated with IMRT, addition of induction chemotherapy to concurrent chemotherapy significantly improved 5-year OS and 5-year DMFS. This study provides a basis for selection of

  10. Nasopharyngeal carcinoma in Indonesia: epidemiology, incidence, signs, and symptoms at presentation

    PubMed Central

    Adham, Marlinda; Kurniawan, Antonius N.; Muhtadi, Arina Ika; Roezin, Averdi; Hermani, Bambang; Gondhowiardjo, Soehartati; Tan, I Bing; Middeldorp, Jaap M.

    2012-01-01

    Among all head and neck (H&N) cancers, nasopharyngeal carcinoma (NPC) represents a distinct entity regarding epidemiology, clinical presentation, biological markers, carcinogenic risk factors, and prognostic factors. NPC is endemic in certain regions of the world, especially in Southeast Asia, and has a poor prognosis. In Indonesia, the recorded mean prevalence is 6.2/100 000, with 13 000 yearly new NPC cases, but otherwise little is documented on NPC in Indonesia. Here, we report on a group of 1121 NPC patients diagnosed and treated at Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia between 1996 and 2005. We studied NPC incidence among all H&N cancer cases (n=6000) observed in that period, focusing on age and gender distribution, the ethnic background of patients, and the disease etiology. We also analyzed most prevalent signs and symptoms and staging of NPC patients at first presentation. In this study population, NPC was the most frequent H&N cancer (28.4%), with a male-to-female ratio of 2.4, and was endemic in the Javanese population. Interestingly, NPC appeared to affect patients at a relatively young age (20% juvenile cases) without a bimodal age distribution. Mostly, NPC initiated in the fossa of Rosenmuller and spreaded intracranially or locally as a mass in the head. Occasionally, NPC developed at the submucosal level spreading outside the anatomic limits of the nasopharynx. At presentation, NPC associated with hearing problems, serous otitis media, tinnitus, nasal obstruction, anosmia, bleeding, difficulty in swallowing and dysphonia, and even eye symptoms with diplopia and pain. The initial diagnosis is difficult to make because early signs and symptoms of NPC are not specific to the disease. Early-age Epstein-Barr virus (EBV) infection combined with frequent exposure to environmental carcinogenic co-factors is suggested to cause NPC development. Undifferentiated NPC is the most frequent histological type and is closely associated with EBV

  11. Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma

    PubMed Central

    Zhao, Yuanyuan; Zhang, Jing; Tian, Ying; Xue, Cong; Hu, Zhihuang; Zhang, Li

    2015-01-01

    Purpose We explored the effect of hepatocyte growth factor (HGF)/Met signaling pathway on nasopharyngeal carcinoma (NPC) cells in vitro and in vivo, and investigated the ability of Met tyrosine kinase inhibitor (TKI) to block HGF-induced biological signaling. Experimental design Met TKI inhibitor PF-2341066 alone, or in combination with cisplatin, was investigated for its ability to block HGF-induced signaling and biological effects in vitro and in vivo. HGF/Met expression and activation of signaling in NPC cells were detected by using Western blot and immunohistochemistry. Biological evaluation, including wound healing, cell proliferation, and invasion of NPC cells, was also examined, and the correlation between HGF/Met expression of primary and metastatic tumor in NPC patients and clinical prognosis were also analyzed. Results Met TKI inhibitor, PF-2341066, inhibited growth of NPC cells in vivo with half maximal inhibitory concentration of 0.79±0.21 μmol/L, and suppressed invasion and migration of NPC cells; also, the inhibition of PF-2341066 was synergized with cisplatin treatment. Compared with the control group, Met TKI inhibited metastasis of transplanted NPC in nude mice (the number of live metastases [mean ± SD]: 5.8±2.2 versus 11.8±2.2, P=0.03; the number of lung metastases: 2.3±1.5 versus 5.3±0.9, P=0.06). HGF was widely expressed in both primary and metastatic lesions while Met expression of metastatic lesions was higher than that of primary lesions (primary lesions: 24.7%; liver metastases: 40%; lung metastases: 29%; lymph node metastases: 29%, P<0.05), and overall survival of NPC patients with higher expression of Met was shorter (P=0.13). Conclusion Our results demonstrated that HGF/Met signaling promoted NPC growth, further resulting in metastasis and poor prognosis. Met TKI, PF-2341066, showed potent antitumor activity in vivo and in vitro which was enhanced by combination with cisplatin. Our study implied that HGF/Met signaling was the

  12. High prevalence of the EBER variant EB-8m in endemic nasopharyngeal carcinomas.

    PubMed

    Shen, Zhi-chao; Luo, Bing; Chen, Jian-ning; Chao, Yan; Shao, Chun-kui; Liu, Qian-qian; Wang, Yun

    2015-01-01

    Epstein-Barr virus (EBV)-encoded small RNAs (EBERs) are the most highly expressed transcripts in all EBV-associated tumors and are involved in both lymphoid and epithelioid carcinogenesis. Our previous study on Chinese isolates from non-endemic area of nasopharyngeal carcinoma (NPC) identified new EBER variants (EB-8m and EB-10m) which were less common but relatively more frequent in NPC cases than healthy donors. In the present study, we determined the EBER variants in NPC cases and healthy donors from endemic and non-endemic areas of NPC within China and compared the EBER variants, in relation to the genotypes at BamHI F region (prototype F and f variant), between population groups and between two areas. According to the phylogenetic tree, four EBER variants (EB-6m, EB-8m, EB-10m and B95-8) were identified. EB-6m was dominant in all population groups except for endemic NPC group, in which EB-8m was dominant. EB-8m was more common in endemic NPC cases (82.0%, 41/50) than non-endemic NPC cases (33.7%, 32/95) (p<0.0001), and it was also more frequent in healthy donors from endemic area (32.4%, 24/74) than healthy donors from non-endemic area (1.1%, 1/92) (p<0.0001). More importantly, the EB-8m was more prevalent in NPC cases than healthy donors in both areas (p<0.0001). The f variant, which has been suggested to associate with endemic NPC, demonstrated preferential linkage with EB-8m in endemic isolates, however, the EB-8m variant seemed to be more specific to NPC isolates than f variant. These results reveal high prevalence of EBER EB-8m variant in endemic NPC cases, suggesting an association between NPC development and EBV isolates carrying EB-8m variant. Our finding identified a small healthy population group that shares the same viral strain which predominates in NPC cases. It could be interesting to carry extensive cohort studies following these individuals to evaluate the risk to develop NPC. PMID:25807550

  13. Whole-Field Simultaneous Integrated-Boost Intensity-Modulated Radiotherapy for Patients With Nasopharyngeal Carcinoma

    SciTech Connect

    Wong, Frank C.S.; Ng, Alice W.Y.; Lee, Victor H.F.; Lui, Collin M.M.; Yuen, K.-K.; Sze, W.-K.; Leung, T.-W.; Tung, Stewart Y.

    2010-01-15

    Purpose: To retrospectively review the outcomes of our patients with newly diagnosed nondisseminated nasopharyngeal carcinoma treated with intensity-modulated radiotherapy using a whole-field simultaneous integrated-boost technique. Methods and Materials: A total of 175 patients treated with WF-SIB between mid-2004 and 2005 were eligible for study inclusion. The distribution of disease by stage was Stage IA in 10.9%, Stage IIA in 2.3%, Stage IIB in 21.7%, Stage III in 41.1%, Stage IVA in 14.9%, and Stage IVB in 9.1%. Of the 175 patients, 2 (1.2%), 10 (5.7%), and 163 (93.1%) had World Health Organization type I, II, and III histologic features, respectively. We prescribed 70 Gy, 60 Gy, and 54 Gy delivered in 33 fractions within 6.5 weeks at the periphery of three planning target volumes (PTV; PTV70, PTV60, and PTV54, respectively). Of the 175 patients, 46 with early T-stage disease received a brachytherapy boost, and 127 with advanced local or regional disease received chemotherapy. Results: The median follow-up period was 34 months. The overall 3-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 93.6%, 93.3%, 86.6%, and 87.2%, respectively. Cox regression analysis showed Stage N2-N3 disease (p = .029) and PTV (p = .024) to be independent factors predicting a greater risk of distant failure and poor overall survival, respectively. Grade 3 acute mucositis/pharyngitis occurred in 23.4% of patients, and Stage T4 disease was the only significant predictor of mucositis/pharyngitis (p = .021). Conclusion: Whole-field simultaneous integrated-boost intensity-modulated radiotherapy with a dose >70 Gy achieved excellent locoregional control, without an excess incidence of severe, acute mucositis/pharyngitis, in the present study. Strategies for using such highly conformal treatment for patients with a large tumor and late N-stage disease are potential areas of investigation for future studies.

  14. Synergistic Effect of Combination Topotecan and Chronomodulated Radiation Therapy on Xenografted Human Nasopharyngeal Carcinoma

    SciTech Connect

    Zhang, YanLing; Chen, Xin; Ren, PeiRong; Su, Zhou; Cao, HongYing; Zhou, Jie; Zou, XiaoYan; Fu, ShaoZhi; Lin, Sheng; Fan, Juan; Yang, Bo; Sun, XiaoYang; Zhou, Yan; Chen, Yue; Yang, LingLin; Wu, JingBo

    2013-10-01

    Purpose: To investigate the in vivo chronomodulated radiosensitizing effect of topotecan (TPT) on human nasopharyngeal carcinoma (NPC) and its possible mechanisms. Methods and Materials: Xenografted BALB/c (nu/nu) NPC mice were synchronized with an alternation of 12 hours of light from 0 to 12 hours after light onset (HALO) and 12 hours of darkness to establish a unified biological rhythm. Chronomodulated radiosensitization of TPT was investigated by analysis of tumor regrowth delay (TGD), pimonidazole hydrochloride, histone H2AX phosphorylation, (γ-H2AX) topoisomerase I (Top I), cell cycle, and apoptosis after treatment with (1) TPT (10 mg/kg) alone; (2) radiation therapy alone (RT); and (3) TPT+RT at 3, 9, 15, and 21 HALO. The tumor-loaded mice without any treatment were used as controls. Results: The TPT+RT combination was more effective than TPT or RT as single agents. The TPT+RT combination at 15 HALO was best (TGD = 58.0 ± 3.6 days), and TPT+RT at 3 HALO was worst (TGD = 35.0 ± 1.5 days) among the 4 TPT+RT groups (P<.05). Immunohistochemistry analysis revealed a significantly increased histone H2AX phosphorylation expression and decreased pimonidazole hydrochloride expression in the TPT+RT group at the same time point. The results suggested that the level of tumor hypoxia and DNA damage varied in a time-dependent manner. The expression of Top I in the TPT+RT group was also significantly different from the control tumors at 15 HALO (P<.05). Cell apoptosis index was increased and the proportion of cells in S phase was decreased (P<.05) with the highest value in 15 HALO and the lowest in 3 HALO. Conclusions: This study suggested that TPT combined with chronoradiotherapy could enhance the radiosensitivity of xenografted NPC. The TPT+RT group at 15 HALO had the best therapeutic effect. The chronomodulated radiosensitization mechanisms of TPT might be related to circadian rhythm of tumor hypoxia, cell cycle redistribution, DNA damage, and expression of Top I.

  15. Forkhead box C1 induces epithelial-mesenchymal transition and is a potential therapeutic target in nasopharyngeal carcinoma

    PubMed Central

    OU-YANG, LEI; XIAO, SHENG-JUN; LIU, PENG; YI, SHI-JANG; ZHANG, XIAO-LING; OU-YANG, SHI; TAN, SHENG-KUI; LEI, XUN

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is a highly invasive malignancy with cervical lymphopathy as the initial presentation. Epithelial-mesenchymal transition (EMT), a process by which epithelial cells lose cell-cell adhesion and gain migratory and invasive properties, has a pivotal role in metastasis. Forkhead box C1 (FoxC1), a member of the forkhead family of transcription factors, induces EMT and has a critical role in metastasis of multiple human cancers. However, the role of FoxC1 in the progression of NPC has remained elusive. The present study revealed that the expression of FoxC1 was markedly elevated in NPC tissues compared with that in chronically inflamed nasopharyngeal tissues and was closely correlated with vimentin, fibronectin and N-cadherin expression as indicated by immunohisto-chemical assays. In addition, high FoxC1 expression was positively associated with lymph node metastasis, distant metastasis and an advanced clinical stage in patients with NPC. Furthermore, FoxC1 expression was high in NPC cell lines while being low in an immortalized normal nasopharyngeal epithelial cell line. In vitro, knockdown of FoxC1 in the CNE2 human NPC cell line by small interfering RNA downregulated vimentin, fibronectin and N-cadherin expression and reduced the migratory and invasive capacity of CNE2 cells. In conclusion, the present study indicated that FoxC1 has a pivotal role in EMT through the upregulation of vimentin, fibronectin and N-cadherin expression. Thus, FoxC1 may be a potential therapeutic target in NPC. PMID:26461269

  16. Forkhead box C1 induces epithelial‑mesenchymal transition and is a potential therapeutic target in nasopharyngeal carcinoma.

    PubMed

    Ou-Yang, Lei; Xiao, Sheng-Jun; Liu, Peng; Yi, Shi-Jang; Zhang, Xiao-Ling; Ou-Yang, Shi; Tan, Sheng-Kui; Lei, Xun

    2015-12-01

    Nasopharyngeal carcinoma (NPC) is a highly invasive malignancy with cervical lymphopathy as the initial presentation. Epithelial‑mesenchymal transition (EMT), a process by which epithelial cells lose cell‑cell adhesion and gain migratory and invasive properties, has a pivotal role in metastasis. Forkhead box C1 (FoxC1), a member of the forkhead family of transcription factors, induces EMT and has a critical role in metastasis of multiple human cancers. However, the role of FoxC1 in the progression of NPC has remained elusive. The present study revealed that the expression of FoxC1 was markedly elevated in NPC tissues compared with that in chronically inflamed nasopharyngeal tissues and was closely correlated with vimentin, fibronectin and N‑cadherin expression as indicated by immunohistochemical assays. In addition, high FoxC1 expression was positively associated with lymph node metastasis, distant metastasis and an advanced clinical stage in patients with NPC. Furthermore, FoxC1 expression was high in NPC cell lines while being low in an immortalized normal nasopharyngeal epithelial cell line. In vitro, knockdown of FoxC1 in the CNE2 human NPC cell line by small interfering RNA downregulated vimentin, fibronectin and N‑cadherin expression and reduced the migratory and invasive capacity of CNE2 cells. In conclusion, the present study indicated that FoxC1 has a pivotal role in EMT through the upregulation of vimentin, fibronectin and N‑cadherin expression. Thus, FoxC1 may be a potential therapeutic target in NPC. PMID:26461269

  17. Prognostic Value of Subclassification Using MRI in the T4 Classification Nasopharyngeal Carcinoma Intensity-Modulated Radiotherapy Treatment

    SciTech Connect

    Chen Lei; Liu Lizhi; Chen Mo; Li Wenfei; Yin Wenjing; Lin Aihua; Sun Ying; Li Li; Ma Jun

    2012-09-01

    Purpose: To subclassify patients with the T4 classification nasopharyngeal carcinoma (NPC), according to the seventh edition of the American Joint Committee on Cancer staging system, using magnetic resonance imaging (MRI), and to evaluate the prognostic value of subclassification after intensity-modulated radiotherapy (IMRT). Methods and Materials: A total of 140 patients who underwent MRI and were subsequently histologically diagnosed with nondisseminated classification T4 NPC received IMRT as their primary treatment and were included in this retrospective study. T4 patients were subclassified into two grades: T4a was defined as a primary nasopharyngeal tumor with involvement of the masticator space only; and T4b was defined as involvement of the intracranial region, cranial nerves, and/or orbit. Results: The 5-year overall survival (OS) rate and distant metastasis-free survival (DMFS) rate for T4a patients (82.5% and 87.0%, respectively), were significantly higher than for T4b patients (62.6% and 66.8%; p = 0.033 and p = 0.036, respectively). The T4a/b subclassification was an independent prognostic factor for OS (hazard ratio = 2.331, p = 0.032) and DMFS (hazard ratio = 2.602, p = 0.034), and had no significant effect on local relapse-free survival. Conclusions: Subclassification of T4 patients, as T4a or T4b, using MRI according to the site of invasion, has prognostic value for the outcomes of IMRT treatment in NPC.

  18. MicroRNA-92a promotes metastasis of nasopharyngeal carcinoma by targeting the PTEN/AKT pathway

    PubMed Central

    Zhang, Haixiong; Cao, Hui; Xu, Dadao; Zhu, Kang

    2016-01-01

    MicroRNAs have been confirmed to be a group of important regulators during the pathogenesis of nasopharyngeal carcinoma (NPC). This study confirmed that the expression of microRNA-92a (miR-92a) was significantly upregulated in NPC as compared to noncancerous nasopharyngeal epithelial tissues. Furthermore, high expression of miR-92a was observed in all NPC cell lines, especially in high metastatic cell lines. Clinical analysis indicated that high expression of miR-92a was associated with adverse clinicopathological features including the advanced tumor-node-metastasis stage and distant metastasis, and conferred poor prognosis of patients. In vitro assays showed that miR-92a overexpression potentiated the migration and invasion of 6-10B cells, and miR-92a silencing reduced the number of migrated and invaded 5-8F cells. Phosphatase and tensin homolog (PTEN) was confirmed as a direct downstream target of miR-92a in NPC cells. Otherwise, alteration of miR-92a expression regulated PTEN/AKT pathway in NPC cells. Mechanistically, miR-92a exerted its promoting effects on the metastatic behaviors of NPC cells through suppressing PTEN/AKT pathway. Taken together, this study demonstrates that miR-92a is a promising prognostic biomarker for patients with NPC, and may be a potential therapeutic target to prevent the metastasis of NPC. PMID:27366095

  19. MicroRNA-205 promotes the tumorigenesis of nasopharyngeal carcinoma through targeting tumor protein p53-inducible nuclear protein 1

    PubMed Central

    NIE, GUOHUI; DUAN, HONGFANG; LI, XIAOQING; YU, ZHENDONG; LUO, LIANG; LU, RUIJING; JI, ZILIANG; ZHANG, WEI

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is a common type of cancer in southern China, miRNAs have been shown to be involved in the tumorigenesis of multiple cancer types. The present study aimed to explore the potential role of miR-205 in NPC. Reverse transcription quantitative polymerase chain reaction was used to determine the expression levels of miR-205 in 20 fresh NPC specimens and 20 normal nasopharyngeal tissues. The function of miR-205 in the proliferation, migration, invasion and apoptosis of NPC-derived cells was detected by MTT assay, colony formation assay, wound healing assay, Transwell assay and flow cytometry. Furthermore, a target gene of miR-205 was identified using the luciferase reporter assay. The expression of miR-205 was increased in NPC tissues compared with that in normal tissues. Overexpression of miR-205 was found to promote the proliferation, migration and invasion of NPC-derived cells, while apoptosis was suppressed. Tumor protein p53-inducible nuclear protein 1 was identified as a target gene of miR-205. Overall, the present study demonstrated that miR-205 may function as an oncogene in NPC tumorigenesis. PMID:26252115

  20. URG4 expression is a novel prognostic factor for the progression of nasopharyngeal carcinoma and overall survival of patient

    PubMed Central

    Yu, Guodong; Meng, Qingxiang; Zhang, Tian; Zeng, Chen; He, Benfu; Zhang, Shanshan

    2016-01-01

    URG4, a novel oncogene, is involved in the development and progression of various tumors. This study investigated the clinicopathological significance of URG4 in nasopharyngeal carcinoma (NPC). We used five NPC tissues and adjacent normal nasopharyngeal tissues to determine URG4 expression and found that URG4 was upregulated in NPC tissues. Immunohistochemistry analysis found URG4 was expressed positively in 97.1% (99/102) of NPC samples and highly expressed in 41.2% (42/102) of NPC samples. Its level was positively correlated with advancing clinical stage. Kaplan–Meier analysis with the log-rank test found that patients with high URG4 expression had poor outcome and patients with low URG4 expression had better survival. Statistical analysis showed that there was a significant correlation between URG4 expression and clinical stage, larger tumor size, and lymph node involvement. Cox-regression analysis showed that URG4 expression could serve as a prognostic factor for NPC patients. In summary, this study showed that URG4 was upregulated in NPC tissues, patients with high URG4 expression had poor outcome, and URG4 was found to be a valuable biomarker for NPC progression. PMID:27284257

  1. A real-time in vivo dosimetric verification method for high-dose rate intracavitary brachytherapy of nasopharyngeal carcinoma

    SciTech Connect

    Qi Zhenyu; Deng Xiaowu; Cao Xinping; Huang Shaomin; Lerch, Michael; Rosenfeld, Anatoly

    2012-11-15

    Purpose: A real-time in vivo dosimetric verification method using metal-oxide-semiconductor field effect transistor (MOSFET) dosimeters has been developed for patient dosimetry in high-dose rate (HDR) intracavitary brachytherapy of nasopharyngeal carcinoma (NPC). Methods: The necessary calibration and correction factors for MOSFET measurements in {sup 192}Iridium source were determined in a water phantom. With the detector placed inside a custom-made nasopharyngeal applicator, the actual dose delivered to the tumor was measured in vivo and compared to the calculated values using a commercial brachytherapy planning system. Results: Five MOSFETs were independently calibrated with the HDR source, yielding calibration factors of 0.48 {+-} 0.007 cGy/mV. The maximum sensitivity variation was no more than 7% in the clinically relevant distance range of 1-5 cm from the source. A total of 70 in vivo measurements in 11 NPC patients demonstrated good agreement with the treatment planning. The mean differences between the planned and the actually delivered dose within a single treatment fraction were -0.1%{+-} 3.8% and -0.1%{+-} 3.7%, respectively, for right and left side assessments. The maximum dose deviation was less than 8.5%. Conclusions: In vivo measurement using the real-time MOSFET dosimetry system is possible to evaluate the actual dose to the tumor received by the patient during a treatment fraction and thus can offer another line of security to detect and prevent large errors.

  2. The interplay of host genetic factors and Epstein-Barr virus in the development of nasopharyngeal carcinoma

    PubMed Central

    Lung, Maria Li; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Lung, Hong Lok; Cheng, Yue; Dai, Wei

    2014-01-01

    The interplay between host cell genetics and Epstein-Barr virus (EBV) infection contributes to the development of nasopharyngeal carcinoma (NPC). Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as well as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen (HLA) complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify the genes and pathways driving its molecular pathogenesis. PMID:25367335

  3. DC120, a novel AKT inhibitor, preferentially suppresses nasopharyngeal carcinoma cancer stem-like cells by downregulating Sox2

    PubMed Central

    Tang, Jun; Yang, Fen; Feng, Gong-Kan; Chen, Wen-Dan; Wu, Xiao-Qi; Qian, Xiao-Jun; Ding, Ke; Zhu, Xiao-Feng

    2015-01-01

    Side population (SP) contains cancer stem-like cells (CSLCs). In this study, we characterized SP cells from nasopharyngeal carcinoma (NPC) cell lines and found that SP cells had a higher self-renewal ability in vitro and greater tumorigenicity in vivo. The AKT pathway was activated in NPC SP cells. DC120, a 2-pyrimidyl-5-amidothiazole inhibitor of the ATP binding site of AKT, inhibited phosphorylation of FKHRL1 and GSK-3β. DC120 inhibited SP fraction, the sphere-forming ability in vitro and growth of primary xenografts as well as secondary xenografts’ tumor recurrence. This inhibition was accompanied by reduced expression of stem-related gene Sox2 due to induction of p27 and miR-30a. A combination of DC120 and CDDP more effectively inhibited NPC cells compared with monotherapy in vitro and in vivo. Clinical evaluation of DC120 is warranted. PMID:25749514

  4. Notch1 Signaling Is Activated in Cells Expressing Embryonic Stem Cell Proteins in Human Primary Nasopharyngeal Carcinoma

    PubMed Central

    Zhang, Yue; Peng, Jianhua; Zhang, Huxiang; Zhu, Yi; Wan, Li; Chen, Jianfu; Chen, Xiaoyun; Lin, Renyu; Li, He; Mao, XiaoOu; Jin, Kunlin

    2010-01-01

    Objective: To explore the expression of Notch1 signaling pathway in nasopharyngeal carcinoma (NPC). Methods: We performed immunocytochemistry on surgically resected NPC using antibodies against embryonic stem (ES) cell proteins and against Notch1 signaling components. Results: We found that ES cell protein markers SOX2 and OCT4 were expressed in a subpopulation of cells for all three subtypes of NPC but barely in the normal control. Double immunostaining shows that SOX2- and OCT4-positive cells coexpressed proliferative markers, suggesting that human NPC may contain cancer stem–like cells. In addition, we found that Notch1 signaling was activated in NPC. Confocal images show that the Notch1 signaling activated form and Hes1, a downstream target of Notch1 signaling, was predominantly found in SOX2- and OCT4-positive cells. Conclusion: Our findings suggest that the Notch1 signaling pathway might be a regulator of cancer stem–like cells in NPC. PMID:20211102

  5. Long-term prognostic implications and therapeutic target role of hexokinase II in patients with nasopharyngeal carcinoma

    PubMed Central

    Wang, Hai-Yun; Zhou, Ling; Mai, Hai-Qiang; Guo, Xiang; Zhao, Chong; Huang, Wen-Lin; Hong, Ming-Huang; Chen, Ming-Yuan

    2016-01-01

    Tumor cells preferentially use anaerobic glycolysis rather than oxidative phosphorylation to generate energy. Hexokinase II (HK-II) is necessary for anaerobic glycolysis and displays aberrant expression in malignant cells. The current study aimed to evaluate the role of HK-II in the survival and biological function of nasopharyngeal carcinoma (NPC). Our study demonstrated that high expression of HK-II was associated with poor survival outcomes in NPC patients. When using 3-BrOP (an HK-II inhibitor) to repress glycolysis, cell proliferation and invasion were attenuated, accompanied by the induction of apoptosis and cell cycle arrest at the G1 stage. Furthermore, 3-BrOP synergized with cisplatin (DDP) to induce NPC cell death. Collectively, we provided that the aberrant expression of HK-II was associated with the malignant phenotype of NPC. A combined treatment modality that targets glycolysis with DDP holds promise for the treatment of NPC patients. PMID:26848773

  6. Activities of gamma-glutamyl transpeptidase and erythrocyte glutathione dependent enzymes in nasopharyngeal carcinoma patients and normal controls.

    PubMed

    Ngah, W Z; Shamaan, N A; Said, M H; Azhar, M T

    1993-01-01

    Plasma gamma-glutamyltranspeptidase (gamma-GT), glutathione peroxidase (GPx) and glutathione reductase (GR) activities were determined in normal and nasopharyngeal carcinoma (NPC) patients. No difference in enzyme activities was observed in the three major races of the Malaysian population, i.e. Malay, Chinese and Indian patients. However, plasma gamma-GT, erythrocyte glutathione S-transferase (GST) and GPx activities were significantly increased in all NPC patients, while GR activity remained unchanged. Patients with elevated plasma gamma-GT activities also had increased GST and GPx activities. Plasma gamma-GT and GPx activities were then found to be affected by treatment. Patients with plasma gamma-GT activity greater than 70 IU/l had very poor prognoses but patients with decreased gamma-GT activities were found to be in remission. PMID:8105826

  7. Transcriptional expression of Epstein-Barr virus genes and proto-oncogenes in north African nasopharyngeal carcinoma.

    PubMed

    Sbih-Lammali, F; Djennaoui, D; Belaoui, H; Bouguermouh, A; Decaussin, G; Ooka, T

    1996-05-01

    Cases of nasopharyngeal carcinoma (NPC) from North Africa show an unusual bimodal age distribution. As elsewhere, the tumor is closely associated with the presence of Epstein-Barr virus (EBV). The expression of EBV genes and c-onc genes was studied in biopsy specimens from tumors at different clinical stages from 11 young (10 to 30-year-old) and 11 adult (30 to 65-year-old) patients. It was found that the two age groups do not differ in their pattern of gene expression, that there is a tendency for later stage biopsies to express more viral and c-onc transcripts, and that samples expressing larger numbers of EBV genes also tend to express many different c-onc specificities. PMID:8732865

  8. Effects of epigallocatechin gallate on the proliferation and apoptosis of the nasopharyngeal carcinoma cell line CNE2

    PubMed Central

    ZHANG, WEIJUN; YANG, PING; GAO, FEI; YANG, JIE; YAO, KAITAI

    2014-01-01

    The present study explored the effects of epigallocatechin gallate (EGCG) on the cell cycle, proliferation and apoptosis of the nasopharyngeal carcinoma cell line CNE2 in vitro. The proliferation of CNE2 cells was detected using the cell counting kit-8 method. Cell cycle distribution and apoptosis were detected using flow cytometry. The human telomerase reverse transcriptase (hTERT) mRNA expression was determined using reverse transcription polymerase chain reactions. The protein expression of hTERT and Myc proto-oncogene protein (c-Myc) was observed using western blot analysis. EGCG inhibited the proliferation of CNE2 cells in a concentration-dependent manner (P<0.05) and blocked the cell cycle progression of the cells. In the low concentration (100 μg/ml) group, the cell cycle arrest showed a time-dependent manner. However, as the concentration increased and action time was prolonged, this time dependency became less marked. EGCG promoted the apoptosis of CNE2 cells in a time-dependent manner. In addition, EGCG downregulated the mRNA and protein expression of hTERT and downregulated the expression of c-Myc protein. Downregulation of the expression of hTERT and c-Myc was more evident in the high-dose group (200 μg/mL). In conclusion, EGCG has proliferation-inhibiting, cell cycle-blocking and apoptosis-promoting effects on CNE2 cells. EGCG may be developed into an auxiliary therapeutic agent for the treatment of nasopharyngeal carcinoma. PMID:25371733

  9. Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting NF-κB and COX-2 signaling.

    PubMed

    Zhuang, Mingzhu; Zhao, Mouming; Qiu, Huijuan; Shi, Dingbo; Wang, Jingshu; Tian, Yun; Lin, Lianzhu; Deng, Wuguo

    2014-01-01

    Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC) cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-κB proteins. Moreover, effusanin E abrogated the binding of NF-κB to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-κB-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate) had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-κB/COX-2 (lipopolysaccharides) abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-κB and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma. PMID:25333664

  10. Effusanin E Suppresses Nasopharyngeal Carcinoma Cell Growth by Inhibiting NF-κB and COX-2 Signaling

    PubMed Central

    Zhuang, Mingzhu; Zhao, Mouming; Qiu, Huijuan; Shi, Dingbo; Wang, Jingshu; Tian, Yun; Lin, Lianzhu; Deng, Wuguo

    2014-01-01

    Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC) cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-κB proteins. Moreover, effusanin E abrogated the binding of NF-κB to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-κB-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate) had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-κB/COX-2 (lipopolysaccharides) abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-κB and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma. PMID:25333664

  11. Experience with combination of nimotuzumab and intensity-modulated radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma

    PubMed Central

    Zhai, Rui-ping; Ying, Hong-mei; Kong, Fang-fang; Du, Cheng-run; Huang, Shuang; Zhou, Jun-jun; Hu, Chao-su

    2015-01-01

    Aim To evaluate the efficacy and safety of using nimotuzumab in combination with intensity-modulated radiotherapy (IMRT) in the primary treatment of locoregionally advanced nasopharyngeal carcinoma. Methods Between December 2009 and December 2013, 38 newly diagnosed patients with stage III–IV nasopharyngeal carcinoma were treated with IMRT and nimotuzumab concomitantly. The distribution of disease was stage III in 20 (52.6%), stage IV A in 9 (23.7%), and stage IV B in 9 (23.7%). All the patients received at least two cycles of cisplatin-based neoadjuvant chemotherapy followed by nimotuzumab 200 mg/week concurrently with IMRT. Acute and late radiation-related toxicities were graded according to the Acute and Late Radiation Morbidity Scoring Criteria of Radiation Therapy Oncology Group. Results With a median follow-up of 39.7 months (range, 13.3–66.5 months), the estimated 3-year local recurrence-free survival, regional recurrence-free survival, distant metastasis-free survival, progression failure-free survival, and overall survival rates were 92.8%, 92.9%, 89.5%, 78.7%, and 87.5%, respectively. The median cycle for nimotuzumab addition was 6 weeks. Grade 3 radiation-induced mucositis accounted for 36.8% of treated people. No skin rash and infusion reaction were observed, distinctly from what is reported in cetuximab-treated patients. Conclusion Nimotuzumab plus IMRT showed promising outcomes in terms of locoregional control and survival, without increasing the incidence of radiation-related toxicities for patients. PMID:26604795

  12. Tumor Regression and Patterns of Distant Metastasis of T1-T2 Nasopharyngeal Carcinoma with Intensity-Modulated Radiotherapy

    PubMed Central

    Wu, Ming-Yao; He, Xia-Yun; Hu, Chao-Su

    2016-01-01

    Purpose To study tumor regression and failure patterns in T1-T2 non-metastatic nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). Methods A retrospective analysis of 139 nasopharyngeal carcinoma patients treated with IMRT between January 2005 and December 2010 in our center was performed. According to the AJCC staging system, all primary lesions were attributed to T1 and T2. The prescription doses were 66 Gy at 30 fractions to gross tumor volume of the nasopharynx and the positive neck nodes, 60 Gy to high-risk clinical target volume and 54 Gy to low-risk clinical target volume. Patients staged III, IV A/B or II (lymph node measured 4 cm or more in diameter) received platinum-based chemotherapy. Results By the end of radiotherapy, 7.2% (10/139), 23.7% (33/139), and 9.4% (13/139) of patients had residual lesions in the nasopharynx, cervical lymph nodes and retropharyngeal lymph nodes, respectively. The majority of patients had complete remission within 6 months of radiotherapy completion. Five months after IMRT, three patients with residual tumors in the cervical lymph nodes underwent surgery. Among these patients, two patients had positive pathological findings, and one patient had negative findings. With a median follow-up of 59 months, the 5-year overall survival, local control, regional control and distant metastasis-free rates were 87.8%, 96.7%, 94.9% and 89.1%, respectively. Fifteen patients developed distant metastases, representing the primary failure pattern. Conclusions Most residual lesions that persisted after IMRT vanished completely in six months. Considering the potential damage to normal structures, clinicians should be cautious when considering the use of boost irradiation after radiotherapy. Distant metastasis was the primary cause of treatment failure, which was significantly higher in N2-3 patients than in N0-1. Additional studies to better understand distant metastases are needed. PMID:27119991

  13. Different setup errors assessed by weekly cone-beam computed tomography on different registration in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy

    PubMed Central

    Su, Jiqing; Chen, Wen; Yang, Huiyun; Hong, Jidong; Zhang, Zijian; Yang, Guangzheng; Li, Li; Wei, Rui

    2015-01-01

    The study aimed to investigate the difference of setup errors on different registration in the treatment of nasopharyngeal carcinoma based on weekly cone-beam computed tomography (CBCT). Thirty nasopharyngeal cancer patients scheduled to undergo intensity-modulated radiotherapy (IMRT) were prospectively enrolled in the study. Each patient had a weekly CBCT before radiation therapy. In the entire study, 201 CBCT scans were obtained. The scans were registered to the planning CT to determine the difference of setup errors on different registration sites. Different registration sites were represented by bony landmarks. Nasal septum and pterygoid process represent head, cervical vertebrae 1–3 represent upper neck, and cervical vertebrae 4–6 represent lower neck. Patient positioning errors were recorded in the right–left (RL), superior–inferior (SI), and anterior–posterior (AP) directions over the course of radiotherapy. Planning target volume margins were calculated from the systematic and random errors. In this study, we can make a conclusion that there are setup errors in RL, SI, and AP directions of nasopharyngeal carcinoma patients undergoing IMRT. In addition, the head and neck setup error has the difference, with statistical significance, while patient setup error of neck is greater than that of head during the course of radiotherapy. In our institution, we recommend a planning target volume margin of 3.0 mm in RL direction, 1.3 mm in SI direction, and 2.6 mm in AP direction for nasopharyngeal cancer patients undergoing IMRT with weekly CBCT scans. PMID:26396530

  14. On the trails of markers and proxies: the socio-cognitive technologies of human movement, knowledge assemblage, and their relevance to the etiology of nasopharyngeal carcinoma

    PubMed Central

    Turnbull, David

    2011-01-01

    Bacteria, pigs, rats, pots, plants, words, bones, stones, earrings, diseases, and genetic indicators of all varieties are markers and proxies for the complexity of interweaving trails and stories integral to understanding human movement and knowledge assemblage in Southeast Asia and around the world. Understanding human movement and knowledge assemblage is central to comprehending the genetic basis of disease, especially of a cancer like nasopharyngeal carcinoma. The problem is that the markers and trails, taken in isolation, do not all tell the same story. Human movement and knowledge assemblage are in constant interaction in an adaptive process of co-production with genes, terrain, climate, sea level changes, kinship relations, diet, materials, food and transport technologies, social and cognitive technologies, and knowledge strategies and transmission. Nasopharyngeal carcinoma is the outcome of an adaptive process involving physical, social, and genetic components. PMID:21272440

  15. [Nasopharyngeal adenoid cystic carcinoma, a rare but highly challenging disease with unmet therapeutic needs: A case-report and review of the literature].

    PubMed

    Afani, L; Errihani, H; Benchafai, I; Lalami, Y

    2016-07-01

    Nasopharyngeal adenoid cystic carcinoma is a rare tumour. Compared with others nasopharyngeal tumours, it is characterised by slow evolution but it is locally aggressive and has a high tendency to recurrences. Due to the rarity of cases, no consensus exists about treatment approaches. We report the case of 45-year-old-man with a locally advanced adenoid cystic carcinoma. The patient received concurrent chemoradiation and had a good objective response. After one year, he developed a paucisymptomatic lung metastasis. The follow-up showed local recurrence after 3 years. One cycle of chemotherapy was given but poorly supported. Carbon ion radiotherapy was proposed. The aim of this work is to review the literature concerning this rare malignancy and discusses treatment approaches in initial situations and during recurrences. PMID:27131394

  16. Parthenolide Inhibits Cancer Stem-Like Side Population of Nasopharyngeal Carcinoma Cells via Suppression of the NF-κB/COX-2 Pathway

    PubMed Central

    Liao, Kun; Xia, Bin; Zhuang, Qun-Ying; Hou, Meng-Jun; Zhang, Yu-Jing; Luo, Bing; Qiu, Yang; Gao, Yan-Fang; Li, Xiao-Jie; Chen, Hui-Feng; Ling, Wen-Hua; He, Cheng-Yong; Huang, Yi-Jun; Lin, Yu-Chun; Lin, Zhong-Ning

    2015-01-01

    Cancer stem cells play a central role in the pathogenesis of nasopharyngeal carcinoma and contribute to both disease initiation and relapse. In this study, cyclooxygenase-2 (COX-2) was found to regulate cancer stem-like side population cells of nasopharyngeal carcinoma cells and enhance cancer stem-like cells' characteristics such as higher colony formation efficiency and overexpression of stemness-associated genes. The regulatory effect of COX-2 on cancer stem-like characteristics may be mediated by ABCG2. COX-2 overexpression by a gain-of-function experiment increased the proportion of side population cells and their cancer stemness properties. The present study also demonstrated that in contrast to the classical chemotherapy drug 5-fluorouracil, which increased the proportion of side population cells and upregulated the expression of COX-2, parthenolide, a naturally occurring small molecule, preferentially targeted the side population cells of nasopharyngeal carcinoma cells and downregulated COX-2. Moreover, we found that the cancer stem-like cells' phenotype was suppressed by using COX-2 inhibitors NS-398 and CAY10404 or knocking down COX-2 with siRNA and shRNA. These findings suggest that COX-2 inhibition is the mechanism by which parthenolide induces cell death in the cancer stem-like cells of nasopharyngeal carcinoma. In addition, parthenolide exhibited an inhibitory effect on nuclear factor-kappa B (NF-κB) nucler translocation by suppressing both the phosphorylation of IκB kinase complex and IκBα degradation. Taken together, these results suggest that parthenolide may exert its cancer stem cell-targeted chemotherapy through the NF-κB/COX-2 pathway. PMID:25553117

  17. Phase II Sequential and Concurrent Chemoradiation for Advanced Nasopharyngeal Carcinoma (NPC)

    ClinicalTrials.gov

    2016-07-20

    Stage II Lymphoepithelioma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx

  18. 1,8-dihydroxy-3-acetyl-6-methyl-9,10 anthraquinone exhibits a potent radiosensitizing effect with induced oncosis in human nasopharyngeal carcinoma cells.

    PubMed

    Hou, Huaxin; Li, Danrong; Jiang, Wei; Liang, Yan; Chen, Donglian; Mo, Yuanyuan

    2014-08-01

    1,8‑dihydroxy‑3‑acetyl‑6‑methyl‑9,10 anthraquinone (DAMA) was synthesized from emodin. In the present study, the activity and the oncosis‑like mechanism of DAMA‑enhanced nasopharyngeal carcinoma (NPC) cell sensitivity to ionizing radiation was examined. The results demonstrated that DAMA has a 1.46‑fold radiosensitisation activity for nasopharyngeal carcinoma CNE 1 cells with a non‑cytotoxic concentration of 10 µg/ml DAMA combined with 2 Gy. Following treatment of DAMA combined with radiation, CNE‑1 cells revealed severe cytoplasmic swelling and vacuolization, swollen mitochondria and dilation of the nuclei without chromatin condensation, yielding a typical morphology of oncosis. Oncosis‑related gene expression of ATP synthase F0 subunit 6, chromatin modifying protein 6 and cyclophilin D mRNA increased significantly in the 8 Gy radiation group and the 2 Gy radiation combined with DAMA group. A significant decrease of ATP synthase protein 8 mRNA was observed and the levels of intracellular ATP were also reduced. In addition, the levels of intracellular Ca2+ were increased. In conclusion, DAMA is a potent radiation sensitizer in nasopharyngeal carcinoma cells and mediates its radiosensitisation via oncosis. PMID:24912934

  19. Morphine, a potential antagonist of cisplatin cytotoxicity, inhibits cisplatin-induced apoptosis and suppression of tumor growth in nasopharyngeal carcinoma xenografts

    PubMed Central

    Cao, Long-Hui; Li, Hui-Ting; Lin, Wen-Qian; Tan, Hong-Ying; Xie, Lan; Zhong, Zhong-Jian; Zhou, Jian-Hua

    2016-01-01

    Morphine is an opioid analgesic drug often used for pain relief in cancer patients. However, there is growing evidence that morphine may modulate tumor growth, progression and metastasis. In this study, we evaluated whether morphine modulates cisplatin-induced apoptosis in human nasopharyngeal carcinoma CNE-2 cells and whether morphine affects the antitumor activity of cisplatin on tumor growth in human nasopharyngeal carcinoma CNE-2 xenografts in nude mice. We showed that a pretreatment with morphine (1 μg/ml) inhibited the sensitivity of CNE-2 cells to cisplatin by inhibiting cisplatin-induced CNE-2 cell apoptosis, decreasing caspase-3 activity and increasing the Bcl-2/Bax ratio. However, a high dose of morphine (1000 μg/ml) had the opposite effect. We also showed that at a low dose, morphine enhances chemoresistance in an in vivo nasopharyngeal carcinoma (NPC) model by inhibiting cisplatin-induced apoptosis and decreasing neovascularization. Taken together, our results indicate that a low dose of morphine may lead to chemoresistance of cisplatin in NPC models in vitro and in vivo by inhibiting cisplatin-induced apoptosis and decreasing neovascularization. PMID:26729257

  20. Eating ability predicts subsequent quality of life in Chinese patients with breast, liver, lung, or nasopharyngeal carcinoma: a longitudinal analysis.

    PubMed

    Wong, Wing S; Fielding, Richard

    2008-01-01

    Eating dysfunction is a well-recognized consequence of orophagic tract cancers, but also occurs with other cancers. There is a relative absence of data assessing the impact of eating function on QoL in cancer populations other than those with disease of the oro-phagic tract. We assessed longitudinal changes in eating function and quality of life (QoL), and examined whether eating function predicted QoL over time in a sample of Chinese patients with breast, lung, liver, and nasopharyngeal cancers. Overall, 1 079 patients with breast, liver, lung, or nasopharyngeal carcinoma were assessed during their first outpatient visit (baseline) and at two follow-up interviews (FU1 and FU2). Three dimensions of eating function, including ability, appetite, and enjoyment, were assessed using three 11-point self-rated items. QoL was measured by the Chinese version of the Functional Assessment of Cancer Therapy-General Scale (FACT-G (Ch)). Linear mixed effects (LME) models evaluated mean differences on eating function and QoL scores across interviews and across cancer groups, and the effects of eating function on QoL. After adjustment for socio-demographic and medical variables, pain and depression, eating function significantly predicted patient overall (standardized betas ranged from 0.091 to 0.163, ps < 0.05), physical (standardized betas ranged from 0.101 to 0.200, ps < 0.05), and functional (standardized betas ranged from 0.120 to 0.162, ps < 0.05) aspects of QoL scores over time. Eating dysfunction significantly impacts QoL in cancer populations other than those with orophagic disease. Change of eating function appears to be a common problem in cancer patients regardless of cancer site. PMID:18097779

  1. The efficacy and toxicity of individualized intensity-modulated radiotherapy based on the tumor extension patterns of nasopharyngeal carcinoma

    PubMed Central

    Zhou, Guan-Qun; Guo, Rui; Zhang, Fan; Zhang, Yuan; Xu, Lin; Zhang, Lu-Lu; Lin, Ai-Hua; Ma, Jun; Sun, Ying

    2016-01-01

    Background To evaluate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) using individualized clinical target volumes (CTVs) based on the loco-regional extension patterns of nasopharyngeal carcinoma (NPC). Methods From December 2009 to February 2012, 220 patients with histologically-proven, non-disseminated NPC were prospectively treated with IMRT according to an individualized delineation protocol. CTV1 encompassed the gross tumor volume, entire nasopharyngeal mucosa and structures within the pharyngobasilar fascia with a margin. CTV2 encompassed bilateral high risk anatomic sites and downstream anatomic sites adjacent to primary tumor, bilateral retropharyngeal regions, levels II, III and Va, and prophylactic irradiation was gave to one or two levels beyond clinical lymph nodes involvement. Clinical outcomes and toxicities were evaluated. Results Median follow-up was 50.8 (range, 1.3–68.0) months, four-year local relapse-free, regional relapse-free, distant metastasis-free, disease-free and overall survival rates were 94.7%, 97.0%, 91.7%, 87.2% and 91.9%, respectively. Acute severe (≥ grade 3) mucositis, dermatitis and xerostomia were observed in 27.6%, 3.6% and zero patients, respectively. At 1 year, xerostomia was mild, with frequencies of Grade 0, 1, 2 and 3 xerostomia of 27.9%, 63.3%, 8.3% and 0.5%, respectively. Conclusions IMRT using individualized CTVs provided high rates of local and regional control and a favorable toxicity profile in NPC. Individualized CTV delineation strategy is a promising one that may effectively avoid unnecessary or missed irradiation, and deserve optimization to define more precise individualized CTVs. PMID:26980744

  2. Effect of Prolonged Radiotherapy Treatment Time on Survival Outcomes after Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma

    PubMed Central

    Luo, Dong-Hua; Shen, Ting; Mai, Dong-Mei; Hu, Wei-Han; Mo, Hao-Yuan

    2015-01-01

    Purpose To estimate the influence of prolonged radiation treatment time (RTT) on survival outcomes in nasopharyngeal carcinoma after continuous intensity-modulated radiation therapy. Methods and Materials Retrospectively review 321 patients with NPC treated between October 2009 and December 2010 and all of them underwent simultaneous accelerated intensity-modulated radiation therapy. The fractionated dose was 2–2.47 Gy/F (median 2.27 Gy), and the total dose for nasopharyngeal region was 64–74 Gy/ 28–33 fractions. The association of prolonged RTT and treatment interruption with PFS, LRFS and DFFS were assessed by univariate analysis and multivariate analysis. Survival analyses were carried out using Kaplan–Meier methodology and the log-rank test was used to assess the difference. The Cox regression proportional hazard model was used for multivariate analyses and evaluating the prognostic parameters for PFS, LRFS and DFFS. Results Univariate analysis revealed no significant associations between prolonged RTT and PFS, LRFS, DFFS when dichotomized using various cut-off values (all P>0.05). In multivariate analysis, RTT (range, 36–63 days) as a continuous variable, had no influence on any survival outcome as well (P>0.05). T and N classification were independent prognostic factors for PFS, LRFS and DFFS (all P<0.05, except T classification for LRFS, P = 0.057). Age was an independent prognostic factor for PFS (hazard ratio [HR], 1.033; P = 0.008) and DFFS (HR, 1.032; P = 0.043). Conclusion We conclude that no such association between survival outcomes and radiation treatment duration (range: 36–63 days) can be found in the present retrospective study, however, we have to remind that prolongation in treatment should be limited in clinical application and interruptions caused by any reason should be minimized as much as possible. PMID:26506559

  3. Nasopharyngeal Case-Control Study

    Cancer.gov

    A case-control study conducted in Taiwan between 1991-1994 among approximately 1,000 individuals to examine the role of viral, environmental, and genetic factors associated with the development of nasopharyngeal carcinoma

  4. Functional expression of chloride channels and their roles in the cell cycle and cell proliferation in highly differentiated nasopharyngeal carcinoma cells

    PubMed Central

    Huang, Weiyuan; Liu, Mei; Zhu, Linyan; Liu, Shanwen; Luo, Hai; Ma, Lianshun; Wang, Haibo; Lu, Ruiling; Sun, Xiaoxue; Chen, Lixin; Wang, Liwei

    2014-01-01

    Abstract We previously demonstrated that the growth of the poorly differentiated nasopharyngeal carcinoma cells (CNE‐2Z) was more dependent on the activities of volume‐activated chloride channels than that of the normal nasopharyngeal epithelial cells (NP69‐SV40T). However, the activities and roles of such volume‐activated chloride channels in highly differentiated nasopharyngeal carcinoma cells (CNE‐1) are not clarified. In this study, it was found that a volume‐activated chloride current and a regulatory volume decrease (RVD) were induced by 47% hypotonic challenges. The current density and the capacity of RVD in the highly differentiated CNE‐1 cells were lower than those in the poorly differentiated CNE‐2Z cells, and higher than those in the normal cells (NP69‐SV40T). The chloride channel blockers, 5‐nitro‐2‐(3‐phenylpropylamino) benzoic acid (NPPB) and tamoxifen inhibited the current and RVD. Depletion of intracellular Cl− abolished the RVD. The chloride channel blockers reversibly inhibited cell proliferation in a concentration‐ and time‐dependent manner, and arrested cells at the G0/G1 phases, but did not change cell viability. The sensitivity of the three cell lines to the chloride channel blockers was different, with the highest in poorly differentiated cells (CNE‐2Z) and the lowest in the normal cells (NP69‐SV40T). ClC‐3 proteins were expressed in the three cells and distributed inside the cells as well as on the cell membrane. In conclusion, the highly differentiated nasopharyngeal carcinoma CNE‐1 cells functionally expressed the volume‐activated chloride channels, which may play important roles in controlling cell proliferation through modulating the cell cycle, and may be associated with cell differentiation. Chloride channels may be a potential target of anticancer therapy. PMID:25214521

  5. Syphilis manifesting as a nasopharyngeal carcinoma with cervical lymphadenopathy: A case report

    PubMed Central

    PAN, XINBIN; ZHU, XIAODONG; LI, QINGDI QUENTIN

    2012-01-01

    The present case report describes a case of syphilitic lymphadenopathy and raises the awareness of the differential diagnosis of cervical lymphadenopathy. A 50-year-old male worker presented with a 6-month history of enlarged and growing lymph nodes in the right upper neck and a blood-tinged post-nasal drip. Physical examination showed multiple enlarged lymph nodes located in the right upper neck. On nasopharyngoscopy, a mass was found in the nasopharynx. The histopathology of both the nasopharyngeal mass and the enlarged lymph nodes revealed non-specific inflammation. Rapid plasma reagin test results (titer, 1:1280) and Treponema pallidum particle assay results (titer, 1:2560) were positive. Subsequently, a diagnosis of syphilis was confirmed clinically and serologically. The reaction after penicillin treatment further confirmed the syphilis diagnosis. Thus, syphilis should be considered as a possibility in the differential diagnosis of cervical lymphadenopathy. PMID:22970011

  6. Concurrent alterations of RAGE, RECK, and MMP9 protein expression are relevant to Epstein-Barr virus infection, metastasis, and survival in nasopharyngeal carcinoma.

    PubMed

    Zhou, Dong-Ni; Deng, Yan-Fei; Li, Rong-Hua; Yin, Ping; Ye, Chun-Sheng

    2014-01-01

    This study aimed to concurrently investigate the expressions of receptor for advanced glycation end products (RAGE), reversion inducing cysteine-rich protein with Kazal motifs (RECK) and matrix metalloproteinase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and their correlations with clinicopathological properties. Using immunohistochemistry, we found that RECK expression was downregulated in NPC tissues compared with chronic nasopharyngitis (CNT) tissues, while RAGE and MMP9 expressions were upregulated. We further found that RECK expression level was inversely correlated with MMP9 expression level in NPC, whereas RAGE expression level was positively correlated with MMP9 expression level. Moreover, aberrant expressions of these proteins had a positive correlation with the titers of EBVCA-IgA, lymphatic metastasis, recurrence and survival. Together, these findings suggest that dysregulations of RECK and RAGE expressions may be collectively involved in tumor progression of NPC by regulating MMP9 expression and that they may be a good prognostic predictors for NPC. PMID:25031745

  7. Epigenetic downregulation of the ISG15–conjugating enzyme UbcH8 impairs lipolysis and correlates with poor prognosis in nasopharyngeal carcinoma

    PubMed Central

    Chen, Fu; Xiao, Xue; Huang, Tingting; He, Qian; Wang, Shumin; Du, Chunping; Mo, Yingxi; Lin, Longde; Xie, Ying; Wei, Lili; Lan, Ying; Murata, Mairiko; Huang, Guangwu; Ernberg, Ingemar; Matskova, Liudmila; Zhang, Zhe

    2015-01-01

    We identified the UBE2L6 gene, encoding the ISG15-conjugating enzyme UbcH8, as one gene significantly downregulated by promoter hypermethylation in nasopharyngeal carcinoma (NPC). Reduced expression of the UbcH8 protein correlated with poor outcome in NPC patients. Restored expression of UBE2L6 suppressed proliferation and colony formation in NPC cells, while inducing apoptosis. Of particular interest, we found that aberrant lipid turnover was controlled by UbcH8 in NPC through ISG15-conjugation of valosin-containing protein (VCP). Tumor tissue and NPC cell lines showed conspicuously strong accumulation of lipid droplets (LDs) compared to control nasopharyngeal epithelium and non-cancerous cell lines. We demonstrated that UbcH8 counteracts degradation of adipocyte triglyceride lipase (ATGL), a key enzyme in lipid catabolism. PMID:26506425

  8. Upregulated TRIM29 promotes proliferation and metastasis of nasopharyngeal carcinoma via PTEN/AKT/mTOR signal pathway

    PubMed Central

    Sun, Jian; Zhang, Mei-Yin; Wang, Meng-He; Yang, Yang; Wang, Hui-Yun; Mai, Shi-Juan

    2016-01-01

    Tripartite motif–containing 29 (TRIM29) has been reported to be dysregulated in human cancers. Up-regulation of TRIM29 was first observed in NPC cell lines by a genome-wide transcriptome analysis in our previous study. However, its expression biological function and clinical significance in nasopharyngeal carcinoma (NPC) remain unclear. In this study, TRIM29 expression was validated by qRT-PCR and immunohistochemistry in 69 NPC samples. Notably, TRIM29 protein expression was significantly and positively correlated with the tumor size, clinical stage and metastasis. TRIM29 was identified as the direct target of miR-335-5p and miR-15b-5p, both of which were down-regulated and negatively associated with TRIM29 expression in NPC cell lines and clinical samples. Ectopic TRIM29 expression promoted proliferation, epithelial-mesenchymal transition (EMT), migration and invasion in NPC cells, while its depletion inhibited cell invasion and EMT phenotype. Mechanistically, TRIM29 overexpression reduced PTEN expression and increase phosphorylated protein level of AKT, p70S6K and 4E-BP1. Correspondingly, AKT inhibitor and Rapamycin blocked the effect of TRIM29 on cell invasion. In conclusion, our results suggest that miR-335-5p and miR-15b-5p down-regulation results in TRIM29 over-expression, which induces proliferation, EMT and metastasis of NPC through the PTEN/AKT/mTOR signaling pathway. PMID:26872369

  9. The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT

    PubMed Central

    Xu, Tingting; Shen, Chunying; Ou, Xiaomin; He, Xiayun; Ying, Hongmei; Hu, Chaosu

    2016-01-01

    Nasopharyngeal carcinoma (NPC) patients with N2–3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2–3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194–0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187–0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation. PMID:26942700

  10. RBM24 suppresses cancer progression by upregulating miR-25 to target MALAT1 in nasopharyngeal carcinoma.

    PubMed

    Hua, Wen-Feng; Zhong, Qian; Xia, Tian-Liang; Chen, Qi; Zhang, Mei-Yin; Zhou, Ai-Jun; Tu, Zi-Wei; Qu, Chen; Li, Man-Zhi; Xia, Yun-Fei; Wang, Hui-Yun; Xie, Dan; Claret, Francois-Xavier; Song, Er-Wei; Zeng, Mu-Sheng

    2016-01-01

    Abnormal interaction between non-coding RNAs has been demonstrated to be a common molecular event in various human cancers, but its significance and underlying mechanisms have not been well documented. RNA-binding proteins (RBPs) are key regulators of RNA transcription and post-transcriptional processing. In this study, we found that RNA-binding protein 24 (RBM24) was frequently downregulated in nasopharyngeal carcinoma (NPC). The restoration of RBM24 expression suppressed NPC cellular proliferation, migration and invasion and impeded metastatic colonization in mouse models. Microarray analyses revealed that miR-25 expression was upregulated by RBM24 expression in NPC cells. Similarly, ectopic miR-25 expression suppressed NPC cellular growth and motility by targeting the pro-oncogenic lncRNA MALAT1, and the knockdown of MALAT1 expression exhibited similar effects as RBM24 restoration in NPC cells. Overall, these findings suggest a novel role of RBM24 as a tumor suppressor. Mechanistically, RBM24 acts at least in part through upregulating the expression of miR-25, which in turn targets MALAT1 for degradation. PMID:27584791

  11. CD38 is a putative functional marker for side population cells in human nasopharyngeal carcinoma cell lines.

    PubMed

    Zheng, Danwei; Liao, Shan; Zhu, Guangchao; Luo, Gengqiu; Xiao, Songshu; He, Junyu; Pei, Zhen; Li, Guiyuan; Zhou, Yanhong

    2016-03-01

    Cancer stem cells (CSCs) are thought to be responsible for cancer progression and therapeutic resistance but identification of this subpopulation requires selective markers. Fortunately, side population (SP) cells analysis brings a novel method to CSCs study. In this study, we identified SP cells, which are demonstrated rich in CSCs, in four nasopharyngeal carcinoma (NPC) cell lines. We investigated SP cells from HK-1 NPC cell line and showed CSCs characteristics in this subpopulation. SP cells displayed greater proliferation and invasion and expressed high levels of CSCs markers than NSP cells. Furthermore, our microRNA microarray analysis of SP versus NSP cells revealed that CD38-related miRNAs were down-regulated in SP cell, but the mRNA and protein level of CD38 were highly expressed in SP cells. We further searched for molecules interacting with CD38 and identified ZAP70, which was also well expressed in SP cells at both mRNA and protein levels. Our results uncover a CD38 pathway that may regulate the proliferation and migration of SP cells from HK-1 NPC cell line. PMID:25630761

  12. Prognostic implications of dynamic serum lactate dehydrogenase assessments in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy

    PubMed Central

    Zhou, Guan-Qun; Ren, Xian-Yue; Mao, Yan-Ping; Chen, Lei; Sun, Ying; Liu, Li-Zhi; Li, Li; Lin, Ai-Hua; Mai, Hai-Qiang; Ma, Jun

    2016-01-01

    The prognostic value of dynamic serum lactate dehydrogenase (LDH) levels in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) hasn’t been explored. We retrospectively analyzed 1,428 cases of NPC treated with IMRT with or without chemotherapy. Elevated pre- and/or post-treatment LDH levels were found to be associated with unfavorable overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS), but not with local relapse-free survival (LRFS). The dynamic variations in LDH levels were prognostic factors for OS, DFS and DMFS, but not for LRFS. Multivariate analysis revealed that the N category, T category, post-treatment serum LDH level and age were independent prognostic factors for OS. Our results demonstrated that dynamic variations in LDH levels were associated with risk of distant failure and death, which may shed light on the dynamics of the disease and the response to therapy. We consider that LDH measurements will be of great clinical importance in the management of NPC, especially, when considering “decision points” in treatment algorithms. Therefore, we strongly recommend that LDH levels should be determined before and after treatment in NPC patients and the results integrated into decisions regarding treatment strategies. PMID:26928265

  13. MET inhibitor PHA-665752 suppresses the hepatocyte growth factor-induced cell proliferation and radioresistance in nasopharyngeal carcinoma cells

    SciTech Connect

    Liu, Tongxin; Li, Qi; Sun, Quanquan; Zhang, Yuqin; Yang, Hua; Wang, Rong; Chen, Longhua; Wang, Wei

    2014-06-20

    Highlights: • We demonstrated that irradiation induced MET overexpression and activation. • The aberrant MET signal mediated by HGF induced proliferation and radioresistance of NPC cells. • MET inhibitor PHA-665752 effectively suppressed HGF induced cell proliferation and radioresistance in NPC cells. • PHA-665752 suppressed the three downstream pathway of HGF/MET signal in a dose-dependent manner. - Abstract: Although ionizing radiation (IR) has provided considerable improvements in nasopharyngeal carcinoma (NPC), in subsets of patients, radioresistance is still a major problem in the treatment. In this study, we demonstrated that irradiation induced MET overexpression and activation, and the aberrant MET signal mediated by hepatocyte growth factor (HGF) induced radioresistance. We also found that MET inhibitor PHA-665752 effectively suppressed HGF induced cell proliferation and radioresistance in NPC cells. Further investigation indicated that PHA-665752 suppressed the phosphorylation of the Akt, ERK1/2, and STAT3 proteins in a dose-dependent manner. Our data indicated that the combination of IR with a MET inhibitor, such as PHA-665752, might be a promising therapeutic strategy for NPC.

  14. IL-8 suppresses E-cadherin expression in nasopharyngeal carcinoma cells by enhancing E-cadherin promoter DNA methylation.

    PubMed

    Zhang, Rui-Li; Peng, Li-Xia; Yang, Jun-Ping; Zheng, Li-Sheng; Xie, Ping; Wang, Meng-Yao; Huang, Bi-Jun; Zhao, Hua-Rong; Bao, Yong-Xing; Qian, Chao-Nan

    2016-01-01

    Nasopharyngeal carcinoma (NPC) has the highest metastasis potential among head and neck cancers. Distant metastasis is the major cause of treatment failure. Recent studies from our laboratory have revealed that IL-8 promotes NPC metastasis via activation of AKT signaling and induction of epithelial-mesenchymal transition (EMT) in the cells. In the present study, we found that IL-8 treatment for NPC cells resulted in an accumulation of DNMT1 protein through activating AKT1 pathway and consequent DNMT1 protein stabilization. Then DNMT1 suppressed E-cadherin expression by increasing the methylation of its promoter region. LY-294002 blocked IL-8-induced p-AKT1 activation resulting in reduction of DNMT1 and increase of E-cadherin expression, whereas forced demethylation using 5-aza-2'-deoxycytidine restored E-cadherin expression. In conclusion, our study, for the first time, shows that the IL-8/AKT1 signaling pathway stabilizes DNMT1 protein, consequently enhancing hypermethylation of E-cadherin promoter regions and downregulating E-cadherin protein level in NPC cells. Upon blockage of the IL-8/AKT pathway and inhibition of DNMT1, E-cadherin expression can be reversed. These data suggest that targeting the IL-8/AKT1 signaling pathway and DNMT1 may provide a potential therapeutic approach for blocking NPC metastasis. PMID:26530812

  15. Down-regulation of GnT-V enhances nasopharyngeal carcinoma cell CNE-2 radiosensitivity in vitro and in vivo

    SciTech Connect

    Zhuo, Enqing; He, Jiao; Wei, Ting; Zhu, Weiliang; Meng, Hui; Li, Yan; Guo, Linlang; Zhang, Jian

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer First investigated the role of GnT-V on the radiosensitivity of NPC cells in vitro and in vivo. Black-Right-Pointing-Pointer The mechanisms of the changing radiosensitivity were also investigated. Black-Right-Pointing-Pointer In this study, more than one experiment methods were used to investigate a problem. -- Abstract: The purpose of this study was to investigate the role of GnT-V on radiosensitivity in human nasopharyngeal carcinoma (NPC) both in vitro and in vivo, and the possible mechanism. The GnT-V stably suppressed cell line CNE-2 GnT-V/2224 was constructed from CNE-2 by transfection. The radiosensitivity of the cells was studied by CCK-8 assay, flow-cytometry, caspases-3 activity analysis and tumor xenografts model. The expression of Bcl-2, Bax and Bcl-xl was analyzed with or without radiation. The results showed that down-regulation of GnT-V enhanced CNE-2 radiosensitivity. The underlying mechanisms may be link to the cell cycle G2-M arrest and the reduction of Bcl-2/Bax ratio. The results suggest that GnT-V may be a potential target for predicting NPC response to radiotherapy.

  16. Cetuximab and Cisplatin Show Different Combination Effect in Nasopharyngeal Carcinoma Cells Lines via Inactivation of EGFR/AKT Signaling Pathway

    PubMed Central

    Gu, Jiajia; Yin, Li; Wu, Jing; Zhang, Nan; Huang, Teng; Ding, Kai; Cao, Haixia; Xu, Lin; He, Xia

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is a common malignant cancer in South China. Cisplatin is a classical chemotherapeutic employed for NPC treatment. Despite the use of cisplatin-based concurrent chemoradiotherapy, distant failure still confuses clinicians and the outcome of metastatic NPC remains disappointing. Hence, a potent systemic therapy is needed for this cancer. Epidermal growth factor receptor (EGFR) represents a promising new therapeutic target in cancer. We predicted that combining the conventional cytotoxic drug cisplatin with the novel molecular-targeted agent cetuximab demonstrates a strong antitumor effect on NPC cells. In this study, we selected HNE1 and CNE2 cells, which have been proved to possess different EGFR expression levels, to validate our conjecture. The two-drug regimen showed a significant synergistic effect in HNE1 cells but an additive effect in CNE2 cells. Our results showed that cisplatin-induced apoptosis was significantly enhanced by cetuximab in the high EGFR-expressing HNE1 cells but not in CNE2 cells. Further molecular mechanism study indicated that the EGFR/AKT pathway may play an important role in cell apoptosis via the mitochondrial-mediated intrinsic pathway and lead to the different antitumor effects of this two-drug regimen between HNE1 and CNE2 cells. Thus, the regimen may be applied in personalized NPC treatments. PMID:27313893

  17. Treatment of stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation

    SciTech Connect

    Lee, Anne W.M. . E-mail: awmlee@ha.org.hk; Yau, T.K.; Wong, Dominique H.M.; Chan, Elian W.K.; Yeung, Rebecca M.W.; Ng, W.T.; Tong, Macy; Soong, Inda S.; Sze, W.M.

    2005-12-01

    Purpose: To explore a more effective strategy for treating nasopharyngeal carcinoma with extensive locoregional disease. Methods and Materials: Between October 1998 and January 2003, 49 patients with Stage IV(A-B) disease infiltrating or abutting neurologic structures were treated with induction-concurrent chemotherapy and accelerated radiotherapy (RT). A combination of cisplatin and 5-fluorouracil was used in the induction phase and single-agent cisplatin in the concurrent phase. All patients were irradiated with conformal techniques at 2 Gy/fraction, six daily fractions weekly, to a total dose of 70 Gy. Results: Although 92% of patients had one or more acute toxicities Grade 3 or worse, 96% completed the whole course of RT, and 92% had five or more cycles of chemotherapy. The great majority of toxicities were uneventful, but 1 patient died of neutropenic sepsis. With a median follow-up of 3.1 years, 20 patients had failure at one or more sites and 15 patients died. The 3-year locoregional and distant failure-free rate was 77% and 75%, respectively, and the overall survival rate was 71%. At last follow-up, 27% of patients had developed late Grade 3 or worse toxicity (24% were hearing impairments), but none had radiation-induced neurologic damage. Conclusion: The current strategy achieved encouraging results for this poor prognostic group, and confirmation of the therapeutic gain by a prospective randomized trial is warranted.

  18. miR-133b, a microRNA targeting S1PR1, suppresses nasopharyngeal carcinoma cell proliferation

    PubMed Central

    CHENG, NAN; WANG, GUANG-HUI

    2016-01-01

    MicroRNAs (miRs) are a class of short and non-coding RNA molecules, which function as either oncogenes or tumor suppressors in the development of various human cancers, including nasopharyngeal carcinoma (NPC). The aim of the present study was to investigate the expression of miR-133b in NPC tissue samples, as compared with adjacent normal tissues, and to examine its roles and underlying mechanisms. Analysis using reverse transcription-quantitative polymerase chain reaction demonstrated that miR-133b was downregulated in NPC tissue samples, as compared with adjacent tissues. In vitro experiments using NPC cell lines transfected with miR-133b mimics or antisense oligonucleotides further demonstrated that the overexpression of miR-133b mimics impaired, whereas knockdown of its expression promoted, the proliferation of NPC cells. Sphingosine-1-phosphate receptor 1 (S1PR1) was predicted to be a target of miR-133b. Luciferase reporter assays showed that miR-133b inhibited the protein expression of S1PR1 by targeting its 3′-untranslated region. Furthermore, western blot analysis demonstrated that miR-133B altered the regulation of the signal transducer and activator of transcription-3 (STAT3) signaling pathway and the expression of downstream proteins in NPC cells. Therefore, the results of the present study suggested that a previously unknown miR-133b/S1PR1 molecular network may regulate NPC progression. PMID:27073467

  19. Potential surrogate endpoints for overall survival in locoregionally advanced nasopharyngeal carcinoma: an analysis of a phase III randomized trial

    PubMed Central

    Chen, Yu-Pei; Chen, Yong; Zhang, Wen-Na; Liang, Shao-Bo; Zong, Jing-Feng; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Guo, Ying; Lin, Ai-Hua; Liu, Meng-Zhong; Sun, Ying; Ma, Jun

    2015-01-01

    The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS, and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice’s four criteria. The Spearman’s rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice’s second criterion. Being consistent with all Prentice’s criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival. PMID:26219568

  20. The cytological diagnosis of nasopharyngeal carcinoma from exfoliated cells collected by suction method. An eight-year experience.

    PubMed

    Hanji, D; Shujing, S; Shuwei, H; Gohao, L

    1983-08-01

    A specially designed metallic tube, which is connected to a suction-pump and passed through the oral cavity into the nasopharynx for collecting exfoliative cells by negative pressure suction, is recommended in the diagnosis of nasopharyngeal carcinoma (NPC). From the beginning of 1973 through October 1976, among 458 cases of NPC, 405 cases were cytologically positive (with a positive rate of 88.4 per cent), and 433 cases were biopsy positive (with a positive rate of 94.3 per cent). In 1977, from January to October, among 116 cases of NPC, 103 cases were cytologically positive (with a positive rate of 88.8 per cent), and 108 cases were biopsy positive (with a positive rate of 93.1 per cent). The cytopathological features of the exfoliative NPC cells were correlated with the histopathological types of NPC. The degree of lymphocytic infiltration among the cancer cells in smears was compared with that in biopsies. They coincided roughly with each other. It indicates that one might interpret the immunological lymphocytic reaction by the number and typing of lymphocytes in smears too. The authors conclude that this cytological method is fairly dependable, less traumatic to the mucosa, convenient, and easily managed. A large number of tumor cells can be collected. It can also reflect the histologic typing of cancer cells. It can be used as a routine procedure in the clinico-pathological diagnosis of NPC, as well as in a mass screening program. PMID:6350514

  1. Volumetric modulation arc radiotherapy with flattening filter-free beams compared with conventional beams for nasopharyngeal carcinoma: a feasibility study

    PubMed Central

    Zhuang, Mingzan; Zhang, Tuodan; Chen, Zhijian; Lin, Zhixiong; Li, Derui; Peng, Xun; Qiu, Qingchun; Wu, Renhua

    2013-01-01

    There is increasing interest in the clinical use of flattening filter-free (FFF) beams. In this study, we aimed to investigate the dosimetric characteristics of volumetric modulated arc radiotherapy (VMAT) with FFF beams for nasopharyngeal carcinoma (NPC). Ten NPC patients were randomly selected to undergo a RapidArc plan with either FFF beams (RA-FFF) or conventional beams (RA-C). The doses to the planning target volumes (PTVs), organs at risk (OARs), and normal tissues were compared. The technical delivery parameters for RapidArc plans were also assessed to compare the characteristics of FFF and conventional beams. Both techniques delivered adequate doses to PTVs. For PTVs, RA-C delivered lower maximum and mean doses and improved conformity and homogeneity compared with RA-FFF. Both techniques provided similar maximum doses to the optic nerves and lenses. For the brain stem, spinal cord, larynx, parotid glands, oral cavity, and skin, RA-FFF showed significant dose increases compared to RA-C. The dose to normal tissue was lower in RA-FFF. The monitor units (MUs) were (536 ± 46) MU for RA-FFF and (501 ± 25) MU for RA-C. The treatment duration did not significantly differ between plans. Although both treatment plans could meet clinical needs, RA-C is dosimetrically superior to RA-FFF for NPC radiotherapy. PMID:23237224

  2. Radiation-induced optic neuropathy following external beam radiation therapy for nasopharyngeal carcinoma: A retrospective case-control study

    PubMed Central

    WANG, WEI; YANG, HUI; GUO, LING; SU, HONGYU; WEI, SHIHUI; ZHANG, XIULAN

    2016-01-01

    Radiation-induced optic neuropathy (RION) is a severe ocular complication in patients with nasopharyngeal carcinoma (NPC) following external beam radiation therapy. However, the systemic risk factors for this condition remain unclear. Therefore, patients with NPC who received radiotherapy between 2004 and 2007 at the Sun Yat-Sen University Cancer Center were retrospectively reviewed in this case-control study. The study included 40 RION patients and 40 patients in the control group, who were strictly matched to the RION patients by tumor histopathology, location, Union for International Cancer Control-Tumor Node Metastasis classification and radiotherapy protocol. Univariate and multivariate statistical regression analyses were performed to identify factors predictive of RION. The univariate analysis demonstrated that age (>60 years), gender (female) and chemotherapy significantly affected the risk of RION, whereas diabetes, hypertension and hepatitis B virus infection did not exert a significant effect. The results of the multivariate analysis suggested that only gender and chemotherapy were significantly associated with an increased incidence of RION. Therefore, the results of the present study suggested that female gender and chemotherapy constitute risk factors for the development of RION following radiotherapy for NPC. The ocular symptoms of high-risk patients should be carefully investigated and reported by ophthalmologists. PMID:27123298

  3. Knockdown of phosphodiesterase 4D inhibits nasopharyngeal carcinoma proliferation via the epidermal growth factor receptor signaling pathway

    PubMed Central

    XU, TING; WU, SIHAI; YUAN, YUAN; YAN, GUOXIN; XIAO, DAJIANG

    2014-01-01

    Phosphodiesterase 4D (PDE4D) is a subtype of metallohydrolases, and it has been reported that PDE4D functions as a proliferation promoting factor in certain types of cancer, including head and neck cancer. The present study first investigated the function of PDE4D in nasopharyngeal carcinoma (NPC). Western blot analysis was applied to detect PDE4D expression in NPC samples and cells. A lentiviral infection technique was used to stabilize the knockdown of PDE4D, which was subsequently examined in vitro and in vivo. The results showed that PDE4D was overexpressed in the NPC tissues and cells. Knockdown of PDE4D inhibited the growth of CNE2 and 5–8F, inducing cell cycle arrest in the G0/G1 phase in CNE2. These effects could be reversed by epidermal growth factor (EGF) stimulation. Furthermore, knockdown of PDE4D significantly inhibited the phosphorylation of epidermal growth factor receptor (EGFR) and AKT. The results were further validated in an NPC xenograft in nude mice. In conclusion, this study demonstrated that PDE4D may function as a proliferation promoting factor in NPC, by affecting the EGFR/PI3K/AKT signaling pathway. Therefore, the targeting of PDE4D may be a rational strategy in the treatment of NPC. PMID:25289091

  4. Assessment of ERCC1 and XPF Protein Expression Using Quantitative Immunohistochemistry in Nasopharyngeal Carcinoma Patients Undergoing Curative Intent Treatment

    SciTech Connect

    Jagdis, Amanda; Phan, Tien; Klimowicz, Alexander C.; Laskin, Janessa J.; Lau, Harold Y.; Petrillo, Stephanie K.; Siever, Jodi E.; Thomson, Thomas A.; Magliocco, Anthony M.; Hao, Desirée

    2013-04-01

    Purpose: We sought to evaluate the prognostic/predictive value of ERCC1 and XPF in patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with curative intent. Methods and Materials: ERCC1 and XPF protein expression was evaluated by immunofluorescence combined with automated quantitative analysis (AQUA) using the FL297 and 3F2 antibodies, respectively. ERCC1 and XPF protein expression levels were correlated with clinical outcomes. Results: Patient characteristics were as follows: mean age 52 years (range, 18-85 years), 67% male, 72% Karnofsky performance status (KPS) ≥90%, World Health Organization (WHO) type 1/2/3 = 12%/28%/60%, stage III/IV 65%. With a median follow-up time of 50 months (range, 2.9 to 120 months), the 5-year overall survival (OS) was 70.8%. Median standardized nuclear AQUA scores were used as cutpoints for ERCC1 (n=138) and XPF (n=130) protein expression. Agreement between dichotomized ERCC1 and XPF scores was high at 79.4% (kappa = 0.587, P<.001). Neither biomarker predicted locoregional recurrence, DFS, or OS after adjustment for age and KPS, irrespective of stratification by stage, WHO type, or treatment. Conclusions: Neither ERCC1 nor XPF, analyzed by quantitative immunohistochemistry using the FL297 and 3F2 antibodies, was prognostic or predictive in this cohort of NPC patients.

  5. Capsaicin mediates apoptosis in human nasopharyngeal carcinoma NPC-TW 039 cells through mitochondrial depolarization and endoplasmic reticulum stress.

    PubMed

    Ip, S-W; Lan, S-H; Lu, H-F; Huang, A-C; Yang, J-S; Lin, J-P; Huang, H-Y; Lien, J-C; Ho, C-C; Chiu, C-F; Wood, Wg; Chung, J-G

    2012-06-01

    Capsaicin, a pungent compound found in hot chili peppers, has been reported to have antitumor activities in many human cancer cell lines, but the induction of precise apoptosis signaling pathway in human nasopharyngeal carcinoma (NPC) cells is unclear. Here, we investigated the molecular mechanisms of capsaicin-induced apoptosis in human NPC, NPC-TW 039, cells. Effects of capsaicin involved endoplasmic reticulum (ER) stress, caspase-3 activation and mitochondrial depolarization. Capsaicin-induced cytotoxic effects (cell death) through G0/G1 phase arrest and induction of apoptosis of NPC-TW 039 cells in a dose-dependent manner. Capsaicin treatment triggered ER stress by promoting the production of reactive oxygen species (ROS), increasing levels of inositol-requiring 1 enzyme (IRE1), growth arrest and DNA-damage-inducible 153 (GADD153) and glucose-regulated protein 78 (GRP78). Other effects included an increase in cytosolic Ca(2+), loss of the mitochondrial transmembrane potential (ΔΨ(m)), releases of cytochrome c and apoptosis-inducing factor (AIF), and activation of caspase-9 and -3. Furthermore, capsaicin induced increases in the ratio of Bax/Bcl-2 and abundance of apoptosis-related protein levels. These results suggest that ER stress- and mitochondria-mediated cell death is involved in capsaicin-induced apoptosis in NPC-TW 039 cells. PMID:21859781

  6. A prospective study on radiation doses to organs at risk (OARs) during intensity-modulated radiotherapy for nasopharyngeal carcinoma patients

    PubMed Central

    Zhou, Guan-Qun; Zhang, Wang-Jian; Xu, Lin; Wang, Xiao-Ju; Lin, Li; Ma, Jun; Sun, Ying

    2016-01-01

    This study is to investigate the dose distribution of organs at risk (OARs) in cases of nasopharyngeal carcinoma (NPC). From July 2013 to October 2014, a prospective cohort study involving 148 patients was carried out at our center. OARs surrounding the nasopharynx were contoured on axial CT planning images in all patients. Dose-volume histograms of OARs and gross tumor volumes (GTV) were calculated. Multivariate analysis showed that radiation dose to OARs was associated with T stage and, especially, GTV. Seven OARs, including the spinal cord, eye and mandible, easily tolerated radiation doses in all patients; six OARs including the brain stem, chiasm and temporal lobe easily tolerated radiation doses in patients with a small GTV, but with difficulty when GTV was large; and other nine OARs including the parotid gland, cochlea and tympanic cavity met tolerance doses with difficulty in all patients. According to the patterns of radiation doses to OARs, it may help us to further reduce subsequent complications by improving the efficiency of plan optimization and evaluation. PMID:26942881

  7. miR-34b inhibits nasopharyngeal carcinoma cell proliferation by targeting ubiquitin-specific peptidase 22

    PubMed Central

    Xiao, Jianyong; Li, Yingying; Zhang, Wenyin; Jiang, Yanni; Du, Biaoyan; Tan, Yuhui

    2016-01-01

    Objectives This study aimed to investigate the precise role of miR-34b in nasopharyngeal carcinoma (NPC). Materials and methods: The expression of miR-34b and transcription of ubiquitin-specific peptidase 22 (USP22) were examined using quantitative reverse transcription-polymerase chain reaction. Western blot analysis was used to measure the protein expression of USP22. A dualluciferase assay was used to investigate the interaction between miR-34b and USP22. Cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. The cell cycle was analyzed by propidium iodide staining followed by flow cytometry analysis. Results miR-34b was significantly downregulated in NPC tissues and NPC cell lines. Overexpression of miR-34b in NPC SUNE-6-10B cells inhibited cell viability and proliferation. USP22 was highly expressed in NPC cells and promoted cell viability and proliferation. Restoration of USP22 expression could reverse the effect of miR-34b on NPC cell viability and proliferation. Conclusion miR-34b acts as a tumor suppressor in NPC, which is mediated via repression of the oncogene USP22. PMID:27051294

  8. Anatomic and Dosimetric Changes During the Treatment Course of Intensity-Modulated Radiotherapy for Locally Advanced Nasopharyngeal Carcinoma

    SciTech Connect

    Wang Xin; Lu Jiade; Xiong Xiaopeng; Zhu Guopei; Ying Hongmei; He Shaoqin; Hu Weigang; Hu Chaosu

    2010-07-01

    Many patients with nasopharyngeal carcinoma (NPC) have marked anatomic change during intensity-modulated radiation therapy (IMRT). In this study, the magnitude of anatomic changes and its dosimetric effects were quantified. Fifteen patients with locally advanced NPC treated with IMRT had repeated computed tomography (CT) after 18 fractions. A hybrid plan was made to the anatomy of the second computed tomography scan. The dose of the original plan, hybrid plan, and new plan were compared. The mean volume of left and right parotid decreased 6.19 mL and 6.44 mL, respectively. The transverse diameters of the upper bound of odontoid process, the center of odontoid process, and the center of C2 vertebral body slices contracted with the mean contraction of 8.2 mm, 9.4 mm, and 7.6 mm. Comparing the hybrid plan with the treatment plan, the coverage of target was maintained while the maximum dose to the brain stem and spinal cord increased by 0.08 to 6.51 Gy and 0.05 to 7.8 Gy. The mean dose to left and right parotid increased by 2.97 Gy and 2.57 Gy, respectively. A new plan reduced the dose of spinal cord, brain stem, and parotids. Measurable anatomic changes occurring during the IMRT for locally advanced NPC maintained the coverage of targets but increased the dose to critical organs. Those patients might benefit from replanning.

  9. Co-Encapsulation of Combretastatin-A4 Phosphate and Doxorubicin in Polymersomes for Synergistic Therapy of Nasopharyngeal Epidermal Carcinoma.

    PubMed

    Zhu, Jinfang; Xu, Xiaoping; Hu, Mengying; Qiu, Liyan

    2015-06-01

    In this study, we designed biodegradable polymersomes for co-delivery of an antiangiogenic drug combretastatin-A4 phosphate (CA4P) and doxorubicin (DOX) to collapse tumor neovasculature and inhibit cancer cell proliferation with the aim to achieve synergistic antitumor effects. The polymersomes co-encapsulating DOX and CA4P (Ps-DOX-CA4P) were prepared by solvent evaporation method using methoxy poly(ethylene glycol)-b-polylactide (mPEG-PLA) block copolymers as drug carriers. The resulting Ps-DOX-CA4P has vesicles shape with uniform sizes of about 50 nm and controlled co-encapsulation ratios of DOX to CA4P. More importantly, Ps-DOX-CA4P (1:10) showed strong synergistic cytotoxicity (combination index CI = 0.31) against human nasopharyngeal epidermal carcinoma (KB) cells. Furthermore, Ps-DOX-CA4P accumulated remarkably in KB tissues xenografts in nude mice. Consistent with these observations, Ps-DOX-CA4P (1:10) achieved significant antitumor potency because of fast tumor vasculature disruption and sustained tumor cells proliferation inhibition in vivo. The overall findings indicate that co-delivery of an antiangiogenic drug and a chemotherapeutic agent in polymersomes is a potentially promising strategy for cancer therapy. PMID:26353589

  10. The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT.

    PubMed

    Xu, Tingting; Shen, Chunying; Ou, Xiaomin; He, Xiayun; Ying, Hongmei; Hu, Chaosu

    2016-04-12

    Nasopharyngeal carcinoma (NPC) patients with N2-3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2-3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194-0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187-0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation. PMID:26942700

  11. Proteomic analysis of docetaxel resistance in human nasopharyngeal carcinoma cells using the two-dimensional gel electrophoresis method.

    PubMed

    Peng, Xingchen; Gong, Fengming M; Ren, Min; Ai, Ping; Wu, ShaoYong; Tang, Jie; Hu, XiaoLin

    2016-09-01

    Docetaxel-based chemotherapy has been recommended for advanced nasopharyngeal carcinoma (NPC). However, treatment failure often occurs because of acquired drug resistance. In this study, a docetaxel-resistant NPC cell line CNE-2R was established with increasing doses of docetaxel for more than 6 months. Two-dimensional gel electrophoresis and ESI-Q-TOF-MS were used to compare the differential expression of docetaxel-resistance-associated proteins between human NPC CNE-2 cells and docetaxel-resistant CNE-2R cells. As a result, 24 differentially expressed proteins were identified, including 11 proteins with increased expression and 13 proteins with decreased expression. These proteins function in diverse biological processes such as metabolism, signal transduction, calcium ion binding, immune response, proteolysis, and so on. Among these, α-enolase (ENO1), significantly upregulated in CNE-2R, was selected for detailed analysis. Inhibition of ENO1 by shRNA restored CNE-2R cells' sensitivity to docetaxel. Moreover, overexpression of ENO1 could facilitate the development of acquired resistance of docetaxel in CNE-2 cells. Western blot and reverse-transcription PCR data of clinical samples confirmed that α-enolase was upregulated in docetaxel-resistant human NPC tissues. Finding such proteins might improve interpretation of the molecular mechanisms leading to the acquisition of docetaxel chemoresistance. PMID:27333594

  12. Efficacy of BIBF 1120 or BIBF 1120 plus chemotherapy on nasopharyngeal carcinoma in vitro and in vivo

    PubMed Central

    Xue, Cong; Tian, Ying; Zhang, Jing; Zhao, Yuanyuan; Zhan, Jianhua; Fang, Wenfeng; Zhang, Li

    2016-01-01

    Purpose BIBF 1120 is a potent triple angiokinase inhibitor now being evaluated in many types of tumors. We examine the antitumor effects of BIBF 1120 on nasopharyngeal carcinoma (NPC) in vitro and in vivo. Materials and methods The effect of BIBF 1120 on NPC cell proliferation was evaluated using the Cell Counting Kit 8 assay. The activities of BIBF 1120 as a single agent and in combination with cisplatin (DDP) in NPC tumor xenografts were evaluated by measuring microvessel density and expression of vascular endothelial growth factor signaling. Results BIBF 1120 exhibited limited inhibition of the growth of three NPC cell lines. Concurrent administration of BIBF 1120 and DDP provided greater antitumor effects compared to that observed with the use of either inhibitor as a single agent in the NPC xenograft model. Microvessel density and expression of vascular endothelial growth factor signaling were significantly reduced. Conclusion BIBF 1120, either as a single agent or in combination with DDP, demonstrates significant antitumor and antiangiogenic effects in the NPC xenograft model. Our results indicate that BIBF 1120 administered in conjunction with chemotherapy might provide an effective treatment method for NPC. PMID:27042009

  13. Low BRMS1 expression promotes nasopharyngeal carcinoma metastasis in vitro and in vivo and is associated with poor patient survival

    PubMed Central

    2012-01-01

    Background Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene. This study aimed to investigate the impact of BRMS1 on metastasis in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic significance of BRMS1 in NPC patients. Methods BRMS1 expression was examined in NPC cell lines using quantitative reverse transcription-polymerase chain reaction and Western blotting. NPC cells stably expressing BRMS1 were used to perform wound healing and invasion assays in vitro and a murine xenograft assay in vivo. Immunohistochemical staining was performed in 274 paraffin-embedded NPC specimens divided into a training set (n = 120) and a testing set (n = 154). Results BRMS1 expression was down-regulated in NPC cell lines. Overexpression of BRMS1 significantly reversed the metastatic phenotype of NPC cells in vitro and in vivo. Importantly, low BRMS1 expression was associated with poor distant metastasis-free survival (DMFS, P < 0.001) and poor overall survival (OS, P < 0.001) in the training set; these results were validated in the testing set and overall patient population. Cox regression analysis demonstrated that low BRMS1 expression was an independent prognostic factor for DMFS and OS in NPC. Conclusions Low expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in NPC patients. PMID:22931099

  14. miR-185-3p regulates nasopharyngeal carcinoma radioresistance by targeting WNT2B in vitro

    PubMed Central

    Li, Guo; Wang, Yunyun; Liu, Yong; Su, Zhongwu; Liu, Chao; Ren, Shuling; Deng, Tengbo; Huang, Donghai; Tian, Yongquan; Qiu, Yuanzheng

    2014-01-01

    Aberrant microRNA (miRNA) expression contributes to a series of malignant cancer behaviors, including radioresistance. Our previous study showed differential expression of miR-185-3p in post-radiation nasopharyngeal carcinoma (NPC) cells. To investigate the role of miR-185-3p in NPC radioresistance, CNE-2 and 5-8F cells were transfected with miR-185-3p mimic and miR-185-3p inhibitor, respectively. CCK-8 assay and colony formation experiment confirmed that the expression of miR-185-3p affected the radioresistance of NPC cells. A negative correlation between miR-185-3p and WNT2B expression was observed in NPC cells and tissues. Luciferase reporter assays confirmed that miR-185-3p directly targeted the coding region of WNT2B. Furthermore, we found radioresistance decreased in WNT2B-silenced NPC cells. Activation of the WNT2B/β-catenin pathway was accompanied by epithelial–mesenchymal transition biomarker changes in NPC. We concluded that miR-185-3p contributed to the radioresistance of NPC via modulation of WNT2B expression in vitro. PMID:25297925

  15. Reactivity of radioiodinated serum antibody from Burkitt's lymphoma and nasopharyngeal carcinoma patients against culture lines derived from Burkitt's lymphoma

    PubMed Central

    Inoue, M.; Klein, G.

    1970-01-01

    The IgG serum immunoglobulin fraction of two Burkitt's lymphoma (Mutua and Kiliopa) and one African nasopharyngeal carcinoma patient (Kipkoech) was conjugated to iodine-131 (131I). It is known from previous studies with fluorescein labelled conjugates that all three sera contain antibody against the Epstein–Barr virus (EBV)-associated membrane antigen complex, present on the surface of lymphoblastoid cells in EBV-carrier cultures. All three radioiodinated conjugates attached to live cells of an EBV-carrying Burkitt line (Maku), but not to EBV-free Raji cells. A Swedish control serum (Berith) did not block the binding of any of the three conjugates, whereas unconjugated sera of Mutua, Kiliopa and Kipkoech showed various degrees of blocking and cross-blocking. The blocking patterns were in good agreement with previous tests, performed with the same sera against their fluorescein conjugated derivatives. Antibody release tests, involving preincubation of live cells with one of the three conjugates, followed by incubation with unlabelled serum revealed a certain `hierarchy' between the three sera with regard to their ability to displace radioiodinated surface-coupled immunoglobulin. This ability could be related to the competitive behaviour of the same sera in the cross blocking tests. The results are believed to reflect differences in the affinity of the three antibodies, due either to differences in fit in relation to the surface antigen(s) carried by the Maku target cell, or to differences in the duration of immunization in the three patients. PMID:4320551

  16. Prevertebral space effusion caused by the breaking of swollen lymphonodi retropharynici in nasopharyngeal carcinoma: A case report

    PubMed Central

    LIU, LIAN-HUA; YANG, XIAO-FENG

    2016-01-01

    A 20-year-old male presented to hospital with blood in the mucus, which had occurred for 6 months, and was diagnosed with nasopharyngeal carcinoma (NPC). Due to passive smoking, the patient developed a constant and violent cough, pain behind the right ear and swelling of the retropharynx. The results of a computed tomography scan, which was performed during re-examination of the patient, revealed that the right lymphonodi retropharynici had decreased in size and the hypodense shadow of the prevertebral space had become clear. Therefore, the retropharyngeal pressure was suspected to be increased due to the violent cough. Consequently, the increased pressure may have caused the swollen lymph nodes on the right side of the pharynx to break, which allowed the necrotic liquid to seep into the prevertebral space and result in effusion. Subsequent to 5 days of treatment with methylprednisolone (40 mg ivgtt qd, d1-5), the results from the cone bean computed tomography examination, which had been performed prior to radiotherapy, indicated that the retropharyngeal swelling had improved and the prevertebral space had returned to normal. To the best of our knowledge, the present study is the first reported case of effusion in the prevertebral space caused by the breaking of swollen lymphonodi retropharynici in NPC. The present study acts as a reminder of the possible delays in the treatments for head and neck tumor patients that demonstrate swollen retropharyngeal lymph nodes due to the occurrence of effusion in the prevertebral space. PMID:27313690

  17. Red Meat and Processed Meat Consumption and Nasopharyngeal Carcinoma Risk: A Dose-response Meta-analysis of Observational Studies.

    PubMed

    Li, Fuqin; Duan, Fujiao; Zhao, Xia; Song, Chunhua; Cui, Shuli; Dai, Liping

    2016-01-01

    The purpose of this study is to clarify and quantify the potential dose-response association between the intake of total red and total processed meat and risk of nasopharyngeal carcinoma (NPC). Relevant studies were identified by searching PubMed, EMBASE, and Chinese databases (CNKI and Wanfang). The summary relative risk (RR) with 95% confidence interval (95%CI) was calculated. A total of 15 independent studies with 12,735 subjects were identified. Compared with the low-rank intake, the summary RR of NPC was 1.35 (95%CI, 1.21-1.51) for total red meat and 1.46 (95%CI, 1.34-1.64) for total processed meat. For the moderate-rank intake, the summary RR of NPC was 1.54 (95%CI, 1.36-1.79) for total red meat and 1.59 (95%CI, 1.3-1.90) for total processed meat. The summary RR for high-rank intake was 1.71 (95%CI, 1.14-2.55) for total red meat and 2.11 (95%CI, 1.31-3.42) for total processed meat. The combined estimates showed obvious evidence of statistically significant association between total red and total processed meat consumption dose and risk of NPC (Ptrend< 0.01). In conclusion, our data suggest that a high intake of total red or total processed meat is associated with a significantly increased risk of NPC. PMID:27367552

  18. EphA2 silencing in nasopharyngeal carcinoma leads to decreased proliferation, invasion and increased sensitization to paclitaxel.

    PubMed

    Tan, Pingqing; Liu, Yong; Yu, Changyun; Su, Zhongwu; Li, Guo; Zhou, Xiaojuan; Huang, Donghai; Zhang, Xin; Qiu, Yuanzheng; Tian, Yongquan

    2012-09-01

    EphA2 is frequently overexpressed and functionally altered in a variety of human cancers. However, its roles in human nasopharyngeal carcinoma (NPC) remain unclear. To investigate the roles of EphA2 in the development and progression of NPC, we initially evaluated the expression pattern of EphA2 protein in NPC tissues using western blotting and CCK-8 assay. Fluorescence-activated cell sorting analysis and invasion assay were conducted to observe the effects of EphA2 inhibition in vivo. Our results demonstrated that EphA2 was overexpressed in NPC specimens and the expression of EphA2 was significantly associated with T classification, advanced clinical stage and lymph node metastasis. Moreover, human NPC 5-8F cells were infected with lentiviral vector-mediated EphA2-specific shRNA, which resulted in the significant inhibition of cell growth, invasion of 5-8F cells and markedly enhanced the sensitivity of 5-8F cells to the chemotherapeutic agent paclitaxel in vitro. Collectively, our results demonstrate that EphA2 is involved in malignant cell behavior and is a potential therapeutic target in human NPC. PMID:23741245

  19. Clinicopathologic features and treatment of breast metastasis from nasopharyngeal carcinoma: A report of two cases and literature review

    PubMed Central

    XIAO, WEIWEI; HE, ZHENYU; XING, CHAO; ZHEN, WEI; WANG, SHAOXIANG; LIN, HUANXIN

    2015-01-01

    Breast metastasis is a rare pattern of distant metastasis from nasopharyngeal carcinoma (NPC) following curative treatment. The present study reported two patients with breast metastasis from NPC and reviewed four such patients reported in the literature, including the analysis of clinical profiles, pathological diagnoses, treatment strategies and outcomes. The breast is a potential metastatic site for patients with NPC following curative treatment; however, thus far, only metachronous breast metastasis has been reported. Infection with Epstein-Barr virus (EBV) was identified in the breast metastasis sites of the two patients investigated in the current study using in situ hybridization for EBV-encoded small RNAs. Patients with breast metastases from NPC consistently and simultaneously develop metastases in other sites. In addition, the two current patients had poor prognoses. Therefore, chemotherapy was the primary treatment strategy administered. A solitary breast metastasis was identified in the male patient. At the most recent follow-up 10 years subsequent to undergoing a Halsted mastectomy, the patient remained alive, however the patient is now lost to follow-up. This case indicates that patients exhibiting NPC with a solitary breast metastasis may still gain long-term survival by undergoing radical mastectomy; therefore, radical mastectomy should be considered in such patients. PMID:26788190

  20. Pretreatment Diffusion-Weighted MRI Can Predict the Response to Neoadjuvant Chemotherapy in Patients with Nasopharyngeal Carcinoma

    PubMed Central

    Zhang, Guo-Yi; Wang, Yue-Jian; Liu, Jian-Ping; Zhou, Xin-Han; Xu, Zhi-Feng; Chen, Xiang-Ping; Xu, Tao; Wei, Wei-Hong; Zhang, Yang; Huang, Ying

    2015-01-01

    Purpose. To explore the potential of diffusion-weighted (DW) magnetic resonance imaging (MRI) using apparent diffusion coefficient (ADC) for predicting the response to neoadjuvant chemotherapy in nasopharyngeal carcinoma (NPC). Methods and Materials. Ninety-two consecutive patients with NPC who underwent three cycles of neoadjuvant chemotherapy were retrospectively analyzed. DW and anatomical MRI were performed before and after neoadjuvant chemotherapy prior to radiotherapy. Pretreatment ADCs and percentage increases in ADC after chemotherapy were calculated for the primary lesions and metastatic adenopathies. Receiver operating characteristic curve analysis was used to select optimal pretreatment ADCs. Results. Pretreatment mean ADCs were significantly lower for responders than for nonresponders (primary lesions, P = 0.012; metastatic adenopathies, P = 0.013). Mean percentage increases in ADC were higher for responders than for nonresponders (primary lesions, P = 0.008; metastatic adenopathies, P < 0.001). The optimal pretreatment primary lesion and metastatic adenopathy ADCs for differentiating responders from nonresponders were 0.897 × 10−3 mm2/sec and 1.031 × 10−3 mm2/sec, respectively. Conclusions. NPC patients with low pretreatment ADCs tend to respond better to neoadjuvant chemotherapy. Pretreatment ADCs could be used as a new pretreatment imaging biomarker of response to neoadjuvant chemotherapy. PMID:26413513

  1. Nucleolin antisense oligodeoxynucleotides induce apoptosis and may be used as a potential drug for nasopharyngeal carcinoma therapy.

    PubMed

    Wu, Cheng-Der; Chou, Hung-Wen; Kuo, Yuan-Sung; Lu, Ruei-Min; Hwang, Yu-Chyi; Wu, Han-Chung; Lin, Chin-Tarng

    2012-01-01

    Nucleolin (C23, NCL) mRNA was up-regulated in nasopharyngeal carcinoma (NPC) cells compared to that of normal nasomucosal (NNM) cells using a cDNA microarray approach. The level of nucleolin protein was also up-regulated in 13 NPC cell lines, 30 biopsy specimens and nine other cancer cell lines compared to five NNM cells or normal stromal cells, which were analyzed using immunoblotting or immunohistochemistry. We transfected nucleolin antisense oligodeoxynucleotides (phosphorothioate-modified oligodeoxynucleotides; S-ODNs) into NPC-TW01 cells to knockdown nucleolin expression to evaluate the function of nucleolin in cancer cells. Nucleolin knockdown induced NPC cells but not NNM cells to undergo apoptosis. Furthermore, treatment of NPC-TW01 xenograft tumors with nucleolin antisense oligodeoxynucleotides suppressed the growth of xenograft tumors without obvious side effects. Therefore, we suggest that nucleolin may be a potential cancer therapeutic target and that nucleolin antisense oligodeoxynucleotides may be used as a potential drug for therapy in NPC. PMID:21956494

  2. The long-term outcomes of alternating chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multiinstitutional phase II study

    PubMed Central

    Fuwa, Nobukazu; Kodaira, Takeshi; Daimon, Takashi; Yoshizaki, Tomokazu

    2015-01-01

    To examine the long-term outcomes of alternating chemoradiotherapy (ALCRT) for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to assess the efficacy of ALCRT for NPC. Patients with stage IIB to IVB, ECOG PS 0–2, 18–70 years-old, and sufficient organ function were eligible for this study. First, chemotherapy, consisting of 5-fluorouracil (800 mg/m2 per 24 h on days 1–5) and cisplatin (100 mg/m2 per 24 h on day 6), was administered, then a wide field of radiotherapy (36 Gy/20 fraction), chemotherapy, a shrinking field of radiotherapy (34 Gy/17 fraction), and chemotherapy were performed alternately. Between December 2003 and March 2006, 90 patients in 25 facilities were enrolled in this study, 87 patients were finally evaluated. A total of 67 patients (76.1%) completed the course of treatment. The overall survival and the progression-free survival rates at 5 years were 78.04% (95% CI: 69.1∼87.0%), and 68.74% (95% CI: 58.8∼78.7%), respectively. The long-term outcomes of ALCRT for NPC were thought to be promising. ALCRT will be considered to be a controlled trial to compare therapeutic results with those of concurrent chemoradiotherapy for NPC. PMID:25991077

  3. Inhibition of nasopharyngeal carcinoma cell proliferation and synergism of cisplatin with silvestrol and episilvestrol isolated from Aglaia stellatopilosa

    PubMed Central

    DAKER, MAELINDA; YEO, JIUN-TZEN; BAKAR, NORHASIMAH; ABDUL RAHMAN, ASMA' SAIYIDATINA AISHAH ABDUL; AHMAD, MUNIRAH; YEO, TIONG-CHIA; KHOO, ALAN SOO-BENG

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is a type of tumour that arises from the epithelial cells that line the surface of the nasopharynx. NPC is treated with radiotherapy and cytotoxic chemotherapeutic drugs such as cisplatin and 5-fluorouracil. However, current strategies are often associated with potential toxicities. This has prompted efforts to identify alternative methods of treatment. The present study aimed to investigate silvestrol and episilvestrol-mediated inhibition of cell proliferation in human NPC cells. The growth kinetics of NPC cells treated with silvestrol or episilvestrol were monitored dynamically using a real-time, impedance-based cell analyzer, and dose-response profiles were generated using a colorimetric cell viability assay. Furthermore, apoptosis was evaluated using flow cytometry and high content analysis. In addition, flow cytometry was performed to determine cell cycle distribution. Finally, the effects of combining silvestrol or episilvestrol with cisplatin on NPC cells was examined. Apoptosis was not observed in silvestrol and episilvestrol-treated NPC cells, although cell cycle perturbation was evident. Treatment with both compounds induced a significant increase in the percentage of cells in the G2/M phase, as compared with the control. In vitro cultures combining silvestrol or episilvestrol with cisplatin showed synergistic effects against NPC cells. The results of the present study suggested that silvestrol and episilvestrol had an anti-tumour activity in NPC cells. Silvestrol and episilvestrol, particularly in combination with cisplatin, merit further investigation, so as to determine the cellular mechanisms underlying their action(s) as anti-NPC agents. PMID:27284293

  4. Microtubule depolymerization activates the Epstein-Barr virus lytic cycle through protein kinase C pathways in nasopharyngeal carcinoma cells.

    PubMed

    Liu, Yi-Ru; Huang, Sheng-Yen; Chen, Jen-Yang; Wang, Lily Hui-Ching

    2013-12-01

    Elevated levels of antibodies against Epstein-Barr virus (EBV) and the presence of viral DNA in plasma are reliable biomarkers for the diagnosis of nasopharyngeal carcinoma (NPC) in high-prevalence areas, such as South-East Asia. The presence of these viral markers in the circulation suggests that a minimal level of virus reactivation may have occurred in an infected individual, although the underlying mechanism of reactivation remains to be elucidated. Here, we showed that treatment with nocodazole, which provokes the depolymerization of microtubules, induces the expression of two EBV lytic cycle proteins, Zta and EA-D, in EBV-positive NPC cells. This effect was independent of mitotic arrest, as viral reactivation was not abolished in cells synchronized at interphase. Notably, the induction of Zta by nocodazole was mediated by transcriptional upregulation via protein kinase C (PKC). Pre-treatment with inhibitors for PKC or its downstream signalling partners p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) abolished the nocodazole-mediated induction of Zta and EA-D. Interestingly, the effect of nocodazole, as well as colchicine and vinblastine, on lytic gene expression occurred only in NPC epithelial cells but not in cells derived from lymphocytes. These results establish a novel role of microtubule integrity in controlling the EBV life cycle through PKC and its downstream pathways, which represents a tissue-specific mechanism for controlling the life-cycle switch of EBV. PMID:24062531

  5. Choline and betaine intakes are associated with reduced risk of nasopharyngeal carcinoma in adults: a case–control study

    PubMed Central

    Zeng, F-f; Xu, C-h; Liu, Y-t; Fan, Y-y; Lin, X-l; Lu, Y-k; Zhang, C-x; Chen, Y-m

    2014-01-01

    Background: Intakes of choline and betaine have been inversely related to the risk of various neoplasms, but scant data exist on nasopharyngeal carcinoma (NPC). We examined the association between consumption of choline and betaine and risk of NPC. Methods: We conducted a case–control study with 600 incident NPC patients and 600 controls 1 : 1 matched by age, sex and household type in Guangdong, China. Dietary intake was assessed by a food frequency questionnaire through face-to-face interview. Results: Intakes of total choline, betaine and choline+betaine were inversely related to NPC after adjustment for various lifestyle and dietary factors (all P-trend <0.001). Adjusted odds ratios (95% CI) for quartile 4 (vs quartile 1) were 0.42 (0.29, 0.61) for total choline, 0.50 (0.35, 0.72) for betaine and 0.44 (0.30, 0.64) for betaine+total choline. Regarding various sources of choline, lower NPC risk was associated with greater intakes of choline from phosphatidylcholine, free choline, glycerophosphocholine and phosphocholine, but not sphingomyelin. Conclusion: These findings are consistent with a beneficial effect of choline and betaine intakes on carcinogenesis. PMID:24169354

  6. Knockdown of NFBD1/MDC1 enhances chemosensitivity to cisplatin or 5-fluorouracil in nasopharyngeal carcinoma CNE1 cells.

    PubMed

    Zeng, Quan; Wang, Zhihai; Liu, Chuan; Gong, Zhitao; Yang, Li; Jiang, Liang; Ma, Zuxia; Qian, Yi; Yang, Yucheng; Kang, Houyong; Hong, Suling; Bu, Youquan; Hu, Guohua

    2016-07-01

    Nasopharyngeal carcinoma (NPC) is a rare but highly invasive cancer that is prevalent among people of southern Chinese ancestry in southern China and Southeast Asia. Radiotherapy and cisplatin (CDDP)-based chemotherapy are the main treatment options. Unfortunately, disease response to concurrent chemoradiotherapy varies among patients with NPC, and many cases are resistant to CDDP and radiotherapy. NFBD1 functions in cell cycle checkpoint activation and DNA repair following DNA damage. In this study, we identified the NFBD1 as a tractable molecular target to chemosensitize NPC cells. NFBD1 expression in NPC CNE1 cell lines was depleted using lentivirus-mediated short hairpin RNA, and the elevated sensitivity of these NFBD1-inhibited NPC cells to therapeutic reagent CDDP and 5-fluorouracil (5-FU) was evaluated using MTS assays. Flow cytometry analysis also showed that NFBD1 knockdown led to an obvious induction of apoptosis in CDDP- or 5-FU-treated CNE1 cells. Furthermore, we implicated the involvement of NFBD1 in Rad51 and DNA-PKcs foci formation following CDDP or 5-FU chemotherapy. In conclusion, NFBD1 knockdown improves the chemosensitivity of NPC cells by inhibiting cell growth and promoting apoptosis through the impairment of DNA damage repair, suggesting NFBD1 as a novel therapeutic target for NPC. PMID:27334757

  7. Evaluation of the Dosimetric Feasibility of Hippocampal Sparing Intensity-Modulated Radiotherapy in Patients with Locally Advanced Nasopharyngeal Carcinoma

    PubMed Central

    Gan, Hua; Denniston, Kyle A.; Li, Sicong; Tan, Wenyong; Wang, Zhaohua

    2014-01-01

    Purpose The objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced nasopharyngeal carcinoma (NPC). Materials/Methods Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs. Results All plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs) were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, Dmean, Dmedian, D98% and Dmin) and volume (V5, V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower in the HPC sparing plans (p<0.05), except for Dmin (P = 0.06) and V5 (P = 0.12). Conclusions IMRT for patients with locally advanced NPC exposes the HPC to a significant radiation dose. HPC sparing IMRT planning significantly decreases this dose, with minimal impact on the therapeutic targets and other OARs. PMID:24587184

  8. miR-31 is consistently inactivated in EBV-associated nasopharyngeal carcinoma and contributes to its tumorigenesis

    PubMed Central

    2014-01-01

    Background As a distinctive type of head and neck cancers, nasopharyngeal carcinoma (NPC) is genesis from the clonal Epstein-Barr virus (EBV)-infected nasopharyngeal epithelial cells accumulated with multiple genetic lesions. Among the recurrent genetic alterations defined, loss of 9p21.3 is the most frequent early event in the tumorigenesis of EBV-associated NPC. In addition to the reported CDKN2A/p16, herein, we elucidated the role of a miRNA, miR-31 within this 9p21.3 region as NPC-associated tumor suppressor. Methods The expression and promoter methylation of miR-31 were assessed in a panel of NPC tumor lines and primary tumors. Its in vitro and in vivo tumor suppression function was investigated through the ectopic expression of miR-31 in NPC cells. We also determined the miR-31 targeted genes and its involvement in the growth in NPC. Results Downregulation of miR-31 expression was detected in almost all NPC cell line, patient-derived xenografts (PDXs) and primary tumors. Both homozygous deletion and promoter hypermethylation were shown to be major mechanisms for miR-31 silencing in this cancer. Strikingly, loss of miR-31 was also obviously observed in the dysplastic lesions of nasopharynx. Restoration of miR-31 in C666-1 cells inhibited the cell proliferation, colony-forming and migratory capacities. Dramatic reduction of in vitro anchorage-independent growth and in vivo tumorigenic potential were demonstrated in the stable clones expressing miR-31. Furthermore, we proved that miR-31 suppressed the NPC cell growth via targeting FIH1 and MCM2. Conclusions The findings provide strong evidence to support miR-31 as a new NPC-associated tumor suppressor on 9p21.3 region. The inactivation of miR-31 may contribute to the early development of NPC. PMID:25098679

  9. The time frame of Epstein-Barr virus latent membrane protein-1 gene to disappear in nasopharyngeal swabs after initiation of primary radiotherapy is an independently significant prognostic factor predicting local control for patients with nasopharyngeal carcinoma

    SciTech Connect

    Lin, S.-Y.; Chang, K.-P.; Hsieh, M.-S.; Ueng, S.-H.; Hao, S.-P.; Tseng, C.-K.; Pai, P.-C.; Chang, F.-T.; Tsai, M.-H.; Tsang, N.-M. . E-mail: rt3126@adm.cgmh.org.tw

    2005-12-01

    Purpose: The presence of Epstein-Barr virus latent membrane protein-1 (LMP-1) gene in nasopharyngeal swabs indicates the presence of nasopharyngeal carcinoma (NPC) mucosal tumor cells. This study was undertaken to investigate whether the time taken for LMP-1 to disappear after initiation of primary radiotherapy (RT) was inversely associated with NPC local control. Methods and Materials: During July 1999 and October 2002, there were 127 nondisseminated NPC patients receiving serial examinations of nasopharyngeal swabbing with detection of LMP-1 during the RT course. The time for LMP-1 regression was defined as the number of days after initiation of RT for LMP-1 results to turn negative. The primary outcome was local control, which was represented by freedom from local recurrence. Results: The time for LMP-1 regression showed a statistically significant influence on NPC local control both univariately (p < 0.0001) and multivariately (p = 0.004). In multivariate analysis, the administration of chemotherapy conferred a significantly more favorable local control (p = 0.03). Advanced T status ({>=} T2b), overall treatment time of external photon radiotherapy longer than 55 days, and older age showed trends toward being poor prognosticators. The time for LMP-1 regression was very heterogeneous. According to the quartiles of the time for LMP-1 regression, we defined the pattern of LMP-1 regression as late regression if it required 40 days or more. Kaplan-Meier plots indicated that the patients with late regression had a significantly worse local control than those with intermediate or early regression (p 0.0129). Conclusion: Among the potential prognostic factors examined in this study, the time for LMP-1 regression was the most independently significant factor that was inversely associated with NPC local control.

  10. An in silico analysis of dynamic changes in microRNA expression profiles in stepwise development of nasopharyngeal carcinoma

    PubMed Central

    2012-01-01

    Background MicroRNAs (miRNAs) are small non-coding RNAs that participate in the spatiotemporal regulation of messenger RNA (mRNA) and protein synthesis. Recent studies have shown that some miRNAs are involved in the progression of nasopharyngeal carcinoma (NPC). However, the aberrant miRNAs implicated in different clinical stages of NPC remain unknown and their functions have not been systematically studied. Methods In this study, miRNA microarray assay was performed on biopsies from different clinical stages of NPC. TargetScan was used to predict the target genes of the miRNAs. The target gene list was narrowed down by searching the data from the UniGene database to identify the nasopharyngeal-specific genes. The data reduction strategy was used to overlay with nasopharyngeal-specifically expressed miRNA target genes and complementary DNA (cDNA) expression data. The selected target genes were analyzed in the Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway. The microRNA-Gene-Network was build based on the interactions of miRNAs and target genes. miRNA promoters were analyzed for the transcription factor (TF) binding sites. UCSC Genome database was used to construct the TF-miRNAs interaction networks. Results Forty-eight miRNAs with significant change were obtained by Multi-Class Dif. The most enriched GO terms in the predicted target genes of miRNA were cell proliferation, cell migration and cell matrix adhesion. KEGG analysis showed that target genes were significantly involved in adherens junction, cell adhesion molecules, p53 signalling pathway et al. Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-29a/c, miR-34b, miR-34c-3p, miR-34c-5p, miR-429, miR-203, miR-222, miR-1/206, miR-141, miR-18a/b, miR-544, miR-205 and miR-149 may play important roles on the development of NPC. We proposed an integrative strategy for identifying the miRNA-mRNA regulatory modules and

  11. Involvement of Difference in Decrease of Hemoglobin Level in Poor Prognosis of Stage I and II Nasopharyngeal Carcinoma: Implication in Outcome of Radiotherapy

    SciTech Connect

    Gao Jin; Tao Yalan; Li Guo; Yi Wei; Xia Yunfei

    2012-03-15

    Purpose: To investigate the effect of hemoglobin (Hb) concentration and the difference in its decrease during treatment on outcome of radiotherapy (RT) alone for patients with Stage I and II nasopharyngeal carcinoma. Methods and Materials: A total of 572 patients with Stage I-II nasopharyngeal carcinoma with RT alone between January 2001 and December 2004 were retrospectively analyzed. Patient characteristics, tumor variables, and Hb level, including pre-RT Hb, mid-RT Hb, and dynamic change of Hb between pre- and post- RT and its difference in decrease ( White-Up-Pointing-Small-Triangle Hb) were subjected to univariate and multivariable analysis to identify factors that predict disease-specific survival (DSS), local regional recurrence-free survival (LRFS), and metastases-free survival (MFS). Results: The 5-year DSS was poorer in the Hb continuous decrease group than in the Hb noncontinuous decrease group (84% vs. 89%; p = 0.008). There was poorer 5-year DSS in patients with White-Up-Pointing-Small-Triangle Hb of >11.5 g/L than in those with White-Up-Pointing-Small-Triangle Hb of {<=}11.5 g/L (82% vs. 89%; p = 0.001), and poorer LRFS (79% vs. 83%; p = 0.035). Univariate and multivariate analysis showed that Hb decrease difference with greater than 11.5 g/L was an independent prognostic factor for DSS and LRFS. Conclusions: The difference in decrease of Hb level during the course of radiation treatment appeared as a poor prognostic factor in Stage I and II nasopharyngeal carcinoma patients.

  12. Can Epstein-Barr virus DNA load in nasopharyngeal brushings or whole blood predict recurrent nasopharyngeal carcinoma in a non-endemic region? A prospective nationwide study of the Dutch Head and Neck Oncology Cooperative Group.

    PubMed

    Stoker, Sharon D; Wildeman, Maarten A; Novalic, Zlata; Fles, Renske; van der Noort, Vincent; de Bree, Remco; Braunius, Weibel W; van den Broek, Guido B; Kreike, Bas; Kross, Kenneth W; Juwana, Hedy; Ramayanti, Octavia; Verkuijlen, Sandra A W M; de Boer, Jan Paul; Greijer, Astrid E; Middeldorp, Jaap M; Tan, I Bing

    2016-06-01

    This study estimated the value of quantitative measurements of EBV markers in the clinical management of nasopharyngeal carcinoma in a non-endemic area. The aim was to predict prognosis and detect recurrent and residual disease. In 72 patients, EBV DNA load in blood and nasopharyngeal brushes, and IgA VCA-p18 and EBNA1 in plasma were measured at different time points. At diagnosis and post-treatment, a cut-off value was used for detecting disease [positive (PPV) and negative (NPV) predictive value]. The markers were correlated as a continuous variable with tumor stage, disease-free survival (DFS) and overall survival (OS). The Cox hazard ratio model assessed hazard ratios. At diagnosis, the markers were above the COV in 45, 92, 85 and 83 % of the patients, respectively. Post-treatment, DNA load test in blood and brush had the best discriminating power (blood DNA load test: PPV 39 % and NPV 97 %, brush for local disease: PPV 75 % and NPV 99 %). Post-treatment, DNA load in blood was the best predictor for OS and DFS [hazard ratio 3.2 (95 % CI 1.51-3.5) and 2.3 (95 % CI 1.72-5.8)]. Assessing the EBV DNA load in blood has significant prognostic value, although the clinical value is for discussion. The EBV DNA load in the brush might improve early detection of local failures post-treatment. PMID:25929413

  13. In vivo fluence rate measurements during Foscan-mediated photodynamic therapy of persistent and recurrent nasopharyngeal carcinomas using a dedicated light applicator.

    PubMed

    van Veen, R L P; Nyst, H; Rai Indrasari, S; Adham Yudharto, M; Robinson, D J; Tan, I B; Meewis, C; Peters, R; Spaniol, S; Stewart, F A; Levendag, P C; Sterenborg, H J C M

    2006-01-01

    The objective of this study was to evaluate the performance of a dedicated light applicator for light delivery and fluence rate monitoring during Foscan-mediated photodynamic therapy of nasopharyngeal carcinoma in a clinical phase I/II study. We have developed a flexible silicone applicator that can be inserted through the mouth and fixed in the nasopharyngeal cavity. Three isotropic fibers, for measuring of the fluence (rate) during therapy, were located within the nasopharyngeal tumor target area and one was manually positioned to monitor structures at risk in the shielded area. A flexible black silicon patch tailored to the patient's anatomy is attached to the applicator to shield the soft palate and oral cavity from the 652-nm laser light. Fourteen patients were included in the study, resulting in 26 fluence rate measurements in the risk volume (two failures). We observed a systematic reduction in fluence rate during therapy in 20 out of 26 illuminations, which may be related to photodynamic therapy-induced increased blood content, decreased oxygenation, or reduced scattering. Our findings demonstrate that the applicator was easily inserted into the nasopharynx. The average light distribution in the target area was reasonably uniform over the length of the applicator, thus giving an acceptably homogeneous illumination throughout the cavity. Shielding of the risk area was adequate. Large interpatient variations in fluence rate stress the need for in vivo dosimetry. This enables corrections to be made for differences in optical properties and geometry resulting in comparable amounts of light available for Foscan absorption. PMID:16965135

  14. How Does Magnetic Resonance Imaging Influence Staging According to AJCC Staging System for Nasopharyngeal Carcinoma Compared With Computed Tomography?

    SciTech Connect

    Liao Xinbiao; Mao Yanping; Liu Lizhi; Tang Linglong; Sun Ying; Wang Yan; Lin Aihua; Cui Chunyan; Li Li; Ma Jun

    2008-12-01

    Purpose: To analyze the degree and pattern of influence of magnetic resonance imaging (MRI) on staging according to the 6th edition of the American Joint Committee on Cancer staging system compared with computed tomography (CT). Methods and Materials: The MRI and CT scans and medical records of 420 consecutive patients with newly diagnosed nasopharyngeal carcinoma (NPC) were analyzed retrospectively. The tumors of all patients were staged according to the 6th edition of the American Joint Committee on Cancer staging system. Results: A significant difference (p <0.05) was found between CT and MRI in demonstrating involvement in the oropharynx (CT, 25.0% vs. MRI, 14.5%), prevertebral muscle (CT, 18.4% vs. MRI, 36.0%), parapharyngeal space (CT, 82.6% vs. MRI, 68.8%), skull base (CT, 31.0% vs. MRI, 52.6%), sphenoid sinus (CT, 13.6% vs. MRI, 16.7%), ethmoid sinus (CT, 7.1% vs. MRI, 3.3%), intracranial area (CT, 4.8% vs. MRI, 16.0%), and retropharyngeal lymph nodes (CT, 52.1% vs. MRI, 69.0%). The incidence of cervical lymph node metastasis and lymph node metastasis at each level was similar according to CT and MRI. MRI resulted in changes in 49.8% of T stage cases, 10.7% of N stage cases, and 38.6% of clinical stage cases. Conclusion: MRI demonstrated early primary tumor involvement more precisely and deep primary tumor infiltration more easily. The use of MRI caused dramatic changes in the results of the T stage and clinical staging and should be preferred to CT in staging NPC. Patients would benefit from changes in treatment strategies resulting from the use of MRI.

  15. Parotid area lymph node metastases from preliminarily diagnosed patients with nasopharyngeal carcinoma: report on tumor characteristics and oncologic outcomes

    PubMed Central

    Xiao, Youping; Zong, Jingfeng; Qiu, Sufang; Bai, Penggang; Dai, Yitao; Zhou, Lin; Chen, Xiaolin; Zheng, Wei; Chen, Yunbin; Lin, Shaojun; Pan, Jianji

    2016-01-01

    The parotid area lymph node (PLN) is an uncommon site of metastasis originating from nasopharyngeal carcinoma (NPC). The study aimed to investigate clinical characteristics and outcomes of patients with preliminarily diagnosed NPC with PLN metastases. Here we retrospectively reviewed Magnetic resonance imaging (MRI) scans of 2221 patients with untreated nonmetastatic NPC who received intensity-modulated radiation therapy (IMRT). Finally, 64 (2.9%) patients were identified with PLN metastases, of which, 34 received PLN-sparing IMRT and 30 received PLN-radical IMRT. We also found that 42.2% had N3 disease and 95.3% had stages III-IVb. PLN metastases on MRI were characterized by ipsilateral retropharyngeal lymph node (RLN) or level II nodal extracapsular spread (ECS), ipsilateral giant cervical nodes, ipsilateral parapharyngeal extension, or solitary parotid metastasis. The 5-year overall survival, distant metastasis-free survival, regional relapse-free survival, and parotid relapse-free survival rates were 70.4%, 64.3%, 76.7%, and 87.9%, respectively. Distant metastases were the main cause of treatment failure and death. Using PLN-sparing IMRT, sparing PLN with minimal axial diameter of <10 mm, could increase the risk of parotid recurrence. However, it was not an independent prognostic factor. N classification and concurrent-based chemotherapy were almost statistically significant for distant failure and death. Overall, we demonstrated that the PLN metastases might be derived from RLN or level II nodal ECS, giant cervical nodes in a retrograde fashion, or parapharyngeal extension. Sparing PLN of <10 mm by IMRT should consider the risk of parotid recurrence. Distant metastases remained the dominant treatment failure. Further effective systemic chemotherapy should be explored. PMID:26934439

  16. The AQP-3 water channel is a pivotal modulator of glycerol-induced chloride channel activation in nasopharyngeal carcinoma cells.

    PubMed

    Zhang, Haifeng; Deng, Zhiqin; Yang, Lili; Luo, Hai; Liu, Shanwen; Li, Yuan; Wei, Yan; Peng, Shuang; Zhu, Linyan; Wang, Liwei; Chen, Lixin

    2016-03-01

    Aquaporin (AQP) and chloride channels are ubiquitous in virtually all living cells, playing pivotal roles in cell proliferation, migration and apoptosis. We previously reported that AQP-3 aquaglyceroporin and ClC-3 chloride channels could form complexes to regulate cell volume in nasopharyngeal carcinoma cells. In this study, the roles of AQP-3 in their hetero-complexes were further investigated. Glycerol entered the cells via AQP-3 and induced two different Cl(-) currents through cell swelling-dependent or -independent pathways. The swelling-dependent Cl(-) current was significantly inhibited by pretreatment with CuCl2 and AQP-3-siRNA. After siRNA-induced AQP-3 knock-down, the 140 mM glycerol isoosmotic solution swelled cells by 22% (45% in AQP-3-intact cells) and induced a smaller Cl(-) current; this current was smaller than that activated by 8% cell volume swelling, which induced by the 140 mM glycerol hyperosmotic solution in AQP-3-intact cells. This suggests that the interaction between AQP-3 and ClC-3 plays an important role in cell volume regulation and that AQP-3 may be a modulator that opens volume-regulated chloride channels. The swelling-independent Cl(-) current, which was activated by extracellular glycerol, was reduced by CuCl2 and AQP-3-siRNA pretreatment. Dialyzing glycerol into cells via the pipette directly induced the swelling-independent Cl(-) current; however this current was blocked by AQP-3 down-regulation, suggesting AQP-3 is essential for the opening of chloride channels. In conclusion, AQP-3 is the pathway for water, glycerol and other small solutes to enter cells, and it may be an essential modulator for the gating of chloride channels. PMID:26794461

  17. Dosimetric Comparison of Intensity-Modulated Stereotactic Radiotherapy With Other Stereotactic Techniques for Locally Recurrent Nasopharyngeal Carcinoma

    SciTech Connect

    Kung, Shiris Wai Sum; Wu, Vincent Wing Cheung; Kam, Michael Koon Ming; Leung, Sing Fai; Yu, Brian Kwok Hung; Ngai, Dennis Yuen Kan; Wong, Simon Chun Fai; Chan, Anthony Tak Cheung

    2011-01-01

    Purpose: Locally recurrent nasopharyngeal carcinoma (NPC) patients can be salvaged by reirradiation with a substantial degree of radiation-related complications. Stereotactic radiotherapy (SRT) is widely used in this regard because of its rapid dose falloff and high geometric precision. The aim of this study was to examine whether the newly developed intensity-modulated stereotactic radiotherapy (IMSRT) has any dosimetric advantages over three other stereotactic techniques, including circular arc (CARC), static conformal beam (SmMLC), and dynamic conformal arc (mARC), in treating locally recurrent NPC. Methods and Materials: Computed tomography images of 32 patients with locally recurrent NPC, previously treated with SRT, were retrieved from the stereotactic planning system for contouring and computing treatment plans. Treatment planning of each patient was performed for the four treatment techniques: CARC, SmMLC, mARC, and IMSRT. The conformity index (CI) and homogeneity index (HI) of the planning target volume (PTV) and doses to the organs at risk (OARs) and normal tissue were compared. Results: All four techniques delivered adequate doses to the PTV. IMSRT, SmMLC, and mARC delivered reasonably conformal and homogenous dose to the PTV (CI <1.47, HI <0.53), but not for CARC (p < 0.05). IMSRT presented with the smallest CI (1.37) and HI (0.40). Among the four techniques, IMSRT spared the greatest number of OARs, namely brainstem, temporal lobes, optic chiasm, and optic nerve, and had the smallest normal tissue volume in the low-dose region. Conclusion: Based on the dosimetric comparison, IMSRT was optimal for locally recurrent NPC by delivering a conformal and homogenous dose to the PTV while sparing OARs.

  18. The Impact of the Overall Radiotherapy Time on Clinical Outcome of Patients with Nasopharyngeal Carcinoma; A Retrospective Study

    PubMed Central

    Stoker, S. D.; Fles, R.; Herdini, C.; Rijntjes, F. J. F.; Dwidanarti, S. R.; Sikorska, K.; Leemans, C. R.; Schmidt, M. K.; Al-Mamgani, A.; Wildeman, M. A.; Haryana, S. M.; Indrasari, S. R.; Tan, I. B.

    2016-01-01

    Purpose In Yogyakarta, nasopharyngeal carcinoma (NPC) shows a poor response to radiotherapy treatment. Previous study showed a prolonged overall treatment time (OTT), due to interruptions during treatment. This study explores the association between clinical outcome and OTT. Secondary, the relation between clinical outcome and disease stage, waiting time to radiation (WT) and chemotherapy schedule was explored. Methods In this retrospective cohort, 142 patients who started curative intent radiotherapy for NPC between March 2009 and May 2014, with or without chemotherapy, were included. The median follow up time was 1.9 years. Data was collected on WT, OTT, disease stage, and chemotherapy schedule. Time factors were log-transformed. Clinical outcome was defined as therapy response, loco-regional control (LRC), disease free survival (DFS) and overall survival (OS). Results The median WT was 117 days (range 12–581) and OTT was 58 days (43–142). OTT and disease stage were not associated to any of the clinical outcome parameters. The log- WT was associated to poor therapy outcome (HR 1.68; 95% ci: 1.09–2.61), LRC (HR 1.66; 95% ci: 1.15–2.39), and DFS (HR 1.4; 95% ci: 1.09–1.81). In the multivariable analysis, significant hazard risk for poor therapy response, LRC, DFS and OS were seen for patients who didn’t received concurrent chemotherapy. Conclusion Not receiving concurrent chemotherapy showed the strongest risk for poor outcome. Since the choice of chemotherapy is related to a variety of factors, like the WT and patient’s physical condition when radiation can start, careful interpretation is needed. Reason for not finding a relation between OTT and clinical outcome might be the low number of patients who finished radiotherapy within 7 weeks, or by a stronger detrimental effect of other factors. PMID:27030990

  19. Silencing Fibronectin Extra Domain A Enhances Radiosensitivity in Nasopharyngeal Carcinomas Involving an FAK/Akt/JNK Pathway

    SciTech Connect

    Ou Juanjuan; Pan Feng; Geng Peiliang; Wei Xing; Xie Ganfeng; Deng Jia; Pang Xueli; Liang Houjie

    2012-03-15

    Purpose: Fibronectin extra domain A (EDA) is known to play important roles in angiogenesis, lymphangiogenesis, and metastasis in malignant tumors. The present study examined the effect of EDA on the radioresistance potential of nasopharyngeal carcinoma (NPC). Methods and Materials: EDA expression levels in blood samples and tumor tissues of NPC patients were tested by enzyme-linked immunosorbent assay and immunohistochemistry. Radiosensitivity was tested by colony survival assay. Apoptosis was determined by flow cytometry. The expressions of EDA, cleaved caspase 9, cleaved caspase 3, cleaved PARP, Bcl-2, and the levels of phosphorylated FAK, Akt, and JNK were measured by Western blot. Xenografts were used to confirm the effect of EDA on radiosensitivity in vivo. Results: EDA levels in blood samples of advanced NPC patients were much higher than those in early-stage patients. In tumor tissues, the positive expressions of EDA in NPC tumor tissues were shown to be correlated with the differentiation degrees of cancer cells and lymph node metastases. Additionally, the expression of EDA is positively correlated with the expression of antiapoptotic gene (Bcl2), but negatively correlated with the expressions of apoptotic genes (cleaved caspase-3, cleaved caspase-9, cleaved PARP). In vitro, EDA-silenced NPC cells CNE-2 shows substantially enhanced radiosensitivity with lower colony survival and more apoptosis in response to radiation. In vivo, EDA-silenced xenografts were more sensitive to radiation. At the molecular level, FAK/Akt/JNK signaling was demonstrated to be inactivated in EDA-silenced CNE-2 cells. Conclusions: EDA strongly affected the radiosensitivity of NPC cells. FAK/Akt/JNK signaling was found to be a potential signaling mediating EDA function.

  20. High serum levels of soluble CD40-L in patients with undifferentiated nasopharyngeal carcinoma: pathogenic and clinical relevance

    PubMed Central

    Caggiari, Laura; Guidoboni, Massimo; Vaccher, Emanuela; Barzan, Luigi; Franchin, Giovanni; Gloghini, Annunziata; Martorelli, Debora; Zancai, Paola; Bortolin, Maria Teresa; Mazzucato, Mario; Serraino, Diego; Carbone, Antonino; De Paoli, Paolo; Dolcetti, Riccardo

    2007-01-01

    Background Engagement of CD40 promotes survival of undifferentiated nasopharyngeal carcinoma (UNPC) cells and similar effects are induced by the EBV oncoprotein LMP-1 that is expressed in a fraction of cases. Considering that CD40 may be activated also by the soluble isoform of CD40L (sCD40L), we investigated the serum levels of sCD40L in a series of 61 UNPC patients from Italy, a non-endemic area for this disease. Results At diagnosis, serum samples of UNPC patients contained significantly higher levels of sCD40L than age-matched healthy controls (p < 0.001). High levels of sCD40L (i.e., >18 ng/ml) were more frequently found in patients <40 years of age (p = 0.03) and with distant metastases at presentation (p = 0.03). Serum levels of sCD40L were inversely associated with the expression of the EBV oncoprotein LMP-1 (p = 0.03), which mimics a constitutively activated CD40. The amount of sCD40L decreased in a fraction of patients treated with local radiotherapy alone. Moreover, CD40L+ lymphoid cells admixed to neoplastic UNPC cells were detected in cases with high serum levels of sCD40L, suggesting that sCD40L is probably produced within the tumor mass. Conclusion sCD40L may contribute to CD40 activation in UNPC cells, particularly of LMP-1-negative cases, further supporting the crucial role of CD40 signalling in the pathogenesis of UNPC. sCD40L levels may be useful to identify UNPC patients with occult distant metastases at presentation. PMID:17331231

  1. Pathogenic role of Epstein-Barr virus latent membrane protein-1 in the development of nasopharyngeal carcinoma.

    PubMed

    Yoshizaki, Tomokazu; Kondo, Satoru; Wakisaka, Naohiro; Murono, Shigeyuki; Endo, Kazuhira; Sugimoto, Hisashi; Nakanishi, Sayaka; Tsuji, Akira; Ito, Makoto

    2013-08-28

    Undifferentiated nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignant tumor. A consistent elevation in EBV antibody titers is a well-established risk factor for the development of NPC. The pathophysiological relationship and molecular mechanisms of EBV-mediated carcinogenesis have not been fully elucidated. While NPC tumors are known to express three EBV-encoded proteins, EBNA1, LMP1, and LMP2, they also express a large number of virus-encoded small RNAs (EBERs) and microRNAs (miRNAs). Among them, LMP1 may be a central player in the development of NPC. LMP1, an EBV-encoded primary oncogene, functions as a viral mimic of the TNFR family member, CD40, and engages in a number of signaling pathways that induce morphological and phenotypic alterations in epithelial cells. LMP1 upregulates EMT, and contributes to the highly metastatic features of NPC. Moreover, LMP1-associated EMT is accompanied by the expression of cancer stem cell (CSC)/cancer progenitor cell (CPC) markers (CD44high/CD24low) and the acquisition of stem cell/progenitor cell-like properties. BART miRNAs, encoded from the BamHI-A region of the viral genome, are the most abundant transcripts. They modulate apoptosis and host innate immune defense mechanisms. Some BART1 miRNAs are considered to negatively regulate LMP1 protein expression. LMP1 is secreted via exosomes, is incorporated into EBV-uninfected cells by endocytosis, and affects the environment surrounding the tumor. Here we reviewed the contribution of EBV gene products to NPC pathogenesis in relation with LMP1. PMID:23689138

  2. Topical use of olive oil preparation to prevent radiodermatitis: results of a prospective study in nasopharyngeal carcinoma patients

    PubMed Central

    Cui, Zhaoyang; Xin, Mei; Yin, Haiying; Zhang, Jiandong; Han, Fei

    2015-01-01

    Background: Radiodermatitis is a common side effect of radiotherapy. However, an effective method for the prevention of radiodermatitis has not yet been identified. The purpose of this study was to evaluate the effectiveness of topical olive oil in the prevention of acute radiodermatitis in patients with nasopharyngeal carcinoma (NPC) who were undergoing concurrent chemoradiotherapy. Methods: A prospective study was conducted in patients with NPC. The patients were randomized into the intervention (n = 47) and control (n = 47) groups. Patients in the control group were treated with a general skin care regimen (placebo), whereas patients in the intervention group were treated with olive oil thrice daily for 7 weeks during chemoradiotherapy and for two weeks thereafter. On a weekly basis for a total duration of 9 weeks, a blinded observer assessed the severity of dermatitis, which was graded from 0 to 4 according to the Radiation Therapy Oncology Group (RTOG) criteria and the Visual Analog Scale (VAS) score. Results: Mild reactions due to radiation (grades I and II) occurred in 93.6% of the intervention group and in 72.3% of the control group. Patients in the intervention group encountered significantly less severe dermatitis during chemoradiotherapy compared with patients in the control group (P < 0.01). A multivariate analysis revealed that the use of olive oil (P < 0.01) was significantly associated with a decrease in skin injuries. Conclusions: The prophylactic use of olive oil was associated with a significant decrease in the intensity of acute dermatitis in NPC patients. The results of this trial indicate that olive oil holds promise as a safe and effective prophylactic treatment for radiodermatitis. PMID:26379896

  3. Evaluation of tumor angiogenesis measured with microvessel density (MVD) as a prognostic indicator in nasopharyngeal carcinoma: Results of RTOG 9505

    SciTech Connect

    Foote, Robert L. . E-mail: foote.robert@mayo.edu; Weidner, Noel; Harris, Jonathan; Hammond, Elizabeth; Lewis, Jean E.; Vuong, Te; Ang, K. Kian; Fu, Karen K.

    2005-03-01

    Purpose: The objective of this study was to evaluate tumor angiogenesis as measured by microvessel density (MVD) as an independent prognostic factor in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy alone. Methods and materials: Eligible patients included those with NPC treated with radiotherapy. Paraffin blocks of the primary tumor had a hematoxylin and eosin-stained section prepared at the block face. One representative section for tumor was stained for factor VIII-related antigen using a standard immunoperoxidase staining technique. MVD was determined by light microscopy in areas of invasive tumor containing the highest numbers of capillaries and microvessels per area. Individual microvessel counts were made on a 200x field within the area of most intense tumor neovascularization. Results were expressed as the highest number of microvessels identified within any single 200x field. Using a breakpoint of MVD < 60 vs. {>=}60, the distributions between the two MVD groups were compared by the method of Gray. Overall survival rates were estimated by the Kaplan-Meier method and compared by the log-rank test. A multivariate Cox proportional hazard model was employed to examine the relationship between MVD and disease outcomes while adjusting for other concomitant variables. Results: One hundred sixty-six were eligible, of whom 123 had values determined for MVD. The MVD values ranged from 9 to 243 with a median of 70. In the multivariate analysis of overall survival, distant metastases, and local-regional failure, MVD did not significantly improve the model containing T stage, N stage, age, radiation dose, and World Health Organization class. Conclusions: We found no significant differences in overall survival, time to distant metastasis, or time to local-regional failure using a breakpoint of MVD < 60 vs. MVD {>=}60. The study was perhaps limited by the small size of the NPC samples.

  4. Overexpression of PIN1 Enhances Cancer Growth and Aggressiveness with Cyclin D1 Induction in EBV-Associated Nasopharyngeal Carcinoma

    PubMed Central

    Xu, Meng; Cheung, Chartia Ching-Mei; Chow, Chit; Lun, Samantha Wei-Man; Cheung, Siu-Tim; Lo, Kwok-Wai

    2016-01-01

    Background Nasopharyngeal carcinoma (NPC) is a peculiar Epstein Barr virus (EBV)-associated malignancy that is prevalent in South-East Asia. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) isomerizes specific phosphorylated amino acid residues, which makes it an important regulator in cell survival and apoptosis. In this study, we investigated the contribution made by PIN1 in NPC tumorigenesis and PIN1’s potential role as a therapeutic target. Methods The expression of PIN1 was examined in a panel of NPC cell lines, xenografts and primary tumors. The functional roles of PIN1 in NPC cells were elucidated by the knockdown and overexpression of PIN1 in in vitro and in vivo nude mice models by siRNA and lenti-viral transfection, respectively. The antitumor effects of the PIN1 inhibitor Juglone in NPC cells were also evaluated. Results We revealed the consistent overexpression of PIN1 in almost all EBV-associated NPC cell lines, xenografts and primary tumors. PIN1 suppression was capable of inhibiting cyclin D1 expression and activating caspase-3 in NPC cells. It positively regulated NPC cell proliferation, colony formation and anchorage-independent growth. The inhibition of PIN1 suppressed tumor growth in vitro and in vivo. Conclusions This study demonstrates the oncogenic role of PIN1 in NPC tumorigenesis, and shows that its overexpression can enhance tumor cell growth via the upregulation of cyclinD1. Our findings inform the development of novel treatments targeting PIN1 for NPC patients. PMID:27258148

  5. Protein expression of nucleophosmin, annexin A3 and nm23-H1 correlates with human nasopharyngeal carcinoma radioresistance in vivo

    PubMed Central

    QU, SONG; LI, XIAO-YU; LIANG, ZHONG-GUO; LI, LING; HUANG, SHI-TING; LI, JIA-QUAN; LI, DAN-RONG; ZHU, XIAO-DONG

    2016-01-01

    Radioresistance is a significant obstacle in the treatment of endemic nasopharyngeal carcinoma (NPC). The present study aimed to identify proteins associated with radioresistance in NPC in vitro and in vivo. Proteomics analyses were conducted to screen for differentially-expressed proteins (DEPs) in parental CNE-2 cells and CNE-2R cells. Using proteomics approaches, 16 DEPs were identified. Of these DEPs, nucleophosmin (NPM1), annexin A3 and nm23-H1, were verified using western blot analyses. The tumorigenicity was investigated using mouse xenograft tumorigenicity assays, and tumor growth curves were generated. The protein expression of NPM1, annexin A3 and nm23-H1 was examined by immunohistochemically staining tumor tissues. NPM1 and annexin A3 protein levels were downregulated in the CNE-2R cells, whereas nm23-H1 expression was upregulated. In vivo tests showed that compared with the CNE-2 tumors, CNE-2R tumor growth was significantly retarded (P<0.05). CNE-2 tumor progression was inhibited by irradiation, but CNE-2R tumor progression was not, indicating that the CNE-2R cells were also radioresistant in vivo. NPM1 and annexin A3 expression was significantly lower in non-irradiated (NIR)-CNE-2R tumors compared with NIR-CNE-2 tumors (P<0.01). However, Nm23-H1 protein levels were significantly higher (P<0.05). Overall, the present study established comparable radioresistant and radiosensitive tumor models of human NPC, and identified candidate biomarkers that may correlate with radioresistance. The data showed that dysregulation of NPM1, annexin A3 and nm23-H1 expression correlated with the cellular and tumor radioresponse. These proteins are involved in the regulation of intracellular functions, including stress responses, cell proliferation and DNA repair. However, further clinical evaluations are required. PMID:27347189

  6. Prognostic effect of pregnancy on young female patients with nasopharyngeal carcinoma: results from a matched cohort analysis

    PubMed Central

    Tang, Lin-Quan; Chen, Qiu-Yan; Guo, Shan-Shan; Liu, Li-Ting; Guo, Ling; Mo, Hao-Yuan; Zhao, Chong; Guo, Xiang; Cao, Ka-Jia; Qian, Chao-Nan; Zeng, Mu-Sheng; Shao, Jian-Yong; Sun, Ying; Ma, Jun; Hong, Ming-Huang; Mai, Hai-Qiang

    2016-01-01

    Objectives We aimed to evaluate the prognosis of pregnancy-associated patients with nasopharyngeal carcinoma (NPC) in a young population. Methods From June 1999 to December 2010, 51 patients aged ≤ 35 years who were diagnosed with NPC during pregnancy or within one year after delivery were admitted into the pregnancy-associated group in our institution. An additional 51 patients who were not pregnant at diagnosis were selected from 451 patients based on the matching criteria to match the pregnancy-associated female patients. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and distant-metastasis failure-free survival (DMFS) and locoregional failure-free survival (LRFS). Results The advanced stage was not different between the pregnant and the non-pregnant group before matching (69.8% vs. 70.3%, P = 0.690). No difference in OS at the median follow-up time of 92 months was observed between the pregnancy-associated and the non-pregnant group (85.4% vs. 92.2%, P = 0.478); likewise, no differences were observed regarding PFS and DMFS. However, the pregnancy-associated group had worse LRFS than the non-pregnant group (84.8% vs. 95.9%, P = 0.033). When the pregnancy-associated patients were dichotomized into an early pregnancy group and a late pregnancy group, our data showed that pregnancy interval did not seem to impact the risk of death or relapse. Conclusion Our results show that patients in the pregnant group did not seem to have more advanced stage or inferior survival than that in the non-pregnant group. PMID:26980734

  7. How Does Intensity-Modulated Radiotherapy Versus Conventional Two-Dimensional Radiotherapy Influence the Treatment Results in Nasopharyngeal Carcinoma Patients?

    SciTech Connect

    Lai Shuzhen; Li Wenfei; Chen Lei; Luo Wei; Chen Yuanyuan; Liu Lizhi; Sun Ying; Lin Aihua; Liu Mengzhong; Ma Jun

    2011-07-01

    Purpose: To compare the results of intensity-modulated radiotherapy (IMRT) with those of two-dimensional conventional radiotherapy (2D-CRT) in the treatment of patients with nasopharyngeal carcinoma (NPC). Methods and Materials: A retrospective review of data from 1,276 patients with biopsy-proven, nonmetastatic NPC was performed. All patients had undergone magnetic resonance imaging and were staged according to the sixth edition of the American Joint Committee on Cancer staging criteria. Radiotherapy was the primary treatment for all patients. Results: Of the 1,276 patients, 512 were treated with IMRT and 764 with 2D-CRT. The 5-year actuarial local relapse-free survival (LRFS), the nodal relapse-free survival (NRFS), the distant metastasis-free survival (DMFS), and the disease-free survival (DFS) rates were 92.7%, 97.0%, 84.0%, and 75.9%, respectively, for the IMRT group, and 86.8%, 95.5%, 82.6%, and 71.4%, respectively, for the 2D-CRT group. In stage T1 patients, improvement of LRFS in the IMRT group was even significantly higher than in the 2D-CRT group (100% vs. 94.4%; p = 0.016). A trend of improvement of DFS was observed in the IMRT group compared with the 2D-CRT group but without reaching statistical significance. NRFS and DMFS rates were similar in the two groups. Conclusions: A greater improvement of treatment results with IMRT than with 2D-CRT was demonstrated primarily by achieving a higher local tumor control rate in NPC patients, especially in the early T stage patients. The goal of better control of both local failure in advanced, nonmetastatic NPC patients and of distant failure should be addressed in future studies.

  8. Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

    SciTech Connect

    Twu, C.-W.; Wang, W.-Y.; Liang, W.-M.; Jan, J.-S.; Jiang, R.-S.; Chao, Jeffrey; Jin, Y.-T.; Lin, J.-C. . E-mail: jclin@vghtc.gov.tw

    2007-01-01

    Purpose: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. Methods and Materials: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. Results: Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p < 0.0001) and relapse-free survival rates (54.4% vs. 77.9%, p = 0.0009) were significantly lower in patients with higher pretreatment EBV DNA load than in those with lower EBV DNA load. Patients with persistently detectable EBV DNA after treatment had significantly worse 4-year overall (30.8% vs. 84.6%, p < 0.0001) and relapse-free survival rates (15.4% vs. 74.0%, p < 0.0001) than those with undetectable EBV DNA. The VCA-IgA and VCA-IgG titer could not predict survivals (all p > 0.1). Cox multivariate analyses also showed the same results. Conclusion: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC.

  9. Functional polymorphism in the 5′-UTR of CR2 is associated with susceptibility to nasopharyngeal carcinoma

    PubMed Central

    FAN, QIN; HE, JUN-FANG; WANG, QI-RUI; CAI, HONG-BING; SUN, XUE-GANG; ZHOU, XIN-XI; QIN, HAI-DE; SHUGART, YIN YAO; JIA, WEI-HUA

    2013-01-01

    Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is a squamous cell cancer endemic in Southern China and Southeast Asia. It has been shown that inflammatory and immune responses during EBV infection contribute to the development of NPC. The complement receptor 2 (CR2) gene plays central roles during inflammatory and immune responses and, therefore, is a good candidate susceptibility gene for NPC. We performed PCR-based sequencing to identify multiple single-nucleotide polymorphisms (SNPs) within the exon regions of the CR2 gene in a Cantonese population. Two SNPs were screened in 528 NPC patients and 408 normal individuals to perform a case-control study matched according to age, gender and residence. Furthermore, we cloned the entire 5′-UTR and entire CR2 promoter into a luciferase report system and compared the luciferase activities between the different allelic constructs. A SNP in the 5′-UTR of CR2 (24 T/C, rs3813946) showed a significant association (P<0.01) with NPC in the Cantonese population studied. The subjects were categorized into 2 age groups: group 1, age ≤45 years and group 2, age >45 years. In group 1, the allelic frequencies of 24 T/C in the patients were significantly different from those of the controls (P=0.0034). The odds ratio (OR=1.81) also indicated a higher risk of NPC in individuals who carried the minor allele C. All constructs exerted allelic differences on luciferase activities, but only the susceptible allele +24C construct showed increased activity. Our findings implicate CR2 as a susceptibility gene for NPC and suggest that enhanced CR2 expression may be involved in the oncogenesis and development of NPC. PMID:23612877

  10. Prognostic Value of Cavernous Sinus Invasion in Patients with Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiotherapy

    PubMed Central

    Du, Xiao-Jing; Lan, Mei; Guo, Ying; Zheng, Lie; Xia, Yun-Fei; Luo, Wei

    2016-01-01

    Purpose To investigate the prognostic value of cavernoussinus invasion (CSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Patients and Methods Retrospective review of data from 1,087 patients with biopsy-proven, non-metastatic NPC. All patients were diagnosed using magnetic resonance imaging (MRI) scans and received IMRT as the primary treatment. Results The incidence of cavernoussinus invasion in this cohort was 12.1%. In univariate analysis, 5-year overall survival (OS) (70.6% vs. 88.5%, P < 0.001) and distant metastasis-free survival (DMFS) (71.4% vs. 87.7%, P < 0.001), but not locoregional relapse-free survival (LRFS) (93.9% vs. 93.7%, P = 0.341), were significantly different between patients with and without cavernoussinus invasion. In the T4 subgroup, the 5-year OS, DMFS, and LRFS of patients with and without cavernoussinus extension were 70.6% vs. 81.9% (P = 0.011), 71.4% vs. 84.1% (P = 0.011), and 91.2% vs. 89.7% (P = 0.501), respectively. In multivariate analysis, cavernoussinus invasion was an independent prognostic factor for poorer OS (HR = 1.782; P = 0.013) and DMFS (HR = 1.771; P = 0.016), but not LRFS (HR = 0.632; P = 0.294). In patients with lymph node metastasis, the DMFS rates of patients with and without cavernoussinus invasion were significantly different (P < 0.001). Preliminaryanalysis indicated that neoadjuvant chemotherapy led to better DMFS and OS in patients with cavernoussinus invasion than concurrent chemotherapy or radiotherapy alone; however, the differences were not significant. Conclusions In the IMRT era, cavernoussinus invasion remains a prognostic factor for poor DMFS and OS in NPC, even in patients with T4 disease. PMID:26824230

  11. Prognostic score models for survival of nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy and chemotherapy

    PubMed Central

    Zeng, Lei; Guo, Pi; Li, Jin-Gao; Han, Fei; Li, Qiang; Lu, Yong; Deng, Xiao-Wu; Zhang, Qing-Ying; Lu, Tai-Xiang

    2015-01-01

    Purpose To establish accurate prognostic score models to predict survival for patients with nasopharyngeal carcinoma (NPC), treated with intensity-modulated radiotherapy (IMRT) and chemotherapy. Materials and methods Six hundred and seventy-five patients with newly diagnosed, nonmetastatic and histologically proven NPC who were treated with IMRT and chemotherapy were analyzed retrospectively. Samples were split randomly into a training set (n = 338) and a test set (n = 337) to analyze. All data from the training set were used to perform an extensive survival analysis and to develop multivariate nomograms based on Cox regression. Data from the test set was used as an external validation set. Risk group stratification was proposed for the nomograms. Results The nomograms are able to predict survival with a C-index for external validation of local recurrence-free survival (LRFS; 0.66, 95% CI: 0.58-0.74), distant metastasis-free survival (DMFS; 0.73, 95% CI: 0.66-0.79), and disease-specific survival (DSS; 0.73, 95% CI: 0.67-0.79). The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. The C-index of the nomogram for LRFS, DMFS and DSS were statistically higher than the C-index values of the AJCC seventh edition (P < 0.001). In the test set, the nomogram discrimination was also superior to the AJCC Staging systems (P < 0.001). The stratification in risk groups allows significant distinction between Kaplan-Meier curves for outcome. Conclusions Prognostic score models were successfully established and validated to predict LRFS, DMFS, and DSS over a 5-year period after IMRT and chemotherapy, which will be useful for individual treatment. PMID:26415223

  12. Prognostic value of wait time in nasopharyngeal carcinoma treated with intensity modulated radiotherapy: a propensity matched analysis.

    PubMed

    Chen, Yu-Pei; Mao, Yan-Ping; Zhang, Wen-Na; Chen, Lei; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Zhou, Guan-Qun; Guo, Rui; Sun, Ying; Kang, Tie-Bang; Zeng, Mu-Sheng; Ma, Jun

    2016-03-22

    The aim of this study was to determine the prognostic value of wait time from histological diagnosis to primary treatmen for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Between October 2009 and February 2012, a total of 1672 NPC patients were retrospectively analyzed. A cutoff value of > 4 weeks was used to define prolonged wait time. Matched patients according to the wait time were identified using propensity score matching (PSM), which was also used to identify matched patients for subsequent stratified analyses. Differences in progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) were estimated using the Kaplan-Meier method and Cox proportional hazards models. In total, 407 pairs of NPC patients were selected by PSM. The 3-year PFS rate was significantly lower for patients with a prolonged wait time (> 4 weeks) than for those with an acceptable wait time (P = 0.035). Stratified analyses revealed that the negative effects of a prolonged wait time occurred primarily in patients with advanced NPC without neoadjuvant chemotherapy (NACT; PFS:P = 0.040; DMFS:P = 0.028). In multivariate analysis, a prolonged wait time was found to be an independent unfavorable prognostic factor for PFS and DMFS in advanced-staged patients without NACT. These results suggest that a prolonged time (> 4 weeks) between diagnosis and primary radical radiotherapy is a disadvantage for NPC patients, particularly those with advanced disease receiving no NACT. Thus, it is necessary to optimize resources for decreasing this wait time, although additional studies are warranted to further clarify our findings. PMID:26942870

  13. Curcumin exerts inhibitory effects on undifferentiated nasopharyngeal carcinoma by inhibiting the expression of miR-125a-5p.

    PubMed

    Gao, Wei; Chan, Jimmy Yu-Wai; Wong, Thian-Sze

    2014-11-01

    Curcumin suppresses proliferation, migration, invasion, metastasis and angiogenesis and induces apoptosis by regulating multiple signalling pathways and miRNAs in a wide variety of human malignancies. miRNAs play crucial roles in various steps of carcinogenesis in nasopharyngeal carcinoma (NPC); thus, they could serve as critical therapeutic targets for NPC treatment. Curcumin could provide a novel strategy to block or induce specific miRNAs for miRNA-based gene therapies. Nevertheless, there are no reports to date on the miRNAs regulated by curcumin in NPC. In the present study, we have carried out an miRNA microarray to identify the miRNAs regulated by curcumin in NPC. Curcumin treatment down-regulated the expression of hsa-miR-125a-5p, hsa-miR-574-3p and hsa-miR-210 as determined by miRNA microarray analysis and qPCR (real-time quantitative reverse transcription-PCR). Forced expression of miR-125a-5p enhanced proliferation, migration and invasion of HONE1 cells. Primary NPC exhibited a significantly higher expression level of miR-125a-5p than healthy controls. miR-125a-5p inhibited the expression of tumour protein 53 (TP53), and curcumin treatment up-regulated the expression of TP53. Taken together, these results indicate that curcumin exerted inhibitory effects on NPC by inhibiting the expression of miR-125a-5p and, subsequently, enhancing the expression of TP53. Curcumin could provide a novel strategy to block miR-125a-5p for miRNA-based gene therapies in NPC. PMID:24896104

  14. Preliminary results of a phase I/II study of simultaneous modulated accelerated radiotherapy for nondisseminated nasopharyngeal carcinoma

    SciTech Connect

    Lee, Sang-wook . E-mail: lsw@amc.seoul.kr; Back, Geum Mun; Yi, Byong Yong; Choi, Eun Kyung; Ahn, Seung Do; Shin, Seong Soo; Kim, Jung-hun; Kim, Sang Yoon; Lee, Bong-Jae; Nam, Soon Yuhl; Choi, Seung-Ho; Kim, Seung-Bae; Park, Jin-hong; Lee, Kang Kyoo; Park, Sung Ho; Kim, Jong Hoon

    2006-05-01

    Purpose: To present preliminary results of intensity-modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiotherapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). Methods and Materials: Twenty patients who underwent IMRT for nondisseminated NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. Intensity-modulated radiotherapy was delivered with the 'step and shoot' SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume, 60 Gy (2 Gy/day) to the clinical target volume and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received cisplatin once per week. Results: The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had Radiation Therapy Oncology Group Grade 3 mucositis, whereas 9 (45%) had Grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no Grade 3 or 4 xerostomia. All patients showed complete response. Two patients had distant metastases and locoregional recurrence, respectively. Conclusion: Intensity-modulated radiotherapy with the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and might also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.

  15. Pretreatment Dynamic Contrast-Enhanced MRI Improves Prediction of Early Distant Metastases in Patients With Nasopharyngeal Carcinoma

    PubMed Central

    Chin, Shy-Chyi; Lin, Chien-Yu; Huang, Bing-Shen; Tsang, Ngan-Ming; Fan, Kang-Hsing; Ku, Yi-Kang; Hsu, Cheng-Lung; Chan, Sheng-Chieh; Huang, Shiang-Fu; Li, Cheng-He; Tseng, Hsiao-Jung; Liao, Chun-Ta; Liu, Ho-Ling; Sung, Kyunghyun

    2016-01-01

    Abstract The identification of early distant metastases (DM) in patients with newly diagnosed, previously untreated nasopharyngeal carcinoma (NPC) plays an important role in selecting the most appropriate treatment approach. Here, we sought to investigate the predictive value of distinct MRI parameters for the detection of early DM. Between November 2010 and June 2011, a total of 51 newly diagnosed NPC patients were included. All of the study participants were followed until December 2014 at a single institution after completion of therapy. DM was defined as early when they were detected on pretreatment FDG-PET scans or within 6 months after initial diagnosis. The following parameters were tested for their ability to predict early DM: pretreatment FDG-PET standardized uptake value (SUV), MRI-derived AJCC tumor staging, tumor volume, and dynamic contrast-enhanced (DCE) values. The DCE-derived ve was defined as the volume fraction of the extravascular, extracellular space. Compared with patients without early DM, patients with early DM had higher SUV, tumor volume, DCE mean (median) ve, ve skewness, ve kurtosis, and the largest mean ve selected among sequential slices (P < 0.05). No differences were identified when early DM were defined only according to the results of pretreatment FDG-PET. Among different quantitative DCE parameters, the mean ve had the highest area under curve (AUC, 0.765). However, the AUCs of SUV, tumor volume, mean ve, ve skewness, ve kurtosis, or the largest mean ve selected among the sequential slices did not differ significantly from one another (P = 0.82). Taken together, our results suggest that DCE-derived ve may be a useful parameter in combination with SUV and tumor volume for predicting early DM. Dynamic contrast-enhanced MRI may be complementary to FDG-PET for selecting the most appropriate treatment approach in NPC patients. PMID:26871776

  16. MiR-451 inhibits cell growth and invasion by targeting MIF and is associated with survival in nasopharyngeal carcinoma

    PubMed Central

    2013-01-01

    Background MiRNAs play important roles in diverse biological processes including tumorigenesis. However, little is known about the function and mechanism of miR-451 in nasopharyngeal carcinoma (NPC). Methods Quantitative RT-PCR was used to quantify miR-451 expression in NPC cell lines and clinical tissues. Kaplan-Meier curves were used to estimate the association between miR-451 expression and survival. The MTT, colony formation, Transwell migration and invasion assays, and a xenograft model were performed. A miR-451 target was confirmed using luciferase reporter assays, quantitative RT-PCR, and Western blotting. Results MiR-451 was significantly downregulated in NPC cell lines and clinical tissues (P < 0.01). Patients with low expression of miR-451 had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) than patients with high expression. MiR-451 was an independent prognostic factor in NPC in multivariate Cox regression analysis. Ectopic expression of miR-451 suppressed cell viability, colony formation, and cell migration and invasion in vitro, and inhibited xenograft tumor growth in vivo. MIF was verified as a direct target of miR-451, and MIF regulated NPC cell growth and invasion. Conclusions The newly identified miR-451/MIF pathway provides insight into NPC initiation and progression, and may represent a novel therapeutic target. PMID:24138931

  17. A Treatment Planning Analysis of Inverse-Planned and Forward-Planned Intensity-Modulated Radiation Therapy in Nasopharyngeal Carcinoma

    SciTech Connect

    Poon, Ian M Xia Ping; Weinberg, Vivien; Sultanem, Khalil; Akazawa, Clayton C.; Akazawa, Pamela C.; Verhey, Lynn; Quivey, Jeanne Marie; Lee, Nancy

    2007-12-01

    Purpose: To compare dose-volume histograms of target volumes and organs at risk in 57 patients with nasopharyngeal carcinoma (NPC) with inverse- (IP) or forward-planned (FP) intensity-modulated radiation treatment (IMRT). Methods and Materials: The DVHs of 57 patients with NPC with IMRT with or without chemotherapy were reviewed. Thirty-one patients underwent IP IMRT, and 26 patients underwent FP IMRT. Treatment goals were to prescribe a minimum dose of 66-70 Gy for gross tumor volume and 59.4 Gy for planning target volume to greater than 95% of the volume. Multiple selected end points were used to compare dose-volume histograms of the targets, including minimum, mean, and maximum doses; percentage of target volume receiving less than 90% (1-V90%), less than 95% (1-V95%), and greater than 105% (1-V105%). Dose-volume histograms of organs at risk were evaluated with characteristic end points. Results: Both planning methods provided excellent target coverage with no statistically significant differences found, although a trend was suggested in favor of improved target coverage with IP IMRT in patients with T3/T4 NPC (p = 0.10). Overall, IP IMRT statistically decreased the dose to the parotid gland, temporomandibular joint, brain stem, and spinal cord overall, whereas IP led to a dose decrease to the middle/inner ear in only the T1/T2 subgroup. Conclusions: Use of IP and FP IMRT can lead to good target coverage while maintaining critical structures within tolerance. The IP IMRT selectively spared these critical organs to a greater degree and should be considered the standard of treatment in patients with NPC, particularly those with T3/T4. The FP IMRT is an effective second option in centers with limited IP IMRT capacity. As a modification of conformal techniques, the human/departmental resources to incorporate FP-IMRT should be nominal.

  18. The Cumulative Cisplatin Dose Affects the Long-Term Survival Outcomes of Patients with Nasopharyngeal Carcinoma Receiving Concurrent Chemoradiotherapy

    PubMed Central

    Peng, Hao; Chen, Lei; Li, Wen-Fei; Guo, Rui; Mao, Yan-Ping; Zhang, Yuan; Zhang, Fan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    The prognostic value of the cumulative cisplatin dose (CCD) remains controversial for patients with nasopharyngeal carcinoma (NPC) receiving only concurrent chemoradiotherapy (CCRT). We retrospectively reviewed 549 consecutive patients with non-metastatic, histologically-proven NPC treated using intensity-modulated radiotherapy (IMRT) at Sun Yat-sen university cancer center. Patient survival between different CCD groups were compared. The cut-off value of pre-treatment plasma EBV DNA (pre-DNA) and CCD based on disease-free survival (DFS) were 1460 copies/ml (AUC, 0.691; sensitivity, 0.717; specificity, 0.635) and 240 mg/m2 (AUC, 0.506; sensitivity, 0.526; specificity, 0.538), respectively. Of the entire cohort, 92/549 (16.8%) patients received a CCD ≥ 240 mg/m2 and 457 (83.2%) patients, <240 mg/m2. For CCD ≥ 240 mg/m2 vs. < 240 mg/m2, the estimated 4-year DFS, overall survival (OS), locoregional-free survival (LRFFS) and distant metastasis-free survival (DMFS) rates were 89.1% vs. 81.3% (P = 0.097), 92.4% vs. 90.0% (P = 0.369), 95.6% vs. 91.2% (P = 0.156), and 91.3% vs. 88.4% (P = 0.375), respectively. For the whole cohort, multivariate analysis identified the CCD was an independent prognostic factor for DFS (HR, 0.515; 95% CI, 0.267–0.995; P = 0.048). However, CCD (≥240 mg/m2) had no prognostic value in subgroup analysis with stratification by the cut-off value of pre-DNA (P > 0.05 for all rates). PMID:27071833

  19. Cognitive Function Before and After Intensity-Modulated Radiation Therapy in Patients With Nasopharyngeal Carcinoma: A Prospective Study

    SciTech Connect

    Hsiao, Kuan-Yin; Yeh, Shyh-An; Chang, Chiung-Chih

    2010-07-01

    Purpose: To evaluate the effects of radiation therapy (RT) on neurocognitive function in patients with nasopharyngeal carcinoma (NPC). Methods and Materials: Thirty patients with NPC treated with intensity-modulated RT were included. Dose-volume histograms of the temporal lobes were obtained in every patient. Neurocognitive tests were administered individually to each patient 1 day before initiation of RT and at least 12 months after completion of RT. Cognitive functioning status was evaluated as change in scores over time. Results: Among the total of 30 patients, 23 patients (76.7%) had significantly lower post-RT cognitive functioning scores compared with their pre-RT scores (p = 0.033). The cognitive functioning scores had significantly declined in the domains of short-term memory, language abilities, and list-generating fluency (p = 0.020, 0.023, and 0.001, respectively). Compared with patients with a mean dose to the temporal lobes of 36 Gy or less, patients with a mean dose of greater than 36 Gy had a significantly greater reduction in cognitive functioning scores (p = 0.017). Patients in whom V60 of the temporal lobes (i.e., the percentage of the temporal lobe volume that had received >60 Gy) was greater than 10% also had a greater reduction in cognitive functioning scores than those in whom V60 was 10% or less (p = 0.039). Conclusions: The results of our study indicated that RT could have deleterious effects on cognitive function in patients with NPC. Efforts should be made to reduce the radiation dose and irradiated volume of temporal lobes without compromising the coverage of target volume.

  20. Intensity-modulated radiotherapy for nasopharyngeal carcinoma: Clinical correlation of dose to the pharyngo-esophageal axis and dysphagia

    SciTech Connect

    Fua, Tsien F. . E-mail: tsien-fei.fua@petermac.org; Corry, June; Milner, Alvin D.; Cramb, Jim; Walsham, Sue F.; Peters, Lester J.

    2007-03-15

    Purpose: The aim of this study was to quantify the dose delivered to the pharyngo-esophageal axis using different intensity-modulated radiation therapy (IMRT) techniques for treatment of nasopharyngeal carcinoma and to correlate this with acute swallowing toxicity. Methods and Materials: The study population consisted of 28 patients treated with IMRT between February 2002 and August 2005: 20 with whole field IMRT (WF-IMRT) and 8 with IMRT fields junctioned with an anterior neck field with central shielding (j-IMRT). Dose to the pharyngo-esophageal axis was measured using dose-volume histograms. Acute swallowing toxicity was assessed by review of dysphagia grade during treatment and enteral feeding requirements. Results: The mean pharyngo-esophageal dose was 55.2 Gy in the WF-IMRT group and 27.2 Gy in the j-IMRT group, p < 0.001. Ninety-five percent (19/20) of the WF-IMRT group developed Grade 3 dysphagia compared with 62.5% (5/8) of the j-IMRT group, p = 0.06. Feeding tube duration was a median of 38 days for the WF-IMRT group compared with 6 days for the j-IMRT group, p = 0.04. Conclusions: Clinical vigilance must be maintained when introducing new technology to ensure that unanticipated adverse effects do not result. Although newer planning systems can reduce the dose to the pharyngo-esophageal axis with WF-IMRT, the j-IMRT technique is preferred at least in patients with no gross disease in the lower neck.

  1. Risk stratification based on change in plasma Epstein-Barr virus DNA load after treatment in nasopharyngeal carcinoma

    PubMed Central

    Mao, Yan-Ping; Guo, Rui; Tang, Ling-Long; Peng, Hao; Sun, Ying; Liu, Qing; Chen, Lei; Ma, Jun

    2016-01-01

    Background: Nasopharyngeal carcinoma is associated with Epstein-Barr virus (EBV). The current study investigated change in the plasma EBV DNA load in the first 3 months after treatment and its clinical significance in NPC. Methods: A total of 273 patients with non-metastatic, histologically-proven NPC treated with radiotherapy or chemoradiotherapy were retrospectively reviewed. Results: EBV DNA was detectable in 19/273 (7.0%) patients at the end of therapy (end-DNA). Three months later, 16/273 (5.9%) patients had detectable EBV DNA (3-month-DNA). To investigate risk stratified by the pattern of change in post-treatment EBV-DNA, we divided patients into four subgroups: Group 1, undetectable end-DNA and 3-month-DNA (n = 244); Group 2, detectable end-DNA and undetectable 3-month-DNA (n = 13); Group 3, undetectable end-DNA and detectable 3-month-DNA (n = 7); and Group 4, detectable end-DNA and 3-month-DNA (n = 2). Patients with delayed remission of EBV DNA after treatment (Group 2) had significantly poorer 3-year DFS (48.6% vs. 89.7%, P < 0.001), DMFS (48.6% vs. 94.6%, P < 0.001) and OS (91.7% vs. 97.5%, P < 0.001) than those with persistently undetectable EBV DNA post-treatment (Group 1). Five of the seven patients with re-emergent EBV DNA (Group 3) and both patients with persistent EBV DNA post-treatment (Group 4) developed disease failure. Conclusion: Plasma EBV DNA load continues to change during the first 3 months after treatment. The pattern of change in EBV DNA load post-treatment could help identify patients with different prognoses. PMID:26840023

  2. Treatment of nasopharyngeal carcinoma using simultaneous modulated accelerated radiation therapy via helical tomotherapy: a phase II study

    PubMed Central

    Du, Lei; Zhang, Xin Xin; Feng, Lin Chun; Chen, Jing; Yang, Jun; Liu, Hai Xia; Xu, Shou Ping; Xie, Chuan Bin

    2016-01-01

    Abstract Background The aim of the study was to evaluate short-term safety and efficacy of simultaneous modulated accelerated radiation therapy (SMART) delivered via helical tomotherapy in patients with nasopharyngeal carcinoma (NPC). Methods Between August 2011 and September 2013, 132 newly diagnosed NPC patients were enrolled for a prospective phase II study. The prescription doses delivered to the gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), were 67.5 Gy (2.25 Gy/F), 60 Gy (2.0 Gy/F), and 54 Gy (1.8 Gy/F), in 30 fractions, respectively. Acute toxicities were evaluated according to the established RTOG/EORTC criteria. This group of patients was compared with the 190 patients in the retrospective P70 study, who were treated between September 2004 and August 2009 with helical tomotherapy, with a dose of 70-74 Gy/33F/6.5W delivered to pGTVnx and pGTVnd. Results The median follow-up was 23.7 (12–38) months. Acute radiation related side-effects were mainly problems graded as 1 or 2. Only a small number of patients suffered from grade 4 leucopenia (4.5%) or thrombocytopenia (2.3%). The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), local-nodal relapse-free survival (LNRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.7%, 95.5%, 92.2%, 92.7% and 93.2%, at 2 years, respectively, with no significant difference compared with the P70 study. Conclusions Smart delivered via the helical tomotherapy technique appears to be associated with an acceptable acute toxicity profile and favorable short-term outcomes for patients with NPC. Long-term toxicities and patient outcomes are under investigation. PMID:27247555

  3. Pharmacophore-based screening targeted at upregulated FN1, MMP-9, APP reveals therapeutic compounds for nasopharyngeal carcinoma.

    PubMed

    Lai, Catherine Jessica; Tay, Boon Hunt

    2016-02-01

    Nasopharyngeal carcinoma (NpC) is rare in the west but common in Southeast Asia and only a few other locations. With the limited geographic incidence, it is relatively under-studied. It also has as co-determinant the Epstein-Barr virus (EBV), which may adapt to NpC therapies, so not only must a therapeutic compound be found, the discovery process must be rapid, to cope with the changing basis of the EBV. An R-based computer workbench, Mendel, was developed so biologists could quickly upload genomic data, pre-process them, and identify upregulated and downregulated genes. Mendel was used on 10 control and 31 diseased cell lines to discover 3 differentially expressed genes (DEGs) that meet thresholds on fold-changes, 3-clique membership, pathway constraints, and druggability. From the DEGs, we conducted a pharmacophore-based screening of 22,723,923 compounds using protein-protein interaction anchor-residue clusters as binding sites. Of the 4 hits, 3 passed all the ADME-Tox tests. These 3 hit compounds, 6-(4-iminiocyclohexa-2,5-dien-1-ylidene)-4-(thiazol-2-ylcarbamoyl)-1H-pyrimidine-2-thiolate, 1-[4-[2-[(3R)-3-hydroxy-2-oxo-indolin-3-yl]acetyl]phenyl]-3-phenyl-urea, and (2R)-N4-[4-(1-piperidyl)cyclohexyl]morpholine-2,4-dicarboxamide have predicted pIC50 values superior to the current drugs fluorouracil (5-FU) and taxotere, which have side effects and face EBV drug resistance. PMID:26773938

  4. Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

    SciTech Connect

    Fogg, Mark; Murphy, John R.; Lorch, Jochen; Posner, Marshall; Wang, Fred

    2013-07-05

    Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients. - Highlights: • Viral proteins are tumor antigens in Epstein–Barr virus associated Nasopharyngeal Carcinoma. • CD8+ T cell responses against EBV proteins EBNA-1 and LMP2 are suppressed in NPC patients. • T regulatory cells are responsible for suppressing EBV immunity in NPC patients. • Depletion of Tregs with Ontak can rescue EBV-specific CD8+ T cell responses in NPC patients. • This clinically approved drug may be effective for enhancing anti-tumor immunity in NPC patients.

  5. Nasopharyngeal carcinoma with cranial nerve palsy: The importance of MRI for radiotherapy

    SciTech Connect

    Chang, Joseph T.-C.; Lin, C.-Y.; Chen, T.-M.; Kang, C.-J.; Ng, S.-H.; Chen, I.-H.; Wang, H.-M.; Cheng, A.-J.; Liao, C.-T. . E-mail: cgmhnog@yahoo.com

    2005-12-01

    Purpose: To evaluate various prognostic factors and the impact of imaging modalities on tumor control in patients with nasopharyngeal cancer (NPC) with cranial nerve (China) palsy. Material and Methods: Between September 1979 and December 2000, 330 NPC patients with CN palsy received radical radiotherapy (RT) by the conventional opposing technique at Chang Gung Memorial Hospital-Linkou. Imaging methods used varied over that period, and included conventional tomography (Tm) for 47 patients, computerized tomography (CT) for 195 patients, and magnetic resonance image (MRI) for 88 patients. Upper CN (II-VI) palsy was found in 268 patients, lower CN (IX-XII) in 13, and 49 patients had both. The most commonly involved CN were V or VI or both (23%, 12%, and 16%, respectively). All patients had good performance status (World Health Organization <2). The median external RT dose was 70.2 Gy (range, 63-77.5 Gy). Brachytherapy was also given to 156 patients in addition to external RT, delivered by the remote after-loading, high-dose-rate technique. A total of 139 patients received cisplatin-based chemotherapy, in 115 received as neoadjuvant or adjuvant chemotherapy and in 24 concomitant with RT. Recovery from CN palsy occurred in 171 patients during or after radiotherapy. Patients who died without a specific cause identified were regarded as having died with persistent disease. Results: The 3-year, 5-year, and 10-year overall survival was 47.1%, 34.4%, and 22.2%. The 3-year, 5-year, and 10-year disease-specific survival (DSS) rates were 50.4%, 37.8%, and 25.9%. The 5-year DSS for patients staged with MRI, CT, and Tm were 46.9%, 36.7%, and 21.9%, respectively (p = 0.016). The difference between MRI and CT was significant (p = 0.015). The 3-year and 5-year local control rates were 62% and 53%, respectively. The 5-year local control was 68.2% if excluding patients who died without a specific cause. Patients who had an MRI had a significantly better tumor control rate than those

  6. Meta-analysis of the differentially expressed microRNA profiles in nasopharyngeal carcinoma

    PubMed Central

    Luan, Junwen; Wang, Junfu; Su, Qinghong; Chen, Xuemei; Jiang, Guosheng; Xu, Xiaoqun

    2016-01-01

    MicroRNAs(miRNAs), as non-coding molecules, were proved to be correlated with gene expression in naspharyngeal carcinoma (NPC) development. In this research, a comprehensive meta-analysis of eight independent miRNA expression studies in NPC was preformed by using robust rank aggregation method (RRA), which contained a total of 775 tumor and 227 non-cancerous samples. There were 7 significant dysregulated miRNAs identified including three increased (miR-483–5p, miR-29c-3p and miR-205–5p) and four decreased (miR-29b-3p, let-7d-5p, miR-100– 5p and let-7g-5p) miRNAs. Subsequently, the miRNA target prediction and pathway enrichment analysis were carried out to find out the biological and functional relevant genes involved in the meta-signature miRNA regulation. Finally, several signaling and cancer pathogenesis pathways were suggested to be more frequently associated with the progression of NPC. In this research the meta-signature miRNA identified may be used to develop a series of diagnostic and prognostic biomarkers for NPC that serve specificity for use in clinics. PMID:26824418

  7. SPLUNC1 is associated with nasopharyngeal carcinoma prognosis and plays an important role in all-trans-retinoic acid-induced growth inhibition and differentiation in nasopharyngeal cancer cells.

    PubMed

    Zhang, Wenling; Zeng, Zhaoyang; Wei, Fang; Chen, Pan; Schmitt, David C; Fan, Songqing; Guo, Xiaofang; Liang, Fang; Shi, Lei; Liu, Zixin; Zhang, Zuping; Xiang, Bo; Zhou, Ming; Huang, Donghai; Tang, Ke; Li, Xiaoling; Xiong, Wei; Tan, Ming; Li, Guiyuan; Li, Xiayu

    2014-11-01

    Human SPLUNC1 can suppress nasopharyngeal carcinoma (NPC) tumor formation; however, the correlation between SPLUNC1expression and NPC patient prognosis has not been reported. In the present study, we used a large-scale sample of 1015 tissue cores to detect SPLUNC1 expression and its association with patient prognosis. SPLUNC1 expression was reduced in NPC samples compared to nontumor nasopharyngeal epithelium tissues. Positive expression of SPLUNC1 in NPC predicted a better prognosis (disease-free survival, P = 0.034; overall survival, P = 0.048). Cox's proportional hazards model revealed that SPLUNC1 could be a significant prognostic factor affecting disease-free survival (P = 0.027). A cDNA micro-array analyzed by significant analysis of micro-array (SAM) and ingenuity pathway analysis (IPA) revealed that an indirect interaction existed between SPLUNC1 and retinoic acid (RA) in the cancer regulatory network. To further investigate the molecular mechanisms involved, we utilized several bioinformatics tools and identified 12 retinoid X receptors heterodimer binding sites in the promoter region of the SPLUNC1 gene. The transcriptional activity of the SPLUNC1 promoter was up-regulated significantly by all-trans-retinoic acid (ATRA). SPLUNC1 and retinoic acid receptor expression were induced significantly by ATRA, and removal of ATRA led to a progressive loss of SPLUNC1 and retinoic acid receptor expression. ATRA inhibited proliferation and induced the differentiation of NPC cells. Interestingly, over-expression of SPLUNC1 sensitized NPC cells to ATRA, whereas knockdown of SPLUNC1 in HNE1 cells increased cell viability. Under SPLUNC1 knockdown conditions, differentiation was reversed by ATRA treatment. We concluded that SPLUNC1 could potentially predict prognosis for NPC patients and play an important role in ATRA-induced growth inhibition and differentiation in NPC cells. PMID:25161098

  8. Establishment of an integrated model incorporating standardised uptake value and N-classification for predicting metastasis in nasopharyngeal carcinoma

    PubMed Central

    Mao, Yan-Ping; Zhou, Guan-Qun; Peng, Hao; Sun, Ying; Liu, Qing; Chen, Lei; Ma, Jun

    2016-01-01

    Background Previous studies reported a correlation between the maximum standardised uptake value (SUVmax) obtained by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and distant metastasis in nasopharyngeal carcinoma (NPC). However, an integrated model incorporating SUVmax and anatomic staging for stratifying metastasis risk has not been reported. Results The median SUVmax for primary tumour (SUV-T) and cervical lymph nodes (SUV-N) was 13.6 (range, 2.2 to 39.3) and 8.4 (range, 2.6 to 40.9), respectively. SUV-T (HR, 3.396; 95% CI, 1.451-7.947; P = 0.005), SUV-N (HR, 2.688; 95%CI, 1.250-5.781; P = 0.011) and N-classification (HR, 2.570; 95%CI, 1.422-4.579; P = 0.001) were identified as independent predictors for DMFS from multivariate analysis. Three valid risk groups were derived by RPA: low risk (N0-1 + SUV-T <10.45), medium risk (N0-1 + SUV-T >10.45) and high risk (N2-3). The three risk groups contained 100 (22.3%), 226 (50.3%), and 123 (27.4%) patients, respectively, with corresponding 3-year DMFS rates of 99.0%, 91.5%, and 77.5% (P <0.001). Moreover, multivariate analysis confirmed the RPA-based prognostic grouping as the only significant prognostic indicator for DMFS (HR, 3.090; 95%CI, 1.975-4.835; P <0.001). Methods Data from 449 patients with with histologically-confirmed, stage I-IVB NPC treated with radiotherapy or chemoradiotherapy were retrospectively analysed. A prognostic model for distant metastasis-free survival (DMFS) was derived by recursive partitioning analysis (RPA) combining independent predictors identified by multivariate analysis. Conclusion SUV-T, SUV-N and N-classification were identified as independent predictors for DMFS. An integrated RPA-based prognostic model for DMFS incorporating SUV-N and N-classification was proposed. PMID:26871291

  9. Genomic Sequencing and Comparative Analysis of Epstein-Barr Virus Genome Isolated from Primary Nasopharyngeal Carcinoma Biopsy

    PubMed Central

    Kwok, Hin; Tong, Amy H. Y.; Lin, Chi Ho; Lok, Si; Farrell, Paul J.; Kwong, Dora L. W.; Chiang, Alan K. S.

    2012-01-01

    Whether certain Epstein-Barr virus (EBV) strains are associated with pathogenesis of nasopharyngeal carcinoma (NPC) is still an unresolved question. In the present study, EBV genome contained in a primary NPC tumor biopsy was amplified by Polymerase Chain Reaction (PCR), and sequenced using next-generation (Illumina) and conventional dideoxy-DNA sequencing. The EBV genome, designated HKNPC1 (Genbank accession number JQ009376) is a type 1 EBV of approximately 171.5 kb. The virus appears to be a uniform strain in line with accepted monoclonal nature of EBV in NPC but is heterogeneous at 172 nucleotide positions. Phylogenetic analysis with the four published EBV strains, B95-8, AG876, GD1, and GD2, indicated HKNPC1 was more closely related to the Chinese NPC patient-derived strains, GD1 and GD2. HKNPC1 contains 1,589 single nucleotide variations (SNVs) and 132 insertions or deletions (indels) in comparison to the reference EBV sequence (accession number NC007605). When compared to AG876, a strain derived from Ghanaian Burkitt's lymphoma, we found 322 SNVs, of which 76 were non-synonymous SNVs and were shared amongst the Chinese GD1, GD2 and HKNPC1 isolates. We observed 88 non-synonymous SNVs shared only by HKNPC1 and GD2, the only other NPC tumor-derived strain reported thus far. Non-synonymous SNVs were mainly found in the latent, tegument and glycoprotein genes. The same point mutations were found in glycoprotein (BLLF1 and BALF4) genes of GD1, GD2 and HKNPC1 strains and might affect cell type specific binding. Variations in LMP1 and EBNA3B epitopes and mutations in Cp (11404 C>T) and Qp (50134 G>C) found in GD1, GD2 and HKNPC1 could potentially affect CD8+ T cell recognition and latent gene expression pattern in NPC, respectively. In conclusion, we showed that whole genome sequencing of EBV in NPC may facilitate discovery of previously unknown variations of pathogenic significance. PMID:22590638

  10. Feasibility and efficacy of chemoradiotherapy for elderly patients with locoregionally advanced nasopharyngeal carcinoma: results from a matched cohort analysis

    PubMed Central

    2013-01-01

    Background To clarify the feasibility and efficacy of chemoradiotherapy (CRT) in elderly (age≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Methods From January 2000 to December 2006, 101 newly diagnosed elderly non-metastatic NPC patients (age≥65 years) who received cisplatin 3-weekly or weekly concurrent CRT with/without sequential chemotherapy were recruited. Each patient from the CRT group was matched to another patient treated with radiotherapy (RT) alone based on age, gender, pathological type, performance status, overall stage, stage method, Adult Comorbidity Evaluation-27 (ACE-27) score and RT technique, from the same institute and time period. We also recruited 101 young patients (age<65 years) as the referent group, which had been matched to the CRT group based on patient characteristics and treatment parameters. Treatment tolerability and toxicity were clarified, and treatment outcomes were calculated and compared among groups. Results CRT was feasible in elderly NPC patients, while a concurrent regimen of weekly cisplatin was more tolerable. Grade≥3 acute toxicity in CRT group was similar with referent group, although it was significantly higher than the RT alone group (65.3% vs. 43.6%, P=0.002). Furthermore, patients with ACE-27 score≥2 in the CRT group had significantly higher severe acute toxicity and dose reduction. Survival was poorer in elderly patients than the referent group. Compared to RT alone, CRT significantly improved the 5-year overall survival (OS: 54.6% vs. 39.3%, P=0.009), cancer-specific survival (CSS: 56.6% vs. 42.7%, P=0.022), disease-free survival (DFS: 51.6% vs. 30.2%, P=0.028) and locoregional relapse-free survival (LRRFS: 78.4% vs. 52.2%, P=0.003), but not distant metastasis-free survival (DMFS: 69.6% vs. 63.6%, P=0.669). However, CRT did not significantly improve 5-year OS (43.6% vs. 27.3%, P=0.893) or CSS (43.6% vs. 34.1%, P=0.971) in elderly NPC patients with ACE-27 score≥2

  11. Relationship between pretreatment level of plasma Epstein-Barr virus DNA, tumor burden, and metabolic activity in advanced nasopharyngeal carcinoma

    SciTech Connect

    Ma, Brigette; King, Ann; Lo, Y.M. Dennis; Yau, Y.Y.; Zee, Benny; Hui, Edwin P.; Leung, Sing F.; Mo, Frankie; Kam, Michael K.; Ahuja, Anil; Kwan, Wing H.; Chan, Anthony . E-mail: anthony@clo.cuhk.edu.hk

    2006-11-01

    Purpose: Plasma Epstein-Barr virus DNA (pEBV DNA) is an important prognostic marker in nasopharyngeal carcinoma (NPC). This study tested the hypotheses that pEBV DNA reflects tumor burden and metabolic activity by evaluating its relationship with tumor volume and {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) uptake in NPC. Methods and Materials: Pre-treatment pEBV DNA analysis, {sup 18}F-FDG positron emission tomography-computed tomography scan (PET-CT) and magnetic resonance imaging (MRI) of the head and neck were performed in 57 patients. Net volume (cm{sup 3}) of the primary tumor (T{sub vol}) and regional nodes (N{sub vol}) were quantified on MRI. {sup 18}F-FDG uptake was expressed as the maximum standardized uptake value (SUV{sub max}) at the primary tumor (T{sub suv}) and regional nodes (N{sub suv}). Lesions with SUV{sub max} {>=} 2.5 were considered malignant. Relationship between SUV{sub max}, natural logarithm (log) of pEBV DNA, and square root (sq) of MRI volumes was analyzed using the Wilcoxon test. A linear regression model was constructed to test for any interaction between variables and disease stage. Results: Log-pEBV DNA showed significant correlation with sq-T{sub vol} (r = 0.393), sq-N{sub vol} (r = 0.452), total tumor volume (sq-Total{sub vol} = T{sub vol} + N{sub vol}, r = 0.554), T{sub suv} (r = 0.276), N{sub suv} (r = 0.434), and total SUV{sub max} (Total{sub suv} = T{sub suv} + N{sub suv}, r = 0.457). Likewise, sq-T{sub vol} was correlated to T{sub suv} (r 0.426), and sq-N{sub vol} with N{sub suv} (r = 0.651). Regression analysis showed that only log-pEBV DNA was significantly associated with sq-Total{sub vol} (p < 0.001; parameter estimate = 8.844; 95% confidence interval = 3.986-13.703), whereas Sq-T{sub vol} was significantly associated with T{sub suv} (p = 0.002; parameter estimate = 3.923; 95% confidence interval = 1.498-6.348). Conclusion: This study supports the hypothesis that cell-free plasma EBV DNA is a marker of tumor burden in EBV

  12. A Comparison Between Electronic Portal Imaging Device and Cone Beam CT in Radiotherapy Verification of Nasopharyngeal Carcinoma

    SciTech Connect

    Wu, W.C. Vincent; Leung, Wan Shun; Kay, Shu San; Cheung, Hiu Ching; Wah, Yan Kit

    2011-04-01

    The demand of greater accuracy in intensity-modulated radiotherapy (IMRT) has driven the development of more advanced verification systems. The purpose of this study is to investigate the differences in verification accuracy in terms of the position error detected between cone-beam computed tomography (CBCT) and electronic portal imaging device (EPID) in the IMRT of nasopharyngeal carcinoma (NPC). Two groups of NPC patients (n = 22 and n = 28) verified by CBCT (G1-CB), EPID (G1-EP), and EPID (G2-EP) only, respectively, were recruited. The positional errors between the G1-CB group and the G2-EP group were compared. In addition, the magnitudes of the position errors of EPID taken in the same session of the CBCT, but after necessary corrections (G1-EP), were analyzed. In the CBCT group, 455 CBCT images (G1-CB) and 206 EPID images (G1-EP) were collected, whereas 319 EPID images (G2-EP) for the EPID group, were recorded. The median position errors detected in CBCT were between 0.80 and 0.90 mm in the antero-posterior (A-P), left-right (L-R), and supero-inferior (S-I) directions, whereas those of the EPID were all 0.50 mm. The magnitude of position deviation detected by the CBCT was higher than that of the EPID and their differences were extremely significant (p < 0.001). The frequencies in the G2-EP group with position errors greater than the tolerance (2 mm) were 32, 42, and 27 in the A-P, L-R, and S-I directions, respectively, which accounted for 16.5%, 21.6%, and 13.9% of the total number of EPID. There was difference in verification capability between the CBCT and EPID when applied to IMRT of NPC patients. Because an average of 1 of 6 verifications in EPID was inferior to that of the CBCT, verification by CBCT is recommended.

  13. MiRNA-125a-5p: a regulator and predictor of gefitinib’s effect on nasopharyngeal carcinoma

    PubMed Central

    2014-01-01

    Background Nasopharyngeal carcinoma (NPC) is a common malignancy in China and Southeast Asia. Radiotherapy is the major treatment modality for patients with NPC, but does not always achieve fully satisfactory outcomes. Studies have shown that epidermal growth factor receptor (EGFR) is highly expressed in NPC, and EGFR-targeted treatment is expected to be a new strategy for NPC. Recently, clinical trials have shown that NPC patients have different responses to gefitinib. Thus, the identification of indicators that can regulate and predict the sensitivity of NPC to gefitinib is very valuable. MiRNAs (MicroRNAs) are closely related to cancer development. We studied miRNAs in NPC cell lines to identify those that can regulate and predict the effectiveness of gefitinib on NPC. Methods CCK8, Annexin V-FITC assays and animal models were carried out to evaluate the inhibitory effect of gefitinib on NPC cell lines HNE-1 and HK-1. MiRNA microarrays were used to detect and compare the miRNAs expression levels in the two cells with gefitinib or not, and qRT-PCR was used to evaluate miR-125a-5p expression in NPC cells and in serum of the tumor animal models. Loss-of-function and gain-of-function experiments were taken to evaluate the effect of miR-125a-5p on gefitinib effectiveness. Western blots were used to evaluate the effect of miR-125a-5p on p53 and Her2 in HNE-1 and HK-1 cells. Results Gefitinib inhibited two NPC cell lines proliferation in vitro and in vivo,and HNE-1 cells were less sensitive than HK-1 cells to gefitinib.MiR-125a-5p expression levels were increased by geftinib in the two cell lines and in the serum of NPC tumor bearing-mice. This phenomenon was weak in HNE-1 cells and strong in HK-1 cells. MiR-125a-5p over expression improved anti-proliferative and pro-apoptotic effects of gefitinib on the NPC cells and that miR-125a-5p down-regulation decreased those effects. MiR-125a-5p also increased p53 protein expression in HNE-1 cells, and decreased Her2 protein

  14. Association of the p53 or GSTM1 polymorphism with the risk of nasopharyngeal carcinoma: A meta-analysis

    PubMed Central

    WU, MUYUN; HUANG, SHUJING; LIU, DONG; PENG, MIAO; YANG, FAN; WANG, XICHENG

    2016-01-01

    p53 and glutathione S-transferase M1 (GSTM1) are the most popular suppressor genes. Several previous studies demonstrated positive associations of these gene polymorphisms with numerous cancer types, including hepatocellular cancer, while the association between p53/GSTM1 polymorphisms and the nasopharyngeal carcinoma (NPC) risk was inconsistent and underpowered. However, no studies investigating the combinational effect of these two genes on NPC risk were performed. To confirm the effects of p53 and GSTM1 polymorphisms on the risk of NPC, a meta-analysis of all the available previous studies associating p53 and GSTM1 with the risk of NPC was performed. A comprehensive search of PubMed, Web of Science and SD database until November 2014 was performed to identify the relevant studies. The data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. Finally, five studies with 1,419 cases and 1,707 controls were included for the p53 polymorphism and three studies with 837 cases and 1,299 controls were included for the GSTM1 polymorphism. Regarding p53, a significantly increased NPC risk was observed in the overall population (C vs. G, OR, 1.245; 95% CI, 1.045–1.483; P=0.014; additive models: CC vs. GG, OR, 1.579; 95% CI, 1.100–2.265; P=0.013 and CG vs. GG, OR, 1.230; 95% CI, 1.039–1.456; P=0.016; dominant model, OR, 1.321; 95% CI, 1.127–1.549; P=0.001; recessive model, OR, 1.429; 95% CI, 1.017–2.009; P=0.040). Concerning GSTM1, a significantly increased NPC risk was observed in the overall population (null versus non-null, OR, 1.282; 95% CI, 1.075–1.530; P=0.006). In the subgroup analyses stratified by the source of controls, a significant association of p53 with NPC risk was also demonstrated, while no association with GSTM1 was observed. Therefore, the p53 G72C polymorphism may have a susceptible

  15. Overexpression of Transient Receptor Protein Cation Channel Subfamily A Member 1, Confers an Independent Prognostic Indicator in Nasopharyngeal Carcinoma

    PubMed Central

    Wu, You-Ting; Yen, Shao-Lun; Li, Chien-Feng; Chan, Ti-Chun; Chen, Tzu-Ju; Lee, Sung-Wei; He, Hong-Lin; Chang, I-Wei; Hsing, Chung-Hsi; Shiue, Yow-Ling

    2016-01-01

    Background: Detection of oncogenes provides chances to understand tumor development and progression. Transient receptor protein cation channel subfamily A, member 1 (TRPA1) transcript was significantly upregulated in nasopharyngeal carcinoma (NPC) with a stepwise upregulation from low- to high-stage NPCs from a preliminary data analysis in the Gene Expression Omnibus database. The TRPA1 gene is a member of the TRP channel family, encoding integral membrane proteins that functions as cation channels. Loss of calcium homeostasis takes place in cancer cells. Methods: Immunostaining of TRPA1 was analyzed on 124 biopsies from NPC patients retrospectively. The H-score method was used to evaluate the immunoexpression of TRPA1. The correlations between H-score of TRPA1 protein level and clinicopathological factors, as well as the significances of TRPA1 protein level for disease-specific, distal-metastasis-free and local recurrence-free survivals were assessed. Results: These patients were characterized to be no initial metastasis and medicated with the traditional procedure. The TRPA1 score was found to be associated with clinicopathological parameters and patient survivals. Along with the guideline of 7th edition of the American Joint Committee on Cancer, we found that TRPA1 upregulation (50%) was associated with advanced primary tumor (P = 0.009) and overall clinical stage (P = 0.019). In univariate log-rank testing, primary tumor, nodal status, stage and TRPA1 protein level significantly contributed to worse disease-specific survival, distal metastasis-free survival and local recurrence-free survival. In multivariate analysis, high TRPA1 protein level and tumor stage emerged as independent prognostic indicators for inferior disease-specific survival (P = 0.014; P = 0.003), distal metastasis-free survival (P = 0.004; P = 0.034) and recurrence-free survival (P = 0.017; P = 0.015). Conclusions: The upregulation of TRPA1 protein level is frequently correlated to unfavorable

  16. The effects of hemoglobin levels and their interactions with cigarette smoking on survival in nasopharyngeal carcinoma patients.

    PubMed

    Zeng, Qi; Shen, Lu-Jun; Li, Sheng; Chen, Ling; Guo, Xiang; Qian, Chao-Nan; Wu, Pei-Hong

    2016-05-01

    There is very little published information regarding the prognostic value of hemoglobin (Hb) levels combined with smoking on the survival of patients with nasopharyngeal carcinoma (NPC), and the interactions between them remain unclear. A total of 2440 NPC patients were confirmed, and multivariate analysis was performed to identify valuable prognostic Hb levels in the entire population and in the cohort of smokers. The survival differences were compared using log-rank tests. The multiplicative and additive interactions were assessed using Cox regression and a Microsoft Word Excel spreadsheet. Postradiotherapy (RT) Hb was an independent prognostic factor for overall survival (OS) (HR = 0.797; P = 0.006), failure-free survival (FFS) (HR=0.811; P = 0.010), and loco-regional failure-free survival (LR-FFS) (HR = 0.725; P = 0.000). In the cohort of smokers, pack-years was also an independent predictor of OS (HR = 0.673; P < 0.001) and FFS (HR = 0.681; P < 0.001), LR-FFS (HR = 0.663; P = 0.001). A significant positive additive effect was found for the interaction between low post-RT Hb and high SI on OS, with RERI = 5.616, AP = 0.665, and S = 4.078. Stratified analyses demonstrated that heavy smokers with low post-RT Hb had HRs of 2.295 (P < 0.001) for death, 2.222 (P < 0.001) for disease failure, and 2.267 (P < 0.001) loco-regional recurrence compared with light smokers with high post-RT Hb levels, and post-RT Hb level is an important predictor of survival in patients with NPC. The positive interaction between post-RT Hb level and pack-years contributes to the elevated risk of poor survival. Oncologists should devote particular attention to heavy smokers with low post-RT Hb levels in the future. PMID:26817420

  17. Minicircle-oriP-IFNγ: A Novel Targeted Gene Therapeutic System for EBV Positive Human Nasopharyngeal Carcinoma

    PubMed Central

    Xu, Zumin; Yang, Shiping; Yan, Haijiao; Tan, Li; Meng, Xiangqi; Ying, Xiaofang; Liu, Ranyi; Kang, Tiebang; Huang, Wenlin

    2011-01-01

    Background Nonviral vectors are attractively used for gene therapy owing to their distinctive advantages. Our previous study has demonstrated that transfer of human IFNγ gene into nasopharyngeal carcinoma (NPC) by using a novel nonviral vector, minicircle (mc), under the control of cytomegalovirus (CMV) promoter was effective to inhibit tumor growth. However, therapies based on CMV promoter cannot express the targeted genes in cancer tissues. Previous studies indicated that the development of human NPC was closely associated with Epstein-Barr virus (EBV) and demonstrated the transcriptional enhancer function of oriP when bound by EBV protein. Therefore, the present study is to explore the targeted gene expression and the anti-tumor effect of a novel tumor-specific gene therapeutic system (mc-oriP-IFNγ) in which the transgene expression was under the transcriptional regulation of oriP promoter. Methodology/Principal Findings Dual-luciferase reporter assay and ELISA were used to assess the expression of luciferase and IFNγ. WST assay was used to assess the cell proliferation. RT-PCR was used to detect the mRNA level of EBNA1. RNAi was used to knockdown the expression of EBNA1. NPC xenograft models in nude mice were used to investigate the targeted antitumor efficacy of mc-oriP-IFNγ. Immunohistochemistry was used to detect the expression and the activity of the IFNγ in tumor sections. Our results demonstrated that mc-oriP vectors mediated comparable gene expression and anti-proliferative effect in the EBV-positive NPC cell line C666-1 compared to mc-CMV vectors. Furthermore, mc-oriP vectors exhibited much lower killing effects on EBV-negative cell lines compared to mc-CMV vectors. The targeted expression of mc-oriP vectors was inhibited by EBNA1-siRNA in C666-1. This selective expression was corroborated in EBV-positive and -negative tumor models. Conclusions/Significance This study demonstrates the feasibility of mc-oriP-IFNγ as a safe and highly effective

  18. SU-E-T-16: A Hybrid VMAT/IMRT Technique for the Treatment of Nasopharyngeal Carcinoma

    SciTech Connect

    Zhao, N; Yang, R; Wang, J

    2014-06-01

    Purpose: To investigate a Hybrid VMAT/IMRT technique which combines volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC). Methods: 2 full arcs VMAT, 9-field IMRT and Hybrid VMAT/IMRT plans were created for 10 patients with NPC. The Hybrid VMAT/IMRT technique consisted of 1 full VMAT arc and 7 IMRT fields. The dose distribution of planning target volume (PTV) and organs at risk (OARs) for Hybrid VMAT/IMRT was compared with IMRT and VMAT. The monitor units (MUs) were also evaluated. Results: The Hybrid VMAT/IMRT technique significantly improved target dose homogeneity compared with IMRT and VMAT for PTV70 and PTV54. For PTV70 and PTV60, the Hybrid VMAT/IMRT technique significantly improved target dose conformity compared with IMRT (0.62 vs 0.47; p<0.05 and 0.64 vs 0.58; p<0.05, respectively) and VMAT (0.62 vs 0.43; p<0.05 and 0.64 vs 0.6; p<0.05, respectively). The near maximum dose (D2%) of temporomandibular joint (TMJ), temporal lobe and mandible for Hybrid plans were 5.5%, 7.9% and 5.2% lower than IMRT plans (p<0.05). The mean dose of TMJ, temporal lobe, mandible and unspecified tissue for Hybrid plans were 12.8%, 11.4%, 4.2% and 4.1% lower than IMRT plans (p<0.05). The mean dose of right parotid, mandible and unspecified tissue for Hybrid plans were 3.3%, 2.4% and 3.1% lower than VMAT plans (p<0.05). The mean MUs needed for IMRT, VMAT and Hybrid plans were 2256, 507 and 1394, respectively. Conclusion: Hybrid VMAT/IMRT technique significantly improved the target dose homogeneity and conformity compared with IMRT and VMAT and reduced the dose of OARs and unspecified tissue compared with IMRT with fewer MUs. Compared with VMAT, Hybrid VMAT/IMRT technique can better protect parotid gland, mandible and unspecified tissue. Ruijie Yang was funded by the grant project: National Natural Science Foundation of China (No. 81071237). Other authors have no competing interest for this work.

  19. Study of single nucleotide polymorphisms of tumour necrosis factors and HSP genes in nasopharyngeal carcinoma in North East India.

    PubMed

    Lakhanpal, Meena; Singh, Laishram Chandreshwor; Rahman, Tashnin; Sharma, Jagnnath; Singh, M Madhumangal; Kataki, Amal Chandra; Verma, Saurabh; Pandrangi, Santhi Latha; Singh, Y Mohan; Wajid, Saima; Kapur, Sujala; Saxena, Sunita

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is an epithelial tumour with a distinctive racial and geographical distribution. High incidence of NPC has been reported from China, Southeast Asia, and northeast (NE) region of India. The immune mechanism plays incredibly role in pathogenesis of NPC. Tumour necrosis factors (TNFs) and heat shock protein 70 (HSP 70) constitute significant components of innate as well as adaptive host immunity. Multi-analytical approaches including logistic regression (LR), classification and regression tree (CART) and multifactor dimensionality reduction (MDR) were applied in 120 NPC cases and 100 controls to explore high order interactions among TNF-α (-308 G>A), TNF β (+252 A>G), HSP 70-1 (+190 G>C), HSP 70-hom (+2437 T>C) genes and environmental risk factors. TNF β was identified as the primary etiological factor by all three analytical approaches. Individual analysis of results showed protective effect of TNF β GG genotype (adjusted odds ratio (OR2) = 0.27, 95 % CI = 0.125-0.611, P = 0.001), HSP 70 (+2437) CC genotype (OR2 = 0.17, 95 % CI = 0.0430.69, P = 0.013), while AG genotype of TNF β was found significantly associated with risk of NPC (OR2 = 1.97, 95 % CI = 1.019-3.83, P = 0.04). Analysis of environmental factors demonstrated association of alcohol consumption, living in mud houses and use of firewood for cooking as major risk factors for NPC. Individual haplotype association analysis showed significant risk associated with GTGA haplotype (OR = 68.61, 95 % CI = 2.47-190.37, P = 0.013) while a protective effect with CCAA and GCGA haplotypes (OR = 0.19, 95 % CI = 0.05-0.75, P = 0.019; OR = 0.01 95 % CI = 0.05-0.30, P = 0.007). The multi-analytical approaches applied in this study helped in identification of distinct gene-gene and gene-environment interactions significant in risk assessment of NPC. PMID:26198046

  20. In vivo fluence rate measurements during Foscan®-mediated photodynamic therapy of persistent and recurrent nasopharyngeal carcinomas using a dedicated light applicator

    NASA Astrophysics Data System (ADS)

    van Veen, R. L. P.; Nyst, H.; Indrasari, S. R.; Yudharto, M. A.; Robinson, D. J.; Tan, I. B.; Meewis, C.; Peters, R.; Spaniol, Stefan B.; Stewart, Fiona A.; Levendag, P. C.; Sterenborg, Henricus J. C. M.

    2006-07-01

    The objective of this study was to evaluate the performance of a dedicated light applicator for light delivery and fluence rate monitoring during Foscan®-mediated photodynamic therapy of nasopharyngeal carcinoma in a clinical phase I/II study. We have developed a flexible silicone applicator that can be inserted through the mouth and fixed in the nasopharyngeal cavity. Three isotropic fibers, for measuring of the fluence (rate) during therapy, were located within the nasopharyngeal tumor target area and one was manually positioned to monitor structures at risk in the shielded area. A flexible black silicon patch tailored to the patient's anatomy is attached to the applicator to shield the soft palate and oral cavity from the 652-nm laser light. Fourteen patients were included in the study, resulting in 26 fluence rate measurements in the risk volume (two failures). We observed a systematic reduction in fluence rate during therapy in 20 out of 26 illuminations, which may be related to photodynamic therapy-induced increased blood content, decreased oxygenation, or reduced scattering. Our findings demonstrate that the applicator was easily inserted into the nasopharynx. The average light distribution in the target area was reasonably uniform over the length of the applicator, thus giving an acceptably homogeneous illumination throughout the cavity. Shielding of the risk area was adequate. Large interpatient variations in fluence rate stress the need for in vivo dosimetry. This enables corrections to be made for differences in optical properties and geometry resulting in comparable amounts of light available for Foscan® absorption.

  1. Assessment of quality of life of nasopharyngeal carcinoma patients with EORTC QLQ-C30 and H and N-35 modules

    SciTech Connect

    Cengiz, Mustafa . E-mail: mcengiz@hacettepe.edu.tr; Ozyar, Enis; Esassolak, Mustafa; Altun, M.; Akmansu, Muege; Sen, Mehmet; Uzel, Omer; Yavuz, Aydin; Dalmaz, Gamze; Uzal, Cem; Hicsoenmez, Ayse; Sarihan, Suereyya; Kaplan, Buenyamin; Atasoy, Beste Melek; Ulutin, Cueneyt; Abacioglu, Ufuk; Demiral, Ayse Nur; Hayran, Mutlu

    2005-12-01

    Purpose: The current study reports on long-term quality of life (QoL) status after conventional radiotherapy in 187 nasopharyngeal carcinoma patients from 14 centers in Turkey. Patients and Methods: Patients with the diagnosis of nasopharyngeal carcinoma, who were treated in 14 centers in Turkey with minimum 6 months of follow-up and were in complete remission, were asked to complete Turkish versions of EORTC QLQ-C30 questionnaire and the HN-35 module. Each center participated with the required clinical data that included age at diagnosis, gender, symptoms on admission, follow-up period, treatment modalities, radiotherapy dose, and AJCC 1997 tumor stage. Each patient's 33 QoL scores, which included function, global health status, and symptoms, were calculated as instructed in EORTC QLQ-C30 scoring manual. All of the scales and single-item measures range from 0 to 100. A high score represents a higher response level. Kruskal-Wallis and Mann-Whitney U nonparametric tests were used for comparisons. Results: One hundred eighty-seven patients with median age of 46 years (range, 16-79 years) participated and completed the questionnaires. Median follow-up time was 3.4 years (range, 6 months-24 years). All patients have received external-beam radiotherapy. Beside external-beam radiotherapy, 59 patients underwent brachytherapy boost, 70 patients received concomitant chemotherapy, and 95 patients received adjuvant/neoadjuvant chemotherapy. Most of the patients in the analysis (75%) were in advanced stage (Stage III, n = 85 [45.4%]; Stage IV, n = 55 [29%]). Mean global health status was calculated as 73. Parameters that increased global health status were male gender, early-stage disease, and less than 4-year follow-up (p < 0.05). Functional parameters were better in males and in early-stage disease. Factors that yielded better symptom scores were short interval after treatment (10 scores), male gender (7 scores), and lower radiation dose (6 scores). Neoadjuvant or adjuvant

  2. Limb-bud and Heart (LBH) functions as a tumor suppressor of nasopharyngeal carcinoma by inducing G1/S cell cycle arrest.

    PubMed

    Liu, Qicai; Guan, Xiaoying; Lv, Jingli; Li, Xiaoyan; Wang, Yingfeng; Li, Li

    2015-01-01

    Epstein-Barr virus-encoded latent membrane protein-1 (LMP1) plays a fundamental role in the malignant transformation of nasopharyngeal carcinoma (NPC), although the mechanism is not well understood. Here, we showed that Limb-bud and Heart (LBH) is considerably downregulated in patient NPC tissues. The expression of LBH in biopsies of 40 consecutive NPC patients devoid of initial distant metastasis and treated according to consistent guidelines was also analyzed, and we found the LBH expression level was correlated with some of clinicopathological features, disease-specific survival (DSS), distant metastasis-free survival (DMFS). We further determined that LBH normally induces NPC cell cycle arrest at the G1/S transition, and LBH can suppress the growth of transplanted NPC tumors in vivo by downregulating LMP1-mediated NF-κB transcriptional activity. Transforming growth factor-beta 1 (TGF-β1) normally protects against tumor development by suppressing cell proliferation, but NPC cells acquire resistance to TGF-β1-mediated inhibition. We found that TGF-β1 inhibits NF-κB transcriptional activity and nasopharyngeal epithelial cell proliferation through upregulating LBH expression. These data reveal a previously unknown NPC transformation mechanism and provide a new concept and treatment strategy for LMP1-driven oncogenesis in NPC. PMID:25557837

  3. Upregulated long non-coding RNA AFAP1-AS1 expression is associated with progression and poor prognosis of nasopharyngeal carcinoma

    PubMed Central

    Bo, Hao; Gong, Zhaojian; Zhang, Wenling; Li, Xiayu; Zeng, Yong; Liao, Qianjin; Chen, Pan; Shi, Lei; Lian, Yu; Jing, Yizhou; Tang, Ke; Li, Zheng; Zhou, Yanhong; Zhou, Ming; Xiang, Bo; Li, Xiaoling; Yang, Jianbo; Xiong, Wei; Li, Guiyuan; Zeng, Zhaoyang

    2015-01-01

    Altered expression of long noncoding RNAs (lncRNAs) associated with human carcinogenesis. We performed a cDNA microarray analysis of lncRNA expression in 12 cases of nasopharyngeal carcinoma (NPC) and 4 non-tumor nasopharyngeal epitheliums. One lncRNA, actin filament associated protein 1 antisense RNA1 (AFAP1-AS1), was identified and selected for further study. AFAP1-AS1 expression was upregulated in NPC and associated with NPC metastasis and poor prognosis. In vitro experiments demonstrated that AFAP1-AS1 knockdown significantly inhibited the NPC cell migration and invasive capability. AFAP1-AS1 knockdown also increased AFAP1 protein expression. Proteomic and bioinformatics analyses suggested that AFAP1-AS1 affected the expression of several small GTPase family members and molecules in the actin cytokeratin signaling pathway. AFAP1-AS1 promoted cancer cell metastasis via regulation of actin filament integrity. AFAP1-AS1 might be a potential novel marker that can predict cancer patient prognosis and as a potential therapeutic target for NPC. PMID:26246469

  4. Endoscope-Guided Interstitial Intensity-Modulated Brachytherapy and Intracavitary Brachytherapy as Boost Radiation for Primary Early T Stage Nasopharyngeal Carcinoma

    PubMed Central

    Qi, Zhen-Yu; Li, Ai-Ju; Ye, Wei-Jun; Hua, Yi-Jun; Zhu, Yu-Liang; Zou, Xiong; Guo, Ling; Mai, Hai-Qiang; Guo, Xiang; Hong, Ming-Huang; Chen, Ming-Yuan

    2014-01-01

    Background Intracavitary brachytherapy (ICBT) is usually applied as boost radiotherapy for superficial residual of nasopharyngeal carcinoma (NPC) after primary extern-beam radiptherapy (ERT). Here, we evaluated the outcome of endoscope-guided interstitial intensity-modulated brachytherapy (IMBT) boost radiation for deep-seated residual NPC. Methodology/Principal Findings Two hundred and thirteen patients with residual NPC who were salvaged with brachytherapy boost radiation during 2005–2009 were analyzed retrospectively. Among these patients, 171 patients had superficial residual NPC (≤1 cm below the nasopharyngeal epithelium) were treated with ICBT boost radiation, and interstitial IMBT boost radiation was delivered to 42 patients with deep-seated residual NPC (>1 cm below the nasopharyngeal epithelium). We found that IMBT boost subgroup had a higher ratio of T2b (81.0% VS 34.5%, P<0.001) and stage II (90.5% VS 61.4%, P = 0.001) than that of ICBT boost subgroup. The dosage of external-beam radiotherapy in the nasopharyngeal (63.0±3.8 VS 62.6±4.3 Gray (Gy), P = 0.67) and regional lymph nodes (55.8±5.0 VS 57.5±5.7 Gy, P = 0.11) was comparable in both groups. For brachytherapy, IMBT subgroup had a lower boost radiation dosage than ICBT subgroup (11.0±2.9 VS 14.8±3.2 Gy, P<0.01). Though the IMBT group had deeper residual tumors and received lower boost radiation dosages, both subgroups had the similar 5-year actuarial overall survival rate (IMBT VS ICBT group: 96.8% VS 93.6%, P = 0.87), progression-free survival rate (92.4% VS 86.5%, P = 0.41) and distant metastasis-free survival rate (94.9% VS 92.7%, P = 0.64). Moreover, IMBT boost radiation subgroup had a similar local (97.4% VS 94.4%, P = 0.57) and regional (95.0% VS 97.2%, P = 0.34) control to ICBT subgroup. The acute and late toxicities rates were comparable between the both subgroups. Conclusions/Significance IMBT boost radiation may be a promising therapeutic selection

  5. Re-Evaluation of 6th Edition of AJCC Staging System for Nasopharyngeal Carcinoma and Proposed Improvement Based on Magnetic Resonance Imaging

    SciTech Connect

    Mao Yanping; Xie Fangyun; Liu Lizhi; Sun Ying; Li Li; Tang Linglong; Liao Xinbiao; Xu Hongyao; Chen Lei; Lai Shuzhen; Lin Aihua; Liu Mengzhong; Ma Jun

    2009-04-01

    Purpose: To use magnetic resonance imaging to re-evaluate and improve the 6th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma. Methods and Materials: We performed a retrospective review of the data from 924 biopsy-proven nonmetastatic nasopharyngeal carcinoma cases. All patients had undergone magnetic resonance imaging examinations and received radiotherapy as their primary treatment. Results: The T classification, N classification, and stage group were independent predictors. No significant differences in the local failure hazards between adjacent T categories were observed between Stage T2b and T1, Stage T2b and T2a, and Stage T2b and T3. Although the disease failure hazards for Stage T1 were similar to those for Stage T2a, those for Stage T2b were similar to those for Stage T3. Survival curves of the different T/N subsets showed a better segregation when Stage T2a was downstaged to T1, T2b and T3 were incorporated into T2, and the nodal greatest dimension was rejected. The disease failure hazard for T3N0-N1 subsets were similar to those of the T1-T2N1 subsets belonging to Stage II; the same result was found for the T4N0-N2 subsets in the sixth American Joint Committee on Cancer staging system. However, the staging system we propose shows more consistent hazards within the same stage group and better survival discrimination among T categories, N categories, and overall stages. Conclusion: Using the 6th American Joint Committee on Cancer staging system produces an acceptable distribution of patient numbers and segregation of survival curves among the different stage groups. The prognostic accuracy of the staging system could be improved by recategorizing the T, N, and group stage criteria.

  6. Evaluation of Body Mass Index and Survival of Nasopharyngeal Carcinoma by Propensity-Matched Analysis: An Observational Case-Control Study.

    PubMed

    OuYang, Pu-Yun; Zhang, Lu-Ning; Tang, Jie; Lan, Xiao-Wen; Xiao, Yao; Gao, Yuan-Hong; Ma, Jun; Xie, Fang-Yun

    2016-01-01

    The effect of pretreatment body mass index on survival of nasopharyngeal carcinoma remains contradictory.All patients (N = 1778) underwent intensity-modulated radiotherapy with or without chemotherapy. Body mass index was categorized as underweight (<18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (22.9-27.5 kg/m2), and obesity (≥27.5 kg/m2). Propensity score matching method was used to identify patients with balanced characteristics and treatment regimen. Disease-specific survival (DSS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival were estimated by Kaplan-Meier method and Cox regression.Following propensity matching, 115 (underweight vs normal), 399 (overweight vs normal), and 93 (obese vs normal) pairs of patients were selected, respectively. In univariate analysis, underweight patients had inferior DSS/OS (P = 0.042) and DMFS (P = 0.025) while both overweight and obese patients showed similar survival across all the endpoints (P ≥ 0.098) to those with normal weight. In multivariate analysis, underweight remained predictive of poor DSS/OS (P = 0.044) and DMFS (P = 0.040), whereas overweight (P ≥ 0.124) or obesity (P ≥ 0.179) was not associated with any type of survival.Underweight increased the risk of death and distant metastasis, whereas overweight or obese did not affect the survival of nasopharyngeal carcinoma. This provides support for early nutritional intervention during the long waiting time before treatment. PMID:26765414

  7. Variability of Gross Tumor Volume in Nasopharyngeal Carcinoma Using 11C-Choline and 18F-FDG PET/CT.

    PubMed

    Jiang, Jun; Wu, Hubing; Huang, Meiyan; Wu, Yao; Wang, Quanshi; Zhao, Jianqi; Yang, Wei; Chen, Wufan; Feng, Qianjin

    2015-01-01

    This study was conducted to evaluate the variability of gross tumor volume (GTV) using 11C-Choline and 18F-FDG PET/CT images for nasopharyngeal carcinomas boundary definition. Assessment consisted of inter-observer and inter-modality variation analysis. Four radiation oncologists were invited to manually contour GTV by using PET/CT fusion obtained from a cohort of 12 patients with nasopharyngeal carcinoma (NPC) and who underwent both 11C-Choline and 18F-FDG scans. Student's paired-sample t-test was performed for analyzing inter-observer and inter-modality variability. Semi-automatic segmentation methods, including thresholding and region growing, were also validated against the manual contouring of the two types of PET images. We observed no significant variation in the results obtained by different oncologists in terms of the same type of PET/CT volumes. Choline fusion volumes were significantly larger than the FDG volumes (p < 0.0001, mean ± SD = 18.21 ± 8.19). While significantly consistent results were obtained between the oncologists and the standard references in Choline volumes compared with those in FDG volumes (p = 0.0025). Simple semi-automatic delineation methods indicated that 11C-Choline PET images could provide better results than FDG volumes (p = 0.076, CI = [-0.29, 0.025]). 11C-Choline PET/CT may be more advantageous in GTV delineation for the radiotherapy of NPC than 18F-FDG. Phantom simulations and clinical trials should be conducted to prove the possible improvement of the treatment outcome. PMID:26161910

  8. A comparison of anatomical and dosimetric variations in the first 15 fractions, and between fractions 16 and 25, of intensity-modulated radiotherapy for nasopharyngeal carcinoma.

    PubMed

    Yang, Haihua; Tu, Yu; Wang, Wei; Hu, Wei; Ding, Weijun; Yu, Changhui; Zhou, Chao

    2013-01-01

    The purpose of this study was to compare anatomical and dosimetric variations in first 15 fractions, and between fractions 16 and 25, during intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Twenty-three NPC patients who received IMRT in 33 fractions were enrolled. Each patient had two repeat computed tomography (CT) scans before the 16th and 25th fraction. Hybrid IMRT plans were generated to evaluate the dosimetric changes. There was a significant decrease of the transverse diameter of nasopharyngeal and neck as well as gross tumor volume (GTV) in the primary nasopharyngeal carcinoma (GTVnx) and involved lymph nodes (GTVnd) during the first 15 fractions, and between fraction 16 and 25 (p < 0.05). Consequently, there was a significant reduction of the percentage of the volume receiving the prescribed dose (V100) of CTV1 and GTVnd, which was more prominent after the first 15 fractions treatment compared to that between fraction 16 and 25 (p < 0.05). Additionally, there was a significant increase in the mean dose (Dmean) and percentage of volume receiving ≥ 30 Gy (V30) to the bilateral parotid in the first 15 fractions (p < 0.05), but not between fraction 16 and 25. While the maximum dose to the spinal cord was significantly increased both in the first 15 fractions, and between fraction 16 and 25 (p < 0.05), the increase of the percent of spinal cord volume receiving ≥ 40 Gy (V40) was significantly higher in the first 15 fractions compared to that between fraction 16 and 25 (p < 0.05). Based on the dose constraint criterion in the RTOG0225 protocol, a total 39.1% (9/23) of phantom plan 1 (generated by applying the beam configurations of the original IMRT treatment plan to the anatomy of the second CT scan) and 17.4% (4/23) of phantom 2 (generated by applying the beam configurations of the replan 1 to the anatomy of the third CT scan) were out of limit for the dose to the normal critical structures. In conclusion, our data indicated that

  9. Phase I/II Trial Evaluating Carbon Ion Radiotherapy for Salvaging Treatment of Locally Recurrent Nasopharyngeal Carcinoma

    PubMed Central

    Kong, Lin; Hu, Jiyi; Guan, Xiyin; Gao, Jing; Lu, Rong; Lu, Jiade J.

    2016-01-01

    Background: Radiation therapy is the mainstay strategy for the treatment of nasopharyngeal cancer (NPC). Intensity-modulated X-ray therapy (IMXT) alone is the current standard for stage I and II NPC. For stage III and IV A/B diseases, concurrent chemotherapy should be provided in addition to IMXT. However, optimal treatment for locally recurrent NPC after previous definitive dose of radiotherapy is lacking. Various techniques including brachytherapy, IMXT, stereotactic radiosurgery or radiotherapy (SRS or SBRT) have been used in the management of locally recurrent NPC. Due to the inherent limitation of these techniques, i.e., limited range of irradiation or over-irradiation to surrounding normal tissues, moderate efficacy has been observed at the cost of severe toxicities. Carbon ion radiotherapy (CIRT) offers potential physical and biological advantages over photon and proton radiotherapy. Due to the inverted dose profile of particle beams and their greater energy deposition within the Bragg peak, precise dose delivery to the target volume(s) without exposing the surrounding organs at risk to extra doses is possible. In addition, CIRT provides an increased relative biological effectiveness (RBE) as compared to photon and proton radiotherapy. Such advantages may translate to improved outcomes after irradiation in terms of disease control in radio-resistant and previously treated, recurrent malignancies. It is therefore reasonable to postulate that recurrent NPC after high-dose radiotherapy could be more resistant to re-irradiation using photons. Reports on the treatment of radio-resistant malignancies in the head and neck region such as melanoma, sarcoma, and adenoid cystic carcinoma (ACC) have demonstrated superior local control rates from CIRT as compared to photon irradiation. Thus patients with recurrent NPC are likely to benefit from the enhanced biological effectiveness of carbon ions. As effective retreatment strategy is lacking for locally recurrent NPC

  10. Image-based Multilevel Subdivision of M1 Category in TNM Staging System for Metastatic Nasopharyngeal Carcinoma.

    PubMed

    Shen, Lujun; Li, Wang; Wang, Siyang; Xie, Guofeng; Zeng, Qi; Chen, Chen; Shi, Feng; Zhang, Ying; Wu, Ming; Shu, Wanhong; Pan, Changchuan; Xia, Yunfei; Wu, Peihong

    2016-09-01

    Purpose To establish an image-based M1 category subdivision system for personalized prognosis prediction and treatment planning in patients with metastatic nasopharyngeal carcinoma (NPC). Materials and Methods A total of 1172 patients with metachronous metastasic NPC were retrospectively enrolled (the dataset is from Sun Yat-sen University Cancer Center for derivation, and the combined datasets are from Guangzhou Medical University Cancer Center and the Fifth Affiliated Hospital of Sun Yat-sen University for validation). The Ethics Committee of the three centers approved this study. A general subdivision system of the M1 category was established on the basis of the most influential metastatic features for overall survival (OS). The following multilevel subdivision system for precise subdivision of the M1 category was designed: M [number of locations]-Location [number of lesions], with B indicating bone, L indicating the lung, H indicating the liver, and N indicating a node. The correlation of the M1 subdivisions with OS was determined with Cox regression. The best treatment response was assessed with Response Evaluation Criteria in Solid Tumors 1.1 guidelines and modified Response Evaluation Criteria in Solid Tumors criteria. Results Multivariate analysis in the derivation cohort showed that the number of metastatic lesions (multiple or single), the number of metastatic locations (multiple or single), liver involvement, and bone involvement were independent prognostic factors for OS. In general, subdividing the cohort by the number of metastatic lesions and the number of metastatic locations resulted in three subcategories of differential OS: M1a, a single lesion in a single organ or location; M1b, multiple lesions in a single organ or location; and M1c, metastases in multiple locations (for M1b vs M1a, hazard ratio [HR] = 2.28, 95% confidence interval [CI]: 1.71, 3.05; for M1c vs M1a, HR = 3.65, 95% CI: 2.75, 4.85); these subdivisions were externally validated

  11. Nanoformulation of D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) diblock copolymer for siRNA targeting HIF-1α for nasopharyngeal carcinoma therapy

    PubMed Central

    Chen, Yuhan; Xu, Gang; Zheng, Yi; Yan, Maosheng; Li, Zihuang; Zhou, Yayan; Mei, Lin; Li, Xianming

    2015-01-01

    Hypoxia-inducible factor-1α (HIF-1α) is a crucial transcription factor that plays an important role in the carcinogenesis and development of nasopharyngeal carcinoma. In this research, a novel biodegradable D-α-tocopheryl polyethylene glycol 1000 succinate-b-poly(ε-caprolactone-ran-glycolide) (TPGS-b-(PCL-ran-PGA)) nanoparticle (NP) was prepared as a delivery system for small interfering ribonucleic acid (siRNA) molecules targeting HIF-1α in nasopharyngeal carcinoma gene therapy. The results showed that the NPs could efficiently deliver siRNA into CNE-2 cells. CNE-2 cells treated with the HIF-1α siRNA-loaded TPGS-b-(PCL-ran-PGA) NPs showed reduction of HIF-1α expression after 48 hours of incubation via real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. The cytotoxic effect on CNE-2 cells was significantly increased by HIF-1α siRNA-loaded NPs when compared with control groups. In a mouse tumor xenograft model, the HIF-1α siRNA-loaded NPs efficiently suppressed tumor growth, and the levels of HIF-1α mRNA and protein were significantly decreased. These results suggest that TPGS-b-(PCL-ran-PGA) NPs could function as a promising genetic material carrier in antitumor therapy, including therapy for nasopharyngeal carcinoma. PMID:25733830

  12. Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8.

    PubMed

    Jiang, Y; Yan, B; Lai, W; Shi, Y; Xiao, D; Jia, J; Liu, S; Li, H; Lu, J; Li, Z; Chen, L; Chen, X; Sun, L; Muegge, K; Cao, Y; Tao, Y

    2015-12-10

    Epstein-Barr virus (EBV) causes human lymphoid malignancies, and the EBV product latent membrane protein 1 (LMP1) has been identified as an oncogene in epithelial carcinomas such as nasopharyngeal carcinoma (NPC). EBV can epigenetically reprogram lymphocyte-specific processes and induce cell immortalization. However, the interplay between LMP1 and the NPC host cell remains largely unknown. Here, we report that LMP1 is important to establish the Hox gene expression signature in NPC cell lines and tumor biopsies. LMP1 induces repression of several Hox genes in part via stalling of RNA polymerase II (RNA Pol II). Pol II stalling can be overcome by irradiation involving the epigenetic regulator TET3. Furthermore, we report that HoxC8, one of the genes silenced by LMP1, has a role in tumor growth. Ectopic expression of HoxC8 inhibits NPC cell growth in vitro and in vivo, modulates glycolysis and regulates the expression of tricarboxylic acid (TCA) cycle-related genes. We propose that viral latency products may repress via stalling key mediators that in turn modulate glycolysis. PMID:25745994

  13. Repression of Hox genes by LMP1 in nasopharyngeal carcinoma and modulation of glycolytic pathway genes by HoxC8

    PubMed Central

    Jiang, Yiqun; Yan, Bin; Lai, Weiwei; Shi, Ying; Xiao, Desheng; Jia, Jiantao; Liu, Shuang; Li, Hongde; Lu, Jinchen; Li, Zhi; Chen, Ling; Chen, Xue; Sun, Lunqun; Muegge, Kathrin; Cao, Ya; Tao, Yongguang

    2015-01-01

    Epstein-Barr virus (EBV) causes human lymphoid malignancies, and the EBV product latent membrane protein 1 (LMP1) has been identified as an oncogene in epithelial carcinomas such as nasopharyngeal carcinoma (NPC). EBV can epigenetically reprogram lymphocyte specific processes and induce cell immortalization. However, the interplay between LMP1 and the NPC host cell remains largely unknown. Here, we report that LMP1 is important to establish the Hox gene expression signature in NPC cell lines and tumor biopsies. LMP1 induces repression of several Hox genes in part via stalling of RNA Pol II. Pol II stalling can be overcome by irradiation involving the epigenetic regulator TET3. Furthermore, we report that HoxC8, one of the genes silenced by LMP1, plays a role in tumor growth. Ectopic expression of HoxC8 inhibits NPC cell growth in vitro and in vivo, modulates glycolysis and regulates the expression of TCA-cycle related genes. We propose that viral latency products may repress via stalling key mediators that in turn modulate glycolysis. PMID:25745994

  14. Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma.

    PubMed

    Zheng, Jun; Li, Jiao; Xu, Lina; Xie, Guiyuan; Wen, Qiuyuan; Luo, Jiadi; Li, Duo; Huang, Donghai; Fan, Songqing

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor rare throughout most of the world but common in Southeast Asia, especially in Southern China. The phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 promotes cellular proliferation, survival, malignant transformation and metastasis. However, whether the alterations of the expression of p-eIF4E and p-Mnk1 protein are associated with clinicopathologic/prognostic implication for NPC has not been reported. The purposes of the present study are to examine the expression of p-eIF4E and p-Mnk1 protein in NPC and non-cancerous nasopharyngeal epithelial tissues by immunohistochemistry and evaluate the association between the expression of p-eIF4E and p-Mnk1 protein and clinicopathological characteristics of NPC. The results showed that the positive percentage of p-Mnk1 and p-eIF4E proteins expression in NPC (83.5% and 75.4%, respectively) was significantly higher than that in non-cancerous nasopharyngeal epithelium (40.0% and 32.9%, respectively). The positive expression of p-eIF4E and p-Mnk1 in the NPC with cervical lymph node metastasis was significantly higher than those without lymph node metastasis. Additionally, p-eIF4E expression was more pronouncedly increased in metastatic NPC than the matched primary NPC. Increase of p-eIF4E and p-Mnk1 expression was significantly correlated inversely with overall survival. Spearman's rank correlation test further showed that expression of p-Mnk1 was strongly positive correlated with expression of p-eIF4E in NPC. The expression of p-Mnk1 and p-eIF4E in NPC was proved to be the independent prognostic factors regardless of lymph node metastasis, clinical stages and combination of radiotherapy and chemotherapy, histological type, age and gender by multivariate analysis. Taken together, high expression of p-Mnk1 and p-eIF4E might be novel valuable biomarkers to predict poor prognosis of NPC and

  15. MiR-744 functions as a proto-oncogene in nasopharyngeal carcinoma progression and metastasis via transcriptional control of ARHGAP5.

    PubMed

    Fang, Yuan; Zhu, Xiaoxia; Wang, Jian; Li, Na; Li, Dianhe; Sakib, Nazmus; Sha, Zhou; Song, Wen

    2015-05-30

    Nasopharyngeal carcinoma (NPC) is a highly invasive and metastasis-prone epithelial cancer. The paucity of effective treatment strategies for recurrent and metastatic NPC is the major cause for stagnating survival rate of NPC. Therefore, it's urgent to understand the molecular mechanisms underlying NPC progression and identify novel avenues for targeted therapy. It has emerged recently that microRNAs are potential pro-tumorigenic or tumor-suppressive factors that participate in oncogenesis. In this study, we found that miR-744 expression was upregulated in NPC specimens compared to nasopharyngeal epithelium (NPE) tissue, and miR- 744 upregulation was significantly associated with TNM stage, tumorigenesis and metastasis. Functional studies revealed that miR-744 acts as a novel tumor promotor in NPC. Moreover, we determined that miR-744 targets ARHGAP5 (Rho GTPase activating protein 5), a protumorigenic gene, by directly interacting with its promoter and thereby regulating its expression at transcriptional level. Reintroduction of ARHGAP5 resembled the effects of miR-744 and silencing of ARHGAP5 clearly abrogated miR-744-induced enhancement of cell migration and invasion. High level of ARHGAP5 was positively correlated with that of miR-744 and with advanced stages of NPC, as well as with lymph node metastasis. Taken together, these data reveal for the first time that miR-744 exerts its proto-oncogenic function by directly targeting ARHGAP5 promoter. This newly identified miR-744/ARHGAP5 pathway provides further insight into the progression and metastasis of NPC and indicates potential novel therapeutic targets for NPC. PMID:25961434

  16. LPLUNC1 Inhibits Nasopharyngeal Carcinoma Cell Growth via Down-Regulation of the MAP Kinase and Cyclin D1/E2F Pathways

    PubMed Central

    Li, Xiaoling; Zhang, Wenling; Fan, Songqing; Shi, Lei; Li, Xiayu; Gong, Zhaojian; Ma, Jian; Zhou, Ming; Xiang, Juanjuan; Peng, Shuping; Xiang, Bo; Deng, Hao; Yang, Yunbo; Li, Yong; Xiong, Wei; Zeng, Zhaoyang; Li, Guiyuan

    2013-01-01

    Long-palate, lung and nasal epithelium clone 1 (LPLUNC1) gene expression is relatively tissue specific. It is highly expressed in nontumor nasopharyngeal epithelial tissues, but its expression is reduced in nasopharyngeal carcinoma (NPC), indicating that LPLUNC1 may be associated with the tumorigenesis of NPC. To study the effects of LPLUNC1 on NPC tumorigenesis, a full-length LPLUNC1 expression plasmid was stably transfected into the NPC cell line, 5-8F. Our data indicated that LPLUNC1 inhibited NPC cell proliferation in vitro and tumor formation in vivo. LPLUNC1 also delayed cell cycle progression from G1 to S phase and inhibited the expression of cyclin D1, cyclin-dependent kinase 4 (CDK4) and phosphorylated Rb. To further investigate the molecular mechanisms underlying the suppressive effects of LPLUNC1 on NPC tumorigenesis, cDNA microarray was performed. These studies revealed that LPLUNC1 inhibited the expression of certain mitogen-activated protein (MAP) kinases (MAPK) kinases and cell cycle-related molecules. Western blotting confirmed that the expression of MEK1, phosphorylated ERK1/2, phosphorylated JNK1/2, c-Myc and c-Jun were inhibited by LPLUNC1. Furthermore, the transcriptional activity of AP-1 was down-regulated by LPLUNC1, suggesting that the MAPK signaling pathway is regulated by LPLUNC1. Taken together, the present study indicates that LPLUNC1 delays NPC cell growth by inhibiting the MAPK and cyclin D1/E2F pathways and suggests that LPLUNC1 may represent a promising candidate tumor suppressor gene associated with NPC. PMID:23650533

  17. Preferential cytotoxicity of the type I ribosome inactivating protein alpha-momorcharin on human nasopharyngeal carcinoma cells under normoxia and hypoxia.

    PubMed

    Pan, Wen Liang; Wong, Jack Ho; Fang, Evandro Fei; Chan, Yau Sang; Ng, Tzi Bun; Cheung, Randy Chi Fai

    2014-06-01

    All primary nasopharyngeal carcinoma (NPC) tumors contain hypoxic regions which are implicated in decreased local control and increased distant metastases, as well as resistance to chemotherapy in advanced NPC patients. One of the promising therapeutic approaches for NPC is to use drugs that can target hypoxic factors in tumors. In the present investigation, the type I ribosome inactivating protein α-momorcharin (α-MMC), isolated from seeds of the bitter gourd Momordica charantia, reduced cell viability and inhibited clonogenic formation of human NPC CNE2 and HONE1 cells under normoxia and cobalt chloride-induced hypoxia. By comparison, α-MMC exhibited only slight cytotoxicity on human nasopharyngeal epithelial NP69 cells under normoxia. Interestingly, α-MMC suppressed the expression levels of hypoxia-inducible factor 1-alpha (HIF1α) and vascular endothelial growth factor (VEGF) in hypoxic NPC, as well as the growth of human umbilical vein endothelial cells. Further study disclosed that α-MMC targeted endoplasmic reticulum and down-regulated unfolded protein response (UPR) in NPC cells. Moreover, α-MMC induced apoptosis in NPC cells in a dose- and time-dependent manner. It initiated mitochondrial- and death receptor-mediated apoptotic signaling in CNE2 cells, but there was hardly any effect on HONE1 cells. In addition, α-MMC brought about G0/G1 phase cell cycle arrest in CNE2 cells and S phase arrest in HONE1 cells. Collectively, α-MMC preferentially exhibited inhibitory effect on normoxic and hypoxic NPC cells partly by blocking survival signaling (e.g. HIF1α, VEGF and UPR), and triggering apoptotic pathways mediated by mitochondria or death receptor. These observations indicate the potential utility of α-MMC for prophylaxis and therapy of NPC. PMID:24637239

  18. A Dosimetric Study of Using Fixed-Jaw Volumetric Modulated Arc Therapy for the Treatment of Nasopharyngeal Carcinoma with Cervical Lymph Node Metastasis

    PubMed Central

    Chen, Jian-Zhou; Zhai, Tian-Tian; Huang, Bao-Tian; Li, De-Rui; Chen, Chuang-Zhen

    2016-01-01

    Purpose To study the dosimetric difference between fixed-jaw volumetric modulated radiotherapy (FJ-VMAT) and large-field volumetric modulated radiotherapy (LF-VMAT) for nasopharyngeal carcinoma (NPC) with cervical lymph node metastasis. Methods Computed tomography (CT) datasets of 10 NPC patients undergoing chemoradiotherapy were used to generate LF-VMAT and FJ-VMAT plans in the Eclipse version 10.0 treatment planning system. These two kinds of plans were then compared with respect to planning-target-volume (PTV) coverage, conformity index (CI), homogeneity index (HI), organ-at-risk sparing, monitor units (MUs) and treatment time (TT). Results The FJ-VMAT plans provided lower D2% of PGTVnd (PTV of lymph nodes), PTV1 (high-risk PTV) and PTV2 (low-risk PTV) than did the LF-VMAT plans, whereas no significant differences were observed in PGTVnx (PTV of primary nasopharyngeal tumor). The FJ-VMAT plans provided lower doses delivered to the planning organ at risk (OAR) volumes (PRVs) of both brainstem and spinal cord, both parotid glands and normal tissue than did the LF-VMAT plans, whereas no significant differences were observed with respect to the oral cavity and larynx. The MUs of the FJ-VMAT plans (683 ± 87) were increased by 22% ± 12% compared with the LF-VMAT plans (559 ± 62). In terms of the TT, no significant difference was found between the two kinds of plans. Conclusions FJ-VMAT was similar or slightly superior to LF-VMAT in terms of PTV coverage and was significantly superior in terms of OAR sparing, at the expense of increased MUs. PMID:27231871

  19. Common variations in TERT-CLPTM1L locus are reproducibly associated with the risk of nasopharyngeal carcinoma in Chinese populations

    PubMed Central

    Zhang, Hongxing; Zhai, Yun; Wang, Zhifu; Li, Peiyao; Yu, Lixia; Xia, Xia; Zhang, Ying; Zeng, Yixin; He, Fuchu; Zhou, Gangqiao

    2016-01-01

    Associations between single nucleotide polymorphisms (SNPs) at 5p15 (TERT-CLPTM1L) and multiple cancer types have been reported. We examined whether polymorphisms in the TERT-CLPTM1L locus were related to the risk of developing nasopharyngeal carcinoma (NPC) among Chinese populations. In the first stage, 26 tag SNPs were genotyped in a Guangxi population (855 patients and 1036 controls). In the second stage, the SNPs, which showed significant association, were further genotyped in a Guangdong population (997 patients and 972 controls). Functional analyses were conducted to verify the biological relevance of the associated polymorphism. In the 1st stage, four SNPs (rs2736098, rs2735845, rs402710, and rs401681) were significantly associated with the risk of developing NPC. After the 2nd stage validation, rs2735845 and rs401681 were independently associated with the risk of developing NPC in the additive model (rs2735845, OR = 1.19, 95% CI = 1.04–1.37, P = 0.011; rs401681, OR = 0.85, 95% CI = 0.74–0.99, P = 0.034). Furthermore, we observed higher CLPTM1L messenger RNA levels in fetal mesenchymal stem cells from the rs2735845 G allele carriers compared with that from non-carriers. In addition, using an immunohistochemistry assay, we observed higher TERT and CLPTM1L levels in NPC tissues compared with that in non-cancerous nasopharyngeal tissues. Our findings suggest that polymorphisms in the TERT-CLPTM1L locus may play a role in mediating the susceptibility to NPC in Chinese populations. PMID:26621837

  20. EGCG Inhibits Proliferation, Invasiveness and Tumor Growth by Up-Regulation of Adhesion Molecules, Suppression of Gelatinases Activity, and Induction of Apoptosis in Nasopharyngeal Carcinoma Cells

    PubMed Central

    Fang, Chih-Yeu; Wu, Chung-Chun; Hsu, Hui-Yu; Chuang, Hsin-Ying; Huang, Sheng-Yen; Tsai, Ching-Hwa; Chang, Yao; Tsao, George Sai-Wah; Chen, Chi-Long; Chen, Jen-Yang

    2015-01-01

    (−)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol, has been shown to inhibit the proliferation of a variety of tumor cells. Epidemiological studies have shown that drinking green tea can reduce the incidence of nasopharyngeal carcinoma (NPC), yet the underlying mechanism is not well understood. In this study, the inhibitory effect of EGCG was tested on a set of Epstein Barr virus-negative and -positive NPC cell lines. Treatment with EGCG inhibited the proliferation of NPC cells but did not affect the growth of a non-malignant nasopharyngeal cell line, NP460hTert. Moreover, EGCG treated cells had reduced migration and invasive properties. The expression of the cell adhesion molecules E-cadherin and β-catenin was found to be up-regulated by EGCG treatment, while the down-regulation of matrix metalloproteinases (MMP)-2 and MMP-9 were found to be mediated by suppression of extracellular signal-regulated kinase (ERK) phosphorylation and AP-1 and Sp1 transactivation. Spheroid formation by NPC cells in suspension was significantly inhibited by EGCG. Oral administration of EGCG was capable of suppressing tumor growth in xenografted mice bearing NPC tumors. Treatment with EGCG was found to elevate the expression of p53 and p21, and eventually led to apoptosis of NPC cells via caspase 3 activation. The nuclear translocation of NF-κB and β-catenin was also suppressed by EGCG treatment. These results indicate that EGCG can inhibit the proliferation and invasiveness, and induce apoptosis, of NPC cells, making it a promising agent for chemoprevention or adjuvant therapy of NPC. PMID:25625511

  1. Nasopharyngeal Actinomycosis

    PubMed Central

    Ouertatani, Lamia; Jeblaoui, Yassine; Kharrat, Salima; Sahtout, Samia; Besbes, Ghazi

    2011-01-01

    Nasopharyngeal actinomycosis is a rarely encountered bacterial infection which usually occurs after nasal trauma or surgery. In some clinical cases, nasopharyngeal actinomycosis has appeared in patients without prior trauma, making diagnosis difficult. Here we present three such cases successfully treated with appropriate dosages of penicillin. One 16-year-old boy with no previous medical antecedents showed an important thickening of the posterior wall of the nasopharynx. A similar nasopharyngeal thickening was found in a 42-year-old woman exhibiting poor dental hygiene. In another 42-year-old woman, nasopharyngeal inflammation was accompanied by multiple right lymphoadenopathies. Like the first two patients, the woman had no prior trauma but did exhibit poor dental hygiene and teeth rottenness. In all three patients, actinomycosis diagnosis was confirmed by anaerobic microbial culturing of the biopsy specimen. Although diagnosis is delayed in patients with no prior trauma, treatment with antibiotics has greatly improved the prognosis for all forms of actinomycosis, and neither death nor deformity is common. PMID:22937364

  2. Proteomic profiling between CNE-2 and its strongly metastatic subclone S-18 and functional characterization of HSP27 in metastasis of nasopharyngeal carcinoma.

    PubMed

    Li, Guo-Ping; Wang, Hua; Lai, Yiu-Kay; Chen, Shao-Chun; Lin, Marie C M; Lu, Gang; Zhang, Jing-Fang; He, Xiao-Guang; Qian, Chao-Nan; Kung, Hsiang-Fu

    2011-07-01

    Metastasis to secondary sites remains the leading cause of nasopharyngeal carcinoma (NPC)-associated death. In order to identify the candidate protein(s) responsible for the differential metastatic capacity, the protein expression profiling between NPC cell line CNE-2 and its highly metastatic subclone S-18 were compared by 2-DE. In total, 18 spots were differentially expressed between these two cell lines. Among all, seven proteins were identified with further MS analysis. Western blotting further validated upregulation of HSP27 and ezrin, and downregulation of valosin containing protein and keratin 18 in S-18. Moreover, the knockdown of HSP27 was found to significantly decrease the invasive ability of S-18. On the other hand, overexpression of HSP27 in NP460 cells, which generated little endogenous HSP27 and less invasive, was noted to gain enhanced metastatic capability. Real-time PCR confirmed that the transcriptional levels of NF-κB and MMP9, MMP11 were downregulated after inhibition of HSP27 in S-18, which implicated that HSP27 enhanced the metastatic property of NPC cells probably via the NF-κB-mediated activation of MMPs. The findings in this work provided us a platform for further elucidating the underlying mechanisms of NPC metastasis and demonstrated that HSP27 would be a valid target for anti-cancer drug development. PMID:21717573

  3. A Novel LMP1 Antibody Synergizes with Mitomycin C to Inhibit Nasopharyngeal Carcinoma Growth in Vivo Through Inducing Apoptosis and Downregulating Vascular Endothelial Growth Factor

    PubMed Central

    Mao, Yuan; Zhang, Da-Wei; Wen, Juan; Cao, Qing; Chen, Ren-Jie; Zhu, Jin; Feng, Zhen-Qing

    2012-01-01

    Combined therapy emerges as an attractive strategy for cancer treatment. The aim of this study was to investigate the inhibitory effects of mitomycin C (MMC) combined with a novel antibody fragment (Fab) targeting latent membrane protein 1 (LMP1) on nasopharyngeal carcinoma (NPC) xenograft nude mice. The inhibitory rates of MMC (2 mg/kg), Fab (4 mg/kg), MMC (2 mg/kg) + Fab (4 mg/kg), and MMC (1 mg/kg) + Fab (4 mg/kg) were 20.1%, 7.3%, 42.5% and 40.5%, respectively. Flow cytometry analysis showed that the apoptotic rate of xenograft tumor cells in the MMC and Fab combination group was 28 ± 4.12%, significantly higher than the MMC (2 mg/kg) group (P < 0.01). Immunohistochemical staining showed that VEGF expression in NPC xenografts was significantly inhibited in the combination group compared to the Fab (4 mg/kg) group (P < 0.05). In conclusion, both MMC and Fab could inhibit NPC xenograft tumor growth in vivo and combination therapy showed apparent synergistic anti-tumor effects, which may be due to the induction of tumor cell apoptosis and the downregulation of VEGF expression. These results suggest that the novel combined therapy utilizing traditional chemotherapeutics and antibody-targeted therapy could be a promising strategy for the treatment of NPC. PMID:22408448

  4. Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study.

    PubMed

    Luo, Yangkun; Feng, Mei; Fan, Zixuan; Zhu, Xiaodong; Jin, Feng; Li, Rongqing; Wu, Jingbo; Yang, Xia; Jiang, Qinghua; Bai, Hongfang; Huang, Yecai; Lang, Jinyi

    2016-01-01

    Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application. PMID:27375766

  5. Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study

    PubMed Central

    Luo, Yangkun; Feng, Mei; Fan, Zixuan; Zhu, Xiaodong; Jin, Feng; Li, Rongqing; Wu, Jingbo; Yang, Xia; Jiang, Qinghua; Bai, Hongfang; Huang, Yecai; Lang, Jinyi

    2016-01-01

    Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group) or compound borax gargle (control group) during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v3.0 and the Verbal Rating Scale (VRS). Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P = 0.01). The time to different grade of oral mucositis occurrence (grade 1, 2, or 3) was longer in test group (P < 0.01), and the accumulated radiation dose was also higher in test group comparing to the control group (P < 0.05). The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P < 0.01). No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application. PMID:27375766

  6. In vitro and in vivo efficacy of afatinib as a single agent or in combination with gemcitabine for the treatment of nasopharyngeal carcinoma

    PubMed Central

    Xue, Cong; Tian, Ying; Zhang, Jing; Zhao, Yuanyuan; Zhan, Jianhua; Fang, Wenfeng; Zhang, Li

    2016-01-01

    Purpose Epidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC). We tested the antitumor effects of irreversible ErbB family inhibitor afatinib on human NPC using in vitro and in vivo models. Materials and methods The effect of afatinib on NPC cells was evaluated using the Cell Counting Kit 8 (CCK8) assay, flow cytometry, and Western blot analyses. The effect of afatinib, as either a single agent or in combination with gemcitabine (GEM), on tumor growth was determined using NPC tumor xenografts in mice. Results Afatinib inhibited cell growth in all three NPC cell lines tested in a dose-dependent manner. Afatinib promoted cell cycle arrest at the S and G2/M phases, and it significantly inhibited epidermal growth factor (EGF)-induced activation of EGFR and its downstream signaling factors. Co-treatment with afatinib and GEM more effectively inhibited tumor growth than either drug alone but was associated with increased toxicity. Conclusion Afatinib induced cell cycle arrest and inhibited the proliferation of NPC cell lines. Afatinib in combination with GEM demonstrated significant antitumor effect in an NPC xenograft model. The administration of afatinib with GEM in NPC needs to be modified in order to be effective and tolerable. PMID:27099475

  7. Nasopharyngeal carcinoma with intracranial extension in the era of intensity-modulated radiotherapy: case-control study using propensity score matching method.

    PubMed

    Cao, Cai-Neng; Luo, Jing-Wei; Gao, Li; Xu, Guo-Zhen; Yi, Jun-Lin; Huang, Xiao-Dong; Li, Su-Yan; Xiao, Jian-Ping; Zhang, Zhong

    2016-08-01

    The objective of the study was to evaluate long-term survival outcomes and toxicity of T4 classification nasopharyngeal carcinoma (NPC) with intracranial extension (IE group) or without intracranial extension (non-IE group) after intensity-modulated radiotherapy (IMRT) using the propensity score matching method. After generating propensity scores given the covariates of age, sex, N classification, and concurrent chemotherapy, 132 patients in each group were matched. The 5-year local failure-free survival rate and the 5-year overall survival rate in the IE group were lower than the patients in the non-IE group (74.6 vs. 88.9 %, p = .008; 51.1 vs. 71.9 %, p = .005). Grade 2 hypothyroidism was more common in the IE group (13.2 vs. 3.4 %, p = .029). For patients with T4 classification NPC after IMRT, patients with intracranial extension need more attention to the thyroid gland function and are more likely to experience local failure and death than patients without intracranial extension. PMID:26282900

  8. The preclinical study of predicting radiosensitivity in human nasopharyngeal carcinoma xenografts by 18F-ML-10 animal- PET/CT imaging

    PubMed Central

    Wang, Siyang; Zheng, Yujia; Wang, Mingwei; Gu, Bingxin; Zhang, Jianping; Zhang, Yongping; Zhang, Yingjian

    2016-01-01

    Previous studies have reported that the radiosensitivity is associated with apoptosis. Hereby, we aimed to investigate the value of 18F-ML-10 PET/CT, which selectively targeted cells undergoing apoptosis, in predicting radiosensitivity of human nasopharyngeal carcinoma (NPC) xenografts. We used CNE1 (highly differentiated) and CNE2 (poorly differentiated) NPC cell lines to construct tumor models, which had very different radiosensitivities. After irradiation, the volumes of CNE2 tumors decreased significantly while those of CNE1 tumors increased. In 18F-ML-10 imaging, the values of tumor/muscle (T/M) between CNE1 and CNE2 mice were statistically different at both 24 h and 48 h after irradiation. Besides, ΔT/M1-0 and ΔT/M2-0 of CNE2 mice were higher than those of CNE1 mice, demonstrating obvious discrepancy. Furthermore, we observed obvious changes of radioactive distribution in CNE2 group. On the contrary, T/M of 18F-FDG in irradiation group revealed no obvious change in both CNE1 and CNE2 groups. In conclusion, 18F-ML-10 animal PET/CT showed its potential to predict radiosensitivity in NPC. PMID:26942701

  9. Long non-coding RNA XIST exerts oncogenic functions in human nasopharyngeal carcinoma by targeting miR-34a-5p.

    PubMed

    Song, Peng; Ye, Lin-Feng; Zhang, Cen; Peng, Tao; Zhou, Xu-Hong

    2016-10-30

    Long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been verified as an oncogenic gene in several human malignant tumors, and its dysregulation was closed associated with tumor initiation, development and progression. Nevertheless, whether the aberrant expression of XIST in human nasopharyngeal carcinoma (NPC) is corrected with malignancy, metastasis or prognosis has not been elaborated. Here, we discovered that XIST was up-regulated in NPC tissues and higher expression of XIST contributed to a markedly poorer survival time. In addition, multivariate analysis demonstrated XIST was an independent risk factor for prognosis. XIST over-expression enhanced, while XIST silencing hampered the cell growth in NPC. Additionally, mechanistic analysis revealed that XIST up-regulated the expression of miR-34a-5p targeted gene E2F3 through acting as a competitive 'sponge' of miR-34a-5p. Taking all into account, we concluded that XIST functioned as an oncogene in NPC through up-regulating E2F3 in part through 'spongeing' miR-34a-5p. PMID:27461945

  10. Patient- and therapy-related factors associated with the incidence of xerostomia in nasopharyngeal carcinoma patients receiving parotid-sparing helical tomotherapy

    PubMed Central

    Lee, Tsair-Fwu; Liou, Ming-Hsiang; Ting, Hui-Min; Chang, Liyun; Lee, Hsiao-Yi; Wan Leung, Stephen; Huang, Chih-Jen; Chao, Pei-Ju

    2015-01-01

    We investigated the incidence of moderate to severe patient-reported xerostomia among nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT) and identified patient- and therapy-related factors associated with acute and chronic xerostomia toxicity. The least absolute shrinkage and selection operator (LASSO) normal tissue complication probability (NTCP) models were developed using quality-of-life questionnaire datasets from 67 patients with NPC. For acute toxicity, the dosimetric factors of the mean doses to the ipsilateral submandibular gland (Dis) and the contralateral submandibular gland (Dcs) were selected as the first two significant predictors. For chronic toxicity, four predictive factors were selected: age, mean dose to the oral cavity (Doc), education, and T stage. The substantial sparing data can be used to avoid xerostomia toxicity. We suggest that the tolerance values corresponded to a 20% incidence of complications (TD20) for Dis = 39.0 Gy, Dcs = 38.4 Gy, and Doc = 32.5 Gy, respectively, when mean doses to the parotid glands met the QUANTEC 25 Gy sparing guidelines. To avoid patient-reported xerostomia toxicity, the mean doses to the parotid gland, submandibular gland, and oral cavity have to meet the sparing tolerance, although there is also a need to take inherent patient characteristics into consideration. PMID:26289304

  11. Overexpression of Mitochondria Mediator Gene TRIAP1 by miR-320b Loss Is Associated with Progression in Nasopharyngeal Carcinoma

    PubMed Central

    Yang, Xiaojing; Ren, Xianyue; Wen, Xin; Zhang, Jian; Wang, Yaqin; Liu, Na; Ma, Jun

    2016-01-01

    The therapeutic strategy for advanced nasopharyngeal carcinoma (NPC) is still challenging. It is an urgent need to uncover novel treatment targets for NPC. Therefore, understanding the mechanisms underlying NPC tumorigenesis and progression is essential for the development of new therapeutic strategies. Here, we showed that TP53-regulated inhibitor of apoptosis (TRIAP1) was aberrantly overexpressed and associated with poor survival in NPC patients. TRIAP1 overexpression promoted NPC cell proliferation and suppressed cell death in vitro and in vivo, whereas TRIAP1 knockdown inhibited cell tumorigenesis and enhanced apoptosis through the induction of mitochondrial fragmentation, membrane potential alteration and release of cytochrome c from mitochondria into the cytosol. Intersecting with our previous miRNA data and available bioinformatic algorithms, miR-320b was identified and validated as a negative regulator of TRIAP1. Further studies showed that overexpression of miR-320b suppressed NPC cell proliferation and enhanced mitochondrial fragmentation and apoptosis both in vitro and in vivo, while silencing of miR-320b promoted tumor growth and suppressed apoptosis. Additionally, TRIAP1 restoration abrogated the proliferation inhibition and apoptosis induced by miR-320b. Moreover, the loss of miR-320b expression was inversely correlated with TRIAP1 overexpression in NPC patients. This newly identified miR-320b/TRIAP1 pathway provides insights into the mechanisms leading to NPC tumorigenesis and unfavorable clinical outcomes, which may represent prognostic markers and potential therapeutic targets for NPC treatment. PMID:27428374

  12. LASSO-based NTCP model for radiation-induced temporal lobe injury developing after intensity-modulated radiotherapy of nasopharyngeal carcinoma

    PubMed Central

    Kong, Cheng; Zhu, Xiang-zhi; Lee, Tsair-Fwu; Feng, Ping-bo; Xu, Jian-hua; Qian, Pu-dong; Zhang, Lan-fang; He, Xia; Huang, Sheng-fu; Zhang, Yi-qin

    2016-01-01

    We investigated the incidence of temporal lobe injury (TLI) in 132 nasopharyngeal carcinoma (NPC) patients who had undergone intensity-modulated radiotherapy (IMRT) in our hospital between March 2005 and November 2009; and identified significant dosimetric predictors of TLI development. Contrast-enhanced lesions or cysts in the temporal lobes, as detected by magnetic resonance imaging (MRI), were regarded as radiation-induced TLIs. We used the least absolute shrinkage and selection operator (LASSO) method to select Dmax (the maximum point dose) and the D1cc (the top dose delivered to a 1-mL volume) from 15 dose-volume-histogram-associated and four clinically relevant candidate factors; the Dmax and the D1cc were the most significant predictors of TLI development. We drew dose-response curves for Dmax and D1cc. The tolerance dose (TD) for the 5% and 50% probabilities of TLI development were 69.0 ± 1.6 and 82.1 ± 2.4 Gy for Dmax and 62.8 ± 2.2 and 80.9 ± 3.4 Gy for D1cc, respectively. The incidence of TLI in NPC patients after IMRT was higher than expected because the therapeutic window is narrow. High-quality longitudinal studies are needed to gain further insight into the complex spatiotemporal effects of non-uniform irradiation on TLI development in NPC patients. PMID:27210263

  13. In vivo and in vitro study on the role of 3,3'-diindolylmethane in treatment and prevention of nasopharyngeal carcinoma.

    PubMed

    Chen, Chen; Chen, Shi-Ming; Xu, Bin; Chen, Zhe; Wang, Fei; Ren, Jie; Xu, Yong; Wang, Yan; Xiao, Bo-Kui; Tao, Ze-Zhang

    2013-08-01

    Nasopharyngeal carcinoma (NPC) is characterized by insidious progression and atypical early symptoms and mostly diagnosed in middle or late stages. The long-term prognosis is poor after conventional radiotherapy or chemotherapy, and the therapy often has strong toxic effects on normal tissue and organs. There were in vitro and in vivo preclinical evidences to support chemotherapeutic and chemopreventive effects of 3,3'-diindolylmethane (DIM), which was a natural compound extracted from cruciferous plants. The in vitro experiments showed that 100 µM DIM could induce remarkable apoptosis of NPC cells, and no obvious damage was observed in normal human bronchial epithelial cells and human liver cells (P < 0.01). DIM could simultaneously regulate several signaling pathways directly related to NPC, such as PI3K, MAPK, Akt and NF-κB. In animal model, the volume of transplanted tumor in animals raised by feed containing DIM was significantly less than that of control group (P < 0.01). The animals with 2 weeks of preventive feeding with feed containing DIM before inoculation had the smallest volume of transplanted tumor (P < 0.01). Intake of DIM had no toxic effects on vital organs such as heart, liver and kidney of experimental animals. In summary, the results of this study confirmed that the DIM effectively induced apoptosis of NPC cells, and had a preventive and curative role in the development and progression of NPC. The drug was safe and had no toxic effects on normal tissues and organs. PMID:23568953

  14. A novel LMP1 antibody synergizes with mitomycin C to inhibit nasopharyngeal carcinoma growth in vivo through inducing apoptosis and downregulating vascular endothelial growth factor.

    PubMed

    Mao, Yuan; Zhang, Da-Wei; Wen, Juan; Cao, Qing; Chen, Ren-Jie; Zhu, Jin; Feng, Zhen-Qing

    2012-01-01

    Combined therapy emerges as an attractive strategy for cancer treatment. The aim of this study was to investigate the inhibitory effects of mitomycin C (MMC) combined with a novel antibody fragment (Fab) targeting latent membrane protein 1 (LMP1) on nasopharyngeal carcinoma (NPC) xenograft nude mice. The inhibitory rates of MMC (2 mg/kg), Fab (4 mg/kg), MMC (2 mg/kg) + Fab (4 mg/kg), and MMC (1 mg/kg) + Fab (4 mg/kg) were 20.1%, 7.3%, 42.5% and 40.5%, respectively. Flow cytometry analysis showed that the apoptotic rate of xenograft tumor cells in the MMC and Fab combination group was 28 ± 4.12%, significantly higher than the MMC (2 mg/kg) group (P < 0.01). Immunohistochemical staining showed that VEGF expression in NPC xenografts was significantly inhibited in the combination group compared to the Fab (4 mg/kg) group (P < 0.05). In conclusion, both MMC and Fab could inhibit NPC xenograft tumor growth in vivo and combination therapy showed apparent synergistic anti-tumor effects, which may be due to the induction of tumor cell apoptosis and the downregulation of VEGF expression. These results suggest that the novel combined therapy utilizing traditional chemotherapeutics and antibody-targeted therapy could be a promising strategy for the treatment of NPC. PMID:22408448

  15. Human Leukocyte Antigen (HLA) A*1101-restricted Epstein-Barr Virus-specific T-cell Receptor Gene Transfer to Target Nasopharyngeal Carcinoma

    PubMed Central

    Zheng, Yong; Parsonage, Greg; Zhuang, Xiaodong; Machado, Lee R; James, Christine H.; Salman, Asmaa; Searle, Peter F.; Hui, Edwin P.; Chan, Anthony T.C.; Lee, Steven P.

    2015-01-01

    Infusing virus-specific T cells is effective treatment for rare Epstein-Barr virus (EBV)-associated post-transplant lymphomas and more limited success has been reported using this approach to treat a far more common EBV-associated malignancy, nasopharyngeal carcinoma (NPC). However, current approaches using EBV-transformed lymphoblastoid cell lines to reactivate EBV-specific T cells for infusion take 2 to 3 months of in vitro culture and favour outgrowth of T cells targeting viral antigens expressed within EBV+ lymphomas but not in NPC. Here we explore T-cell receptor (TCR) gene transfer to rapidly and reliably generate T cells specific for the NPC-associated viral protein LMP2. We cloned a HLA A*1101-restricted TCR, which would be widely applicable since 40% of NPC patients carry this HLA allele. Studying both the wild-type and modified forms we have optimised expression of the TCR and demonstrated high avidity antigen-specific function (proliferation, cytotoxicity, cytokine release) in both CD8+ and CD4+ T cells. The engineered T cells also inhibited LMP2+ epithelial tumour growth in a mouse model. Furthermore, transduced T cells from patients with advanced NPC lysed LMP2-expressing NPC cell lines. Using this approach, within a few days large numbers of high avidity LMP2-specific T cells can be generated reliably to treat NPC, thus providing an ideal clinical setting to test TCR gene transfer without the risk of autoimmunity through targeting self-antigens. PMID:25711537

  16. Gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p inhibit growth of EBV-positive nasopharyngeal carcinoma

    PubMed Central

    Wang, Jianguo; Lyu, Xiaoming; Chen, Yuxiang; Liu, Jinkun; Cai, Hongbing; Wang, Ying; Li, Xin

    2015-01-01

    Epstein-Barr virus (EBV) infection is a major etiological factor for nasopharyngeal carcinoma (NPC). Several EBV-encoded BART miRNAs have been associated with viral latency, immune escape, cell survival, cell proliferation and apoptosis. Here, we report that EBV-miR-BART7-3p, an EBV-encoded BART miRNA highly expressed in NPC, was correlated with cell-cycle progression in vitro and increased tumor formation in vivo. This viral miRNA stimulated the PTEN/PI3K/Akt pathway and induced c-Myc and c-Jun. Knockdown of PTEN mimicked EBV-miR-BART7-3p-induced tumorigenic phenotype. Based on these results, we conducted a therapeutic experiment by using gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p. Silencing of EBV-miR-BART7-3p reduced tumor growth in animal model. We conclude that EBV-miR-BART7-3p favors carcinogenesis, representing a potential target for miRNA-based therapy. PMID:25691053

  17. Association of miR-146a gene polymorphism with risk of nasopharyngeal carcinoma in the central-southern Chinese population.

    PubMed

    Huang, Guo-Liang; Chen, Mei-Ling; Li, Ya-Zhen; Lu, Yan; Pu, Xing-Xiang; He, Yu-Xiang; Tang, Shu-Yin; Che, Hua; Zou, Ying; Ding, Congcong; He, Zhiwei

    2014-03-01

    This case-control study focused on estimating the association between miR-146a polymorphism and risk of nasopharyngeal carcinoma (NPC) in central-south China. In total, 160 patients with NPC and 200 healthy controls in central-south China were genotyped using polymerase chain reaction-restriction fragment length polymorphism assay. Chi-square test was used to assess the different distribution of miR-146a polymorphism between NPC patients and controls; and logistic regression analysis was applied to analyze the associations between miR-146a polymorphism with cancer risk in different contrast models. Significant differences between NPC patients and controls were found in genotype (P=0.033 for GG versus CG versus CC; and odds ratio (OR)=0.568, 95% confidence interval (CI)=0.354-0.912, P=0.019 for CG versus CC; and OR=0.503, 95% CI=0.261-0.971, P=0.041 for CG versus CC; and OR=0.564, 95% CI=0.360-0.884, P=0.012 for GG+CG versus CC, respectively) and allelic analysis (P=0.025 for G versus C). Our findings suggested that polymorphism of mir-146a was associated with NPC in the central-southern Chinese population. PMID:24430575

  18. Long noncoding RNA H19 regulates EZH2 expression by interacting with miR-630 and promotes cell invasion in nasopharyngeal carcinoma.

    PubMed

    Li, Xudong; Lin, Yan; Yang, Xi; Wu, Xiaoguang; He, Xiaoguang

    2016-05-13

    The long non-coding RNA (lncRNA) H19 has been recently shown to participate in the progression of cancer, including metastasis. However, the biological role of H19 and the underlying mechanisms mediating its functions in nasopharyngeal carcinoma (NPC) remain unclear. Herein, we found that H19 was overexpressed in NPC tissues and poorly differentiated cell lines. Knockdown of H19 significantly inhibited the invasive ability of NPC cells. Moreover, H19 affected the expression of enhancer of zeste homolog 2 (EZH2), which has also been observed to be up-regulated in NPC and to promote cell invasion. Rather than direct interaction, H19 regulated EZH2 expression by suppressing the activity of miR-630, which is a repressor of EZH2 and interacts with H19 in a sequence-specific manner. Furthermore, H19 inhibited E-cadherin expression and promoted cell invasion of NPC cells via the miR-630/EZH2 pathway. Our data suggest an important role for H19 in NPC metastasis and suggest the feasibility of therapy for NPC involving modulation of the novel regulatory network. PMID:27040767

  19. PDZ binding kinase (PBK) is a theranostic target for nasopharyngeal carcinoma: driving tumor growth via ROS signaling and correlating with patient survival.

    PubMed

    Wang, Meng-Yao; Lin, Zhi-Rui; Cao, Yun; Zheng, Li-Sheng; Peng, Li-Xia; Sun, Rui; Meng, Dong-Fang; Xie, Ping; Yang, Jun-Ping; Cao, Li; Xu, Liang; Huang, Bi-Jun; Qian, Chao-Nan

    2016-05-01

    Nasopharyngeal carcinoma (NPC) is well known as one of the most common malignancies in southern China and Southeast Asia. However, the mechanisms underlying NPC progression remain poorly understood. Herein, through overlapping the differentially expressed genes from 3 microarray data sets with the human kinome, we identified PBK, a serine-threonine kinase, is highly upregulated and has not been intensively investigated in NPC. PBK was required for malignant phenotypes of NPC, as PBK depletion by RNAi and inhibition by specific inhibitor HI-TOPK-032 obviously reduced cell proliferation and xenograft tumor growth in mice. Moreover, we determined that targeting PBK could accelerate apoptosis by inducing ROS that activates JNK/p38 signaling pathway. In NPC patients, elevated PBK expression in primary tumor positively correlated to clinical severity such as advanced T stage, high death risk and disease progression, and it could serve as an unfavorable independent indicator of overall survival and disease-free survival. Altogether, our results indicate that PBK is a novel significant regulator of NPC progression and a potential therapeutic target for NPC patients. PMID:27049917

  20. Lowered Risk of Nasopharyngeal Carcinoma and Intake of Plant Vitamin, Fresh Fish, Green Tea and Coffee: A Case-Control Study in Taiwan

    PubMed Central

    Hsu, Wan-Lun; Pan, Wen-Harn; Chien, Yin-Chu; Yu, Kelly J.; Cheng, Yu-Juen; Chen, Jen-Yang; Liu, Mei-Ying; Hsu, Mow-Ming; Lou, Pei-Jen; Chen, I-How; Yang, Czau-Siung; Hildesheim, Allan; Chen, Chien-Jen

    2012-01-01

    Background A case-control study was conducted to evaluate the role of adult diet on nasopharyngeal carcinoma (NPC) in Taiwan. Methods A total of 375 incident NPC cases and 327 controls matched to the cases on sex, age, and residence were recruited between July 1991 and December 1994. A structured questionnaire inquiring complete dietary history, socio-demographic characteristics, and other potential confounding factors was used in the personal interview. Unconditional logistic regression analysis was used to estimate multivariate-adjusted odds ratio (ORadj) with 95% confidence interval (CI) after accounting for known risk factors. Results Fresh fish (ORadj, 0.56; 95% CI, 0.38–0.83 for the highest vs. lowest tertile of intake), green tea (ORadj, 0.61; 95% CI, 0.40–0.91 for drinking ≥1 times/week vs. never) and coffee (ORadj, 0.56; 95% CI, 0.37–0.85 for drinking ≥0.5 times/week vs. never) were inversely associated with the NPC risk. No association with NPC risk was observed for the intake of meats, salted fish, fresh vegetables, fruits and milk. Intake of vitamin A from plant sources was associated with a decreased NPC risk (ORadj, 0.62; 95% CI, 0.41–0.94 for the highest vs. lowest tertile). Conclusion The study findings suggest that certain adult dietary patterns might protect against the development of NPC. PMID:22848600

  1. Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

    PubMed Central

    Fogg, Mark; Murphy, John R.; Lorch, Jochen; Posner, Marshall; Wang, Fred

    2013-01-01

    Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients. PMID:23601786

  2. EBV-driven LMP1 and IFN-γ up-regulate PD-L1 in nasopharyngeal carcinoma: Implications for oncotargeted therapy

    PubMed Central

    Chen, Nan; Qin, Tao; Tang, Yanna; Zhang, Yaxiong; Kang, Shiyang; Zhou, Ting; Wu, Xuan; Liang, Wenhua; Hu, Zhihuang; Ma, Yuxiang; Zhao, Yuanyuan; Tian, Ying; Yang, Yunpeng; Xue, Cong; Yan, Yue; Hou, Xue; Huang, Peiyu; Huang, Yan; Zhao, Hongyun; Zhang, Li

    2014-01-01

    PD-L1 expression is a feature of Epstein-Barr virus (EBV) associated malignancies such as nasopharyngeal carcinoma (NPC). Here, we found that EBV-induced latent membrane protein 1 (LMP1) and IFN-γ pathways cooperate to regulate programmed cell death protein 1 ligand (PD-L1). Expression of PD-L1 was higher in EBV positive NPC cell lines compared with EBV negative cell lines. PD-L1 expression could be increased by exogenous and endogenous induction of LMP1 induced PD-L1. In agreement, expression of PD-L1 was suppressed by knocking down LMP1 in EBV positive cell lines. We further demonstrated that LMP1 up-regulated PD-L1 through STAT3, AP-1, and NF-κB pathways. Besides, IFN-γ was independent of but synergetic with LMP1 in up-regulating PD-L1 in NPC. Furthermore, we showed that PD-L1 was associated with worse disease-free survival in NPC patients. These results imply that blocking both the LMP1 oncogenic pathway and PD-1/PD-L1 checkpoints may be a promising therapeutic approach for EBV positive NPC patients. PMID:25361008

  3. Epstein-Barr virus oncoprotein LMP1 mediates survivin upregulation by p53 contributing to G1/S cell cycle progression in nasopharyngeal carcinoma

    PubMed Central

    GUO, LILI; TANG, MIN; YANG, LIFANG; XIAO, LANBO; BODE, ANN M.; LI, LILI; DONG, ZIGANG; CAO, YA

    2012-01-01

    Latent membrane protein 1 (LMP1) is an important oncogenic protein encoded by Epstein-Barr virus (EBV) and plays an important role in the development of nasopharyngeal carcinoma (NPC). Our previous study has shown that p53 protein was accumulated and phosphorylated in NPC, implying its transcription factor activity in NPC tumorigenesis. However, the biological function and potential downstream target of p53 mediated by LMP1 in NPC remain unknown. In this study, we found that LMP1 simultaneously induced upregulation of both p53 and survivin at the protein level, as well as their phosphorylation. Knockdown of p53 by siRNA revealed that LMP1 increased survivin expression by p53 directly. Furthermore, we found that LMP1 upregulated survivin by p53 at the transcriptional level by increasing p53-mediated survivin promoter activity and DNA binding activity. Moreover, LMP1 induced the co-localization of p53 and survivin in the nucleus, conferring to their related functions in NPC tumorigenesis. We further found that p53 promoted G1/S cell cycle progression, but did not induce apoptosis in LMP1-positive NPC cells. Collectively, these findings suggest that p53 acting as a transcription factor promotes the transcriptional activity of survivin, and further increases its protein expression and phosphorylation in the regulation of LMP1, thus, leading to G1/S cell cycle progression with no effect on apoptosis in NPC tumorigenesis. PMID:22266808

  4. Tumour inflammasome-derived IL-1β recruits neutrophils and improves local recurrence-free survival in EBV-induced nasopharyngeal carcinoma

    PubMed Central

    Chen, Lih-Chyang; Wang, Li-Jie; Tsang, Nang-Ming; Ojcius, David M; Chen, Chia-Chun; OuYang, Chun-Nan; Hsueh, Chuen; Liang, Ying; Chang, Kai-Ping; Chen, Chiu-Chin; Chang, Yu-Sun

    2012-01-01

    Inflammasomes sense infection and cellular damage and are critical for triggering inflammation through IL-1β production. In carcinogenesis, inflammasomes may have contradictory roles through facilitating antitumour immunity and inducing oncogenic factors. Their function in cancer remains poorly characterized. Here we show that the NLRP3, AIM2 and RIG-I inflammasomes are overexpressed in Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), and expression levels correlate with patient survival. In tumour cells, AIM2 and RIG-I are required for IL-1β induction by EBV genomic DNA and EBV-encoded small RNAs, respectively, while NLRP3 responds to extracellular ATP and reactive oxygen species. Irradiation and chemotherapy can further activate AIM2 and NLRP3, respectively. In mice, tumour-derived IL-1β inhibits tumour growth and enhances survival through host responses. Mechanistically, IL-1β-mediated anti-tumour effects depend on infiltrated immunostimulatory neutrophils. We show further that presence of tumour-associated neutrophils is significantly associated with better survival in NPC patients. Thus, tumour inflammasomes play a key role in tumour control by recruiting neutrophils, and their expression levels are favourable prognostic markers and promising therapeutic targets in patients. PMID:23065753

  5. LASSO-based NTCP model for radiation-induced temporal lobe injury developing after intensity-modulated radiotherapy of nasopharyngeal carcinoma.

    PubMed

    Kong, Cheng; Zhu, Xiang-Zhi; Lee, Tsair-Fwu; Feng, Ping-Bo; Xu, Jian-Hua; Qian, Pu-Dong; Zhang, Lan-Fang; He, Xia; Huang, Sheng-Fu; Zhang, Yi-Qin

    2016-01-01

    We investigated the incidence of temporal lobe injury (TLI) in 132 nasopharyngeal carcinoma (NPC) patients who had undergone intensity-modulated radiotherapy (IMRT) in our hospital between March 2005 and November 2009; and identified significant dosimetric predictors of TLI development. Contrast-enhanced lesions or cysts in the temporal lobes, as detected by magnetic resonance imaging (MRI), were regarded as radiation-induced TLIs. We used the least absolute shrinkage and selection operator (LASSO) method to select Dmax (the maximum point dose) and the D1cc (the top dose delivered to a 1-mL volume) from 15 dose-volume-histogram-associated and four clinically relevant candidate factors; the Dmax and the D1cc were the most significant predictors of TLI development. We drew dose-response curves for Dmax and D1cc. The tolerance dose (TD) for the 5% and 50% probabilities of TLI development were 69.0 ± 1.6 and 82.1 ± 2.4 Gy for Dmax and 62.8 ± 2.2 and 80.9 ± 3.4 Gy for D1cc, respectively. The incidence of TLI in NPC patients after IMRT was higher than expected because the therapeutic window is narrow. High-quality longitudinal studies are needed to gain further insight into the complex spatiotemporal effects of non-uniform irradiation on TLI development in NPC patients. PMID:27210263

  6. Dose-volume relationships for moderate or severe neck muscle atrophy after intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma.

    PubMed

    Zhang, Lu-Lu; Wang, Xiao-Ju; Zhou, Guan-Qun; Tang, Ling-Long; Lin, Ai-Hua; Ma, Jun; Sun, Ying

    2015-01-01

    This study aimed to identify the dosimetric parameters and radiation dose tolerances associated with moderate or severe sternocleidomastoid muscle (SCM) atrophy after intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). We retrospectively analysed 138 patients treated with IMRT between 2011 and 2012 for whom IMRT treatment plans and pretreatment and 3-year post-IMRT MRI scans were available. The association between mean dose (Dmean), maximum dose (Dmax), VX (% SCM volume that received more than X Gy), DX (dose to X% of the SCM volume) at X values of 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80 and SCM atrophy at 3 years after IMRT were analyzed. All dosimetric parameters, except V40, V50 and V80, were significantly associated with moderate or severe SCM atrophy. Multivariate analysis showed that V65 was an independent predictor of moderate or severe SCM atrophy (P < 0.001). Receiver operating characteristic (ROC) curve indicated a V65 of 21.47% (area under ROC curves, 0.732; P < 0.001) was the tolerated dose for moderate or severe SCM atrophy. We suggest a limit of 21.47% for V65 to optimize NPC treatment planning, whilst minimizing the risk of moderate or severe SCM atrophy. PMID:26678599

  7. Efficacy of the Additional Neoadjuvant Chemotherapy to Concurrent Chemoradiotherapy for Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: a Bayesian Network Meta-analysis of Randomized Controlled Trials

    PubMed Central

    Chen, Yu-Pei; Guo, Rui; Liu, Na; Liu, Xu; Mao, Yan-Ping; Tang, Ling-Long; Zhou, Guan-Qun; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2015-01-01

    Background: Due to the lack of studies, it remains unclear whether the additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) is superior to CCRT alone for locoregionally advanced nasopharyngeal carcinoma (NPC). The main objective of this Bayesian network meta-analysis was to determine the efficacy of NACT+CCRT as compared with CCRT alone. Methods: We comprehensively searched databases and extracted data from randomized controlled trials involving NPC patients who received NACT+CCRT, CCRT, NACT+radiotherapy (RT), or RT. Overall survival (OS) with hazard ratio (HR), and locoregional recurrence rate (LRR) and distant metastasis rate (DMR) with relative risks (RRs), were concerned. Results: Nine trials involving 1988 patients were analyzed. In the network meta-analysis, there was significant benefit of NACT+CCRT over CCRT for DMR (RR=0.54, 95% credible interval [CrI]=0.27-0.94). However, NACT+CCRT had a tendency to worsen locoregional control significantly as compared with CCRT (RR =1.71, 95%CrI =0.94-2.84), and no significant improvement in OS was found (HR =0.73, 95%CrI=0.40-1.23). Conclusions: NACT+CCRT is associated with reduced distant failure as compared with CCRT alone, and whether the additional NACT can improve survival for locoregionally advanced NPC should be further explored. Optimizing regimens and identifying patients at high risk of metastasis may enhance the efficacy of NACT+CCRT. PMID:26284140

  8. The Evolution of and Risk Factors for Neck Muscle Atrophy and Weakness in Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy

    PubMed Central

    Zhang, Lu-Lu; Mao, Yan-Ping; Zhou, Guan-Qun; Tang, Ling-Long; Qi, Zhen-Yu; Lin, Li; Yao, Ji-Jin; Ma, Jun; Lin, Ai-Hua; Sun, Ying

    2015-01-01

    Abstract The aim of this study was to investigate the evolution of sternocleidomastoid muscle (SCM) atrophy in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT), and the relationship between SCM atrophy and neck weakness. Data were retrospectively analyzed from 223 biopsy-proven NPC patients with no distant metastasis who underwent IMRT with or without chemotherapy. The volume of SCM was measured on pretreatment magnetic resonance imaging (MRI), and MRIs were conducted 1, 2, and 3 years after the completion of IMRT. Change in SCM volume was calculated and classified using the late effects of normal tissues–subjective, objective, management, and analytic system. The grade of neck muscle weakness, classified by the Common Terminology Criteria for Adverse Events V 3.0, was measured 3 years after the completion of IMRT. The average SCM atrophy ratio was −10.97%, −18.65%, and −22.25% at 1, 2, and 3 years postirradiation, respectively. Multivariate analysis indicated N stage and the length of time after IMRT were independent prognostic variables. There were significant associations between the degree of SCM atrophy and neck weakness. Radical IMRT can cause significant SCM atrophy in NPC patients. A more advanced N stage was associated with more severe SCM atrophy, but no difference was observed between N2 and N3. SCM atrophy progresses over time during the 3 years following IMRT. Grade of SCM atrophy is significantly associated with neck weakness. PMID:26252307

  9. Dose-volume relationships for moderate or severe neck muscle atrophy after intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma

    PubMed Central

    Zhang, Lu-Lu; Wang, Xiao-Ju; Zhou, Guan-Qun; Tang, Ling-Long; Lin, Ai-Hua; Ma, Jun; Sun, Ying

    2015-01-01

    This study aimed to identify the dosimetric parameters and radiation dose tolerances associated with moderate or severe sternocleidomastoid muscle (SCM) atrophy after intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). We retrospectively analysed 138 patients treated with IMRT between 2011 and 2012 for whom IMRT treatment plans and pretreatment and 3-year post-IMRT MRI scans were available. The association between mean dose (Dmean), maximum dose (Dmax), VX (% SCM volume that received more than X Gy), DX (dose to X% of the SCM volume) at X values of 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80 and SCM atrophy at 3 years after IMRT were analyzed. All dosimetric parameters, except V40, V50 and V80, were significantly associated with moderate or severe SCM atrophy. Multivariate analysis showed that V65 was an independent predictor of moderate or severe SCM atrophy (P < 0.001). Receiver operating characteristic (ROC) curve indicated a V65 of 21.47% (area under ROC curves, 0.732; P < 0.001) was the tolerated dose for moderate or severe SCM atrophy. We suggest a limit of 21.47% for V65 to optimize NPC treatment planning, whilst minimizing the risk of moderate or severe SCM atrophy. PMID:26678599

  10. Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma.

    PubMed

    Cai, Longmei; Ye, Yanfen; Jiang, Qiang; Chen, Yuxiang; Lyu, Xiaoming; Li, Jinbang; Wang, Shuang; Liu, Tengfei; Cai, Hongbing; Yao, Kaitai; Li, Ji-Liang; Li, Xin

    2015-01-01

    Epstein-Barr virus (EBV), aetiologically linked to nasopharyngeal carcinoma (NPC), is the first human virus found to encode many miRNAs. However, how these viral miRNAs precisely regulate the tumour metastasis in NPC remains obscure. Here we report that EBV-miR-BART1 is highly expressed in NPC and closely associated with pathological and advanced clinical stages of NPC. Alteration of EBV-miR-BART1 expression results in an increase in migration and invasion of NPC cells in vitro and causes tumour metastasis in vivo. Mechanistically, EBV-miR-BART1 directly targets the cellular tumour suppressor PTEN. Reduction of PTEN dosage by EBV-miR-BART1 activates PTEN-dependent pathways including PI3K-Akt, FAK-p130(Cas) and Shc-MAPK/ERK1/2 signalling, drives EMT, and consequently increases migration, invasion and metastasis of NPC cells. Reconstitution of PTEN rescues all phenotypes generated by EBV-miR-BART1, highlighting the role of PTEN in EBV-miR-BART-driven metastasis in NPC. Our findings provide new insights into the metastasis of NPC regulated by EBV and advocate for developing clinical intervention strategies against NPC. PMID:26135619

  11. Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities

    PubMed Central

    Guo, Rui; Tang, Ling-Long; Mao, Yan-Ping; Zhou, Guan-Qun; Qi, Zhen-Yu; Liu, Li-Zhi; Lin, Ai-Hua; Liu, Meng-Zhong

    2015-01-01

    Background To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC). Material and Methods 205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68–70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria. Results The median follow-up period was 37.3 months (range, 6.3–45.1 months). The 3-year estimated local failure–free survival, regional failure–free survival, locoregional failure–free survival, distant metastasis–free survival, disease–free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05). The most common acute and late side effects were grade 2–3 mucositis (78%) and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT), respectively. Conclusions VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy. PMID:26146828

  12. Reversal effect of GnT-V on the radioresistance of human nasopharyngeal carcinoma cells by alteration β1, 6-GlcNAc branched N-glycans

    PubMed Central

    Wu, Jun-Bo; Shen, Li; Qiu, Li; Duan, Qi-Wen; Luo, Zhi-Guo; Dong, Xiao-Xia

    2015-01-01

    Radiotherapy is the primary treatment for human nasopharyngeal carcinoma (NPC), yet radioresistance remains a major obstacle to successful treatment in many cases. N-acetylglucosaminyltransferase V (GnT-V), which synthesizes β1, 6-GlcNAc branched N-glycans, is closely related to the radiosensitivity of NPC cells. However, a better understanding of the functional role of GnT-V in NPC radioresistance and the related mechanisms is urgently needed. In the present study, a radioresistant NPC cell line, CNE-2R, was established by repeated γ-irradiation. We found that GnT-V levels, as well as β1, 6-GlcNAc branched N-glycans were significantly increased in the CNE-2R cells as compared with that in the parental cells. Meanwhile, knockdown of GnT-V in the CNE-2R cells enhanced cell radiosensitivity and inhibited the formation of β1, 6-branched N-glycans. In addition, the regulated expression of GnT-V in the CNE-2R cells converted the heterogeneous N-glycosylated forms of CD147. Furthermore, swainsonine, an inhibitor of N-glycan biosynthesis, was also able to reverse the radioresistance of the CNE-2R cells. Taken together, the present study revealed a novel mechanism of GnT-V as a regulator of radioresistance in NPC cells, which may be useful for fully understanding the biological role of N-glycans in NPC radioresistance. PMID:26617699

  13. An open-label, single-arm phase II clinical study of docetaxel plus lobaplatin for Chinese patients with pulmonary and hepatic metastasis of nasopharyngeal carcinoma.

    PubMed

    Zhang, Shuai; Chen, Junni; Yang, Shiping; Lin, Shaomin

    2016-08-01

    To evaluate the efficacy and safety of the chemotherapy program of docetaxel combined with lobaplatin for Chinese patients with pulmonary and hepatic metastasis of nasopharyngeal carcinoma (NPC). This study included 37 NPC patients with pulmonary and hepatic metastasis. The chemotherapy program included docetaxel (75 mg/m, day 1) plus lobaplatin (30 mg/m, day 1). Cycle repetition was every 21 days. Patients were monitored for 7-41 months, with a median follow-up duration of 18 months. The total efficiency of this group was 67.6% and the disease control rate was 81.1%. The median progression-free survival was 9.4 months (95% confidence interval, 6.8-14.3 months), the median overall survival was 18.3 months (95% confidence interval, 13.7-22.8 months), and the 2-year survival rate was 37.8%. The main hematological toxicities were leukopenia (91.9%), anemia (81.1%), and thrombocytopenia (70.3%); other adverse reactions were mild. Changes in Epstein-Barr-DNA levels can basically reflect the dynamic changes in the efficacy of chemotherapy. Docetaxel combined with lobaplatin has a favorable outcome for the treatment of pulmonary and hepatic metastatic NPC. It has been a convenient regimen with tolerable toxicity. PMID:27088576

  14. Baseline Serum Lactate Dehydrogenase Levels for Patients Treated With Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: A Predictor of Poor Prognosis and Subsequent Liver Metastasis

    SciTech Connect

    Zhou Guanqun; Tang Linglong; Mao Yanping; Chen Lei; Li Wenfei; Sun Ying; Liu Lizhi; Li Li; Lin Aihua; Ma Jun

    2012-03-01

    Purpose: To evaluate the prognostic value of baseline serum lactate dehydrogenase (LDH) levels in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Cases of NPC (n = 465) that involved treatment with IMRT with or without chemotherapy were retrospectively analyzed. Results: The mean ({+-}SD) and median baseline serum LDH levels for this cohort were 172.77 {+-} 2.28 and 164.00 IU/L, respectively. Levels of LDH were significantly elevated in patients with locoregionally advanced disease (p = 0.016). Elevated LDH levels were identified as a prognostic factor for rates of overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS), with p values <0.001 in the univariate analysis and p < 0.001, p = 0.004, and p = 0.003, respectively, in the multivariate analysis. Correspondingly, the prognostic impact of patient LDH levels was found to be statistically significant for rates of OS, DFS, and DMFS (p = 0.028, 0.024, and 0.020, respectively). For patients who experienced subsequent liver failure after treatment, markedly higher pretreatment serum LDH levels were detected compared with patients experiencing distant metastasis events at other sites (p = 0.032). Conclusions: Elevated baseline LDH levels are associated with clinically advanced disease and are a poor prognosticator for OS, DFS, and DMFS for NPC patients. These results suggest that elevated serum levels of LDH should be considered when evaluating treatment options.

  15. Selenium-binding protein 1 in head and neck cancer is low-expression and associates with the prognosis of nasopharyngeal carcinoma

    PubMed Central

    Chen, Fasheng; Chen, Chen; Qu, Yangang; Xiang, Hua; Ai, Qingxiu; Yang, Fei; Tan, Xueping; Zhou, Yi; Jiang, Guang; Zhang, Zixiong

    2016-01-01

    Abstract Background: Selenium-binding protein 1 (SELENBP1) expression is reduced markedly in many types of cancers and low SELENBP1 expression levels are associated with poor patient prognosis. Methods: SELENBP1 gene expression in head and neck squamous cell carcinoma (HNSCC) was analyzed with GEO dataset and characteristics of SELENBP1 expression in paraffin embedded tissue were summarized. Expression of SELENBP1 in nasopharyngeal carcinoma (NPC), laryngeal cancer, oral cancer, tonsil cancer, hypopharyngeal cancer and normal tissues were detected using immunohistochemistry, at last, 99 NPC patients were followed up more than 5 years and were analyzed the prognostic significance of SELENBP1. Results: Analysis of GEO dataset concluded that SELENBP1 gene expression in HNSCC was lower than that in normal tissue (P < 0.01), but there was no significant difference of SELENBP1 gene expression in different T-stage and N-stage (P > 0.05). Analysis of pathological section concluded that SELENBP1 in the majority of HNSCC is low expression and in cancer nests is lower expression than surrounding normal tissue, even associated with the malignant degree of tumor. Further study indicated the low SELENBP1 expression group of patients with NPC accompanied by poor overall survival and has significantly different comparing with the high expression group. Conclusion: SELENBP1 expression was down-regulated in HNSCC, but has no associated with T-stage and N-stage of tumor. Low expression of SELENBP1 in patients with NPC has poor over survival, so SELENBP1 could be a novel biomarker for predicting prognosis. PMID:27583873

  16. SU-E-J-111: The Contouring Error of the Parotids Based On the CT and MRI Images in Radiotherapy Planning for Nasopharyngeal Carcinoma

    SciTech Connect

    Gong, G; Liu, C

    2014-06-01

    Purpose: To analyze the variation of sketching the parotid for patients with nasopharyngeal carcinoma who underwent radiotherapy based on computed tomography (CT) and magnetic resonance(MR) images. Methods: 41 nasopharyngeal cancer patients were randomly selected. Each patient underwent MR and CT scanning. The Gross Tumor Volume and Organs at risk were contoured on both contrasted CT and T1-MR images. For each patient, one radiotherapist sketched the parotid on CT and MR images for 10 times, and 10 different radiotherapists were asked to sketching the parotid on CT and MR images only one time. The inter- and intra-observers volumes and outline variations were compared. Results: The volumes of parotid contoured by inter-observer on CT and MR images were 34.6±12.1cm{sup 3}(left),34.3±9.0cm{sup 3}(right) and 24.6±7.6cm{sup 3}(L),23.2±8.1cm{sup 3}(R); In the same way, for intra-observer on CT and MR images the volumes were 28.2±7.6cm{sup 3}(L),29.4±9.4cm{sup 3}(R) and 24.4±7.6cm{sup 3}(L),22.5±7.4cm{sup 3}(R), respectively. The variable ratios of volume on MR images were 4.7±0.7%(L),5.0±0.6%(R) for inter-observer and 2.3±0.4%(L),2.1±0.7%(R) for intra-observer. Similarly, The inter- and intra-observer ratios for contouring on CT images reached 18.0±4.8%(L),17.4±4.6%(R) and 6.3±1.5%(L),6.8±1.5%(R), respectively. Conclusion: Contouring the parotids on MR images was more accurate and reproducible than that on CT images.

  17. A Glucosamine-Specific Lectin from Green Dragon No. 8 Beans (Phaseolus vulgaris) Induced Apoptosis on Nasopharyngeal Carcinoma Cells

    PubMed Central

    Chan, Yau Sang; Xia, Lixin; Ng, Tzi Bun

    2015-01-01

    A lectin exhibiting antiproliferative activity on tumor cell lines but devoid of antifungal activity has been purified from Phaseolus vulgaris cv. Green Dragon no. 8 seeds. The lectin was a 60 kDa dimeric protein with two 30 kDa subunits. It was a glucosamine-specific lectin as implied from the inhibitory effect of glucosamine on hemagglutinating activity of the lectin. The steps for isolation of the lectin involved Affi-gel blue gel (affinity gel), Mono Q (anion exchanger), and Superdex 75 column (size exclusion). The lectin was purified 20.8-fold from the crude extract of the beans. The purified lectin showed antiproliferative activity on breast cancer MCF7 cell line and nasopharyngeal cancer HONE1 and CNE2 cell lines, but a low activity on normal skin fibroblast HSF98 cell line. The lectin was shown to induce apoptosis on HONE1 cells, as indicated by increased phosphatidylserine externalization and mitochondrial depolarization. It also blocked HONE1 cell division and kept the cells at the G2/M phase of the cell cycle. PMID:26290674

  18. Comprehensive High-Throughput RNA Sequencing Analysis Reveals Contamination of Multiple Nasopharyngeal Carcinoma Cell Lines with HeLa Cell Genomes

    PubMed Central

    Strong, Michael J.; Baddoo, Melody; Nanbo, Asuka; Xu, Miao; Puetter, Adriane

    2014-01-01

    ABSTRACT In an attempt to explore infectious agents associated with nasopharyngeal carcinomas (NPCs), we employed our high-throughput RNA sequencing (RNA-seq) analysis pipeline, RNA CoMPASS, to investigate the presence of ectopic organisms within a number of NPC cell lines commonly used by NPC and Epstein-Barr virus (EBV) researchers. Sequencing data sets from both CNE1 and HONE1 were found to contain reads for human papillomavirus 18 (HPV-18). Subsequent real-time reverse transcription-PCR (RT-PCR) analysis on a panel of NPC cell lines identified HPV-18 in CNE1 and HONE1 as well as three additional NPC cell lines (CNE2, AdAH, and NPC-KT). Further analysis of the chromosomal integration arrangement of HPV-18 in NPCs revealed patterns identical to those observed in HeLa cells. Clustering based on human single nucleotide variation (SNV) analysis of two separate HeLa cell lines and several NPC cell lines demonstrated two distinct clusters with CNE1, as well as HONE1 clustering with the two HeLa cell lines. In addition, duplex-PCR-based genotyping showed that CNE1, CNE2, and HONE1 do not have a HeLa cell-specific L1 retrotransposon insertion, suggesting that these three HPV-18+ NPC lines are likely products of a somatic hybridization with HeLa cells, which is also consistent with our RNA-seq-based gene level SNV analysis. Taking all of these findings together, we conclude that a widespread HeLa contamination may exist in many NPC cell lines, and authentication of these cell lines is recommended. Finally, we provide a proof of concept for the utility of an RNA-seq-based approach for cell authentication. IMPORTANCE Nasopharyngeal carcinoma (NPC) cell lines are important model systems for analyzing the complex life cycle and pathogenesis of Epstein-Barr virus (EBV). Using an RNA-seq-based approach, we found HeLa cell contamination in several NPC cell lines that are commonly used in the EBV and related fields. Our data support the notion that contamination resulted from

  19. Comparison of 3D anatomical dose verification and 2D phantom dose verification of IMRT/VMAT treatments for nasopharyngeal carcinoma

    PubMed Central

    2014-01-01

    Background The two-dimensional phantom dose verification (2D-PDV) using hybrid plan and planar dose measurement has been widely used for IMRT treatment QA. Due to the lack of information about the correlations between the verification results and the anatomical structure of patients, it is inadequate in clinical evaluation. A three-dimensional anatomical dose verification (3D-ADV) method was used in this study to evaluate the IMRT/VMAT treatment delivery for nasopharyngeal carcinoma and comparison with 2D-PDV was analyzed. Methods Twenty nasopharyngeal carcinoma (NPC) patients treated with IMRT/VMAT were recruited in the study. A 2D ion-chamber array was used for the 2D-PDV in both single-gantry-angle composite (SGAC) and multi-gantry-angle composite (MGAC) verifications. Differences in the gamma pass rate between the 2 verification methods were assessed. Based on measurement of irradiation dose fluence, the 3D dose distribution was reconstructed for 3D-ADV in the above cases. The reconstructed dose homogeneity index (HI), conformity index (CI) of the planning target volume (PTV) were calculated. Gamma pass rate and deviations in the dose-volume histogram (DVH) of each PTV and organ at risk (OAR) were analyzed. Results In 2D-PDV, the gamma pass rate (3%, 3 mm) of SGAC (99.55% ± 0.83%) was significantly higher than that of MGAC (92.41% ± 7.19%). In 3D-ADV, the gamma pass rates (3%, 3 mm) were 99.75% ± 0.21% in global, 83.82% ± 16.98% to 93.71% ± 6.22% in the PTVs and 45.12% ± 32.78% to 98.08% ± 2.29% in the OARs. The maximum HI increment in PTVnx was 19.34%, while the maximum CI decrement in PTV1 and PTV2 were -32.45% and -6.93%, respectively. Deviations in dose volume of PTVs were all within ±5%. D2% of the brainstem, spinal cord, left/right optic nerves, and the mean doses to the left/right parotid glands maximally increased by 3.5%, 6.03%, 31.13%/26.90% and 4.78%/4.54%, respectively. Conclusion The 2D-PDV and global gamma

  20. NF-κB Signaling Regulates Expression of Epstein-Barr Virus BART MicroRNAs and Long Noncoding RNAs in Nasopharyngeal Carcinoma

    PubMed Central

    Verhoeven, Rob J. A.; Tong, Shuang; Zhang, Gaohong; Zong, Jingfeng; Chen, Yixin; Chen, Mei-Ru; Pan, Jianji

    2016-01-01

    ABSTRACT Epstein-Barr virus (EBV) expresses few viral proteins in nasopharyngeal carcinoma (NPC) but high levels of BamHI-A rightward transcripts (BARTs), which include long noncoding RNAs (lncRNAs) and BART microRNAs (miRNAs). It is hypothesized that the mechanism for regulation of BARTs may relate to EBV pathogenesis in NPC. We showed that nuclear factor-κB (NF-κB) activates the BART promoters and modulates the expression of BARTs in EBV-infected NPC cells but that introduction of mutations into the putative NF-κB binding sites abolished activation of BART promoters by NF-κB. Binding of p50 subunits to NF-κB sites in the BART promoters was confirmed in electrophoretic mobility shift assays (EMSA) and further demonstrated in vivo using chromatin immunoprecipitation (ChIP) analysis. Expression of BART miRNAs and lncRNAs correlated with NF-κB activity in EBV-infected epithelial cells, while treatment of EBV-harboring NPC C666-1 cells with aspirin (acetylsalicylic acid [ASA]) and the IκB kinase inhibitor PS-1145 inhibited NF-κB activity, resulting in downregulation of BART expression. Expression of EBV LMP1 activates BART promoters, whereas an LMP1 mutant which cannot induce NF-κB activation does not activate BART promoters, further supporting the idea that expression of BARTs is regulated by NF-κB signaling. Expression of LMP1 is tightly regulated in NPC cells, and this study confirmed that miR-BART5-5p downregulates LMP1 expression, suggesting a feedback loop between BART miRNA and LMP1-mediated NF-κB activation in the NPC setting. These findings provide new insights into the mechanism underlying the deregulation of BARTs in NPC and identify a regulatory loop through which BARTs support EBV latency in NPC. IMPORTANCE Nasopharyngeal carcinoma (NPC) cells are ubiquitously infected with Epstein-Barr virus (EBV). Notably, EBV expresses very few viral proteins in NPC cells, presumably to avoid triggering an immune response, but high levels of EBV BART mi

  1. Effect of Dosimetric Factors on Occurrence and Volume of Temporal Lobe Necrosis Following Intensity Modulated Radiation Therapy for Nasopharyngeal Carcinoma: A Case-Control Study

    SciTech Connect

    Zhou, Xin; Ou, Xiaomin; Xu, Tingting; Wang, Xiaosheng; Shen, Chunying; Ding, Jianhui; Hu, Chaosu

    2014-10-01

    Purpose: To determine dosimetric risk factors for the occurrence of temporal lobe necrosis (TLN) among nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT) and to investigate the impact of dose-volume histogram (DVH) parameters on the volume of TLN lesions (V-N). Methods and Materials: Forty-three NPC patients who had developed TLN following IMRT and 43 control subjects free of TLN were retrospectively assessed. DVH parameters included maximum dose (Dmax), minimum dose (Dmin), mean dose (Dmean), absolute volumes receiving specific dose (Vds) from 20 to 76 Gy (V20-V76), and doses covering certain volumes (Dvs) from 0.25 to 6.0 cm{sup 3} (D0.25-D6.0). V-Ns were quantified with axial magnetic resonance images. Results: DVH parameters were ubiquitously higher in temporal lobes with necrosis than in healthy temporal lobes. Increased Vds and Dvs were significantly associated with higher risk of TLN occurrence (P<.05). In particular, Vds at a dose of ≥70 Gy were found with the highest odds ratios. A common increasing trend was detected between V-N and DVH parameters through trend tests (P for trend of <.05). Linear regression analysis showed that V45 had the strongest predictive power for V-N (adjusted R{sup 2} = 0.305, P<.0001). V45 of <15.1 cm{sup 3} was relatively safe as the dose constraint for preventing large TLN lesions with V-N of >5 cm{sup 3}. Conclusions: Dosimetric parameters are significantly associated with TLN occurrence and the extent of temporal lobe injury. To better manage TLN, it would be important to avoid both focal high dose and moderate dose delivered to a large area in TLs.

  2. Comparison of the short-term efficacy between docetaxel plus carboplatin and 5-fluorouracil plus carboplatin in locoregionally advanced nasopharyngeal carcinoma

    PubMed Central

    Lv, Xing; Xia, Wei-Xiong; Ke, Liang-Ru; Yang, Jing; Qiu, Wen-Zhe; Yu, Ya-Hui; Liang, Hu; Huang, Xin-Jun; Liu, Guo-Yin; Zeng, Qi; Guo, Xiang; Xiang, Yan-Qun

    2016-01-01

    Objective Platinum-based chemotherapy in combination with radiotherapy is a standard treatment strategy for locoregionally advanced nasopharyngeal carcinoma (NPC). This study aimed to investigate the long-term efficacy and tolerability of inductive chemotherapy with docetaxel plus carboplatin (TC) or 5-fluorouracil plus carboplatin (FC) followed by concurrent radiation therapy in patients with NPC. Methods Patients (N=88) were randomized to receive TC or FC as inductive therapy followed by concurrent radiotherapy (60–70 Gy) with two cycles of carboplatin (area under the curve =5 mg·h/L). Patients were followed up for 8 years. Primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, tumor response, distant metastasis-free survival, and local recurrence-free survival. Results At the end of the follow-up period, 31 patients died, 32 had disease progression, eleven had cancer recurrence, and 25 had distant metastasis. Overall, there was no difference between treatment groups with regard to response or survival. We found that following induction and concurrent chemoradiotherapy, the majority of patients showed a complete response (~96%–98% for induction therapy and 82%–84% for comprehensive therapy) to both therapies. PFS and OS were also similar between groups. The rate of PFS was 63.6% for both FC and TC and that of OS was 65.9% and 63.5%, respectively. The overall incidence of grade 3–4 adverse events in the TC group (20.5%) was higher than in the FC group (10.7%). Neutropenia and leukopenia were the most common grade 3–4 adverse events in the TC group, and mucositis was the most common in the FC group. Conclusion These data indicate that TC and FC therapies have similar efficacy in treating locally advanced NPC and both are well tolerated. PMID:27574453

  3. Folate, vitamin B6, vitamin B12 and methionine intakes and risk for nasopharyngeal carcinoma in Chinese adults: a matched case-control study.

    PubMed

    Zeng, Fang-fang; Liu, Yuan-ting; Lin, Xiao-ling; Fan, Yu-Ying; Zhang, Xing-lan; Xu, Chun-hua; Chen, Yu-ming

    2016-01-14

    Many studies have suggested that folate-related one-carbon metabolism-related nutrients may play a role in certain cancer risks, but few studies have assessed their associations with the risk for nasopharyngeal carcinoma (NPC). In this study, we investigated the association between four folate-related one-carbon metabolism-related nutrients (folate, vitamin B6, vitamin B12 and methionine) and NPC risk in Chinese adults. A total of 600 patients newly diagnosed (within 3 months) with NPC were individually matched with 600 hospital-based controls by age, sex and household type (urban v. rural). Folate, vitamin B6, vitamin B12 and methionine intakes were measured using a validated seventy-eight-item FFQ. A higher dietary folate or vitamin B6 intake was associated with a lower NPC risk after adjusting for potential confounders. The adjusted OR of NPC for quartiles 2-4 (v. 1) were 0·66 (95% CI 0·48, 0·91), 0·52 (95% CI 0·37, 0·74) and 0·34 (95% CI 0·23, 0·50) (P(trend)<0·001) for folate and 0·72 (95% CI 0·52, 1·00), 0·55 (95% CI 0·39, 0·78) and 0·44 (95% CI 0·30, 0·63) (P(trend)<0·001) for vitamin B6. No significant association with NPC risk was observed for dietary vitamin B12 or methionine intake. The risk for NPC with dietary folate intake was more evident in the participants who were not exposed to toxic substances than in those who were exposed (P(interaction)=0·014). This study suggests that dietary folate and vitamin B6 may be protective for NPC in a high-risk population. PMID:26515433

  4. A Broadly Adaptive Array of Dose-Constraint Templates for Planning of Intensity-Modulated Radiation Therapy for Advanced T-Stage Nasopharyngeal Carcinoma

    SciTech Connect

    Chau, R.M.-C. Leung, S.-F.; Kam, M.K.-M.; Cheung, K.-Y.; Kwan, W.-H.; Yu, K.-H.; Chiu, K.-W.; Cheung, M.L.-M.; Chan, A.T.-C.

    2009-05-01

    Purpose: To develop and validate adaptive dose-constraint templates in intensity-modulated radiotherapy (IMRT) planning for advanced T-stage nasopharyngeal carcinoma (NPC). Method and Materials: Dose-volume histograms of clinically approved plans for 20 patients with advanced T-stage NPC were analyzed, and the pattern of distribution in relation to the degree of overlap between targets and organs at risk (OARs) was explored. An adaptive dose constraint template (ADCT) was developed based on the degree of overlap. Another set of 10 patients with advanced T-stage NPC was selected for validation. Results of the manual arm optimization protocol and the ADCT optimization protocol were compared with respect to dose optimization time, conformity indices, multiple-dose end points, tumor control probability, and normal tissue complication probability. Results: For the ADCT protocol, average time required to achieve an acceptable plan was 9 minutes, with one optimization compared with 94 minutes with more than two optimizations of the manual arm protocol. Target coverage was similar between the manual arm and ADCT plans. A more desirable dose distribution in the region of overlap between planning target volume and OARs was achieved in the ADCT plan. Dose end points of OARs were similar between the manual arm and ADCT plans. Conclusions: With the developed ADCT, IMRT treatment planning becomes more efficient and less dependent on the planner's experience on dose optimization. The developed ADCT is applicable to a wide range of advanced T-stage NPC treatment and has the potential to be applied in a broader context to IMRT planning for other cancer sites.

  5. Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma

    SciTech Connect

    Lee, Anne W.M. . E-mail: awmlee@ha.org.hk; Tung, Stewart Y.; Chan, Anthony T.C.; Chappell, Rick; Fu, Y.-T.; Lu, Tai-Xiang; Tan, Terence; Chua, Daniel T.T.; O'Sullivan, Brian; Xu, Shirley L.; Pang, Ellie S.Y.; Sze, W.-M.; Leung, T.-W.; Kwan, W.-H.; Chan, Paddy; Liu, X.-F.; Tan, E.-H.; Sham, Jonathan; Siu, Lillian; Lau, W.-H.

    2006-09-01

    Purpose: To compare the benefit achieved by concurrent chemoradiotherapy (CRT) and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with conventional fractionation (CF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma (NPC). Methods and Materials: All patients were irradiated with the same RT technique to {>=}66 Gy at 2 Gy per fraction, conventional five fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5-fluorouracil). Results: Between 1999 and April 2004, 189 patients were randomly assigned; the trial was terminated early because of slow accrual. The median follow-up was 2.9 years. When compared with the CF arm, significant improvement in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3 years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p {>=} 0.38). Multivariate analyses showed that CRT was a significant factor: hazard ratio (HR) = 0.52 (0.28-0.97), AF per se was insignificant: HR = 0.68 (0.37-1.25); the interaction of CRT by AF was strongly significant (p = 0.006). Both CRT arms had significant increase in acute toxicities (p < 0.005), and the AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3 years, p = 0.05). Conclusions: Preliminary results suggest that concurrent chemoradiotherapy with accelerated fractionation could significantly improve tumor control when compared with conventional RT alone; further confirmation of therapeutic ratio is warranted.

  6. Epstein-Barr virus glycoprotein gH/gL antibodies complement IgA-viral capsid antigen for diagnosis of nasopharyngeal carcinoma

    PubMed Central

    Tang, Lin-Quan; Zhang, Hua; Li, Yan; Liu, Wan-Li; Zhong, Qian; Zeng, Mu-Sheng; Huang, Xiao-Ming

    2016-01-01

    To determine whether measuring antibodies against Epstein-Barr virus (EBV) glycoprotein gH/gL in serum could improve diagnostic accuracy in nasopharyngeal carcinoma (NPC) cases, gH/gL expressed in a recombinant baculovirus system was used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in two independent cohorts. Binary logistic regression analyses were performed using results from a training cohort (n = 406) to establish diagnostic mathematical models, which were validated in a second independent cohort (n = 279). Levels of serum gH/gL antibodies were higher in NPC patients than in healthy controls (p < 0.001). In the training cohort, the IgA-gH/gL ELISA had a sensitivity of 83.7%, specificity of 82.3% and area under the curve (AUC) of 0.893 (95% CI, 0.862-0.924) for NPC diagnosis. Furthermore, gH/gL maintained diagnostic capacity in IgA-VCA negative NPC patients (sensitivity = 78.1%, specificity = 82.3%, AUC = 0.879 [95% CI, 0.820 - 0.937]). Combining gH/gL and viral capsid antigen (VCA) detection improved diagnostic capacity as compared to individual tests alone in both the training cohort (sensitivity = 88.5%, specificity = 97%, AUC = 0.98 [95% CI, 0.97 - 0.991]), and validation cohort (sensitivity = 91.2%, specificity = 96.5%, AUC = 0.97 [95% CI, 0.951-0.988]). These findings suggest that EBV gH/gL detection complements VCA detection in the diagnosis of NPC and aids in the identification of patients with VCA-negative NPC. PMID:27093005

  7. UBE2T promotes nasopharyngeal carcinoma cell proliferation, invasion, and metastasis by activating the AKT/GSK3β/β-catenin pathway

    PubMed Central

    Cao, Chuanhui; Hua, Shengni; Wu, Dehua

    2016-01-01

    Increasing evidence has shown that UBE2T plays an important role in genomic integrity and carcinogenesis; however, its role in nasopharyngeal carcinoma (NPC) has not been investigated. Here, we evaluated the clinicopathological significance of UBE2T in NPC and its underlying mechanisms. Using immunohistochemical analysis of UBE2T expression in NPC samples, we demonstrated that UBE2T is highly expressed in NPC tissues, which correlated with the T/M classification, skull invasion, and poor prognosis. The in vitro assay showed that UBE2T overexpression promoted proliferation, migration, and invasion of NPC cells, while UBE2T knockdown inhibited these processes. Consistent with our in vitro results, in vivo studies indicated that UBE2T overexpression promoted the growth of NPC xenografts and NPC cell metastasis. We found that UBE2T overexpression activated, whereas UBE2T knockdown inhibited, the AKT/GSK3β/β-catenin pathway. Moreover, the pathway-activation and in vitro pro-metastasis effects of UBE2T were blocked by the AKT inhibitor, MK-2206 2HCl. Additionally, UBE2T and p-GSK3 β co-expressed in NPC samples by serial section, and their expressions are correlated. Collectively, our findings demonstrated that UBE2T is a possible diagnostic/prognostic biomarker for NPC and may promote the development and progression of NPC by activating the AKT/GSK3β/β-catenin pathway. Thus, UBE2T could serve as an alternative target for the treatment of NPC. PMID:26943030

  8. Prognostic Value of Neoadjuvant Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma with Low Pre-treatment Epstein-Barr Virus DNA: a Propensity-matched Analysis

    PubMed Central

    Peng, Hao; Chen, Lei; Li, Wen-Fei; Guo, Rui; Zhang, Yuan; Zhang, Fan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    Background: The aim of this study is to investigate the prognostic value of neoadjuvant chemotherapy (NCT) in locoregionally advanced nasopharyngeal carcinoma (NPC) with low pre-treatment Epstein-Barr virus (EBV) DNA in the era of intensity-modulated radiotherapy (IMRT). Methods: Data on 1099 locoregionally advanced NPC patients treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance influence of covariates. Patient survival between NCT and non-NCT groups were compared. Results: The cut-off value of pre-treatment Epstein-Barr virus DNA (pre-DNA) was 1550 copies/ml for DMFS (area under curve [AUC], 0.655; sensitivity, 0.819; specificity, 0.445). For the 145 pairs selected by PSM, the 3-year distant metastasis-free survival (DMFS), overall survival (OS), disease-free survival (DFS) and locoregional relapse-free survival (LRRFS) rates were 98.6% vs. 93.7% (P = 0.101), 95.8% vs. 94.4% (P = 0.881), 91.7% vs. 87.5% (P = 0.309) and 94.4% vs. 95.0% (P = 0.667), respectively. Multivariate analysis did not identify NCT as an independent prognostic factor (P > 0.05 for all rates), and stratified analysis based on overall stage (III and IV) and N category (N0-1 and N2-3) also got the same results. Conclusion: NCT was not established as an independent prognostic factor, and it should not be used in locoregionally advanced NPC with low pre-DNA. PMID:27471562

  9. Clinical Study of the Necessity of Replanning Before the 25th Fraction During the Course of Intensity-Modulated Radiotherapy for Patients With Nasopharyngeal Carcinoma

    SciTech Connect

    Wang Wei; Yang Haihua; Hu Wei; Shan Guoping; Ding Weijun; Yu Changhui; Wang Biyun; Wang Xufeng; Xu Qianyi

    2010-06-01

    Purpose: To quantify the target and normal structures on dose distributing variations during intensity-modulated radiotherapy (IMRT) and to assess the value of replanning for nasopharyngeal carcinoma (NPC) patients. Methods and Materials: Twenty-eight NPC patients treated with IMRT were recruited. The IMRT was delivered in 33 fractions, to 70 to 76Gy, to the gross tumor volume (GTV). Before the 25th fraction of IMRT, a new simulation computed tomography (CT) scan was acquired for all patients. According to the dose constraint criterion in the Radiation Therapy Oncology Group (RTOG) 0225 protocol, the replanning was generated on the new simulation CT. With the Quality Assessment Center of a CORVUS 6.3 treatment planning system, a phantom plan was generated for each patient by applying the beam configurations of the initial plan to the anatomy of the new simulation CT. The dose-volume histograms of the phantom plan were compared with the replanning. Results: The percentage of prescription dose delivered to the clinical target volume (CTV1) was significantly increased by 4.91% +- 10.89%, whereas the maximum dose to the spinal cord, mean dose to the left parotid, and V30 to the right parotid were significantly decreased by 5.00 +- 9.23Gy, 4.23 +- 10.03Gy, and 11.47% +- 18.89% respectively in the replanning, compared with the phantom plan (p < 0.05). Based on the dose constraint criterion in the RTOG0225 protocol, 50% of phantom plans (14/28) were out of limit for the dose to the normal critical structures, whereas no plan was out of limit in replanning (p < 0.001). Conclusion: Replanning for patients with NPC before the 25th fraction during IMRT helps to ensure adequate dose to the target volumes and safe doses to critical normal structures.

  10. miR-504 mediated down-regulation of nuclear respiratory factor 1 leads to radio-resistance in nasopharyngeal carcinoma

    PubMed Central

    Zhao, Luqing; Tang, Min; Hu, Zheyu; Yan, Bin; Pi, Weiwei; Li, Zhi; Zhang, Jing; Zhang, Liqin; Jiang, Wuzhong; Li, Guo; Qiu, Yuanzheng; Hu, Fang; Liu, Feng; Lu, Jingchen; Chen, Xue; Xiao, Lanbo; Xu, Zhijie; Tao, Yongguang; Yang, Lifang; Bode, Ann M.; Dong, Zigang; Zhou, Jian; Fan, Jia; Sun, Lunquan; Cao, Ya

    2015-01-01

    microRNAs (miRNAs) are involved in the various processes of DNA damage repair and play crucial roles in regulating response of tumors to radiation therapy. Here, we used nasopharyngeal carcinoma (NPC) radio-resistant cell lines as models and found that the expression of miR-504 was significantly up-regulated. In contrast, the expression of nuclear respiratory factor 1 (NRF1) and other mitochondrial metabolism factors, including mitochondrial transcription factor A (TFAM) and oxidative phosphorylation (OXPHOS) complex III were down-regulated in these cell lines. At the same time, the Seahorse cell mitochondrial stress test results indicated that the mitochondrial respiratory capacity was impaired in NPC radio-resistant cell lines and in a miR-504 over-expressing cell line. We also conducted dual luciferase reporter assays and verified that miR-504 could directly target NRF1. Additionally, miR-504 could down-regulate the expression of TFAM and OXPHOS complexes I, III, and IV and impaired the mitochondrial respiratory function of NPC cells. Furthermore, serum from NPC patients showed that miR-504 was up-regulated during different weeks of radiotherapy and correlated with tumor, lymph nodes and metastasis (TNM) stages and total tumor volume. The radio-therapeutic effect at three months after radiotherapy was evaluated. Results indicated that patients with high expression of miR-504 exhibited a relatively lower therapeutic effect ratio of complete response (CR), but a higher ratio of partial response (PR), compared to patients with low expression of miR-504. Taken together, these results demonstrated that miR-504 affected the radio-resistance of NPC by down-regulating the expression of NRF1 and disturbing mitochondrial respiratory function. Thus, miR-504 might become a promising biomarker of NPC radio-resistance and targeting miR-504 might improve tumor radiation response. PMID:26201446

  11. Treatment of Stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation: Impact of chemotherapy schemes

    SciTech Connect

    Yau, T.K. . E-mail: tkokyau@gmail.com; Lee, Anne; Wong, Dominique; Pang, Ellie S.Y.; Ng, W.T.; Yeung, Rebecca; Soong, Inda S.

    2006-11-15

    Purpose: The aim of this study was to evaluate the impact of different chemotherapy regimens in patients with advanced nasopharyngeal carcinoma (NPC) treated by induction-concurrent chemoradiotherapy. Methods and Materials: Between 1998 and 2003, 75 Stage IV(A-B) NPC patients were treated with 3 cycles of induction chemotherapy with cisplatin plus 5-fluorouracil (PF) (n = 41) or cisplatin plus gemcitabine (PG) (n = 34), followed by accelerated radiotherapy in concurrence with 2 cycles of cisplatin. In 18 (24%) patients, cisplatin was completely replaced by carboplatin in both concurrent cycles, mainly because of borderline renal functions. Results: The median follow-up was 3.6 years. The 3-year locoregional failure-free survival, progression-free survival, and overall survival of the whole group were 80%, 68%, and 80% respectively. No significant difference was found between patients treated with either induction regimens. However, patients with only carboplatin in the 2 concurrent cycles had significantly inferior 3-year locoregional failure-free survival (56% vs. 86%, p = 0.014), progression-free survival (39% vs. 72%, p = 0.001), and overall survival (61% vs. 87%, p = 0.046) when compared with the rest of the group. In multivariate analysis, the complete replacement of cisplatin by carboplatin during concurrent chemoradiotherapy was still an independent adverse factor in locoregional failure-free survival (hazard ratio, 3.662; 95% CI, 1.145-11.765; p = 0.029) and progression-free survival (hazard ratio, 3.390; 95% CI, 1.443-7.937; p = 0.005). Conclusions: The more convenient PG regimen is as effective as the PF regimen as induction chemotherapy for patients with advanced NPC. Replacing cisplatin with carboplatin in the concurrent phase carries a poor prognosis.

  12. miR-29a/b enhances cell migration and invasion in nasopharyngeal carcinoma progression by regulating SPARC and COL3A1 gene expression.

    PubMed

    Qiu, Feifei; Sun, Rui; Deng, Ning; Guo, Tianyu; Cao, Yange; Yu, Ying; Wang, Xuejun; Zou, Bingcheng; Zhang, Songmei; Jing, Tao; Ling, Tao; Xie, Jun; Zhang, Qing

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with a genetic predisposition, Epstein-Barr virus infection and chromosomal abnormalities. Recently, several miRNAs have been shown to target specific mRNAs to regulate NPC development and progression. However, the involvement of miRNAs in processes leading to NPC migration and invasion remains to be elucidated. We predicted that miR-29a/b are associated with dysregulated genes controlling NPC through an integrated interaction network of miRNAs and genes. miR-29a/b over-expression in NPC cell lines had no significant effect on proliferation, whereas miR-29b mildly increased the percentage of cells in the G1 phase with a concomitant decrease in the percentage of cells in S phase. Furthermore, we demonstrated that miR-29a/b might be responsible for increasing S18 cell migration and invasion, and only COL3A1 was identified as a direct target of miR-29b despite the fact that both SPARC and COL3A1 were inhibited by miR-29a/b over-expression. Meanwhile, SPARC proteins were increased in metastatic NPC tissue and are involved in NPC progression. Unexpectedly, we identified that miRNA-29b expression was elevated in the serum of NPC patients with a high risk of metastasis. The 5-year actuarial overall survival rates in NPC patients with high serum miR-29b expression was significantly shorter than those with low serum miR-29b expression; therefore, serum miR-29b expression could be a promising prognostic marker. PMID:25786138

  13. Polymorphisms of XRCC1 and XRCC2 DNA Repair genes and Interaction with Environmental Factors Influence the Risk of Nasopharyngeal Carcinoma in Northeast India.

    PubMed

    Singh, Seram Anil; Ghosh, Sankar Kumar

    2016-01-01

    Multiple genetic and environmental factors have been reported to play key role in the development of nasopharyngeal carcinoma (NPC). Here, we investigated interactions of XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms and environmental factors in modulating susceptibility to NPC in Northeast India. One-hundred NPC patients, 90 first-degree relatives of patients and 120 controls were enrolled in the study. XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms were determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. The XRCC1 Gln/Gln genotype showed increased risk (OR=2.76; <0.024) of NPC. However, individuals with both XRCC1 and XRCC2 polymorphic variants had 3.2 fold elevated risk (<0.041). An enhanced risk of NPC was also observed in smoked meat (OR=4.07; P=0.004) and fermented fish consumers (OR=4.34, P=0.001), and tobacco-betel quid chewers (OR=7.00; P=0.0001) carrying XRCC1 polymorphic variants. However, smokers carrying defective XRCC1 gene showed the highest risk (OR = 7.47; <0.0001). On MDR analysis, the best model for NPC risk was the five-factor model combination of XRCC1 variant genotype, fermented fish, smoked meat, smoking and chewing (CVC=10/10; TBA=0.636; <0.0001); whereas in interaction entropy graphs, smoked meat and tobacco chewing showed synergistic interactions with XRCC1. These findings suggest that interaction of genetic and environmental factors might increase susceptibility to NPC in Northeast Indian populations. PMID:27356695

  14. Fabrication of multiwalled carbon nanotubes-magnetite nanocomposite as an effective ultra-sensing platform for the early screening of nasopharyngeal carcinoma by luminescence immunoassay.

    PubMed

    Liu, Chia-Ching; Sadhasivam, S; Savitha, S; Lin, Feng-Huei

    2014-05-01

    The hybrid nanocomposite that consists of multiwalled carbon nanotubes (MWCNTs) and magnetite (Fe₃O4) was fabricated by chemical co-precipitation method. Briefly, CNTs were oxidized with acids to form carboxylic group and then co-precipitated with Fe₃O4 to form CNT-Fe₃O4 nanocomposites. The nanocomposites were characterized by SEM, HRTEM, XRD, FTIR X-ray photoelectron spectrometry (XPS) and SQUID. The XRD results indicated the high crystallinity of Fe₃O₄ nanoparticles with spinel structure and the transmission electron microscope images depicted the intercalated iron oxide magnetic particles on the surface of CNTs. The MWCNTs-Fe₃O₄ was applied as a sensing interface to perform luminescence enzyme immunoassays. Firstly, EBNA-1 antigen was immobilized onto the carboxyl group functionalized MWCNTs-Fe₃O₄, followed by binding with anti-EBNA-1 IgA antibodies. The diluted secondary antibodies (anti-human IgA-HRP) were then added to the CNTs/Fe₃O₄-PEG-EBNA-1-anti-EBV IgA ab complex and act as a catalyst to produce a visible light upon reaction with the substrate luminol. The formed RLU is proportional to the amount of IgA anti-EBV antiobodies on the MWCNTs. The detection limit of proposed CNTs/Fe₃O₄ based luminescence enzyme immunoassay was in the order of 0.00128 EU/mL (1:100,000 fold dilution) for the detection of anti-EBV IgA antibodies, whereas the commercial ELISA and magnetic beads' assay was accounted for up to the dilution fold of 1000 (i.e., 0.128 EU/mL). The initial findings showed that CNTs/Fe₃O₄ nanocomposites have a great potential in luminescent enzyme immunoassays and could be used as a sensing platform for the early screening of nasopharyngeal carcinoma. PMID:24720983

  15. Analysis of Epstein Barr Virus Encoded RNA Expression in Nasopharyngeal Carcinoma in North-Eastern India: A Chromogenic in Situ Hybridization Based Study

    PubMed Central

    Saikia, Anjan; Raphael, Vandana; Shunyu, N-Brian; Khonglah, Yookarin; Mishra, Jaya; Jitani, Ankit-Kumar; Medhi, Jayanta

    2016-01-01

    Introduction: Nasopharyngeal carcinoma (NPC) is a common cancer in the North-East region of India. Though the role of environmental contributors of NPC in the North-Eastern part of India is firmly established, EBV as an etiological agent in the region remains unexplored. Material and Methods: Fifty-one patients, who presented at the department of ENT, NEIGRIHMS and were confirmed as NPC upon histopathological examination, were included in the study. Chromogenic in-situ hybridization (CISH) was used for the evaluation of EBER (Epstein Barr Virus Encoded RNA). Presence of nuclear signals was taken as positive for EBER expression. EBER status was correlated with various clinicopathological parameters like age, sex, dietary habits, histological types of NPC, and ethnicity of the patients. Results: The age range of the study group was 25 to 70 years with a mean age of 44.64 years and a male:female ratio of 3:2. Non-keratinizing undifferentiated type of NPC was the most common histological type. EBV was positive in 59% (30/51) of our cases. It showed a statistically significant correlation with the Naga community (P=0.01), with consumption of smoked food (P=0.02), and cigarette smoking (P=0.02). There was no correlation of EBV with age, sex, lymph node metastasis, stage, and histology. Conclusion: Our result indicates that EBV may be an additional risk factor in the pathogenesis of NPC in this region of India. So apart from lifestyle modification, a future study for a screening test for EBV viral load even in asymptomatic patients may be considered, for determination of disease susceptibility, early diagnosis, and proper management. PMID:27602338

  16. Dosimetric benefits of placing dose constraints on the brachial plexus in patients with nasopharyngeal carcinoma receiving intensity-modulated radiation therapy: a comparative study

    PubMed Central

    Jiang, Hailan; Lu, Heming; Yuan, Hong; Huang, Huixian; Wei, Yinglin; Zhang, Yanxian; Liu, Xu

    2015-01-01

    This study aimed to evaluate whether placing dose constraints on the brachial plexus (BP) could provide dosimetric benefits in patients with nasopharyngeal carcinoma (NPC) undergoing intensity-modulated radiation therapy (IMRT). Planning CT images for 30 patients with NPC treated with definitive IMRT were retrospectively reviewed. Target volumes, the BP and other critical structures were delineated; two separate IMRT plans were designed for each patient: one set no restrictions for the BP; the other considered the BP as a critical structure for which a maximum dose limit of ≤66 Gy was set. No significant differences between the two plans were observed in the conformity index, homogeneity index, maximum dose to the planning target volumes (PTVs), minimum dose to the PTVs, percentages of the volume of the PTVnx and PTVnd receiving more than 110% of the prescribed dose, or percentages of the volume of the PTVs receiving 95% and > 93% of the prescribed dose. Dose constraints significantly reduced the maximum dose, mean dose, V45, V50, V54, V60, V66 and V70 to the BP. Dose constraints significantly reduced the maximum dose to the BP, V45, V60 and V66 in both N0–1 and N2–3 disease; however, the magnitude of the dosimetric gain for each parameter between N0–1 and N2–3 disease was not significantly different, except for the V60 and V66. In conclusion, placing dose constraints on the BP can significantly decrease the irradiated volume and dose, without compromising adequate dose delivery to the target volume. PMID:25173085

  17. Interfractional and intrafractional errors assessed by daily cone-beam computed tomography in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: a prospective study

    PubMed Central

    Lu, Heming; Lin, Hui; Feng, Guosheng; Chen, Jiaxin; Shu, Liuyang; Pang, Qiang; Cheng, Jinjian; Peng, Luxing; Wu, Danling; Liao, Chaolong; Mo, Ying

    2012-01-01

    This prospective study was to assess interfractional and intrafractional errors and to estimate appropriate margins for planning target volume (PTV) by using daily cone-beam computed tomography (CBCT) guidance in nasopharyngeal carcinoma (NPC). Daily pretreatment and post-treatment CBCT scans were acquired separately after initial patient setup and after the completion of each treatment fraction in 10 patients treated with IMRT. Online corrections were made before treatment if any translational setup error was found. Interfractional and intrafractional errors were recorded in the right–left (RL), superior–inferior (SI) and anterior–posterior (AP) directions. For the translational shifts, interfractional errors >2 mm occurred in 21.7% of measurements in the RL direction, 12.7% in the SI direction and 34.1% in the AP direction, respectively. Online correction resulted in 100% of residual errors ≤2 mm in the RL and SI directions, and 95.5% of residual errors ≤2 mm in the AP direction. No residual errors >3 mm occurred in the three directions. For the rotational shifts, a significant reduction was found in the magnitudes of residual errors compared with those of interfractional errors. A margin of 4.9 mm, 4.0 mm and 6.3 mm was required in the RL, SI and AP directions, respectively, when daily CBCT scans were not performed. With daily CBCT, the margins were reduced to 1.2 mm in all directions. In conclusion, daily CBCT guidance is an effective modality to improve the accuracy of IMRT for NPC. The online correction could result in a 70–81% reduction in margin size. PMID:22843373

  18. The Clinical Usefulness of 18F-Fluorodeoxyglucose Positron Emission Tomography (PET) to Predict Oncologic Outcomes and PET-Based Radiotherapeutic Considerations in Locally Advanced Nasopharyngeal Carcinoma

    PubMed Central

    Yoon, Hong In; Kim, Kyung Hwan; Lee, Jeongshim; Roh, Yun Ho; Yun, Mijin; Cho, Byoung Chul; Lee, Chang Geol; Keum, Ki Chang

    2016-01-01

    Purpose We investigated 18F-fluorodeoxyglucose positron emission tomography (PET)-derived parameters as prognostic indices for disease progression and survival in locally advanced nasopharyngeal carcinoma (NPC) and the effect of high-dose radiotherapy for a subpopulation with PET-based poor prognoses. Materials and Methods Ninety-seven stage III and Iva-b NPC patients who underwent definitive treatment and PET were reviewed. For each primary, nodal, and whole tumor, maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG) were evaluated. Results Based on the C-index (0.666) and incremental area under the curve (0.669), the whole tumor TLGwas the most useful predictorfor progression-free survival (PFS); thewhole tumor TLG cut-off value showing the best predictive performance was 322.7. In multivariate analysis, whole tumor TLG was a significant prognostic factor for PFS (hazard ratio [HR], 0.3; 95% confidence interval [CI], 0.14 to 0.65; p=0.002) and OS (HR, 0.29; 95% CI, 0.11 to 0.79; p=0.02). Patients with low whole tumor TLG showed the higher 5-year PFS in the subgroup for only patients receiving intensity modulated radiotherapy (77.4% vs. 53.0%, p=0.01). In the subgroup of patients with high whole tumor TLG, patients receiving an EQD2 ≥ 70 Gy showed significantly greater complete remission rates (71.4% vs. 33.3%, p=0.03) and higher 5-year OS (74.7% vs. 19.6%, p=0.02). Conclusion Our findings demonstrated that whole tumor TLG could be an independent prognostic factor and high-dose radiotherapy could improve outcomes for NPC showing high whole tumor TLG. PMID:26693913

  19. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    SciTech Connect

    Twu, Chih-Wen; Wang, Wen-Yi; Chen, Chien-Chih; Liang, Kai-Li; Jiang, Rong-San; Wu, Ching-Te; Shih, Yi-Ting; Lin, Po-Ju; Liu, Yi-Chun; Lin, Jin-Ching

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  20. Cytokine-induced killer cells efficiently kill stem-like cancer cells of nasopharyngeal carcinoma via the NKG2D-ligands recognition.

    PubMed

    Wei, Fang; Rong, Xiao-Xiang; Xie, Rao-Ying; Jia, Li-Ting; Wang, Hui-Yan; Qin, Yu-Juan; Chen, Lin; Shen, Hong-Fen; Lin, Xiao-Lin; Yang, Jie; Yang, Sheng; Hao, Wei-Chao; Chen, Yan; Xiao, Sheng-Jun; Zhou, Hui-Rong; Lin, Tao-Yan; Chen, Yu-Shuang; Sun, Yan; Yao, Kai-Tai; Xiao, Dong

    2015-10-27

    Cancer stem cells (CSCs) are considered to be the root cause for cancer treatment failure. Thus, there remains an urgent need for more potent and safer therapies against CSCs for curing cancer. In this study, the antitumor activity of cytokine-induced killer (CIK) cells against putative CSCs of nasopharyngeal carcinoma (NPC) was fully evaluated in vitro and in vivo. To visualize putative CSCs in vitro by fluorescence imaging, and image and quantify putative CSCs in tumor xenograft-bearing mice by in vivo bioluminescence imaging, NPC cells were engineered with CSC detector vector encoding GFP and luciferase (Luc) under control of Nanog promoter. Our study reported in vitro intense tumor-killing activity of CIK cells against putative CSCs of NPC, as revealed by percentage analysis of side population cells, tumorsphere formation assay and Nanog-promoter-GFP-Luc reporter gene strategy plus time-lapse recording. Additionally, time-lapse imaging firstly illustrated that GFP-labeled or PKH26-labeled putative CSCs or tumorspheres were usually attacked simultaneously by many CIK cells and finally killed by CIK cells, suggesting the necessity of achieving sufficient effector-to-target ratios. We firstly confirmed that NKG2D blockade by anti-NKG2D antibody significantly but partially abrogated CIK cell-mediated cytolysis against putative CSCs. More importantly, intravenous infusion of CIK cells significantly delayed tumor growth in NOD/SCID mice, accompanied by a remarkable reduction in putative CSC number monitored by whole-body bioluminescence imaging. Taken together, our findings suggest that CIK cells demonstrate the intense tumor-killing activity against putative CSCs of NPC, at least in part, by NKG2D-ligands recognition. These results indicate that CIK cell-based therapeutic strategy against CSCs presents a promising and safe approach for cancer treatment. PMID:26418951

  1. Low Prognostic Nutritional Index (PNI) Predicts Unfavorable Distant Metastasis-Free Survival in Nasopharyngeal Carcinoma: A Propensity Score-Matched Analysis

    PubMed Central

    Hong, Shaodong; Chen, Haiyang; Liang, Shaobo; Peng, Peijian; Chen, Yong

    2016-01-01

    Background Poor nutritional status is associated with progression and advanced disease in patients with cancer. The prognostic nutritional index (PNI) may represent a simple method of assessing host immunonutritional status. This study was designed to investigate the prognostic value of the PNI for distant metastasis-free survival (DMFS) in patients with nasopharyngeal carcinoma (NPC). Methods A training cohort of 1,168 patients with non-metastatic NPC from two institutions was retrospectively analyzed. The optimal PNI cutoff value for DMFS was identified using the online tool “Cutoff Finder”. DMFS was analyzed using stratified and adjusted analysis. Propensity score-matched analysis was performed to balance baseline characteristics between the high and low PNI groups. Subsequently, the prognostic value of the PNI for DMFS was validated in an external validation cohort of 756 patients with NPC. The area under the receiver operating characteristics curve (AUC) was calculated to compare the discriminatory ability of different prognostic scores. Results The optimal PNI cutoff value was determined to be 51. Low PNI was significantly associated with poorer DMFS than high PNI in univariate analysis (P<0.001) as well as multivariate analysis (P<0.001) before propensity score matching. In subgroup analyses, PNI could also stratify different risks of distant metastases. Propensity score-matched analyses confirmed the prognostic value of PNI, excluding other interpretations and selection bias. In the external validation cohort, patients with high PNI also had significantly lower risk of distant metastases than those with low PNI (Hazards Ratios, 0.487; P<0.001). The PNI consistently showed a higher AUC value at 1-year (0.780), 3-year (0.793) and 5-year (0.812) in comparison with other prognostic scores. Conclusion PNI, an inexpensive and easily assessable inflammatory index, could aid clinicians in developing individualized treatment and follow-up strategies for patients

  2. Ancient migration routes of Austronesian-speaking populations in oceanic Southeast Asia and Melanesia might mimic the spread of nasopharyngeal carcinoma.

    PubMed

    Trejaut, Jean; Lee, Chien-Liang; Yen, Ju-Chen; Loo, Jun-Hun; Lin, Marie

    2011-02-01

    Mitochondrial DNA (mtDNA) and non-recombining Y chromosome (NRY) are inherited uni-parentally from mother to daughter or from father to son respectively. Their polymorphism has initially been studied throughout populations of the world to demonstrate the "Out of Africa" hypothesis. Here, to correlate the distribution of nasopharyngeal carcinoma (NPC) in different populations of insular Asia, we analyze the mtDNA information (lineages) obtained from genotyping of the hyper variable region (HVS I & II) among 1400 individuals from island Southeast Asia (ISEA), Taiwan and Fujian and supplemented with the analysis of relevant coding region polymorphisms. Lineages that best represented a clade (a branch of the genetic tree) in the phylogeny were further analyzed using complete genomic mtDNA sequencing. Finally, these complete mtDNA sequences were used to construct a most parsimonious tree which now constitutes the most up-to-date mtDNA dataset available on ISEA and Taiwan. This analysis has exposed new insights of the evolutionary history of insular Asia and has strong implications in assessing possible correlations with linguistic, archaeology, demography and the NPC distribution in populations within these regions. To obtain a more objective and balanced genetic point of view, slowly evolving biallelic Y single nucleotide polymorphism (Y-SNP) was also analyzed. As in the first step above, the technique was first applied to determine affinities (macro analysis) between populations of insular Asia. Secondly, sixteen Y short tandem repeats (Y-STR) were used as they allow deeper insight (micro analysis) into the relationship between individuals of a same region. Together, mtDNA and NRY allowed a better definition of the relational, demographic, cultural and genetic components that constitute the make up of the present day peoples of ISEA. Outstanding findings were obtained on the routes of migration that occurred along with the spread of NPC during the settlement of

  3. A Phase II Clinical Trial of Concurrent Helical Tomotherapy plus Cetuximab Followed by Adjuvant Chemotherapy with Cisplatin and Docetaxel for Locally Advanced Nasopharyngeal Carcinoma

    PubMed Central

    Zhang, Xinxin; Du, Lei; Zhao, Feifang; Wang, Qiuju; Yang, Shiming; Ma, Lin

    2016-01-01

    Purpose: The present clinical trial was designed to evaluate the efficacy and safety of concurrent helical tomotherapy (HT) with cetuximab followed by adjuvant chemotherapy with docetaxel and cisplatin (TP) in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Materials and Methods: This phase II clinical trial included 43 patients with Stage III/IV LANC (33 Stage III and 10 Stage IV). The treatment consisted of concurrent HT with cetuximab (400 mg/m2 loading dose and weekly 250mg/m2), followed by four cycles of chemotherapy [docetaxel (70 mg/m2 on Day 1) and cisplatin (40 mg/m2 on Days 1 and 2 every 3 weeks). Side effects were evaluated with CTCAE criteria (Common Terminology Criteria for Adverse Events 3.0). Results: The median follow-up duration was 48.0 months [95% confidence interval (CI) 41.7-58.0 months], the 2-year locoregional failure-free rate (LFFR), progression-free survival (PFS), distant failure-free rate (DFFR) and overall survival (OS) were 95.2%, 79.1%, 88.1% and 93.0% respectively; the 3-year LFFR, DFFR, PFS and OS were 92.7%, 85.6%, 72.0% and 85.7% respectively. The most common grade 3 toxicities were oropharyngeal mucositis (81.4%) and RT-related dermatitis (7.0%). No patients had more than grade 3 radiation related toxicities and no patients required nasogastric feeding. One patient experienced grade 3 osteonecrosis at 18 months after treatment. Conclusions: Concurrent HT with cetuximab followed by adjuvant chemotherapy with TP is an effective strategy for the treatment of LANC with encouraging survival rates and minimal side effects. PMID:27019628

  4. An oncolytic adenovirus enhances antiangiogenic and antitumoral effects of a replication-deficient adenovirus encoding endostatin by rescuing its selective replication in nasopharyngeal carcinoma cells

    SciTech Connect

    Liu, Ran-yi; Zhou, Ling; Zhang, Yan-ling; Huang, Bi-jun; Ke, Miao-la; Chen, Jie-min; Li, Li-xia; Fu, Xiang; Wu, Jiang-xue; Huang, Wenlin

    2013-12-13

    Highlights: •H101 promotes endostatin expression by Ad-Endo via rescuing Ad-Endo replication. •H101 rescued Ad-Endo replication by supplying E1A and E1B19k proteins. •Ad-Endo enhanced the cytotoxicity of H101 in NPC cells. •Ad-Endo and oncolytic Ad H101 have synergistic antitumor effects on NPC. -- Abstract: A replication-deficient adenovirus (Ad) encoding secreted human endostatin (Ad-Endo) has been demonstrated to have promising antiangiogenic and antitumoral effects. The E1B55k-deleted Ad H101 can selectively lyse cancer cells. In this study, we explored the antitumor effects and cross-interactions of Ad-Endo and H101 on nasopharyngeal carcinoma (NPC). The results showed that H101 dramatically promoted endostatin expression by Ad-Endo via rescuing Ad-Endo replication in NPC cells, and the expressed endostatin proteins significantly inhibited the proliferation of human umbilical vein endothelial cells. E1A and E1B19k products are required for the rescuing of H101 to Ad-Endo replication in CNE-1 and CNE-2 cells, but not in C666-1 cells. On the other hand, Ad-Endo enhanced the cytotoxicity of H101 by enhancing Ad replication in NPC cells. The combination of H101 and Ad-Endo significantly inhibited CNE-2 xenografts growth through the increased endostatin expression and Ad replication. These findings indicate that the combination of Ad-Endo gene therapy and oncolytic Ad therapeutics could be promising in comprehensive treatment of NPC.

  5. Ionizing radiation promotes advanced malignant traits in nasopharyngeal carcinoma via activation of epithelial-mesenchymal transition and the cancer stem cell phenotype

    PubMed Central

    SU, ZHONGWU; LI, GUO; LIU, CHAO; REN, SHULING; TIAN, YONGQUAN; LIU, YONG; QIU, YUANZHENG

    2016-01-01

    Post-irradiation residual mass and recurrence always suggest a worse prognosis for nasopharyngeal carcinoma (NPC). Our study aimed to investigate the malignant behaviors of post-irradiation residual NPC cells, to identify the potential underlying mechanisms and to search for appropriate bio-targets to overcome this malignancy. Two NPC cell lines were firstly exposed to 60 Gy irradiation, and residual cells were collected. In our previous study, colony formation assay detected the radioresistance of these cells. Here, the CCK-8 assay examined the cell sensitivity to paclitaxel and cisplatin. Wound-healing and Transwell assays were performed to investigate cell motility and invasion capabilities. Inverted phase-contrast microscopy was used to observe and photograph the morphology of cells. Expression levels of epithelial-mesenchymal transition (EMT)-related proteins were detected by western blot assay in NPC cells and tissues. The mRNA levels of cancer stem cell (CSC)-related genes were detected via qRT-PCR. The results revealed that residual NPC cells exhibited enhanced radioresistance and cross-resistance to paclitaxel and cisplatin. Higher capacities of invasion and migration were also observed. An elongated morphology with pseudopodia formation and broadening in the intercellular space was observed in the residual cells. Downregulation of E-cadherin and upregulation of vimentin were detected in the residual NPC cells and tissues. CSC-related Lgr5 and c-myc were significantly upregulated in the CNE-2-Rs and 6-10B-Rs radioresistance cells. Higher proportions of Lgr5+ cells were observed in radioresistant cells via immunofluorescent staining and flow cytometry. In conclusion, our study demonstrated that residual NPC cells had an advanced malignant transition and presented with both EMT and a CSC phenotype. This provides a possible clue and treatment strategy for advanced and residual NPC. PMID:27108809

  6. Exploration and Validation of C-Reactive Protein/Albumin Ratio as a Novel Inflammation-Based Prognostic Marker in Nasopharyngeal Carcinoma

    PubMed Central

    Zhang, Yuan; Zhou, Guan-Qun; Liu, Xu; Chen, Lei; Li, Wen-Fei; Tang, Ling-Long; Liu, Qing; Sun, Ying; Ma, Jun

    2016-01-01

    Background: The prognostic value of C-reactive protein/albumin ratio (CRP/Alb), a novel inflammation-based marker, remains unknown in nasopharyngeal carcinoma (NPC). Methods: We conducted a retrospective review of 1572 consecutive patients with non-metastatic NPC. Patients were randomly divided into a training set (n = 514) and validation set (n = 1058). The prognostic value of the CRP/Alb ratio and the modified Glasgow prognostic score (mGPS; a well-recognized inflammation-based score) was assessed. Results: Receiver-operating characteristic analysis identified 0.05 as the optimal CRP/Alb cut-off value for disease failure in the training set. Patients with a CRP/Alb > 0.05 had poorer overall survival (OS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) in the training set (all P < 0.05). These results were confirmed in the validation set (all P < 0.05) and the whole cohort (all P < 0.001). In multivariate analysis of the entire cohort, the pretreatment CRP/Alb ratio was an independent prognostic factor for OS (HR, 1.394; 95% CI, 1.004-1.937; P = 0.048) and DMFS (HR, 1.545; 95% CI, 1.124-2.122; P = 0.007), but not for DFS (P = 0.083). The mGPS had no significant independent prognostic value for any end-point. Conclusion: CRP/Alb ratio is an useful prognostic indicator in patients with NPC, independent of disease stage. PMID:27471556

  7. Epstein - Barr virus Serology as a Potential Screening Marker for Nasopharyngeal Carcinoma among High-risk Individuals from Multiplex Families in Taiwan

    PubMed Central

    Coghill, Anna E.; Hsu, Wan-Lun; Pfeiffer, Ruth M.; Juwana, Hedy; Yu, Kelly J.; Lou, Pei-Jen; Wang, Cheng-Ping; Chen, Jen-Yang; Chen, Chien-Jen; Middeldorp, Jaap M.; Hildesheim, Allan

    2014-01-01

    Background Nasopharyngeal carcinoma (NPC) is an EBV associated cancer that is highly treatable when diagnosed early, with 5-year disease-free survival of ~90%. However, NPC is typically diagnosed at advanced stages, where disease-free survival is <50%. There is therefore a need for clinical tools to assist in early NPC detection, particularly in high-risk individuals. Methods We evaluated the ability of anti-EBV IgA antibodies to detect incident NPC among high-risk Taiwanese individuals. NPC cases (N=21) and age and sex-matched controls (N=84) were selected. Serum collected prior to NPC diagnosis was tested for ELISA-based IgA markers against the following EBV peptides: EBNA1, VCAp18, EAp138, Ead_p47, and VCAp18 + EBNA1 peptide mixture. The sensitivity, specificity, and screening program parameters were calculated. Results EBNA1 IgA had the best performance characteristics. At an optimized threshold value, EBNA1 IgA measured at baseline identified 80% of the high-risk individuals who developed NPC during follow-up (80% sensitivity). However, approximately 40% of high-risk individuals who did not develop NPC also tested positive (false positives). Application of EBNA1 IgA as a biomarker to detect incident NPC in a previously unscreened, high-risk population revealed that 164 individuals needed to be screened to detect 1 NPC and that 69 individuals tested positive per case detected. Conclusions EBNA1 IgA proved to be a sensitive biomarker for identifying incident NPC, but future work is warranted to develop more specific screening tools to decrease the number of false positives. Impact Results from this study could inform decisions regarding screening biomarkers and referral thresholds for future NPC early-detection program evaluations. PMID:24769890

  8. Will weight loss cause significant dosimetric changes of target volumes and organs at risk in nasopharyngeal carcinoma treated with intensity-modulated radiation therapy?

    SciTech Connect

    Chen, Chuanben; Fei, Zhaodong; Chen, Lisha; Bai, Penggang; Lin, Xiang; Pan, Jianji

    2014-04-01

    This study aimed to quantify dosimetric effects of weight loss for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Overall, 25 patients with NPC treated with IMRT were enrolled. We simulated weight loss during IMRT on the computer. Weight loss model was based on the planning computed tomography (CT) images. The original external contour of head and neck was labeled plan 0, and its volume was regarded as pretreatment normal weight. We shrank the external contour with different margins (2, 3, and 5 mm) and generated new external contours of head and neck. The volumes of reconstructed external contours were regarded as weight during radiotherapy. After recontouring outlines, the initial treatment plan was mapped to the redefined CT scans with the same beam configurations, yielding new plans. The computer model represented a theoretical proportional weight loss of 3.4% to 13.7% during the course of IMRT. The dose delivered to the planning target volume (PTV) of primary gross tumor volume and clinical target volume significantly increased by 1.9% to 2.9% and 1.8% to 2.9% because of weight loss, respectively. The dose to the PTV of gross tumor volume of lymph nodes fluctuated from −2.0% to 1.0%. The dose to the brain stem and the spinal cord was increased (p < 0.001), whereas the dose to the parotid gland was decreased (p < 0.001). Weight loss may lead to significant dosimetric change during IMRT. Repeated scanning and replanning for patients with NPC with an obvious weight loss may be necessary.

  9. Hes1 triggers epithelial-mesenchymal transition (EMT)-like cellular marker alterations and promotes invasion and metastasis of nasopharyngeal carcinoma by activating the PTEN/AKT pathway.

    PubMed

    Wang, Sheng-Chun; Lin, Xiao-Lin; Wang, Hui-Yan; Qin, Yu-Juan; Chen, Lin; Li, Jing; Jia, Jun-Shuang; Shen, Hong-Fen; Yang, Sheng; Xie, Rao-Ying; Wei, Fang; Gao, Fei; Rong, Xiao-Xiang; Yang, Jie; Zhao, Wen-Tao; Zhang, Ting-Ting; Shi, Jun-Wen; Yao, Kai-Tai; Luo, Wei-Ren; Sun, Yan; Xiao, Dong

    2015-11-01

    Overexpression of the transcriptional factor Hes1 (hairy and enhancer of split-1) has been observed in numerous cancers, but the precise roles of Hes1 in epithelial-mesenchymal transition (EMT), cancer invasion and metastasis remain unknown. Our current study firstly revealed that Hes1 upregulation in a cohort of human nasopharyngeal carcinoma (NPC) biopsies is significantly associated with the EMT, invasive and metastatic phenotypes of cancer. In the present study, we found that Hes1 overexpression triggered EMT-like cellular marker alterations of NPC cells, whereas knockdown of Hes1 through shRNA reversed the EMT-like phenotypes, as strongly supported by Hes1-mediated EMT in NPC clinical specimens described above. Gain-of-function and loss-of-function experiments demonstrated that Hes1 promoted the migration and invasion of NPC cells in vitro. In addition, exogenous expression of Hes1 significantly enhanced the metastatic ability of NPC cells in vivo. Chromatin immunoprecipitation (ChIP) assays showed that Hes1 inhibited PTEN expression in NPC cells through binding to PTEN promoter region. Increased Hes1 expression and decreased PTEN expression were also observed in a cohort of NPC biopsies. Additional studies demonstrated that Hes1-induced EMT-like molecular changes and increased motility and invasion of NPC cells were mediated by PTEN. Taken together, our results suggest, for what we believe is the first time, that Hes1 plays an important role in the invasion and metastasis of NPC through inhibiting PTEN expression to trigger EMT-like phenotypes. PMID:26452025

  10. Overexpression of CIP2A is an independent prognostic indicator in nasopharyngeal carcinoma and its depletion suppresses cell proliferation and tumor growth

    PubMed Central

    2014-01-01

    Background Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that acts as a prognostic marker for several human malignancies. In this study, we investigated the clinical significance of CIP2A and its function in nasopharyngeal carcinoma (NPC). Methods Quantitative RT-PCR, western blot, and immunohistochemistry analyses were used to quantify CIP2A expression in NPC cell lines and clinical samples. Kaplan-Meier curves were used to estimate the association between CIP2A expression and patient survival. The functional role of CIP2A in NPC cell lines was evaluated by small interfering RNA-mediated depletion of the protein followed by analyses of cell proliferation and xenograft growth. Results CIP2A levels were upregulated in NPC cell lines and clinical samples at both the mRNA and protein levels (P < 0.01). Patients with high CIP2A expression had poorer overall survival (HR, 1.98; 95% CI, 1.16-3.34; P = 0.01) and poorer disease-free survival (HR, 1.68; 95% CI, 1.07-2.62; P = 0.02) rates than patients with low CIP2A expression. In addition, CIP2A expression status was an independent prognostic indicator for NPC patients. The depletion of CIP2A expression inhibited c-Myc protein expression in NPC cell lines, suppressed cell viability, colony formation, and anchorage-independent growth in vitro, and inhibited xenograft tumor growth in vivo. Conclusions Our data demonstrate that high CIP2A expression in patients was associated with poor survival in NPC, and depletion of CIP2A expression inhibited NPC cell proliferation and tumor growth. Thus, these results warrant further investigation of CIP2A as a novel therapeutic target for the treatment of NPC. PMID:24884612

  11. Hes1 triggers epithelial-mesenchymal transition (EMT)-like cellular marker alterations and promotes invasion and metastasis of nasopharyngeal carcinoma by activating the PTEN/AKT pathway

    PubMed Central

    Qin, Yu-Juan; Chen, Lin; Li, Jing; Jia, Jun-Shuang; Shen, Hong-Fen; Yang, Sheng; Xie, Rao-Ying; Wei, Fang; Gao, Fei; Rong, Xiao-Xiang; Yang, Jie; Zhao, Wen-Tao; Zhang, Ting-Ting; Shi, Jun-Wen; Yao, Kai-Tai; Luo, Wei-Ren; Sun, Yan; Xiao, Dong

    2015-01-01

    Overexpression of the transcriptional factor Hes1 (hairy and enhancer of split-1) has been observed in numerous cancers, but the precise roles of Hes1 in epithelial-mesenchymal transition (EMT), cancer invasion and metastasis remain unknown. Our current study firstly revealed that Hes1 upregulation in a cohort of human nasopharyngeal carcinoma (NPC) biopsies is significantly associated with the EMT, invasive and metastatic phenotypes of cancer. In the present study, we found that Hes1 overexpression triggered EMT-like cellular marker alterations of NPC cells, whereas knockdown of Hes1 through shRNA reversed the EMT-like phenotypes, as strongly supported by Hes1-mediated EMT in NPC clinical specimens described above. Gain-of-function and loss-of-function experiments demonstrated that Hes1 promoted the migration and invasion of NPC cells in vitro. In addition, exogenous expression of Hes1 significantly enhanced the metastatic ability of NPC cells in vivo. Chromatin immunoprecipitation (ChIP) assays showed that Hes1 inhibited PTEN expression in NPC cells through binding to PTEN promoter region. Increased Hes1 expression and decreased PTEN expression were also observed in a cohort of NPC biopsies. Additional studies demonstrated that Hes1-induced EMT-like molecular changes and increased motility and invasion of NPC cells were mediated by PTEN. Taken together, our results suggest, for what we believe is the first time, that Hes1 plays an important role in the invasion and metastasis of NPC through inhibiting PTEN expression to trigger EMT-like phenotypes. PMID:26452025

  12. Flotillin-2 promotes metastasis of nasopharyngeal carcinoma by activating NF-κB and PI3K/Akt3 signaling pathways

    PubMed Central

    Liu, Jie; Huang, Wei; Ren, Caiping; Wen, Qiuyuan; Liu, Weidong; Yang, Xuyu; Wang, Lei; Zhu, Bin; Zeng, Liang; Feng, Xiangling; Zhang, Chang; Chen, Huan; Jia, Wei; Zhang, Lihua; Xia, Xiaomeng; Chen, Yuxiang

    2015-01-01

    Lipid raft proteins have been confirmed to be important in cell signal transduction. Some reports have shown that the aberrant expression of lipid raft proteins is associated with malignant phenotypes in some cancers. However, the role of the lipid raft protein flotillin-2 (Flot-2) in nasopharyngeal carcinoma (NPC) remains to be comprehensively characterized. Here, overexpression of Flot-2 in NPC tissues and cell lines was detected by immunostaining, and Flot-2 expression was found to be positively associated with NPC metastasis. Furthermore, inhibiting Flot-2 expression impaired the malignancy of the highly metastatic NPC cell line 5-8F by constraining its growth and proliferation, mobility and migration, and decreasing the capacity of 5-8F cells to metastasize in nude mice. In contrast, forced overexpression of Flot-2 increased the malignancy of 6-10B, a non-metastatic NPC cell line that weakly expresses Flot-2. Moreover, in 5-8F-shFlot-2 cells, which have inhibited Flot-2 expression, the NF-κB and PI3K/Akt3 pathways were inactivated. Subsequently, MMPs expression were decreased, and Foxo1 activity was increased. In addition, enhanced NF-κB and PI3K/Akt3 activities were observed in Flot-2 overexpressing 6-10B cells. Thus, Flot-2 exerts a pro-neoplastic role in NPC and is involved in tumor progression and metastasis. Moreover, Flot-2 exerts its role through NF-κB and PI3K/Akt3 signaling. PMID:26206082

  13. Quality of Life and Survival Outcome for Patients With Nasopharyngeal Carcinoma Receiving Three-Dimensional Conformal Radiotherapy vs. Intensity-Modulated Radiotherapy-A Longitudinal Study

    SciTech Connect

    Fang, F.-M. Chien, C.-Y.; Tsai, W.-L.; Chen, H.-C.; Hsu, H.-C.; Lui, C.-C.; Huang, T.-L.

    2008-10-01

    Purpose: To investigate the changes of quality of life (QoL) and survival outcomes for patients with nasopharyngeal carcinoma (NPC) treated by three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT). Methods and Materials: Two hundred and three newly diagnosed NPC patients, who were curatively treated by 3D-CRT (n = 93) or IMRT (n = 110) between March 2002 and July 2004, were analyzed. The distributions of clinical stage according to American Joint Committee on Cancer 1997 were I: 15 (7.4%), II: 78 (38.4%), III: 74 (36.5%), and IV: 36 (17.7%). QoL was longitudinally assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC QLQ-H and N35 questionnaires at the five time points: before RT, during RT (36 Gy), and 3 months, 12 months, and 24 months after RT. Results: The 3-year locoregional control, metastasis-free survival, and overall survival rates were 84.8%, 76.7%, and 81.7% for the 3D-CRT group, respectively, compared with 84.2%, 82.6%, and 85.4% for the IMRT group (p value > 0.05). A general trend of maximal deterioration in most QoL scales was observed during RT, followed by a gradual recovery thereafter. There was no significant difference in most scales between the two groups at each time point. The exception was that patients treated by IMRT had a both statistically and clinically significant improvement in global QoL, fatigue, taste/smell, dry mouth, and feeling ill at the time point of 3 months after RT. Conclusions: The potential advantage of IMRT over 3D-CRT in treating NPC patients might occur in QoL outcome during the recovery phase of acute toxicity.

  14. CCL2-CCR2 axis promotes metastasis of nasopharyngeal carcinoma by activating ERK1/2-MMP2/9 pathway

    PubMed Central

    Xie, Changqing; Xia, Weixiong; Jiang, Chen; Zeng, Tingting; Ye, Yanfang; Ke, Liangru; Yu, Yahui; Liang, Hu; Guan, Xin-Yuan; Guo, Xiang; Xiang, Yanqun

    2016-01-01

    Distant metastasis remains the major failure of nasopharyngeal carcinoma (NPC). In this study, the roles of chemokine C-C motif ligand 2 (CCL2), and its receptor chemokine C-C motif receptor type 2 (CCR2) on NPC metastasis were investigated. Serum CCL2 and CCL2/CCR2 expression level were remarkably increased in NPC patients compared to non-tumor patients by ELISA and IHC analyses. High expressions of CCL2/CCR2 were significantly associated with NPC metastasis and poor overall survival (OS). High expression of CCR2 is an independent adverse prognostic factor of OS and distant metastasis free survival (DMFS). Overexpressions of CCL2 and CCR2 were detected in high-metastatic NPC cell lines. Upregulating CCL2 and CCR2 respectively in low-metastatic NPC cell lines could promote cell migration and invasion, and exogenous CCL2 enhanced the motility in CCR2-overexpressing cells. On the other hand, downregulating CCL2 and CCR2 respectively in high-metastatic NPC cell lines by shRNA could decrease cell migration and invasion. However, exogenous CCL2 could not rescue the weaken ability of motility of CCR2-silencing cells. In nude mouse model, distant metastasis was significantly facilitated in either CCL2-overexpressing or CCR2-overexpressing groups, which was more obvious in CCR2-overexpressing group. Also, distant metastasis was considerably inhibited in either CCL2-silencing or CCR2-silencing groups. Dual overexpression of CCL2/CCR2 could activate extracellular signal-regulated kinase (ERK1/2) signaling pathway, which sequentially induced matrix metalloproteinase (MMP) 2 and 9 upregulations in the downstream. In conclusion, CCL2-CCR2 axis could promote NPC metastasis by activating ERK1/2-MMP2/9 pathway. This study helps to develop novel therapeutic targets for distant metastasis in NPC. PMID:26701209

  15. A Retrospective Comparison of Robotic Stereotactic Body Radiotherapy and Three-Dimensional Conformal Radiotherapy for the Reirradiation of Locally Recurrent Nasopharyngeal Carcinoma

    SciTech Connect

    Ozyigit, Gokhan; Cengiz, Mustafa; Yazici, Gozde; Yildiz, Ferah; Gurkaynak, Murat; Zorlu, Faruk; Yildiz, Demet; Hosal, Sefik; Gullu, Ibrahim; Akyol, Fadil

    2011-11-15

    Purpose: We assessed therapeutic outcomes of reirradiation with robotic stereotactic radiotherapy (SBRT) for locally recurrent nasopharyngeal carcinoma (LRNPC) patients and compared those results with three-dimensional conformal radiotherapy (CRT) with or without brachytherapy (BRT). Methods and Materials: Treatment outcomes were evaluated retrospectively in 51 LRNPC patients receiving either robotic SBRT (24 patients) or CRT with or without BRT (27 patients) in our department. CRT was delivered with a 6-MV linear accelerator, and a median total reirradiation dose of 57 Gy in 2 Gy/day was given. Robotic SBRT was delivered with CyberKnife (Accuray, Sunnyvale, CA). Patients in the SBRT arm received 30 Gy over 5 consecutive days. We calculated actuarial local control and cancer-specific survival rates for the comparison of treatment outcomes in SBRT and CRT arms. The Common Terminology Criteria for Adverse Events v3.0 was used for toxicity evaluation. Results: The median follow-up was 24 months for all patients. Two-year actuarial local control rates were 82% and 80% for SBRT and CRT arms, respectively (p = 0.6). Two-year cancer-specific survival rates were 64% and 47% for the SBRT and CRT arms, respectively (p = 0.4). Serious late toxicities (Grade 3 and above) were observed in 21% of patients in the SBRT arm, whereas 48% of patients had serious toxicity in the CRT arm (p = 0.04). Fatal complications occurred in three patients (12.5%) of the SBRT arm, and four patients (14.8%) of the CRT arm (p = 0.8). T stage at recurrence was the only independent predictor for local control and survival. Conclusion: Our robotic SBRT protocol seems to be feasible and less toxic in terms of late effects compared with CRT arm for the reirradiation of LRNPC patients.

  16. Should All Nasopharyngeal Carcinoma with Paranasal Sinus Invasion Be Staged as T3 in the Intensity-Modulated Radiotherapy Era? A Study of 1811 Cases

    PubMed Central

    Zhang, Yuan; Peng, Hao; Guo, Rui; Li, Wen-Fei; Chen, Lei; Liu, Xu; Tang, Ling-Long; Liu, Li-Zhi; Li, Li; Liu, Qing; Sun, Ying; Ma, Jun

    2016-01-01

    Background: Currently, there is no uniform consensus regarding the appropriate staging for invasion of the paranasal sinuses in nasopharyngeal carcinoma (NPC). In the current AJCC staging system for NPC, paranasal sinus invasion is defined within the T3 classification. However, according to the Chinese 2008 staging system, which is also widely used in the regions where NPC is endemic in China, paranasal sinus invasion is classified as T4 disease. Methods: Patients (n = 1811) with non-metastatic, histologically-proven NPC treated with intensity-modulated radiotherapy (IMRT) were retrospectively analyzed. Results: Paranasal sinus invasion was identified in 289/1811 patients (16.0%). Multivariate analysis revealed ethmoid sinus invasion (HR, 2.889; 95% CI, 1.362-6.131; P = 0.006) and maxillary sinus invasion (HR, 3.110; 95% CI, 1.439-6.721; P = 0.004) were independent prognostic factors for local relapse-free survival (LRFS). T3 patients with ethmoid sinus or maxillary sinus invasion had similar 3-year LRFS (83.6% vs. 92.2%, P = 0.132) as T4 patients, and had poorer LRFS (83.6% vs. 98.3%, P = 0.006) than T3 patients with sphenoid sinus invasion alone. Also, T3 patients with sphenoid sinus invasion alone had similar 3-year LRFS (98.3 vs. 96.4%, P = 0.391) as T3 patients without paranasal sinus invasion, and a trend toward higher LRFS (98.3% vs. 92.2%, P = 0.065) than T4 patients. Conclusion: In patients underwent IMRT, tumors with ethmoid sinus or maxillary sinus invasion had a higher risk of local failure than those with sphenoid sinus invasion alone. Sphenoid sinus invasion alone should be classified as T3 disease and ethmoid sinus or maxillary sinus involvement as T4 disease in the current AJCC staging system for NPC. PMID:27390611

  17. Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma

    PubMed Central

    Tao, Hengmin; Wei, Yumei; Huang, Wei; Gai, Xiujuan; Li, Baosheng

    2016-01-01

    Aim In recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF) have been involved in the treatment of nasopharyngeal carcinoma (NPC). However, the potential clinical effects and toxicities are still controversial. Methods Here, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS), 5-year progression-free survival (PFS), 5-year locoregional recurrence-free survival (LRFS), and relevant toxicities were analyzed. Results In the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8–126 months). The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568). In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773) and 5-year LRFS (88.1% vs 90.8%, P=0.903). Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland) in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all P<0.05). Conclusion Both IMRT-SIB and IMRT-CF techniques are effective in treating locally advanced NPC, with similar OS, PFS, and LRFS. However, IMRT-CF has more advantages than IMRT-SIB in protecting spinal cord, brainstem, and parotid gland from acute and late toxicities, such as xerostomia. Further prospective study is warranted to confirm our findings. PMID:27099518

  18. The Role of Neoadjuvant Chemotherapy in the Treatment of Nasopharyngeal Carcinoma: A Multi-institutional Retrospective Study (KROG 11-06) Using Propensity Score Matching Analysis

    PubMed Central

    Song, Jin Ho; Wu, Hong-Gyun; Keam, Bhum Suk; Hah, Jeong Hun; Ahn, Yong Chan; Oh, Dongryul; Noh, Jae Myoung; Park, Hyo Jung; Lee, Chang Geol; Keum, Ki Chang; Cha, Jihye; Cho, Kwan Ho; Moon, Sung Ho; Kim, Ji-Yoon; Chung, Woong-Ki; Oh, Young Taek; Kim, Won Taek; Cho, Moon-June; Kay, Chul Seung; Kim, Yeon-Sil

    2016-01-01

    Purpose We compared the treatment results and toxicity in nasopharyngeal carcinoma (NPC) patients treated with concurrent chemotherapy (CCRT) alone (the CRT arm) or neoadjuvant chemotherapy followed by CCRT (the NCT arm). Materials and Methods A multi-institutional retrospective study was conducted to review NPC patterns of care and treatment outcome. Data of 568 NPC patients treated by CCRT alone or by neoadjuvant chemotherapy followed by CCRT were collected from 15 institutions. Patients in both treatment arms were matched using the propensity score matching method, and the clinical outcomes were analyzed. Results After matching, 300 patients (150 patients in each group) were selected for analysis. Higher 5-year locoregional failure-free survival was observed in the CRT arm (85% vs. 72%, p=0.014). No significant differences in distant failure-free survival (DFFS), disease-free survival (DFS), and overall survival were observed between groups. In subgroup analysis, the NCT arm showed superior DFFS and DFS in stage IV patients younger than 60 years. No significant difference in compliance and toxicity was observed between groups, except the radiation therapy duration was slightly shorter in the CRT arm (50.0 days vs. 53.9 days, p=0.018). Conclusion This study did not show the superiority of NCT followed by CCRT over CCRT alone. Because NCT could increase the risk of locoregional recurrences, it can only be considered in selected young patients with advanced stage IV disease. The role of NCT remains to be defined and should not be viewed as the standard of care. PMID:26727716

  19. Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: Initial report on a randomized controlled clinical trial

    SciTech Connect

    Pow, Edmond; Kwong, Dora; McMillan, Anne S. . E-mail: annemcmillan@hku.hk; Wong, May; Sham, Jonathan; Leung, Lucullus; Leung, W. Keung

    2006-11-15

    Purpose: To compare directly the effect of intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) on salivary flow and quality of life (QoL) in patients with early-stage nasopharyngeal carcinoma (NPC). Methods and Materials: Fifty-one patients with T2, N0/N1, M0 NPC took part in a randomized controlled clinical study and received IMRT or CRT. Stimulated whole (SWS) and parotid (SPS) saliva flow were measured and Medical Outcomes Short Form 36 (SF-36), European Organization for Research and Treatment of Cancer (EORTC) core quetionnaire, and EORTC head-and-neck module (QLQ-H and N35) were completed at baseline and 2, 6, and 12 months after radiotherapy. Results: Forty-six patients (88%) were in disease remission 12 months after radiotherapy. At 12 months postradiotherapy, 12 (50.0%) and 20 patients (83.3%) in the IMRT group had recovered at least 25% of preradiotherapy SWS and SPS flow respectively, compared with 1 (4.8%) and 2 patients (9.5%), respectively, in the CRT group. Global health scores showed continuous improvement in QoL after both treatments (p < 0.001). However, after 12 months subscale scores for role-physical, bodily pain, and physical function were significantly higher in the IMRT group, indicating a better condition (p < 0.05). Dry mouth and sticky saliva were problems in both groups 2 months after treatment. In the IMRT group, there was consistent improvement over time with xerostomia-related symptoms significantly less common than in the CRT group at 12 months postradiotherapy. Conclusions: IMRT was significantly better than CRT in terms of parotid sparing and improved QoL for early-stage disease. The findings support the case for assessment of health-related QoL in relation to head-and-neck cancer using a site-specific approach.

  20. The effect of the target-organ geometric complexity on the choice of delivery between RapidArc and sliding-window IMRT for nasopharyngeal carcinoma

    SciTech Connect

    Kan, Monica W.K.; Leung, Lucullus H.T.; Yu, Peter K.N.

    2013-10-01

    We attempted to assess the effect of target-organ geometric complexity on the plan quality of sliding-window intensity-modulated radiotherapy (IMRT), double-arc (RA2), and triple-arc (RA3) RapidArc volumetric-modulated arc radiotherapy for nasopharyngeal carcinoma (NPC). Plans for 9-field sliding-window IMRT, RA2, and RA3 were optimized for 36 patients with NPC ranging from T1 to T4 tumors. Initially the patients were divided into 2 groups, with group A representing the most simple early stage (T1 and T2) cases, whereas group B represented the more complex advanced cases (T3 and T4). Evaluation was performed based on target conformity, target dose homogeneity, organ-sparing capability, and delivery efficiency. Based on the plan quality results, a subgroup of advanced cases, group B2, representing the most demanding task was distinguished and reported separately from the rest of the group B cases, B1. Detailed analysis was performed on the anatomic features for each group of cases, so that planners can easily identify the differences between B1 and B2. For the group A cases, RA3 plans were superior to the IMRT plans in terms of organ sparing, whereas target conformity and dose homogeneity were similar. For the group B1 cases, the RA3 plans produced almost equivalent plan quality as the IMRT plans. For the group B2 cases, for most of which large target volumes were adjacent to (5 mm or less) and wrapping around the brain stem, RA2 and RA3 were inferior to the IMRT regarding both target dose homogeneity and conformity. RA2 plans were slightly inferior to IMRT and RA3 plans for most cases. The plan comparison results depend on the target to brain stem distances and the target sizes. The plan quality results together with the anatomic information may allow the evaluation of the 3 treatment options before actual planning.

  1. Dosimetric Impact of Using the Acuros XB Algorithm for Intensity Modulated Radiation Therapy and RapidArc Planning in Nasopharyngeal Carcinomas

    SciTech Connect

    Kan, Monica W.K.; Leung, Lucullus H.T.; Yu, Peter K.N.

    2013-01-01

    Purpose: To assess the dosimetric implications for the intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy with RapidArc (RA) of nasopharyngeal carcinomas (NPC) due to the use of the Acuros XB (AXB) algorithm versus the anisotropic analytical algorithm (AAA). Methods and Materials: Nine-field sliding window IMRT and triple-arc RA plans produced for 12 patients with NPC using AAA were recalculated using AXB. The dose distributions to multiple planning target volumes (PTVs) with different prescribed doses and critical organs were compared. The PTVs were separated into components in bone, air, and tissue. The change of doses by AXB due to air and bone, and the variation of the amount of dose changes with number of fields was also studied using simple geometric phantoms. Results: Using AXB instead of AAA, the averaged mean dose to PTV{sub 70} (70 Gy was prescribed to PTV{sub 70}) was found to be 0.9% and 1.2% lower for IMRT and RA, respectively. It was approximately 1% lower in tissue, 2% lower in bone, and 1% higher in air. The averaged minimum dose to PTV{sub 70} in bone was approximately 4% lower for both IMRT and RA, whereas it was approximately 1.5% lower for PTV{sub 70} in tissue. The decrease in target doses estimated by AXB was mostly contributed from the presence of bone, less from tissue, and none from air. A similar trend was observed for PTV{sub 60} (60 Gy was prescribed to PTV{sub 60}). The doses to most serial organs were found to be 1% to 3% lower and to other organs 4% to 10% lower for both techniques. Conclusions: The use of the AXB algorithm is highly recommended for IMRT and RapidArc planning for NPC cases.

  2. A new staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy: results of a prospective multicentric clinical study

    PubMed Central

    Kang, Min; Long, Jianxiong; Li, Guisheng; Yan, Haolin; Feng, Guosheng; Liu, Meilian; Zhu, Jinxian; Wang, Rensheng

    2016-01-01

    Purpose To establish a new clinical staging standard for nasopharyngeal carcinoma (NPC), based on intensity-modulated radiotherapy (IMRT), through a prospective multicenter clinical trial. Experiment Design 492 NPC patients were selected from six hospitals in the Guangxi Zhuang Autonomous Region, China from January 2006 to December 2009. Kaplan-Meier method was adopted to calculate survival rates. Log-rank test was used to compare survival differences. Results According to the seventh edition of the UICC/AJCC staging system, the differences between T1, T2 and T3 are not statistically significant, suggesting that T1, T2 and T3 could be combined as new T1. There were significant differences between all N stages except those of N3a and N3b, suggesting that N3a and N3b could be combined as new N3. Additionally, the overall survival (OS) curves of stages I, II, III and IVa were not significantly different. Therefore, we propose a new clinical NPC staging standard based on magnetic resonance imaging (MRI) and IMRT as T stage (including T1 and T2), N stage (including N0, N1, N2 and N3) and clinical staging includes I (T1N0M0), II (T1N1-2M0, T2N0M0), III (T2N1-2M0), IVa (TxN3M0) and IVb (TxNxM1). Recommended staging system performs better in risk difference and distribution balance. Furthermore, the differences in the 5-year curves of local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and OS were all statistically more significant than the seventh edition of the UICC/AJCC staging system. Conclusions Proposed staging system is more adaptable to IMRT and predicts the prognosis of NPC patients more accurately. PMID:26918446

  3. Prognostic Impact of Plasma Epstein-Barr Virus DNA in Patients with Nasopharyngeal Carcinoma Treated using Intensity-Modulated Radiation Therapy.

    PubMed

    Peng, Hao; Guo, Rui; Chen, Lei; Zhang, Yuan; Li, Wen-Fei; Mao, Yan-Ping; Sun, Ying; Zhang, Fan; Liu, Li-Zhi; Lin, Ai-Hua; Ma, Jun

    2016-01-01

    The prognostic value of plasma Epstein-Barr virus (EBV) DNA remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). We retrospectively reviewed medical records of 584 newly diagnosed patients with nonmetastatic and biopsy-proven NPC treated using IMRT. Plasma EBV DNA concentration was measured before therapy (pre-DNA) and within 1 month of completing therapy (post-DNA) using real-time quantitative polymerase chain reaction. Receiver operating characteristic (ROC) curves were generated to identify pre-DNA and post-DNA cut-off values. Prognostic value was assessed using a multivariate Cox proportional hazards model .Three-year disease-free survival (DFS), overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free (DMFS) for pre-DNA >2010 vs.≤2010 were 78.1% vs. 93.6% (P < 0.001), 92.3% vs. 98.9% (P < 0.001), 90.9% vs. 96.6% (P = 0.004) and 85.5% vs. 96.6% (P < 0.001), respectively. Three-year DFS, OS, LRRFS and DMFS for post-DNA >0 vs. = 0 were 49.9% vs. 88.5% (P < 0.001), 72.1% vs. 97.5% (P < 0.001), 86.6% vs. 94.3% (P = 0.019), and 60.5% vs. 93.3% (P < 0.001), respectively. Plasma EBV DNA remains a prognostic factor in IMRT era and should be incorporated into TNM staging to guide individualized treatment strategies in NPC. PMID:26924234

  4. Targeting FoxM1 inhibits proliferation, invasion and migration of nasopharyngeal carcinoma through the epithelial‑to-mesenchymal transition pathway.

    PubMed

    Yu, Chao; Chen, Lili; Yie, Lin; Wei, Lei; Wen, Taoyu; Liu, Yanan; Chen, Hongyan

    2015-05-01

    High expression levels of the forkhead box M1 (FoxM1) transcription factor are associated with metastasis and poor prognosis of malignancies. However, little is known concerning its function in nasopharyngeal carcinoma (NPC). The present study aimed to investigate the impact of FoxM1 inhibition on the migration and invasion of NPC cells and the potential mechanisms. The