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Sample records for nasopharyngeal carcinoma stenose

  1. Nasopharyngeal carcinoma

    SciTech Connect

    Ho, J.H.C.

    1985-07-01

    In this editorial comment, the author presents a review of recent achievements in the diagnosis and treatment of squamous cell carcinoma of the nasopharynx. The value of the use of CT scans for differentiating between cranial nerve involvement by recurring tumors and irradiation neuropathy, and between temporal lobe irradiation encephalopathy and other nonneoplastic neurologic disorders and meningeal metastasis is discussed. Magnetic resonance imaging is said to be superior to CT for finding soft tissue involvement or abnormalities in the brain. 13 references.

  2. Nasopharyngeal Carcinoma Database.

    PubMed

    Pua, K C; Khoo, A S B; Yap, Y Y; Subramaniam, S K; Ong, C A; Gopala Krishnan, G; Shahid, H

    2008-09-01

    Nasopharyngeal carcinoma (NPC) is a cancer which is common in Asia. We report the establishment and early results of a multi-institutional prospective study of nasopharyngeal carcinoma, which seeks to systematically collect data as well as blood and tumour tissue samples from patients diagnosed with nasopharyngeal cancer at six centres in Malaysia. A total of 484 confirmed NPC cases were reported from the six participating centres between 1st July 2007 and 29th February 2008. Of these, 225 were newly diagnosed cases, 53 were recurrent cases and 206 were in remission at the time of reporting. Amongst the newly diagnosed cases, the most common presenting symptom was the presence of neck lumps (42%). Ophthalmo-neurologic symptoms were the presenting symptoms of 11% of the new cases. The majority of cases (75%) presented at stage III/IV.

  3. [Radiotherapy for nasopharyngeal carcinoma].

    PubMed

    Maingon, P; Blanchard, P; Bidault, F; Calmels, L

    2016-09-01

    Nasapharyngeal carcinoma is a rare disease. Oftenly, the diagnostic is made for advanced disease. Localized tumors, T1 or T2 NO observed a good prognosis and are locally controlled in more than 90 % of the cases by radiotherapy alone. The standard treatment of locally advanced disease is combined chemoradiation. A special vigilance of fast decrease of the volume of the pathological lymph nodes, sometimes associated to loss of weight might indicate an adaptive dosimetric revision. The treatment of recurrent disease is of great importance. Surgical indications are limited but should be discussed in multidisciplinary tumor board when possible. Surgical nodal sampling has to be proposed for nodal recurrence as well as reirradiation, which could be indicated according to the technical issues.

  4. [Primary radiotherapy of nasopharyngeal carcinoma].

    PubMed

    Rübe, C; Grevers, G; Grimminger, H; Wendt, T; Rohloff, R

    1995-02-01

    One hundred twenty-one patients treated for nasopharyngeal carcinoma with radiation therapy were analyzed; 85 were male, 36 were female. Twenty-one percent had tumour stage T0/T1; 32.5%, T2; 27.5%, T3; and 19%, T4. In 75% of the cases, the lymph nodes were involved. Twelve patients underwent a neck dissection. Histology showed squamous cell carcinoma in 38%, lymphoepitheloid carcinoma in 41.4%, undifferentiated carcinoma in 19%, and adenocarcinoma in 2%. Beginning in 1980, a modified radiation technique with large portals and an increase of the dose from 57.1 Gy to 61.5 Gy targe volume dose was used. Five year overall survival was 32.1%, recurrence-free survival, 30.7%; and local recurrence free survival, 45.8%. Age, sex, and T stage had no significant influence on survival. Multivariate analysis (Cox model) showed that involvement of the lymph nodes, histology, and the new irradiation technique with the higher total dose significantly influenced survival.

  5. Paraneoplastic Neurological Disorder in Nasopharyngeal Carcinoma

    PubMed Central

    Ng, Sze Yin; Kongg, Min Han; Yunus, Mohd Razif Mohamad

    2017-01-01

    Paraneoplastic neurological disorder (PND) is a condition due to immune cross-reactivity between the tumour cells and the normal tissue, whereby the “onconeural” antibodies attack the normal host nervous system. It can present within weeks to months before or after the diagnosis of malignancies. Nasopharyngeal carcinoma is associated with paraneoplastic syndrome, for example, dermatomyositis, and rarely with a neurological disorder. We report on a case of nasopharyngeal carcinoma with probable PND. Otolaryngologists, oncologists and neurologists need to be aware of this condition in order to make an accurate diagnosis and to provide prompt treatment. PMID:28381934

  6. Nasopharyngeal carcinoma presented as cavernous sinus tumour.

    PubMed

    Moona, Mohammad Shafi; Mehdi, Itrat

    2011-12-01

    A 32 year Libyan male presented with the complaints of headache and diplopia. He was diagnosed with a cavernous sinus meningioma on the basis of MRI findings but no initial biopsy was taken. Depending on the radiologic diagnosis the patient was treated with gamma knife surgery twice, abroad. During follow up he developed left ear deafness and left cervical lymph adenopathy. An ENT evaluation with biopsy from the nasopharynx and cervical lymph node was taken. The histopathologic diagnosis of the resected tumour showed a nasopharyngeal carcinoma with cervical lymph node metastasis (poorly differentiated lympho-epithelial carcinoma). The cavernous sinus tumour which was initially treated as a meningioma was in fact metastasis from the nasopharyngeal carcinoma, making this an interesting and rare occurrence.

  7. 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.

  8. 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

  9. Extracting autofluorescence spectral features for diagnosis of nasopharyngeal carcinoma

    NASA Astrophysics Data System (ADS)

    Lin, L. S.; Yang, F. W.; Xie, S. S.

    2012-09-01

    The aim of this study is to investigate the autofluorescence spectral characteristics of normal and cancerous nasopharyngeal tissues and to extract the potential spectral features for diagnosis of nasopharyngeal carcinoma (NPC). The autofluorescence excitation-emission matrix (EEM) of 37 normal and 34 cancerous nasopharyngeal tissues were recorded by a FLS920 spectrofluorimeter system in vitro. Based on the alteration in proportions of collagen and NAD(P)H, the integrated fluorescence intensity of I 455 ± 10 nm and I 380 ± 10 nm were used to calculated the ratio values by a two-peak ratio algorithm to diagnose NPC tissues at 340 nm excited. Furthermore by applying the receiver operating characteristic curve (ROC), the 340 nm excitation yielded an average sensitivity and specificity of 88.2 and 91.9%, respectively. These results may have practical implications for diagnosis of NPC.

  10. 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.

  11. 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

  12. 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.

  13. Current and emerging treatment options for nasopharyngeal carcinoma

    PubMed Central

    Spratt, Daniel E; Lee, Nancy

    2012-01-01

    In this article, we focus on the current and emerging treatments in nasopharyngeal cancer (NPC). A detailed evolution of the current standard of care, and new techniques and treatment options will be reviewed. Intergroup 0099 established the role for chemoradiotherapy (chemo-RT) in the treatment of nasopharyngeal carcinoma. Multiple randomized Phase III trials have shown the benefit of chemo-RT; however, none of these studies utilized modern radiotherapy (RT) techniques of intensity-modulated radiation therapy (IMRT). IMRT has the ability to deliver high doses of radiation to the target structures while sparing adjacent bystander healthy tissues, and has now become the preferred RT treatment modality. Chemotherapy also has had a shifting paradigm of induction and/or adjuvant chemotherapy combined with RT alone, to the investigation with concurrent chemo-RT. New treatment options including targeted monoclonal antibodies and small molecule tyrosine kinase inhibitors are being studied in NPC. These new biologic therapies have promising in vitro activity for NPC, and emerging clinical studies are beginning to define their role. RT continues to expand its capabilities, and since IMRT and particle therapy, specifically intensity-modulated proton therapy (IMPT), has reports of impressive dosimetric efficacy in-silica. Adaptive RT is attempting to reduce toxicity while maintaining treatment efficacy, and the clinical results are still in their youth. Lastly, Epstein– Barr virus (EBV) DNA has recently been studied for prediction of tumor response and its use as a biomarker is increasingly promising to aid in early detection as well as supplementing the current staging system. RT with or without chemotherapy remains the standard of care for nasopharyngeal carcinoma. Advances in RT technique, timing of chemotherapy, biologically targeted agents, particle therapy, adaptive RT, and the incorporation of EBV DNA as a biomarker may aid in the current and future treatment of

  14. A case series of Nasopharyngeal Carcinoma among Indians, a low risk population, in Perak State, Malaysia.

    PubMed

    Anusha, B; Philip, R; Norain, K; Harvinder, S; Gurdeep, S M

    2012-12-01

    Nasopharyngeal carcinoma (NPC) is rare among people of Indian ethnicity. A short retrospective case review of clinical records of Indian patients diagnosed with nasopharyngeal carcinoma in a period of 5 years was conducted. Their slides were further subjected to EBV encoded RNA (EBER) - In- situ Hybridization (ISH). The histologic subtype was nonkeratinizing carcinoma in all 4 patients. All were Epstein Barr Virus (EBV) positive. We believe that the crucial factor responsible for nasopharyngeal carcinoma is genetics; either a genetic susceptibility among high risk groups or genetic resistance/immunity in low risk groups. Further genetic studies are required to look for somatic or inherited chromosomal mutations among the various risk populations.

  15. Interleukin 35 is an independent prognostic factor and a therapeutic target for nasopharyngeal carcinoma

    PubMed Central

    Zhang, Yongquan; Wu, Hui; Tan, Qindong; Xiang, Kai

    2015-01-01

    Aim of the study Interleukin (IL)-35 is composed of two subunits: Epstein-Barr virus-induced gene 3 (EBI3) and IL-12p35. Recently, overexpression of IL-35 has been found in several types of cancers. However, its clinical significance in nasopharyngeal carcinoma is still obscure. We have studied the clinical significance of IL-35 expression and its correlation with outcome of nasopharyngeal carcinoma patients. Material and methods Interleukin 35 expression was investigated in 80 nasopharyngeal carcinoma cases by immunohistochemistry. Moreover, Fisher's exact test, Kaplan-Meier plots, and Cox proportional hazards regression were utilized to analyse these results. Results In the present study, IL-35 is highly expressed in the majority of nasopharyngeal carcinoma samples. EBI3 and p35 immunoreactivity in nasopharyngeal carcinoma samples was 67.5% and 51.3%, respectively. Both EBI3 and p35 expressions were significantly associated with advancement of tumour stage. In addition, EBI3 expression was also correlated with lymph node metastasis. Further analysis showed that EBI3 or p35 staining indicated unfavourable prognosis (p < 0.05). Multivariate analysis suggested EBI3 was an independent prognostic predictor (p < 0.05). Conclusions Our results indicate for the first time that IL-35 is correlated with progression of nasopharyngeal carcinoma. Therefore, IL-35 may be a useful target for the treatment of nasopharyngeal carcinoma. PMID:26034389

  16. Expression Trend of Selected Ribosomal Protein Genes in Nasopharyngeal Carcinoma

    PubMed Central

    Ma, Xiang-Ru; Sim, Edmund Ui-Hang; Ling, Teck-Yee; Tiong, Thung-Sing; Subramaniam, Selva Kumar; Khoo, Alan Soo-Beng

    2012-01-01

    Background: Ribosomal proteins are traditionally associated with protein biosynthesis until recent studies that implicated their extraribosomal functions in human diseases and cancers. Our previous studies using GeneFishing™ DEG method and microarray revealed underexpression of three ribosomal protein genes, RPS26, RPS27, and RPL32 in cancer of the nasopharynx. Herein, we investigated the expression pattern and nucleotide sequence integrity of these genes in nasopharyngeal carcinoma to further delineate their involvement in tumourigenesis. The relationship of expression level with clinicopathologic factors was also statistically studied. Methods: Quantitative Polymerase Chain Reaction was performed on nasopharyngeal carcinoma and their paired normal tissues. Expression and sequence of these three genes were analysed. Results: All three ribosomal protein genes showed no significant difference in transcript expressions and no association could be established with clinicopathologic factors studied. No nucleotide aberrancy was detected in the coding regions of these genes. Conclusion: There is no early evidence to substantiate possible involvement of RPS26, RPS27, and RPL32 genes in NPC tumourigenesis. PMID:23613646

  17. 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.

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

    PubMed

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

    2015-09-17

    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.

  19. Metabolic disorders and the risk of nasopharyngeal carcinoma: a case-control study in Italy.

    PubMed

    Zucchetto, Antonella; Taborelli, Martina; Bosetti, Cristina; Montella, Maurizio; La Vecchia, Carlo; Franchin, Gianni; Libra, Massimo; Serraino, Diego; Polesel, Jerry

    2016-07-29

    The aim of this study is to evaluate the association between metabolic disorders and the risk of nasopharyngeal carcinoma, considering different histological subtypes. Between 1992 and 2008, we carried out a multicentre case-control study in Italy. One-hundred and ninety-seven White patients with histologically confirmed nasopharyngeal carcinoma were enrolled as cases. The control group included 592 cancer-free patients, frequency matched by study centre, area of residence, sex, age and period of interview. Odds ratios (OR) and corresponding 95% confidence intervals (CI), for nasopharyngeal carcinoma according to obesity and self-reported history of other metabolic disorders, were calculated through logistic regression models adjusted for matching variables and tobacco smoking and drinking habits. Obesity (OR=1.44; 95% CI: 0.88-2.36), diabetes mellitus (OR=0.91; 95% CI: 0.42-1.98), hypertension (OR=0.79; 95% CI: 0.48-1.32), hypercholesterolaemia (OR=1.41; 95% CI: 0.84-2.35) and metabolic syndrome (i.e. at least three among the four previously cited metabolic disorders; OR=1.11; 95% CI: 0.86-1.43) were not significantly associated with the overall risk of nasopharyngeal carcinoma. However, the associations observed for diabetes mellitus, hypercholesterolaemia and metabolic syndrome were stronger among differentiated nasopharyngeal carcinomas than among undifferentiated ones. In particular, 21.7% of differentiated nasopharyngeal carcinoma cases and 7.8% of controls reported a history of metabolic syndrome (OR=3.37; 95% CI: 1.05-10.81). The results of the study indicated no overall association between metabolic disorders and nasopharyngeal carcinoma. Nonetheless, although the small sample size calls for caution in interpretation, metabolic disorders could increase the risk of differentiated nasopharyngeal carcinoma. This finding further supports a different aetiology of the two histological subtypes.

  20. Clinical presentation of nasopharyngeal carcinoma in Sarawak Malaysia.

    PubMed

    Tiong, T S; Selva, K S

    2005-12-01

    Nasopharyngeal carcinoma (NPC) is a common cancer in Malaysia. The clinical presentation in Sarawak has not been well documented. A retrospective review of 213 selected NPC cases was undertaken on the clinical records in Sarawak General Hospital, Sarawak, from June 1999 to June 2003. There were 116 patients in Kuching and 97 in Serian. There were twice as many males as females. The youngest patient was 16 and the oldest 88 years old with a mean age of 51 years. The four most common symptoms in order of frequencies were cervical lymphadenopathy, epistaxis, hearing loss and diplopia. 80.8% of the patients presented with cervical lymphadenopathy and about 85% of the patients presented in the advanced stages. Very small percentages of the patients were found to have single presenting symptoms of epistaxis (2.4%) and hearing loss (0.5%).

  1. DNA Methylation Biomarkers for Nasopharyngeal Carcinoma: Diagnostic and Prognostic Tools.

    PubMed

    Jiang, Wei; Cai, Rui; Chen, Qiu-Qiu

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is a common tumor in southern China and south-eastern Asia. Effective strategies for the prevention or screening of NPC are limited. Exploring effective biomarkers for the early diagnosis and prognosis of NPC continues to be a rigorous challenge. Evidence is accumulating that DNA methylation alterations are involved in the initiation and progression of NPC. Over the past few decades, aberrant DNA methylation in single or multiple tumor suppressor genes (TSGs) in various biologic samples have been described in NPC, which potentially represents useful biomarkers. Recently, large-scale DNA methylation analysis by genome-wide methylation platform provides a new way to identify candidate DNA methylated markers of NPC. This review summarizes the published research on the diagnostic and prognostic potential biomarkers of DNA methylation for NPC and discusses the current knowledge on DNA methylation as a biomarker for the early detection and monitoring of progression of NPC.

  2. Differentiation of highly metastatic nasopharyngeal carcinoma cells using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Zhan, Zhenlin; Sun, Zhenzhen; Li, Jingwen; Ye, Qing; Zhuo, Shuangmu; Xie, Shusen

    2016-10-01

    The primary hypothesis tested in the study was that nasopharyngeal carcinoma (NPC) cells at different stage of invasion and metastasis can be differentiated using multiphoton microscopy (MPM). CNE1 and CNE2Z cells were cultured and used in this study. The activity of cell migration and invasion was measured using Transwell assays. At the same time, the morphologic features were quantified from the multiphoton images. The measurements of Transwell migration and invasion showed that the invasion and migration of CNE2Z cells were significantly enhanced when compared with that of CNE1 cells. Also, statistically significant differences in the morphologic features were found between two kinds of cancer cells. In conclusion, it is feasible to use MPM to differentiate cancer cells with different stage of invasion and metastasis.

  3. 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

  4. Stenosing tenosynovitis.

    PubMed

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

    2012-02-01

    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.

  5. Nasopharyngeal carcinoma presenting with rapidly progressive severe visual disturbance: a case report

    PubMed Central

    2014-01-01

    Introduction Nasopharyngeal carcinoma is one of the most difficult tumors to diagnose correctly at the initial phase because of the occasional lack of nasal symptoms. The perineural spread of the trigeminal nerve is one of the most common and important routes in the intracranial paracavernous extension of nasopharyngeal carcinoma, but visual loss is very rare. Case presentation We report the case of a 54-year-old Japanese man with nasopharyngeal carcinoma, who presented with rapid and severe disturbance of left monocular visual acuity and eye movement with a 10-month history of ipsilateral otitis media and facial pain. Magnetic resonance imaging revealed a lesion in the left fossa of Rosenmüller, pterygopalatine fossa, sphenoid and ethmoid sinus, and the left cavernous sinus extending to the orbital apex through the superior orbital fissure. The histopathological diagnosis was nonkeratinizing undifferentiated nasopharyngeal carcinoma. Epstein–Barr virus was detected by in situ hybridization. Although focal radiotherapy induced remarkable tumor shrinkage and relieved ocular motor disturbance and facial pain, his visual acuity did not improve. Conclusion The awareness of cranial nerves in addition to intracranial and orbital apex involvement, as in this case, is important for appropriate diagnosis and treatment planning of nasopharyngeal carcinoma. PMID:25373786

  6. TNFα antagonization alters NOS2 dependent nasopharyngeal carcinoma tumor growth.

    PubMed

    Bourouba, Mehdi; Zergoun, Ahmed-Amine; Maffei, Joseph S; Chila, Dalia; Djennaoui, Djamel; Asselah, Fatima; Amir-Tidadini, Zine-Charef; Touil-Boukoffa, Chafia; Zaman, Muhammad H

    2015-07-01

    Tumor necrosis factor (TNFα) is a pro-inflammatory cytokine which mediates via nitric oxide (NO) several carcinogenic processes. Increasing evidences suggest that NO promotes inflammation induced growth of nasopharyngeal carcinoma (NPC). In patients, TNFα synthesis associates with poor survival. To explore the effect of the cytokine on NO production and NOS2 dependent NPC growth, NO2(-) (nitrite) producing cells in patients were analyzed in vitro. We observed that patients' monocytes/macrophages (Mo/Ma) and primary tumor biopsies synthesized significant amounts of NO2(-). Interestingly, tumor explants derived NO2(-) levels were more important in elderly patients in comparison with juveniles. Endogenous TNFα neutralization with an anti-TNFα monoclonal antibody (mAb) successfully inhibited NO2(-) synthesis by blood mononuclear cells and tumor explants. Recombinant TNFα (rTNFα) enhanced NO2(-) synthesis and C666-1 NPC cell proliferation. NOS2 selective inhibition (1400W) and TNFα antagonization with an anti-TNFα mAb potently inhibited rTNFα induced C666-1 proliferation and NO2(-) production. Importantly, primary tumors treated with the anti-TNFα mAb also displayed reduced proliferation index (Ki67). Altogether, our results define monocytes/macrophages and the primary tumor as major sources of circulating NO2(-) in NPC patients and support the idea that antibody dependent inhibition of the TNFα/NOS2 pathway may alter NPC tumor growth.

  7. Incidental pheochromocytoma in a patient with nasopharyngeal carcinoma.

    PubMed

    Baldane, S; Ipekci, S H; Celik, E; Gedik, G K; Ozaslan, E; Guler, I; Kebapcilar, L

    2015-10-01

    Because the adrenal glands are common locations for metastases, pheochromocytoma is frequently misdiagnosed as adrenal metastasis in patients with a history of cancer. An incidental adrenal mass was detected during an abdominal computed tomography (CT) scan performed to stage the nasopharyngeal carcinoma in a 35-year-old male patient. The features of an adrenal mass on the CT, magnetic resonance imaging (MRI), and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were thought to show adrenal metastasis. However, the patient did not complain about flushing, palpitation, headache or excessive sweating. His blood pressure was 132/74 mmHg, and his pulse rate was 82 bpm. A pheochromocytoma was found during a biochemical diagnosis that evaluated the catecholamine in urine collected over a 24-hour period. The urine had elevated urinary adrenaline, metanephrine, and vanillylmandelic. An I123 MIBG scan showed avid tracer uptake in the right adrenal mass with no evidence of abnormal uptake elsewhere. A right adrenalectomy operation was performed and a diagnosis of pheochromocytoma was confirmed histopathologically. Incidental adrenal masses detected in the presence history of cancer should always be subjected to hormonal evaluation. Although patients may be asymptomatic, the probability of incidental pheochromocytoma should not be ignored.

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

    PubMed

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

    1979-10-01

    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.

  9. 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

  10. 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.

  11. Classification of progression free survival with nasopharyngeal carcinoma tumors

    NASA Astrophysics Data System (ADS)

    Farhidzadeh, Hamidreza; Kim, Joo Y.; Scott, Jacob G.; Goldgof, Dmitry B.; Hall, Lawrence O.; Harrison, Louis B.

    2016-03-01

    Nasopharyngeal carcinoma (NPC) is an abnormal growth of tissue which arises from the back of the nose. At the time of diagnosis, detection of tumor features with prognostic significance, including patient demographics, imaging characteristics and molecular characteristics, can enable the treating clinician to select a treatment that is optimized for the individual patient. At present, the analysis of tumor imaging features is limited to size criteria and macroscopic textural semantic descriptors, but computerized quantification of intratumoral heterogeneity and their temporal evolution may provide another metric for predicting prognosis. We propose medical imaging feature analysis methods and radiomics machine learning methods to predict failure of treatment. NPC tumors on contrast-enhanced T1 (T1Gd) sequences of 25 NPC patients' diagnostic magnetic resonance images (MRI) were manually contoured. Otsu segmentation was applied to segment the tumor into highly enhancing vs. weakly enhancing signal intensity subregions. Within these subregions, texture features were extracted to numerically quantify the intraregional heterogeneity. Patients were divided into two prognostic groups; a progression-freesurvival group (those without locoregional recurrence or distant metastases), and the disease progression group (those with locoregional recurrence or distant metastases). We used Support Vector Machines (SVM) to perform classification (prediction of prognosis). The features from the highly enhancing subregion classify prognosis with 80% predictive accuracy with AUC=0.60, while the captured features from the weakly enhancing subregion classify prognosis with 76% accuracy with AUC= 0.76.

  12. 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

  13. Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma

    PubMed Central

    Chow, Yock Ping; Tan, Lu Ping; Chai, San Jiun; Abdul Aziz, Norazlin; Choo, Siew Woh; Lim, Paul Vey Hong; Pathmanathan, Rajadurai; Mohd Kornain, Noor Kaslina; Lum, Chee Lun; Pua, Kin Choo; Yap, Yoke Yeow; Tan, Tee Yong; Teo, Soo Hwang; Khoo, Alan Soo-Beng; Patel, Vyomesh

    2017-01-01

    In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies. PMID:28256603

  14. Proteomic Characterization Reveals a Molecular Portrait of Nasopharyngeal Carcinoma Differentiation

    PubMed Central

    Xiao, Zhefeng; Li, Maoyu; Li, Guoqing; Fu, Ying; Peng, Fang; Chen, Yongheng; Chen, Zhuchu

    2017-01-01

    Nasopharyngeal carcinoma (NPC) is categorized into three different differentiated subtypes by World Health Organization (WHO). Based on an earlier comparative proteomic database of the three histological subtypes, the study was to deepen our understanding of molecular mechanisms associated with NPC differentiation through bio-information mining. Among the three subtypes were 194 differentially expressed proteins (DEPs) of 725 identified proteins. Two DEPs, heat shock protein family B (small) member 1 (HSPB1) and keratin 5 (KRT5), were validated in a series of NPC tissue samples by using immunohistochemistry. Quantified protein families including keratins, S100 proteins (S100s) and heat shock proteins exhibited characteristic expression alterations. Comparisons of predicted bio-function activation states among different subtypes, including formation of cellular protrusion, metastasis, cell death, and viral infections, were conducted. Canonical pathway analysis inferred that Rho GTPases related signaling pathways regulated the motility and invasion of dedifferentiated NPC. In conclusion, the study explored the proteomic characteristics of NPC differentiation, which could deepen our knowledge of NPC tumorigenesis and allow the development of novel targets of therapeutic and prognostic value in NPC. PMID:28367237

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

    PubMed Central

    DAKER, MAELINDA; BHUVANENDRAN, SAATHEEYAVAANE; AHMAD, MUNIRAH; TAKADA, KENZO; KHOO, ALAN SOO-BENG

    2012-01-01

    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

  16. Nasopharyngeal carcinoma mimicking Aspergillosis rhinosinusitis: an unusual case report and review of the literature.

    PubMed

    Ren, Kexing; Wang, Weiya; Ma, Xuelei; Guo, Fuchun; Li, Ping; Liu, Lei

    2014-01-01

    Clinical symptoms and imaging features of fungal infection are confused with those of atypical nasopharyngeal carcinoma (NPC), and therefore development of a more effective diagnostic method is essential. It is a common knowledge that there is a significant association between Epstein-Barr virus (EBV) and nonkeratinizing NPC. However, fungal infection may be considered to be a vital etiologic agent contributing to the NPC and more evidence is needed to be approved this theory. We report on a rare case of a patient with atypical nasopharyngeal carcinoma (NPC) who suffered from chronic fungal infection and was diagnosed initially as Aspergillosis. Following anti-aspergillus infection therapy, the repeated deep biopsy of the maxillary sinus and MRI confirmed the diagnosis of nasopharyngeal carcinoma (NPC).

  17. Chloroquine Sensitizes Nasopharyngeal Carcinoma Cells but Not Nasoepithelial Cells to Irradiation by Blocking Autophagy

    PubMed Central

    Makowska, Anna; Eble, Michael; Prescher, Kirsten; Hoß, Mareike; Kontny, Udo

    2016-01-01

    Background Treatment of nasopharyngeal carcinoma requires the application of high dosages of radiation, leading to severe long-term complications in the majority of patients. Sensitizing tumor cells to radiation could be a means to increase the therapeutic window of radiation. Nasopharyngeal carcinoma cells display alterations in autophagy and blockade of autophagy has been shown to sensitize them against chemotherapy. Methods We investigated the effect of chloroquine, a known inhibitor of autophagy, on sensitization against radiation-induced apoptosis in a panel of five nasopharyngeal carcinoma cell lines and a SV40-transformed nasoepithelial cell line. Autophagy was measured by immunoblot of autophagy-related proteins, immunofluorescence of autophagosomic microvesicles and electron microscopy. Autophagy was blocked by siRNA against autophagy-related proteins 3, 5, 6 and 7 (ATG3, ATG5, ATG6 and ATG7). Results Chloroquine sensitized four out of five nasopharyngeal cancer cell lines towards radiation-induced apoptosis. The sensitizing effect was based on the blockade of autophagy as inhibition of ATG3, ATG5, ATG6 and ATG7 by specific siRNA could substitute for the effect of chloroquine. No sensitization was seen in nasoepithelial cells. Conclusion Chloroquine sensitizes nasopharyngeal carcinoma cells but not nasoepithelial cells towards radiation-induced apoptosis by blocking autophagy. Further studies in a mouse-xenograft model are warranted to substantiate this effect in vivo. PMID:27902742

  18. Olfactory Training in Improving Sense of Smell After Radiation Therapy in Patients With Paranasal Sinus or Nasopharyngeal Cancer

    ClinicalTrials.gov

    2017-04-06

    Stage 0 Nasopharyngeal Carcinoma; Stage 0 Paranasal Sinus Cancer; Stage I Nasopharyngeal Carcinoma; Stage I Paranasal Sinus Cancer; Stage II Nasopharyngeal Carcinoma; Stage II Paranasal Sinus Cancer; Stage IIA Nasopharyngeal Carcinoma; Stage IIB Nasopharyngeal Carcinoma; Stage III Nasopharyngeal Carcinoma; Stage III Paranasal Sinus Cancer; Stage IV Nasopharyngeal Carcinoma; Stage IV Paranasal Sinus Cancer; Stage IVA Nasopharyngeal Carcinoma; Stage IVA Paranasal Sinus Cancer; Stage IVB Nasopharyngeal Carcinoma; Stage IVB Paranasal Sinus Cancer; Stage IVC Nasopharyngeal Carcinoma; Stage IVC Paranasal Sinus Cancer

  19. 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.

  20. 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.

  1. BEX3 contributes to cisplatin chemoresistance in nasopharyngeal carcinoma.

    PubMed

    Gao, Wei; Li, John Zeng-Hong; Chen, Si-Qi; Chu, Chiao-Yun; Chan, Jimmy Yu-Wai; Wong, Thian-Sze

    2017-02-01

    Nasopharyngeal carcinoma (NPC) can develop cisplatin-resistant phenotype. Research has revealed that enriched in cancer stem cell population is involved in developing cisplatin-resistant phenotype. CD271 is a candidate stem cell maker in head and neck cancers. The CD receptor does not possess any enzymatic property. Signal transduction function of CD271 is mediated by the cellular receptor-associated protein. Our data showed that Brain-expressed X-linked 3 (BEX3), a CD271 receptor-associated protein, was overexpressed in NPC. BEX3 overexpression was a unique event in cancer developed in the head and neck regions, especially NPC. BEX3 expression was inducible by cisplatin in NPC. In cisplatin-resistant NPC xenograft, treatment with nontoxic level of cisplatin led to a remarkable increase in BEX3 level. High BEX3 expression was accompanied with high octamer-binding transcription factor 4 (OCT4) expression in cisplatin-resistant NPC. To confirm the inducing role of BEX3 on OCT4 expression, we knockdown BEX3 using siRNA and compared the expression of OCT4 with mock transfectants. Suppressing BEX3 transcripts led to a significant reduction in OCT4. In addition, targeting BEX3 using shRNA could increase the sensitivity of NPC cells to cisplatin. In summary, our results indicated a unique functional role of BEX3 in mediating the sensitivity of NPC cells to cisplatin. Targeting or blocking BEX3 activity might be useful in reversing the cisplatin-resistant phenotype in NPC.

  2. 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.

  3. 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.

  4. Dropped head syndrome induced by chemoradiotherapy for nasopharyngeal carcinoma: a case report.

    PubMed

    Hashimoto, Yaichiro; Maebayashi, Katsuya; Izumi, Sachiko; Motegi, Atsushi; Mitsuhashi, Norio

    2012-11-01

    'Dropped head syndrome' (DHS) is characterized by severe weakness of the muscles of the back of the neck, resulting in chin-on-chest deformity. Dropped head syndrome induced by radiotherapy is very rare. We report a case of DHS following chemoradiotherapy with a total of 64.8 Gy in 36 fractions for nasopharyngeal carcinoma.

  5. miR-150 inhibits proliferation and tumorigenicity via retarding G1/S phase transition in nasopharyngeal carcinoma

    PubMed Central

    Li, Xiangyong; Liu, Fumei; Lin, Bihua; Luo, Haiqing; Liu, Meilian; Wu, Jinhua; Li, Caihong; Li, Ronggang; Zhang, Xin; Zhou, Keyuan; Ren, Dong

    2017-01-01

    Cancer cells are characterized by a pathological manifestation of uncontrolled proliferation, which results in tumor formation. Therefore, it is necessary to improve understanding of the underlying mechanism of cell cycle control. Here, we report that miR-150 is downregulated in nasopharyngeal carcinoma tissues and cells. Upregulation of miR-150 suppresses nasopharyngeal carcinoma (NPC) cell proliferation and induces G1/S arrest in vitro, and inhibits tumorigenesis in vivo. Conversely, silencing miR-150 yields the opposite effect. Our results further demonstrate that miR-150 retards nasopharyngeal carcinoma cell proliferation and G1/S transition via targeting multiple cell cycle-related genes, including CCND1, CCND2, CDK2 and CCNE2. Therefore, our results uncover a novel mechanistic understanding of miR-150-mediated tumor suppression in NPC, which will facilitate the development of effective cancer therapies against nasopharyngeal carcinoma. PMID:28350089

  6. Reducing radiation-related morbidity in the treatment of nasopharyngeal carcinoma.

    PubMed

    Chan, Jason W; Parvathaneni, Upendra; Yom, Sue S

    2017-02-01

    While radiation therapy is the mainstay of treatment for nasopharyngeal carcinoma, the anatomic location of the nasopharynx in close proximity to radiation-sensitive organs such as the salivary glands, optic nerves and chiasm, cochlea, brainstem and temporal lobes presents a special challenge. Technological approaches to reducing the morbidity of nasopharyngeal cancer irradiation have been historically successful with the evolution from 2D techniques to increasingly conformal forms of radiation therapy. This report reviews normal tissue dose constraints and major considerations in target delineation for patients with nasopharyngeal cancer in the intensity-modulated radiation therapy era. Furthermore, this report discusses more contemporary approaches to toxicity reduction such as the judicious reduction or omission of radiation to low-risk regions and the potential role of particle beam therapy.

  7. Meta-analysis of the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese.

    PubMed

    Jin, Bin; Dong, Pin; Li, Keyong; Shen, Bin; Xie, Jin

    2014-01-01

    Glutathione S-transferase T1 (GSTT1) null genotype has been proven to be associated with risks of many cancers. There were also many studies assessing on the association between GSTT1 null genotype and nasopharyngeal carcinoma risk in Chinese, but the findings from those studies were inconsistent. We performed a meta-analysis to provide a more precise assessment on the effect of GSTT1 null genotype on nasopharyngeal carcinoma risk. The PubMed and Wanfang databases were searched to identify eligible case-control studies on the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese. The pooled odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were used to assess the association. Eight case-control studies with a total of 3,702 individuals were finally included in the meta-analysis. Meta-analysis of a total of eight studies showed that GSTT1 null genotype was significantly associated with increased risk of nasopharyngeal carcinoma in Chinese (OR = 2.27; 95% CI 1.41-3.67; P = 0.001). The finding from cumulative meta-analysis showed that there was a trend of more obvious association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese as data accumulated by publication year. Therefore, the GSTT1 null genotype is significantly associated with increased risk of nasopharyngeal carcinoma in Chinese.

  8. Inflammation-Related DNA Damage and Cancer Stem Cell Markers in Nasopharyngeal Carcinoma

    PubMed Central

    Zhao, Weilin; Midorikawa, Kaoru; Hiraku, Yusuke; Oikawa, Shinji; Zhang, Zhe; Huang, Guangwu

    2016-01-01

    Nitrative and oxidative DNA damage plays an important role in inflammation-related carcinogenesis. To investigate the involvement of stem cells in Epstein-Barr virus infection-related nasopharyngeal carcinoma (NPC), we used double immunofluorescence staining to examine several cancer stem/progenitor cell markers (CD44v6, CD24, and ALDH1A1) in NPC tissues and NPC cell lines. We also measured 8-nitroguanine formation as an indicator of inflammation-related DNA lesions. The staining intensity of 8-nitroguanine was significantly higher in cancer cells and inflammatory cells in the stroma of NPC tissues than in chronic nasopharyngitis tissues. Expression levels of CD44v6 and ALDH1A1 were significantly increased in cancer cells of primary NPC specimens in comparison to chronic nasopharyngitis tissues. Similarly, more intense staining of CD44v6 and ALDH1A1 was detected in an NPC cell line than in an immortalized nasopharyngeal epithelial cell line. In the case of CD24 staining, there was no significant difference between NPC and chronic nasopharyngitis tissues. 8-Nitroguanine was detected in both CD44v6- and ALDH1A1-positive stem cells in NPC tissues. In conclusion, CD44v6 and ALDH1A1 are candidate stem cell markers for NPC, and the increased formation of DNA lesions by inflammation may result in the mutation of stem cells, leading to tumor development in NPC. PMID:27647953

  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. 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

  11. Andrographolide suppresses proliferation of nasopharyngeal carcinoma cells via attenuating NF-κB pathway.

    PubMed

    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.

  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. Nasopharyngeal carcinoma in the people's Republic of China: incidence, treatment, and survival rates

    SciTech Connect

    Hwang, H.N.

    1983-10-01

    The incidence, treatment regimens, and survival rates for nasopharyngeal carcinoma in China, one of the most common cancers in that country, are reviewed. Although treated almost exclusively with megavoltage photon therapy, in some cancer centers intracavitary radium insertions are used to increase the radiation dose to the primary tumor site. A histological study of these tumors shows that patients whose tumors are well-differentiated and contain an abundance of lymphocytes have the best prognosis.

  14. Prognostic aspects in the treatment of juvenile nasopharyngeal carcinoma: a systematic review.

    PubMed

    Gioacchini, Federico Maria; Tulli, Michele; Kaleci, Shaniko; Magliulo, Giuseppe; Re, Massimo

    2017-03-01

    To systematically review and discuss the published data about treatments and outcomes for children and adolescents affected by nasopharyngeal carcinoma. In April 2015, an appropriate string was run on PubMed to retrieve all relevant articles. A cross-check was performed by two of the authors on abstracts and full-text articles found using the selected inclusion and exclusion criteria. A meta-analysis concerning the rate of reported disease-free survival and overall survival was performed. Fifteen studies were identified comprising a total of 865 subjects affected by nasopharyngeal carcinoma. According to the American Joint Committee for Cancer Staging system, the majority of tumors were classified as Stage IV (57.3 %). All included patients underwent radiotherapy, while 687 (79.4 %) received also some regimen of chemotherapy. On the basis of our statistical analysis, the mean (95 % CI) rate of disease-free survival was 66 % (95 % CI 56-76). The mean (95 % CI) rate of the overall survival resulted 68 % (95 % CI 58-78). On the basis of our analysis, it may be affirmed that the prognosis of juvenile nasopharyngeal carcinoma is still unsatisfactory. New reports on homogeneous populations are needed to better define the most influencing prognostic factors and to evaluate the introduction of possible alternative therapeutic protocols.

  15. 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

  16. Two legume defense proteins suppress the mobility of nasopharyngeal carcinoma cells.

    PubMed

    Dan, Xiuli; Ng, Tzi Bun

    2016-12-01

    A 16-kDa trypsin inhibitor was isolated from an edible legume using various chromatographic procedures. The protein was unadsorbed on Affi-gel blue gel but adsorbed on DEAE-Sepharose and Mono Q following which media the protein was subsequently subjected to gel filtration on Superdex 75 and a final 21-fold purification was achieved. This trypsin inhibitor showed remarkable pH and thermal stability. Its inhibitory activity was impaired in the presence of 1 mM dithiothreitol. The anti-proliferative and anti-mobility activities of this trypsin inhibitor and a hemagglutinin isolated from the same legume were tested on nasopharyngeal carcinoma cells. These two defense proteins demonstrated discrepant anti-proliferative efficacies that the hemagglutinin could greatly suppress the proliferation of nasopharyngeal carcinoma cells, while the trypsin inhibitor revealed a minor effect. However, these two proteins could both attenuate the mobility of nasopharyngeal carcinoma cells. The present study revealed the potential of applying plant defense proteins in cancer treatment.

  17. Correlation of metallothionein expression with apoptosis in nasopharyngeal carcinoma

    PubMed Central

    Jayasurya, A; Bay, B H; Yap, W M; Tan, N G

    2000-01-01

    The expression of metallothionein (MT), an intracellular ubiquitous low molecular weight protein thiol with antioxidant properties, was studied in nasopharyngeal cancer (NPC) and correlated with the apoptotic index. Immunohistochemical staining of randomly selected, formalin-fixed and paraffin-embedded normal and malignant nasopharyngeal tissues were analysed for the expression of MT using the commercially available E9 antibody directed against MT I and MT II isoforms. The corresponding apoptosis labelling indices were evaluated by the TUNEL method. Localization of MT at the ultrastructural level was studied by immunogold labelling. All the tumour sections (17 specimens) showed MT-immunopositivity. A direct correlation between the percentage of MT-positive cells and the staining intensity was noted (P< 0.001; Pearson's r = 0.95). There was absence of cytoplasmic staining and only nuclear staining (with localization in the nucleoplasm) was demonstrated in the tumour cells. In normal epithelium of the nasopharynx, the basal layer was stained. An inverse relationship was observed between the level of MT expression and the apoptotic index in the NPC tissues (P = 0.0059; Pearson's r = –0.6380). The results suggest that overexpression of MT in NPC may protect the tumour cells from entering into the apoptotic process and thereby contribute to tumour expansion. Preferential localization of MT in the nuclei of NPC cells may possibly enhance radioresistance since radiotherapy is known to eradicate tumour cells by free radical-induced apoptosis. © 2000 Cancer Research Campaign PMID:10735506

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

    PubMed

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

    2016-08-01

    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.

  19. 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

  20. 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.

  1. New BZLF1 sequence variations in EBV-associated undifferentiated nasopharyngeal carcinoma in southern China.

    PubMed

    Ji, Kun-Mei; Li, Chun-Lin; Meng, Guang; Han, Ai-Dong; Wu, Xu-Li

    2008-01-01

    The viral lytic gene BZLF1 triggers replication of the Epstein-Barr virus (EBV), which is commonly found in nasopharyngeal carcinoma (NPC). Here, RT-PCR revealed five new BZLF1 variants in 8 of 12 NPC and 4 of 12 non-NPC nasopharyngeal biopsies from an NPC-endemic area in southern China. The deduced peptide sequence of the dominant BZLF1 variant differed by 11 amino acids from that of the prototypical strain B95.8 (V01555). Anti-ZEBRA antibody levels were higher in NPC than that in non-NPC patients (P < 0.001). These findings demonstrated a dominant BZLF1 variant in southern Chinese EBV-associated NPC and non-NPC patients.

  2. Diffuse reflectance spectroscopy study of in vitro tissue for nasopharyngeal carcinoma diagnosis

    NASA Astrophysics Data System (ADS)

    Xu, Zhihong; Lin, Xueliang; Ge, Xiaosong; Lin, Duo; Huang, Wei

    2016-10-01

    Diffuse reflectance spectroscopy is a non-contact, non-invasive, and low-cost optical technique that provides real-time feedback about the absorptive characteristics and the microstructure properties of biological tissue. This optical technique shows the potential for monitoring metabolic status associated with malignancy transformation. Nasopharyngeal carcinoma (NPC) is the third most frequently diagnosed cancer associated with virus and is the most common male malignancy with a characteristic regional and racial distribution worldwide. This paper investigates the current screening state of nasopharyngeal malignancies and also provides an overview on the applications of diffuse reflectance spectroscopy in the cancer detection. Furthermore, the latest research relevant to the diagnosis of NPC in vitro tissue using diffuse reflectance spectroscopy is introduced. The results of diffuse reflectance spectroscopy are summarized, showing a significant experimental and clinical value for further NPC detection in vivo in the future.

  3. Cancer stem-like cell: a novel target for nasopharyngeal carcinoma therapy

    PubMed Central

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is the most common cancer originating in the nasopharynx, and is extremely common in southern regions of China. Although the standard combination of radiotherapy and chemotherapy has improved the efficiency in patients with NPC, relapse and early metastasis are still the common causes of mortality. Cancer stem-like cells (CSCs) or tumor initial cells are hypothesized to be involved in cancer metastasis and recurrence. Over the past decade, increasing numbers of studies have been carried out to identify CSCs from human NPC cells and tissues. The present paper will summarize the investigations on nasopharyngeal CSCs, including isolation, characteristics, and therapeutic approaches. Although there are still numerous challenges to translate basic research into clinical applications, understanding the molecular details of CSCs is essential for developing effective strategies to prevent the recurrence and metastasis of NPC. PMID:25158069

  4. BCL2L12 Is a Novel Biomarker for the Prediction of Short-Term Relapse in Nasopharyngeal Carcinoma

    PubMed Central

    Fendri, Ali; Kontos, Christos K; Khabir, Abdelmajid; Mokdad-Gargouri, Raja; Scorilas, Andreas

    2011-01-01

    BCL2-like 12 (BCL2L12 ) is a new member of the apoptosis-related BCL2 gene family, members of which are implicated in various malignancies. Nasopharyngeal carcinoma is a highly metastatic, malignant epithelial tumor, with a high prevalence in Southeast Asia and North Africa. The purpose of the current study was to quantify and investigate the expression levels of the BCL2L12 gene in nasopharyngeal carcinoma biopsies and to assess its prognostic value. Total RNA was isolated from 89 malignant and hyperplastic nasopharyngeal biopsies from Tunisian patients. After testing the quality of the extracted RNA, cDNA was prepared by reverse transcription. A highly sensitive real-time polymerase chain reaction (PCR) method for BCL2L12 mRNA quantification was developed using SYBR® Green chemistry. GAPDH served as a reference gene. Relative quantification analysis was performed using the comparative CT (2−ΔΔCT) method. Higher BCL2L12 mRNA levels were detected in undifferentiated carcinomas of the nasopharynx, rather than in nonkeratinizing nasopharyngeal tumors (P = 0.045). BCL2L12 expression status was also found to be positively associated with the presence of distant metastases (P = 0.014). Kaplan-Meier survival analysis demonstrated that patients with BCL2L12-positive nasopharyngeal tumors have significantly shorter disease-free survival (P = 0.020). Cox regression analysis showed BCL2L12 expression to be an unfavorable and independent prognostic indicator of short-term relapse in nasopharyngeal carcinoma (P = 0.042). Our results suggest that mRNA expression of BCL2L12 may constitute a novel biomarker for the prediction of short-term relapse in nasopharyngeal carcinoma. PMID:21152697

  5. Matrix metalloproteinase 13-containing exosomes promote nasopharyngeal carcinoma metastasis.

    PubMed

    You, Yiwen; Shan, Ying; Chen, Jing; Yue, Huijun; You, Bo; Shi, Si; Li, Xingyu; Cao, Xiaolei

    2015-12-01

    Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. Metastasis is the major cause of death in NPC patients. Increasing evidence indicates that exosomes play a pivotal role in promoting cancer metastasis by enhancing angiogenesis and ECM degradation. Matrix metalloproteinase 13 is an important kind of matrix proteinase that is often overexpressed in various tumors and increases the risk of metastasis. However, little is known about the potential role of MMP13-containing exosomes in NPC. In this study, we found that MMP13 was overexpressed in NPC cells and exosomes purified from conditioned medium (CM) as well as NPC patients' plasma. Transwell analysis revealed that MMP13-containing exosomes facilitated the metastasis of NPC cells. Furthermore, siRNA inhibited the effect of MMP13-containing exosomes on tumor cells metastasis as well as angiogenesis. The current findings provided novel insight into the vital role of MMP13-containing exosomes in NPC progression which might offer unique insights for potential therapeutic strategies for NPC progressions.

  6. 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

  7. Evaluation of Radiation-induced Xerostomia in Patients with Nasopharyngeal Carcinomas

    PubMed Central

    Mohammadi, Narmin; Seyyednejhad, Farshad; Alizadeh Oskoee, Parnian; Savadi Oskoee, Siavash; Mofidi, Niloofar

    2007-01-01

    Background and aims Salivary glands are extremely susceptible to radiation injuries. The aim of this study was to evaluate radiation-induced xerostomia in patients with nasopharyngeal carcinomas, referring to Tabriz Imam Khomeini Hospital in 2005-2006. Materials and methods Thirty patients with nasopharyngeal carcinomas, who received conventional radiotherapy, were included in the present study. The patients’ unstimulated saliva samples were collected at three intervals, i.e. before treatment, 3 weeks after the initiation of treatment and at the end of treatment by spitting, and measured with a graduated pipette. Results The differences in the mean values of the patients’ salivary flow rates at three afore-mentioned intervals were statistically significant (p<0.001). Two-by-two comparison of the mean values of salivary flow rates of all the patients and of males and females, carried out separately, demonstrated statistically significant differences (p<0.0025). However, there were no statistically significant differences between males and females before treatment (p = 0.723), 3 weeks after the initiation of treatment (p = 0.724) and at the end of treatment (p = 0.595). There were no statistically significant relationships between age and a decrease in salivary flow rate in the total sample (p = 0.76, r = -0.057), in males (p = 0.96, r = 0.011) and in females (p = 0.539, r = -0.208). Conclusion Conventional radiotherapy results in severe xerostomia in 3 weeks in patients with nasopharyngeal carcinomas. Age and sex do not influence radiotherapy-induced xerostomia. PMID:23277836

  8. 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.

  9. 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.

  10. A generic RNA pulsed DC based approach for developing therapeutic intervention against nasopharyngeal carcinoma.

    PubMed

    Tyagi, Rajeev K; Parmar, Rajesh; Patel, Naisargee

    2016-11-30

    The recurrent nasopharyngeal carcinoma of head-and-neck cancers pathology showed unique symptoms and clinical characteristics. The complexity of pathology poses challenges for developing therapeutic interventional approaches against nasopharyngeal carcinoma (NPC). The conventional treatment regimens offer limited local control and survival, which, leads to adverse delayed complications. Our study present a generic monocyte derived dendritic cell (MoDC) vaccine strategy for NPC in which RNA is used as a source of tumor-associated antigens (TAAgs). The RNA extracted from well-characterized highly immunogenic NPC cells (C666-1) was transfected into MoDCs. The formulated and characterized cationic liposomes were used to achieving efficient RNA transfection of immature DCs. Further, DCs were forcibly matured with a cytokine cocktail to achieve greater expression of MHC and co-stimulatory molecules. Moreover, our results did not see any effect of RNA or lipids on MoDCs phenotype or cytokine expression. RNA loaded DCs derived from HLA-A2-positive donors were shown to activate effector memory cytotoxic T lymphocytes (CTLs) specific for TAAg ligand expressed by C666-1 cells. Our results show the comparison of cytotoxic response mounted against RNA-loaded DCs with those directly stimulated by C666-1 tumor cells. Our findings suggest that DCs expressing tumor cell RNA primed naïve T cells show T cells priming with lesser cytotoxicity and cytokine secretion when exposed with with C666-1 tumor cells. These results surface the potential of DCs to deliver RNA in NPCs, sufficient presentation of RNA to provoke perdurable immune responses against nasopharyngeal carcinoma. Our results implies that DC based vaccine approach may be useful to develop therapeutic interventional approach in the form of vaccine to address NPCs.

  11. Wernicke’s Encephalopathy in a Patient with Nasopharyngeal Carcinoma: Magnetic Resonance Imaging Findings

    PubMed Central

    Law, Huong Ling; Tan, Suzet; Sedi, Rosleena

    2011-01-01

    We report a case of Wernicke’s encephalopathy in a patient with nasopharyngeal carcinoma with a 3-month history of poor oral intake related to nausea and vomiting due to chemotherapy. The patient later developed deep coma while receiving in-patient therapy. Magnetic resonance imaging of the brain revealed typical findings of Wernicke’s encephalopathy. The patient was treated with thiamine injections, which resulted in subsequent partial recovery of neurological function. This paper stresses the importance of magnetic resonance imaging for prompt diagnosis of Wernicke’s encephalopathy. PMID:22135604

  12. Physcion, a naturally occurring anthraquinone derivative, induces apoptosis and autophagy in human nasopharyngeal carcinoma

    PubMed Central

    Pang, Ming-jie; Yang, Zhun; Zhang, Xing-lin; Liu, Zhao-fang; Fan, Jun; Zhang, Hong-ying

    2016-01-01

    Aim: Physcion is a major bioactive ingredient in the traditional Chinese medicine Radix et Rhizoma Rhei, which has an anthraquinone chemical structure and exhibits a variety of pharmacological activities including laxative, hepatoprotective, anti-inflammatory, anti-microbial and anti-proliferative effects. In this study we investigated the effect of physcion on human nasopharyngeal carcinoma in vitro and in vivo, as well as the mechanisms underlying the anti-tumor action. Methods: The nasopharyngeal carcinoma cell line CNE2 was treated with physcion, and cell viability was detected using MTT and colony formation assays. Flow cytometry was used to assess the cell cycle arrest, mitochondrial membrane potential loss, apoptosis, autophagy and intracellular ROS generation. Apoptotic cell death was also confirmed by a TUNEL assay. The expression of target or marker molecules was determined using Western blotting. The activity of caspase-3, 8, and 9 was detected with an ELISA kit. A xenograft murine model was used to evaluate the in vivo anti-tumor action of physcion, the mice were administered physcion (10, 20 mg·kg−1·d−1, ip) for 30 d. Results: Treatment with physcion (5, 10, and 20 μmol/L) dose-dependently suppressed the cell viability and colony formation in CNE2 cells. Physcion (10 and 20 μmol/L) dose-dependently blocked cell cycle progression at G1 phase and induced both caspase-dependent apoptosis and autophagy in CNE2 cells. Furthermore, physcion treatment induced excessive ROS generation in CNE2 cells, and subsequently disrupted the miR-27a/ZBTB10 axis, resulting in repression of the transcription factor Sp1 that was involved in physcion-induced apoptosis and autophagy. Moreover, physcion-induced autophagy acted as a pro-apoptotic factor, and possibly contributed to physcion-induced apoptosis. In the xenograft murine model, administration of physcion dose-dependently suppressed the tumor growth without affecting the body weight. Furthermore, the anti

  13. Synthesis and photodynamic activities of modified benzochlorin derivatives on nasopharyngeal carcinoma cells

    NASA Astrophysics Data System (ADS)

    Chang, Chi K.; Lau, Yan-Kin; Lai, Tat-Shing; Yeung, Lam-Lung; Leung, Wing-Nang; Mak, Nai-Ki

    2004-06-01

    Nasopharyngeal carcinoma (NPC), endemic in Southern China, is ranked as the fourth leading cause of cancer deaths in Hong Kong. In an effort to develop new PDT agents for cancer treatment, with a particular emphasis on the NPC, we have investigated the benzochlorin-type photosensitizers. The chromophore is functionalized with side chains containing polar and/or cationic groups. Synthetic methods have been developed for such purposes; e.g. 5-chlorosulfonyloctaethylbenzochlorin and 5-bromooctaethylbenzochlorin are used as versatile precursors for the preparation of ammonium and amidinium salts. Preliminary in vitro study of the photodynamic activity of the synthetic compounds indicated that the cationic benzochlorin derivatives display significant photocytotoxicity towards NPC cells.

  14. Angiotensin-(1-7) Decreases Cell Growth and Angiogenesis of Human Nasopharyngeal Carcinoma Xenografts.

    PubMed

    Pei, Nana; Wan, Renqiang; Chen, Xinglu; Li, Andrew; Zhang, Yanling; Li, Jinlong; Du, Hongyan; Chen, Baihong; Wei, Wenjin; Qi, Yanfei; Zhang, Yi; Katovich, Michael J; Sumners, Colin; Zheng, Haifa; Li, Hongwei

    2016-01-01

    Angiotensin-(1-7) [Ang-(1-7)] is an endogenous, heptapeptide hormone acting through the Mas receptor (MasR), with antiproliferative and antiangiogenic properties. Recent studies have shown that Ang-(1-7) has an antiproliferative action on lung adenocarcinoma cells and prostate cancer cells. In this study, we report that MasR levels were significantly upregulated in nasopharyngeal carcinoma (NPC) specimens and NPC cell lines. Viral vector-mediated expression of Ang-(1-7) dramatically suppressed NPC cell proliferation and migration in vitro. These effects were completely blocked by the specific Ang-(1-7) receptor antagonist A-779, suggesting that they are mediated by the Ang-(1-7) receptor Mas. In this study, Ang-(1-7) not only caused a significant reduction in the growth of human nasopharyngeal xenografts, but also markedly decreased vessel density, suggesting that the heptapeptide inhibits angiogenesis to reduce tumor size. Mechanistic investigations revealed that Ang-(1-7) inhibited the expression of the proangiogenic factors VEGF and PlGF. Taken together, the data suggest that upregulation of MasR could be used as a diagnostic marker of NPC and Ang-(1-7) may be a novel therapeutic agent for nasopharyngeal cancer therapy because it exerts significant antiangiogenic activity.

  15. Detection of Mucosal Recurrent Nasopharyngeal Carcinomas After Radiotherapy With Narrow-Band Imaging Endoscopy

    SciTech Connect

    Wang, Wen-Hung; Lin, Yen-Chun; Chen, Wen-Cheng; Chen, Miao-Fen; Chen, Chih-Cheng; Lee, Kam-Fai

    2012-07-15

    Purpose: This study evaluated the feasibility of screening mucosal recurrent nasopharyngeal carcinoma with narrow-band imaging (NBI) endoscopy. Methods and Materials: One hundred and six patients were enrolled. All patients underwent conventional white-light (WL) endoscopic examination of the nasopharynx followed by NBI endoscopy. Biopsies were performed if recurrence was suspected. Results: We identified 32 suspected lesions by endoscopy in WL and/or NBI mode. Scattered brown spots (BS) were identified in 22 patients, and 4 of the 22 who had negative MRI findings were histopathologically confirmed to be neoplasias that were successfully removed via endoscopy. A comparison of the visualization in NBI closer view corresponded to histopathological findings in 22 BS, and the prevalence rates of neoplasias in tail signs, round signs, and irregularities signs were 0% (0/6), 0% (0/7), and 44.4% (4/9), respectively (p = 0.048). The sensitivity, specificity, and diagnostic capability were 37.5%, 92.9% and 0.652 for WL, 87.5%, 74.5% and 0.810 for NBI, and 87.5%, 87.8%, and 0.876 for NBI closer view, respectively. NBI closer view was effective in increasing specificity compared with NBI alone (87.8% vs. 74.5%, p < 0.05), and in increasing sensitivity and diagnostic capability compared to WL alone (87.5% vs. 37.5%, p < 0.05; 0.876 vs. 0.652, p = 0.0001). Conclusions: Although NBI in endoscopy can improve sensitivity of mucosal recurrent nasopharyngeal neoplasias, false-positive (nonneoplasia BS) results may be obtained in areas with nonspecific inflammatory changes due to postradiation effects. NBI closer view not only can offer a timely, convenient, and highly reliable assessment of mucosal recurrent nasopharyngeal carcinoma, it can also make endoscopic removal possible.

  16. Cetuximab concurrent with IMRT versus cisplatin concurrent with IMRT in locally advanced nasopharyngeal carcinoma

    PubMed Central

    Wu, Xin; Huang, Jingwen; Liu, Lei; Li, Hongmei; Li, Ping; Zhang, Jing; Xie, Li

    2016-01-01

    Abstract To evaluate the treatment efficacies and toxicities of concurrent cetuximab-based bioradiotherapy (BRT) or cisplatin-based chemoradiotherapy (CRT) in locally advanced nasopharyngeal carcinoma. :Patients with previously untreated locally advanced nasopharyngeal carcinoma were matched into pairs, and enrolled into the study. All patients were given either BRT or CRT. Survival outcomes, toxicities, and prognostic factors were evaluated. :A total of 112 patients were enrolled. The 5-year overall survival was 79.3% and 79.5% in CRT and BRT arm, respectively (P = 0.797) and the 5-year DFS was 73.5% and 74.6%, respectively (P = 0.953). In toxicity analysis, CRT arm had more significant decrease in white blood cell, platelet, hemoglobin, and severe vomiting, while more severe skin reactions and mucositis were shown in BRT arm. :BRT was not less efficacious than traditional CRT. They lead to different aspects of toxicities. If patients cannot stand more severe toxicities caused by CRT, BRT could be an ideal alternative. PMID:27684830

  17. Effect of intensity-modulated radiotherapy versus two-dimensional conventional radiotherapy alone in nasopharyngeal carcinoma

    PubMed Central

    OuYang, Pu-Yun; Shi, Dingbo; Sun, Rui; Zhu, Yu-Jia; Xiao, Yao; Zhang, Lu-Ning; Zhang, Xu-Hui; Chen, Ze-Ying; Lan, Xiao-Wen; Tang, Jie; Gao, Yuan-Hong; Ma, Jun; Deng, Wuguo; Xie, Fang-Yun

    2016-01-01

    Background Albeit intensity-modulated radiotherapy (IMRT) is currently the recommended radiation technique in treating nasopharyngeal carcinoma, the effect of IMRT versus two-dimensional conventional radiotherapy (2DCRT) alone is still contradictory. Results In the original unmatched cohort of 1198 patients, IMRT obtained comparable 5-year overall survival (OS) (91.3% vs 87.1%, P = 0.120), locoregional relapse-free survival (LRFS) (92.3% vs 90.4%, P = 0.221) and distant metastasis-free survival (DMFS) (92.9% vs 92.1%, P = 0.901) to 2DCRT. In the propensity-matched cohort of 604 patients, no significant survival differences were observed between the two arms (5-year OS 90.9% vs 90.5%, P = 0.655; LRFS 92.5% vs 92.4%, P = 0.866; DMFS 92.5% vs 92.9%, P = 0.384). In multivariate analysis, IMRT did not significantly lower the risk of death, locoregional relapse or distant metastasis, irrespective of tumor stage. Methods Overall, 1198 patients who underwent IMRT (316 patients) or 2DCRT (882 patients) without any chemotherapy was retrospectively analyzed. Patients in both arms were matched at equal ratio using propensity-score matching method. OS, LRFS and DMFS were assessed with Kaplan-Meier method, log-rank test and Cox regression. Conclusions In this propensity-matched study, IMRT showed no survival advantage over 2DCRT alone in nasopharyngeal carcinoma. PMID:27058901

  18. Salinomycin radiosensitizes human nasopharyngeal carcinoma cell line CNE-2 to radiation.

    PubMed

    Zhang, Yongqin; Zuo, Yun; Guan, Zhifeng; Lu, Weidong; Xu, Zheng; Zhang, Hao; Yang, Yan; Yang, Meilin; Zhu, Hongcheng; Chen, Xiaochen

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is primarily treated by chemoradiation. However, how to promote radiation sensitivity in NPC remains a challenge. Salinomycin is potentially useful for the treatment of cancer. This study aimed to explore the radiosensitivity of salinomycin on human nasopharyngeal carcinoma cell line CNE-2. CNE-2 were treated with salinomycin or irradiation, alone or in combination. The cytotoxicity effects of salinomycin were measured using CCK-8 assay. Clonogenic survival assay was used to evaluate the effects of salinomycin on the radiosensitivity of CNE-2. The changes of cell cycle distribution and apoptosis were assayed using flow cytometry. The expression of Caspase3/Bax/Bal-2 was detected by Western blotting. DNA damage was detected via γ-H2AX foci counting. The results showed that salinomycin induced apoptosis and G2/M arrest, increased Bax and cleaved Caspase3, decreased Bcl-2 expression, and increased the formation of γ-H2AX nuclear foci. These data suggest that salinomycin may be a radiosensitizer for NPC radiotherapy.

  19. 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.

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

    ClinicalTrials.gov

    2017-04-10

    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 AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7

  1. 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.

  2. Epstein-barr virus latent membrane protein 1 polymorphism in nasopharyngeal carcinoma and other oral cavity tumors in Russia.

    PubMed

    Senyuta, Natalia; Yakovleva, Larissa; Goncharova, Elena; Scherback, Liana; Diduk, Sergey; Smirnova, Ksenia; Maksimovich, Dmitry; Gurtsevitch, Vladimir

    2014-02-01

    The genetic structure of EBV LMP1 alleles isolated from tumor, blood, and throat washing samples of 22 nasopharyngeal carcinoma patients, 17 patients with other non-EBV-related tumors of the oral cavity, and 19 blood donors have been studied in representatives of Central Russia and the Republics of Northern Caucasus, regions which are non-endemic for nasopharyngeal carcinoma. The analysis of the LMP1 alleles collected revealed that they practically matched previously described LMP1 variants; however, some characteristic features were also detected. In particular, the G212S substitution in LMP1 isolates investigated was not observed at all. Tumor samples obtained from nasopharyngeal carcinoma and other tumors of the oral cavity did not differ significantly either in the frequency of "high oncogenic" LMP1 alleles with 10 aa and/or 23 aa deletions (LMP1(China1) and/or LMP1(Med+)), nor in the number of 11 aa repeats and the frequency of 5 aa motif insertions. No differences in the frequency of amino acid substitutions between LMP1 alleles obtained from tumor and throat washing samples of both patient groups were also detected. The data obtained may indicate that in both nasopharyngeal carcinoma patients and patients with other tumors of the oral cavity, the EBV strains with similar LMP1 variants are found to persist. This observation allows us to suggest that in non-endemic areas, EBV strains with any LMP1 alleles can initiate the nasopharyngeal carcinoma development but only in those individuals who have a genetic predisposition to the disease and are subjected to specific environmental, and/or dietary factors present in certain geographic areas.

  3. Cyclooxygenase-2 expression is positively associated with lymph node metastasis in nasopharyngeal carcinoma

    PubMed Central

    Yang, Gui; Deng, Qiaoling; Fan, Wei; Zhang, Zheng; Xu, Peipei; Tang, Shihui; Wang, Ping; Wang, Jun’e

    2017-01-01

    Background Accumulating evidence has demonstrated that cyclooxygenase-2 (COX-2) is involved in head and neck cancers, especially in nasopharyngeal carcinoma (NPC). However, the association between COX-2 expression and lymph node metastasis in NPC remains uncertain. This systematic review and meta-analysis meta-analysis investigated the relationship between COX-2 expression and lymph node metastasis and other signs of disease progression in NPC. Methods Previously published studies assessing COX-2 expression and lymph node metastasis in NPC were identified in four English databases and three Chinese ones (Pubmed, Embase, Cochrane Database of Systematic Reviews, Web of Science, China National Knowledge Infrastructure, Wanfang, Vip Journal Integration Platform) up to November 2016. Quality of all eligible studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Pooled odds ratios (OR) and their 95% confidence intervals (95%CI) were calculated with fixed-effects or random-effects model to evaluate the effects of COX-2 expression on lymph node metastasis. Results A total of 27 studies with 1797 NPC patients met the inclusion criteria. The expression of COX-2 was significantly higher in patients with nasopharyngeal carcinoma than those without the carcinoma, with a combined OR of 21.17 (95%CI = 15.02–29.85, I2 = 35.1%, Pheterogeneity = 0.070). A statistically significant association between COX-2 expression and lymph node metastasis in NPC patients, with an OR of 4.44 (95%CI = 3.46–5.70, I2 = 38.3%, Pheterogeneity = 0.024), and with other indicators of disease progression. Subgroup analyses based on COX-2 assay and staging criteria of TNM showed no significant heterogeneity. Conclusions The results suggest that expression of COX-2 is associated with lymph node metastasis and disease progression in NPC, indicating a potential role in evaluation of prognosis and in treatment decisions. COX-2 inhibitors have potential in the treatment of NPC that

  4. STGC3 inhibits xenograft tumor growth of nasopharyngeal carcinoma cells by altering the expression of proteins associated with apoptosis

    PubMed Central

    Qiu, Qing-chao; Hu, Bo; He, Xiu-pei; Luo, Qiao; Tang, Guo-hua; Long, Zhi-feng; Chen, Zhu-chu; He, Xiu-sheng

    2012-01-01

    STGC3 is a potential tumor suppressor that inhibits the growth of the nasopharyngeal carcinoma cell line CNE2; the expression of this protein is reduced in nasopharyngeal carcinoma compared with normal nasopharyngeal tissue. In this study, we investigated the tumor-suppressing activity of STGC3 in nude mice injected subcutaneously with Tet/pTRE-STGC3/CNE2 cells. STGC3 expression was induced by the intraperitoneal injection of doxycycline (Dox). The volume mean of Tet/pTRE-STGC3/CNE2+Dox xenografts was smaller than that of Tet/pTRE/CNE2+Dox xenografts. In addition, Tet/pTRE-STGC3/CNE2+Dox xenografts showed an increase in the percentage of apoptotic cells, a decrease in Bcl-2 protein expression and an increase in Bax protein expression. A proteomic approach was used to assess the protein expression profile associated with STGC3-mediated apoptosis. Western blotting confirmed the differential up-regulation of prohibitin seen in proteomic analysis. These results indicate that overexpression of STGC3 inhibits xenograft growth in nude mice by enhancing apoptotic cell death through altered expression of apoptosis-related proteins such as Bcl-2, Bax and prohibitin. These data contribute to our understanding of the function of STGC3 in human nasopharyngeal carcinoma and provide new clues for investigating other STGC3-associated tumors. PMID:22481869

  5. Identification of genes involved in Epstein-Barr virus-associated nasopharyngeal carcinoma

    PubMed Central

    Wang, Junguo; Mei, Fang; Gao, Xia; Wang, Shoulin

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is the most common cancer originating from the nasopharynx, and can be induced by infection with Epstein-Barr virus (EBV). To study the mechanisms of EBV-associated NPC, a microarray of the GSE12452 dataset was analyzed. GSE12452 was downloaded from Gene Expression Omnibus and consisted of 31 NPC samples and 10 normal healthy nasopharyngeal tissue samples. The differentially-expressed genes (DEGs) were screened using the linear models for microarray data package in R. Using Database for Annotation, Visualization and Integrated Discovery software, potential functions of the DEGs were predicted by Gene Ontology and pathway enrichment analyses. With the information from the Search Tool for the Retrieval of Interacting Genes/Proteins database, the protein-protein interaction (PPI) network was visualized by Cytoscape. Furthermore, modules of the PPI network were searched using ClusterONE in Cytoscape. A total of 951 DEGs were screened in the NPC samples compared with the normal healthy nasopharyngeal tissue samples. Function enrichment indicated that the upregulated genes were associated with the cell cycle, cytoskeleton organization and DNA metabolism. Meanwhile, the downregulated genes were mainly associated with cell differentiation, hormone metabolism, inflammatory response and immune response. PPI networks for the DEGs suggested that upregulated mitotic arrest deficient 2-like 1 (MAD2L1; degree=133), proliferating cell nuclear antigen (PCNA; degree=125) and cyclin B1 (CCNB1; degree=115), and downregulated member A1 of aldehyde dehydrogenase 1 (ALDH1A1; degree=15) may be of great importance as they exhibited higher degrees on interaction. Mucin 1 (MUC1) was a key node of module 4. Overall, the study indicated that MAD2L1, CCNB1, PCNA, ALDH1A1 and MUC1 may have a correlation with EBV-associated NPC. PMID:27698802

  6. Radiation-Guided Peptide Delivery in a Mouse Model of Nasopharyngeal Carcinoma

    PubMed Central

    Lin, Pei-cheng; He, Jun-yan; Le, Yu-yin; Du, Kai-xin; Zhu, Wei-feng; Peng, Qing-qin; Dong, Ya-ping

    2016-01-01

    Purpose. This study aimed to evaluate the characteristics of the HVGGSSV peptide, exploring radiation-guided delivery in a mouse model of nasopharyngeal carcinoma. Methods. Mice with CNE-1 nasopharyngeal carcinoma were assigned to two different groups treated with Cy7-NHS and Cy7-HVGGSSV, respectively. Meanwhile, each mouse received a single dose of 3 Gy radiation. Biological distribution of the recombinant peptide was assessed on an in vivo small animal imaging system. Results. The experimental group showed maximum fluorescence intensity in irradiated tumors treated with Cy7-labeled HVGGSSV, while untreated (0 Gy) control tumors showed lower intensity levels. Fluorescence intensities of tumors in the right hind limbs of experimental animals were 7.84 × 107 ± 1.13 × 107, 1.35 × 108 ± 2.66 × 107, 4.05 × 108 ± 1.75 × 107, 5.57 × 108 ± 3.47 × 107, and 9.26 × 107 ± 1.73 × 107 photons/s/cm2 higher compared with left hind limb values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence intensities of tumor in the right hind limbs of the experimental group were 1.66 × 108 ± 1.71 × 107, 1.51 × 108 ± 3.23 × 107, 5.38 × 108 ± 1.96 × 107, 5.89 × 108 ± 3.57 × 107, and 1.62 × 108 ± 1.69 × 107 photons/s/cm2 higher compared with control group values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence was not specifically distributed in the control group. Compared with low fluorescence intensity in the heart, lungs, and tumors, high fluorescence distribution was found in the liver and kidney at 48 h. Conclusions. HVGGSSV was selectively bound to irradiated nasopharyngeal carcinoma, acting as a targeting transport carrier for radiation-guided drugs that are mainly metabolized in the kidney and liver. PMID:27738632

  7. 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

  8. P300 promotes migration, invasion and epithelial-mesenchymal transition in a nasopharyngeal carcinoma cell line

    PubMed Central

    Liao, Zhi-Wei; Zhao, Lei; Cai, Mu-Yan; Xi, Mian; He, Li-Ru; Yu, Fang; Zhou, Tong-Chong; Liu, Meng-Zhong

    2017-01-01

    A previous study demonstrated that p300 is overexpressed in nasopharyngeal carcinoma (NPC), and that its expression is an independent prognostic factor. The aim of the present study is to investigate the role of p300 in human NPC development. A small hairpin (sh) RNA lentiviral expression vector targeting the p300 gene was constructed to suppress the expression of p300 in NPC cells. Knockdown of p300 was verified by reverse transcription-quantitative polymerase chain reaction and western blotting. Wound-healing, invasion, immunofluorescence and immunoprecipitation assays were performed to assess the influence of p300 on nasopharyngeal tumorigenesis and metastasis in vitro. The expression of p300 was upregulated in NPC cell lines. After knockdown of p300, the migration and invasion ability of shp300 cells were significantly inhibited (P<0.05). Furthermore, the depletion of p300 expression in NPC cell lines resulted in the upregulation of epithelial phenotype marker E-cadherin and α-catenin, and downregulation of mesenchymal phenotype markers N-cadherin and vimentin. p300 promotes epithelial-mesenchymal transition (EMT) through the acetylation of Smad2 and Smad3 in the tumor growth factor-β signaling pathway. In conclusion, p300 may be involved in the invasion and metastasis of NPC through the induction of EMT. PMID:28356956

  9. Cancer stem-like cells in Epstein-Barr virus-associated nasopharyngeal carcinoma.

    PubMed

    Lun, Samantha Wei-Man; Cheung, Siu-Tim; Lo, Kwok-Wai

    2014-11-01

    Although the Epstein-Barr virus (EBV) has spread to all populations in the world, EBV-associated nasopharyngeal carcinoma (NPC) is prevalent only in South China and Southeast Asia. The role of EBV in the malignant transformation of nasopharyngeal epithelium is the main focus of current researches. Radiotherapy and chemoradiotherapy have been successful in treating early stage NPC, but the recurrence rates remain high. Unfortunately, local relapse and metastasis are commonly unresponsive to conventional treatments. These recurrent and metastatic lesions are believed to arise from residual or surviving cells that have the properties of cancer stem cells. These cancer stem-like cells (CSCs) have the ability to self-renew, differentiate, and sustain propagation. They are also chemo-resistant and can form spheres in anchorage-independent environments. This review summarizes recent researches on the CSCs in EBV-associated NPC, including the findings regarding cell surface markers, stem cell-related transcription factors, and various signaling pathways. In particular, the review focuses on the roles of EBV latent genes [latent membrane protein 1 (LMP1) and latent membrane protein 2A (LMP2A)], cellular microRNAs, and adenosine triphosphate (ATP)-binding cassette chemodrug transporters in contributing to the properties of CSCs, including the epithelial-mesenchymal transition, stem-like transition, and chemo-resistance. Novel therapeutics that enhance the efficacy of radiotherapy and chemoradiotherapy and inhibitors that suppress the properties of CSCs are also discussed.

  10. [Genetic polymorphism of cytochrome P450 2E1 and the risk of nasopharyngeal carcinoma].

    PubMed

    Ben Chaaben, Arij; Abaza, Hajer; Douik, Hayet; Chaouch, Leila; Ayari, Fayza; Ouni, Nesrine; Mamoghli, Tasnim; Ben Guezella, Dorra; Mejri, Rachida; Harzallah, Latifa; Guemira, Fethi

    2015-12-01

    Cytochrome P450 2E1 (CYP2E1) is a detoxifying enzyme that belongs to the phase I metabolism of xenobiotics. This enzyme is encoded by a highly polymorphic gene whose common polymorphism corresponds to the substitution of cytosine (C) and thymine (T) at position -1019 (rs2031920). This polymorphism has been identified in several cancers including nasopharyngeal cancer (NPC). The study involved 124 patients with nasopharyngeal carcinoma, compared with 166 healthy controls. The presence or absence of the polymorphism is determined by PCR-RFLP. The frequency comparison between the two groups is determined by the χ(2) test. The analysis of our results showed a significant difference between the two groups regarding the mutant genotype (C2/C2) (5% vs. 0.5%, P=0.04) and has a risk factor for NPC in Tunisia (OR=8.39; CI 95% [0.99-388.1]). Also, the C2 allele was significantly associated with the group of patients than the control group (6% vs. 2%, P=0.016) and increased three times the risk of NPC in Tunisia (OR=2.99, CI 95% [1.12-8.79]). Our results confirm the results reported in other populations and emphasize the importance of the involvement of this gene in the development of detoxification of the NPC, which seems more and more strongly associated with environmental factors.

  11. Early discrimination of nasopharyngeal carcinoma based on tissue deoxyribose nucleic acid surface-enhanced Raman spectroscopy analysis

    NASA Astrophysics Data System (ADS)

    Qiu, Sufang; Li, Chao; Lin, Jinyong; Xu, Yuanji; Lu, Jun; Huang, Qingting; Zou, Changyan; Chen, Chao; Xiao, Nanyang; Lin, Duo; Chen, Rong; Pan, Jianji; Feng, Shangyuan

    2016-12-01

    Surface-enhanced Raman spectroscopy (SERS) was employed to detect deoxyribose nucleic acid (DNA) variations associated with the development of nasopharyngeal carcinoma (NPC). Significant SERS spectral differences between the DNA extracted from early NPC, advanced NPC, and normal nasopharyngeal tissue specimens were observed at 678, 729, 788, 1337, 1421, 1506, and 1573 cm-1, which reflects the genetic variations in NPC. Principal component analysis combined with discriminant function analysis for early NPC discrimination yielded a diagnostic accuracy of 86.8%, 92.3%, and 87.9% for early NPC, advanced NPC, and normal nasopharyngeal tissue DNA, respectively. In this exploratory study, we demonstrated the potential of SERS for early detection of NPC based on the DNA molecular study of biopsy tissues.

  12. Notch inhibition suppresses nasopharyngeal carcinoma by depleting cancer stem-like side population cells.

    PubMed

    Yu, Shudong; Zhang, Ruxin; Liu, Fenye; Wang, Hong; Wu, Jing; Wang, Yanqing

    2012-08-01

    The cancer stem cell (CSC) is responsible for the initiation, proliferation and radiation resistance. Side population (SP) cells are a rare subset of cells enriched with CSCs. The targeting of key signaling pathways that are active in CSCs is a therapeutic approach to treating cancer. Notch signaling is important for the self-renewal and maintenance of stem cells. Our previous studies demonstrated that downregulation of Notch signaling could enhance radiosensitivity of nasopharyngeal carcinoma (NPC) cells. In this study, we found that Notch signaling was highly activated in SP cells compared with that of non-SP (NSP) cells of NPC. Therefore, Notch inhibition could reduce the proportion of SP cells. As SP cells decreased, proliferation, anti-apoptosis and tumorigenesis were also decreased. This study shows that Notch inhibition may be a promising clinical approach in CSC-targeting therapy for NPC.

  13. Light-activated hypericin induces cellular destruction of nasopharyngeal carcinoma cells

    NASA Astrophysics Data System (ADS)

    Xu, C. S.; Leung, A. W. N.

    2010-01-01

    Hypericin from Hypericum perforatum plants shows an important promise in the photodynamic therapy on malignant tumor. The present study investigated that light-activated hypericin induced the cellular destruction of nasopharyngeal carcinoma cells. The result showed that hypericin resulted in a drug- and light-dose dependent cytotoxicity in the CNE-2 cells, meaning the photocytotoxicity of hypericin depends on both of the drug concentration (0 - 2.5 μM) and light-doses (1 - 8 J/cm2). We further investigated the apoptosis of the CNE-2 cells 8 hours after photosensitization of hypericin using fluorescence microscopy with Hoechst 33258 staining. Flow cytometry with annexin V-FITC and PI staining was used to analyze early and late apoptosis. These data demonstrated that light-activated hypericin could significantly lead to the cellular destruction of the CNE-2 cells and induce early apoptosis as a prominent mode of cell death.

  14. Incidence of nasopharyngeal carcinoma in Malaysia, with special reference to the state of Selangor.

    PubMed

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

    1974-07-01

    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.

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

    PubMed

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

    2015-10-06

    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 directly suppressing 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.

  16. Multidisciplinary Treatment Approach in a Patient with History of Nasopharyngeal Carcinoma

    PubMed Central

    Yavuz, Atacan; Ağralı, Ömer Birkan; Çalışkan, Zeynep Lale; Türkaydın, Dilek; Sertgöz, Atilla; Doğan, Başak

    2014-01-01

    Radiotherapy in NPC patients has side effects on the dentition, which affects quality of life dramatically. This case report presents multidisciplinary dental treatment approach in a 17-year-old male patient with a history of nasopharyngeal carcinoma (NPC), which was treated with chemotherapy and radiotherapy. The adolescent patient applied to dental hospital 4 years after the radiotherapy with aesthetic and functional problems on dentition affecting psychological, social, and physical aspects of his life. The dentition of the patient demonstrated the severe destruction as a devastating side effect of radiotherapy. With a successful multidisciplinary approach, our patient's aesthetics, function, and self-confidence were obtained. Well-established procedures, which include preventative care and maintenance, can reduce the duration and expenses of the treatment and help in challenging the life-long complications of radiotherapy. PMID:24523971

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

    PubMed Central

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

    2016-01-01

    Abstract 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. Molecular pathological study of the human nasopharyngeal carcinoma CNE3 cell line

    PubMed Central

    LIU, FEI; JIAO, WEI; MO, XIANG-LAN; LAN, JIAO; XIAO, RUI-PING; ZHOU, XIANG-ZHEN; HUANG, ZHEN-LU; MO, XIAO-MIN; LI, GANG

    2013-01-01

    The present study aimed to identify the molecular pathological changes of the nasopharyngeal carcinoma (NPC) epithelial CNE3 cell line, which has been used in experimental studies for 20 years in a culture environment. The pathological type of NPC and the presence of the Epstein-Barr virus (EBV) were identified. CNE3 short tandem repeats (STRs) were amplified, analyzed and compared using metastatic carcinoma tissue from primary NPC. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to identify the immunophenotype and EBV-encoded small RNA (EBER) expression in nude mice transplanted CNE3 tumor cells. Polymerase chain reaction (PCR) and DNA sequencing were used to identify the EBV oncogene, BamH1-A right frame 1 (BARF1) and electron microscopy was used to analyze the organization of the ultrastructure. CNE3 was not cross-contaminated by other human cell lines and the EBV was no longer present in the CNE3 cells. The pathological type of CNE3 was transformed from an undifferentiated non-keratinizing carcinoma with focal adenocarcinoma differentiation into a poorly-differentiated adenocarcinoma. In conclusion, this knowledge on the molecular pathological changes of CNE3 may aid in the development of new research approaches for NPC. PMID:24137449

  4. Surgical management of extensive osteoradionecrosis in nasopharyngeal carcinoma patients with the maxillary swing approach and free muscular flaps.

    PubMed

    Choi, N Y; Kim, H J; Baek, Chung-Hwan

    2017-03-17

    Radiation therapy has been a standard treatment for nasopharyngeal carcinoma. However, it can cause extensive osteoradionecrosis which is associated with catastrophic complications including carotid artery rupture, cerebral infection, brain necrosis and cachexia.(1,2,3,4) Most of the cases of limited osteoradionecrosis of the nasopharynx have been treated by endoscopic debridement with a favorable success rate.(3.) This article is protected by copyright. All rights reserved.

  5. Functional evidence for a nasopharyngeal carcinoma tumor suppressor gene that maps at chromosome 3p21.3

    PubMed Central

    Cheng, Yue; Poulos, Nicholas E.; Lung, Maria L.; Hampton, Garret; Ou, Baoxiang; Lerman, Michael I.; Stanbridge, Eric J.

    1998-01-01

    Nasopharyngeal carcinoma is a malignancy that is prevalent among populations from Southeast Asia. Epidemiological studies indicate that genetic predisposition, Epstein–Barr virus, and environmental conditions may play a role in determining incidence. Molecular studies have implicated a tumor suppressor gene(s) on the short arm of chromosome 3. In this study we provide functional evidence, via monochromosome transfer, for a tumor suppressor gene(s) activity in chromosome 3p21.3. PMID:9501212

  6. 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.

  7. 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

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

    PubMed Central

    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

    2016-01-01

    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 the MST1R pathogenic heterozygous germ-line variants, and 53.8% of these cases were diagnosed with NPC aged at or even younger than 20 y, indicating that MST1R germ-line variants are relevant to disease early-age onset (EAO) (age of ≤20 y). In total, five MST1R missense 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 the MST1R variant c.G917A:p.R306H is highly associated with NPC (odds ratio of 9.0). MST1R is 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 of MST1R was identified in the sporadic NPC tumors, copy number alterations and promoter hypermethylation at MST1R were often observed. Our findings provide new insights into the pathogenesis of NPC by highlighting the involvement of the MST1R-mediated signaling pathways. PMID:26951679

  9. 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.

  10. Chemosensitizing Effect of Astragalus Polysaccharides on Nasopharyngeal Carcinoma Cells by Inducing Apoptosis and Modulating Expression of Bax/Bcl-2 Ratio and Caspases

    PubMed Central

    Zhou, Zhen; Meng, Minhua; Ni, Haifeng

    2017-01-01

    Background Platinum-based chemotherapy is the most effective regimen for nasopharyngeal carcinoma, which presents highly invasive and metastatic activity. However, the dose-related toxicity of chemotherapy agents limits the dose administration. Astragalus polysaccharide (APS) is the major active ingredient extracted from Chinese herb Radix Astragali and is proven to be active against carcinomas. We aimed to assess the chemosensitizing effects of Astragalus polysaccharides on nasopharyngeal carcinoma in vitro and in vivo and to explore the underlying mechanism. Material/Methods We used BALB/c nu/nu mice and human nasopharyngeal carcinoma cell lines CNE-1, CNE-2, and SUNE-1. MTT, Annexin V/PI, Western blot analysis, and TUNEL assay were carried out. Results APS significantly promoted anti-proliferative and apoptotic effects of cisplatin on nasopharyngeal carcinoma cells. APS also enhanced the anti-tumor effects and cisplatin-induced apoptosis in the xenograft model. The level of Bcl-2 decreased, while the levels of Bax, caspase-3, and caspase-9 increased in cisplatin combined with APS treatment compared to cisplatin only treatment. The ratio of Bax to Bcl-2 was significantly enhanced by the APS to cisplatin. Conclusions APS enhanced the anti-proliferative and apoptotic effect of cisplatin by modulating expression of Bax/Bcl-2 ratio and caspases on nasopharyngeal carcinoma cells and in the xenograft model. PMID:28124680

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

    PubMed

    Zheng, Xiao-Hui; Lu, Li-Xia; Cui, Cui; Chen, Ming-Yuan; Li, Xi-Zhao; Jia, Wei-Hua

    2016-01-26

    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.

  12. 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

  13. Diet, living conditions and nasopharyngeal carcinoma in Tunisia--a case-control study.

    PubMed

    Jeannel, D; Hubert, A; de Vathaire, F; Ellouz, R; Camoun, M; Ben Salem, M; Sancho-Garnier, H; de-Thé, G

    1990-09-15

    We conducted a case-control study of nasopharyngeal carcinoma (NPC) in Tunisia, on diet, dietary patterns and life style, the characteristics of which had been defined by an anthropological study. Eighty incident cases, diagnosed in Tunisia between November 1986 and November 1987, were each matched for sex, age and place of residence to 2 controls. The subjects were asked for dietary data referring to the year preceding the diagnosis of NPC and, with help of their families, during childhood and after weaning. After adjustment for an empirical living conditions score, the following food items were found to be associated with an increased risk for NPC: preserved spiced meat (quaddid), basic stewing preparation (mixture of red and black pepper, garlic, oil, caraway and coriander), and harissa (red pepper, olive oil, garlic, caraway, salt) taken with bread as a snack during childhood and youth. Moreover, subjects who had been directly weaned from mother's milk on to an adult diet were found to be at higher risk for NPC.

  14. Targeting annexin A2 reduces tumorigenesis and therapeutic resistance of nasopharyngeal carcinoma

    PubMed Central

    Chao, Pin-Zhir; Chiou, Jeng-Fong; Kuo, Chia-Chun; Lee, Fei-Peng; Lin, Yung-Feng; Sung, Yu-Hsuan; Lin, Yun-Tien; Li, Chang-Fan

    2015-01-01

    The expression of annexin A2 (ANXA2) in nasopharyngeal carcinoma (NPC) cells induces the immunosuppressive response in dendritic cells; however, the oncogenic effect and clinical significance of ANXA2 have not been fully investigated in NPC cells. Immunohistochemical staining for ANXA2 was performed in 61 patients and the association with clinicopathological status was determined. Short hairpin (sh)RNA knockdown of ANXA2 was used to examine cellular effects of ANXA2, by investigating alterations in cell proliferation, migration, invasion, adhesion, tube-formation assay, and chemo- and radiosensitivity assays were performed. RT-qPCR, Western blotting, and immunofluorescence were applied to determine molecular expression levels. Clinical association studies showed that the expression of ANXA2 was significantly correlated with metastasis (p = 0.0326) and poor survival (p = 0.0256). Silencing of ANXA2 suppressed the abilities of cell proliferation, adhesion, migration, invasion, and vascular formation in NPC cell. ANXA2 up-regulated epithelial-mesenchymal transition associated signal proteins. Moreover, ANXA2 reduced sensitivities to irradiation and chemotherapeutic drugs. These results define ANXA2 as a novel prognostic factor for malignant processes, and it can serve as a molecular target of therapeutic interventions for NPC. PMID:26196246

  15. A rare case of nasopharyngeal carcinoma in a patient with multiple myeloma after treatment by lenalidomide

    PubMed Central

    Xu, Gaixiang; Wang, Bo; Yang, Min; Qian, Wenbin

    2015-01-01

    Multiple myeloma (MM) is a plasma-cell malignancy leading to a significant life-expectancy shortening. Lenalidomide is an oral immunomodulatory drug (IMiD) approved in the United States for patients with MM. Although the introduction of lenalidomide combined with dexamethasone (Len/Dex) has improved the outcome of patients with relapsed/refractory multiple myeloma (RRMM), it is a common knowledge that lenalidomide has been linked to the development of secondary primary malignancies in the MM patients, especially in those who use lenalidomide as a maintenance therapy. In the published literature, these are also many cases reported by clinicians in different secondary primary malignancies after the diagnosis of MM treated with lenalidomide. In this present article, we provided our patient who was identified nasopharyngeal carcinoma (NPC) 46 months after the diagnosis of MM and 21 months after lenalidomide treatment. To the best of our knowledge, this is the first case report related to the occurrence of NPC in a patient with MM after treatment by lenalidomide. Although it is not very sure that the incidence of NPC was associated with the use of lenalidomide, we clinicians should pay adequate attention to this phenomenon in the clinical processing. And much more cooperative studies of large numbers of MM patients are needed to evaluate a possible association between lenalidomide and NPC. PMID:26823839

  16. 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

  17. SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma

    PubMed Central

    Luo, Yanzhang; Mok, Tin Seak; Lin, Xiuxian; Zhang, Wanling; Cui, Yizhi; Guo, Jiahui; Chen, Xing; Zhang, Tao; Wang, Tong

    2017-01-01

    Nasopharyngeal carcinoma (NPC) is a serious threat to public health, and the biomarker discovery is of urgent needs. The data-independent mode (DIA) based sequential window acquisition of all theoretical fragment-ion spectra (SWATH) mass spectrometry (MS) has been proved to be precise in protein quantitation and efficient for cancer biomarker researches. In this study, we performed the first SWATH-MS analysis comparing the NPC and normal tissues. Spike-in stable isotope labeling by amino acids in cell culture (super-SILAC) MS was used as a shotgun reference. We identified and quantified 1414 proteins across all SWATH-MS analyses. We found that SWATH-MS had a unique feature to preferentially detect proteins with smaller molecular weights than either super-SILAC MS or human proteome background. With SWATH-MS, 29 significant differentially express proteins (DEPs) were identified. Among them, carbonic anhydrase 2 (CA2) was selected for further validation per novelty, MS quality and other supporting rationale. With the tissue microarray analysis, we found that CA2 had an AUC of 0.94 in differentiating NPC from normal tissue samples. In conclusion, SWATH-MS has unique features in proteome analysis, and it leads to the identification of CA2 as a potentially new diagnostic biomarker for NPC. PMID:28117408

  18. Domestic incense burning and nasopharyngeal carcinoma: a case-control study in Hong Kong Chinese.

    PubMed

    Xie, Shao-Hua; Yu, Ignatius Tak-sun; Tse, Lap Ah; Au, Joseph Siu Kie; Wang, Feng; Lau, June Sze Man; Zhang, Bo

    2014-12-01

    Incense burning is a powerful producer of carcinogens and has been considered as a risk factor for nasopharyngeal carcinoma (NPC). We conducted a case-control study and case-only analyses to investigate the effect of incense burning and its interaction with genetic background on NPC risk among Hong Kong Chinese. Between June 2010 and December 2012, we recruited 352 incident cases of NPC and 410 controls. We collected information on lifelong practice of domestic incense burning via interviews and genotyped 80 single nucleotide polymorphisms (SNPs) in DNA repair genes. We observed an increased NPC risk associated with daily burning in women [Adjusted OR = 2.49, 95% confidence interval (CI): 1.33, 4.66] but not in men. The adjusted OR for daily burning with poor ventilation was 2.08 (95% CI: 1.02, 4.24), while that with good ventilation was 1.35 (95% CI: 0.92, 1.98). Interactions between 2 SNPs (rs2074517 and rs4771436) and incense burning were significantly associated with NPC risk and tended to have a SNP exposure-response effect. Evidence for gene-environment interactions supported the knowledge that NPC is a multi-factorial disease resulting from the joint effects of environmental exposures and inherited susceptibility.

  19. Fisetin inhibits migration, invasion and epithelial-mesenchymal transition of LMP1-positive nasopharyngeal carcinoma cells.

    PubMed

    Li, Rong; Zhao, Yinhai; Chen, Jin; Shao, Songjun; Zhang, Xiujuan

    2014-02-01

    Fisetin (3,3',4',7-tetrahydroxyflavone) has been reported to possess certain anticancer properties. It may inhibit tumor cell proliferation, metastasis and induce apoptosis. However, the effects of fisetin in preventing the metastasis of nasopharyngeal carcinoma (NPC) cells remain to be determined. The epithelial-mesenchymal transition (EMT) is involved in several metastatic malignancies including NPC. It has been reported that the Epstein-Barr virus latent membrane protein-1 (LMP1) induced EMT and is associated with the metastasis of NPC. The aim of this study was to examine the effects of fisetin in preventing the migration and invasion of LMP1-expressing NPC cells (CNE1-LMP1 cells), as well as to investigate whether fisetin may inhibit the molecular changes associated with EMT induced by LMP1. The investigation demonstrated that fisetin suppressed the migration and invasion of CNE1-LMP1 cells under non-cytotoxic concentrations. Fisetin inhibited molecular changes associated with EMT induced by LMP1, upregulated the epithelial marker, E-cadherin protein, and downregulated the mesenchymal marker, vimentin protein, levels. Fisetin also significantly reduced the levels of Twist protein, an EMT regulator. The investigation suggested that fisetin inhibits the migration and invasion of LMP1-positive NPC cells, and the molecular mechanism involves fisetin reversing the EMT induced by LMP1 and downregulates the expression of Twist. This study indicated that fisetin serves as a potential candidate for the treatment of cancer metastasis.

  20. NOS1 S-nitrosylates PTEN and inhibits autophagy in nasopharyngeal carcinoma cells

    PubMed Central

    Zhu, Lingqun; Li, Linlin; Zhang, Qianbing; Yang, Xiao; Zou, Zhiwei; Hao, Bingtao; Marincola, Francesco M; Liu, Zhengjun; Zhong, Zhuo; Wang, Meng; Li, Xiaoxuan; Wang, Qianli; Li, Keyi; Gao, Wenwen; Yao, Kaitai; Liu, Qiuzhen

    2017-01-01

    Autophagy is a cellular survival mechanism that involves the catabolic degradation of damaged proteins and organelles during periods of metabolic stress, and when overly stimulated, commonly contributes to cell death. Nitric oxide (NO), a potent cellular messenger, participates in a complex mechanism which assists in controlling autophagy. However, the mechanism by which endogenous NO formed by distinct isoforms of nitric oxide synthase (NOS) helps to regulate autophagy in cancer cells remains unclear. Here we report that NOS1 reduces excessive levels of autophagy and promotes the survival of nasopharyngeal carcinoma cells. We found that inhibition of NOS1 increased cell death resulting from siRNA or the use of pharmacologic agents; and this effect was reversed by the autophagy inhibitor, chloroquine. The role of NOS1 in the autophagy process depended on the activation of AKT/mTOR signaling by S-nitrosylation of phosphatase and tensin homolog (PTEN) proteins. The mechanism by which NOS1 modifies PTEN protein might involve a direct interaction between these two molecules. Moreover, in an in vivo study, the NOS1 inhibitor N(G)-nitro-L-arginine methyl ester activated AKT/mTOR signaling and promoted autophagy in xenograph tumors. Our studies demonstrated that NOS1 prevents excessive autophagy via S-nitrosylation of PTEN, and activation of the AKT/mTOR signaling pathway. PTEN and the AKT/mTOR signaling pathway are promising targets for improving the chemotherapeutic treatment of cancer. PMID:28243469

  1. 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.

  2. 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

  3. A rare case of nasopharyngeal carcinoma in a patient with multiple myeloma after treatment by lenalidomide.

    PubMed

    Xu, Gaixiang; Wang, Bo; Yang, Min; Qian, Wenbin

    2015-01-01

    Multiple myeloma (MM) is a plasma-cell malignancy leading to a significant life-expectancy shortening. Lenalidomide is an oral immunomodulatory drug (IMiD) approved in the United States for patients with MM. Although the introduction of lenalidomide combined with dexamethasone (Len/Dex) has improved the outcome of patients with relapsed/refractory multiple myeloma (RRMM), it is a common knowledge that lenalidomide has been linked to the development of secondary primary malignancies in the MM patients, especially in those who use lenalidomide as a maintenance therapy. In the published literature, these are also many cases reported by clinicians in different secondary primary malignancies after the diagnosis of MM treated with lenalidomide. In this present article, we provided our patient who was identified nasopharyngeal carcinoma (NPC) 46 months after the diagnosis of MM and 21 months after lenalidomide treatment. To the best of our knowledge, this is the first case report related to the occurrence of NPC in a patient with MM after treatment by lenalidomide. Although it is not very sure that the incidence of NPC was associated with the use of lenalidomide, we clinicians should pay adequate attention to this phenomenon in the clinical processing. And much more cooperative studies of large numbers of MM patients are needed to evaluate a possible association between lenalidomide and NPC.

  4. Neurosurgical interventions for patients with nasopharyngeal carcinoma: a single institution experience

    PubMed Central

    2013-01-01

    Background Nasopharyngeal carcinoma (NPC) is a frequent head and neck cancer in southern China and Southeast Asia. The majority of NPC patients are managed by radiation oncologists, medical oncologists and head and neck surgeons. Actually, neurosurgical interventions are warranted under specific circumstances. In this article, we described our experience as neurosurgeons in the management of NPC patients. Methods Medical records of NPC patients who received neurosurgical procedure at Sun Yat-sen University Cancer Center were reviewed. Results Twenty-seven patients were identified. Among 27 cases, neurosurgical procedures were performed in 18 (66.7%) with radiation-induced temporal necrosis, 2 (7.4%) with radiation-induced sarcoma, 4 (14.8%) with synchronous NPC with primary brain tumors, 2 (7.4%) with recurrent NPC involving skull base, and 1 (3.7%) with metachronous skull eosinophilic granuloma, respectively. The diagnosis is challenging in specific cases and initial misdiagnoses were found in 6 (22.2%) patients. Conclusions For NPC patients with intracranial or skull lesions, the initial diagnosis can be occasionally difficult because of the presence or a history of NPC and related treatment. Unawareness of these entities can result in misdiagnosis and subsequent improper treatment. Neurosurgical interventions are necessary for the diagnosis and treatment for these patients. PMID:24034781

  5. Plasma Fibrinogen Correlates with Metastasis and is Associated with Prognosis in Human Nasopharyngeal Carcinoma

    PubMed Central

    He, Sha-Sha; Wang, Yan; Yang, Lin; Chen, Hai-Yang; Liang, Shao-Bo; Lu, Li-Xia; Chen, Yong

    2017-01-01

    Background: The purpose of this observational study was to evaluate the prognostic significance of the pre-treatment plasma fibrinogen level for survival outcomes in nasopharyngeal carcinoma (NPC). Methods: A total of 998 patients with NPC treated at a single centre in China were retrospectively enrolled, of whom 182 (18.2%) developed distant metastasis during follow-up. Survival analyses were performed by the Kaplan-Meier method and Cox regression modelling to measure 3-year overall survival (OS) and distant metastasis-free survival (DMFS). Results: Median OS for the entire cohort was 37.8 months. Using the cut-off value of 3.345 g/L identified in receiver operating curve analysis for fibrinogen, a high pre-treatment plasma fibrinogen level were associated with older age (P = 0.034), advanced TNM stage (P = 0.004) and development of distant metastasis (P < 0.001; Chi-square test). Multivariate Cox proportional hazard analysis demonstrated the pre-treatment plasma fibrinogen level was an independent significant prognostic factor for OS and DMFS in both the entire cohort and also among patients who developed distant metastasis during follow-up. Conclusions: This study suggests the pre-treatment plasma fibrinogen level may serve as an independent prognostic marker to predict the survival outcomes of patients with NPC, including patients with metastatic disease. PMID:28261341

  6. Targeting nasopharyngeal carcinoma by artesunate through inhibiting Akt/mTOR and inducing oxidative stress.

    PubMed

    Li, Qin; Ni, Wei; Deng, Zhifeng; Liu, Minghe; She, Lazhi; Xie, Qiong

    2017-01-11

    Drug repurposing has become an alternative therapeutic strategy for cancer treatment given the known pharmacokinetics and toxicity. The inhibitory effects of artesunate have been reported in various cancers. In this work, we investigated the effects of artesunate in nasopharyngeal carcinoma (NPC). We demonstrate that artesunate significantly inhibits proliferation via arresting NPC cells at G2/M phase. It also induces apoptosis through caspase-dependent and mitochondria-independent pathways in multiple NPC cell lines. The combination of artesunate and cisplatin is synergistic in targeting NPC cells in in vitro cellular culture system and in vivo xenograft tumor models. Artesunate inhibits phosphorylation of essential molecules involved in Akt/mTOR pathway in NPC cells, such as Akt, mTOR, and 4EBP1, and its inhibitory effects are partially abolished by overexpression of constitutively active Akt. In addition, artesunate also induces mitochondrial dysfunction and oxidative stress via inhibiting mitochondrial respiration, increasing levels of mitochondrial superoxide and cellular reactive oxygen species (ROS), leading to decreased ATP levels. Two ROS scavengers partially abolish the inhibitory effects of artesunate in NPC cells. These data suggest that both inhibition of Akt/mTOR pathway and induction of ROS are required for the action of artesunate in NPC cells. Our work demonstrates that artesunate is a potential candidate for NPC treatment. Our work also highlights the critical roles of Akt/mTOR pathway and mitochondrial function in NPC cells.

  7. 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

  8. 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.

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

    PubMed

    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.

  10. CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis

    PubMed Central

    Tu, Ziwei; Chen, Qu; Zhang, Jie Ting; Jiang, Xiaohua; Xia, Yunfei; Chan, Hsiao Chang

    2016-01-01

    While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) development remains unknown. In this study, we aimed to explore the prognostic value of CFTR in NPC patients. The expression of CFTR was determined in NPC cell lines and tissues. Statistical analysis was utilized to evaluate the correlation between CFTR expression levels and clinicopathological characteristics and prognosis in 225 cases of NPC patients. The results showed that CFTR was down-regulated in NPC tissues and cell lines. Low expression of CFTR was correlated with advanced stage (p = 0.026), distant metastasis (p < 0.001) and poor prognosis (p < 0.01). Multivariate analysis identified CFTR as an independent prognostic factor (p = 0.003). Additionally, wound healing and transwell assays revealed that overexpression of CFTR inhibited NPC cell migration and invasion, whereas knockdown of CFTR promoted cell migration and invasion. Thus, the current study indicates that CFTR, as demonstrated to play an important role in tumor migration and invasion, may be used as a potential prognostic indicator in NPC. PMID:27769067

  11. Is Gemcitabine and Cisplatin Induction Chemotherapy Superior in Locoregionally Advanced Nasopharyngeal Carcinoma?

    PubMed Central

    Zheng, Wei; Qiu, Sufang; Huang, Lingling; Pan, Jianji

    2015-01-01

    Objective: To investigate the outcome of locoregionally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy followed by chemoradiotherapy. Methods: Between June 2005 and October 2007, 604 patients with locoregionally advanced NPC were analyzed, of whom 399 and 205 were treated with conventional radiotherapy and intensity-modulated radiotherapy (IMRT) respectively. Meanwhile, 153 patients received concurrent chemotherapy, and 520 were given induction chemotherapy. Results: With a median follow-up time of 65 months, the 3-, and 5-year overall survival (OS), locoregional free survival (LRFS), and distant-metastasis free survival (DMFS) rates were 82.5% vs. 72.6%, 90.6% vs. 87.1%, and 82.5% vs. 81.2%, respectively. Induction chemotherapy was not an independent prognostic factor for OS (P=0.193) or LRFS, but there was a positive tendency for DMFS (P=0.088). GP regimen (gemcitabine + cisplatin) was an independent prognostic factor for OS (P = 0.038) and it had a trend toward improved DMFS (P = 0.109). TP regimen (taxol + cisplatin) was only a significant prognostic factor for DMFS (P =0.038). Conclusions: Adding induction chemotherapy had no survival benefit, but GP regimen benefited overall survival and had a trend toward improved DMFS. GP regimen may be superior to TP/FP regimen (fluorouracil + cisplatin) in treating locoregionally advanced NPC. PMID:26430402

  12. 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.

  13. BART miRNAs: an unimaginable force in the development of nasopharyngeal carcinoma

    PubMed Central

    Wang, Youhong; Guo, Zhen; Shu, Yan; Zhou, Honghao; Wang, Hui

    2017-01-01

    Nasopharyngeal carcinoma (NPC) is a head and neck cancer that represents a major health burden in Southern China and Southeast Asia. Although the close association of NPC with Epstein–Barr virus (EBV) infection has been demonstrated, its exact role in the pathogenesis of this malignancy is still unclear. The expression of EBV-encoded microRNAs, especially BART miRNAs, which are encoded from the BamHI-A region of the viral genome, is detected at a high level in NPC. miRNAs are small noncoding mRNAs that can positively regulate the virus to ensure accurate expression of viral genomes and to modify the gene expression of host cells by negative regulation. Accumulating evidence suggests that ebv-mir-BARTs play a critical role in host cell survival, immune escape, cell proliferation, cell apoptosis, and cancer metabolism, promoting the generation of NPC. This review will summarize our current understanding of the nature and function of ebv-mir-BARTs in NPC. PMID:26909566

  14. [Endoscopic surgery and reconstruction for extensive osteoradionecrosis of skull base after radiotherapy for nasopharyngeal carcinoma].

    PubMed

    Chen, Z; Qiu, Q H; Zhan, J B; Zhu, Z C; Peng, Y; Liu, H

    2016-12-07

    Objective: To investigate the clinical efficacy of endoscopic surgery for extensive osteoradionecrosis (ORN) of skull base in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Methods: Seventeen patients diagnosed as ORN of skull base after radiotherapy for NPC and underwent endoscopic surgery were retrospectively studied with their clinic data. Results: Based on the CT and endoscopic examination, all patients had large skull base defects with bone defects averaged 7.02 cm(2) (range, 3.60 - 14.19 cm(2)). Excepting for curetting the sequestra, endoscopic surgery was also used to repair the wound or to protect the internal carotid artery with flap in 12 patients. No bone reconstructions were conducted in all patients with the bone defects of skull base. CT examinations were taken after endoscopic surgery when required. The postoperative follow-up ranged from 8 months to 6 years (average, 14 months). Aside from 1 patient with delayed cerebrospinal fluid (CSF), others had no related complications. Conclusions: The patients with extensive ORN can be treated with endoscopic surgery to curette the necrotic bone of skull base, and endoscopic reconstruction provides an alternative technique. It may not be necessary to reconstruct the bone defects at skull base, however, the exposed important structures of skull base, such as internal carotid artery, need to repair with soft tissue such as flap.

  15. Suspected nasopharyngeal carcinoma in three workers with long-term exposure to sulphuric acid vapour.

    PubMed

    Ho, C K; Lo, W C; Huang, P H; Wu, M T; Christiani, D C; Lin, C T

    1999-06-01

    Sulphuric acid vapour has been suspected of being an industrial carcinogen. In this study, a cluster is presented of three patients with nasopharyngeal carcinoma (NPC) who worked in the same building of a telecommunications conveyance station in southern Taiwan with long term exposure to sulphuric acid vapour concentrations as high as 0.18 mg/m3. All three workers were diagnosed with NPC within a 5 month period between September 1992, and March 1993. Compared with 19 other healthy workers from the same building, these three workers with NPC had worked significantly longer in this building than had the others (mean (SD) (years): 12.7 (0.6) v 7.4 (4.4); p = 0.01). With an in situ nucleic acid hybridisation and immunostaining method for colocalised Epstein-Barr virus (EBV) and secretory component (SC) protein among biopsy specimens of these three patients with NPCs, it was found that some tumour cells did not contain EBV and SC protein staining signals. These results indicate that EBV infection is not the only risk factor for NPC and long term exposure to relatively low concentrations of sulphuric acid vapour may be associated with the development of NPC.

  16. Downregulation of Annexin A1 is correlated with radioresistance in nasopharyngeal carcinoma

    PubMed Central

    Huang, Lifang; Liao, Li; Wan, Yanping; Cheng, Ailan; Li, Meixiang; Chen, Sihan; Li, Maoyu; Tan, Xing; Zeng, Guqing

    2016-01-01

    Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), but radioresistance often remains an obstacle to successful treatment. In our previous study, it was demonstrated that Annexin A1 (ANXA1) was involved in the p53-mediated radioresponse in NPC cells, which suggested that it may be associated with radioresistance in NPC; however, the role of ANXA1 in NPC radioresistance is unknown. In the present study, CNE2 cells were stably transfected with pLKO.1-ANXA1-small hairpin (sh)RNAs to investigate the effects of ANXA1 on the radiosensitivity of NPC. CNE2 cells transfected with pLKO.1 were used as the control. The radiosensitivities of the cells in vitro were analyzed using the clonogenic survival assay, cell growth analysis, flow cytometry and Hoechst 33258 staining. ANXA1 downregulation significantly enhanced clonogenic survival and cell growth following treatment of CNE2 cells with ionizing radiation (IR), increased the number of cells in the S phase and decreased IR-induced apoptosis. These results suggested that the radiosensitivity of CNE2 cells transfected with ANXA1-specific shRNA was significantly lower compared with the control cells. Therefore, ANXA1 downregulation may be involved in the radioresistance of NPC, and ANXA1 may be considered a novel biomarker for predicting NPC response to radiotherapy. PMID:28101240

  17. 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

  18. miR-519 suppresses nasopharyngeal carcinoma cell proliferation by targeting oncogene URG4/URGCP.

    PubMed

    Yu, Guodong; Zhang, Tian; Jing, Ying; Bao, Qingmin; Tang, Qiang; Zhang, Yu

    2017-03-15

    Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumor in Southeast Asia, its regulatory mechanism is still to be understood. miR-519 inhibits the progression of several tumors, including cervical cancer, ovarian cancer and gastric cancer. But its role in NPC hasn't been studied. In present study, we found miR-519 was downregulated in NPC cells, its overexpression inhibited NPC cell proliferation and arrested cell cycle at G0/G1 phase, while its knockdown promoted NPC cell proliferation and cell cycle progression. An oncogene URG4/URGCP (upregulated gene-4/upregulator of cell proliferation) was the target of miR-519, URG4 was upregulated in NPC cells, miR-519 inhibited URG4 expression by directly binding to the 3'UTR of URG4. miR-519 inhibited Cyclin D1 expression and the phosphorylation level of Rb, and increased p21 and p27 expression, confirming miR-519 blocked G1/S transition. Moreover, miR-519 level was negative correlated with URG4 level in NPC tissues. In summary, we found miR-519 NPC cell proliferation by inhibiting URG4.

  19. Epigallocatechin-3-gallate Modulates MicroRNA Expression Profiles in Human Nasopharyngeal Carcinoma CNE2 Cells

    PubMed Central

    Li, Bin-Bin; Huang, Guo-Liang; Li, Hua-Hui; Kong, Xia; He, Zhi-Wei

    2017-01-01

    Background: Epigallocatechin-3-gallate (EGCG) has exhibited antitumor properties in several types of cancers, including nasopharyngeal carcinoma (NPC), but the molecular mechanisms underlying this function remain incompletely understood. The aim of the present study was to characterize the global impact of EGCG on the expression of microRNAs (miRNAs) in NPC cells. Methods: Using microarray analysis, the alterations of miRNA expression profiles were investigated in EGCG-treated CNE2 cells. Furthermore, the target genes and signaling pathways regulated by EGCG-specific miRNAs were identified using target prediction program and gene ontology analysis. Results: A total of 14 miRNAs exhibited >2-fold expression changes in a dose-dependent manner after treatment with 20 μmol/L and 40 μmol/L EGCG. Totally 43, 49, and 52 target genes from these differentially expressed miRNAs were associated with the apoptosis, cell cycle regulation, and cell proliferation, respectively. A total of 66 signaling pathways, primarily involved in cancer development and lipid and glucose metabolism, were shown to be regulated by EGCG-specific miRNAs. Conclusion: EGCG induces considerable alterations of miRNA expression profiles in CNE2 cells, which provides mechanistic insights into cellular responses and antitumor activity mediated by EGCG. PMID:28051030

  20. Mc-hES, a novel plasmid carrying human endostatin gene, inhibits nasopharyngeal carcinoma growth.

    PubMed

    Xu, B-L; Yuan, L; Wu, J-X; Xu, N; Fang, W-J; Zhao, P; Huang, W-L

    2012-02-01

    Conventional plasmids for gene therapy produce low-level and short-term gene expression. Here, we first created minicircle carrying endostatin (mc-hES) for measurement of transfection efficiency. Compared with pcDNA-hES, MC-mediated endostatin gene transfer in vitro resulted in seven-fold greater endostatin expression levels in transfected cells and inhibited the growth of Human umbilical vein endothelial cells (HUVEC) more efficiently. HUVEC cell migration and tube-formation assays suggested that MC-mediated endostatin gene has significant anti-migration and anti-tube-formation capacity than that in pcDNA-hES. In vivo experiments showed that after transfection, mc-hES inhibited the growth of nasopharyngeal carcinoma xenografts. The tumor inhibition rates of mc-hES and pcDNA-hES were 60.8% and 26.9%, respectively (P<0.05). MC-mediated intratumoral endostatin expression in vivo was 2.2-17.9 times higher than pcDNA-hES in xenografted mice and lasted for 20 days. Our results suggest that minicircle DNA vectors might be a promising vector for biotherapy and should be further investigated.

  1. HOPX hypermethylation promotes metastasis via activating SNAIL transcription in nasopharyngeal carcinoma

    PubMed Central

    Ren, Xianyue; Yang, Xiaojing; Cheng, Bin; Chen, Xiaozhong; Zhang, Tianpeng; He, Qingmei; Li, Bin; Li, Yingqin; Tang, Xinran; Wen, Xin; Zhong, Qian; Kang, Tiebang; Zeng, Musheng; Liu, Na; Ma, Jun

    2017-01-01

    Nasopharyngeal carcinoma (NPC) is characterized by a high rate of local invasion and early distant metastasis. Increasing evidence indicates that epigenetic abnormalities play important roles in NPC development. However, the epigenetic mechanisms underlying NPC metastasis remain unclear. Here we investigate aberrantly methylated transcription factors in NPC tissues, and we identify the HOP homeobox HOPX as the most significantly hypermethylated gene. Consistently, we find that HOXP expression is downregulated in NPC tissues and NPC cell lines. Restoring HOPX expression suppresses metastasis and enhances chemosensitivity of NPC cells. These effects are mediated by HOPX-mediated epigenetic silencing of SNAIL transcription through the enhancement of histone H3K9 deacetylation in the SNAIL promoter. Moreover, we find that patients with high methylation levels of HOPX exhibit poor clinical outcomes in both the training and validation cohorts. In summary, HOPX acts as a tumour suppressor via the epigenetic regulation of SNAIL transcription, which provides a novel prognostic biomarker for NPC metastasis and therapeutic target for NPC treatment. PMID:28146149

  2. ABO blood group and nasopharyngeal carcinoma risk in a population of Southeast China.

    PubMed

    Sheng, Liming; Sun, Xiaojiang; Zhang, Lizhen; Su, Dan

    2013-08-15

    Previous studies found that the ABO blood type alters the individual susceptibility of some malignancies. However, whether such an association exists between ABO blood type and nasopharyngeal carcinoma (NPC) remains unknown. A case-control study was conducted, with 1,538 patients who had NPC and 1,260 cancer-free controls. The association between ABO blood type and NPC incidence was evaluated using unconditional logistic regression analysis. Compared with subjects with blood type O, a relatively higher risk was observed among cases with blood types A or AB, with ORs (95% confidence interval) of 1.287 (1.072 - 1.545), p = 0.007 and 1.390 (1.007 - 1.919), p = 0.045, respectively, after adjusting for gender, age, smoking status and family history of cancer. The rate of distant metastasis was significantly higher among male patients with blood type A than in patients with non-A blood types (6.8 vs. 3.5%, p = 0.027). Our results suggest that blood types A or AB is associated with an increased risk of NPC. Further studies are needed to confirm this association and to explore the mechanisms involved.

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

    PubMed

    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

    2016-01-18

    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.

  4. 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

  5. Overexpression of IGFBP3 is associated with poor prognosis and tumor metastasis in nasopharyngeal carcinoma.

    PubMed

    Bao, Lili; Liu, Hao; You, Bo; Gu, Miao; Shi, Si; Shan, Ying; Li, Li; Chen, Jing; You, Yiwen

    2016-11-01

    Insulin-like growth factor-binding protein-3 (IGFBP3) is an N-linked glycosylated, phosphorylated protein, which has been reported to regulate cancer progression and metastasis. However, the role of IGFBP3 in tumor metastasis remains under debate. Nasopharyngeal carcinoma (NPC) is a highly metastatic head and neck cancer. And it fails to achieve the desired therapeutic efficacy in patients with metastasis, while the role of IGFBP3 in NPC is still unclear. In this study, we first used immunohistochemistry to explore the expression of IGFBP3 in NPC tissues. We found that IGFBP3 was significantly elevated in NPC and its expression level was correlated with N classification, distant metastasis, and TNM clinical stage (all P < 0.05). Patients with high expression of IGFBP3 had poorer survival rate (P < 0.05). In addition, we found that downregulation of IGFBP3 inhibited cell migration and adhesion by Transwell migration assay, wounding healing assay, and cell adhesion assays in vitro. Besides, NPC cells stimulated with recombinant IGFBP3 accelerated migration and adhesion. These data suggest overexpression of IGFBP3 promotes tumor metastasis in NPC, which makes it a potential therapeutic target.

  6. 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

  7. CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis.

    PubMed

    Tu, Ziwei; Chen, Qu; Zhang, Jie Ting; Jiang, Xiaohua; Xia, Yunfei; Chan, Hsiao Chang

    2016-11-22

    While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) development remains unknown. In this study, we aimed to explore the prognostic value of CFTR in NPC patients. The expression of CFTR was determined in NPC cell lines and tissues. Statistical analysis was utilized to evaluate the correlation between CFTR expression levels and clinicopathological characteristics and prognosis in 225 cases of NPC patients. The results showed that CFTR was down-regulated in NPC tissues and cell lines. Low expression of CFTR was correlated with advanced stage (p = 0.026), distant metastasis (p < 0.001) and poor prognosis (p < 0.01). Multivariate analysis identified CFTR as an independent prognostic factor (p = 0.003). Additionally, wound healing and transwell assays revealed that overexpression of CFTR inhibited NPC cell migration and invasion, whereas knockdown of CFTR promoted cell migration and invasion. Thus, the current study indicates that CFTR, as demonstrated to play an important role in tumor migration and invasion, may be used as a potential prognostic indicator in NPC.

  8. Contribution of double strand break repair gene XRCC3 genotypes to nasopharyngeal carcinoma risk in Taiwan.

    PubMed

    Liu, Juhn-Cherng; Tsai, Chia-Wen; Hsu, Chin-Mu; Chang, Wen-Shin; Li, Chi-Yuan; Liu, Shih-Ping; Shen, Wu-Chung; Bau, Da-Tian

    2015-02-28

    The DNA double strand break repair protein XRCC3 plays a central role in removing double strand breaks from the genome and defects in cellular repair capacity is closely related to human cancer initiation. Therefore, we aimed to investigate the contribution of XRCC3 genotypes to individual nasopharyngeal carcinoma (NPC) susceptibility. In this hospital-based population research, the genotyping and analyzing of XRCC3 rs1799794, rs45603942, rs861530, rs3212057, rs1799796, rs861539, rs28903081 in a large Taiwanese population was performed. Totally, 176 NPC patients and 880 age- and gender-matched healthy controls were genotyped and analyzed by PCR-RFLP method. The results showed that there was a differential distribution among NPC and control subjects in the genotypic (P = 0.000488) and allelic (P = 0.0002) frequencies of XRCC3 rs861539. As for the gene-environment interaction, we have firstly provided evidence showing that there is an obvious joint effect of XRCC3 rs861539 CT and TT genotypes with individual smoking habits on increased NPC risk. In conclusion, the T allele of XRCC3 rs861539, interacts with smoking habit in increasing NPC risk, may be an early detection marker for NPC.

  9. Functional analysis of the nasopharyngeal carcinoma primary tumor‑associated gene interaction network.

    PubMed

    An, Fengwei; Zhang, Zhiqiang; Xia, Ming

    2015-10-01

    The aim of the present study was to investigate the molecular mechanism of nasopharyngeal carcinoma (NPC) primary tumor development through the identification of key genes using bioinformatics approaches. Using the GSE53819 microarray dataset, acquired from the Gene Expression Omnibus database, differentially expressed genes (DEGs) were screened out between NPC primary tumor and control samples, followed by hierarchical clustering analysis. The Search Tool for the Retrieval of Interacting Genes database was utilized to build a protein‑protein interaction network to identify key node proteins. In total, 1,067 DEGs, including 326 upregulated genes and 741 downregulated genes, were identified between the NPC and control samples. The results of the hierarchical clustering analysis demonstrated that 95% of the DEGs were sample‑specific. Furthermore, PDZ binding kinase (PBK), centromere protein F (CENPF), actin‑binding protein anillin (ANLN), exonuclease 1 (EXO1) and chromosome 15 open reading frame 42 (C15ORF42) were included in the obtained network module, which was closely associated with the cell cycle and nucleic acid metabolic process GO functions. The results of the present study revealed that EXO1, CENPF, ANLN, PBK and C15ORF42 may be involved in the mechanism of NPC via modulating the cell cycle and nucleic acid metabolic processes, and may serve as molecular biomarkers for the diagnosis of this disease.

  10. Comparisons of quality of life for patients with nasopharyngeal carcinoma after treatment with different RT technologies.

    PubMed

    Jang-Chun, L; Jing-Min, H; Yee-Min, J; Dai-Wei, L; Chang-Ming, C; Chun-Shu, L; Wen-Yen, H; Yu-Fu, S; Kuen-Tze, L; Chao-Yueh, F; Cheng-Hsiang, L; Hsing-Lung, C

    2014-08-01

    The objectives of this study were determine the quality of life (QoL) for patients with nasopharyngeal carcinoma (NPC) after treatment with different advanced technologies in radiotherapy (RT). A total of 150 patients with NPC were consecutively treated using curative RT in the Department of Radiation Oncology at Tri-service General Hospital in Taiwan. Data were collected prospectively from medical records and questionnaires. We used the Short-Form-36 (SF36) health survey questionnaire to evaluate general QoL, and a modified EORTC QLQH& N35 questionnaire to evaluate the correlation of xerostomia with QoL. The selection of RT methodology among two-dimensional radiotherapy (2D-RT), three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) was a significant factor for predicting difficulty of speech (P = 0.003), difficulty in chewing (P = 0.012), swallowing ability (P = 0.004), dry throat sensation during meals (P = 0.006) and the frequency of drinking water to maintain a moist mouth (P = 0.01). Our data suggest that the intensity-modulated radiotherapy technique plays a significant role in improving the QoL of NPC patients in our study.

  11. Preliminary results of radiation dose escalation for locally advanced nasopharyngeal carcinoma

    SciTech Connect

    Kwong, Dora L.W. . E-mail: dlwkwong@hkucc.hku.hk; Sham, Jonathan S.T.; Leung, Lucullus H.T.; Cheng, Ashley C.K.; Ng, W.M.; Kwong, Philip W.K.; Lui, W.M.; Yau, C.C.; Wu, P.M.; Wei, William; Au, Gordon

    2006-02-01

    Purpose: To study the safety and efficacy of dose escalation in tumor for locally advanced nasopharyngeal carcinoma (NPC). Methods and Materials: From September 2000 to June 2004, 50 patients with T3-T4 NPC were treated with intensity-modulated radiotherapy (IMRT). Fourteen patients had Stage III and 36 patients had Stage IVA-IVB disease. The prescribed dose was 76 Gy to gross tumor volume (GTV), 70 Gy to planning target volume (PTV), and 72 Gy to enlarged neck nodes (GTVn). All doses were given in 35 fractions over 7 weeks. Thirty-four patients also had concurrent cisplatin and induction or adjuvant PF (cisplatin and 5-fluorouracil). Results: The average mean dose achieved in GTV, GTVn, and PTV were 79.5 Gy, 75.3 Gy, and 74.6 Gy, respectively. The median follow-up was 25 months, with 4 recurrences: 2 locoregional and 2 distant failures. All patients with recurrence had IMRT alone without chemotherapy. The 2-year locoregional control rate, distant metastases-free and disease-free survivals were 95.7%, 94.2%, and 93.1%, respectively. One treatment-related death caused by adjuvant chemotherapy occurred. The 2-year overall survival was 92.1%. Conclusions: Dose escalation to 76 Gy in tumor is feasible with T3-T4 NPC and can be combined with chemotherapy. Initial results showed good local control and survival.

  12. Treatment outcomes and late complications of 849 patients with nasopharyngeal carcinoma treated with radiotherapy alone

    SciTech Connect

    Yeh, S.-A. . E-mail: yehsa@hotmail.com; Tang Yeh; Lui, C.-C.; Huang, Y.-J.; Huang, E.-Y.

    2005-07-01

    Purpose: The objective of this study was to describe the treatment outcomes and treatment-related complications of nasopharyngeal carcinoma (NPC) patients treated with radiotherapy alone. Methods and Materials: Retrospective analysis was performed on 849 consecutive NPC patients treated between 1983 and 1998 in our institution. Potentially significant patient-related and treatment-related variables were analyzed. Radiation-related complications were recorded. Results: The 5-year overall and disease-free survival rates of these patients were 59% and 52%, respectively. Advanced parapharyngeal space (PPS) invasion showed stronger prognostic value than PPS invasion. Multiple neck lymph node (LN) involvement was demonstrated to be one of the most powerful independent prognostic factors among all LN-related parameters. External beam radiation dose more than 72 Gy was associated with significantly higher incidence of hearing impairment, trismus, and temporal lobe necrosis. Conclusions: We recommend that the extent of PPS should be clarified and stratified. Multiple neck LN involvement could be integrated into the N-classification in further revisions of the American Joint Committee on Cancer stage. Boost irradiation is not suggested for node-negative necks. For node-positive necks, boost irradiation is indicated and a longer interval between initial and boost irradiation would reduce the incidence of neck fibrosis without compromising the neck control rate.

  13. High Expression of LINC01420 indicates an unfavorable prognosis and modulates cell migration and invasion in nasopharyngeal carcinoma

    PubMed Central

    Yang, Liting; Tang, Yanyan; He, Yi; Wang, Yumin; Lian, Yu; Xiong, Fang; Shi, Lei; Zhang, Shanshan; Gong, Zhaojian; Zhou, Yujuan; Liao, Qianjin; Zhou, Ming; Li, Xiaoling; Xiong, Wei; Li, Yong; Li, Guiyuan; Zeng, Zhaoyang; Guo, Can

    2017-01-01

    Recent studies demonstrated that long non-coding RNAs (lncRNAs) deregulated in many cancer tissues including nasopharyngeal carcinoma (NPC) and had critical roles in cancer progression and metastasis. In this study, we aimed to assess a lncRNA LINC01420 expression in NPC and explore its role in NPC pathogenesis. Our research revealed that the expression level of LINC01420 in NPC tissues were higher than nasopharyngeal epithelial (NPE) tissues. Moreover, NPC patients with high LINC01420 expression level showed poor overall survival. Knockdown LINC01420 inhibited NPC cell migration and invasion in vitro. In summary, LINC01420 may play a critical role in NPC progression and may serve as a potential prognostic biomarker in NPC patients. PMID:28123602

  14. Nasopharyngeal Carcinoma with Cystic Cervical Metastasis Masquerading as Branchial Cleft Cyst: A Potential Pitfall in Diagnosis and Management

    PubMed Central

    Sai-Guan, Lum; Min-Han, Kong; Kah-Wai, Ngan; Mohamad-Yunus, Mohd-Razif

    2017-01-01

    Introduction: Most metastatic lymph nodes from head and neck malignancy are solid. Cystic nodes are found in 33% - 61% of carcinomas arise from Waldeyer’s ring, of which only 1.8% - 8% originate are from the nasopharynx. Some cystic cervical metastases were initially presumed to be branchial cleft cyst. This case report aims to highlight the unusual presentation of cystic cervical metastasis secondary to nasopharyngeal carcinoma in a young adult. The histopathology, radiological features and management strategy were discussed. Case Report: A 36-year-old man presented with a solitary cystic cervical swelling, initially diagnosed as branchial cleft cyst. Fine needle aspiration yielded 18 ml of straw-coloured fluid. During cytological examination no atypical cells were observed. Computed tomography of the neck showed a heterogeneous mass with multiseptation medial to the sternocleidomastoid muscle. Histopathological examination of the mass, post excision, revealed a metastatic lymph node. A suspicious mucosal lesion at the nasopharynx was detected after repeated thorough head and neck examinations and the biopsy result confirmed undifferentiated nasopharyngeal carcinoma. Conclusion: Cystic cervical metastasis may occur in young patients under 40 years. The primary tumour may not be obvious during initial presentation because it mimicks benign branchial cleft cyst clinically. Retrospective review of the computed tomography images revealed features that were not characteristic of simple branchial cleft cyst. The inadequacy of assessment and interpretation had lead to the error in diagnosis and subsequent management. Metastatic head and neck lesion must be considered in a young adult with a cystic neck mass.

  15. Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia

    PubMed Central

    Maklad, Ahmed Marzouk; Bayoumi, Yasser; Senosy Hassan, Mohamed Abdalazez; Elawadi, AbuSaleh A; AlHussain, Hussain; Elyamany, Ashraf; Aldhahri, Saleh F; Al-Qahtani, Khalid Hussain; AlQahtani, Mubarak; Tunio, Mutahir A

    2016-01-01

    Background We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. Patients and methods From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66–70 Gy, 63 Gy to clinical target volume, and 50.4–56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. Results The median follow-up time was 52.2 months (range: 11–87 months). Epstein–Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range: 16–50 months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein–Barr virus were independent predictors for disease-free survival. Conclusion Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein–Barr virus status before IMRT were important independent prognostic factors

  16. Sequence variation of Epstein-Barr virus (EBV) BZLF1 gene in EBV-associated gastric carcinomas and nasopharyngeal carcinomas in Northern China.

    PubMed

    Luo, Bing; Tang, Xiuming; Jia, Yuping; Wang, Yun; Chao, Yan; Zhao, Chengquan

    2011-08-01

    Epstein-Barr virus (EBV) BZLF1 gene can trigger EBV from latent infection to lytic replicative phase. The functions of BZLF1 are well known, while little is known about its gene polymorphism. In order to elucidate the sequence variations of BZLF1 and its association with malignancies, we analyzed BZLF1 gene in 24 EBV-associated gastric carcinomas, 41 nasopharyngeal carcinomas and 24 throat washing samples from healthy donors in Northern China using PCR-direct sequencing method. Three types and 8 subtypes of BZLF1 were identified. A dominant type BZLF1-A was found in 67 of 89 (75.3%) isolates. Type BZLF1-B was characterized by a common Ala deletion at residue 127, which was detected in 21 of 89 isolates (23.6%). Type BZLF1-C contained only one isolate (GC103), which had the same sequence with the prototype B95-8. Among 3 functional domains of BZLF1 protein, the transactivation domain had most mutations, followed by the bZIP domains (the DNA binding domain and dimerization domain). No prevalence of any subtypes or mutations in the functional domains among three specimen groups was found (P > 0.05). Our study indicates that BZLF1 subtypes and amino acid changes in functional domains are not preferentially associated with EBV-associated gastric carcinomas or nasopharyngeal carcinomas in Northern China. BZLF1 gene variations are geographically restricted rather than tumor-specific polymorphisms.

  17. 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

  18. 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

  19. 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.

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

    PubMed Central

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

    2016-01-01

    Abstract 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

  1. Functional NBS1 polymorphism is associated with occurrence and advanced disease status of nasopharyngeal carcinoma.

    PubMed

    Zheng, Jian; Zhang, Chun; Jiang, Lan; You, Yonghe; Liu, Yuehui; Lu, Jiachun; Zhou, Yifeng

    2011-09-01

    As a component of the MRN (MRE11/RAD50/NBS1) complex, NBS1 plays an important role in cellular response to DNA damage and the maintenance of chromosomal integrity. The NBS1 E185Q polymorphism (8360G>C, rs1805794) has been frequently studied in some cancers with discordant results, but its association with nasopharyngeal carcinoma (NPC) in Chinese population has not been investigated. Moreover, there is no report about the association between NBS1 3'UTR variant rs2735383 and the risk of NPC. A multiple center case-control analysis was performed to assess the association between NBS1 polymorphisms and NPC risk in Eastern and Southern Chinese population. The genotypes and haplotypes were determined in 1052 cases and 1168 controls and the associations with risk of NPC were estimated by logistic regression. Cell migration assays were performed in 24-well transwell chambers to detect the effects of NBS1 E185Q SNP on cell migration. We observed significant difference in genotype frequencies at the rs1805794 C/G site between cases and controls (P(trend) < 0.0001). The C allele increases the risk for invasive disease or metastatic disease, compared with G allele. More over, CNE-2 cells (NPC cell line) transfected with pcDNA-NBS1-185Q (8360CC) had significantly higher migration levels than those transfected with pcDNA-NBS1-185E (8360GG) (P = 0.024). These findings suggest that E185Q polymorphism in NBS1 may be a genetic modifier for the occurrence and aggression of NPC.

  2. Exosomal HIF1α supports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes.

    PubMed

    Aga, M; Bentz, G L; Raffa, S; Torrisi, M R; Kondo, S; Wakisaka, N; Yoshizaki, T; Pagano, J S; Shackelford, J

    2014-09-11

    It has emerged recently that exosomes are potential carriers of pro-tumorigenic factors that participate in oncogenesis. However, whether oncogenic transcription factors are transduced by exosomes is unknown. Hypoxia-inducible factor-1α (HIF1α) transcriptionally regulates numerous key aspects of tumor development and progression by promoting a more aggressive tumor phenotype, characterized by increased proliferation and invasiveness coupled with neoangiogenesis. It has been shown that the principal oncoprotein of Epstein-Barr virus (EBV), latent membrane protein 1 (LMP1), drives oncogenic processes and tumor progression of the highly invasive EBV malignancy, nasopharyngeal carcinoma (NPC). We now demonstrate that endogenous HIF1α is detectable in exosomes and that LMP1 significantly increases levels of HIF1α in exosomes. HIF1 recovered from exosomes retains DNA-binding activity and is transcriptionally active in recipient cells after exosome uptake. We also show that treatment of EBV-negative cells with LMP1-exosomes increases migration and invasiveness of NP cell lines in functional assays, which correlates with the phenotype associated with epithelial-mesenchymal transition (EMT). In addition, we provide evidence that HIF1α itself participates in exosome-mediated pro-metastatic effects in recipient cells, as exosome-mediated delivery of active and inactive forms of HIF1α results in reciprocal changes in the expression of E- and N-cadherins associated with EMT. Further, immunohistochemical analysis of NPC tumor tissues revealed direct correlation between protein levels of LMP1 and of the endosome/exosome marker tetraspanin, CD63, which suggests an increase in exosome formation in this EBV-positive malignancy. We hypothesize that exosome-mediated transfer of functional pro-metastatic factors by LMP1-positive NPC cells to surrounding tumor cells promotes cancer progression.

  3. Radiation therapy for nasopharyngeal carcinoma: the predictive value of interim survival assessment.

    PubMed

    Toya, Ryo; Murakami, Ryuji; Saito, Tetsuo; Murakami, Daizo; Matsuyama, Tomohiko; Baba, Yuji; Nishimura, Ryuichi; Hirai, Toshinori; Semba, Akiko; Yumoto, Eiji; Yamashita, Yasuyuki; Oya, Natsuo

    2016-09-01

    Pretreatment characteristics are suggested as predictive and/or prognostic factors for nasopharyngeal carcinoma (NPC); however, individual tumor radiosensitivities have previously not been considered. As boost planning is recommended for NPC, we performed interim assessments of magnetic resonance (MR) images for boost planning and retrospectively evaluated their predictive value for the survival of NPC patients. Radiation therapy via elective nodal irradiation (median dose: 39.6 Gy) with/without chemotherapy was used to treat 63 NPC patients. Boost irradiation (median total dose: 70 Gy) was performed based on the interim assessment. The largest lymph node (LN) was measured on MR images acquired at the time of interim assessment. The site of first failure was local in 8 (12.7%), regional in 7 (11.1%), and distant in 12 patients (19.0%). All 7 patients with regional failure harbored LNs ≥15 mm at interim assessment. We divided the 63 patients into two groups based on LN size [large (≥15 mm), n = 10 and small (<15 mm), n = 53]. Univariate analysis showed that 5-year overall survival (OS) and cause-specific survival (CSS) rates for large LNs were significantly lower than for small LNs (OS: 12.5% vs 70.5%, P < 0.001 and CSS: 25.0% vs 80.0%, P < 0.001). Multivariate analysis showed that large LNs were a significantly unfavorable factor for both OS (hazard ratio = 4.543, P = 0.002) and CSS (hazard ratio = 6.020, P = 0.001). The results suggest that LN size at interim assessment could predict survival in NPC patients.

  4. High-density lipoprotein cholesterol as a predictor of poor survival in patients with nasopharyngeal carcinoma

    PubMed Central

    Liu, Li-Na; Bao, Liu-Bin; Tang, Lin-Quan; Ou, Jing-Song; Liu, Zhi-Gang; Chen, Xiao-Zhong; Xu, Yan; Ma, Jun; Chan, Anthony T.; Chen, Ming; Xia, Yun-Fei; Liu, Wan-Li; Zeng, Yi-Xin; Mai, Hai-Qiang; Zeng, Mu-Sheng; Pan, Jian-Ji; Zhang, Xing

    2016-01-01

    Purpose We aimed to assess the prognostic value of pretreatment high density lipoprotein cholesterol (HDL-C) levels in patients with nasopharyngeal carcinoma (NPC) and investigate the possible biological effects of these lipoproteins on NPC cells in vitro. Experimental Design We examined the prognostic value of pretreatment HDL-C levels in 2443 patients with non-metastatic NPC from three independent institutions. The Cox proportional hazard model and log-rank test were used to analyze the correlation between HDL-C levels and overall survival (OS). Cell growth, colony formation, and apoptotic assays were used to determine the biological functions of HDL on NPC cells in vitro. All of the statistical tests were two-sided. Results OS was decreased in patients with high pretreatment HDL-C levels compared with those with low HDL-C levels (P < 0.05). Similarly, a decreased OS was noted in advanced stage (stage III-IV), NPC patients with high pretreatment HDL-C levels (P < 0.01). Multivariate analyses indicated that HDL-C was an independent prognostic factor associated with shorter OS in training cohorts. These findings were confirmed in both independent validation cohorts (P < 0.01). In vitro experiments demonstrated that HDL could increase cell proliferation, invasion, and colony formation, which were largely dependent on the expression of its receptor SR-B1. Finally, HDL could enhance chemoresistance by protecting cancer cells from apoptosis. Conclusions Pretreatment HDL-C is a poor prognostic factor for patients with NPC. This effect may be associated with the ability of HDL to enhance proliferation, colony formation, migration, and chemoresistance in NPC cells. PMID:27304186

  5. Gonadotropin‑releasing hormone inhibits the proliferation and motility of nasopharyngeal carcinoma cells.

    PubMed

    Teng, Loong Hung; Ahmad, Munirah; Ng, Wayne Tiong Weng; Sabaratnam, Subathra; Rasan, Maria Ithaya; Parhar, Ishwar; Khoo, Alan Soo Beng

    2015-10-01

    Gonadotropin‑releasing hormone (GnRH), or its analogues have been demonstrated to exhibit anti‑proliferative effects on tumour cells in ovarian, endometrial and breast cancer through GnRH‑receptors (GnRH‑R). However, the role of GnRH in nasopharyngeal carcinoma (NPC) remains to be elucidated. In order to investigate the effects of GnRH in NPC, the present study examined the expression of the GnRH‑R transcript in NPC and investigated the phenotypic changes in HK1 cells, a recurrent NPC‑derived cell line, upon receiving GnRH treatment. Firstly, the GnRH‑R transcript was demonstrated in the NPC cell lines and four snap frozen biopsies using reverse transcription‑quantitative polymerase chain reaction. In addition, immunohistochemistry revealed the expression of GnRH‑R in two of the eight (25%) NPC specimens. Treatment with GnRH induced a rapid increase in intracellular ionised calcium concentration in the NPC cells. GnRH and its agonists, triptorelin and leuprolide, exerted anti‑proliferative effects on the NPC cells, as determined using an MTS assay. GnRH did not induce any cell cycle arrest in the HK1 cells under the conditions assessed in the present study. Time‑lapse imaging demonstrated a reduction in cell motility in the GnRH‑treated cells. In conclusion, GnRH, or its analogues may have antitumour effects on NPC cells. The consequences of alterations in the levels of GnRH on the progression of NPC require further examination.

  6. Gonadotropin-releasing hormone inhibits the proliferation and motility of nasopharyngeal carcinoma cells

    PubMed Central

    TENG, LOONG HUNG; AHMAD, MUNIRAH; NG, WAYNE TIONG WENG; SABARATNAM, SUBATHRA; RASAN, MARIA ITHAYA; PARHAR, ISHWAR; KHOO, ALAN SOO BENG

    2015-01-01

    Gonadotropin-releasing hormone (GnRH), or its analogues have been demonstrated to exhibit anti-proliferative effects on tumour cells in ovarian, endometrial and breast cancer through GnRH-receptors (GnRH-R). However, the role of GnRH in nasopharyngeal carcinoma (NPC) remains to be elucidated. In order to investigate the effects of GnRH in NPC, the present study examined the expression of the GnRH-R transcript in NPC and investigated the phenotypic changes in HK1 cells, a recurrent NPC-derived cell line, upon receiving GnRH treatment. Firstly, the GnRH-R transcript was demonstrated in the NPC cell lines and four snap frozen biopsies using reverse transcription-quantitative polymerase chain reaction. In addition, immunohistochemistry revealed the expression of GnRH-R in two of the eight (25%) NPC specimens. Treatment with GnRH induced a rapid increase in intracellular ionised calcium concentration in the NPC cells. GnRH and its agonists, triptorelin and leuprolide, exerted anti-proliferative effects on the NPC cells, as determined using an MTS assay. GnRH did not induce any cell cycle arrest in the HK1 cells under the conditions assessed in the present study. Time-lapse imaging demonstrated a reduction in cell motility in the GnRH-treated cells. In conclusion, GnRH, or its analogues may have antitumour effects on NPC cells. The consequences of alterations in the levels of GnRH on the progression of NPC require further examination. PMID:26151677

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

    PubMed

    Wu, Vincent W C; Yang, Zhi-Ning; Zhang, Wu-Zhe; Wu, Li-li; Lin, Zhi-xiong

    2012-01-01

    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.

  8. Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma

    PubMed Central

    Lee, Yi-Ying; Chao, Tung-Bo; Sheu, Ming-Jen; Tian, Yu-Feng; Chen, Tzu-Ju; Lee, Sung-Wei; He, Hong-Lin; Chang, I-Wei; Hsing, Chung-Hsi; Lin, Ching-Yih; Li, Chien-Feng

    2016-01-01

    Background: Glutamate decarboxylase 1 (GAD1) which serves as a rate-limiting enzyme involving in the production of γ-aminobutyric acid (GABA), exists in the GABAergic neurons in the central nervous system (CNS). Little is known about the relevance of GAD1 to nasopharyngeal carcinoma (NPC). Through data mining on a data set derived from a published transcriptome database, this study first identified GAD1 as a differentially upregulated gene in NPC. We aimed to evaluate GAD1 expression and its prognostic effect on patients with early and locoregionally advanced NPC. Methods: We evaluated GAD1 immunohistochemistry and performed an H-score analysis on biopsy specimens from 124 patients with nonmetastasized NPC receiving treatment. GAD1 overexpression was defined as an H score higher than the median value. The findings of such an analysis are correlated with clinicopathological behaviors and survival rates, namely disease-specific survival (DSS), distant-metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) rates. Results: GAD1 overexpression was significantly associated with an increase in the primary tumor status (p < 0.001) and American Joint Committee on Cancer (AJCC) stages III-IV (p = 0.002) and was a univariate predictor of adverse outcomes of DSS (p = 0.002), DMeFS (p < 0.0001), and LRFS (p = 0.001). In the multivariate comparison, in addition to advanced AJCC stages III-IV, GAD1 overexpression remained an independent prognosticator of short DSS (p = 0.004, hazard ratio = 2.234), DMeFS (p < 0.001, hazard ratio = 4.218), and LRFS (p = 0.013, hazard ratio = 2.441) rates. Conclusions: Our data reveal that GAD1 overexpression was correlated with advanced disease status and may thus be a critical prognostic indicator of poor outcomes in NPC and a potential therapeutic target to facilitate the development of effective treatment modalities. PMID:27698909

  9. Targeting Epstein-Barr virus oncoprotein LMP1-mediated glycolysis sensitizes nasopharyngeal carcinoma to radiation therapy.

    PubMed

    Xiao, L; Hu, Z-Y; Dong, X; Tan, Z; Li, W; Tang, M; Chen, L; Yang, L; Tao, Y; Jiang, Y; Li, J; Yi, B; Li, B; Fan, S; You, S; Deng, X; Hu, F; Feng, L; Bode, A M; Dong, Z; Sun, L-Q; Cao, Y

    2014-09-11

    Our goal in this work was to illustrate the Epstein-Barr virus (EBV)-modulated global biochemical profile and provide a novel metabolism-related target to improve the therapeutic regimen of nasopharyngeal carcinoma (NPC). We used a metabolomics approach to investigate EBV-modulated metabolic changes, and found that the exogenous overexpression of the EBV-encoded latent membrane protein 1 (LMP1) significantly increased glycolysis. The deregulation of several glycolytic genes, including hexokinase 2 (HK2), was determined to be responsible for the reprogramming of LMP1-mediated glucose metabolism in NPC cells. The upregulation of HK2 elevated aerobic glycolysis and facilitated proliferation by blocking apoptosis. More importantly, HK2 was positively correlated with LMP1 in NPC biopsies, and high HK2 levels were significantly associated with poor overall survival of NPC patients following radiation therapy. Knockdown of HK2 effectively enhanced the sensitivity of LMP1-overexpressing NPC cells to irradiation. Finally, c-Myc was demonstrated to be required for LMP1-induced upregulation of HK2. The LMP1-mediated attenuation of the PI3-K/Akt-GSK3beta-FBW7 signaling axis resulted in the stabilization of c-Myc. These findings indicate a close relationship between EBV and glycolysis in NPC. Notably, LMP1 is the key regulator of the reprogramming of EBV-mediated glycolysis in NPC cells. Given the importance of EBV-mediated deregulation of glycolysis, anti-glycolytic therapy might represent a worthwhile avenue of exploration in the treatment of EBV-related cancers.

  10. 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.

  11. 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.

  12. Birth order and risk of nasopharyngeal carcinoma in multiplex families from Taiwan.

    PubMed

    Liu, Zhiwei; Coghill, Anna E; Pfeiffer, Ruth M; Hsu, Wan-Lun; Lou, Pei-Jen; Wang, Cheng-Ping; Yu, Kelly J; Niwa, Shelley; Brotzman, Michelle; Ye, Weimin; Chen, Chien-Jen; Hildesheim, Allan

    2016-12-01

    A small proportion of individuals infected with Epstein-Barr virus (EBV) develop nasopharyngeal carcinoma (NPC). Timing of initial exposure could alter immunological responses to primary EBV infection and explain variation in cancer risk later in life. We measured early life family structure as a proxy for the timing of primary EBV infection to examine whether earlier age at infection alters NPC risk. We utilized data from 480 NPC cases and 1,291 unaffected siblings from Taiwanese NPC multiplex families (≥ 2 family members with NPC, N = 2,921). Information on birth order within the family was derived from questionnaires. We utilized logistic regression models to examine the association between birth order and NPC, accounting for correlations between relatives. Within these high-risk families, older siblings had an elevated risk of NPC. Compared with being a first-born child, the risk (95% CIs) of NPC associated with a birth order of two, three, four and five or more was 1.00 (0.71, 1.40), 0.88 (0.62, 1.24), 0.74 (0.53, 1.05) and 0.60 (0.43, 0.82), respectively (P for trend = 0.002). We observed no associations between NPC risk and the number of younger siblings or cumulative infant-years exposure. These associations were not modified by underlying genetic predisposition or family size. We observed that early life family structure was important for NPC risk in NPC multiplex families, with older siblings having a greater risk of disease. Future studies focusing on more direct measures of the immune response to EBV in early childhood could elucidate the underlying mechanisms.

  13. Magnetic resonance imaging of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma: Patterns of spread

    SciTech Connect

    Liu Lizhi; Zhang Guoyi; Xie Chuangmiao; Liu Xuewen; Cui Chunyan; Li Li . E-mail: lililixj@hotmail.com

    2006-11-01

    Purpose: To investigate the incidence, distribution, and spread pattern of retropharyngeal lymph node (RLN) involvement in patients with nasopharyngeal carcinoma (NPC) by using magnetic resonance imaging (MRI). Methods and Materials: The MR images of 275 patients with newly diagnosed NPC were reviewed retrospectively. Nodes were classified as metastatic based on size criteria, the presence of nodal necrosis, and extracapsular spread. Results: Retropharyngeal lymph node involvement was detected in 175 (63.6%) patients. Metastatic RLNs were seen at the following levels: occipital bone, 24 (9.6%) nodes; C1, 157 (62.5%) nodes; C1/2, 40 (15.9%) nodes; C2, 27 (10.8%) nodes; C2/3, 1 (0.4%) node; and C3, 2 (0.8%) nodes. The incidence of RLN involvement was equal to the incidence of cervical lymph node involvement (81.4% vs. 81.4%) in 215 patients with nodal metastases. A significantly higher incidence of metastatic RLNs was observed in the presence of oropharynx, prestyloid parapharyngeal space, post-styloid parapharyngeal space, longus colli muscle, medial pterygoid muscle, levator muscle of velum palatini, tensor muscle of velum palatini, Level II node, Level III node, and Level V node involvement. A significantly lower incidence of metastatic RLNs was found in T1, N0, and Stage I disease. Conversely, no significant difference in the incidence of metastatic RLNs was observed between T1, 2, and, 3; N2 and N3; or Stage II, III, and IV disease. Conclusions: There is an orderly decrease in the incidence of metastatic lateral RLNs from the C1 to C3 level. Metastatic RLNs associate well with involvement of certain structures in early stage primary tumors and lymph node metastases of the upper jugular chain (Level II, Level III nodes) and the posterior triangle (Level V nodes). Both RLNs and cervical Level II nodes appear to be the first-echelon nodes in NPC.

  14. 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

  15. 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.

  16. Clinical value of serum Epstein-Barr virus DNA assay in the diagnosis of nasopharyngeal carcinoma.

    PubMed

    Sun, Dezhong; Yang, Zhaoke; Fu, Yugui; Chen, Yanlin; Wang, Shoufeng; Zhang, Yun; Ma, Yanyi; Zhang, Xiaoyan

    2014-09-01

    Serum Epstein-Barr virus DNA has been approved for diagnosing nasopharyngeal carcinoma (NPC). The goal of this meta-analysis was to evaluate the clinical value of the serum Epstein-Barr virus DNA in the diagnosis of NPC. The PubMed, Embase, Web of Knowledge, Chinese Wanfang Med Online, and National Knowledge Infrastructure (CNKI) databases were searched to identify suitable studies. The pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and diagnostic odds ratio (DOR) of the serum Epstein-Barr virus DNA for the diagnosis of NPC were calculated. Summary receiver operating characteristic curves were used to summarize overall test performances. Meta-Disc 1.4 and Stata 12.0 softwares were used to analyze the data. A total of 2,520 patients from ten trials were subjected to meta-analysis. The summary estimates of the serum Epstein-Barr virus DNA for NPC diagnosis were as follows: sensitivity 0.69 (95 % confidence interval (CI) 0.65-0.72), specificity 0.84 (95 % CI = 0.82-0.86), LR + 4.81 (95 % CI = 2.94-7.88), LR - 0.25 (95 % CI = 0.13-0.48), DOR 24.65 (95 % CI = 12.64-48.07), and area under the summary receiver operator characteristic (SROC) curve (AUC) was 0.8979. Our study demonstrates that the serum Epstein-Barr virus DNA could be a useful tumor marker for NPC diagnosis.

  17. 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.

  18. The FOXM1-ABCC5 axis contributes to paclitaxel resistance in nasopharyngeal carcinoma cells.

    PubMed

    Hou, Youxiang; Zhu, Qianling; Li, Zheng; Peng, Yongbo; Yu, Xiaohui; Yuan, Bowen; Liu, Yijun; Liu, Youhong; Yin, Linglong; Peng, Yuchong; Jiang, Zhenghua; Li, Jinping; Xie, Bowen; Duan, Yumei; Tan, Guolin; Gulina, Kurban; Gong, Zhicheng; Sun, Lunquan; Fan, Xuegong; Li, Xiong

    2017-03-09

    Paclitaxel is clinically used as a first-line chemotherapeutic regimen for several cancer types, including head and neck cancers. However, acquired drug resistance results in the failure of therapy, metastasis and relapse. The drug efflux mediated by ATP-binding cassette (ABC) transporters and the survival signals activated by forkhead box (FOX) molecules are critical in the development of paclitaxel drug resistance. Whether FOX molecules promote paclitaxel resistance through drug efflux remains unknown. In this study, we developed several types of paclitaxel-resistant (TR) nasopharyngeal carcinoma (NPC) cells. These TR NPC cells acquired cancer stem cell (CSC) phenotypes and underwent epithelial to mesenchymal transition (EMT), and developed multidrug resistance. TR cells exhibited stronger drug efflux than parental NPC cells, leading to the reduction of intracellular drug concentrations and drug insensitivity. After screening the gene expression of ABC transporters and FOX molecules, we found that FOXM1 and ABCC5 were consistently overexpressed in the TR NPC cells and in patient tumor tissues. Further studies demonstrated that FOXM1 regulated abcc5 gene transcription by binding to the FHK consensus motifs at the promoter. The depletion of FOXM1 or ABCC5 with siRNA significantly blocked drug efflux and increased the intracellular concentrations of paclitaxel, thereby promoting paclitaxel-induced cell death. Siomycin A, a FOXM1 inhibitor, significantly enhanced in vitro cell killing by paclitaxel in drug-resistant NPC cells. This study is the first to identify the roles of FOXM1 in drug efflux and paclitaxel resistance by regulating the gene transcription of abcc5, one of the ABC transporters. Small molecular inhibitors of FOXM1 or ABCC5 have the potential to overcome paclitaxel chemoresistance in NPC patients.

  19. 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.

  20. 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.

  1. 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.

  2. TP53-induced glycolysis and apoptosis regulator promotes proliferation and invasiveness of nasopharyngeal carcinoma cells

    PubMed Central

    WONG, ELAINE YUE LING; WONG, SZE-CHUEN CESAR; CHAN, CHARLES MING LOK; LAM, EMILY KAI YEE; HO, LOUISA YEUNG; LAU, CECILIA PIK YUK; AU, THOMAS CHI CHUEN; CHAN, AMANDA KIT CHING; TSANG, CHI MAN; TSAO, SAI WAH; LUI, VIVIAN WAI YAN; CHAN, ANTHONY TAK CHEUNG

    2015-01-01

    The TP53-induced glycolysis and apoptosis regulator (TIGAR) is the protein product of the p53 target gene, C12orf5. TIGAR blocks glycolysis and promotes cellular metabolism via the pentose phosphate pathway; it promotes the production of cellular nicotinamide adenine dinucleotide phosphate (NADPH), which leads to enhanced scavenging of intracellular reactive oxygen species, and inhibition of oxidative stress-induced apoptosis in normal cells. Our previous study identified a novel nucleoside analog that inhibited cellular growth and induced apoptosis in nasopharyngeal carcinoma (NPC) cell lines via downregulation of TIGAR expression. Furthermore, the growth inhibitory effects of c-Met tyrosine kinase inhibitors were ameliorated by the overexpression of TIGAR in the NPC cell lines. These results indicate a significant role for TIGAR expression in the survival of NPCs. The present study aimed to further define the function of TIGAR expression in NPC cells. In total, 36 formalin-fixed, paraffin-embedded NPC tissue samples were obtained for the immunohistochemical determination of TIGAR expression. The effects of TIGAR expression on cell proliferation, NADPH production and cellular invasiveness were also assessed in NPC cell lines. Overall, TIGAR was overexpressed in 27/36 (75%) of the NPC tissues compared with the adjacent non-cancer epithelial cells. Similarly, TIGAR overexpression was also observed in a panel of six NPC cell lines compared with normal NP460 hTert and Het1A cell lines. TIGAR overexpression led to increased cellular growth, NADPH production and invasiveness of the NPC cell lines, whereas a knockdown of TIGAR expression resulted in significant inhibition of cellular growth and invasiveness. The expression of the two mesenchymal markers, fibronectin and vimentin, was increased by TIGAR overexpression, but reduced following TIGAR-knockdown. The present study revealed that TIGAR overexpression led to increased cellular growth, NADPH production and

  3. Prognostic Nomogram for Patients with Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy

    PubMed Central

    Wu, Shixiu; Xia, Bing; Han, Fei; Xie, Ruifei; Song, Tao; Lu, Lixia; Yu, Wei; Deng, Xiaowu; He, Qiancheng; Zhao, Cong; Xie, Conghua

    2015-01-01

    This study was aimed to define possible predictors of overall survival in nasopharyngeal carcinoma (NPC). Patients were treated with intensity-modulated radiation therapy (IMRT), to establish an effective prognostic nomogram that could provide individualized predictions of treatment outcome in this setting. We reviewed the records of 533 patients with non-metastatic NPC who underwent IMRT with or without concurrent chemotherapy at the Department of Radiation Oncology of Sun Yat-Sen University from 2002 to 2009; none of these patients received induction or adjuvant chemotherapy. These data sets were used to construct a nomogram based on Cox regression. Nomogram performance was determined via a concordance index (C-index) and a calibration curve which was compared with the TNM staging system for NPC. The results were validated in an external cohort of 442 patients from the Department of Radiation Oncology of Wenzhou Medical College who were treated during the same period. Results showed that the greatest influence on survival were primary gross tumor volume, age, tumor stage and nodal stage (2002 Union for International Cancer Control [UICC] staging system), which were selected into the nomogram. The C-index of the nomogram for predicting survival was 0.748 (95%CI, 0.704–0.785), which was statistically higher than that of TNM staging system (0.684, P<0.001). The calibration curve exhibited agreement between nomogram-predicted and the actual observed probabilities for overall survival. In the validation cohort, the nomogram discrimination was superior to the TNM staging system (C-index: 0.768 vs 0.721; P = 0.026). In conclusion, the nomogram proposed in this study resulted in more-accurate prognostic prediction for patients with NPC after IMRT and compared favorably to the TNM staging system; this individualized information will aid in patient counseling and may be used for de-escalation trials in the future. PMID:26248338

  4. CT and MRI findings of radiation-induced external auditory canal carcinoma in patients with nasopharyngeal carcinoma after radiotherapy

    PubMed Central

    Zhang, X; Bai, S; Li, H; Hu, H; Duan, X; Chen, M; Wang, D; Chen, Y; Zhang, F

    2015-01-01

    Objective: To summarize the radiological and clinical features of radiation-induced external auditory canal carcinomas (RIEACCs) in patients with nasopharyngeal carcinomas (NPCs) after radiation therapy. Methods: CT, MRI and clinical features in 16 patients with histologically proven RIEACCs were retrospectively reviewed. There were 2 females and 14 males, with a median age of 52.5 years at the time of diagnosis of RIEACC. Imaging parameters including lesion extent, size, margin, shape, bone destruction, adjacent structure invasion, density/signal intensity, and pattern and degree of enhancement were assessed. Clinical features including clinical staging, histological type, treatment and radiation dose (RD) of primary NPC as well as the histological type, staging of radiation-induced tumour and the latent period between NPC and RIT were recorded. Results: All patients had a single RIEACC. The lesions had a size of 3.5 ± 1.4 cm and were localized (n = 7) or extensive (n = 9). Most of the lesions were partially or ill defined with an irregular shape and had an intermediate density/signal pattern and moderate homogeneous enhancement. The latent period of RIEACCs ranged from 10 to 20 years in nine patients with a RD of 68–70 Gy; from 2 to 10 years in five patients with a RD of 68–74 Gy; and more than 20 years in two patients with a RD of 70 or 72 Gy. Conclusion: An external auditory canal (EAC) mass with homogeneous, intermediate CT density or signal intensity in patients with NPC after radiotherapy is highly suggestive of RIEACC, which should be included in the routine surveillance for patients with NPC after radiotherapy. Advances in knowledge: RIEACCs could occur as short as 2 years after radiotherapy in patients with NPC and have distinct features from otitis media and sarcomas. This EAC malignancy should be included in routine surveillance for patients with NPC after radiotherapy. PMID:25827205

  5. Recommendations for Updating T and N Staging Systems for Nasopharyngeal Carcinoma in the Era of Intensity-Modulated Radiotherapy

    PubMed Central

    Liang, Zhong-Guo; Chen, Xiao-Qian; Niu, Zhi-Jie; Chen, Kai-Hua; Li, Ling; Qu, Song; Su, Fang; Zhao, Wei; Li, Ye; Pan, Xin-Bin; Zhu, Xiao-Dong

    2016-01-01

    Objective The aim of this study was to compare the 2008 Chinese and the 7th edition of the American Joint Committee on Cancer (AJCC) staging systems for nasopharyngeal carcinoma and to provide proposals for updating T and N staging systems of the present staging system. Methods Between January 2007 and December 2012, a cohort of 752 patients with biopsy-proven, newly diagnosed, non-metastatic nasopharyngeal carcinoma who were treated with intensity-modulated radiotherapy were retrospectively analysed. Prognoses were compared by T stage, N stage, and clinical stage according to the two staging systems for overall survival (OS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS). Results In terms of both the T and N staging systems, the two current staging systems were comparable in predicting OS. The T classification of the 2008 Chinese staging system was better in predicting LRFS, while the N classification of the 7th edition AJCC staging system was superior in predicting DMFS. In the modern era of intensity-modulated radiotherapy, the staging system should be updated by down-staging the current stage T2 to T1, and it might be rational to merge subcategories N1 and N2. Conclusions The two current staging systems each had advantages in predicting prognosis. It seems reasonable to downstage T2 to T1 and to merge N1 and N2. PMID:27973544

  6. 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.

  7. Comparison of SPECT/CT, MRI and CT in diagnosis of skull base bone invasion in nasopharyngeal carcinoma.

    PubMed

    Zhang, Shu-xu; Han, Peng-hui; Zhang, Guo-qian; Wang, Rui-hao; Ge, Yong-bin; Ren, Zhi-gang; Li, Jian-sheng; Fu, Wen-hai

    2014-01-01

    Early detection of skull base invasion in nasopharyngeal carcinoma (NPC) is crucial for correct staging, assessing treatment response and contouring the tumor target in radiotherapy planning, as well as improving the patient's prognosis. To compare the diagnostic efficacy of single photon emission computed tomography/computed tomography (SPECT/CT) imaging, magnetic resonance imaging (MRI) and computed tomography (CT) for the detection of skull base invasion in NPC. Sixty untreated patients with histologically proven NPC underwent SPECT/CT imaging, contrast-enhanced MRI and CT. Of the 60 patients, 30 had skull base invasion confirmed by the final results of contrast-enhanced MRI, CT and six-month follow-up imaging (MRI and CT). The diagnostic efficacy of the three imaging modalities in detecting skull base invasion was evaluated. The rates of positive findings of skull base invasion for SPECT/CT, MRI and CT were 53.3%, 48.3% and 33.3%, respectively. The sensitivity, specificity and accuracy were 93.3%, 86.7% and 90.0% for SPECT/CT fusion imaging, 96.7%, 100.0% and 98.3% for contrast-enhanced MRI, and 66.7%, 100.0% and 83.3% for contrast-enhanced CT. MRI showed the best performance for the diagnosis of skull base invasion in nasopharyngeal carcinoma, followed closely by SPECT/CT. SPECT/CT had poorer specificity than that of both MRI and CT, while CT had the lowest sensitivity.

  8. Triptolide Combined with Radiotherapy for the Treatment of Nasopharyngeal Carcinoma via NF-κB-Related Mechanism

    PubMed Central

    Zhang, Weiying; Kang, Min; Zhang, Tingting; Li, Bo; Liao, Xueyin; Wang, Rensheng

    2016-01-01

    Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis because of the lack of an effective treatment. Here we explored the efficiency and the molecular mechanisms of combined treatment with triptolide and ionizing radiation for treating NPC. Human nasopharyngeal carcinoma (CNE) cells were treated with triptolide, ionizing radiation, or triptolide plus ionizing radiation in vitro. Tumor potency was examined in an in vivo CNE cell xenograft mouse model, which was treated as above. Our results demonstrated that triptolide caused a significant reduction in cell growth and colony number, and induced a marked apoptosis that was further enhanced with increasing doses of ionizing radiation. Combination treatment synergistically reduced tumor weight and volume without obvious toxicity. Western blot analysis in vitro and in vivo showed that triptolide induced apoptotic protein Bax expression and inhibited phosph-NF-κB p65, Bcl-2 and VEGF proteins without affecting other NF-κB related protein expression. In conclusion, our findings revealed that triptolide plus ionizing radiation had synergistic anti-tumor and anti-angiogenesis effects in NPC via down-regulating NF-κB p65 phosphorylation. The combination therapy may provide novel mechanism insights into inhibit NPC. PMID:27999372

  9. Inhibitory effect of endostar in combination with radiotherapy in a mouse model of human CNE2 nasopharyngeal carcinoma.

    PubMed

    Zhou, Ning; Hu, Guangyuan; Mei, Qi; Qiu, Hong; Long, Guoxian; Chen, Chunli; Guoqing, Hu

    2011-02-01

    The inhibitory effects of Endostar in combination with radiotherapy in BALB/c nude mice model of human CNE2 nasopharyngeal carcinoma and the mechanism were investigated. In nude mice model of CNE2 nasopharyngeal carcinoma, the inhibitory rate and the sensitizing enhancement ratio (E/O) were calculated according to the tumor volumes in different groups. The expression of microvascular density (MVD) in tumor tissues was examined by using immunohistochemistry staining. The transcription of VEGF gene was detected by using RT-PCR. The inhibitory rate in Endostar+ radiotherapy group was higher than in other groups. In Endostar+radiotherapy group, the tumor volume was significantly decreased and the E/O ratio was 2.335, suggesting that Endostar could be a radiosensitizer. The expression of MVD of tumor tissues in Endostar+radiotherapy group was reduced significantly. The expression of the MVD in treatment groups was significantly different from that in control group (P<0.05). Compared to other groups, VEGF mRNA expression in Endostar+radiotherapy group was decreased remarkably. Endostar in combination with radiotherapy significantly inhibited the growth of CNE2 tumor. The combination therapy decreased the expression of VEGF, and inhibited tumor angiogenesis and proliferation. When combined with radiotherapy, Endostar acted as a radiosensitizer.

  10. 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

  11. 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

  12. 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

  13. Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma

    PubMed Central

    Su, Li; Zhang, Mingwei; Zhang, Weijian; Cai, Chuanshu; Hong, Jinsheng

    2017-01-01

    Abstract Background: Pretreatment hematologic parameters of the inflammatory response, including lymphocyte, neutrophil, and platelet counts, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio, have emerged as prognostic factors for patients with cancer. This systematic review and meta-analysis aimed to summarize the association between the hematologic markers and prognosis of nasopharyngeal carcinoma (NPC). Methods: A systematic search of PubMed, Google Scholar, MEDLINE, EMBASE, Web of Science, and the Cochrane Library was conducted up to April 2016. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and synthesized to examine prognostic outcomes including cancer-specific survival (CSS), overall survival (OS), progression-free survival (PFS), distant metastasis-free survival, and local relapse-free survival (LRFS). Results: Fourteen studies comprising 11,651 NPC patients were ultimately included, and all eligible studies were conducted in East Asia. The OS, CSS, PFS, distant metastasis-free survival, and LRFS risks differed among patients according to hematologic marker levels. All of the parameters were associated with prognostic outcomes in patients with NPC. NLR and lymphocyte counts were most commonly reported. A high NLR was significantly associated with poor NPC prognosis (pooled HR 1.42, 95% CI 1.21–1.67 for CSS; pooled HR 1.77, 95% CI 1.41–2.23 for OS; pooled HR 1.67, 95% CI 1.36–2.06 for PFS; pooled HR 1.64, 95% CI 1.15–2.34 for LRFS). High lymphocyte count indicated favorable NPC prognosis (pooled HR 0.72, 95% CI 0.64–0.81 for OS; pooled HR 0.71, 95% CI 0.56–0.91 for PFS). Conclusions: Meta-analysis indicated that NLR and lymphocyte counts could be prognostic predictors in NPC for East Asian population. Patients with a high NLR or low lymphocyte count had poor prognosis. However, due to the limitation of included population, the conclusion was limited to East Asian

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

    PubMed

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

    2012-04-01

    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

  15. 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

  16. A Novel Inflammation-Based Stage (I Stage) Predicts Overall Survival of Patients with Nasopharyngeal Carcinoma

    PubMed Central

    Li, Jian-Pei; Chen, Shu-Lin; Liu, Xiao-Min; He, Xia; Xing, Shan; Liu, Yi-Jun; Lin, Yue-Hao; Liu, Wan-Li

    2016-01-01

    Recent studies have indicated that inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified GPS (mGPS) and C-reactive protein/Albumin (CRP/Alb) ratio, platelet–lymphocyte ratio (PLR), and neutrophil–lymphocyte ratio (NLR), have been reported to have prognostic value in patients with many types of cancer, including nasopharyngeal carcinoma (NPC). In this study, we proposed a novel inflammation-based stage, named I stage, for patients with NPC. A retrospective study of 409 newly-diagnosed cases of NPC was conducted. The prognostic factors (GPS, mGPS, CRP/Alb ratios, PLR, and NLR) were evaluated using univariate and multivariate analyses. Then, according to the results of the multivariate analyses, we proposed a I stage combination of independent risk factors (CRP/Alb ratio and PLR). The I stage was calculated as follows: patients with high levels of CRP/Alb ratio (>0.03) and PLR (>146.2) were defined as I2; patients with one or no abnormal values were defined as I1 or I0, respectively. The relationships between the I stage and clinicopathological variables and overall survival (OS) were evaluated. In addition, the discriminatory ability of the I stage with other inflammation-based prognostic scores was assessed using the AUCs (areas under the curves) analyzed by receiver operating characteristics (ROC) curves. The p value of <0.05 was considered to be significant. A total of 409 patients with NPC were enrolled in this study. Multivariate analyses revealed that only the CRP/Alb ratio (Hazard ratio (HR) = 2.093; 95% Confidence interval (CI): 1.222–3.587; p = 0.007) and PLR (HR: 2.003; 95% CI: 1.177–3.410; p = 0.010) were independent prognostic factors in patients with NPC. The five-year overall survival rates for patients with I0, I1, and I2 were 92.1% ± 2.9%, 83.3% ± 2.6%, and 63.1% ± 4.6%, respectively (p < 0.001). The I stage had a higher area under the curve value (0.670) compared with other systemic inflammation

  17. Benefit of percutaneous endoscopic gastrostomy in patients undergoing definitive chemoradiotherapy for locally advanced nasopharyngeal carcinoma

    PubMed Central

    Xu, Yun; Guo, Qiaojuan; Lin, Jin; Chen, Bijuan; Wen, Jiangmei; Lu, Tianzhu; Xu, Yuanji; Zhang, Mingwei; Pan, Jianji; Lin, Shaojun

    2016-01-01

    Background and aim To evaluate the impact of percutaneous endoscopic gastrostomy (PEG) tube on nutritional status, treatment-related toxicity, and treatment tolerance in patients with locally advanced nasopharyngeal carcinoma (NPC) who underwent chemoradiotherapy. Patients and methods We enrolled 133 consecutive non-metastatic NPC (III/IV stage) patients, who were treated with prophylactic PEG feeding before the initiation of concurrent chemoradiotherapy (CCRT) between June 1, 2010 and June 30, 2014. Meanwhile, another 133 non-PEG patients, who were matched for age, gender, and tumor, node, metastases stage, were selected as historical control cohort. Weight and nutritional status changes from pre-radiotherapy to the end of radiotherapy were evaluated, and treatment tolerance and related acute toxicities were analyzed as well. Results We found that significantly more patients (91.73%) in the PEG group could finish two cycles of CCRT, when compared with those in the non-PEG group (57.89%) (P<0.001). We also indicated that more patients (50.38%) in the non-PEG group experienced weight loss of ≥5%, while the phenomenon was only found in 36.09% patients in the PEG group (P=0.019). In addition, the percentage of patients who lost ≥10% of their weight was similar in these two groups. Changes in albumin and prealbumin levels during radiotherapy in the non-PEG group were higher than those obtained for the PEG group with significant differences (P-values of 0.023 and <0.001, respectively). Furthermore, patients in the PEG group had significantly lower incidence of grade III acute mucositis than those in the non-PEG group (22.56% vs 36.84%, P=0.011). Tube-related complications occurred only in 14 (10.53%) patients in the PEG group, including incision infection of various degrees. Conclusion PEG and intensive nutrition support may help to minimize body weight loss, maintain nutritional status, and offer better treatment tolerance for patients with locally advanced NPC who

  18. 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.

  19. Factors influencing the incidence of sinusitis in nasopharyngeal carcinoma patients after intensity-modulated radiation therapy.

    PubMed

    Su, Yan-xia; Liu, Lan-ping; Li, Lei; Li, Xu; Cao, Xiu-juan; Dong, Wei; Yang, Xin-hua; Xu, Jin; Yu, Shui; Hao, Jun-fang

    2014-12-01

    The aim of the study was to investigate the incidence of sinusitis in nasopharyngeal carcinoma (NPC) patients before and after intensity-modulated radiation therapy (IMRT) and to analyze factors associated with the incidence of sinusitis following IMRT. We retrospectively analyzed 283 NPC patients who received IMRT in our hospital from March 2009 to May 2011. The diagnostic criteria for sinusitis are based on computed tomography (CT) or magnetic resonance imaging (MRI) findings. CT or MRI scans were performed before and after IMRT to evaluate the incidence of sinusitis. Factors influencing the incidence of sinusitis were analyzed by log-rank univariate and logistic multivariate analyses. Among the 283 NPC patients, 128 (45.2 %) suffered from sinusitis before radiotherapy. The incidence rates of sinusitis in patients with T1, T2, T3, and T4 NPC before radiotherapy were 22.6, 37.5, 46.8, and 61.3 %, respectively (χ 2 = 14.548, p = 0.002). Among the 155 NPC patients without sinusitis before radiotherapy, the incidence rates of sinusitis at the end of radiotherapy and at 1, 3, 6, 9, 12, and 18 months after radiotherapy were 32.9, 43.2, 61.3, 68.4, 73.5, 69.7, and 61.3 %, respectively (χ 2 = 86.461, p < 0.001). Univariate analysis showed that T stage, invasion of the nasal cavity, nasal irrigation, and radiation dose to the nasopharynx were associated with the incidence of sinusitis in NPC patients after IMRT (p = 0.003, 0.006, 0.002, and 0.020). Multivariate analysis showed that T stage, invasion of the nasal cavity, and nasal irrigation were influential factors for the incidence of sinusitis in NPC patients after IMRT (p = 0.002, 0.002, and 0.000). There was a higher incidence of sinusitis with higher T stage among NPC patients before radiotherapy, and the incidence of sinusitis in NPC patients after IMRT was high (45.2 %). The incidence of sinusitis increased rapidly within the first 3 months after IMRT, and the number of sinusitis cases peaked at 6-9 months after

  20. Prognostic impact of pretherapeutic gamma-glutamyltransferase on patients with nasopharyngeal carcinoma

    PubMed Central

    Peng, Hai-Hua; Huang, Wen-Jin; Cai, Long-Mei; Zhou, Tong-Chong

    2017-01-01

    Background Gamma-glutamyltransferase (GGT) is a membrane-bound enzyme involved in the metabolism of glutathione. Studies suggested that GGT played an important role in the tumor development, progression, invasion and drug resistance and prognosis. The association between GGT and prognosis of patients with nasopharyngeal carcinoma (NPC) was unknown. This study was conducted to investigate the association of pretherapeutic serum level of GGT with clinical-pathological parameters and survival in patients with NPC. Methods Two hundred and twenty-two patients with NPC were recruited in this study and were stratified into two GGT risk groups (≤ 34.5 U/L, > 34.5 U/L). The association of pretherapeutic serum GGT levels with clinical–pathological parameters was examined. Univariate and multivariate survival analyses were performed. Findings The pretherapeutic serum level of GGT was not associated with gender, age, pathology, T stage, N stage, TNM stage, chemotherapy or radiotherapy in patients with NPC. Patients in the high-risk GGT group had a poorer survival than the low-risk GGT group (3-year overall survival, 74.2% vs. 50.2%, P = 0.001; 3-year progression-free survival, 76.4% vs. 47.1%, P < 0.001; 3-year loco-regional relapse-free survival, 76.4% vs. 51.3%, P < 0.001; 3-year distant metastasis-free survival, 89.5% vs. 66.4%, P < 0.001). Multivariate analysis suggested that patients in the high-risk GGT group had 2.117 (95% confidence interval [CI], 1.225 ∼ 3.659, P = 0.007) times the risk of death, 2.836 (95% CI, 1.765 ∼ 4.557, P < 0.001) times the risk of progression, 2.551 (95% CI, 1.573 ∼ 4.138, P < 0.001) times the risk of relapse, and 3.331 (95% CI, 1.676 ∼ 6.622, P < 0.001) times the risk of metastasis compared with those in the low-risk GGT group. Conclusion The pretherapeutic serum level of GGT might serve as a novel independent prognostic factor for overall-survival, progression-free survival, loco-regional relapse-free survival and distant

  1. 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

  2. Sequential chemoradiotherapy with gemcitabine and cisplatin for locoregionally advanced nasopharyngeal carcinoma.

    PubMed

    Gu, Mo-Fa; Liu, Li-Zhi; He, Long-Jun; Yuan, Wen-Xin; Zhang, Rong; Luo, Guang-Yu; Xu, Guo-Liang; Zhang, Hua-Man; Yan, Chao-Xian; Li, Jian-Jun

    2013-01-01

    We investigated a new chemoradiotherapy (CRT) regimen for locoregionally advanced nasopharyngeal carcinoma (NPC). A total of 240 patients were randomly assigned to three different CRT regimens: sequential CRT [1 cycle chemotherapy + Phase I radiotherapy (RT) + 1 cycle chemotherapy + Phase II RT + 2 cycles chemotherapy] with a cisplatin-gemcitabine (GC) regimen (800 mg/m(2) gemcitabine on Days 1 and 8 and 20 mg/m(2) cisplatin on Days 1-5, every 4 weeks) (sGC-RT); sequential chemoradiotherapy with a cisplatin-fluorouracil (PF) regimen (20 mg/m(2) DDP and 500 mg/m(2) 5-FU on Days 1-5, every 4 weeks) (sPF-RT) and cisplatin-based concurrent chemoradiotherapy plus adjuvant PF chemotherapy (Con-RT + PF). The complete response rate was higher in the sGC + RT group than in the other two groups (98.75% vs. 92.50%, p < 0.01). The 3-year overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates in the sGC-RT group were significantly higher than those observed in the Con-RT group (OS, 95.0% vs. 76.3%, p < 0.001; DFS, 89.9% vs. 67.5%, p < 0.001; DMFS, 92.5% vs. 76.0%, p = 0.004) and in the sPF + RT group (OS, 95.0% vs. 73.6%, p < 0.001; DFS, 89.9% vs. 63.3%, p < 0.001; DMFS, 92.5% vs. 74.7%, p = 0.002). There were no significant differences in 3-year OS, DFS and MFS rates between the Con-RT and the sPF-RT groups. The GC-RT group experienced more hematologic toxicity, constipation and rash; however, there were no differences in late RT toxicity between the groups. These results demonstrate that a sGC-RT regimen is effective and well tolerated in patients with locoregionally advanced NPC.

  3. 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

  4. Cervical nodal necrosis is an independent survival predictor in nasopharyngeal carcinoma: an observational cohort study

    PubMed Central

    Luo, Yangkun; Ren, Jing; Zhou, Peng; Gao, Yang; Yang, Guangquan; Lang, Jinyi

    2016-01-01

    Purpose Most nasopharyngeal carcinoma (NPC) patients present with locoregionally advanced disease at the time of diagnosis; however, there is a lack of consensus on specific prognostic factors potentially improving overall survival, especially in late-stage disease. Herein, we conducted a retrospective study to evaluate various potential prognostic factors in order to provide useful information for clinical treatment of T3/T4-stage NPC. Patients and methods A total of 189 previously untreated NPC patients were enrolled in the current study. All patients received intensity-modulated radiotherapy. Survival, death, relapse-free survival (both local and regional), and metastasis were recorded during follow-up. Factors affecting patient survival were assessed by using univariate and multivariate analyses. Results The median follow-up time was 69 months. The 5-year local-regional recurrence-free survival, distant metastasis-free survival, progression-free survival (PFS), and overall survival (OS) of the entire group were 89.8%, 71.5%, 66.3%, and 68.9%, respectively. Univariate analysis revealed significant differences in the 5-year PFS (58.5% vs 72.5%, P=0.015) and OS (59.5% vs 75.8%, P=0.033) rates of patients with and without cervical nodal necrosis (CNN). Subgroup analyses revealed that CNN was associated with poorer distant metastasis-free survival and PFS among patients with N2 stage (P=0.046 and P=0.005) and with poorer PFS among patients with T3 or III stage (all P=0.022). Multivariate analysis revealed CNN to be an independent prognostic factor for PFS and OS (PFS: adjusted hazard ratio, 1.860; 95% CI: 1.134–3.051; P=0.014; OS: adjusted hazard ratio, 1.754; 95% CI: 1.061–2.899; P=0.028). Conclusion CNN is a potential independent negative prognostic factor in NPC patients. Our results suggest that stratification of NPC patients based on their CNN status should be considered as part of NPC disease management. PMID:27843328

  5. Methods and matrices: approaches to identifying miRNAs for Nasopharyngeal carcinoma

    PubMed Central

    2014-01-01

    Background Nasopharyngeal carcinoma (NPC) is a solid tumor of the head and neck. Multimodal therapy is highly effective when NPC is detected early. However, due to the location of the tumor and the absence of clinical signs, early detection is difficult, making a biomarker for the early detection of NPC a priority. The dysregulation of small non-coding RNAs (miRNAs) during carcinogenesis is the focus of much current biomarker research. Herein, we examine several miRNA discovery methods using two sample matrices to identify circulating miRNAs (c-miRNAs) associated with NPC. Methods We tested two miRNA discovery workflows on two sample sources for miRNAs associated with NPC. In the first workflow, we assumed that NPC tumor tissue would be enriched for miRNAs, so we compared miRNA expression in FFPE from NPC cases and controls using microarray and RNA-Seq technologies. Candidate miRNAs from both technologies were verified by qPCR in FFPE and sera from an independent NPC sample set. In a second workflow, we directly interrogated NPC case and control sera by RNA-Seq for c-miRNAs associated with NPC, with candidate c-miRNAs verified by qPCR in the sera from the same independent NPC sample set. Results Both microarray and RNA-Seq narrowed the miRNA signature to 1-5% of the known mature human miRNAs. Moreover, these two methods produced similar results when applied to the same sample type (FFPE), with RNA-Seq additionally indicating “unknown” miRNAs associated with NPC. However, we found different miRNA profiles in NPC sera compared to FFPE using RNA-Seq, with the few overlapping miRNAs found to be significantly up-regulated in FFPE significantly down-regulated in sera (and vice versa). Despite the different miRNA profiles found in FFPE and sera, both profiles strongly associated with NPC, providing two potential sources for biomarker signatures for NPC. Conclusions We determined that the direct interrogation of sera by RNA-Seq was the most informative method for

  6. 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

  7. 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.

  8. Brachytherapy boost in loco-regionally advanced nasopharyngeal carcinoma: a prospective randomized trial of the International Atomic Energy Agency

    PubMed Central

    2014-01-01

    Abstact Background The purpose was to determine whether a brachytherapy boost improves outcomes in patients with advanced nasopharyngeal carcinoma treated with standard chemo-radiotherapy. Methods Patients with nasopharyngeal carcinoma WHO grades I-III and TNM stages III or non-metastatic stage IV were eligible for this phase III study. Patients were randomized to either arm (A) induction chemotherapy, followed by external beam radiotherapy (EBRT) with concomitant cisplatin (n = 139) or arm (B), the same schedule plus a brachytherapy boost to the nasopharynx (n = 135). The EBRT doses given were 70 Gy to the primary tumour and positive lymph nodes and 46 Gy to the negative neck. The additional brachytherapy boost in arm (B) was given by either low dose-rate (LDR – 11 Gy) or high dose-rate (HDR – 3 fractions of 3.0 Gy) brachytherapy. The primary endpoint was 3-year overall survival (OS) and secondary endpoints were: local control, regional control, distant metastasis and grade 3–4 adverse events. Results 274 patients were randomized between September 2004 and December 2008. The two arms were comparable with regard to age, gender, stage and grade. 273 patients completed treatment. Median follow-up was 29 months (0.2-67 months). The effect of treatment arm, country, age, gender, WHO pathology, stage (T3-4, N2-3 versus other) and chemotherapy on overall survival (OS), disease-free survival (DFS) and local recurrence-free survival (LRFS) was studied. Stage significantly affected OS (p = 0.024) and DFS (p = 0.018) while age significantly affected OS (p = 0.014). None of the other factors studied were significant. The 3-year LRFS was 60.5% and 54.4% in arms A and B respectively (p = 0.647). The 3-year regional control rate in the neck was 59.7% and 54.3% respectively (p = 0.7). Distant metastasis developed in 59.7% of patients in arm A and 55.4% in arm B (p = 0.377). Patients with T1/T2 N + had a 3 year LRFS of 51.8% in Arm A (62 patients) versus 57.9% in Arm B (67

  9. High sensitivity of gold nanoparticles co-doped with Gd2O3 mesoporous silica nanocomposite to nasopharyngeal carcinoma cells

    PubMed Central

    Wang, Hui; Zhang, Songjin; Tian, Xiumei; Liu, Chufeng; Zhang, Lei; Hu, Wenyong; Shao, Yuanzhi; Li, Li

    2016-01-01

    Nanoprobes for combined optical and magnetic resonance imaging have tremendous potential in early cancer diagnosis. Gold nanoparticles (AuNPs) co-doped with Gd2O3 mesoporous silica nanocomposite (Au/Gd@MCM-41) can produce pronounced contrast enhancement for T1 weighted image in magnetic resonance imaging (MRI). Here, we show the remarkably high sensitivity of Au/Gd@MCM-41 to the human poorly differentiated nasopharyngeal carcinoma (NPC) cell line (CNE-2) using fluorescence lifetime imaging (FLIM). The upconversion luminescences from CNE-2 and the normal nasopharyngeal (NP) cells (NP69) after uptake of Au/Gd@MCM-41 show the characteristic of two-photon-induced-radiative recombination of the AuNPs. The presence of the Gd3+ ion induces a much shorter luminescence lifetime in CNE-2 cells. The interaction between AuNPs and Gd3+ ion clearly enhances the optical sensitivity of Au/Gd@MCM-41 to CNE-2. Furthermore, the difference in the autofluorescence between CNE-2 and NP69 cells can be efficiently demonstrated by the emission lifetimes of Au/Gd@MCM-41 through the Forster energy transfers from the endogenous fluorophores to AuNPs. The results suggest that Au/Gd@MCM-41 may impart high optical resolution for the FLIM imaging that differentiates normal and high-grade precancers. PMID:27694966

  10. Mechanistic Study of Tetrahydrofuran- acetogenins In Triggering Endoplasmic Reticulum Stress Response-apotoposis in Human Nasopharyngeal Carcinoma

    PubMed Central

    Juang, Shin-Hun; Chiang, Chang-Ying; Liang, Fong-Pin; Chan, Hsiu-Hui; Yang, Jai-Sing; Wang, Shih-Hao; Lin, Yu-Chin; Kuo, Ping-Chung; Shen, Meng-Ru; Thang, Tran Dinh; Nguyet, Bui Thi Minh; Kuo, Sheng-Chu; Wu, Tian-Shung

    2016-01-01

    For past three decades, numerous studies have elucidated the antiproliferative effects of acetogenins in hopes of developing a new class of clinical anticancer agents. However, clear and definitive action mechanisms of acetogenins were less clarified. In the present study, three tetrahydrofuran (THF)-containing acetogenins were found to have potent and selective antiproliferative activity against human nasopharyngeal carcinoma (NPC) cell lines and their methotrexate-resistant counterparts. The THF-containing acetogenins induced G2/M phase arrest, mitochondrial damage and apoptosis, and increased cytosolic and mitochondrial Ca2+ in NPCs. Microarray analysis of NPC-TW01 cells treated with squamostatin A, a non-adjacent bis-THF acetogenin, demonstrated an increased endoplasmic reticulum (ER)-stress response (ESR). Enhanced ESR in squamostatin A-treated cells was confirmed by real-time PCR, Western blot and shRNA gene knockdown experiments. Although our results showed that squamostatin A-induced ESR was independent of extracellular Ca2+, the presence of extracellular Ca2+ enhanced the antiproliferative effect of acetogenins. In vivo analyses demonstrated that squamostatin A showed good pharmacokinetic properties and significantly retarded NPC tumor growth in the xenograft mouse model. Conclusively, our work demonstrates that acetogenins are effective and selective inducers of the ESR that can block NPC proliferation, and illustrate a previously unappreciated antitumor mechanism of acetogenins that is effective against nasopharyngeal malignancies. PMID:28000792

  11. High sensitivity of gold nanoparticles co-doped with Gd2O3 mesoporous silica nanocomposite to nasopharyngeal carcinoma cells

    NASA Astrophysics Data System (ADS)

    Wang, Hui; Zhang, Songjin; Tian, Xiumei; Liu, Chufeng; Zhang, Lei; Hu, Wenyong; Shao, Yuanzhi; Li, Li

    2016-10-01

    Nanoprobes for combined optical and magnetic resonance imaging have tremendous potential in early cancer diagnosis. Gold nanoparticles (AuNPs) co-doped with Gd2O3 mesoporous silica nanocomposite (Au/Gd@MCM-41) can produce pronounced contrast enhancement for T1 weighted image in magnetic resonance imaging (MRI). Here, we show the remarkably high sensitivity of Au/Gd@MCM-41 to the human poorly differentiated nasopharyngeal carcinoma (NPC) cell line (CNE-2) using fluorescence lifetime imaging (FLIM). The upconversion luminescences from CNE-2 and the normal nasopharyngeal (NP) cells (NP69) after uptake of Au/Gd@MCM-41 show the characteristic of two-photon-induced-radiative recombination of the AuNPs. The presence of the Gd3+ ion induces a much shorter luminescence lifetime in CNE-2 cells. The interaction between AuNPs and Gd3+ ion clearly enhances the optical sensitivity of Au/Gd@MCM-41 to CNE-2. Furthermore, the difference in the autofluorescence between CNE-2 and NP69 cells can be efficiently demonstrated by the emission lifetimes of Au/Gd@MCM-41 through the Forster energy transfers from the endogenous fluorophores to AuNPs. The results suggest that Au/Gd@MCM-41 may impart high optical resolution for the FLIM imaging that differentiates normal and high-grade precancers.

  12. 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.

  13. EBV LMP-1 negatively regulates expression and pro-apoptotic activity of Par-4 in nasopharyngeal carcinoma cells.

    PubMed

    Lee, Jeng-Woei; Liu, Po-Fan; Hsu, Lee-Ping; Chen, Peir-Rong; Chang, Chung-Hsing; Shih, Wen-Ling

    2009-07-08

    Latent membrane protein-1 (LMP-1) of the Epstein-Barr virus (EBV) is closely associated with nasopharyngeal carcinoma (NPC), and in this study we sought to determine whether the pro-apoptotic activity of prostate apoptosis response-4 (Par-4) is modulated by LMP-1 in NPC cells. We found that LMP-1 diminished the pro-apoptotic activity of Par-4 and negatively regulated Par-4 protein by de novo synthesis; moreover, although LMP-1 accelerated a Par-4 activator, PKA, we demonstrated that LMP-1 also activated the PI3K/Akt pathway and increased Bcl-2 expression to suppress the activity of Par-4. Consequently, our results revealed a novel negative action of LMP-1 on the pro-apoptosis protein Par-4 by the coordination of multiple signaling pathways.

  14. 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

  15. 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

  16. Phase I trial of recombinant modified vaccinia ankara encoding Epstein-Barr viral tumor antigens in nasopharyngeal carcinoma patients.

    PubMed

    Hui, Edwin P; Taylor, Graham S; Jia, Hui; Ma, Brigette B Y; Chan, Stephen L; Ho, Rosalie; Wong, Wai-Lap; Wilson, Steven; Johnson, Benjamin F; Edwards, Ceri; Stocken, Deborah D; Rickinson, Alan B; Steven, Neil M; Chan, Anthony T C

    2013-03-15

    Epstein-Barr virus (EBV) is associated with several malignancies including nasopharyngeal carcinoma, a high incidence tumor in Chinese populations, in which tumor cells express the two EBV antigens EB nuclear antigen 1 (EBNA1) and latent membrane protein 2 (LMP2). Here, we report the phase I trial of a recombinant vaccinia virus, MVA-EL, which encodes an EBNA1/LMP2 fusion protein designed to boost T-cell immunity to these antigens. The vaccine was delivered to Hong Kong patients with nasopharyngeal carcinoma to determine a safe and immunogenic dose. The patients, all in remission more than 12 weeks after primary therapy, received three intradermal MVA-EL vaccinations at three weekly intervals, using five escalating dose levels between 5 × 10(7) and 5 × 10(8) plaque-forming unit (pfu). Blood samples were taken during prescreening, immediately before vaccination, one week afterward and at intervals up to one year later. Immunogenicity was tested by IFN-γ ELIspot assays using complete EBNA1 and LMP2 15-mer peptide mixes and known epitope peptides relevant to patient MHC type. Eighteen patients were treated, three per dose level one to four and six at the highest dose, without dose-limiting toxicity. T-cell responses to one or both vaccine antigens were increased in 15 of 18 patients and, in many cases, were mapped to known CD4 and CD8 epitopes in EBNA1 and/or LMP2. The range of these responses suggested a direct relationship with vaccine dose, with all six patients at the highest dose level giving strong EBNA1/LMP2 responses. We concluded that MVA-EL is both safe and immunogenic, allowing the highest dose to be forwarded to phase II studies examining clinical benefit.

  17. Chemotherapy in locally advanced nasopharyngeal carcinoma: An individual patient data meta-analysis of eight randomized trials and 1753 patients

    SciTech Connect

    Baujat, Bertrand; Audry, Helene; Bourhis, Jean; Chan, Anthony T.C.; Onat, Haluk; Chua, Daniel T.T.; Kwong, Dora L.W.; Al-Sarraf, Muhyi; Chi, K.-H.; Hareyama, Masato; Leung, Sing F.; Thephamongkhol, Kullathorn; Pignon, Jean-Pierre . E-mail: jppignon@igr.fr

    2006-01-01

    Objectives: To study the effect of adding chemotherapy to radiotherapy (RT) on overall survival and event-free survival for patients with nasopharyngeal carcinoma. Methods and Materials: This meta-analysis used updated individual patient data from randomized trials comparing chemotherapy plus RT with RT alone in locally advanced nasopharyngeal carcinoma. The log-rank test, stratified by trial, was used for comparisons, and the hazard ratios of death and failure were calculated. Results: Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis included 11 comparisons using the data from 1975 patients. The median follow-up was 6 years. The pooled hazard ratio of death was 0.82 (95% confidence interval, 0.71-0.94; p = 0.006), corresponding to an absolute survival benefit of 6% at 5 years from the addition of chemotherapy (from 56% to 62%). The pooled hazard ratio of tumor failure or death was 0.76 (95% confidence interval, 0.67-0.86; p < 0.0001), corresponding to an absolute event-free survival benefit of 10% at 5 years from the addition of chemotherapy (from 42% to 52%). A significant interaction was observed between the timing of chemotherapy and overall survival (p = 0.005), explaining the heterogeneity observed in the treatment effect (p = 0.03), with the highest benefit resulting from concomitant chemotherapy. Conclusion: Chemotherapy led to a small, but significant, benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with RT.

  18. Enhancer of Zeste Homolog 2 Overexpression in Nasopharyngeal Carcinoma: An Independent Poor Prognosticator That Enhances Cell Growth

    SciTech Connect

    Hwang, Chung-Feng; Huang, Hsuan-Ying; Chen, Chang-Han; Chien, Chih-Yen; Hsu, Yao-Chung; Li, Chien-Feng; and others

    2012-02-01

    Purpose: As a key component of polycomb-repressive complex 2, enhancer of zeste homolog 2 (EZH2) represses target genes through histone methylation and is frequently overexpressed and associated with poor prognosis in common carcinomas. For the first time, we reported EZH2 expression and its biological and clinical significance in nasopharyngeal carcinoma (NPC). Methods and Materials: In NPC cell lines and specimens, endogenous expression of EZH2 mRNA and protein was determined by semiquantitative reverse transcription-polymerase chain reaction and immunoblotting, respectively. To analyze the effect on cell growth, stable silencing of EZH2 was established in EZH2-expressing TW02 NPC cells with RNA interference. EZH2 immunolabeling was assessable for 89 primary NPC biopsy samples and correlated with clinicopathological variables, disease-specific survival (DSS), and overall survival (OS). Results: Growth activity of TW02 cells was significantly suppressed (p < 0.001) with stable EZH2 silencing. Compared with normal nasopharyngeal tissue, expression levels of EZH2 transcript and protein were apparently upregulated in NPC specimens. As a continuous variable, higher EZH2 expression preferentially occurred in NPCs of T3 to T4 stages (p = 0.03) and significantly predicted inferior DSS (p = 0.0010) and OS (p = 0.004). The prognostic implications for DSS (p = 0.010) and OS (p = 0.006) still remained valid when using the median ({>=}60%) of EZH2 immunolabeling index to dichotomize the cohort. In the multivariate model, higher EZH2 expression was an independent adverse factor of both DSS (p = 0.012) and OS (p = 0.011), along with American Joint Committee on Cancer Stages III to IV (p = 0.024 for DSS, p = 0.017 for OS). Conclusion: At least partly through promoting cell growth, EZH2 implicates disease progression, confers tumor aggressiveness, and represents an independent adverse prognosticator in patients with NPC.

  19. Major Late Toxicities After Conformal Radiotherapy for Nasopharyngeal Carcinoma-Patient- and Treatment-Related Risk Factors

    SciTech Connect

    Lee, Anne W.M. Ng, W.T.; Hung, W.M.; Choi, C.W.; Tung, Raymond; Ling, Y.H.; Cheng, Peter T.C.; Yau, T.K.; Chang, Amy T.Y.; Leung, Samuel K.C.; Lee, Michael C.H.; Bentzen, Soren M.

    2009-03-15

    Purpose: To retrospectively analyze the factors affecting late toxicity for nasopharyngeal carcinoma. Methods and Materials: Between 1998 and 2003, 422 patients were treated with a conformal technique with 2-Gy daily fractions to a total dose of 70 Gy. Conventional fractionation (5 fractions weekly) was used in 232 patients and accelerated fractionation (6 fractions weekly) in 190 patients. One hundred seventy-one patients were treated with the basic radiotherapy course alone (Group 1), 55 patients had an additional boost of 5 Gy in 2 fractions (Group 2), and 196 patients underwent concurrent cisplatin-based chemotherapy (Group 3). Results: The 5-year overall toxicity rate was significantly greater in Group 3 than in Group 1 (37% vs. 27%, p = 0.009). Although the overall rate in Group 2 was not elevated (28% vs. 27%, p = 0.697), a significant increase in temporal lobe necrosis was observed (4.8% vs. 0%, p = 0.015). Multivariate analyses showed that age and concurrent chemotherapy were significant factors. The hazard ratio of overall toxicity attributed to chemotherapy was 1.99 (95% confidence interval, 1.32-2.99, p = 0.001). The mean radiation dose to the cochlea was another significant factor affecting deafness, with a hazard ratio of 1.03 (95% confidence interval, 1.01-1.05, p = 0.005) per 1-Gy increase. The cochlea that received >50 Gy had a significantly greater deaf rate (Group 1, 18% vs. 7%; and Group 3, 22% vs. 14%). Conclusion: The therapeutic margin for nasopharyngeal carcinoma is extremely narrow, and a significant increase in brain necrosis could result from dose escalation. The significant factors affecting the risk of deafness included age, concurrent chemoradiotherapy, and greater radiation dose to the cochlea.

  20. 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

  1. [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.

  2. 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

  3. Metastasis-suppressing NID2, an epigenetically-silenced gene, in the pathogenesis of nasopharyngeal carcinoma and esophageal squamous cell carcinoma

    PubMed Central

    Chai, Annie Wai Yeeng; Cheung, Arthur Kwok Leung; Dai, Wei; Ko, Josephine Mun Yee; Ip, Joseph Chok Yan; Chan, Kwok Wah; Kwong, Dora Lai-Wan; Ng, Wai Tong; Lee, Anne Wing Mui; Ngan, Roger Kai Cheong; Yau, Chun Chung; Tung, Stewart Yuk; Lee, Victor Ho Fun; Lam, Alfred King-Yin; Pillai, Suja; Law, Simon; Lung, Maria Li

    2016-01-01

    Nidogen-2 (NID2) is a key component of the basement membrane that stabilizes the extracellular matrix (ECM) network. The aim of the study is to analyze the functional roles of NID2 in the pathogenesis of nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC). We performed genome-wide methylation profiling of NPC and ESCC and validated our findings using the methylation-sensitive high-resolution melting (MS-HRM) assay. Results showed that promoter methylation of NID2 was significantly higher in NPC and ESCC samples than in their adjacent non-cancer counterparts. Consistently, down-regulation of NID2 was observed in the clinical samples and cell lines of both NPC and ESCC. Re-expression of NID2 suppresses clonogenic survival and migration abilities of transduced NPC and ESCC cells. We showed that NID2 significantly inhibits liver metastasis. Mechanistic studies of signaling pathways also confirm that NID2 suppresses the EGFR/Akt and integrin/FAK/PLCγ metastasis-related pathways. This study provides novel insights into the crucial tumor metastasis suppression roles of NID2 in cancers. PMID:27793011

  4. 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

  5. Vicious circle of acute radiation toxicities and weight loss predicts poor prognosis for nasopharyngeal carcinoma patients receiving intensity modulated radiotherapy

    PubMed Central

    Li, Guo; Jiang, Xiong-ying; Qiu, Bo; Shen, Lu-Jun; Chen, Chen; Xia, Yun-Fei

    2017-01-01

    Background: Weight loss during radiotherapy has been known as a negative prognostic factor for nasopharyngeal carcinoma (NPC) patients, but the factors related to weight loss during radiotherapy were not fully understood. Methods: A total of 322 newly diagnosed NPC patients receiving intensity modulated radiotherapy (IMRT) in Sun Yat-sen University Cancer Center between June 2002 and August 2006 were enrolled. Kaplan-Meier methods and log-rank test were applied for survival analysis; a multiple regression was used to identify the factors related to weight loss during radiotherapy. Results: The mean and median values of weight loss (%) during radiotherapy were 6.85% and 6.70%. NPC patients with critical weight loss (> 5.4%) have poorer overall survival (OS) and distant metastasis-free survival (DMFS) than the patients without critical weight loss (p = 0.002 and 0.021, respectively). Pre-radiotherapy weight, acute mucosal toxicity, acute pharynx and esophagus toxicity, and acute upper gastrointestinal toxicity were related to the weight loss during radiotherapy independently (p = 0.01, p < 0.001, p < 0.001, and p = 0.009, respectively). Conclusions: Acute radiation toxicities had significant and independent impact on weight loss during radiotherapy. The vicious circle of acute radiation toxicities and weight loss had bad effect on prognosis of NPC patients. PMID:28382146

  6. Homozygous Wildtype of XPD K751Q Polymorphism Is Associated with Increased Risk of Nasopharyngeal Carcinoma in Malaysian Population

    PubMed Central

    Lye, Munn-Sann; Visuvanathan, Shaneeta; Chong, Pei-Pei; Yap, Yoke-Yeow; Lim, Chin-Chye; Ban, Eng-Zhuan

    2015-01-01

    The xeroderma pigmentosum group D (XPD) gene encodes a DNA helicase, an important component in transcription factor IIH (TFIIH) complex. XPD helicase plays a pivotal role in unwinding DNA at the damaged region during nucleotide excision repair (NER) mechanism. Dysfunctional XPD helicase protein from polymorphic diversity may contribute to increased risk of developing cancers. This study aims to determine the association between XPD K751Q polymorphism (rs13181) and risk of nasopharyngeal carcinoma (NPC) in the Malaysian population. In this hospital-based matched case-control study, 356 controls were matched by age, gender and ethnicity to 356 cases. RFLP-PCR was used to genotype the XPD K751Q polymorphism. A significant association was observed between XPD K751Q polymorphism and the risk of NPC using conditional logistic regression. Subjects with homozygous Lys/Lys (wildtype) genotype have 1.58 times higher odds of developing NPC compared to subjects with recessive combination of heterozygous Lys/Gln and homozygous Gln/Gln genotypes (OR = 1.58, 95% CI = 1.05–2.38 p = 0.028) adjusted for cigarette smoking, alcohol and salted fish consumption. Our data suggests that Lys/Lys (wildtype) of XPD K751Q contributes to increased risk of NPC in the Malaysian population. PMID:26086338

  7. Weighted risk score-based multifactor dimensionality reduction to detect gene-gene interactions in nasopharyngeal carcinoma.

    PubMed

    Li, Chao-Feng; Luo, Fu-Tian; Zeng, Yi-Xin; Jia, Wei-Hua

    2014-06-13

    Determining the complex relationships between diseases, polymorphisms in human genes and environmental factors is challenging. Multifactor dimensionality reduction (MDR) has been proven to be capable of effectively detecting the statistical patterns of epistasis, although classification accuracy is required for this approach. The imbalanced dataset can cause seriously negative effects on classification accuracy. Moreover, MDR methods cannot quantitatively assess the disease risk of genotype combinations. Hence, we introduce a novel weighted risk score-based multifactor dimensionality reduction (WRSMDR) method that uses the Bayesian posterior probability of polymorphism combinations as a new quantitative measure of disease risk. First, we compared the WRSMDR to the MDR method in simulated datasets. Our results showed that the WRSMDR method had reasonable power to identify high-order gene-gene interactions, and it was more effective than MDR at detecting four-locus models. Moreover, WRSMDR reveals more information regarding the effect of genotype combination on the disease risk, and the result was easier to determine and apply than with MDR. Finally, we applied WRSMDR to a nasopharyngeal carcinoma (NPC) case-control study and identified a statistically significant high-order interaction among three polymorphisms: rs2860580, rs11865086 and rs2305806.

  8. 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

  9. Significant survival benefit of adjuvant chemotherapy after concurrent chemoradiotherapy in locally advanced high-risk nasopharyngeal carcinoma

    PubMed Central

    Liang, Zhong-Guo; Chen, Xiao-Qian; Lin, Guo-Xiang; Yu, Bin-Bin; Chen, Kai-Hua; Zhong, Qiu-Lu; Nong, Si-Kai; Li, Ling; Qu, Song; Su, Fang; Zhao, Wei; Li, Ye; Zhu, Xiao-Dong

    2017-01-01

    The present study aimed to define high-risk patients who may benefit from additional adjuvant chemotherapy (AC) after concurrent chemotherapy in combination with intensity-modulated radiotherapy among patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). A cohort of 511 NPC patients who received concomitant chemoradiotherapy (CCRT) with or without AC between January 2007 and December 2012 were retrospectively analysed. One hundred seventy-seven patients received CCRT alone, whereas 334 received CCRT + AC. The survival analysis showed that ages >45 years old, T3-T4 stages, N2-N3 disease and serum albumin levels ≤42 g/L were significant independent prognostic factors for overall survival (OS). Using these four risk factors, a prognostic model for OS was created as follows: (1) low-risk group: 0–1 risk factors; and (2) high-risk group: 2–4 risk factors. In the CCRT alone and CCRT + AC groups, significant differences in survival were found between the high- and low-risk groups. Patients in the high-risk group exhibited improved OS due to the addition of AC to CCRT, but no survival benefits were found in the low-risk group. In conclusion, high-risk patients may benefit from the addition of AC to CCRT regarding OS. PMID:28150694

  10. CD109 is identified as a potential nasopharyngeal carcinoma biomarker using aptamer selected by cell-SELEX

    PubMed Central

    Jia, Wenting; Ren, Caiping; Wang, Lei; Zhu, Bin; Jia, Wei; Gao, Menghui; Zeng, Fei; Zeng, Liang; Xia, Xiaomeng; Zhang, Xiaobing; Fu, Ting; Li, Shasha; Du, Can; Jiang, Xingjun; Chen, Yuxiang; Tan, Weihong; Zhao, Zilong; Liu, Weidong

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is one of the most prevailing cancers in southern China and southern Asia. Because of the nonspecific symptoms and lack of effective biomarker, most patients are diagnosed at advanced stages, resulting in poor 5-year survival rate. To identify a novel NPC biomarker facilitating early detection and effective therapy of NPC, a two-step strategy consisting of cancer cell-Systematic Evolution of Ligands by EXponential enrichment (cell-SELEX) procedure and aptamer-based purification approach was developed. Using cell-SELEX procedure, four aptamers (S3, S5, S12 and S27) differentiating the molecular differences between NPC cells and NP cells were successfully screened. Then, using aptamer-based protein purification, membrane protein CD109 was identified as the target of aptamer S3. CD109 protein was further identified to be over-expressed in NPC cell lines and clinic tissues, but not or low in NP cell line and clinic NP tissues, detected by western blot and immunohistochemistry experiments. Our study demonstrated that CD109 identified by cell-SELEX and aptamer-based purification strategy might be used as a potential NPC biomarker for early diagnosis and targeted therapy. PMID:27419372

  11. Comparison of protein profiles between acetonitrile- and non-acetonitrile-treated sera from patients with nasopharyngeal carcinomas.

    PubMed

    Huang, Yuan-Jiao; Deng, Kai-Feng; Xuan, Chao; Zhang, Bei-Bei; Zhou, Yi; Yang, Xiaoli; He, Ming

    2011-05-01

    Serum proteins may be abnormally increased or decreased during the occurrence and development of nasopharyngeal carcinoma (NPC). However, currently there are no simple or effective methods to collect and differentiate these abnormally secreted proteins from abundant serum proteins. In this study, acetonitrile was used to remove the majority of high-abundance proteins from serum samples obtained from patients with NPC. The samples were subjected to surface-enhanced laser desorption/ionization time-of-flight mass spectrometry with a CM10 (weak cation exchange) ProteinChip, and the resulting protein profiles were compared with those of non-acetonitrile-treated serum samples. The results showed that the protein profiles differed between the acetonitrile- and non-acetonitrile-treated sera from patients with NPC. A large proportion of the non-acetonitrile-treated NPC serum protein peaks were <6000 kDa, while the detection rate of protein peaks >6000 kDa was relatively higher in the acetonitrile-treated NPC sera, accounting for more than half of all protein peaks (26.2+37.5%). Few differentially upregulated proteins were lost, and the peak value density increased after acetonitrile treatment. In conclusion, acetonitrile treatment of serum samples is effective in removing high-abundance macromolecular proteins. Therefore, acetonitrile treatment can be applied for the investigation of serum proteomics and may aid in the identification of differentially expressed proteins.

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

    PubMed

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

    2014-01-10

    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.

  13. Inhibitory effects of Cinnamomum burmannii Blume stem bark extract and trans-cinnamaldehyde on nasopharyngeal carcinoma cells; synergism with cisplatin

    PubMed Central

    DAKER, MAELINDA; LIN, VOON YEE; AKOWUAH, GABRIEL AKYIREM; YAM, MUN FEI; AHMAD, MARIAM

    2013-01-01

    Nasopharyngeal carcinoma (NPC) is a malignancy that occurs in the epithelium of the nasopharynx. The standard treatment of NPC patients with locoregionally advanced stages is problematic and is often associated with toxicities. Therefore, it is essential to screen for naturally occurring compounds with strong apoptosis-inducing activity and minimal toxicity. This study investigated the effects of the standardized methanol extract of Cinnamomum burmannii Blume stem bark and its main constituent, trans-cinnamaldehyde (TCA), on human NPC cell lines. The content of TCA in C. burmannii methanol extract was standardized to be 13.61% w/w by means of gas chromatography-mass spectrometry (GC-MS). NPC cell proliferation was clearly inhibited within 24 h of treatment, with TCA exhibiting greater activity than the methanol extract. TCA was more active against NPC cells compared with cisplatin. There was a pronounced downregulation of the proliferation markers, Ki67 and proliferating cell nuclear antigen (PCNA) in the TCA-treated cells; while morphological observation indicated the induction of apoptosis. Caspase activation and prominent DNA damage, which are markers of apoptosis induction were detected. TCA demonstrated the ability to scavenge nitric oxide. The simultaneous combination of TCA and cisplatin produced synergistic anti-proliferative effects. Collectively, these data indicate the potential use of TCA for the treatment of NPC. PMID:23837058

  14. Inhibitory effects of Cinnamomum burmannii Blume stem bark extract and trans-cinnamaldehyde on nasopharyngeal carcinoma cells; synergism with cisplatin.

    PubMed

    Daker, Maelinda; Lin, Voon Yee; Akowuah, Gabriel Akyirem; Yam, Mun Fei; Ahmad, Mariam

    2013-06-01

    Nasopharyngeal carcinoma (NPC) is a malignancy that occurs in the epithelium of the nasopharynx. The standard treatment of NPC patients with locoregionally advanced stages is problematic and is often associated with toxicities. Therefore, it is essential to screen for naturally occurring compounds with strong apoptosis-inducing activity and minimal toxicity. This study investigated the effects of the standardized methanol extract of Cinnamomum burmannii Blume stem bark and its main constituent, trans-cinnamaldehyde (TCA), on human NPC cell lines. The content of TCA in C. burmannii methanol extract was standardized to be 13.61% w/w by means of gas chromatography-mass spectrometry (GC-MS). NPC cell proliferation was clearly inhibited within 24 h of treatment, with TCA exhibiting greater activity than the methanol extract. TCA was more active against NPC cells compared with cisplatin. There was a pronounced downregulation of the proliferation markers, Ki67 and proliferating cell nuclear antigen (PCNA) in the TCA-treated cells; while morphological observation indicated the induction of apoptosis. Caspase activation and prominent DNA damage, which are markers of apoptosis induction were detected. TCA demonstrated the ability to scavenge nitric oxide. The simultaneous combination of TCA and cisplatin produced synergistic anti-proliferative effects. Collectively, these data indicate the potential use of TCA for the treatment of NPC.

  15. Anatomic and dosimetric changes during the treatment course of intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma.

    PubMed

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

    2010-01-01

    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.

  16. Delivery system for DNAzymes using arginine-modified hydroxyapatite nanoparticles for therapeutic application in a nasopharyngeal carcinoma model

    PubMed Central

    Chen, Yan; Yang, Lifang; Huang, Suping; Li, Zhi; Zhang, Lu; He, Jiang; Xu, Zhijie; Liu, Liyu; Cao, Ya; Sun, Lunquan

    2013-01-01

    DNAzymes are synthetic, single-stranded, catalytic nucleic acids that bind and cleave target mRNA in a sequence-specific manner, and have been explored for genotherapeutics. One bottleneck restricting their application is the lack of an efficient delivery system. As an inorganic nanomaterial with potentially wide application, nano-hydroxyapatite particles (nHAP) have attracted increasing attention as new candidates for nonviral vectors. In this study, we developed an nHAP-based delivery system and explored its cellular uptake mechanisms, intracellular localization, and biological effects. Absorption of arginine-modified nanohydroxyapatite particles (Arg-nHAP) and DZ1 (latent membrane protein 1 [LMP1]-targeted) reached nearly 100% efficiency under in vitro conditions. Using specific inhibitors, cellular uptake of the Arg-nHAP/DZ1 complex was shown to be mediated by the energy-dependent endocytosis pathway. Further, effective intracellular delivery and nuclear localization of the complex was confirmed by confocal microscopy. Biologically, the complex successfully downregulated the expression of LMP1 in nasopharyngeal carcinoma cells. In a mouse tumor xenograft model, the complex was shown to be delivered efficiently to tumor tissue, downregulating expression of LMP1 and suppressing tumor growth. These results suggest that Arg-nHAP may be an efficient vector for nucleic acid-based drugs with potential clinical application. PMID:23983464

  17. MicroRNA-152 Targets Phosphatase and Tensin Homolog to Inhibit Apoptosis and Promote Cell Migration of Nasopharyngeal Carcinoma Cells

    PubMed Central

    Huang, Shunde; Li, Xiaohua; Zhu, Haotu

    2016-01-01

    Background Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with very high prevalence in southern China. Phosphatase and tensin homolog (PTEN), a tumor suppressor, was reported to be downregulated in NPC patients and correlated with pathological grade and clinical stage of NPC. Material/Methods Luciferase reporter assay, qPCR, and Western blot analysis were used to determine if PTEN is a target of miR-152. The function of miR-152 in cell apoptosis and cell proliferation was examined as well. Tissue samples from NPC patients were also analyzed for PTEN and miR-152 expressions. Results Reporter assay indicated miR-152 targets the 3′UTR of PTEN mRNA to inhibit PTEN expression. Transfection of the NPC-derived cell line with miR-152 mimic confirmed these findings. Overexpression of miRNA-152 inhibits apoptosis induced by Cisplatin in NPC cancer cells in vitro. Moreover, overexpression miR-152 also promotes NPC cancer cell invasion and proliferation. Samples from EBV-negative NPC patients demonstrated the down-regulated level of PTEN may be related with overexpression of miR-152. Conclusions The miR-152 targets PETN to inhibit cell apoptosis and promote cancer cell proliferation and migration in NPC development. PMID:27840403

  18. Establishment and Analysis of the 3-dimensional (3D) Spheroids Generated from the Nasopharyngeal Carcinoma Cell Line HK1

    PubMed Central

    Muniandy, Kalaivani; Sankar, Prabu Siva; Xiang, Benedict Lian Shi; Soo-Beng, Alan Khoo; Balakrishnan, Venugopal; Mohana-Kumaran, Nethia

    2016-01-01

    Spheroids have been shown to recapitulate the tumour in vivo with properties such as the tumour microenvironment, concentration gradients, and tumour phenotype. As such, it can serve as a platform for determining the growth and invasion behaviour pattern of the cancer cells as well as be utilised for drug sensitivity assays; capable of exhibiting results that are closer to what is observed in vivo compared to two-dimensional (2D) cell culture assays. This study focused on establishing a three-dimensional (3D) cell culture model using the Nasopharyngeal Carcinoma (NPC) cell line, HK1 and analysing its growth and invasion phenotypes. The spheroids will also serve as a model to elucidate their sensitivity to the chemotherapeutic drug, Flavopiridol. The liquid overlay method was employed to generate the spheroids which was embedded in bovine collagen I matrix for growth and invasion phenotypes observation. The HK1 cells formed compact spheroids within 72 hours. Our observation from the 3 days experiments revealed that the spheroids gradually grew and invaded into the collagen matrix, showing that the HK1 spheroids are capable of growth and invasion. Progressing from these experiments, the HK1 spheroids were employed to perform a drug sensitivity assay using the chemotherapeutic drug, Flavopiridol. The drug had a dose-dependent inhibition on spheroid growth and invasion. PMID:27965750

  19. PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load

    PubMed Central

    Zhou, Yajuan; Shi, Dingbo; Miao, Jingjing; Wu, Haijun; Chen, Jiewei; Zhou, Xiaoyi; Hu, Desheng; Zhao, Chong; Deng, Wuguo; Xie, Conghua

    2017-01-01

    Programmed death-1 (PD-1) is an immunosuppressive receptor functionally bound with programmed death-ligand 1 (PD-L1), which has been reported in various malignancies. However, only a few studies are available for the clinical significance of PD-1/PD-L1 in nasopharyngeal carcinoma (NPC). In this study, we aim to investigate alterations in PD-1/PD-L1 by using immunohistochemistry analysis in a cohort of consecutively enrolled NPC patients (n = 99). To further analyse the correlation between PD-1/PD-L1 and factors involved in clinico-pathology, haematologic biomarkers, EBV-DNA load and outcomes, we collected clinical data for statistical analysis. We observed that lower haemoglobin (HB) and Body Mass Index (BMI) levels were associated with high levels of PD-L1 staining in NPC patients. Importantly, our results suggested that PD-L1 might be a negative indicator for NPC patients. In contrast, a correlation between the PD-1/PD-L1 level and EBV load was not identified. Moreover, PD-1 positivity was suggested to not be significantly correlated with clinical outcomes. Taken together, our results revealed that PD-L1 might be a potential prognostic biomarker for NPC patients. However, further studies are needed to clarify the underlying mechanism of EBV status in the immunosuppression process induced by the PD-1/PD-L1 axis. PMID:28256540

  20. Dietary intakes of carotenoids and other nutrients in the risk of nasopharyngeal carcinoma: a case–control study in Italy

    PubMed Central

    Polesel, J; Negri, E; Serraino, D; Parpinel, M; Barzan, L; Libra, M; Bosetti, C; Garavello, W; Montella, M; La Vecchia, C; Franceschi, S; Talamini, R

    2012-01-01

    Background: Dietary habits have been related to the risk of nasopharyngeal carcinoma (NPC), but information on a wide range of macro- and micronutrients is still lacking, particularly for low-incidence countries. Methods: We conducted a hospital-based case–control study in Italy on 198, histologically confirmed, NPC cases of Caucasian ethnicity of 18–76 years of age. Controls were 594 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Nutrients intake was assessed through a validated food-frequency questionnaire. Adjusted odds ratios (ORs) and the corresponding confidence intervals (CIs) were estimated through logistic regression. Results: Dietary intake of carotenoids were inversely related to NPC risk, notably carotene (OR for highest vs lowest quartile=0.46; 95% CI: 0.26–0.79), α-carotene (OR=0.57; 95% CI: 0.33–0.97), and β-carotene (OR=0.42; 95% CI: 0.24–0.75). Increased NPC risk was observed for elevate cholesterol intake (OR=1.85; 95% CI: 1.12–3.05). Conclusion: Study findings suggest a protective effect of carotenoids against NPC in a low-risk population, adding further support to a possible beneficial role of a diet rich in fruits and vegetables in cancers of the head and neck. PMID:22968647

  1. COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells.

    PubMed

    Li, Ze-Lei; Ye, Shu-Biao; OuYang, Li-Yin; Zhang, Han; Chen, Yu-Shan; He, Jia; Chen, Qiu-Yan; Qian, Chao-Nan; Zhang, Xiao-Shi; Cui, Jun; Zeng, Yi-Xin; Li, Jiang

    2015-11-01

    The expansion of myeloid-derived suppressor cells (MDSCs) is a common feature of cancer, but its biological roles and molecular mechanism remain unclear. Here, we investigated a molecular link between MDSC expansion and tumor cell metastasis in nasopharyngeal carcinoma (NPC). We demonstrated that MDSCs expanded and were positively correlated with the elevated tumor COX-2 expression and serum IL-6 levels in NPC patients. Importantly, COX-2 and MDSCs were poor predictors of patient disease-free survival (DFS). Knocking down tumor COX-2 expression hampered functional TW03-mediated-MDSC cell (T-MDSC) induction with IL-6 blocking. We identified that T-MDSCs promoted NPC cell migration and invasion by triggering the epithelial-mesenchymal transition (EMT) on cell-to-cell contact, and T-MDSCs enhanced tumor experimental lung metastasis in vivo. Interestingly, the contact between T-MDSCs and NPC cells enhanced tumor COX-2 expression, which subsequently activated the β-catenin/TCF4 pathway, resulting in EMT of the cancer cells. Blocking transforming growth factor β (TGFβ) or inducible nitric oxide synthase (iNOS) significantly abolished the T-MDSC-induced upregulation of COX-2 and EMT scores in NPC cells, whereas the administration of TGFβ or L-arginine supplements upregulated COX-2 expression and EMT scores in NPC cells. These findings reveal that COX-2 is a key factor mediating the interaction between MDSCs and tumor cells, suggesting that the inhibition of COX-2 or MDSCs has the potential to suppress NPC metastasis.

  2. The significance of diffusion tensor magnetic resonance imaging for patients with nasopharyngeal carcinoma and trigeminal nerve invasion

    PubMed Central

    Li, Tian; Sheng, Li; Chunyan, Cui; Haoqiang, He; Kangqiang, Peng; Xiao, Gong; Lizhi, Liu

    2017-01-01

    Abstract To investigate the significance of diffusion tensor imaging (DTI) for patients with nasopharyngeal carcinoma (NPC) and trigeminal nerve invasion. Fifty-two patients with NPC and unilateral infringement and 30 healthy controls were recruited for our study. Routine magnetic resonance imaging (MRI) and DTI were performed for all participants. Within-group and between-group comparisons of DTI metrics, including fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) of the third (V3) branch of the bilateral trigeminal nerves of all participants, were carried out. The FA and ADC values on the affected sides of patients revealed a significant decrease and increase, respectively, when compared with those on the unaffected sides of patients and the healthy controls (P = 0.000 for all), whereas there were no significant differences in DTI metrics between both sides of healthy controls or between the unaffected sides of patients and the healthy controls (P = 0.930, 0.580, 0.095, and 0.360, respectively). The decreasing FA rate on the affected sides of patients correlated negatively with the increasing ADC rate (r = −0.675, P = 0.000). DTI can quantitatively evaluate microstructural abnormalities of the V3 branch of the trigeminal nerve in patients with NPC, which is important for the early detection of trigeminal nerve invasion to achieve a precise T classification, assess prognosis, and guide treatment. PMID:28178163

  3. 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.

  4. Label-Free Classification of a Nasopharyngeal Carcinoma Tissue Test at Different Stages Based on Raman Spectroscopy.

    PubMed

    Liu, Mingyu; Lin, Jinyong; Qiu, Sufang; Wu, Weilin; Liu, Gaoqiang; Li, Yan; Gong, Haiming; Chen, Rong; Chen, Guannan

    2017-03-01

    Raman spectroscopy (RS) of nasopharyngeal carcinoma (NPC) tissue provides substantial biomolecular information and various biomedicine features for tissue at different stages of cancer development. This study suggested an automatic and quick method for the classification of Raman spectra at different stages of NPC by multivariate statistical analysis. During RS measurement, Raman spectra were acquired from all NPC tissues in two groups of samples: 30 early-stage NPC patients (stages I and II) and 46 advanced-stage NPC patients (stages III and IV). In addition, a tentative diagnostic algorithm comprising principal components analysis and support vector machine was used to effectively classify multivariate data from the Raman spectra to yield sensitivities (70%; 21 of 30 samples) and specificities (91%; 42 of 46 samples) by the leave-one-out cross-validation method. Meaningful chemical compositions in the classification process were then deduced by analyzing the classified mathematical model. This beneficial work provides a great potential clinical method for the automatic classification of NPC stages and the speculation of the chemical compositions for NPC staging.

  5. Identification of G2607A mutation in EGFR gene with a significative rate in Moroccan patients with nasopharyngeal carcinoma.

    PubMed

    Naji, F; Attaleb, M; Laantri, N; Benchakroun, N; El Gueddari, B; Benider, A; Azeddoug, H; Ennaji, M M; El Mzibri, M; Khyatti, M

    2010-12-15

    The epidermal growth factor receptor (EGFR) is involved in the regulation of several cellular processes and in the development of many human cancers. Somatic mutations of EGFR at tyrosine kinase domain have been associated with clinical response to tyrosine kinase inhibitors (TKIs) in lung cancer patients. In this study, we evaluated the frequency of point mutations in EGFR for future use of TKI in clinical treatment of nasopharyngeal carcinoma (NPC). Sixty Moroccan patient specimens of NPC were analysed for EGFR mutations in the region delimiting exons 18 and 21 by direct sequencing. Our results showed the absence of mutations in the EGFR kinase domain in these exons in all 60 analysed specimens. Sequence analysis of the EGFR—TK domain, revealed the presence of (G2607A) polymorphism at exon 20. The genotypes AA and GA were found respectively in 39 (65%) and 16 (26.6%) cases. Statistical analysis showed no difference between the polymorphism and either gender or age of patients. Mutations in EGFR kinase domain are rare events in NPC biopsies, suggesting, that treatment of NPC patients with TKI may not be effective. However, EGFR G2607A polymorphism at exon 20 is frequent in NPC cases and could be associated to clinical response to TKI therapy.

  6. 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

  7. Increased Serum Level of MicroRNA-663 Is Correlated with Poor Prognosis of Patients with Nasopharyngeal Carcinoma

    PubMed Central

    Liang, Shaoqiang; Deng, Yanming; Chen, Lusi; Zhang, Yang; Zheng, Zhenhe; Luo, Weijun; Lv, Zhiqian; Li, Shaoen; Xun, Tao

    2016-01-01

    MicroRNAs (miRs) play crucial roles in the carcinogenesis and malignant progression of human cancers including nasopharyngeal carcinoma (NPC). In this study, we aimed to investigate the association of serum miR-663 levels with the clinical factors and prognosis of NPC patients. Real-time PCR was performed to examine the amount of miR-663 in serum in NPC patients and healthy controls. Our data showed that the amount of miR-663 in serum was significantly higher in NPC patients than in healthy controls. Moreover, the serum levels of miR-663 were significantly correlated with the grade, lymph node metastasis, and clinical stage of NPC. Furthermore, higher serum miR-663 levels were closely associated with worse 5-year overall survival (OS) and relapse-free survival (RFS) of patients with NPC, and the serum level of miR-663 was found to be an independent predicator for the prognosis of NPC. In addition, after receiving chemoradiotherapy, the serum levels of miR-663 were significantly reduced in NPC patients. In summary, miR-663 was upregulated in the serum of NPC patients, which was downregulated after chemoradiotherapy, and its increased levels were closely associated with malignant progression and poor prognosis in NPC patients. Therefore, the amount of miR-663 in serum may become a potential predicator for the clinical outcome of NPC patients. PMID:27667893

  8. Downregulation of cancer stem cell properties via mTOR signaling pathway inhibition by rapamycin in nasopharyngeal carcinoma

    PubMed Central

    YANG, CHUNGUANG; ZHANG, YUE; ZHANG, YU; ZHANG, ZIHENG; PENG, JIANHUA; LI, ZHI; HAN, LIANG; YOU, QUANJIE; CHEN, XIAOYU; RAO, XINGWANG; ZHU, YI; LIAO, ZHISU

    2015-01-01

    Rapamycin, a mammalian target of rapamycin (mTOR) signaling inhibitor, inhibits cancer cell proliferation and tumor formation, including in nasopharyngeal carcinoma (NPC), which we proved in a previous study. However, whether rapamycin affects cancer stem cells (CSCs) is unclear. In examining samples of NPCs, we found regions of CD44-positive cancer cells co-expressing the stem cell biomarker OCT4, suggesting the presence of CSCs. Following this, we used double-label immunohistochemistry to identify whether the mTOR signaling pathway was activated in CD44-positive CSCs in NPCs. We used a CCK-8 assay and western blotting to explore whether the stem cell biomarkers CD44 and SOX2 and the invasion protein MMP-2 could be suppressed by treatment with rapamycin in cultured primary NPC cells and secondary tumors in BALB/c nude mice. Interestingly, we found that rapamycin inhibited mTOR signaling in addition to simultaneously downregulating the expression of CD44, SOX2 and MMP-2 and that it affected cell growth and tumor size and weight both in vitro and in vivo. Collectively, we confirmed for the first time that CSC properties are reduced and invasion potential is restrained in response to mTOR signaling inhibition in NPC. This evidence indicates that the targeted inhibition of CSC properties may provide a novel strategy to treat cancer. PMID:26202311

  9. Prognostic value of the primary lesion apparent diffusion coefficient (ADC) in nasopharyngeal carcinoma: a retrospective study of 541 cases

    PubMed Central

    Zhang, Yuan; Liu, Xu; Zhang, Yun; Li, Wen-Fei; Chen, Lei; Mao, Yan-Ping; Shen, Jing-Xian; Zhang, Fan; Peng, Hao; Liu, Qing; Sun, Ying; Ma, Jun

    2015-01-01

    The prognostic value of the primary lesion pretreatment apparent diffusion coefficient (ADC), which is obtained by diffusion-weighted magnetic resonance imaging (MR-DWI), remains unknown in nasopharyngeal carcinoma (NPC). Thus, to investigate whether the pretreatment ADC value as measured from the primary site on MR-DWI is an independent prognostic factor in NPC, we retrospectively reviewed a cohort of 541 patients with histologically-proven stage I-IVB NPC. All patients underwent MRI using a 3-Tesla system (Trio Tim; Siemens, Erlangen Germany). To calculate ADC, the primary lesion was designated on the ADC map at the level of the largest tumor diameter to cover most of the lesion, avoiding cystic or necrotic components. Median and mean (±SD) pretreatment ADC were 0.713 and 0.716 ± 0.079 × 10−3 mm2/s, respectively. Univariate and multivariate analysis confirmed high pretreatment ADC was a good prognostic factor for poor local relapse-free survival and disease-free survival. Furthermore, the area under the ROC curve for prediction of local failure significantly increased when pretreatment ADC was combined with T classification (P = 0.004). Thus, pretreatment ADC might provide useful information for predicting outcome and selecting high-risk patients appropriate for more aggressive therapy. Further studies are warranted to investigate the biological basis of this observation. PMID:26184509

  10. CT-diagnosed severe skull base bone destruction predicts distant bone metastasis in early N-stage nasopharyngeal carcinoma

    PubMed Central

    Yi, Wei; Liu, Zhi-Gang; Li, Xian; Tang, Jiao; Jiang, Chang-Bin; Hu, Jing-Ye; Tu, Zi-Wei; Wang, Hui; Niu, Dao-Li; Xia, Yun-Fei

    2016-01-01

    Bone metastasis is the most frequent type of distant metastasis in nasopharyngeal carcinoma (NPC). In this study, we investigated the correlation between the skull base bone destruction and the distant bone metastasis in patients with NPC. A total of 449 cases with NPC who were diagnosed and had definitive radiotherapy from 2001 to 2006 were enrolled in this study. The skull base bone destruction was diagnosed by computed tomography (CT) in all cases, and 191 patients also underwent magnetic resonance imaging scan. Kaplan–Meier method was adopted to perform the univariate analysis; Cox regression model was used to perform multivariate analysis to determine whether the skull base bone destruction when diagnosed by CT was an independent impact factor of the distant bone metastases. The group with skull base bone destruction had a distant bone metastases rate of 9.0% (14/155), whereas the group without skull base bone destruction had rate of 4.1% (12/294). The multivariate analysis showed that the skull base bone destruction, when diagnosed by CT, was an independent impact factor of the distant bone metastases-free survival in the early N-staging cases, but was not an independent impact factor when diagnosed by MRI. The skull base bone destruction diagnosed by CT in patients with NPC had predictive value for the distant bone metastases, especially for the early N-staging cases. PMID:27895493

  11. 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.

  12. Radiation-induced temporo-mandibular joint disorder in post-radiotherapy nasopharyngeal carcinoma patients: assessment and treatment.

    PubMed

    Wu, Vincent W C; Lam, Ying-Na

    2016-06-01

    Nasopharyngeal carcinoma (NPC) is endemic in southern China, and its incidence in Hong Kong is relatively high. Radiotherapy is the mainstay treatment for NPC due to its relatively high radiosensitivity and deep-seated anatomical position, which is not readily accessible by surgery. Although the technique of radiotherapy in NPC has been advancing and offers promising treatment outcome, complications around the irradiation areas are inevitable and the quality of life of the post-radiotherapy patients is often compromised. Trismus, which is defined as the restricted mouth opening or jaw movement due to the disorder of temporo-mandibular joint (TMJ), is one of the possible late complications for radiotherapy of NPC and is found in 5-17% of the post-radiotherapy (post-RT) patients. Trismus at early stage may only affect the speech, but in severe cases nutritional intake and oral hygiene condition may deteriorate seriously. This article reviewed the possible causes of radiation-induced TMJ damage, the various assessments including imaging modalities and possible treatments. The conclusion is that the availability of simple, yet effective examinations for trismus is essential for delaying the progression and restoring TMJ functions. Although there is no absolutely effective treatment for trismus, many supportive, restorative and palliative management are possible under different clinical situations.

  13. Glutaredoxin 3 promotes nasopharyngeal carcinoma growth and metastasis via EGFR/Akt pathway and independent of ROS

    PubMed Central

    Luo, Wenqi; Liao, Zhipeng; Li, Bo; Zhou, Xiaoying; Xiao, Xue; You, Jingping; Chen, Yufeng; Zheng, Shixing; Li, Ping; Murata, Mariko; Huang, Guangwu; Zhang, Zhe

    2016-01-01

    Glutaredoxin 3 (GLRX3) is antioxidant enzyme, maintaining a low level of ROS, thus contributing to the survival and metastasis of several types of cancer. However, the expression and functions of GLRX3 have not been addressed in nasopharyngeal carcinoma (NPC). In this study, we found that GLRX3 was overexpressed in NPC. Knockdown of GLRX3 in NPC cell lines inhibited proliferation in vitro, tumorignesis in vivo, and colony formation. In addition, GLRX3 knockdown decreased the migration and invasion capacity of NPC cells by reversing the epithelial-mesenchymal transition (EMT). Furthermore, stabilization of GLRX3 was positively related to with epidermal growth factor receptor (EGFR) expression and negatively with ROS generation. Phosphorylation of Akt, a key downstream effector, was induced by EGFR signaling but did not rely on increasing ROS level in NPC cells. GLRX3 might be an oncoprotein in NPC, playing important roles in increasing redox reaction and activating EGFR/ Akt signals, so it may be a therapeutic target for NPC. PMID:27203742

  14. MiR-23a sensitizes nasopharyngeal carcinoma to irradiation by targeting IL-8/Stat3 pathway

    PubMed Central

    Jia-Quan, Qu; Hong-Mei, Yi; Xu, Ye; Li-Na, Li; Jin-Feng, Zhu; Ta, Xiao; Li, Yuan; Jiao-Yang, Li; Yuan-Yuan, Wang; Juan, Feng; Qiu-Yan, He; Shan-Shan, Lu; Hong, Yi; Zhi-Qiang, Xiao

    2015-01-01

    Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment, but little is known about how miRNA regulates this phenomenon. In this study, we investigated the function and mechanism of miR-23a in NPC radioresistance, one of downregulated miRNAs in the radioresistant NPC cells identified by our previous microarray analysis. We observed that miR-23a was frequently downregulated in the radioresistant NPC tissues, and its decrement correlated with NPC radioresistance and poor patient survival, and was an independent predictor for reduced patient survival. In vitro radioresponse assays showed that restoration of miR-23a expression markedly increased NPC cell radiosensitivity. In a mouse model, therapeutic administration of miR-23a agomir dramatically sensitized NPC xenografts to irradiation. Mechanistically, we found that reduced miR-23a promoted NPC cell radioresistance by activating IL-8/Stat3 signaling. Moreover, the levels of IL-8 and phospho-Stat3 were increased in the radioresistance NPC tissues, and negatively associated with miR-23a level. Our data demonstrate that miR-23a is a critical determinant of NPC radioresponse and prognostic predictor for NPC patients, and its decrement enhances NPC radioresistance through activating IL-8/Stat3 signaling, highlighting the therapeutic potential of miR-23a/IL-8/Stat3 signaling axis in NPC radiosensitization. PMID:26314966

  15. Knockdown of LMP1-induced miR-155 sensitizes nasopharyngeal carcinoma cells to radiotherapy in vitro

    PubMed Central

    WANG, YUSHENG; SUN, LE

    2016-01-01

    The present study aimed to confirm the promotion of microRNA (miR)-155 expression by latent membrane protein 1 (LMP1), and to recognize the oncogenic role of LMP1 and LMP1-promoted miR-155 in nasopharyngeal carcinoma (NPC), particularly the influence of miR-155 knockdown on the radiosensitivity of CNE-2 cells. Following the regulation of the levels of LMP1 or miR-155 and/or subsequent to radiation treatment, the proliferation ability of CNE-2 cells was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation and Cell Counting Kit-8 assays. The results demonstrated that miR-155 was upregulated by overexpression of LMP1 in CNE-2 cells, and LMP1 overexpression and miR-155 mimic transfection increased CNE-2 cell proliferation, whereas miR-155 knockdown attenuated the promotion of CNE-2 cell growth induced by LMP1 overexpression. Furthermore, knockdown of miR-155 enhanced the radiosensitivity of CNE-2 cells. In conclusion, the present study confirmed the oncogenic role of miR-155 in NPC, and demonstrated that knockdown of miR-155 inhibited the growth of NPC cells and sensitized NPC cells to radiotherapy. PMID:27123134

  16. 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.

  17. Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells.

    PubMed

    Zhai, Xiaoming; Yang, Yang; Wan, Jianmei; Zhu, Ran; Wu, Yiwei

    2013-12-01

    An elevated rate of glucose consumption and the dependency on aerobic glycolysis for ATP generation have long been observed in cancer cells, a phenomenon known as the Warburg effect. the altered energy metabolism in cancer cells provides an attractive opportunity for developing novel cancer therapeutic strategies. Lactate dehydrogenase (LDH), which catalyzes the transformation of pyruvate to lactate, plays a vital role in the process of glycolysis. It has been reported that the level of LDH-A expression is increased both in head and neck cancer cells and in the blood serum of nasopharyngeal carcinoma (NPC) patients, and is associated with poor prognosis. However, the effect of LDH-A inhibition on NPC cells remains unknown. Here, in the present study, we found that oxamate, a classical inhibitor of LDH-A, suppressed cell proliferation in a dose- and time-dependent manner both in CNE-1 and CNE-2 cells, two NPC cancer cell lines. LDH inhibition by oxamate induced G2/M cell cycle arrest via downregulation of the CDK1/cyclin B1 pathway and promoted apoptosis through enhancement of mitochondrial ROS generation. N-acetylcysteine, a specific scavenger of ROS, significantly blocked the growth inhibition effect induced by oxamate. We also identified that oxamate increased sensitivity to ionizing radiation in the two NPC cancer cell lines. Furthermore, we verified similar results in tumor xenograft models. collectively, these results suggest that LDH-A may serve as a promising therapeutic target for NPC treatment.

  18. Downregulation of long non-coding RNA MEG3 in nasopharyngeal carcinoma.

    PubMed

    Chak, Wing-Po; Lung, Raymond Wai-Ming; Tong, Joanna Hung-Man; Chan, Sylvia Yat-Yee; Lun, Samantha Wei-Man; Tsao, Sai-Wah; Lo, Kwok-Wai; To, Ka-Fai

    2017-03-01

    In our previous whole-transcriptome sequencing analysis, downregulation of a long non-coding RNA, maternally expressed gene 3 (MEG3), was identified in NPC samples. This finding suggests the possible role of MEG3 as a tumor suppressor in this distinctive disease. In the present study, two MEG3 variants, AF119863 (MEG3-AF) and BX247998 (MEG3-BX), were found abundantly expressed in a normal nasopharyngeal epithelial cell line, NP69. Significant downregulation of MEG3-AF was further verified in a panel of NPC samples including xenografts and primary biopsies. MEG3 is an imprinted gene located within chromosome 14q32, a common deleted region in NPC. Both DNA copy number loss and aberrant promoter methylation contributed to MEG3 inactivation. Interestingly, MEG3 expression could successfully be rescued by the treatment of a demethylation agent. Besides, ectopic expression of MEG3 in NPC cell lines resulted in considerable repression of in vitro anchorage-independent growth and in vivo tumorigenicity, in addition to significant inhibition in cell proliferation, colony formation, and induction of cell cycle arrest. Finally, we revealed the association between MEG3 activity and the p53 signaling cascade. Our findings characterize MEG3 as a tumor suppressive long non-coding RNA in NPC and encourage the development of precise long non-coding RNA-targeted epigenetic therapy against this malignancy. © 2016 Wiley Periodicals, Inc.

  19. 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.

  20. SU-E-T-302: Dosimetric Comparison Between Volumetric Modulated Arc Radiotherapy and Intensity-Modulated Radiotherapy for Locally Recurrent Nasopharyngeal Carcinoma

    SciTech Connect

    Lu, J-Y; Huang, B-T; Zhang, J-Y; Ma, C-C

    2015-06-15

    Purpose: To compare volumetric modulated arc radiotherapy (VMAT) technique with fixed-gantry intensity-modulated radiotherapy (IMRT) technique for locally recurrent nasopharyngeal carcinoma. Methods: CT datasets of eleven nasopharyngeal-carcinoma patients were included. Dual-arc VMAT and seven-field IMRT plans were created for each case, and were then compared in terms of conformity index (CI), homogeneity index (HI) of the planning target volume (PTV), organ-at-risk (OAR) sparing, monitor unit (MU) and delivery time. Results: The D98% (near-minimal dose) of PTV in the VMAT plans was slightly lower than that of the IMRT plans (P < 0.05), while the CI was higher than that of the IMRT plans (P < 0.05). No significant difference was found in the HI between the two plans (P > 0.05). Compared with the IMRT plans, the VMAT plans demonstrated lower Dmean (mean dose) of the bilateral temporal lobes and the whole surrounding normal tissue (P < 0.05), but slightly higher Dmean of brainstem (P < 0.05). In terms of the other OARs, no significant differences were found (P > 0.05). The MUs of the VMAT plans (672 ± 112) was significantly lower than that of the IMRT plans (917 ± 206), by 25 ± 13% (P < 0.05). The average delivery time of the VMAT plans (2.3 ± 0.1 min) was less than that of the IMRT plans (5.1 ± 0.4 min), by 54 ± 3%. Conclusion: For locally recurrent nasopharyngeal carcinoma, the VMAT technique could achieve equivalent or superior dose distribution of the target and better protect the bilateral temporal lobes, compared with the IMRT technique. Moreover, it could reduce the MU and delivery time effectively.

  1. Pro-apoptotic and anti-proliferative effects of 3,3'-diindolylmethane in nasopharyngeal carcinoma cells via downregulation of telomerase activity.

    PubMed

    Li, Fen; Xu, Yong; Chen, Chen; Chen, Shi-Ming; Xiao, Bo-Kui; Tao, Ze-Zhang

    2015-09-01

    The pro-apoptotic and anti-proliferative effects of 3,3'-diindolylmethane (DIM) in various tumor cell types have been widely investigated. The underlying mechanisms were suggested to include cell cycle arrest, cell signaling inhibition and downregulation of the androgen receptor. The present study demonstrated that DIM induced apoptosis and inhibited proliferation in nasopharyngeal carcinoma cells by downregulating the activity of telomerase. The nasopharyngeal carcinoma cell line 5‑8F was selected for this purpose. A cell counting kit‑8 assay and flow cytometry were performed to detect apoptosis and proliferation of 5‑8F cells, respectively, which revealed the pro‑apoptotic and anti‑proliferative effects of DIM. Telomerase activity was detected using a telomeric repeat amplification protocol assay, which revealed that the telomerase activity was inhibited by DIM in a dose‑dependent manner. Reverse transcription polymerase chain reaction was used to detect the mRNA expression levels of human telomerase reverse transcriptase (hTERT) and human telomerase RNA (hTR), and western blot analysis was used to detect the protein expression of hTERT. The results showed that the mRNA and protein expression of hTERT were downregulated in 5‑8F cells following treatment with DIM; however, the mRNA expression of hTR remained unchanged, suggesting that hTERT was the target of DIM. To further identify the target, the length of telomeres was continually measured using a telomere length detection kit, revealing that the telomeres were shortened by DIM in an concentration‑dependent manner. The present study confirmed that DIM had pro‑apoptotic and anti‑proliferative effects in nasopharyngeal carcinoma cells by regulating telomerase.

  2. 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.

  3. MicroRNA-200a mediates nasopharyngeal carcinoma cell proliferation through the activation of nuclear factor-κB.

    PubMed

    Shi, Zhuliang; Hu, Zhiqiang; Chen, Delu; Huang, Jie; Fan, Jie; Zhou, Subo; Wang, Xin; Hu, Jiandao; Huang, Fei

    2016-02-01

    In nasopharyngeal carcinoma (NPC), the nuclear factor-κB (NF-κB) signaling pathway is highly active. The constitutive activation of NF-κB prompts malignant cell proliferation, and microRNAs are considered an important mediator in regulating the NF-κB signaling pathway. The current study investigated the effect of microRNA-200a (miR-200a) on NF-κB activation. Reverse transcription-quantitative polymerase chain reaction was used to quantify the relative level of miR-200a in NPC tissue samples and CNE2 cells. An MTT assay was used to investigate the effect of miR-200a on cell proliferation. To investigate the activation of NF-κB, western blotting was used to measure the protein levels of NF-κB and its downstream targets. To identify the target genes of miR-200a, a luciferase reporter assay was used. The current study demonstrated that miR-200a was upregulated in NPC tissue samples and cell lines. Overexpression of miR-200a resulted in the proliferation of CNE2 cells. Western blot analysis indicated that the protein levels of p65 increased when CNE2 cells were transfected with miR-200a mimics. Additionally, the downstream targets of miR-200a were upregulated, including vascular cell adhesion molecule, intercellular adhesion molecule and monocyte chemoattractant protein-1. The luciferase assay indicated that IκBα was the target gene of miR-200a. In conclusion, miR-200a was demonstrated to enhance NPC cell proliferation by activating the NF-κB signaling pathway.

  4. Blockage of SSRP1/Ets-1/Pim-3 signalling enhances chemosensitivity of nasopharyngeal carcinoma to docetaxel in vitro.

    PubMed

    Ai, Jingang; Li, Wei; Zeng, Ruifang; Xie, Zuozhong; Liu, Honghui; Hou, Minghua; Tan, Guolin

    2016-10-01

    Nasopharyngeal carcinoma (NPC) is a rare cancer in most parts of the world, but is prevalent in South China area. Besides, therapeutic outcome is still unsatisfactory for patients with refractory and relapsed NPC, even though receiving a second line of docetaxel-based chemotherapy. These reasons require a better understanding of mechanisms underlying the carcinogenesis, malignancy and chemoresistance. In the basis of our previous finding of SSRP1 over-expression in NPC cell lines, this study continuously discovered up-regulated Ets-1, phosphor-Ets-1 and Pim-3 in NPC tissues with immunohistochemistry assay and revealed a close correlation of these up-regulated proteins with NPC proliferation and invasion. Using gene-silencing technology followed by western blot and immunocytochemistry detections, SSRP1 was found to facilitate the translocation of phosphor-Ets-1 from cytoplasm to cell nucleus, but have marginal effect on Ets-1 expression and phosphorylation. Pim-3 was positively regulated by Ets-1. In NPC HNE-1 cells, all SSRP1, Ets-1 and Pim-3 knockdown diminished the cell proliferation, enhanced the apoptosis, as well as inhibited the autophagy, invasion and clonogenicity in the presence or absence of docetaxel at IC25. Exposure of HNE-1 cells to docetaxel (IC25) alone had modest effect on cell proliferation and autophagy, and was not as effective as docetaxel treatment after knockdown of SSRP1, Ets-1 or Pim-3 on induction of the apoptosis and on inhibition of the invasion and clonogenicity. Our data indicate that SSRP1/Ets-1/Pim-3 signalling is tightly associated with the proliferation, apoptosis, autophagy, invasion and clonogenicity of NPC cells, and blockage of this signalling facilitates chemosensitivity of the cells to docetaxel.

  5. 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

  6. High expression of IMPDH2 is associated with aggressive features and poor prognosis of primary nasopharyngeal carcinoma.

    PubMed

    Xu, Yi; Zheng, Zhousan; Gao, Ying; Duan, Shiyu; Chen, Cui; Rong, Jian; Wang, Kebing; Yun, Miao; Weng, Huiwen; Ye, Sheng; Zhang, Jiaxing

    2017-04-07

    Inosine monophosphate dehydrogenase type II (IMPDH2) has been shown to play critical roles in the development and progression of several human cancers. However, little is known about IMPDH2 expression and its clinical significance in nasopharyngeal carcinoma (NPC). Western blotting, qRT-PCR and immunohistochemistry were employed to evaluate IMPDH2 expression in NPC cell lines and tissues. In our study, elevated expression of IMPDH2 was observed at both the protein and mRNA levels in NPC cell lines than in NPEC2 Bmi-1. IMPDH2 protein expression was markedly higher in NPC tissues than in adjacent non-tumorous tissues. Moreover, IMPDH2 expression in NPC correlated with several clinicopathological parameters, including T classification (P = 0.023), TNM stage (P = 0.020), distant metastasis (P = 0.001) and death (P = 0.002). Further Cox regression analysis suggested that IMPDH2 expression was an independent prognostic factor for overall survival (P = 0.001) and disease-free survival (P < 0.001). In addition, stratified survival analysis showed that high expression of IMPDH2 could be a prognostic factor for NPC patients with TNM stage I/II (OS: P = 0.012; DMFS: P = 0.007), TNM stage III/IV (OS: P = 0.028; DMFS: P = 0.020). Our study demonstrates IMPDH2 may be served as an independent prognostic biomarker for NPC patients, in which high IMPDH expression suggests poor prognosis of NPC patients.

  7. MiR-99a suppresses cell invasion and metastasis in nasopharyngeal carcinoma through targeting HOXA1

    PubMed Central

    Wang, Jian-Gang; Tang, Wu-Ping; Liao, Ming-Chu; Liu, Yan-Ping; Ai, Xiao-Hong

    2017-01-01

    Background Recent studies reported that miRNAs play important roles in the carcinogenesis and progression of nasopharyngeal carcinoma (NPC). Therefore, further studies are warranted to better elucidate the function and mechanism of miRNAs in NPC. Methods Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the miR-99a expression in NPC cell lines and tissue samples. Wound healing, transwell migration and invasion, and lung metastatic colonization assays were performed to determine NPC cell migratory, invasive and metastatic abilities of NPC cells. Luciferase reporter assays, quantitative RT-PCR and Western blotting were used to validate the target of miR-99a. Results We found that miR-99a was significantly downregulated in NPC cell lines and tissue samples. Ectopic overexpression of miR-99a significantly inhibited NPC cell migration and invasion in vitro, and suppressed lung macroscopic and microscopic metastatic colonization in vivo. Conversely, silencing of miR-99a significantly promoted the migratory and invasive abilities of NPC cells. Furthermore, HOXA1 was validated as a direct target of miR-99a, and ectopic expression of HOXA1 could rescue the suppressive effect of miR-99a overexpression on NPC cell migration and invasion. Conclusion Together, these results indicated that miR-99a could inhibit NPC invasion and metastasis by targeting HOXA1, thus providing a novel potential target for miRNA-based treatment for NPC patients in the future. PMID:28228659

  8. Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in nasopharyngeal carcinoma patients with cervical nodal necrosis

    PubMed Central

    Lan, Mei; Chen, Chunyan; Huang, Ying; Tian, Li; Duan, Zhijun; Han, Fei; Liao, Junfang; Deng, Meiling; Sio, Terence T.; Prayongrat, Anussara; Zheng, Lie; Wu, Shaoxiong; Lu, Taixiang

    2017-01-01

    The effectiveness of neoadjuvant chemotherapy (NACT) followed by concurrent chemoradiotherapy (CCRT) compared with CCRT alone in nasopharyngeal carcinoma (NPC) patients who presented with cervical nodal necrosis (CNN) is unknown. A total of 792 patients with stage T1-4N1-3M0 NPC and presented with CNN based on magnetic resonance imaging were retrospectively reviewed. Propensity score matching method was used to balance treatment arms for baseline characteristics. Eventually, 508 patients were propensity-matched on a 1:1 basis to create two groups (NACT + CCRT and CCRT groups). Survival rates were calculated by Kaplan–Meier method and differences were compared by using the log-rank test. The 5-year disease specific survival, disease-free survival and distant metastasis-free survival were significantly higher in NACT + CCRT group relative to the matched CCRT group (82.1% vs. 72.5%, P = 0.021; 70.3% vs. 54.1%, P < 0.001; 81.9% vs. 67.3%, P < 0.001, respectively). Although the rates of grade 3–4 leucopenia and mucositis were higher in NACT + CCRT group than CCRT group, compliance with the combined treatment was good and no significant difference was observed between two groups. NACT followed by CCRT was relatively safe and could achieve better survival than CCRT alone in NPC patients with CNN by reducing the risk of death, tumor progression and distant metastasis. PMID:28211482

  9. Combination of autoantibodies against NY-ESO-1 and viral capsid antigen immunoglobulin A for improved detection of nasopharyngeal carcinoma.

    PubMed

    Peng, Yu-Hui; Xu, Yi-Wei; Qiu, Si-Qi; Hong, Chao-Qun; Zhai, Tian-Tian; Li, En-Min; Xu, Li-Yan

    2014-09-01

    Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China and Southeast Asia, and early detection remains a challenge. Autoantibodies have been found to precede the manifestations of symptomatic cancer by several months to years, making their identification of particular relevance for early detection. In the present study, the diagnostic value of serum autoantibodies against NY-ESO-1 in NPC patients was evaluated. The study included 112 patients with NPC and 138 normal controls. Serum levels of autoantibodies against NY-ESO-1 and classical Epstein-Barr virus marker, viral capsid antigen immunoglobulin A (VCA-IgA), were measured by enzyme-linked immunosorbent assay. Measurement of autoantibodies against NY-ESO-1 and VCA-IgA demonstrated a sensitivity/specificity of 42.9/94.9% [95% confidence interval (CI), 33.7-52.6/89.4-97.8%] and 55.4/95.7% (95% CI, 45.7-64.7/90.4-98.2%), respectively. The area under receiver operating characteristic curve for autoantibodies against NY-ESO-1 (0.821; 95% CI, 0.771-0.871) was marginally lower than that for VCA-IgA (0.860; 95% CI, 0.810-0.910) in NPC. The combination of autoantibodies against NY-ESO-1 and VCA-IgA yielded an enhanced sensitivity of 80.4% (95% CI, 71.6-87.0%) and a specificity of 90.6% (95% CI, 84.1-94.7%). Moreover, detection of autoantibodies against NY-ESO-1 could differentiate early-stage NPC patients from normal controls. Our results suggest that autoantibodies against NY-ESO-1 may serve as a potential biomarker, as a supplement to VCA-IgA, for the screening and diagnosis of NPC.

  10. 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.

  11. 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

  12. RSF1 regulates the proliferation and paclitaxel resistance via modulating NF-κB signaling pathway in nasopharyngeal carcinoma

    PubMed Central

    Liu, Yong; Li, Guo; Liu, Chao; Tang, Yaoyun; Zhang, Shuai

    2017-01-01

    Purpose: Aberrant expression and dysfunction of RSF1 has been reported in diverse human malignancies. However, its exact role in nasopharyngeal carcinoma (NPC) remains unclear. Methods: The expression of RSF1 mRNA and protein were assayed by qRT-PCR and western blotting, and their correlations with clinicopathological parameters of patients with NPC were further analysed. Lentivirus mediated RSF1 shRNA and RSF1 cDNA were used to knockdown and upregulate the expression of RSF1. CCK8 assays and flow cytometry were applied to monitor the changes of proliferation and paclitaxel sensitivity caused by RSF1 modulation, inhibition of NF-κB pathway by inhibitor Bay 11-7082 and Survivin knockdown. Western blotting was used to detect protein alterations in NF-κB signaling pathway. Results: Our present study demonstrated that both mRNA and protein expressions of RSF1 were increased and correlated with advanced NPC clinical stage. Functional analyses revealed that RSF1 inhibition or overexpression induced changes in cell cycle, apoptosis, and then led to altered proliferation and paclitaxel sensitivity in diverse NPC cells in vitro. Further mechanism investigation hinted that RSF1 overexpression in NPC CNE-2 cells activated NF-κB pathway and promoted the expression NF-κB dependent genes involved in cell cycle and apoptosis including Survivin. Importantly, inhibition of NF-κB pathway by Bay 11-7082 and knockdown its downstream Survivin reversed the paclitaxel resistance caused by RSF1 overexpression. Conclusions: Taken together, our data indicate that RSF1 regulates the proliferation and paclitaxel resistance via activating NF-κB signaling pathway and NF-κB-dependent Survivin upregulation, suggesting that RSF1 may be used as a potential therapeutic target in NPC. PMID:28261335

  13. Preliminary assessment of nasopharyngeal carcinoma incidence in the Philippines: a second look at published data from four centers

    PubMed Central

    Sarmiento, Mario Paulus Cesar B.; Mejia, Michael Benedict A.

    2014-01-01

    In endemic regions such as southern China and Southeast Asia, the annual incidence of nasopharyngeal carcinoma (NPC) ranges from 3 to 30 per 100,000. In the Philippines, the estimated incidence in 2010 was 1.2 per 100,000. However, this rate is based on data collected from registries covering only two regions in the country. Here, we report the findings from our study to better approximate the incidence of NPC in the Philippines. Between September 1, 2011 and August 31, 2012, data were collected from 49 patients from 4 different institutions—University of Santo Tomas, Makati Medical Center, Philippine Oncology Center Corporation, and Cardinal Santos Memorial Medical Center—using a NPC screening questionnaire. Crude incidence was 0.09 per 100,000. Age-standardized incidences using Segi and WHO standards were 2.08 and 1.79 per 100,000, respectively. Of the 49 patients, 31 were males and 18 were females, and 71% of patients were between 30 and 59 years old. WHO types II and III represented 22% and 78% of the subjects, respectively, and 75.5% of cases were locally advanced (stages III–IVB). Although the age-standardized incidence from the 4 institutions was numerically higher than the published age-standardized incidence (2.07 per 100,000 vs. 1.2 per 100,000), two-proportion z-test showed no significant difference between them (P = 0.68). A more concerted effort is needed for a better approximation of the country's NPC disease burden. PMID:23958058

  14. Type 2 Diabetic Mellitus Is a Risk Factor for Nasopharyngeal Carcinoma: A 1:2 Matched Case–Control Study

    PubMed Central

    Qiu, Wen-Ze; Tian, Yun-Hong; Zhang, Wei-Jun; Cao, Ka-Jia

    2016-01-01

    Background Diabetes has been identified as an adverse prognostic variable which associated with an increased mortality in various cancers, including colorectal, lung, and breast cancers. However, previous studies provided inconsistent results on the association between diabetes and nasopharyngeal carcinoma (NPC). The main aim of this study was to investigate the associations between diabetes mellitus and the survival of NPC patients. Methods This study was designed as a 1:2 matched case–control study. Cases were patients who met the criteria for the diagnosis of type 2 diabetic mellitus (DM) below. Controls, matched 1:2, were patients who were normoglycemic (NDM). The survival rates were assessed by Kaplan–Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model. Results Both locoregional relapse-free survival (LRRFS) and disease-free survival (DFS) in the NDM group were higher than that in the DM group (p = 0.001 and p = 0.033). Additionally, subset analyses revealed that the differences in OS, LRRFS, and DFS were all significant between the two groups in the N0-N1 subset (p = 0.007, p =.000 and p = 0.002). The LRRFS was higher in the NDM group in the III-IV, T3-T4 and N0-N1 subsets (p = 0.004, p = 0.002 and p =.000). In T3-T4 subset, the NDM group experienced higher DFS than the DM group (p = 0.039). In multivariate analysis, T stage and N stage were found to be independent predictors for OS, DMFS and DFS; chemotherapy was a significant prognostic factor for DMFS and DFS, age for OS, and diabetes for LRRFS and DFS. Conclusions Type 2 diabetic mellitus is associated with poorer prognosis among patients with NPC. PMID:27760202

  15. 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.

  16. Aloe-emodin induces apoptosis of human nasopharyngeal carcinoma cells via caspase-8-mediated activation of the mitochondrial death pathway.

    PubMed

    Lin, Meng-Liang; Lu, Yao-Cheng; Chung, Jing-Gung; Li, Yi-Chen; Wang, Shyang-Guang; N G, Sue-Hwee; Wu, Chia-Yin; Su, Hong-Lin; Chen, Shih-Shun

    2010-05-01

    Aloe-emodin (AE), a natural, biologically active compound from the rhizome of Rheum palmatum, has been shown to induce apoptosis in several cancer cell lines in vitro. However, its molecular mechanism of action in the apoptosis induction of human nasopharyngeal carcinoma (NPC) cells has not been explored. This study shows that AE induced G(2)/M phase arrest by increasing levels of cyclin B1 bound to Cdc2, and also caused an increase in apoptosis of NPC cells, which was characterized by morphological changes, nuclear condensation, DNA fragmentation, caspase-3 activation, cleavage of poly (ADP-ribose) polymerase (PARP) and increased sub-G(1) population. Treatment of NPC cells with AE also resulted in a decrease in Bcl-X(L) and an increase in Bax expression. Ectopic expression of Bcl-X(L) but not Bcl-2 or small interfering RNA (siRNA)-mediated attenuation of Bax suppressed AE-induced apoptotic cell death. AE-induced loss of mitochondrial membrane potential (MMP) and increase in cellular Ca(++) content, reactive oxygen species (ROS) and apoptotic cell death were suppressed by the treatment of cyclosporin A (CsA) or caspase-8 inhibitor Z-IETD-FMK. Co-treatment with caspase-9 inhibitor Z-LEHD-FMK could inhibit AE-induced cell death and the activation of caspase-3 and -9. In addition, suppression of caspase-8 with the specific inhibitor Z-IETD-FMK inhibited AE-induced the activation of Bax, the cleavage of Bid, the translocation of tBid to the mitochondria and the release of cytochrome c, apoptosis-inducing factor (AIF) and Endo G from the mitochondria and subsequent apoptosis. Taken together, these results indicate that the caspase-8-mediated activation of the mitochondrial death pathway plays a critical role in AE-induced apoptosis of NPC cells.

  17. 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.

  18. Evaluation of nonviral risk factors for nasopharyngeal carcinoma in a high-risk population of Southern China.

    PubMed

    Guo, Xiuchan; Johnson, Randall C; Deng, Hong; Liao, Jian; Guan, Li; Nelson, George W; Tang, Mingzhong; Zheng, Yuming; de The, Guy; O'Brien, Stephen J; Winkler, Cheryl A; Zeng, Yi

    2009-06-15

    To understand the role of environmental and genetic influences on nasopharyngeal carcinoma (NPC) in populations at high risk of NPC, we have performed a case-control study in Guangxi Province of Southern China in 2004-2005. NPC cases (n = 1,049) were compared with 785 NPC-free matched controls who were seropositive for IgA antibodies (IgA) to Epstein-Barr virus (EBV) capsid antigen (VCA)-a predictive marker for NPC in Chinese populations. A questionnaire was used to capture exposure and NPC family history data. Risk factors associated with NPC in a multivariant analysis model were the following: (i) a first, second or third degree relative with NPC [attributable risk (AR)= 6%, odds ratio (OR) = 3.1, 95% confidence interval (CI) = 2.0-4.9, p < 0.001]; (ii) consumption of salted fish 3 or more than 3 times per month (AR = 3%, OR = 1.9, 95% CI = 1.1-3.5, p = 0.035); (iii) exposure to domestic wood cooking fires for more than 10 years (AR = 69%, OR = 5.8, 95% CI = 2.5-13.6, p < 0.001); and (iv) exposure to occupational solvents for 10 or less years (AR = 4%, OR = 2.6, 95% CI = 1.4-4.8, p = 0.002). Consumption of preserved meats or a history of tobacco smoking were not associated with NPC (p > 0.05). We also assessed the contribution of EBV/IgA/VCA antibody serostatus to NPC risk-32.2% of NPC can be explained by IgA+ status. However, family history and environmental risk factors cumulatively explained only 2.7% of NPC development in NPC high risk population. These findings should have important public health implications for NPC risk reduction in endemic regions.

  19. Correlation of a hypoxia based tumor control model with observed local control rates in nasopharyngeal carcinoma treated with chemoradiotherapy

    SciTech Connect

    Avanzo, Michele; Stancanello, Joseph; Franchin, Giovanni; Sartor, Giovanna; Jena, Rajesh; Drigo, Annalisa; Dassie, Andrea; Gigante, Marco; Capra, Elvira

    2010-04-15

    Purpose: To extend the application of current radiation therapy (RT) based tumor control probability (TCP) models of nasopharyngeal carcinoma (NPC) to include the effects of hypoxia and chemoradiotherapy (CRT). Methods: A TCP model is described based on the linear-quadratic model modified to account for repopulation, chemotherapy, heterogeneity of dose to the tumor, and hypoxia. Sensitivity analysis was performed to determine which parameters exert the greatest influence on the uncertainty of modeled TCP. On the basis of the sensitivity analysis, the values of specific radiobiological parameters were set to nominal values reported in the literature for NPC or head and neck tumors. The remaining radiobiological parameters were determined by fitting TCP to clinical local control data from published randomized studies using both RT and CRT. Validation of the model was performed by comparison of estimated TCP and average overall local control rate (LCR) for 45 patients treated at the institution with conventional linear-accelerator-based or helical tomotherapy based intensity-modulated RT and neoadjuvant chemotherapy. Results: Sensitivity analysis demonstrates that the model is most sensitive to the radiosensitivity term {alpha} and the dose per fraction. The estimated values of {alpha} and OER from data fitting were 0.396 Gy{sup -1} and 1.417. The model estimate of TCP (average 90.9%, range 26.9%-99.2%) showed good correlation with the LCR (86.7%). Conclusions: The model implemented in this work provides clinicians with a useful tool to predict the success rate of treatment, optimize treatment plans, and compare the effects of multimodality therapy.

  20. 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.

  1. 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.

  2. 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

  3. Short-Term Effect of Different Teaching Methods on Nasopharyngeal Carcinoma for General Practitioners in Jakarta, Indonesia

    PubMed Central

    Wildeman, Maarten A.; Fles, Renske; Adham, Marlinda; Mayangsari, Ika D.; Luirink, Ilse; Sandberg, Mara; Vincent, Andrew D.; Fardizza, Faiziah; Musa, Zanil; Armiyanto; Middeldorp, Jaap M.; Gerritsen, Geerten; Suwanto, Ronny; Tan, I. Bing

    2012-01-01

    In Indonesia, Nasopharyngeal Carcinoma (NPC) is the most frequent cancer of the head and neck region. At first presentation in the hospital most patients already have advanced NPC. Our previous study showed that general practitioners (GPs) working in Yogyakarta, Indonesia lack the knowledge necessary for early detection of NPC. By providing training on early symptoms of NPC we hope that the diagnosis and referral will occur at an earlier stage. Here we assess the current NPC knowledge levels of GPs in Jakarta, evaluate improvement after training, compare the effectiveness of two training formats, and estimate the loss of recall over a two week period. Methods Two Indonesian GPs visited 31 Primary Health Care Centres (PHCCs) and provided a lecture on NPC. The alternative format consisted of a symposium at the Universitas Indonesia, Jakarta, presented by local head and neck surgeons, with all GPs in the region being invited. To evaluate the effect of both formats a questionnaire was conducted before and after. Results The lecture in the PHCCs was attended by 130 GPs. Sixty-six GPs attended the training in the university hospital and 40 GPs attended both. Pre training the NPC knowledge level was poor with an average of 1.6 symptoms being correctly identified out of a potential maximum of 12, this was increased to 4.9 post training (p<0.0001). GPs attending the PHCC course recorded a greater increase in correct symptoms than those attending the symposium (3.8 vs. 2.8; p = 0.01). After a two week period the knowledge levels had declined slightly from 5.5 correctly identified symptoms to 4.2 (p = 0.25). Conclusion These results confirm our findings regarding GPs insufficient knowledge of NPC. Lectures in the PHCC and a symposium have both been proven to be effective training tools in the education of GPs. PMID:22431981

  4. A Global View of the Oncogenic Landscape in Nasopharyngeal Carcinoma: An Integrated Analysis at the Genetic and Expression Levels

    PubMed Central

    Hu, Chunfang; Wei, Wenbin; Chen, Xiaoyi; Woodman, Ciaran B.; Yao, Yunhong; Nicholls, John M.; Joab, Irène; Sihota, Sim K.; Shao, Jian-Yong; Derkaoui, K. Dalia; Amari, Aicha; Maloney, Stephanie L.; Bell, Andrew I.; Murray, Paul G.; Dawson, Christopher W.; Young, Lawrence S.; Arrand, John R.

    2012-01-01

    Previous studies have reported that the tumour cells of nasopharyngeal carcinoma (NPC) exhibit recurrent chromosome abnormalities. These genetic changes are broadly assumed to lead to changes in gene expression which are important for the pathogenesis of this tumour. However, this assumption has yet to be formally tested at a global level. Therefore a genome wide analysis of chromosome copy number and gene expression was performed in tumour cells micro-dissected from the same NPC biopsies. Cellular tumour suppressor and tumour-promoting genes (TSG, TPG) and Epstein-Barr Virus (EBV)-encoded oncogenes were examined. The EBV-encoded genome maintenance protein EBNA1, along with the putative oncogenes LMP1, LMP2 and BARF1 were expressed in the majority of NPCs that were analysed. Significant downregulation of expression in an average of 76 cellular TSGs per tumour was found, whilst a per-tumour average of 88 significantly upregulated, TPGs occurred. The expression of around 60% of putative TPGs and TSGs was both up-and down-regulated in different types of cancer, suggesting that the simplistic classification of genes as TSGs or TPGs may not be entirely appropriate and that the concept of context-dependent onco-suppressors may be more extensive than previously recognised. No significant enrichment of TPGs within regions of frequent genomic gain was seen but TSGs were significantly enriched within regions of frequent genomic loss. It is suggested that loss of the FHIT gene may be a driver of NPC tumourigenesis. Notwithstanding the association of TSGs with regions of genomic loss, on a gene by gene basis and excepting homozygous deletions and high-level amplification, there is very little correlation between chromosomal copy number aberrations and expression levels of TSGs and TPGs in NPC. PMID:22815911

  5. Survival analysis of patients with advanced-stage nasopharyngeal carcinoma according to the Epstein-Barr virus status

    PubMed Central

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

    2016-01-01

    Purpose The main aim of this study is to analyze the prognostic differences in nasopharyngeal carcinoma (NPC) patients who are positive and negative for Epstein-Barr virus (EBV). Results Of the 1106 patients, 248 (22.4%) had undetectable pre-treatment plasma EBV DNA levels. The total distant metastasis rate for EBV-negative group vs. EBV-positive group were 3.6% (9/248) vs. 15.0% (128/858) (P < 0.001). The estimated 4-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) for EBV-negative group vs. EBV-positive group were 88.9% vs. 76.9% (P < 0.001), 93.6% vs. 85.9% (P = 0.001), 96.7% vs. 84.8% (P < 0.001) and 94.1% vs. 90.0% (P = 0.1), respectively. Multivariate analysis revealed that the EBV status was an independent prognostic factor for DFS (HR, 1.813; 95% CI, 1.219-2.695; P = 0.003), OS (HR, 1.828; 95% CI, 1.075-3.107; P = 0.026) and DMFS (HR, 3.678; 95% CI, 1.859-7.277; P <0.001), and overall stage still remained the most important prognostic factor in patients with stage III-IVB NPC. Methods and Materials Data on 1106 patients with non-metastatic, histologically proven advanced-stage (III-IVB) NPC who underwent intensity-modulated radiotherapy (IMRT) were retrospectively reviewed. Patient survival between different EBV status groups were compared. Conclusions EBV status was an independent prognostic factor for patients with stage III–IVB NPC. Neoadjuvant chemotherapy (NCT) plus concurrent chemoradiotherapy (CCRT) should be better treatment regimen for EBV-positive patients since distant metastasis was the main failure pattern, and CCRT may be enough for EBV-negative patients. PMID:27008701

  6. 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.

  7. HYOU1, Regulated by LPLUNC1, Is Up-Regulated in Nasopharyngeal Carcinoma and Associated with Poor Prognosis

    PubMed Central

    Zhou, Yujuan; Liao, Qianjin; Li, Xiayu; Wang, Hui; Wei, Fang; Chen, Jie; Yang, Jing; Zeng, Zhaoyang; Guo, Xiaofang; Chen, Pan; Zhang, Wenling; Tang, Ke; Li, Xiaoling; Xiong, Wei; Li, Guiyuan

    2016-01-01

    Objective: This study aims to investigate the roles and mechanisms of long palate, lung and nasal epithelium clone 1 (LPLUNC1) in nasopharyngeal carcinoma (NPC). Methods: The two-dimensional fluorescence difference gel electrophoresis (2-D DIGE) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-TOF-MS/MS) was applied to identify differentially expressed proteins after over-expressing LPLUNC1 in NPC cells. The qRT-PCR and Western Blot were used to further validate differentially expression of Hypoxia up-regulated 1 (HYOU1). We also applied immunohistochemistry (IHC) to validate the expression of HYOU1 protein in NPC tissues. Results: Totally 44 differentially expressed proteins were identified, among which 19 proteins were up-regulated and 25 proteins were down-regulated. Function annotation indicated that these proteins were involved in molecular chaperone, cytoskeleton, metabolism and signal transduction. It was shown that the expression of HYOU1 both at mRNA level and protein level was up-regulated significantly in NPC tissues, and HYOU1 protein expression was positively correlated with clinical staging and metastasis of NPC. Kaplan-Meier survival curves showed that high expression of HYOU1 protein in NPC patients had shorter progression-free survival (PFS) and overall survival (OS). COX multivariate regression analysis further indicated that over-expressed HYOU1 was one of the predictors for poor prognosis in NPC patients. Conclusion: Through regulating proteins in different pathways, LPLUNC1 may inhibit the growth of NPC through participating in cell metabolism, proliferation, transcription and signaling transduction. HYOU1 can be regarded as potential molecular biomarker for progression and prognosis of NPC. PMID:26918051

  8. Expression of Interleukin-8, Interleukin-10 and Epstein-Barr Viral-Load as Prognostic Indicator in Nasopharyngeal Carcinoma

    PubMed Central

    Savitri, Eka; Haryana, Mubarika Sofia

    2015-01-01

    Interleukin-8 (IL-8) is angiogeneic chemokine that plays a potential role in both development and progression of many human malignancies including nasopharyngeal carcinoma (NPC). Epstein- Barr virus (EBV) is recognized to be an important etiologic agent of NPC as the viral gene products are frequently detected in NPC tissue along with the elevation of antibody titre to the viral protein (VCA-p18+ EBNA1) of IgA in the majority of patients. Elevated plasma of Viral Load is regarded as an important marker for the presence of the disease and for the monitoring of disease progression. However, other serum/plasma parameters such as the level of certain interleukins (IL-8 and IL-10) has also been implicated in NPC progression. The study aimed to investigate the correlations between plasma Viral Load and the level of interleukin (IL-8) and Interleukin (IL-10) in relating these parameters to the stages of NPC. In addition of Viral Load (VCA-p18+EBNA1) IgA, Interleukin-8 and Interleukin-10 before and after therapy will be investigated to seek the possible marker for disease progression. A total of 39 NPC patients and 29 healthy control individuals enrolled in this study. Plasma Viral Load was quantified using real-time quantitative PCR. The Level of plasma interleukins both IL-8 and IL-10 were analyzed using ELISA methods. Results indicated there was a significant decrease in viral load was detected in plasma of NPC patients following therapy. Plasma of viral load was shown to be a good prognosticator for disease progression. There were positive correlation between plasma of viral load and IL-8. These non invasive parameters expressed in blood, could be substitutes of viral load using brushing method, which is invasive. In conclusion that: Viral Load, (VCA-p18+EBNA1) IgA and IL-8 levels are promising markers for the presence of NPC and progression of the disease. PMID:25948470

  9. Sequence-based typing of HLA-A gene in 930 patients with nasopharyngeal carcinoma in Hunan province, southern China.

    PubMed

    Tian, W; Zhu, F-M; Wang, W-Y; Cai, J-H; Zhang, W; Li, L-X; Liu, K-L; Jin, H-K; Wang, F

    2015-07-01

    In this study, we typed 930 cases of nasopharyngeal carcinoma (NPC) and 1134 normal controls recruited from Hunan province, southern China for human leukocyte antigen-A (HLA-A) locus by sequencing exons 2-4. Very significant associations between HLA-A*02:07, HLA-A*11:01 and NPC were established [25.7% vs 16.18%; odds ratio, OR (95% confidence interval, CI) = 1.79 (1.54-2.09), P < 0.0001 and 21.1% vs 30.42%, OR (95% CI) = 0.61 (0.53-0.70), P<0.0001, respectively]. Further analysis of the molecular basis underlying these associations suggests that cysteine (C) at codon 99 of α2-helix of HLA-A protein is probably deleterious and confers risk to NPC. Convincing evidence was uncovered for negative association of a rare allele in southern Chinese populations, HLA-A*31:01, with NPC [0.22% vs 2.12%, OR (95% CI) = 0.1 (0.04-0.28), P < 0.0001]. rs1059449-A, which encodes arginine (R) at codon 56 of α1-helix of HLA-A protein, was postulated to be crucial for such a pattern of negative association with NPC. A subset of NPC cases (N = 632) and normal controls (N=712) were tested for anti-virus capsid antigen (anti-VCA) immunoglobulin A (IgA), very significant difference in seropositivity for anti-VCA IgA was observed between the two groups [67.56% vs 6.46%, OR (95% CI) = 30.16 (21.42-42.46), P < 0.0001]. However, seropositivity for anti-VCA IgA did not correlate with HLA-A allelic typing in both groups.

  10. The end-of-treatment telephone response and prognosis of post-radiotherapy nasopharyngeal carcinoma patients in southern China.

    PubMed

    Chen, Mu-Yao; Chen, Yu-Shan; Hu, Li-Jing; Lun, Xue-Ping; He, Dan-Dan; Chen, Pei-Fen; Hu, Lian-Ying

    2015-01-01

    Nasopharyngeal Carcinoma (NPC) patients' end-of-treatment survival status has drawn more attention in recent years. Telephone follow-up, as a most operative approach among all the clinical follow-ups, is an effective means to extend medical service to patients' home and is thus widely used in clinical practice. This study aimed to analyze the post-radiotherapy NPC patients' phone response rate and its factors, and to discuss the independent prognostic factors of NPC patients' radiotherapy. We prospectively designed a nurses-led telephone follow-up to include 2520 NPC patients who received simple radical radiotherapy between Jan. 2007 and Jun. 2012 at Sun Yat-sen University Cancer Center. The patients' response rate and its factors were calculated. Survival analysis was used to estimate the patients' survival and the influencing factors. The overall response rate was 90.5%; Patients with reserved contact type of mobile + landlinephone or landline phone had higher follow-up response rate than patients with mobile contact only; patients with 2 or more reserved contacts, and family cancer history had higher response rate than patients with only 1 number and those without family history. Patients' cumulative survival rate of 1, 3 and 5 years were 98.9%, 75.3%, 50.3%, respectively. T-staging, N-staging, higher clinical staging, with basicranial invasion were the influencing factors of the patients' poor prognosis. The telephone follow-up response was affected by reserved contact type, number of contacts and family medical history; T-staging, N-staging, higher clinical staging, with basicranial invasion were the influencing factors of the patients' poor prognosis. This study provides a scientific basis for increasing the NPC patients' end-of-treatment response and promoting the individualized clinical treatment.

  11. 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

  12. Revalidation of a prognostic score model based on complete blood count for nasopharyngeal carcinoma through a prospective study

    PubMed Central

    Li, Xiaohui; Chang, Hui; Tao, Yalan; Wang, Xiaohui; Gao, Jin; Zhang, Wenwen; Chen, Chen; Xia, Yunfei

    2016-01-01

    Objective In our previous work, we incorporated complete blood count (CBC) into TNM stage to develop a new prognostic score model, which was validated to improve prediction efficiency of TNM stage for nasopharyngeal carcinoma (NPC). The purpose of this study was to revalidate the accuracy of the model, and its superiority to TNM stage, through data from a prospective study. Methods CBC of 249 eligible patients from the 863 Program No. 2006AA02Z4B4 was evaluated. Prognostic index (PI) of each patient was calculated according to the score model. Then they were divided by the PI into three categories: the low-, intermediate-and high-risk patients. The 5-year disease-specific survival (DSS) of the three categories was compared by a log-rank test. The model and TNM stage (7th edition) were compared on efficiency for predicting the 5-year DSS, through comparison of the area under curve (AUC) of their receiver-operating characteristic curves. Results The 5-year DSS of the low-, intermediate-and high-risk patients were 96.0%, 79.1% and 62.2%, respectively. The low-and intermediate-risk patients had better DSS than the high-risk patients (P<0.001 and P<0.005, respectively). And there was a trend of better DSS in the low-risk patients, compared with the intermediate-risk patients (P=0.049). The AUC of the model was larger than that of TNM stage (0.726 vs. 0.661, P=0.023). Conclusions A CBC-based prognostic score model was revalidated to be accurate and superior to TNM stage on predicting 5-year DSS of NPC. PMID:27877005

  13. 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.

  14. Inhibition of store-operated Ca2+ entry counteracts the apoptosis of nasopharyngeal carcinoma cells induced by sodium butyrate

    PubMed Central

    Huang, Wei; Ren, Caiping; Huang, Guoling; Liu, Jie; Liu, Weidong; Wang, Lei; Zhu, Bin; Feng, Xiangling; Shi, Jia; Li, Jinlong; Xia, Xiaomeng; Jia, Wei; Chen, Jiawen; Chen, Yuxiang; Jiang, Xingjun

    2017-01-01

    Sodium butyrate (NaBu), a histone deacetylase inhibitor, has demonstrated anti-tumor effects in several cancers, and is a promising candidate chemotherapeutic agent. However, its roles in nasopharyngeal carcinoma (NPC), an endemic malignant disease in Southern China and Southeast Asia, has rarely been studied. In the present study, MTT assay, colony formation assay, flow cytometry analysis and western blotting were performed to explore the influence of NaBu on NPC cells and its underlying mechanism. NaBu induced morphological changes and inhibited proliferation in 5–8F and 6–10B cells. MTT assay revealed that NaBu was cytotoxic to 5–8F and 6–10B cells in a dose- and time-dependent manner. Furthermore, flow cytometry analysis revealed that NaBu induced obvious cell apoptosis in 5–8F and 6–10B cells due to the activation of the mitochondrial apoptosis axis. In addition, flow cytometry analysis and western blotting demonstrated that NaBu could enhance the Ca2+ influx by promoting store-operated Ca2+ entry (SOCE) in 5–8F and 6–10B cells. Inhibition of SOCE by specific inhibitors or downregulated expression of calcium release-activated calcium channel protein 1 and stromal interaction molecule 1 could counteract the apoptosis of NPC cells induced by NaBu. Thus, the current study revealed that enhanced SOCE and activated mitochondrial apoptosis axis may account for the mechanisms of cytotoxicity of NaBu in NPC cells, and that NaBu serves as a promising chemotherapeutic agent in NPC therapy. PMID:28356979

  15. High-Dose-Rate Intracavitary Brachytherapy Boost for Early T Stage Nasopharyngeal Carcinoma{l_brace}PRIVATE{r_brace}

    SciTech Connect

    Leung, T.-W. Wong, Victy Y.W.; Sze, W.-K.; Lui, Collin M.M.; Tung, Stewart Y.

    2008-02-01

    Purpose: To investigate any possible therapeutic gain from dose escalation with brachytherapy for early T stage nasopharyngeal carcinoma (NPC). Methods and Materials: One hundred forty-five patients with T1-2b N0-3 NPC were boosted with high-dose-rate intracavitary brachytherapy after completion of two-dimensional external radiotherapy (ERT) during the period from 1999 to 2003. To compare the efficacy of brachytherapy boost, another 142 patients with T1-2b N0-3 disease who were treated with ERT alone during 1994 to 1999 were evaluated. All patients were treated with ERT to a total dose of 66 Gy in 6.5 weeks. The brachytherapy boost group was given 10-12 Gy in 2 weekly fractions. Results: Dose escalation beyond 66 Gy with brachytherapy boost was shown to improve local control and survival. The 5-year actuarial local failure-free survival, regional failure-free survival, distant metastasis-free survival, progression-free survival, cancer-specific survival, and overall survival rates for the brachytherapy group and the control group were 95.8% and 88.3% (p = 0.020), 96% and 94.6% (p = 0.40), 95% and 83.2% (p = 0.0045), 89.2% and 74.8% (p = 0.0021), 94.5% and 83.4% (p = 0.0058), and 91.1% and 79.6% (p = 0.0062), respectively. The 5-year major-complication-free survival rate was 89.5% for the brachytherapy group and 85.6% for the control group (p = 0.23). Conclusions: For patients who are treated with two-dimensional treatment techniques, dose escalation with brachytherapy boost improves local control and overall survival of patients with T1-T2a and possibly non-bulky T2b disease.

  16. 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

  17. Selaginella tamariscina extract suppresses TPA-induced invasion and metastasis through inhibition of MMP-9 in human nasopharyngeal carcinoma HONE-1 cells

    PubMed Central

    2013-01-01

    Background Nasopharyngeal carcinoma (NPC) is known for its high incidence of neck lymph node metastasis, which represents poor prognosis. The present study aimed to examine the anti-metastatic properties of Selaginella tamariscina extract (STE) in human nasopharyngeal carcinoma HONE-1 cells in vitro. Methods Cell viability was examined by MTT assay, whereas cell motility was measured by invasive, migration and would healing assays. Real-time PCR, and promoter assays confirmed the inhibitory effects of STE on matrix metalloproteinase-9 (MMP-9) mRNA level in HONE-1 cells. Results The STE inhibits 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced HONE-1 cell migration and invasion in a concentration-dependent manner. By zymographic and Western blot analyses, STE was shown to inhibit the activities and expression of MMP-9. Treatment of STE on TPA-induced HONE-1 cells inhibited MMP-9 expression and ERK1/2 phosphorylation without affecting JNK and p38 phosphorylation. Conclusions STE inhibits MMP-9 expression and HONE-1 cell metastasis. Its inhibitory effects may involve the Src/FAK/ERK 1/2 pathway. STE may have the potential of being an anti-metastatic agent against NPC. PMID:24053256

  18. Folate-targeted star-shaped cationic copolymer co-delivering docetaxel and MMP-9 siRNA for nasopharyngeal carcinoma therapy

    PubMed Central

    Liu, Tao; Wu, Xidong; Wang, Yigang; Zhang, Tao; Wu, Ting; Liu, Fang; Wang, Wansong; Jiang, Gang; Xie, Minqiang

    2016-01-01

    The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate-modified star-shaped copolymer (FA-CD-PLLD) consisting of β-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP-9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vitro and in vivo assays are carried out to confirm the effectiveness of the target strategy and combined treatment. It was found that the conjugation of CD-PLLD with FA could enhance the DOC/MMP-9 delivery effect obviously, inducing a more significant apoptosis and decreasing invasive capacity of HEN-1 cells. In vivo assays showed that FA-CD-PLLD/DOC/MMP-9 could inhibit HNE-1 tumor growth and decrease PCNA expression effectively, indicating a promising strategy for nasopharyngeal carcinoma therapy. Moreover, the in vivo distribution of DOC and MMP-9, blood compatibility and toxicity are also explored. PMID:27259274

  19. 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.

  20. Nasopharyngeal culture

    MedlinePlus

    Culture - nasopharyngeal; Swab for respiratory viruses; Swab for staph carriage ... The test identifies viruses and bacteria that cause upper respiratory ... Staphylococcus aureus Methicillin-resistant Staphylococcus ...

  1. Sequence analysis of EBV immune evasion gene BNLF2a in EBV associated tumors and healthy individuals from nasopharyngeal carcinoma endemic and non-endemic regions of China.

    PubMed

    Liu, Song; Wang, Xiaofeng; Shu, Jun; Zhao, Zhenzhen; Sun, Zhifu; Luo, Bing

    2015-11-01

    BNLF2a is an Epstein-Barr virus (EBV) immune evasion gene. Its protein is located in the endoplasmic reticulum (ER) membrane, and can inhibit the antigen transporting function of TAP, thereby perturbing the immune response to EBV in lytic and prelatent phase. In order to explore whether the polymorphism of BNLF2a gene has a role in different types of EBV associated tumors, we conducted complete sequencing of the gene BNLF2a in 408 cases of EBV positive tumors (76 lymphomas, 45 gastric carcinomas, and 85 nasopharyngeal carcinomas in northern China and 27 lymphomas, 30 gastric carcinomas, and 57 nasopharyngeal carcinomas in southern China) and throat washings from healthy individuals (39 in northern China and 49 in southern China). Two main variant types of BNLF2a were identified. Type BNLF2a-A, which was similar to B95-8, was dominant in all sub-populations (66.7-100%) in this study. Type BNLF2a-B was characterized by the mutations at position 8 and 40. The variation patterns of BNLF2a were significantly different between samples from northern and southern China (P < 0.05), and between the tumors and healthy donor samples from the northern China (P < 0.0167). Type BNLF2a-B was more frequent in healthy donors of northern China (33.3%), and the proportion of this type was higher in the northern than in the southern NPCs. These data demonstrate that the BNLF2a gene is highly conserved, and its polymorphism is geographically restricted. Type BNLF2a-B is more prevalent in northern China and may be less tumor transformative.

  2. Induction chemotherapy for the treatment of non-endemic locally advanced nasopharyngeal carcinoma

    PubMed Central

    Zhao, Lina; Xu, Man; Jiang, Wen; Pan, Haitao; Zang, Jian; Luo, Shanquan; Wang, Jianhua; Zhou, Yongchun; Shi, Mei

    2017-01-01

    Background The role of induction chemotherapy is less clear in non-endemic locally advanced nanopharyngeal carcinomas (NPC). Results With a total of 233 eligible patients and a median follow-up of 36 months, 3-year overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease free survival (DFS) were 84.5%, 94.9%, 78.6% and 69.2%, respectively. The overall failure rate was 21.0% and distant metastasis occurred in 17.2% patients. Multivariate analyses showed that retropharyngeal and bilateral neck lymph node metastasis were significant prognostic factors for DFS and OS. Moreover, patients receiving both GP (gemcitabine+cisplatin) and TP (docetaxel+cisplatin) regimes had significantly higher DFS and OS compared with PF (cisplatin+5-FU) regime. GP regimes lead to significantly improved OS than TP/PF in some subgroup of patients. No severe toxicities were observed. Materials and Methods We retrospectively analyzed stage III-IVb NPC patients treated between Jan 2006 and Dec 2014, with induction chemotherapy followed by concurrent chemoradiation (IC-CCRT). Statistical analyses were performed on survival and failure patterns. Conclusions These results suggested IC-CCRT was safe and effective for NPCs from non-endemic region. The choice of induction regimen appeared to affect patient outcomes. PMID:28036270

  3. 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.

  4. An elective radiation dose of 46 Gy is feasible in nasopharyngeal carcinoma treated by intensity-modulated radiotherapy

    PubMed Central

    Hung, Tsung-Min; Fan, Kang-Hsing; Chen, Eric Yen-Chao; Lin, Chien-Yu; Kang, Chung-Jan; Huang, Shiang-Fu; Liao, Chun-Ta; Ng, Shu-Hang; Wang, Hung-Ming; Chang, Joseph Tung-Chieh

    2017-01-01

    Abstract The purpose of this study is to compare the treatment outcome of different radiation doses of elective neck irradiation (ENI) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). In total, 504 patients with nondisseminated NPC who underwent magnetic resonance imaging before radical IMRT between 2000 and 2008 were retrospectively reviewed. The patients were classified into 2 groups based on the ENI dose: low ENI when the ENI dose was 46 Gy (n = 446) and high ENI when the ENI doses were 50 to 60 Gy (n = 58). All the patients in both the groups received a median dose of 72 Gy to the gross tumor and involved nodes. The fraction size was 2 Gy per fraction. Matching was performed between low ENI and high ENI in a 2:1 ratio, and the matching criteria were N-stage, T-stage, treatment modality, pathology classification, sex, and age. The median follow-up for all patients was 63.5 months. In all patients, the 5-year progression-free survival (PFS), local control (LC), regional control (RC), distant metastasis-free survival (DMFS), overall survival (OS), and cancer-specific survival (CSS) for low ENI and high ENI patients were 69.0% and 63.2% (P = 0.331), 89.0% and 83.9% (P = 0.235), 90.1% and 85.2% (P = 0.246), 86.8% and 76.6% (P = 0.056), 77.5% and 80.8% (P = 0.926), and 84.4% and 82.5% (P = 0.237), respectively. In the matched-pair analysis, the 5-year PFS, LC, RC, DMFS, OS, and CSS for matched low ENI and high ENI patients were 74.1% and 63.2% (P = 0.134), 92.0% and 83.9% (P = 0.152), 90.1% and 85.2% (P = 0.356), 86.2% and 76.6% (P = 0.125), 87.0% and 80.8% (P = 0.102), and 88.6% and 82.5% (P = 0.080), respectively. In the multivariable analysis for all patients, the ENI group was not a significant factor for PFS, LC, RC, DMFS, OS, and CSS. A low ENI dose of 46 Gy in 23 fractions is feasible in NPC patients treated with IMRT, and this concept should be validated in

  5. The clinical characteristics of secondary primary tumors in patients with nasopharyngeal carcinoma after intensity-modulated radiotherapy

    PubMed Central

    Zhao, Wei; Lei, Hao; Zhu, Xiaodong; Li, Ling; Qu, Song; Liang, Xia; Wang, Xiao

    2016-01-01

    Abstract To investigate the clinical characteristics associated with the risk of developing secondary primary tumors (SPTs) in patients with nasopharyngeal carcinoma (NPC) who underwent intensity-modulated radiotherapy (IMRT). Data from 527 patients with biopsy-proven nonmetastatic NPC who were treated with IMRT between January 2007 and December 2011 were analyzed retrospectively. The cumulative incidence of SPTs after IMRT completion was estimated using the Kaplan–Meier method. Intergroup differences in the cumulative incidence were determined using the log-rank test. The Cox proportional hazards regression model was used to confirm the risk factors associated with IMRT-induced SPTs. The median follow-up duration was 45.5 months (range, 4–97 months). Of the 527 patients, 12 (2.3%) developed posttreatment SPTs (9 men, 3 women), 6 of which were located in the irradiation field. SPTs were mostly located in the upper aerodigestive tract (n = 7), head and neck (n = 6), lungs (n = 3), and tongue (n = 2). The 1-, 3-, and 5-year cumulative SPT risk rates were 0.4%, 1.4%, and 3.1%, respectively, and the mean annual growth in cumulative incidence was approximately 0.6%. The 1-, 3-, and 5-year cumulative in-field SPT risk rates were 0.4%, 0.8%, and 1.5%, respectively, and the mean annual growth in the in-field cumulative incidence was approximately 0.3%. Univariate and multivariate analysis revealed that sex, age, clinical stage, chemotherapy, and overall IMRT duration did not significantly affect SPT risk. However, the history of smoking was the independent risk factor associated with SPT. The 5-year SPT incidence among patients with NPC after IMRT is concordant with or lower than that in previous 2-dimensional radiotherapy studies study. Among patients with NPC who underwent IMRT, the upper aerodigestive tract was the most common SPT site, and lung cancer was the most common pathology. Smoking history, but not sex, age, clinical stage, chemotherapy, and

  6. 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

  7. Does MRI-detected cranial nerve involvement affect the prognosis of locally advanced nasopharyngeal carcinoma treated with intensity modulated radiotherapy?

    PubMed

    Zong, Jingfeng; Lin, Shaojun; Chen, Yunbin; Wang, Bingyi; Xiao, Youping; Lin, Jin; Li, Rui; Pan, Jianji

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is one of the common cancers in South China. It can easily invade into cranial nerves, especially in patients with local advanced disease. Despite the fact that the magnetic resonance imaging (MRI) findings are not always consistent with the symptoms of CN palsy, MRI is recommended for the detection of CN involvement (CNI). However, the prognostic impact of MRI-detected CNI in NPC patients is still controversial. To investigate the prognostic value of MRI detected CNI, we performed a retrospective analysis on the clinical data of 375 patients with NPC who were initially diagnosed by MRI. All patients had T3-4 disease and received radical intensity modulated radiation therapy (IMRT) as their primary treatment. The incidence of MRI-detected CNI was 60.8%. A higher incidence of MRI-detected CNI was observed in T4 disease compared with T3 disease (96.8% vs. 42.8%, P<0.001), and a higher incidence was also found in patients with Stage IV disease compared with those with Stage III disease (91.5% vs. 42.3%; P<0.001). The local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) of patients with T3 disease, with or without MRI-detected CNI, was superior to that of patients with T4 disease (P<0.05). No significant differences in LRFS, DMFS or OS were observed between T3 patients with or without MRI-detected CNI. The survival of Stage III patients with or without MRI-detected CNI was significantly superior to that of Stage IV patients (P<0.01), but there was no significant difference between Stage III patients with or without MRI-detected CNI for all endpoints. Therefore, when treated with IMRT, MRI-detected CNI in patients with NPC does not appear to affect the prognosis. In patients with clinical T3 disease, the presence of MRI-detected CNI is not sufficient evidence for defining T4 disease.

  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. Blood cadmium burden and the risk of nasopharyngeal carcinoma: a case-control study in Chinese Chaoshan population.

    PubMed

    Peng, Lin; Wang, Xiaoling; Huo, Xia; Xu, Xijin; Lin, Kun; Zhang, Jingwen; Huang, Yue; Wu, Kusheng

    2015-08-01

    Cadmium is a ubiquitous carcinogenic pollutant with multiple biological effects. Both observational and experimental studies have suggested associations between cadmium and the rates of many types of cancers. The aim of the present study was to evaluate whether cadmium exposure is associated with nasopharyngeal carcinoma (NPC) in a population with a relatively high prevalence in southeast China. Hospital-based 134 NPC cases and 132 cancer-free controls were recruited from a cancer hospital in Chaoshan area, southeast of China. Basic clinical data and information of lifetime styles, smoking, and drinking as well as other demographic characteristics were also collected from medical records. Blood cadmium levels (BCLs) were detected by graphite-furnace atomizer absorption spectrophotometer (GFAAS). BCLs and over-limit ratios between cases and controls were compared. The relationships between BCLs and NPC were explored by comparing BCLs differences between/among different characteristics of related factors and logistic regression analysis. In addition, BCLs within cases were also compared in relation to the disease clinical stages, pathological types, and metastasis. The median concentration of blood cadmium in cases (3.84, interquartile range 2.21-6.10) was significantly higher than that of controls (2.28, interquartile range 1.79-3.45). The over-limit ratio (≥5 μg/L) in cases was also higher than that in controls (35.1 vs. 13.6%, χ(2) = 16.55, p < 0.001). Smokers tended to have high levels of cadmium burden, and smokers with longer smoking pack-years in cases had relatively higher BCLs (p = 0.001). NPC patients with diseases history presented lower cadmium burden (p = 0.020). In the NPC cases, BCLs were positively associated with clinical stages and N classification (r = 0.193, 0.187, respectively, p < 0.05). Cadmium seems to be a risk factor of NPC, and high cadmium exposure may promote the occurrence and development of NPC.

  10. Psychological Disorders, Cognitive Dysfunction and Quality of Life in Nasopharyngeal Carcinoma Patients with Radiation-Induced Brain Injury

    PubMed Central

    Tang, Yamei; Luo, Donghua; Rong, Xiaoming; Shi, Xiaolei; Peng, Ying

    2012-01-01

    Purpose To evaluate factors affecting psychology, cognitive function and quality of life (QOL) of nasopharyngeal carcinoma (NPC) patients with radiation-induced brain injury (RI). Methods and Materials 46 recurrence-free NPC patients with RI and 46 matched control patients without RI were recruited in our study. Subjective and objective symptoms of RI were evaluated with the LENT/SOMA systems. Psychological assessment was measured with Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). Montreal Cognitive Assessment (MoCA) was carried out in these patients for assessing their cognitive function. QOL was evaluated by means of WHOQOL BREF. Results Of the patients with RI, 39(84.8%) had depression and 40(87.0%) had anxiety. The patients with RI got higher scores both in SDS and SAS than those without RI (SDS, 63.48±8.11vs. 58.67±7.52, p = 0.008; SAS, 67.36±10.41vs. 60.34±9.76, p = 0.005). Score in MoCA of patients with RI was significantly lower than that of patients without RI (21.32±2.45vs. 25.98±1.73, p<0.001). SAS was positive correlated with post-radiotherapy interval. Both SAS and SDS had a significantly positive correlation with the rank of SOMA, while MoCA had a significantly negative correlation with SOMA. Chemotherapy was a risk factor for cognitive dysfunction. In addition, patients with RI got significantly lower scores in physical health (16.50±11.05 vs. 35.02±10.43, p<0.001), psychological health (17.70±10.33 vs. 39.48±12.00, p<0.001) and social relationship (48.00±18.65 vs. 67.15±19.70, p<0.001) compared with those in patients without RI. Multiple linear regression analysis revealed that anxiety and cognitive impairment were significant predictors of global QOL. Conclusions NPC patients with RI exhibit negative emotions, impaired cognitive function and QOL. The severity of clinical symptoms of RI plays an important role in both emotions and cognitive function. Anxiety and cognitive impairment are associated with

  11. 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

  12. Chemoradiotherapy Versus Radiotherapy Alone in Stage II Nasopharyngeal Carcinoma: A Systemic Review and Meta-analysis of 2138 Patients

    PubMed Central

    Xu, Cheng; Zhang, Li-He; Chen, Yu-Pei; Liu, Xu; Zhou, Guan-Qun; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2017-01-01

    Background: To explore the value of chemoradiotherapy (CRT) in stage II nasopharyngeal carcinoma (NPC) compared to radiotherapy (RT) alone which includes two-dimensional radiotherapy (2D-RT) and intensity-modulated radiotherapy (IMRT). Methods:All topic-related comparative articles were identified by a comprehensive search of public databases (MEDLINE, EMBASE, Cochrane Library and CBMdisc). The primary outcomes were overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS). Secondary outcomes were grade 3-4 acute toxicity events. We performed subgroup analysis of CRT versus 2D-RT/IMRT alone to investigate the optimal modality. Sensitivity analysis focused on CRT versus IMRT alone was used to assess stability of the study results. Results:Eleven comparative studies (2138 patients) were eligible. CRT had significantly higher OS (HR = 0.67, 95% CI = 0.45-0.98, P = 0.04) and LRRFS (HR = 0.61, 95% CI = 0.46-0.80, P = 0.0003) than RT alone, but no significant difference was observed in DMFS (HR = 0.83, 95% CI = 0.52-1.31, P = 0.41). Meanwhile, CRT was associated with higher frequencies of grade 3-4 leukopenia, mucositis and nausea (P = 0.005, 0.03, < 0.0001, respectively). Subgroup analysis showed that IMRT alone could achieve equivalent OS, LRRFS and DMFS compared to CRT (P = 0.14, 0.06, 0.89, respectively). Significant value was only observed in LRRFS for CRT compared to 2D-RT alone (P = 0.01). Sensitivity analysis for the comparison of CRT and IMRT alone demonstrated generally stable outcomes, in support of the final conclusions. Conclusions:In the treatment of patients with stage II NPC, CRT was better than 2D-RT alone with significant benefit in LRRFS. IMRT alone was superior to CRT with equivalent survival outcomes and fewer grade 3-4 acute toxicities. PMID:28243333

  13. 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.

  14. High expression of Zinc-finger protein X-linked is associated with reduced E-cadherin expression and unfavorable prognosis in nasopharyngeal carcinoma.

    PubMed

    Li, Yin; Yan, Xuebing; Yan, Leilei; Shan, Zezhi; Liu, Sihong; Chen, Xiaojuan; Zou, Jianyin; Zhang, Weitian; Jin, Zhiming

    2015-01-01

    Zinc-finger protein X-linked (ZFX), a novel transcription factor required for self-renewal of embryonic stem cells, has recently been implicated in the initiation and progression of various human malignancies. However, its clinical significance in cancer patients remains largely inconclusive and its role in nasopharyngeal carcinoma (NPC) has never been reported. In this study, quantitative real-time polymerase chain reaction, Western blot and Immunohistochemistry were performed to detect ZFX expression in NPC and normal nasopharyngeal tissues. As a result, we found ZFX expression was significantly elevated in NPC tissues compared with that in normal nasopharyngeal tissues. The statistical analysis based on immunohistochemical staining demonstrated that ZFX expression was significantly correlated with lymph node stage and clinical stage. Furthermore, we found NPC patients with high ZFX expression had lower 5-year overall survival rates, progression-free survival rates, loco-regional relapse-free survival rates and distant metastasis-free survival rates than those with low ZFX expression (all P<0.05). The multivariate analysis indicated that ZFX expression was an independent prognostic factor for patients with NPC. More importantly, we also detected E-cadherin expression in NPC tissues and found it was inversely correlated with ZFX expression in NPC tissues, suggesting a potential involvement of ZFX in Epithelial-mesenchymal transition (EMT). Therefore, it is speculated that ZFX may promote NPC progression partly by regulating EMT. In summary, our study not only for the first time identified that ZFX could serve as an effective prognostic biomarker for NPC patients, but also suggested that targeting ZFX might be a novel therapeutic strategy for preventing NPC progression and metastasis.

  15. Human Ribosomal Proteins RPeL27, RPeL43, and RPeL41 Are Upregulated in Nasopharyngeal Carcinoma Cell Lines

    PubMed Central

    Ng, Kher-Lee

    2016-01-01

    Apart from their canonical role in ribosome biogenesis, there is increasing evidence of ribosomal protein genes' involvement in various cancers. A previous study by us revealed significant differential expression of three ribosomal protein genes (RPeL27, RPeL41, and RPeL43) between cell lines derived from tumor and normal nasopharyngeal epithelium. However, the results therein were based on a semiquantitative assay, thus preliminary in nature. Herein, we provide findings of a deeper analysis of these three genes in the context to nasopharyngeal carcinoma (NPC) tumorigenesis. Their expression patterns were analyzed in a more quantitative manner at transcript level. Their protein expression levels were also investigated. We showed results that are contrary to previous report. Rather than downregulation, these genes were significantly overexpressed in NPC cell lines compared to normal control at both transcript and protein levels. Nevertheless, their association with NPC has been established. Immunoprecipitation pulldown assays indicate the plausible interaction of either RPeL27 or RPeL43 with POTEE/TUBA1A and ACTB/ACTBL2 complexes. In addition, RPeL43 is shown to bind with MRAS and EIF2S1 proteins in a NPC cell line (HK1). Our findings support RPeL27, RPeL41, and RPeL43 as potential markers of NPC and provide insights into the interaction targets of RPeL27 and RPeL43 proteins. PMID:28018022

  16. Genetic polymorphisms of Wnt/β-catenin pathway genes are associated with the efficacy and toxicities of radiotherapy in patients with nasopharyngeal carcinoma

    PubMed Central

    Yu, Jingjing; Huang, Yuling; Liu, Lijuan; Wang, Jing; Yin, Jiye; Huang, Lihua; Chen, Shaojun; Li, Jingao; Yuan, Hong; Yang, Guoping; Liu, Wenyu; Wang, Hai; Pei, Qi; Guo, Chengxian

    2016-01-01

    Radiotherapy (RT) is the normative therapeutic treatment for primary nasopharyngeal carcinoma (NPC). Single nucleotide polymorphisms (SNPs) of genes in Wnt/β-catenin pathway are correlated to the development, prognosis, and treatment benefit of various cancers. However, it has not been established whether SNPs of Wnt/β-catenin pathway are associated with nasopharyngeal tumorigenesis and the efficacy of RT in NPC patients. Therefore, in this study, we aimed to investigate the nine potentially functional SNPs of four genes in the Wnt/β-catenin pathway and genotyped these in 188 NPC patients treated with RT. To achieve this goal, associations between these SNPs and the RT's curative efficacy, as well as acute radiation-induced toxic reaction were determined by multifactorial logistic regression. We observed that catenin beta 1 gene (CTNNB1) rs1880481 and rs3864004, and glycogen synthase kinase 3 beta gene (GSK3β) rs3755557 polymorphisms were significantly associated with poorer efficacy of RT in NPC patients. Moreover, GSK3β rs375557 and adenomatous polyposis coli gene (APC) rs454886 polymorphisms were correlated with acute grade 3–4 radiation-induced dermatitis and oral mucositis, respectively. In conclusion, this study suggests that gene polymorphisms of Wnt/β-catenin may be novel prognostic factors for NPC patients treated with RT. PMID:27769064

  17. Expression of EBV antibody EA-IgA, Rta-IgG and VCA-IgA and SA in serum and the implication of combined assay in nasopharyngeal carcinoma diagnosis.

    PubMed

    Xia, Cui; Zhu, Kang; Zheng, Guoxi

    2015-01-01

    Epstein-Barr virus (EBV) is an important non-invasive index for nasopharyngeal carcinoma. Serum sialic acid (SA) level was known to be related with tumor progression. Rta protein antibody IgG (Rta-IgG), early antigen antibody (EA-IgA) and viral capsid antibody (VCA-IgA) levels in serum can also be used to effectively monitor the progression of cancer. This study investigated serum level of SA, Rta-IgG, EA-IgA and VCA-IgA in nasopharyngeal cancer patients and the diagnostic value of combined assay. A total of 64 nasopharyngeal cancer patients were recruited, in parallel with 60 benign rhinitis and 60 healthy individuals. Serum SA, EA-IgA, Rta-IgG and VCA-IgA levels were measured by enzyme-linked immunosorbent assay (ELISA). The diagnostic value of these indexes was further evaluated by ROC curve analysis. Logistic regression model was used to analyze the diagnostic implication of combined assay. The expression levels of SA, EA-IgA, Rta-IgG, and VCA-IgA were highest in nasopharyngeal cancer patients. Those indexes were also increased with advanced TNM stage of cancer. The overall diagnostic efficacy was ranked as: VCA-IgA, Rta-IgA, EA-IgA and SA. The combined diagnosis increased the sensitivity to 98.44% and the negative predictive value to 99.03%, without compromising specificity. SA, EA-IgA, Rta-IgG and VCA-IgA expression levels were elevated in nasopharyngeal patients. The combined diagnosis of those serum indexes may improve the diagnostic efficacy of nasopharyngeal carcinoma.

  18. Expression of Epstein-Barr virus antibodies EA-IgG, Rta-IgG, and VCA-IgA in nasopharyngeal carcinoma and their use in a combined diagnostic assay.

    PubMed

    Li, Y; Wang, K; Yin, S K; Zheng, H L; Min, D L

    2016-03-18

    Epstein-Barr virus (EBV) infection is closely associated with nasopharyngeal carcinoma, which can be monitored by the levels of Rta protein antibody IgG (Rta-IgG), early antigen antibody (EA-IgG), and viral capsid antibody (VCA-IgA). In the present study, we investigated the serum levels of Rta-IgG, EA-IgG, and VCA-IgA in nasopharyngeal cancer patients, and the diagnostic value of a combined assay that includes these antibodies in addition to the EBV-DNA. A total of 56 nasopharyngeal cancer patients were recruited as the study population, along with 48 benign rhinitis patients and 42 healthy individuals. Serum EA-IgG, Rta-IgG, and VCA-IgA levels were measured by enzyme-linked immunosorbent assay, and EBV-DNA was quantified with PCR. The diagnostic value of these indices was further evaluated by ROC curve analysis. The expression levels of EA-IgG, Rta-IgG, VCA-IgA, and EBV-DNA were elevated in the nasopharyngeal cancer patients, who had higher levels of these antibodies than those in the rhinitis patients, followed by the healthy individuals. These indices were also increased with advanced TNM stage. The overall diagnostic efficacy was ranked as follows: VCA-IgA, Rta-IgA, EA-IgA, and EBV-DNA. The combined diagnosis using these four indices increased the sensitivity to 98.21% and the negative predictive value to 98.61%, without any significant compromise on the test specificity. In conclusion, EA-IgG, Rta-IgG, VCA-IgA, and EBV-DNA expression levels were elevated in nasopharyngeal patients. The combined diagnostic value of these serum indices has important implications in nasopharyngeal carcinoma.

  19. Novel roles and therapeutic targets of Epstein-Barr virus-encoded latent membrane protein 1-induced oncogenesis in nasopharyngeal carcinoma.

    PubMed

    Tao, Yongguang; Shi, Ying; Jia, Jiantao; Jiang, Yiqun; Yang, Lifang; Cao, Ya

    2015-08-18

    Epstein-Barr virus (EBV) was first discovered 50 years ago as an oncogenic gamma-1 herpesvirus and infects more than 90% of the worldwide adult population. Nasopharyngeal carcinoma (NPC) poses a serious health problem in southern China and is one of the most common cancers among the Chinese. There is now strong evidence supporting a role for EBV in the pathogenesis of NPC. Latent membrane protein 1 (LMP1), a primary oncoprotein encoded by EBV, alters several functional and oncogenic properties, including transformation, cell death and survival in epithelial cells in NPC. LMP1 may increase protein modification, such as phosphorylation, and initiate aberrant signalling via derailed activation of host adaptor molecules and transcription factors. Here, we summarise the novel features of different domains of LMP1 and several new LMP1-mediated signalling pathways in NPC. When then focus on the potential roles of LMP1 in cancer stem cells, metabolism reprogramming, epigenetic modifications and therapy strategies in NPC.

  20. SU-E-T-808: Volumetric Modulated Arc Radiotherapy Vs. Intensity-Modulated Radiotherapy for Early-Stage Nasopharyngeal Carcinoma: A Dosimetric Study

    SciTech Connect

    Lu, J-Y; Huang, B-T; Zhang, W-Z

    2015-06-15

    Purpose: To compare volumetric modulated arc radiotherapy (VMAT) technique with fixed-gantry intensity-modulated radiotherapy (IMRT) technique for early-stage nasopharyngeal carcinoma. Methods: CT datasets of ten patients with early-stage nasopharyngeal carcinoma were included. Dual-arc VMAT and nine-field IMRT plans were generated for each case, and were then compared in terms of planning-target-volume (PTV) coverage, conformity index (CI) and homogeneity index (HI), as well as organ-at-risk (OAR) sparing, planning time, monitor units (MUs) and delivery time. Results: Compared with the IMRT plans, the VMAT plans provided comparable HI and CI of PTVnx (PTV of primary tumor of nasopharynx), superior CI and inferior HI of PTVnd (PTV of lymph nodes), as well as superior CI and comparable HI of PTV60 (high-risk PTV). The VMAT plans provided better sparing of the spinal cord, oral cavity and normal tissue, but inferior sparing of the brainstem planning OAR volume (PRV), larynx and parotids, as well as comparable sparing of the spinal cord PRV, brainstem, lenses, optic nerves, optic chiasm. Moreover, the average planning time (181.6 ± 36.0 min) for the VMAT plans was 171% more than that of the IMRT plans (68.1 ± 7.6 min). The MUs of the VMAT plans (609 ± 43) were 70% lower than those of the IMRT plans (2071 ± 262), while the average delivery time (2.2 ± 0.1 min) was 66% less than that of the IMRT plans (6.6 ± 0.4 min). Conclusion: Compared with the IMRT technique, the VMAT technique can achieve similar or slightly superior target dose distribution, with no significant advantages on OAR sparing, and it can achieve significant reductions of MUs and delivery time.

  1. Adding Maximum Standard Uptake Value of Primary Lesion and Lymph Nodes in 18F-Fluorodeoxyglucose PET Helps Predict Distant Metastasis in Patients with Nasopharyngeal Carcinoma

    PubMed Central

    Zhang, Yingjian; Hu, Chaosu

    2014-01-01

    Objective To find out the most valuable parameter of 18F-Fluorodeoxyglucose positron emission tomography for predicting distant metastasis in nasopharyngeal carcinoma. Methods From June 2007 through December 2010, 43 non-metastatic NPC patients who underwent 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) before radical Intensity-Modulated Radiation Therapy were enrolled and reviewed retrospectively. PET parameters including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glucose (TLG) of both primary tumor and cervical lymph nodes were calculated. Total SUVmax were recorded as the sum of SUVmax of primary tumor and cervical lymph nodes. Total SUVmean, Total MTV and Total TLG were calculated in the same way as Total SUVmax. Results The median follow-up was 32 months (range, 23–68 months). Distant metastasis was the main pattern of treatment failure. Univariate analysis showed higher SUVmax, SUVmean, MTV, and TLG of primary tumor, Total SUVmax, Total MTV, Total TLG, and stage T3-4 were factors predicting for significantly poorer distant metastasis-free survival (p = 0.042, p = 0.008, p = 0.023, p = 0.023, p = 0.024, p = 0.033, p = 0.016, p = 0.015). In multivariate analysis, Total SUVmax was the independent predictive factor for distant metastasis (p = 0.046). Spearman Rank correlation analysis showed mediate to strong correlationship between Total SUVmax and SUVmax-T, and between Total SUVmax and SUVmax-N(Spearman coefficient:0.568 and 0.834;p = 0.000 and p = 0.000). Conclusions Preliminary results indicated that Total SUVmax was an independently predictive factor for distant metastasis in patients of nasopharyngeal carcinoma treated with Intensity-Modulated Radiation Therapy. PMID:25068373

  2. Tetrandrine Induces Apoptosis of Human Nasopharyngeal Carcinoma NPC-TW 076 Cells through Reactive Oxygen Species Accompanied by an Endoplasmic Reticulum Stress Signaling Pathway.

    PubMed

    Lin, Ya-Jing; Peng, Shu-Fen; Lin, Meng-Liang; Kuo, Chao-Lin; Lu, Kung-Wen; Liao, Ching-Lung; Ma, Yi-Shih; Chueh, Fu-Shin; Liu, Kuo-Ching; Yu, Fu-Shun; Chung, Jing-Gung

    2016-10-12

    Nasopharyngeal carcinoma (NPC) is an epithelial malignancy of the head and neck and the incidence is higher in Southeast Asia. Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid, a natural product, and exhibits biological activities including action against many human cancer cell lines. However, the molecular mechanism of TET-induced cell apoptosis in human NPC cells is still unclear. In the present study, we investigated TET-induced apoptotic cell death and associated possible signal pathways on human nasopharyngeal carcinoma NPC-TW 076 cells in vitro. Phase contrast microscopy was used to examine cell morphology and DAPI staining was used to examine chromatin condensation. Flow cytometry assay was used to measure total viable cells, cell cycle and sub-G₁ phase distribution, reactive oxygen species (ROS), Ca(2+), and mitochondria membrane potential (ΔΨm) in NPC-TW 076 cells. Results indicate that TET induced cell death through the cell morphological changes, caused G₀/G₁ phase arrest, increased ROS and Ca(2+) production, and finally caused apoptotic cell death in NPC-TW 076 cells. There was no influence on the level of ΔΨm after TET treatment. Western blotting indicated that TET increased endoplasmic reticulum (ER) stress associated protein expression such as GADD153, GRP78, ATF-6α and ATF-6 βwhich indicated that TET induced cell death through ER stress. ER stress is a potential target in cancer treatment, so the ability of TET to induce ER stress response and to activate programming cell death in NPC-TW 076 cells make this molecule become a promising anticancer agent.

  3. TGFβR2 is a major target of miR-93 in nasopharyngeal carcinoma aggressiveness

    PubMed Central

    2014-01-01

    Background MiR-17-92 cluster and its paralogues have emerged as crucial regulators of many oncogenes and tumor suppressors. Transforming growth factor-β receptor II (TGFβR2), as an important tumor suppressor, is involved in various cancer types. However, it is in cancer that only two miRNAs of this cluster and its paralogues have been reported so far to regulate TGFβR2. MiR-93 is oncogenic, but its targetome in cancer has not been fully defined. The role of miR-93 in nasopharyngeal carcinoma (NPC) still remains largely unknown. Methods We firstly evaluated the clinical signature of TGFβR2 down-regulation in clinical samples, and next used a miRNA expression profiling analysis followed by multi-validations, including Luciferase reporter assay, to identify miRNAs targeting TGFβR2 in NPC. In vitro and in vivo studies were performed to further investigate the effects of miRNA-mediated TGFβR2 down-regulation on NPC aggressiveness. Finally, mechanism studies were conducted to explore the associated pathway and genes influenced by this miRNA-mediated TGFβR2 down-regulation. Results TGFβR2 was down-regulated in more than 50% of NPC patients. It is an unfavorable prognosis factor contributing to clinical NPC aggressiveness. A cluster set of 4 TGFβR2-associated miRNAs was identified; they are all from miR-17-92 cluster and its paralogues, of which miR-93 was one of the most significant miRNAs, directly targeting TGFβR2, promoting cell proliferation, invasion and metastasis in vitro and in vivo. Moreover, miR-93 resulted in the attenuation of Smad-dependent TGF-β signaling and the activation of PI3K/Akt pathway by suppressing TGFβR2, further promoting NPC cell uncontrolled growth, invasion, metastasis and EMT-like process. Impressively, the knockdown of TGFβR2 by siRNA displayed a consentaneous phenocopy with the effect of miR-93 in NPC cells, supporting TGFβR2 is a major target of miR-93. Our findings were also substantiated by investigation of the clinical

  4. 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

    2013-11-04

    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

  5. Circulating miR-17, miR-20a, miR-29c, and miR-223 Combined as Non-Invasive Biomarkers in Nasopharyngeal Carcinoma

    PubMed Central

    Zeng, Xi; Xiang, Juanjuan; Wu, Minghua; Xiong, Wei; Tang, Hailin; Deng, Min; Li, Xiayu; Liao, Qianjin; Su, Bo; Luo, Zhaohui; Zhou, Yanhong; Zhou, Ming; Zeng, Zhaoyang; Li, Xiaoling; Shen, Shourong; Shuai, Cijun; Li, Guiyuan; Fang, Jiasheng; Peng, Shuping

    2012-01-01

    Background MicroRNAs have been considered as a kind of potential novel biomarker for cancer detection due to their remarkable stability in the blood and the characteristics of their expression profile in many diseases. Methods We performed microarray-based serum miRNA profiling on the serum of twenty nasopharyngeal carcinoma patients at diagnosis along with 20 non-cancerous individuals as controls. This was followed by a real-time quantitative Polymerase Chain Reaction (RT-qPCR) in a separate cohort of thirty patients with nasopharyngeal carcinoma and thirty age- matched non-cancerous volunteers. A model for diagnosis was established by a conversion of mathematical calculation formula which has been validated by analyzing 74 cases of patients with nasopharyngeal carcinoma and 57 cases of non-cancerous volunteers. Results The profiles showed that 39 and 17 miRNAs are exclusively expressed in the serum of non-cancerous volunteers and of patients with nasopharyngeal carcinoma respectively. 4 miRNAs including miR-17, miR-20a, miR-29c, and miR-223 were found to be expressed differentially in the serum of NPC compared with that of non-cancerous control. Based on this, a diagnosis equation with Ct difference method has been established to distinguish NPC cases and non-cancerous controls and validated with high sensitivity and specificity. Conclusions We demonstrate that the serum miRNA-based biomarker model become a novel tool for NPC detection. The circulating 4-miRNA-based method may provide a novel strategy for NPC diagnosis. PMID:23056289

  6. FAMM Flap in Reconstructing Postsurgical Nasopharyngeal Airway Stenosis

    PubMed Central

    Nangole, Ferdinand Wanjala; Khainga, Stanley Ominde

    2014-01-01

    Introduction. Postsurgical nasopharyngeal airway stenosis can be a challenge to manage. The stenosis could be as a result of any surgical procedure in the nasopharyngeal region that heals extensive scarring and fibrosis. Objective. To evaluate patients with nasopharyngeal stenosis managed with FAMM flap. Study Design. Prospective study of patients with nasopharyngeal stenosis at the Kenyatta National Hospital between 2010 and 2013 managed with FAMM flap. Materials and Methods. Patients with severe nasopharyngeal airway stenosis were reviewed and managed with FAMM flaps at the Kenyatta National Hospital. Postoperatively they were assessed for symptomatic improvement in respiratory distress, patency of the nasopharyngeal airway, and donor site morbidity. Results. A total of 8 patients were managed by the authors in a duration of 4 years with nasopharyngeal stenosis. Five patients were managed with unilateral FAMM flaps in a two-staged surgical procedure. Four patients had complete relieve of the airway obstruction with a patent airway created. One patient had a patent airway created though with only mild improvement in airway obstruction. Conclusion. FAMM flap provides an alternative in the management of postsurgical severe nasopharyngeal stenosis. It is a reliable flap that is easy to raise and could provide adequate epithelium for the stenosed pharynx. PMID:25328699

  7. 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.

  8. Over-expression of the special AT rich sequence binding protein 1 (SATB1) promotes the progression of nasopharyngeal carcinoma: association with EBV LMP-1 expression

    PubMed Central

    2013-01-01

    Background Special AT rich sequence binding protein 1 (SATB1) plays a crucial role in the biology of various types of human cancer. However, the role of SATB1 in human nasopharyngeal carcinoma (NPC) remains unknown. In the present study, we sought to investigate the contribution of aberrant SATB1 expression in the progression of NPC and its association with the Epstein Barr virus (EBV)-encoded latent membrane protein 1 (LMP-1). Methods Immunohistochemical analysis was performed to detect SATB1 and LMP-1 protein in clinical samples, and the association of SATB1 protein expression with patient clinicopathological characteristics and LMP-1 expression were analyzed. SATB1 expression profiles were evaluated in well-differentiated NPC cell line CNE1, poorly-differentiated CNE2Z, undifferentiated C666-1 and immortalized nasopharyngeal epithelia NP-69 cells using quantitative RT-PCR, western blotting and fluorescent staining. After inhibition the SATB1 expression by using SATB1 specific small interfering RNA in these cell lines, the change of cell proliferation was investigated by western blotting analysis of PCNA (proliferating cell nuclear antigen) expression and CCK-8 assay, and the cell migration was assessed by Transwell migration assay. Finally, the expressions of SATB1 and PCNA were examined in CNE1 cells that forced LMP-1 expression by fluorescent staining and RT-PCR. Results Immunohistochemical analysis revealed that SATB1 protein expression was elevated in NPC tissues compared to benign nasopharyngeal tissues (P = 0.005). Moreover, high levels of SATB1 protein expression were positively correlated with clinical stage (P = 0.025), the status of lymph node metastasis (N classification) (P = 0.018), distant metastasis (M classification) (P = 0.041) and LMP-1 expression status (r = 2.35, P < 0.01) in NPC patients. In vitro experiments demonstrated that an inverse relationship between SATB1 expression and NPC differentiation status, with SATB1

  9. 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

  10. The Epstein-Barr Virus-encoded miR-BART22 targets MAP3K5 to promote host cell proliferative and invasive abilities in nasopharyngeal carcinoma

    PubMed Central

    Chen, Ruichao; Zhang, Minfeng; Li, Qiulian; Xiong, Hanzhen; Liu, Shaoyan; Fang, Weiyi; Zhang, Qianbing; Liu, Zhen; Xu, Xuehu; Jiang, Qingping

    2017-01-01

    miR-BART22, a new discovered Epstein-Barr virus (EBV) miRNA, is abundant in Nasopharyngeal carcinoma (NPC). It has been reported that miR-BART22 promoted the tumor development by down-modulating EBV LMP2 expression to evade the host immune response. But its cell target genes have still been obscure. We have reported an inverse correlation between the BART-22 and MAP3K5 protein expression in NPC tissues and NPC cell lines. Meanwhile, MAP3K5 protein expression level was significantly decreased in primary NPC tissues compared with nasopharyngitis when MAP3K5 mRNA expression was consistent in two group tissues. According to our data and target prediction by miRnada, we assume MAP3K5 is an important target gene of NPC. MAP3K5, also named apoptosis signal-regulating kinase1 (ASK1), is an important early answer gene in P38MAPK pathway and an apoptosis-related gene. In present study, MAP3K5 was verified the target gene of miR-BART22 by luciferase assay. miRBART-22 decreased MAP3K5 protein level. Moreover, it also decreased MAP3K5 downstream gene MAP2K4 expression in P38MAPK pathway, and even their activated phosphorylation forms. Additionally, we found stable transfection of miR-BAT22 could improve tumor cells' proliferative and invasive abilities in NPC cell line 5-8F. The data highlight the role of the EBV miR-BART22 in regulating genes involving in apoptosis and some important pathways to promote cancer development. And it also raises the possibility that inhibitors of miR-BART22 can be as a therapeutic strategy for NPC and other EBV-infected tumors treatment. PMID:28243335

  11. Conserved mutation of Epstein-Barr virus-encoded BamHI-A Rightward Frame-1 (BARF1) gene in Indonesian nasopharyngeal carcinoma

    PubMed Central

    2010-01-01

    Background BamHI-A rightward frame-1 (BARF1) is a carcinoma-specific Epstein-Barr virus (EBV) encoded oncogene. Here we describe the BARF1 sequence diversity in nasopharyngeal carcinoma (NPC), other EBV-related diseases and Indonesian healthy EBV carriers in relation to EBV genotype, viral load and serology markers. Nasopharyngeal brushings from 56 NPC cases, blood or tissue from 15 other EBV-related disorders, spontaneous B cell lines (LCL) from 5 Indonesian healthy individuals and several prototype EBV isolates were analysed by PCR-direct sequencing. Results Most NPC isolates revealed specific BARF1 nucleotide changes compared to prototype B95-8 virus. At the protein level these mutations resulted in 3 main substitutions (V29A, W72G, H130R), which are not considered to cause gross tertiary structure alterations in the hexameric BARF1 protein. At least one amino acid conversion was detected in 80.3% of NPC samples compared to 33.3% of non-NPC samples (p < 0.001) and 40.0% of healthy LCLs (p = 0.074). NPC isolates also showed more frequent codon mutation than non-NPC samples. EBV strain typing revealed most isolates as EBV type 1. The viral load of either NPC or non-NPC samples was high, but only in non- NPC group it related to a particular BARF1 variant. Serology on NPC sera using IgA/EBNA-1 ELISA, IgA/VCA-p18 ELISA and immunoblot score showed no relation with BARF1 sequence diversity (p = 0.802, 0.382 and 0.058, respectively). NPC patients had variable antibody reactivity against purified hexameric NPC-derived BARF1 irrespective of the endogenous BARF1 sequence. Conclusion The sequence variation of BARF1 observed in Indonesian NPC patients and controls may reflect a natural selection of EBV strains unlikely to be predisposing to carcinogenesis. The conserved nature of BARF1 may reflect an important role in EBV (epithelial) persistence. PMID:20849661

  12. Antitumor activity of 7RH, a discoidin domain receptor 1 inhibitor, alone or in combination with dasatinib exhibits antitumor effects in nasopharyngeal carcinoma cells.

    PubMed

    Lu, Qiu-Ping; Chen, Wen-Dan; Peng, Jie-Ren; Xu, Yao-Dong; Cai, Qian; Feng, Gong-Kan; Ding, Ke; Zhu, Xiao-Feng; Guan, Zhong

    2016-11-01

    Dysregulation of the discoidin domain receptors (DDRs) has been implicated in the development of numerous types of tumors, including head and neck cancer, and nasopharyngeal, breast, ovarian and esophageal carcinomas. Furthermore, agents that inhibit DDR1 activity are hypothesized to be useful for the treatment of nasopharyngeal carcinoma (NPC). The aim of the present study was to evaluate the effect of the DDR1 inhibitory (3-(2-(pyrazolo(1,5-a)pyrimidin-6-yl)-ethynyl)benzamide compound, 7RH, in NPC cells both in vitro and in vivo, and its effect when used in combination with dasatinib, a SRC family kinase (SFK) inhibitor. The effects of 7RH alone or in combination with dasatinib on cell viability were assessed using MTT assays and apoptosis was detected by flow cytometry. In addition, western blotting was performed to analyze the relative protein expression levels of cell cycle-associated genes in human NPC cell lines (CNE1, CNE2, HONE1 and SUNE1). Cell migration was also assessed using cell adhesion assays. Furthermore, tumor xenografts of CNE2 NPC cells were established in nude mice and the growth inhibitory effects of 7RH treatment alone or in combination with dasatinib were evaluated. Finally, knockdown of DDR1 protein expression was achieved by transfection of CNE2 cells with DDR1-specific small interfering RNA. Treatment with 7RH effectively suppressed the proliferation and induced the apoptosis of NPC cells. In addition, the Janus kinase 1 (JAK1)/signal transducer and activator of transcription (STAT3) signaling pathway was downregulated by 7RH, whereas the activities of the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways were upregulated in response to 7RH treatment. Furthermore, the expression levels of phosphorylated SRC were increased in NPC cells treated with 7RH; thus indicating that SRC exhibits a vital function in the resistance of NPC cells

  13. Antitumor activity of 7RH, a discoidin domain receptor 1 inhibitor, alone or in combination with dasatinib exhibits antitumor effects in nasopharyngeal carcinoma cells

    PubMed Central

    Lu, Qiu-Ping; Chen, Wen-Dan; Peng, Jie-Ren; Xu, Yao-Dong; Cai, Qian; Feng, Gong-Kan; Ding, Ke; Zhu, Xiao-Feng; Guan, Zhong

    2016-01-01

    Dysregulation of the discoidin domain receptors (DDRs) has been implicated in the development of numerous types of tumors, including head and neck cancer, and nasopharyngeal, breast, ovarian and esophageal carcinomas. Furthermore, agents that inhibit DDR1 activity are hypothesized to be useful for the treatment of nasopharyngeal carcinoma (NPC). The aim of the present study was to evaluate the effect of the DDR1 inhibitory (3-(2-(pyrazolo(1,5-a)pyrimidin-6-yl)-ethynyl)benzamide compound, 7RH, in NPC cells both in vitro and in vivo, and its effect when used in combination with dasatinib, a SRC family kinase (SFK) inhibitor. The effects of 7RH alone or in combination with dasatinib on cell viability were assessed using MTT assays and apoptosis was detected by flow cytometry. In addition, western blotting was performed to analyze the relative protein expression levels of cell cycle-associated genes in human NPC cell lines (CNE1, CNE2, HONE1 and SUNE1). Cell migration was also assessed using cell adhesion assays. Furthermore, tumor xenografts of CNE2 NPC cells were established in nude mice and the growth inhibitory effects of 7RH treatment alone or in combination with dasatinib were evaluated. Finally, knockdown of DDR1 protein expression was achieved by transfection of CNE2 cells with DDR1-specific small interfering RNA. Treatment with 7RH effectively suppressed the proliferation and induced the apoptosis of NPC cells. In addition, the Janus kinase 1 (JAK1)/signal transducer and activator of transcription (STAT3) signaling pathway was downregulated by 7RH, whereas the activities of the Ras/Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways were upregulated in response to 7RH treatment. Furthermore, the expression levels of phosphorylated SRC were increased in NPC cells treated with 7RH; thus indicating that SRC exhibits a vital function in the resistance of NPC cells

  14. Comparison between nedaplatin and cisplatin plus docetaxel combined with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multicenter randomized phase II clinical trial

    PubMed Central

    Tang, Chunyuan; Wu, Fang; Wang, Rensheng; Lu, Heming; Li, Guisheng; Liu, Meilian; Zhu, Haisheng; Zhu, Jinxian; Zhang, Yong; Hu, Kai

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is highly incident in southern China. Metastasis is the major cause of death in NPC patients. Concurrent chemoradiotherapy (CCRT) has been accepted as standard in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, induction chemotherapy (IC) also has benefits in this disease, especially in the patients with certain high-risk factors such as bulky and/or extensive nodal disease. It has been presented that adding IC to CCRT might be a reasonable approach and need more work to confirm. The optimal chemotherapeutic regimen combined with radiotherapy has not been determined so far. It is important to explore high effective and low toxic chemotherapy for the patients. In the multicenter prospective study, 223 patients with locoregionally advanced untreated NPC were randomized into experimental group and control group. The patients received two cycles of induction chemotherapy (IC) with docetaxel (DOC) plus nedaplatin (NDP) in experimental group every 3 weeks, followed by IMRT concurrent with weekly NDP for six cycles, and NDP was replaced by cisplatin (CDDP) in control group. More patients in experimental group could receive full courses of IC and concurrent chemoradiotherapy (CCRT) (P=0.013). There was no significant difference between the two groups in the percentage of reduction of GTVnx and GTVnd after IC (P=0.207 and P=0.107) and CR rate three months after completion of chemoradiotherapy (P=0.565 and P=0.738). With a mean follow-up of 35.1 months, no statistically significant difference in the 3-year OS, LRFS, RRFS, DMFS, and PFS was found. During IC, more patients suffered vomiting in control group (P=0.001). During CCRT, grade 3/4 neutropenia/thrombocytopenia were more common in experimental group (P=0.028 and P=0.035); whereas, severe anemia and vomiting were more common in control group (P=0.0001 and P=0.023). In conclusions, patients with locoregionally advanced NPC showed good

  15. The Evolution of and Risk Factors for Neck Muscle Atrophy and Weakness in Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy: A Retrospective Study in an Endemic Area.

    PubMed

    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

    2015-08-01

    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.

  16. Effect of ethanol extract of Selaginella doederleinii Hieron on the proliferation of nasopharyngeal carcinoma CNE-1 and C666-1 cells.

    PubMed

    Lian, Rong; Li, Jing; Ma, Hui-Min; Zhang, Guo-Zheng; Guo, Xi-Ai; Li, Xiao; Yang, Jian-Bin

    2013-01-01

    This paper mainly studied the effect of ethanol extract of Selaginella doederleinii Hieron on the proliferation of two kinds of nasopharyngeal carcinoma cell lines, CNE-1 and C666-1, and their mechanisms of action. Extract was obtained by heat reflux extraction with ethanol, and the effect of extract on the extracellular matrix adhesion of the cells, on their proliferation process, as well as on their colony-forming ability were tested using MTT assay. The results showed that the yield of dry extract was 36.4%. 2.5 g/ml extract in the high concentration group exhibited inhibitory activity that was directly proportional to the concentration on CNE-1 cells, while not exhibiting obvious proportional trend in respect with C666-1 cells. However, the inhibition rates against two types of cells can both reach between 30% ~ 50%. Under the effect of ethanol extract of Selaginella doederleinii Hieron, proliferative capacities of C666-1 and CNE-1 cells were affected to some extent.

  17. Annexin A1 can inhibit the in vitro invasive ability of nasopharyngeal carcinoma cells possibly through Annexin A1/S100A9/Vimentin interaction

    PubMed Central

    Huang, Weiguo; Tang, Yunlian; Fu, Weiting

    2017-01-01

    Annexin A1 is a member of a large superfamily of glucocorticoid-regulated, calcium- and phospholipid-binding proteins. Our previous studies have shown that the abnormal expression of Annexin A1 is related to the occurrence and development of nasopharyngeal carcinoma (NPC). To understand the roles of Annexin A1 in the tumorigenesis of NPC, targeted proteomic analysis was performed on Annexin A1-associated proteins from NPC cells. We identified 436 proteins associated with Annexin A1, as well as two Annexin A1-interacted key proteins, S100A9 and Vimentin, which were confirmed by co-immunoprecipitation. Gene function classification revealed that the Annexin A1-associated proteins can be grouped into 21 clusters based on their molecular functions. Protein–protein interaction analysis indicated that Annexin A1 /S100A9/Vimentin interactions may be involved in the invasion and metastasis of NPC because they can form complexes in NPC cells. The down-regulation of Annexin A1 in NPC may lead to the overexpression of S100A9/Vimentin, which may increase the possibility of the invasion ability of NPC cells by adjusting the function of cytoskeleton proteins. Results suggested that the biological functions of Annexin A1 in NPC were diverse, and that Annexin A1 can inhibit the in vitro invasive ability of NPC cells through Annexin A1 /S100A9/Vimentin interaction. PMID:28355254

  18. Whole-exome sequencing identifies multiple loss-of-function mutations of NF-κB pathway regulators in nasopharyngeal carcinoma

    PubMed Central

    Zheng, Hong; Dai, Wei; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Kan, Rebecca; Wong, Bonnie Wing Yan; Leong, Merrin Man Long; Deng, Mingdan; Kwok, Tommy Chin Tung; Chan, Jimmy Yu-Wai; Kwong, Dora Lai-Wan; Lee, Anne Wing-Mui; Ng, Wai Tong; Ngan, Roger Kai Cheong; Yau, Chun Chung; Tung, Stewart; Lee, Victor Ho-fun; Lam, Ka-On; Kwan, Chung Kong; Li, Wing Sum; Yau, Stephen; Chan, Kwok-Wah; Lung, Maria Li

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with a unique geographical distribution. The genomic abnormalities leading to NPC pathogenesis remain unclear. In total, 135 NPC tumors were examined to characterize the mutational landscape using whole-exome sequencing and targeted resequencing. An APOBEC cytidine deaminase mutagenesis signature was revealed in the somatic mutations. Noticeably, multiple loss-of-function mutations were identified in several NF-κB signaling negative regulators NFKBIA, CYLD, and TNFAIP3. Functional studies confirmed that inhibition of NFKBIA had a significant impact on NF-κB activity and NPC cell growth. The identified loss-of-function mutations in NFKBIA leading to protein truncation contributed to the altered NF-κB activity, which is critical for NPC tumorigenesis. In addition, somatic mutations were found in several cancer-relevant pathways, including cell cycle-phase transition, cell death, EBV infection, and viral carcinogenesis. These data provide an enhanced road map for understanding the molecular basis underlying NPC. PMID:27647909

  19. 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.

  20. Molecular diversity of Epstein-Barr virus IgG and IgA antibody responses in nasopharyngeal carcinoma: a comparison of Indonesian, Chinese, and European subjects.

    PubMed

    Fachiroh, Jajah; Schouten, Tabitha; Hariwiyanto, Bambang; Paramita, Dewi K; Harijadi, Ahmad; Haryana, Sofia M; Ng, Mun H; Middeldorp, Jaap M

    2004-07-01

    Epstein-Barr virus (EBV)-specific immunoblot analysis was used to reveal the molecular diversity of immunoglobulin (Ig) G and IgA antibody responses against Epstein-Barr nuclear antigen (EBNA), early antigen (EA), and viral capsid antigen (VCA) in serum samples from patients with nasopharyngeal carcinoma (NPC) and control subjects, by use of immunofluorescence assay (IFA). Control donors (n=150) showed IgG responses to few EBV proteins--VCA-p18, VCA-p40, EBNA1, and Zebra--and sporadically weak IgA reactivity to EBNA1 and VCA-p18. Patients with NPC stage 1 (n=6) had similar response patterns. Patients with NPC stage 2-4 (n=132) showed significantly more diverse IgG and IgA responses to EA and VCA proteins--VCA-p18/-p40, EBNA1, Z-encoded broadly reactive activator, and EAd-p47/54, -DNAse, -thymidine kinase, and -p138. No correlation was found between IFA titers and the number of EBV proteins recognized by IgG or IgA. Our results reveal dissimilarity between EBV polypeptides recognized by IgG and IgA antibodies, which suggests independent B cell triggering events.

  1. Monocyte-derived factors including PLA2G7 induced by macrophage-nasopharyngeal carcinoma cell interaction promote tumor cell invasiveness

    PubMed Central

    Low, Heng Boon; Png, Chin Wen; Li, Chunwei; Wang, De Yun; Wong, Soon Boon Justin; Zhang, Yongliang

    2016-01-01

    The non-keratinizing undifferentiated subtype of nasopharyngeal carcinoma (NPC) is a malignancy characterized by an intimate relationship between neoplastic cells and a non-neoplastic lymphoid component. Tumor-associated macrophages (TAMs) foster tumor progression through production of soluble mediators that support proliferation, angiogenesis, survival and invasion of malignant cells. However, the role of macrophages in the progression of NPC remains poorly understood. This study aims to investigate the functional and phenotypic changes that occur to macrophages in macrophage-NPC cell co-culture systems, and how these changes influence tumor cells. We found that monocytes, including THP-1 cells and primary human monocytes, co-cultured with C666-1 NPC cells upregulate expression of pro-inflammatory cytokines at the early stages, followed by the induction of metastasis-related genes and interferon-stimulated genes at the later stage of coculture, indicating that TAMs are “educated” by NPC cells for cancer progression. Importantly, the induction of these factors from the TAMs was also found to enhance the migratory capabilities of the NPC cells. We have also identified one of these macrophage-derived factor, phospholipase A2 Group 7 (PLA2G7), to be important in regulating tumor cell migration and a novel tumor-promoting factor in NPC. Further studies to characterize the role of PLA2G7 in tumor metastasis may help determine its potential as a therapeutic target in NPC. PMID:27487154

  2. Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3.

    PubMed

    Lee, Hui Min; Lo, Kwok-Wai; Wei, Wenbin; Tsao, Sai Wah; Chung, Grace Tin Yun; Ibrahim, Maha Hafez; Dawson, Christopher W; Murray, Paul G; Paterson, Ian C; Yap, Lee Fah

    2017-02-27

    Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1 and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is over-expressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease.

  3. Lymphatic drainage of the skull base: comparative anatomic and advanced imaging studies in the rabbit and human with implications for spread of nasopharyngeal carcinoma.

    PubMed

    Qiuhang, Z; Zhenlin, W; Yan, Q; Jun, H; Yongfeng, S; Bo, H

    2010-09-01

    This preliminary study investigated the lymphatic drainage and distribution of lymphatic structures in the skull base. Characteristics of the rabbit skull base were analyzed and compared correspondingly with those of the human skull. The lymphatic circulation in the rabbit cranial base was detected by digital subtraction angiography (DSA), and lymph drainage in the human skull base was illustrated by interstitial magnetic resonance lymphography (MRL). Lymphatic structures and their distribution in MRL were identified by comparing with contrast-enhanced MRI and clinical data on basilar metastasis of nasopharyngeal carcinoma (NPC) in the human skull base. Anatomic similarity was found between the rabbit and human basilar regions. Well-visualized lymphatic pathways were found in the rabbit cranial base, and human lymphatic structures showed high signal intensity in enhanced T1-weighted MRL images. Lymphatic tissues in the human basilar region were found mainly distributed in the areas of the jugular foramen, foramen lacerum, and petrosal section of the internal carotid artery (ICA). Their distribution in the human basilar region was similar to the distribution in the rabbit basilar region and consistent with our clinical findings of the predilection sites of NPC metastasis in the skull base. Our studies show that bilateral symmetrical lymphatic structures were distributed along the ICA, internal jugular vein, and dura of cranial base in the central part of the middle and posterior skull base.

  4. Human Leukocyte Antigen (HLA) A*1101-Restricted Epstein-Barr Virus-Specific T-cell Receptor Gene Transfer to Target Nasopharyngeal Carcinoma.

    PubMed

    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

    2015-10-01

    Infusing virus-specific T cells is effective treatment for rare Epstein-Barr virus (EBV)-associated posttransplant 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 favor 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 human leukocyte antigen (HLA) A*1101-restricted TCR, which would be widely applicable because 40% of NPC patients carry this HLA allele. Studying both the wild-type and modified forms, we have optimized expression of the TCR and demonstrated high-avidity antigen-specific function (proliferation, cytotoxicity, and cytokine release) in both CD8(+) and CD4(+) T cells. The engineered T cells also inhibited LMP2(+) epithelial tumor 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.

  5. 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

  6. Prognostic Significance of Neutrophil to Lymphocyte Ratio, Lymphocyte to Monocyte Ratio, and Platelet to Lymphocyte Ratio in Patients with Nasopharyngeal Carcinoma

    PubMed Central

    Lu, Aiying; Li, Haifeng; Zheng, Yuming; Tang, Minzhong; Li, Jun; Wu, Huihui; Zhong, Weiming; Gao, Jianquan; Ou, Ningjiang

    2017-01-01

    The peripheral blood neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR) have been reported to correlate with the prognosis of many malignancies. This study evaluated the prognostic value of pretreatment NLR, LMR, and PLR in nasopharyngeal carcinoma (NPC). A retrospective analysis of clinical and pathological data of 140 NPC patients without distant metastasis during initial treatment was conducted to identify correlations between NLR, LMR, and PLR and clinicopathological features, overall survival, and progression-free survival. Cox proportional hazard regression analysis was used to reveal the independent factors affecting the prognosis of NPC patients. NLR was associated with T staging, N staging, and overall clinical stage grouping of the NPC patients (P < 0.05). NLR ≥ 2.28, LMR < 2.26, and PLR ≥ 174 were significantly associated with a relatively short overall survival (P < 0.05). In addition, NLR ≥ 2.28 was significantly associated with a relatively short progression-free survival (P < 0.05). Cox proportional hazard regression analysis showed that NLR was an independent prognostic factor in NPC. Pretreatment NLR, LMR, and PLR might be a useful complement to TNM staging in the prognostic assessment of NPC patients. PMID:28321405

  7. Induction of protective and therapeutic anti-cancer immunity by using bispecific anti-idiotype antibody G22-I50 for nasopharyngeal carcinoma.

    PubMed

    Wang, Jia-Jia; Liu, Yan-Hong; Li, Guan-Cheng

    2015-10-01

    Increasing evidence has suggested that bispecific and multivalent antibodies which have more antigen binding sites will improve their immunogenicity. The bispecific anti-idiotype antibody vaccine G22-I50 was obtained through genetic engineering to enhance the immunogenicity of anti-idiotype antibody vaccines G22 and I50. G22-I50 vaccination could induce anti-tumor immunity in the Balb/c mouse model. The protective and therapeutic efficacy of G22-I50 was also evaluated using the hu-PBL-SCID mouse model injected three times with G22-I50, G22, or I50 mixed with Freund's adjuvant. Results demonstrated that the protective anti-tumor effect of G22-I50 could be relevant with the production of Ab3 antibody and activation of CD8(+) cytotoxic T-lymphocytes. In preventive and therapeutic experiments, G22-I50 could reduce tumor size and prolong the survival time of HNE2-bearing mice (p<0.05). Human CD8(+) T lymphocytes infiltrated the tumor sites, and high levels of human IFN-γ, TNF-α, and caspase-3 were also detected in the tumors from G22-I50-vaccinated and -treated mice. Therefore, the bispecific anti-idiotype antibody vaccine G22-I50 can induce strong humoral and cell-mediated immune responses. This vaccine can be potentially applied to prevent and treat nasopharyngeal carcinoma.

  8. 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

  9. 18F-FLT and 18F-FDG PET/CT in Predicting Response to Chemoradiotherapy in Nasopharyngeal Carcinoma: Preliminary Results

    PubMed Central

    Qi, Shi; Zhongyi, Yang; Yingjian, Zhang; Chaosu, Hu

    2017-01-01

    The purpose of this study was to explore the feasibility of 18F-Fluorothymidine (18F-FLT) and 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in predicting treatment response of nasopharyngeal carcinoma (NPC). Patients with NPC of Stage II-IVB were prospectively enrolled, receiving 2 cycles of neoadjuvant chemotherapy (NACT), followed by concurrent chemoradiotherapy. Each patient underwent pretreatment and post-NACT FLT PET/CT and FDG PET/CT. Standard uptake values (SUV) and tumor volume were measured. Tumor response to NACT was evaluated before radiotherapy by MRI (magnetic resonance imaging), and tumor regression at the end of radiotherapy was evaluated at 55 Gy, according to RECIST 1.1 Criteria. Finally, 20 patients were consecutively enrolled. At the end of radiotherapy, 7 patients reached complete regression while others were partial regression. After 2 cycles of NACT both FLT and FDG parameters declined remarkably. Parameters of FDG PET were more strongly correlated to tumor regression than those of FLT PET.70% SUVmax was the best threshold to define contouring margin around the target. Some residual lesions after NACT showed by MRI were negative in PET/CT. Preliminary results showed both 18F-FDG and 18F-FLT PET have the potential to monitor and predict tumor regression. PMID:28091565

  10. High FMNL3 expression promotes nasopharyngeal carcinoma cell metastasis: role in TGF-β1-induced epithelia-to-mesenchymal transition

    PubMed Central

    Wu, Yanxia; Shen, Zhihua; Wang, Keke; Ha, Yanping; Lei, Hong; Jia, Yanan; Ding, Ranran; Wu, Dongmei; Gan, Siyuan; Li, Rujia; Luo, Botao; Jiang, Hanguo; Jie, Wei

    2017-01-01

    Formin-like 3 (FMNL3) plays a crucial role in cytoskeletal mediation and is potentially a biomarker for cell migration; however, its role in cancer metastasis remains unknown. In this study, we found elevated FMNL3 protein expression in clinical nasopharyngeal carcinoma (NPC) tissues. FMNL3 expression positively correlated to the clinical stage, T (tumour), N (lymph node metastasis) and M (distant metastasis) classification of NPC patients. Moreover, FMNL3 positively correlated to Vimentin expression and negatively correlated to E-cadherin expression in clinical NPC samples. In vitro experiments showed that FMNL3 expression was inversely related to NPC cell differentiation status. Overexpression of FMNL3 led to epithelial-to-mesenchymal transition (EMT) in well differentiated CNE1 cells. TGF-β1-treated poorly differentiated CNE2 cells showed changes in EMT accompanied by enhanced FMNL3 expression and cell migration. On the contrary, knockdown of FMNL3 partially attenuated the TGF-β1-promoted CNE2 cell migration, together with associated changes in EMT markers. Finally, knockdown of FMNL3 also weakened EMT in tumours in xenographs. Our study indicates for the first time that TGF-β1/FMNL3 signalling may be a novel mechanism mediating EMT in NPC, which is closely associated with NPC metastasis. PMID:28198387

  11. 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

  12. 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

  13. Genetic predisposition factors and nasopharyngeal carcinoma risk: a review of epidemiological association studies, 2000-2011: Rosetta Stone for NPC: genetics, viral infection, and other environmental factors.

    PubMed

    Hildesheim, Allan; Wang, Cheng-Ping

    2012-04-01

    While infection with Epstein-Barr virus (EBV) is known to be an essential risk factor for the development of nasopharyngeal carcinoma (NPC), other co-factors including genetic factors are thought to play an important role. In this review, we summarize association studies conducted over the past decade to evaluate the role of genetic polymorphisms in NPC development. A review of the literature identified close to 100 studies, including 3 genome-wide association studies (GWAS), since 2000 that evaluated genetic polymorphisms and NPC risk in at least 100 NPC cases and 100 controls. Consistent evidence for associations were reported for a handful of genes, including immune-related HLA Class I genes, DNA repair gene RAD51L1, cell cycle control genes MDM2 and TP53, and cell adhesion/migration gene MMP2. However, for most of the genes evaluated, there was no effort to replicate findings and studies were largely modest in size, typically consisting of no more than a few hundred cases and controls. The small size of most studies, and the lack of attempts at replication have limited progress in understanding the genetics of NPC. Moving forward, if we are to advance our understanding of genetic factors involved in the development of NPC, and of the impact of gene-gene and gene-environment interations in the development of this disease, consortial efforts that pool across multiple, well-designed and coordinated efforts will most likely be required.

  14. CD44 and CD24 coordinate the reprogramming of nasopharyngeal carcinoma cells towards a cancer stem cell phenotype through STAT3 activation

    PubMed Central

    Shen, Yao-An; Wang, Chia-Yu; Chuang, Hui-Yen; Hwang, John Jeng-Jong; Chi, Wei-Hsin; Shu, Chih-Hung; Ho, Ching-Yin; Li, Wing-Yin; Chen, Yann-Jang

    2016-01-01

    Cell surface proteins such as CD44 and CD24 are used to distinguish cancer stem cells (CSCs) from the bulk-tumor population. However, the molecular functionalities of CD24 and CD44, and how these two molecules coordinate in CSCs remain poorly understood. We found that nasopharyngeal carcinoma (NPC) cells with high expression of CD44 and CD24 proteins presented with pronounced CSC properties. Accordingly, a subpopulation of NPC cells with co-expression of CD44 and CD24 were specially enriched in high-stage clinical samples. Furthermore, ectopically expressing the epithelial-mesenchymal transition (EMT) regulator Twist was able to upregulate the stemness factors, and vice versa. This indicates a reciprocal regulation of stemness and EMT. Intriguingly, we found that this reciprocal regulation was differentially orchestrated by CD44 and CD24, and only simultaneous silencing the expression of CD44 and CD24 led to a broad-spectrum suppression of CSC properties. Oppositely, overexpression of CD44 and CD24 induced the reprogramming of parental NPC cells into CSCs through STAT3 activation, which could be blunted by STAT3 inhibition, indicating that CD44 and CD24 collaboratively drive the reprogramming of NPC cells through STAT3-mediated stemness and EMT activation. Consequently, targeting of the CD44/CD24/STAT3 axis may provide a potential therapeutic paradigm for the treatment of NPC through repressing CSC activities. PMID:27521216

  15. 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

  16. Relationship Between the Comprehensive Nutritional Index and the EORTC QLQ-H&N35 in Nasopharyngeal Carcinoma Patients Treated with Intensity-Modulated Radiation Therapy.

    PubMed

    He, Yan; Chen, Liping; Chen, Linmin; Hu, Wen; Wang, Cong; Tang, Linquan; Mai, Haiqiang; Li, Jianmei; Wu, Liping; Fan, Yuying

    2017-04-01

    This study aimed to explore the relationship between the comprehensive nutritional index (CNI) and quality of life in nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiation therapy (IMRT). The nutritional index, which includes total lymphocyte count, hemoglobin and albumin levels, body mass index, and usual body weight percentage, was evaluated pre-treatment and post-treatment in patients who underwent IMRT. The quality of life of NPC patients was measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Cancer Module (EORTC QLQ-H&N35) at four time points: pre-treatment, post-treatment, and 3 and 6 mo after IMRT. A comprehensive nutritional model was used to assess the correlation with QLQ-H&N35. The nutritional index decreased significantly post-treatment. The CNI was associated with immunotherapy; the International Union Against Cancer (UICC) stage; concurrent chemotherapy; speech problems, trouble with social contact, feeling ill and having dental problems at pre-treatment; sexuality at 3 mos post-treatment; and sensory problems and xerostomia at 6 mo post-treatment (P < 0.05). The nutritional status and QLQ-H&N35 scores in NPC patients decreased during IMRT. Our study provides an alternative measure of the CNI to improve the QLQ-H&N35 evaluation system for patients with NPC.

  17. 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.

  18. Long Non-Coding RNA LINC0086 Functions as a Tumor Suppressor in Nasopharyngeal Carcinoma By Targeting miR-214.

    PubMed

    Guo, Jie; Ma, Jinqi; Zhao, Guosheng; Li, Guocai; Fu, Yunfeng; Luo, Yanwei

    2017-02-13

    Nasopharyngeal carcinoma (NPC) is a distinct head and neck cancer, occurring at high frequency in Southern China. Emerging studies have shown that long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and progression, including NPC. Here, we established a comprehensive lncRNA profiles in NPC and found that 35 lncRNAs were differentially expressed in NPC. We found that LINC0086 decreased in NPC patient serum samples and tissues. The Kaplan-Meier survival cure showed that the patients with high LINC0086 expression had higher survival rate than those with low LINC0086 expression. LINC0086 expression was associated with NPC histological grade, Lymph node metastasis and clinical stage. Upregulation of LINC0086 inhibited cancer cell proliferation and promoted apoptosis. In addition, Upregulation of LINC0086 dramatically decreased the expression of miR-214, an oncogene in several cancers, in C666-1 and HK-1 cells. And a miR-214 binding site was found in 3’UTR of LINC0086. We also validated that both miR-214 and LINC0086 presented in the RISC complex, demonstrating that LINC0086 could decrease miR-214 expression by directly interacting with miR-214. Furthermore, the suppressive effects of LINC0086 on NPC cell growth were reversed by overexpression miR-214 expression in vitro and in vivo. Thus, our study reports a novel mechanism underlying NPC carcinogenesis, and provides a potential novel diagnosis and treatment biomarker for NPC.

  19. 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

  20. Reversal effect of GnT-V on the radioresistance of human nasopharyngeal carcinoma cells by alteration β1, 6-GlcNAc branched N-glycans.

    PubMed

    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.

  1. Association of XRCC1 and XRCC3 gene haplotypes with the development of radiation-induced fibrosis in patients with nasopharyngeal carcinoma.

    PubMed

    Cheuk, Isabella Wai Yin; Yip, Shea Ping; Kwong, Dora Lai Wan; Wu, Vincent Wing Cheung

    2014-07-01

    Radiation-induced fibrosis is one of the late complications of radiotherapy (RT) for nasopharyngeal carcinoma (NPC). The aim of this study was to investigate the association between X-ray repair cross-complementing protein 1 and 3 (XRCC1 and XRCC3, respectively) gene haplotypes and radiation-induced fibrosis in NPC patients. Genomic DNA was extracted from blood samples of 120 NPC patients previously treated with RT. In total, 12 tag single-nucleotide polymorphisms (SNPs) were selected from the XRCC1 and XRCC3 genes and were genotyped using restriction fragment length polymorphism analysis or unlabeled probe melting analysis. Single-marker and haplotype analyses were performed using multivariate logistic regression analysis. The functional variant rs861539 of XRCC3 may be associated with radiation-induced fibrosis [asymptotic P-value (Pasym)<0.05]. No significant association was observed between radiation-induced fibrosis and any of the tag SNPs of XRCC1 and XRCC3 in either single-marker or haplotype analysis after 10,000 permutations [empirical P-value (Pemp)>0.05]. Our preliminary results indicated that the rs861539 variant of XRCC3 may be associated with an increased risk of radiation-induced fibrosis; however, a large-scale study is required to confirm this result.

  2. An oncolytic adenovirus enhances antiangiogenic and antitumoral effects of a replication-deficient adenovirus encoding endostatin by rescuing its selective replication in nasopharyngeal carcinoma cells.

    PubMed

    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

    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.

  3. Long non-coding RNA LOC100129148 functions as an oncogene in human nasopharyngeal carcinoma by targeting miR-539-5p.

    PubMed

    Sun, Kai-Yu; Peng, Tao; Chen, Zhe; Song, Peng; Zhou, Xu-Hong

    2017-03-21

    Emerging studies have shown that long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and progression, including human nasopharyngeal carcinoma (NPC). The correlation between lncRNAs expression and NPC development has not been well identified in the recent literature. Recently, high-through put analysis reveals that LOC100129148 is highly expressed in NPC. However, whether the aberrant expression of LOC100129148 in NPC is corrected with tumorigenesis or prognosis has not been investigated. Herein, we identified that LOC100129148 was up-regulated in NPC tissues and cell lines, and higher expression of LOC100129148 resulted in a markedly poorer survival time. Over-expressed LOC100129148 favored, but silenced LOC100129148 hampered cell proliferation in NPC cells. Additionally, LOC100129148 enhanced the KLF12 expression through functioning as a competitive 'sponge' for miR-539-5p. Thus, our study reports a novel mechanism underlying NPC carcinogenesis, and provides a potential novel diagnosis and treatment biomarker for NPC.

  4. 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

    2015-12-18

    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.

  5. Extra-cellular release and blood diffusion of BART viral micro-RNAs produced by EBV-infected nasopharyngeal carcinoma cells

    PubMed Central

    2010-01-01

    Background Nasopharyngeal carcinoma (NPC) is a human epithelial malignancy consistently associated with the Epstein-Barr virus. The viral genome is contained in the nuclei of all malignant cells with abundant transcription of a family of viral microRNAs called BART miRNAs. MicroRNAs are well known intra-cellular regulatory elements of gene expression. In addition, they are often exported in the extra-cellular space and sometimes transferred in recipient cells distinct from the producer cells. Extra-cellular transport of the microRNAs is facilitated by various processes including association with protective proteins and packaging in secreted nanovesicles called exosomes. Presence of microRNAS produced by malignant cells has been reported in the blood and saliva of tumor-bearing patients, especially patients diagnosed with glioblastoma or ovarian carcinoma. In this context, it was decided to investigate extra-cellular release of BART miRNAs by NPC cells and their possible detection in the blood of NPC patients. To address this question, we investigated by quantitative RT-PCR the status of 5 microRNAs from the BART family in exosomes released by NPC cells in vitro as well as in plasma samples from NPC xenografted nude mice and NPC patients. Results We report that the BART miRNAs are released in the extra-cellular space by NPC cells being associated, at least to a large extent, with secreted exosomes. They are detected with a good selectivity in plasma samples from NPC xenografted nude mice as well as NPC patients. Conclusions Viral BART miRNAs are secreted by NPC cells in vitro and in vivo. They have enough stability to diffuse from the tumor site to the peripheral blood. This study provides a basis to explore their potential as a source of novel tumor biomarkers and their possible role in communications between malignant and non-malignant cells. PMID:20950422

  6. Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas

    SciTech Connect

    Glaser, R.; Zhang, Haizhang ); Yao, Kaitai; Zhu, Hecheng; Wang, Fuxi; Li, Guiyuan; Wen, Dongseng; Li, Yingping )

    1989-12-01

    Two epithelia tumor cell lines were established from biopsy specimens of nasopharyngeal carcinomas (NPC). The specimens were taken from poorly differentiated squamous cell carcinomas of the nasopharynx. The tissues were prepared for cell culture and eventually two continuous epithelia cell lines were obtained and designated HONE-1 and HNE-1. Light and electron microscopic examination of these two cell lines demonstrated cells with an epithelial morphology including the presence of desmosomes. It was found that early-passage uncloned HNE-1 cells (passage 23) could be superinfected with B95-8 and NPC-EBV isolates as demonstrated by the induction of Epstein-Barr virus (EBV)-specific early antigen(s) in a small percentage of the cells; HONE-1 cells could also be superinfected with EBV. Southern blot analysis detected EBV DNA in samples from uncloned HNE-1 cells at passages 12, 17, 21, 27, and 35. However, by passage 45, EBV DNA could no longer be detected in HNE-1 cells by Southern blot analysis. The EBV genome was detected in parental HONE-1 cells at subculture 9 and in clone 40 cells up to passage 40 thus far. The data suggest that EBV genome-positive HNE-1 and HONE-1 cells were lost as the cells were cultivated in vitro and that cloning the cells at an early passage level may be critical in maintaining EBV genome-positive epithelial NPC cells. These EBV genome-positive epithelia NPC cell lines will be useful for studying the association of EBV and NPC.

  7. Berberine inhibits the proliferation of human nasopharyngeal carcinoma cells via an Epstein-Barr virus nuclear antigen 1-dependent mechanism.

    PubMed

    Wang, Chao; Wang, Huan; Zhang, Yaqian; Guo, Wei; Long, Cong; Wang, Jingchao; Liu, Limei; Sun, Xiaoping

    2017-04-01

    Nasopharyngeal carcinoma (NPC) is a malignancy derived from the epithelial cells of the nasopharynx cavity, and is closely associated with Epstein-Barr virus (EBV) infection. In addition to NPC, EBV causes various human malignancies, such as gastric cancer, hematological tumors and lymphoepithelioma-like carcinomas. Epstein-Barr nuclear antigen 1 (EBNA1) encoded by EBV is indispensable for replication, partition, transcription and maintenance of viral genomes. Berberine, a naturally occurring isoquinoline alkaloid, shows anti-inflammatory, anticholinergic, antioxidative, and anticancer activities. In the present study, the antitumor effect of berberine was studied. Cell Counting Kit-8 (CCK-8) assays were performed to demonstrate whether the proliferation of EBV-positive NPC cells was inhibited by berberine. Flow cytometric results revealed that berberine induced cell cycle arrest and apoptosis. Quantitative-PCR and western blotting results indicated that berberine decreased the expression of EBNA1 at both the mRNA and protein levels in the EBV-positive NPC cells. The function of EBNA1 promoter Qp which is to drive EBNA1 transcription in type Ⅱ latent infection was strongly suppressed by berberine. Overexpression of EBNA1 attenuated this inhibitory effect. Berberine also suppressed the activity of signal transducer and activator of transcription 3 which is a new therapeutic target in a series of malignancies, including NPC. Viral titer experiments demonstrated that berberine decreased the production of virions in HONE1 and HK1-EBV cells. In a mouse xenograft model of NPC induced by HONE1 cells, berberine significantly inhibited tumor formation. Altogether, these results indicate that berberine decreases the expression of EBNA1 and exhibits an antitumor effect against NPC both in vitro and in vivo.

  8. Id-1 and the p65 subunit of NF-κB promote migration of nasopharyngeal carcinoma cells and are correlated with poor prognosis.

    PubMed

    Sun, Wei; Guo, Ming-Ming; Han, Ping; Lin, Ji-Zhen; Liang, Fa-Ya; Tan, Guang-Mou; Li, Hua-Bin; Zeng, Musheng; Huang, Xiao-Ming

    2012-04-01

    Inhibitor of differentiation (Id)-1 and nuclear factor-kappa B (NF-κB) have been detected in many malignant tumors, and their presence has been correlated with the metastatic potential of these tumors. This study was undertaken to investigate the prognostic significance of the expression of Id-1 and the p65 subunit of NF-κB (NF-κB/p65) and the proteins' roles in the invasion process of nasopharyngeal carcinoma (NPC) cells. The messenger RNA (mRNA) and protein levels of Id-1 and NF-κB/p65 in normal nasopharyngeal epithelial cells and NPC cell lines were examined using reverse transcription-PCR and western blot analysis, whereas the mRNA and protein levels of Id-1 and NF-κB/p65 in clinical NPC specimens were determined by reverse transcription-PCR and immunohistochemistry. Short hairpin RNA (shRNA) was used to silence Id-1 and NF-κB/p65 to allow for the examination of matrix metalloproteinase (MMP)-9 expression and migratory capacity changes in CNE-2 cells. Multivariate Cox analysis revealed that elevated Id-1 expression was a significant independent predictor of the 5 year overall survival rate (hazards ratio = 16.720, P = 0.005). Furthermore, elevated expression of both Id-1 and NF-κB/p65 was associated with poor clinical survival (P = 0.049). Targeting Id-1 and NF-κB/p65 mRNA with shRNA in CNE-2 cells inhibited MMP-9 expression and decreased the migratory capacity of CNE-2 cells. In conclusion, Id-1 expression is a novel independent prognostic marker molecule that helps identify NPC patients with a poor prognosis. Additionally, combined analysis of Id-1 and NF-κB/p65 can be useful for identifying patients at risk for unfavorable clinical outcomes. Id-1 or/and NF-κB/p65 enhanced tumor cell migration, which is associated with the secretion of MMP-9.

  9. 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.

  10. A Glucosamine-Specific Lectin from Green Dragon No. 8 Beans (Phaseolus vulgaris) Induced Apoptosis on Nasopharyngeal Carcinoma Cells.

    PubMed

    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.

  11. 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.

  12. 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

  13. The C-reactive Protein/Albumin Ratio Is an independent Prognostic Factor for Overall Survival in Patients with Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy

    PubMed Central

    Tao, Chang-Juan; Chen, Yuan-Yuan; Jiang, Feng; Feng, Xing-Lai; Jin, Qi-Feng; Jin, Ting; Piao, Yong-Feng; Chen, Xiao-Zhong

    2016-01-01

    This study aims to investigate the prognostic value of the C-reactive protein/albumin (CRP/ALB) ratio in nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. A total of 719 patients with NPC treated between January 2007 and December 2012 were retrospectively reviewed. Serum albumin and CRP levels were measured before treatment. The associations between the CRP/ALB ratio and clinicopathological parameters were analyzed. Multivariate analyses using the Cox proportional hazards model were performed to identify significant prognostic factors associated with overall survival (OS). The prognostic value of the CRP/ALB ratio was determined using receiver operating characteristic (ROC) curve analysis. The optimal CRP/ALB ratio cutoff value was 0.141. High CRP/ALB ratio was significantly associated with older age (P < 0.001), more advanced T category (P < 0.001) and advanced TNM stage (P = 0.024). Patients with an elevated CRP/ALB ratio (≥ 0.141) had poorer OS than those with a CRP/ALB ratio < 0.141 (5-year OS rates: 91.9% vs. 78.1%; P < 0.001). Multivariate analysis suggested clinical T category [hazard ratio (HR) 2.284; 95% confidence interval (CI), 1.429-3.652; P = 0.001]; clinical N category (HR 1.575; 95% CI, 1.007-2.464; P = 0.047) and CRP/ALB ratio (HR 2.173; 95% CI, 1.128-3.059; P = 0.015) were independently associated with OS. In conclusion, pretreatment CRP/ALB ratio is an objective biomarker with significant prognostic value for OS in NPC. The CRP/ALB ratio can enhance conventional TNM staging to stratify patients and may help facilitate individualized treatment of high-risk cases. PMID:27877215

  14. Preclinical evaluation of PI3K inhibitor BYL719 as a single agent and its synergism in combination with cisplatin or MEK inhibitor in nasopharyngeal carcinoma (NPC)

    PubMed Central

    Wong, Chi Hang; Ma, Brigette Buig Yue; Cheong, Hio Teng; Hui, Connie Wun Chun; Hui, Edwin Pun; Chan, Anthony Tak Cheung

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is endemic to Southeast Asia and over 40% of NPC tissues harbor PIK3CA amplifications. This study aims to study the preclinical activity of a novel PI3K inhibitor, BYL719, in 6 NPC cell lines: C666-1, CNE-2, HK1, HK1-EBV, HONE-1 and HONE-1-LMP1. Over 70% of growth inhibition was attained when NPC cell lines were exposed to increasing concentrations of BYL719, with IC50 values at the low micro-molar range. Two BYL719-sensitive cell lines that harbor PIK3CA mutations, CNE-2 and HONE-1, were selected for further analysis on the effect of BYL719 on cell cycle progression, apoptosis and PI3K signaling. BYL719 significantly reduced the phosphorylation of Akt, and the Akt-mTOR axis downstream effector S6 in these 2 cell lines, but a feedback activation of MAPK was observed at 72 hours post-treatment. BYL719 induced G0/G1 cell cycle arrest and apoptosis in both cell lines. In 3D cell culture models, the growth of NPC spheroids was significantly inhibited in a dose-depending manner. When BYL719 was combined with a MEK inhibitor (AZD6244) in a 3D cell culture system, strong synergism on NPC cell growth was observed with attenuation of MAPK activation. A synergistic inhibitory effect on growth was observed when BYL719 was combined with higher dose levels of cisplatin. These data suggest that BYL719 has preclinical activity in NPC cell lines especially in those which harbor PIK3CA mutation. Combination with a MEK inhibitor maybe a useful strategy that warrants further investigation. PMID:26101713

  15. Noninvasive monitoring of early antiangiogenic therapy response in human nasopharyngeal carcinoma xenograft model using MRI with RGD-conjugated ultrasmall superparamagnetic iron oxide nanoparticles

    PubMed Central

    Cui, Yanfen; Zhang, Caiyuan; Luo, Ran; Liu, Huanhuan; Zhang, Zhongyang; Xu, Tianyong; Zhang, Yong; Wang, Dengbin

    2016-01-01

    Purpose Arginine-glycine-aspartic acid (RGD)-based nanoprobes allow specific imaging of integrin αvβ3, a protein overexpressed during angiogenesis. Therefore, this study applied a novel RGD-coupled, polyacrylic acid (PAA)-coated ultrasmall superparamagnetic iron oxide (USPIO) (referred to as RGD-PAA-USPIO) in order to detect tumor angiogenesis and assess the early response to antiangiogenic treatment in human nasopharyngeal carcinoma (NPC) xenograft model by magnetic resonance imaging (MRI). Materials and methods The binding specificity of RGD-PAA-USPIO with human umbilical vein endothelial cells (HUVECs) was confirmed by Prussian blue staining and transmission electron microscopy in vitro. The tumor targeting of RGD-PAA-USPIO was evaluated in the NPC xenograft model. Later, mice bearing NPC underwent MRI at baseline and after 4 and 14 days of consecutive treatment with Endostar or phosphate-buffered saline (n=10 per group). Results The specific uptake of the RGD-PAA-USPIO nanoparticles was mainly dependent on the interaction between RGD and integrin αvβ3 of HUVECs. The tumor targeting of RGD-PAA-USPIO was observed in the NPC xenograft model. Moreover, the T2 relaxation time of mice in the Endostar-treated group decreased significantly compared with those in the control group both on days 4 and 14, consistent with the immunofluorescence results of CD31 and CD61 (P<0.05). Conclusion This study demonstrated that the magnetic resonance molecular nanoprobes, RGD-PAA-USPIOs, allow noninvasive in vivo imaging of tumor angiogenesis and assessment of the early response to antiangiogenic treatment in NPC xenograft model, favoring its potential clinical translation. PMID:27895477

  16. 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.

  17. 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

  18. Association of p53 codon72 Arg>Pro polymorphism with susceptibility to nasopharyngeal carcinoma: evidence from a case-control study and meta-analysis.

    PubMed

    Sahu, S K; Chakrabarti, S; Roy, S D; Baishya, N; Reddy, R R; Suklabaidya, S; Kumar, A; Mohanty, S; Maji, S; Suryanwanshi, A; Rajasubramaniam, S; Asthana, M; Panda, A K; Singh, S P; Ganguly, S; Shaw, O P; Bichhwalia, A K; Sahoo, P K; Chattopadhyay, N R; Chatterjee, K; Kundu, C N; Das, A K; Kannan, R; Zorenpuii; Zomawia, E; Sema, S A; Singh, Y I; Ghosh, S K; Sharma, K; Das, B S; Choudhuri, T

    2016-05-09

    Tumor suppressor p53 is a critical player in the fight against cancer as it controls the cell cycle check point, apoptotic pathways and genomic stability. It is known to be the most frequently mutated gene in a wide variety of human cancers. Single-nucleotide polymorphism of p53 at codon72 leading to substitution of proline (Pro) in place of arginine (Arg) has been identified as a risk factor for development of many cancers, including nasopharyngeal carcinoma (NPC). However, the association of this polymorphism with NPC across the published literature has shown conflicting results. We aimed to conduct a case-control study for a possible relation of p53 codon72 Arg>Pro polymorphism with NPC risk in underdeveloped states of India, combine the result with previously available records from different databases and perform a meta-analysis to draw a more definitive conclusion. A total of 70 NPC patients and 70 healthy controls were enrolled from different hospitals of north-eastern India. The p53 codon72 Arg>Pro polymorphism was typed by polymerase chain reaction, which showed an association with NPC risk. In the meta-analysis consisting of 1842 cases and 2330 controls, it was found that individuals carrying the Pro allele and the ProPro genotype were at a significantly higher risk for NPC as compared with those with the Arg allele and the ArgArg genotype, respectively. Individuals with a ProPro genotype and a combined Pro genotype (ProPro+ArgPro) also showed a significantly higher risk for NPC over a wild homozygote ArgArg genotype. Additionally, the strength of each study was tested by power analysis and genotype distribution by Hardy-Weinberg equilibrium. The outcome of the study indicated that both allele frequency and genotype distribution of p53 codon72 Arg>Pro polymorphism were significantly associated with NPC risk. Stratified analyses based on ethnicity and source of samples supported the above result.

  19. Pretreatment Serum Lactate Dehydrogenase Level as an Independent Prognostic Factor of Nasopharyngeal Carcinoma in the Intensity-Modulated Radiation Therapy Era

    PubMed Central

    Chen, Zhuhong; Guo, Qiaojuan; Lu, Tianzhu; Lin, Shaojun; Zong, Jingfeng; Zhan, Shenghua; Xu, Luying; Pan, Jianji

    2017-01-01

    Background The aims of this study were to analyze the prognostic value of baseline lactate dehydrogenase (LDH) among nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT), and to evaluate the potential application of LDH in monitoring treatment efficacy dynamically. Material/Methods From June 2005 to December 2010, 1188 patients with non-metastatic NPC who underwent IMRT with or without chemotherapy were reviewed. Univariate and multivariate analyses were performed to evaluate the predictive value of baseline LDH. Wilcoxon signed-rank test was used to analyze the difference between baseline and post-radiotherapy LDH, and to compare post-radiotherapy LDH with the LDH in cases of distant failure. Results Patients with elevated LDH had significant inferior survival rates, in terms of overall survival (70.0% vs. 83.2%, p=0.010), disease-specific survival (71.1% vs. 85.7%, p=0.002), and distant metastasis-free survival (71.1% vs. 83.4%, p=0.009), but not correlated with locoregional relapse-free survival (p=0.275) or progression-free survival (p=0.104). Subgroup analysis demonstrated that this predictive effect was more significant with advanced stage. Sixty-five post-radiotherapy LDH levels were available from the 90 patients with high LDH at initial diagnosis, and these levels fell in 65 patients, with 62 cases (95.4%) falling within the normal range. Of the 208 patients who experienced distant metastasis, 87 had an available LDH level at that time. Among them, 69 cases (79.3%) had an increased level compared with the post-radiotherapy LDH level. Conclusions Pretreatment LDH is a simple, cost-effective biomarker that could predict survival rates and might be used in individualized treatment. It is also a potential biomarker that might reflect tumor burden and be used to monitor therapy efficacy. PMID:28120819

  20. Pretreatment Alkaline Phosphatase and Epstein-Barr Virus DNA Predict Poor Prognosis and Response to Salvage Radiotherapy in Patients with Nasopharyngeal Carcinoma and Metachronous Bone-Only Metastasis

    PubMed Central

    He, ShaSha; Wang, Yan; Peng, Hao; Yang, Lin; Chen, HaiYang; Liang, ShaoBo; Lu, LiXia; Chen, Yong

    2017-01-01

    Background: The bones are the most common site of distant metastasis in nasopharyngeal carcinoma (NPC). Few prognostic markers are available to guide treatment and sub-classify patients with bone metastasis. We aimed to identify the prognostic value of pretreatment serum alkaline phosphatase (ALP) and plasma Epstein-Barr virus DNA (EBV DNA) in patients with bone-only metastasis. Methods: A total of 272 patients who developed bone-only metastases after therapy were retrospectively analyzed. Patients were categorized according to pretreatment serum ALP (< or ≥ 110 U/L) and pretreatment plasma EBV DNA (< or ≥ 6,750 copies ml-1). Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Overall survival (OS) was analyzed using the Kaplan-Meier method and compared using the log-rank test. Results: Median OS for the cohort was 34.06 months (range, 2.53-143.87 months). Multivariate Cox proportional hazard analysis verified pretreatment serum ALP and pretreatment plasma EBV DNA were independent prognostic factors for OS. In stratified survival analysis of patients with elevated pretreatment serum ALP and/or plasma EBV DNA, delivery of radiotherapy (RT) to bone metastases provided a significant OS benefit compared to other therapeutic methods (P < 0.05). Conclusions: This study demonstrates two important points: firstly, pretreatment serum ALP and plasma EBV DNA have prognostic value at the first diagnosis of bone-only metastasis in NPC. Secondly, radiotherapy of bone metastasis improves the prognosis of patients with elevated pretreatment serum ALP and plasma EBV DNA. PMID:28261343

  1. A risk score model for the metastasis of level Ib lymph node based on the clinicopathological features of nasopharyngeal carcinoma in a large sample.

    PubMed

    Yi, Wei; Li, Xian; Liu, Zhigang; Jiang, Changbin; Niu, Daoli; Xia, Yunfei

    2014-09-01

    The aim of the present study was to develop a metastatic risk score model of neck level Ib lymph nodes in primary nasopharyngeal carcinoma (NPC) to guide the level Ib radiotherapy. There were a total of 1,557 patients enrolled in the study, and of these patients, 1,145 were included in the training set. Univariate χ(2) analysis and multivariate logistic regression analyses were used to screen the independent risk factors to construct the risk score model. A total of 85 patients in the validating set underwent a pathology biopsy of level Ib lymph nodes to test the model. The remaining 327 patients from the prognostic-research set were used to evaluate the prognostic impact of level Ib irradiation in high- and low-risk groups. The independent risk factors in the model were carotid sheath involvement, the maximal diameter of the neck lymph nodes (≥20 mm) and the involvement of the level II/III/IV lymph nodes. The involvement of level IV was assigned score 2 and the other risk factors were assigned score 1. According to the total scores, the patients were divided into the low- (total score, 0-1; level Ib metastasis rate, 0.5%) and high-risk groups (total score, 2-4; level Ib metastasis rate, 8.5%). In the validating set, the metastatic rate of level Ib in 43 low-risk patients was 0%, and the rate was 31.0% (13/42) in 42 high-risk patients. In the prognostic-research set, the prognosis of 137 low-risk patients was not affected by level Ib irradiation. However, level Ib unirradiation was an independent prognostic factor for the locoregional recurrence in 190 high-risk patients. According to the data, the novel score model could help assess the metastatic risk of level Ib in primary NPC, and the radiotherapy on level Ib may impact the locoregional recurrence in high-risk patients.

  2. Impacts of multileaf collimators leaf width on intensity-modulated radiotherapy planning for nasopharyngeal carcinoma: analysis of two commercial elekta devices.

    PubMed

    Wang, Shichao; Gong, Youling; Xu, Qingfeng; Bai, Sen; Lu, You; Jiang, Qingfeng; Chen, Nianyong

    2011-01-01

    We compared the impacts of multileaf collimator (MLC) widths (standard MLC width of 10 mm [SMLC] and micro-MLC width of 4 mm [MMLC]) on intensity-modulated radiotherapy (IMRT) planning for nasopharyngeal carcinoma (NPC). Ten patients with NPC were recruited in this study. In each patient's case, plans were generated with the same machine setup parameter and optimizing methods in a treatment planning system according to 2 commercial Elekta MLC devices. All of the parameters were collected from dose-volume histograms of paired plans and evaluated. The average conformity index (CI) and homogeneous index (HI) for the planning gross target volume in IMRT plans with MMLC were 0.790 ± 0.036 and 1.062 ± 0.011, respectively. Data in plans with SMLC were 0.754 ± 0.038 and 1.070 ± 0.010, respectively. The differences were statistically significant (p < 0.05). Compared with CI and HI for planning target volume in paired plans, data with MMLC obviously were better than those with SMLC (CI: 0.858 ± 0.026 vs. 0.850 ± 0.021, p < 0.05; and HI: 1.185 ± 0.011 vs. 1.195 ± 0.011, p < 0.05). However, there was no statistical significance between evaluated parameters (Dmean, Dmax, D₅, gEUD, or NTCP) for organs at risk (OARs) in the 2 paired IMRT plans. According to these two kinds of Elekta MLC devices, IMRT plans with the MMLC have significant advantages in dose coverage for the targets, with more efficiency in treatment for NPC but fail to improve dose sparing of the OARs.

  3. Impacts of Multileaf Collimators Leaf Width on Intensity-Modulated Radiotherapy Planning for Nasopharyngeal Carcinoma: Analysis of Two Commercial Elekta Devices

    SciTech Connect

    Wang Shichao; Gong Youling; Xu Qingfeng; Bai Sen; Lu You; Jiang Qingfeng; Chen Nianyong

    2011-07-01

    We compared the impacts of multileaf collimator (MLC) widths (standard MLC width of 10 mm [SMLC] and micro-MLC width of 4 mm [MMLC]) on intensity-modulated radiotherapy (IMRT) planning for nasopharyngeal carcinoma (NPC). Ten patients with NPC were recruited in this study. In each patient's case, plans were generated with the same machine setup parameter and optimizing methods in a treatment planning system according to 2 commercial Elekta MLC devices. All of the parameters were collected from dose-volume histograms of paired plans and evaluated. The average conformity index (CI) and homogeneous index (HI) for the planning gross target volume in IMRT plans with MMLC were 0.790 {+-} 0.036 and 1.062 {+-} 0.011, respectively. Data in plans with SMLC were 0.754 {+-} 0.038 and 1.070 {+-} 0.010, respectively. The differences were statistically significant (p < 0.05). Compared with CI and HI for planning target volume in paired plans, data with MMLC obviously were better than those with SMLC (CI: 0.858 {+-} 0.026 vs. 0.850 {+-} 0.021, p < 0.05; and HI: 1.185 {+-} 0.011 vs. 1.195 {+-} 0.011, p < 0.05). However, there was no statistical significance between evaluated parameters (Dmean, Dmax, D{sub 5}, gEUD, or NTCP) for organs at risk (OARs) in the 2 paired IMRT plans. According to these two kinds of Elekta MLC devices, IMRT plans with the MMLC have significant advantages in dose coverage for the targets, with more efficiency in treatment for NPC but fail to improve dose sparing of the OARs.

  4. ShRNA-mediated silencing of the ubiquitin-specific protease 22 gene restrained cell progression and affected the Akt pathway in nasopharyngeal carcinoma

    PubMed Central

    Zhuang, Ya-Jing; Liao, Zhi-Wei; Yu, Hong-wei; Song, Xian-Lu; Liu, Yuan; Shi, Xing-Yuan; Lin, Xiao-dan; Zhou, Tong-Chong

    2015-01-01

    Ubiquitin-specific protease 22 (USP22) is closely related with poor prognosis of cancer patients. However, the role of USP22 expression in nasopharyngeal carcinoma (NPC) has not been determined. The main aim of this study was to determine the role of USP22 in the pathologic processes of NPC. Immunohistochemistry (IHC), western blot (WB), and real-time polymerase chain reaction (RT-PCR) were used to measure the expression of USP22 in cell lines and tissues of NPC in comparison with expression in non-cancerous cells and tissues. USP22-specific short hairpin RNA (shRNA) was used to knock down USP22 expression in the NPC cell line CNE-1 and CNE-2. Furthermore, the impact of USP22 in cellular proliferation, growth, and cell cycle were detected respectively. WB was used to determine the role of USP22 in the AKT/GSK-3/Cyclin signaling pathway. The expression levels of USP22 were remarkably higher in NPC cell lines and tissues. With cell counting and the MTS assay, cellular growth and proliferation progression of USP22 knockdown cell line was shown to be effectively restrained. The USP22 silencing both in CNE-1 and CNE-2 cells caused them to accumulate in the G0/G1 phase of the cell cycle. USP22 knockdown was also found to modulate the AKT/GSK-3/Cyclin pathway, resulting in downregulation of p-AKT, p-GSK-3β, and cyclinD1. This study suggests that USP22 plays a critical regulatory role in the pathologic processes of NPC, and that it may be a potential biological treatment target in the future. PMID:25482932

  5. Changes of plasma cytokines and chemokines expression level in nasopharyngeal carcinoma patients after treatment with definitive intensity-modulated radiotherapy (IMRT)

    PubMed Central

    Lin, Kai-Rong; Chen, Xiang-ping; Cui, Jin-Huan; Wang, Yue-jian; Luo, Wei

    2017-01-01

    Background Potential clinical application values of certain cytokines and chemokines that participate in the process of tumor growth, invasion, and metastasis have been reported. However, there still lack of biomarkers for a great many of malignancy. This study identified cytokines or chemokines involved in the occurrence and development of nasopharyngeal carcinoma (NPC), which might be a biomarker for noninvasive early diagnosis. Methods The plasma levels of 19 cytokines and chemokines were detected by the luminex liquid array-based multiplexed immunoassays in 39 NPC patients before and after treatment by definitive intensity-modulated radiotherapy (IMRT). Results Plasma levels of almost all of the 19 cytokines and chemokines in NPC patients were higher than healthy controls, while only IFN-γ, IL-1b IL-6, MCP-1, TNF-α, FKN, IL-12P70, IL-2, IL-5 and IP-10 showed significant differences. However, expression levels of most of the 19 cytokines and chemokines decreased after therapy, especially IFN-γ, IL-10, IL-1b, IL-6, IL-8, MCP-1, TNF-α, VEGF, IL-17A, IL-2, IL-5 and MIP-1b, have a dramatic decline. Taking together, plasma levels of IFN-γ, IL-1b, IL-6, MCP-1, TNF-α, IL-2 and IL-5 are significantly increased in NPC patients and dramatically decreased after treatment, suggesting these cytokines and chemokines might play important roles in the progress of NPC. More interestingly, the expression level of MPC-1 is significantly associated with clinical stage. Conclusion MCP-1 might involve in the genesis and development process of NPC, which might serve as a noninvasive biomarker for early diagnosis. PMID:28207826

  6. 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.

  7. Pre-emptive and therapeutic adoptive immunotherapy for nasopharyngeal carcinoma: Phenotype and effector function of T cells impact on clinical response

    PubMed Central

    Smith, Corey; Lee, Victor; Schuessler, Andrea; Beagley, Leone; Rehan, Sweera; Tsang, Janice; Li, Vivian; Tiu, Randal; Smith, David; A. Neller, Michelle; Matthews, Katherine K.; Gostick, Emma; Price, David A.; Burrows, Jacqueline; Boyle, Glen M.; Chua, Daniel; Panizza, Benedict; Porceddu, Sandro V.; Nicholls, John; Kwong, Dora; Khanna, Rajiv

    2017-01-01

    ABSTRACT Adoptive T cell therapy has emerged as a powerful strategy to treat human cancers especially haematological malignancies. Extension of these therapies to solid cancers remains a significant challenge especially in the context of defining immunological correlates of clinical responses. Here we describe results from a clinical study investigating autologous Epstein-Barr virus (EBV)-specific T cells generated using a novel AdE1-LMPpoly vector to treat patients with nasopharyngeal carcinoma (NPC) either pre-emptively in at-risk patients with no or minimal residual disease (N/MRD) or therapeutically in patients with active recurrent/metastatic disease (ARMD). Tolerability, safety and efficacy, including progression-free survival (PFS) and overall survival (OS), were evaluated following adoptive T-cell immunotherapy. Twenty-nine patients, including 20 with ARMD and nine with N/MRD, successfully completed T-cell therapy. After a median follow-up of 18.5 months, the median PFS was 5.5 months (95% CI 2.1 to 9.0 months) and the median OS was 38.1 months (95% CI 17.2 months to not reached). Post-immunotherapy analyses revealed that disease stabilization in ARMD patients was significantly associated with the functional and phenotypic composition of in vitro-expanded T cell immunotherapy. These included a higher proportion of effector CD8+ T-cells and an increased number of EBV-specific T-cells with broader antigen specificity. These observations indicate that adoptive immunotherapy with AdE1-LMPpoly-expanded T cells stabilizes relapsed, refractory NPC without significant toxicity. Promising clinical outcomes in N/MRD patients further suggest a potential role for this approach as a consolidation treatment following first-line chemotherapy.

  8. MiR-34b-3 and miR-449a inhibit malignant progression of nasopharyngeal carcinoma by targeting lactate dehydrogenase A

    PubMed Central

    Li, Huiling; Li, Xiaoling; Ge, Xiaolu; Jia, Liqing; Zhang, Zhezhe; Fang, Renpeng; Yang, Jing; Liu, Jianpin; Peng, Shuping; Zhou, Ming; Xiang, Juanjuan; Zeng, Zhaoyang; Zhou, Wen; Xiong, Wei; Xiao, Gaoming; Fang, Li; Li, Gui-yuan; Li, Zheng

    2016-01-01

    MicroRNA expression profiling assays have shown that miR-34b/c and miR-449a are down-regulated in nasopharyngeal carcinoma (NPC); however, the targets and functions of miR-34b/c and miR-449a in the pathologenesis of NPC remain elusive. In this study, we verified miR-34b/c and miR-449a were significantly reduced with the advance of NPC. Overexpression of miR-34b-3 and miR-449a suppressed the growth of NPC cells in culture and mouse tumor xenografts. Using tandem mass tags for quantitative labeling and LC-MS/MS analysis to investigate protein changes after restoring expression of miR-34b-3, 251 proteins were found to be down-regulated after miR-34b-3 transfection. Through 3 replicate experiments, we found that miR-34b-3 regulated the expression of 15 potential targeted genes mainly clustered in the key enzymes of glycolysis metabolism, including lactate dehydrogenase A (LDHA). Further investigation revealed that miR-34b-3 and miR-449a negatively regulated LDHA by binding to the 3′ untranslated regions of LDHA. Furthermore, LDHA overexpression rescued the miR-34b-3 and miR-449a induced tumor inhibition effect in CNE2 cells. In addition, miR-34b-3 and miR-449a suppressed LDH activity and reduced LD content, which were directly induced by downregulation of the LDHA. Our findings suggest that miR-34b-3 and miR-449a suppress the development of NPC through regulation of glycolysis via targeting LDHA and may be potential therapeutic targets for the treatment of NPC. PMID:27458165

  9. 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.

  10. Changes in Disease Failure Risk of Nasopharyngeal Carcinoma over Time: Analysis of 749 Patients with Long-Term Follow-Up

    PubMed Central

    Liu, Xu; Tang, Ling-Long; Du, Xiao-Jing; Li, Wen-Fei; Chen, Lei; Zhou, Guan-Qun; Guo, Rui; Liu, Qing; Sun, Ying; Ma, Jun

    2017-01-01

    Background: The changes in the risk of disease failure over time in nasopharyngeal carcinoma (NPC) remains unknown. Methods: We analyzed 749 patients treated with intensity-modulated radiotherapy in a single center. The annual hazard rates of disease failure (recurrence or death from any cause) were estimated using the life-table method. Results: In total, 41 (5.5%), 22 (2.9%) and 129 (17.2%) patients developed local, regional and distant recurrences, respectively; 149 (19.9%) patients died. Of the 600 patients who were alive at the last follow-up, 496 (82.7%) had follow-up times longer than 6 years. The 6-year failure-free survival rate was 74.8%. Older age (> 50 years) and advanced stage (Ⅲ-ⅣB) were independent risk factors for disease failure in multivariate analysis. The hazard curve for failure risk in the whole cohort showed a sharp peak at 2 years, changed to a gradually decreasing plateau between years 3 and 5 and then declined sharply. Subgroup analyses revealed similar hazard curves in both sexes. However, the patterns of hazard curve significantly differed between high-risk (> 50 years or stage Ⅲ-ⅣB) and low-risk (≤ 50 years or stage Ⅰ-Ⅱ) patients. Interpretation: The failure hazard rate in NPC didn't decline in a linear manner, but displayed a sharp peak at 2 years. The patterns of hazard function significantly differed between patients with different age and stage. Further studies are warranted to confirm our results. PMID:28261347

  11. 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.

  12. Effects of silencing S100A8 and S100A9 with small interfering RNA on the migration of CNE1 nasopharyngeal carcinoma cells.

    PubMed

    Yan, Lin-Lin; Huang, Yuan-Jiao; Yi, Xiang; Yan, Xue-Min; Cai, Yan; He, Qin; Han, Zi-Jian

    2015-06-01

    The calcium-binding S100 proteins are involved in functions such as cell growth, differentiation, migration, adhesion and signal transduction. S100A8 and S100A9 are highly expressed in a variety of tumor cells, and are implicated in tumor development and progression. However, the role of S100A8 and S100A9 in nasopharyngeal carcinoma (NPC) cell migration is unclear. The present study investigated the effect of S100A8 and S100A9 on migration using a NPC cell line, CNE1. The CNE1 cells were transfected with S100A8 or S100A9 small interfering RNA (siRNA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect S100A8 and S100A9 gene expression. Following the downregulation of S100A8 or S100A9, the effects on cell migration were determined using wound-healing assays. The expression of matrix metalloproteinase-7 (MMP7), a member of the MMP family that is associated with tumor cell invasion and migration, was also detected by RT-qPCR. S100A8 and S100A9 siRNAs effectively suppressed S100A8 and S100A9 gene expression, and substantially inhibited the migration of the CNE1 cells. In addition, MMP7 expression was reduced to varying extents in S100A8 and S100A9 siRNA-treated cells compared with controls. Thus, S100A8 and S100A9 promoted the migration of CNE1 NPC cells.

  13. Further Improvement in Outcomes of Nasopharyngeal Carcinoma With Optimized Radiotherapy and Induction Plus Concomitant Chemotherapy: An Update of the Milan Experience

    SciTech Connect

    Palazzi, Mauro Orlandi, Ester; Bossi, Paolo; Pignoli, Emanuele; Potepan, Paolo; Guzzo, Marco; Franceschini, Marzia; Scaramellini, Gabriele; Cantu, Giulio; Licitra, Lisa; Olmi, Patrizia; Tomatis, Stefano

    2009-07-01

    Purpose: To report the outcome of a consecutive series of patients with nonmetastatic nasopharyngeal carcinoma (NPC), focusing on the impact of treatment-related factors. Methods and Materials: Between 2000 and 2006, 87 patients with NPC were treated with either conventional (two- or three-dimensional) radiotherapy (RT) or with intensity-modulated RT (IMRT). Of these patients, 81 (93%) received either concomitant CHT (24%) or both induction and concomitant chemotherapy (CHT) (69%). Stage was III in 36% and IV in 39% of patients. Outcomes in this study population were compared with those in the previous series of 171 patients treated during 1990 to 1999. Results: With a median follow-up of 46 months, actuarial rates at 3 years were the following: local control, 96%; local-regional control, 93%; distant control (DC), 90%; disease-free survival (DFS), 82%; overall survival, 90%. In Stage III to IV patients, distant control at 3 years was 56% in patients treated with concomitant CHT only and 92% in patients treated with both induction and concomitant CHT (p = 0.014). At multivariate analysis, histology, N-stage, RT technique, and total RT dose had the strongest independent impact on DFS (p < 0.05). Induction CHT had a borderline effect on DC (p = 0.07). Most dosimetric statistics were improved in the group of patients treated with IMRT compared with conventional 3D technique. All outcome endpoints were substantially better in the study population compared with those in the previous series. Conclusions: Outcome of NPC has further improved in the study period compared with the previous decade, with a significant effect of RT technique optimization. The impact of induction CHT remains to be demonstrated in controlled trials.

  14. Time trends of nasopharyngeal carcinoma in urban Guangzhou over a 12-year period (2000-2011): declines in both incidence and mortality.

    PubMed

    Li, Ke; Lin, Guo-Zhen; Shen, Ji-Chuan; Zhou, Qin

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is an uncommon disease in most countries but occurs with much greater frequency in southern China. This study aimed to examine the secular trends of NPC in urban Guangzhou over the time period of 2000-2011 using data from the Guangzhou Cancer Registry. Age-adjusted annual incidence rates of NPC were calculated by the direct method using the WHO World Standard Population (1960) as the reference. The average annual percentage change (AAPC) was used as an estimate of the trend. A total of 7,532 new cases of NPC and 3,449 related deaths were registered. In both genders, the peak incidence occurred in the 50- to 59-year age group, and this age distribution pattern remained similar throughout. The AAPC in NPC incidence rates was -3.26% (95% CI: -5.4%--1.1) for males and -5.74% (95% CI: -8.9%--2.5) for females, resulting in a total decrease of 39.3% (from 22.14 to 13.44 per 100,000 population) for males and 48.6% (from 10.1 to 5.18 per 100,000 population) for females over this 12-year period. The AAPCs in NPC mortality rates were -4.62% (95%CI: -3.5%--5.7) for males and -6.75% (95% CI: -5.2%--8.3) for females, resulting in a total decrease of -46.1% (from 12.1 to 6.54 per 100,000 population) for males and 51.7% (from 4.14 to 2.00 per 100,000 population) for females. The age-adjusted incidence and mortality rates of NPC declined during 2000-2011 in urban Guangzhou but remained high. Future efforts to improve prevention, early detection and treatment strategies are needed.

  15. Molecular Characterization and Clinical Implications of Spindle Cells in Nasopharyngeal Carcinoma: A Novel Molecule-Morphology Model of Tumor Progression Proposed

    PubMed Central

    Luo, Weiren; Yao, Kaitai

    2013-01-01

    Up to now, the precise molecular and morphological changes underlying the invasive and metastatic properties of nasopharyngeal carcinoma (NPC) remain largely unresolved. We speculate that neoplastic spindle cells, which are prominently found in the invasive tumor front and the surrounding stroma, might be responsible for the aggressive patterns. Expression profiling of various biomarkers relevant to cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) was performed by tissue microarray-based immunohistochemistry in NPC samples. The expression of EBER and LMP1 was detected by in situ hybridization and immunohistochemistry, respectively. We found that overexpression of CSCs-related markers (ALDH1, Nanog and ABCG2) and up-regulation of EMT markers (Fibronectin, MMP-2, Periostin, SPARC, Snail and Slug), together with E- to N-cadherin switching, occurred preferentially in tumors containing a large proportion of spindle-shaped malignant cells. Furthermore, CSCs-like properties were highly present in spindle cells compared with non-spindle cells of tumors, and correlated strongly with EMT features. In addition, EBV-related factors EBER and LMP1 were highly expressed and correlated strongly with CSCs and EMT characteristics in neoplastic spindle cells. Importantly, high proportion of spindle cells (≥20%) correlated significantly with various aggressive aspects including lymph node metastasis (P = 0.031) and local recurrence (P = 0.014). Patients with high proportion of spindle cells had poor survival (P = 0.004), though it was not an independent value. In conclusion, we demonstrate that spindle cells could be valuable morphological indicators of tumor progression and unfavorable prognosis of NPC. An integrated molecule-morphology model of NPC firstly constructed may shed significant light on the metastatic cascade and clinical relevance of patients. PMID:24349446

  16. Assessment of anatomical and dosimetric changes by a deformable registration method during the course of intensity-modulated radiotherapy for nasopharyngeal carcinoma.

    PubMed

    Lu, Jie; Ma, Yidong; Chen, Jinhu; Wang, Liming; Zhang, Guifang; Zhao, Mukun; Yin, Yong

    2014-01-01

    The aim of this study was to quantify the anatomic variations and the dosimetric effects accessed by a deformable registration method throughout the entire course of radiotherapy, and to evaluate the necessity of replanning for patients with nasopharyngeal carcinoma (NPC). Plan1(CT1) was based on the original CT, and Plan2(CT2) was generated from the midtreatment CT scan acquired after 25 fractions of IMRT of Plan1. Both sets of CTs, RT structures and RT doses for the two group plans were transferred to a workstation, and then a hybrid IMRT plan, Plan1(CT2), was generated by deforming doses of Plan1 to CT2. Subsequently, the accumulated plan, Plan1 + 2(CT2), was generated to quantify the actual dosimetric effects during the course. The transverse diameter of the neck at the center of the odontoid process was (15.4 ± 1.0) cm and (14.4 ± 1.1) cm in CT1 and CT2, respectively (P < 0.05). Compared with CT1, the mean volumes of the right and left parotid glands were significantly decreased by (24.6 ± 11.9)% and (35.1 ± 20.1)%, respectively. Comparison of Plan1 (CT1) with Plan1 (CT2) indicated that the doses to targets decreased without replanning. With repeated CT and replanning after 25 fractions, the doses to targets would be improved. The doses to normal tissue were increased without replanning. For eight patients out of 12, the doses to the spinal cord and brainstem exceeded the constraints without replanning, while the corresponding values decreased with replanning. During the entire course of IMRT, the volumes of the targets and the parotid glands would be reduced significantly. Midtreatment CT scanning and replanning are recommended to ensure adaptive doses to the targets and critical normal tissues.

  17. miR-29a/b Enhances Cell Migration and Invasion in Nasopharyngeal Carcinoma Progression by Regulating SPARC and COL3A1 Gene Expression

    PubMed Central

    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

  18. Epstein-Barr virus glycoprotein gH/gL antibodies complement IgA-viral capsid antigen for diagnosis of nasopharyngeal carcinoma.

    PubMed

    Li, Rui-Chen; Du, Yong; Zeng, Qiu-Yao; Tang, Lin-Quan; Zhang, Hua; Li, Yan; Liu, Wan-Li; Zhong, Qian; Zeng, Mu-Sheng; Huang, Xiao-Ming

    2016-03-29

    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.

  19. Correlations of the expressions of c-jun and Egr-1 proteins with clinicopathological features and prognosis of patients with nasopharyngeal carcinoma.

    PubMed

    Zhong, Jia-Teng; Wang, Hai-Jun; Yu, Jian; Zhang, Jing-Hang; Wang, Shi-Feng; Yang, Xue; Su, Wei

    2017-02-27

    This study intended to explore the correlation of the expressions of c-Jun and Egr-1 proteins with clinicopathological features and prognosis of patients with nasopharyngeal carcinoma (NPC). From January 2008 to January 2011, 123 NPC patients and 59 patients with chronic rhinitis were enrolled in this study. Fresh NPC and normal nasopharynx tissue specimens were obtained during surgery. Immunohistochemistry (IHC) was adopted to determine the positive expressions of the c-Jun and Egr-1 proteins. A 5-year clinical follow-up was conducted on all NPC patients. The Kaplan-Meier survival curve and Cox regression model were used for survival analysis. Compared with normal nasopharynx tissues, c-Jun expression was up-regulated but Egr-1 expression was down-regulated in NPC tissues. NPC patients with stage T3-T4 or stage III-IV had higher positive rates of c-Jun expression than those with stage T1-T2 or stage I-II. However, the positive rates of Egr-1 expression was higher in patients with stage T1-T2 or stage III-IV than those with stage T3-T4 or stage I-II. The survival rate of NPC patients with high c-Jun expression was lower than those with low/negative c-Jun expression, while the survival rate of NPC patients with high Egr-1 expression was higher than those with low/negative Egr-1 expression. The Cox regression analysis revealed that stage T3-T4, high c-Jun expression, and low Egr-1 expression were risk factors for poor prognosis of NPC patients. In conclusion, our study suggests that the c-Jun and Egr-1 proteins can serve as novel potential biomarkers for the early diagnosis and prognosis prediction of NPC.

  20. Direct sequencing and characterization of a clinical isolate of Epstein-Barr virus from nasopharyngeal carcinoma tissue by using next-generation sequencing technology.

    PubMed

    Liu, Pan; Fang, Xiaodong; Feng, Zizhen; Guo, Yun-Miao; Peng, Rou-Jun; Liu, Tengfei; Huang, Zhiyong; Feng, Yue; Sun, Xiaoqing; Xiong, Zhiqiang; Guo, Xiaosen; Pang, Sha-Sha; Wang, Bo; Lv, Xiaojuan; Feng, Fu-Tuo; Li, Da-Jiang; Chen, Li-Zhen; Feng, Qi-Sheng; Huang, Wen-Lin; Zeng, Mu-Sheng; Bei, Jin-Xin; Zhang, Yong; Zeng, Yi-Xin

    2011-11-01

    Epstein-Barr virus (EBV)-encoded molecules have been detected in the tumor tissues of several cancers, including nasopharyngeal carcinoma (NPC), suggesting that EBV plays an important role in tumorigenesis. However, the nature of EBV with respect to genome width in vivo and whether EBV undergoes clonal expansion in the tumor tissues are still poorly understood. In this study, next-generation sequencing (NGS) was used to sequence DNA extracted directly from the tumor tissue of a patient with NPC. Apart from the human sequences, a clinically isolated EBV genome 164.7 kb in size was successfully assembled and named GD2 (GenBank accession number HQ020558). Sequence and phylogenetic analyses showed that GD2 was closely related to GD1, a previously assembled variant derived from a patient with NPC. GD2 contains the most prevalent EBV variants reported in Cantonese patients with NPC, suggesting that it might be the prevalent strain in this population. Furthermore, GD2 could be grouped into a single subtype according to common classification criteria and contains only 6 heterozygous point mutations, suggesting the monoclonal expansion of GD2 in NPC. This study represents the first genome-wide analysis of a clinical isolate of EBV directly extracted from NPC tissue. Our study reveals that NGS allows the characterization of genome-wide variations of EBV in clinical tumors and provides evidence of monoclonal expansion of EBV in vivo. The pipeline could also be applied to the study of other pathogen-related malignancies. With additional NGS studies of NPC, it might be possible to uncover the potential causative EBV variant involved in NPC.

  1. Serologic biomarkers of Epstein-Barr virus correlate with TNM classification according to the seventh edition of the UICC/AJCC staging system for nasopharyngeal carcinoma.

    PubMed

    Sun, Peng; Chen, Cui; Cheng, Yi-Kan; Zeng, Zhi-Jian; Chen, Xin-Lin; Liu, Li-Zhi; Gu, Mo-Fa

    2014-09-01

    This study aimed to investigate the association between Epstein-Barr virus (EBV)-related biomarkers and TNM classification according to the seventh edition of AJCC/UICC staging system for nasopharyngeal carcinoma. Serum VCA-IgA and EA-IgA titers and plasma EBV-DNA load were quantified at baseline in 779 patients; the rates of positivity and titers/load were compared by TNM classification. The VCA-IgA-positive rate was significantly associated with advanced N classification and stage; the EA-IgA-positive rate with advanced T and N classifications and stage; the EBV-DNA-positive rate with advanced T, N and M classifications and stage. The percentage of triple-positive patients was higher in patients with advanced TNM classification. The VCA-IgA titer and EA-IgA titer correlated positively with T classification, N classification and disease stage (1:117 in Stage I, 1:188.4 in Stage II, 1:231.12 in Stage III, 1:265.91 in Stage IV, and 1:18.34 in Stage I, 1:32.11 in Stage II, 1:34.77 in Stage III, 1:37.65 in Stage IV, respectively). EBV DNA load correlated positively with T, N and M classification and stage [median lg (EBV DNA): 0 (IQ range 0-1.85) in Stage I, 1.32 (0-3.51) in Stage II, 3.33 (0-4.30) in Stage III, 3.83 (2.85-4.71) in Stage IV]. Serum VCA-IgA/EA-IgA titers and plasma EBV DNA correlated strongly with TNM classification according to the seventh edition of the AJCC/UICC; however, plasma EBV DNA load could accurately predict metastatic disease. EBV serological biomarkers may enhance the accuracy of TNM staging and help to avoid excessive imaging examinations in routine evaluation.

  2. Albumin-to-Alkaline Phosphatase Ratio: A Novel Prognostic Index of Overall Survival in Cisplatin-based Chemotherapy-treated Patients with Metastatic Nasopharyngeal Carcinoma

    PubMed Central

    Nie, Man; Sun, Peng; Chen, Cui; Bi, Xiwen; Wang, Yu; Yang, Hang; Liu, Panpan; Li, Zhiming; Xia, Yi; Jiang, Wenqi

    2017-01-01

    The Albumin-to-Alkaline Phosphatase Ratio (AAPR) has been recently revealed as a prognostic index for hepatocellular carcinoma, whereas its role in metastatic nasopharyngeal cancer (NPC) remains unclear. The aim of this study was to evaluate the clinical value of AAPR in patients with metastatic NPC. We retrospectively reviewed 209 metastatic NPC patients treated with cisplatin-based regimens. Survival data were calculated using the Kaplan-Meier method and were compared using the log-rank test. Univariate and multivariate survival analyses were conducted using the Cox proportional hazards regression methodology. The optimal cutoff level of AAPR for assessing overall survival (OS) was 0.447, which was determined by R software. An AAPR less than 0.447 was significantly associated with a higher lactate dehydrogenase (LDH) level (273 vs. 185 U/L, P = 0.004), a higher EBV DNA viral load (5.59×105 vs. 3.49×104 copies/ml, P = 0.001), and more liver and bone metastases (P = 0.005 and P = 0.001, respectively). Additionally, patients with an AAPR < 0.447 had a shorter overall survival and progression-free survival (hazard ratio: 3.269, 95% confidence interval: 1.710-6.248; HR: 2.295, 95% confidence interval: 1.217-4.331, respectively) than those with an AAPR ≥ 0.447. Our study suggested that the AAPR might be a novel prognostic factor in metastatic NPC patients treated with cisplatin-based regimens. However, a prospective study to validate its prognostic value is needed, and the mechanisms underlying the low AAPR and poor survival in metastatic NPC need to be further investigated. PMID:28382143

  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.

  4. Delayed-type hypersensitivity (DTH) immune response related with EBV-DNA in nasopharyngeal carcinoma treated with autologous dendritic cell vaccination after radiotherapy.

    PubMed

    Li, Feng; Song, Dan; Lu, Yue; Zhu, Huanfeng; Chen, Zhenzhang; He, Xia

    2013-04-01

    The aim of this work was to investigate the outcome of an autologous dendritic cell (DC) vaccination in patients with stage II/III nasopharyngeal carcinomas (NPC). From 38 patients with stage II/III Epstein-Barr virus (EBV)-associated NPCs after a radiotherapy, 16 human leukocyte antigen-A2 (HLA-A2)-positive patients were enrolled and medicated with autologous DCs, which were pulsed with HLA-A2-restricted EBV-encoded latent membrane protein 2A (LMP2A) peptides. The lymphocyte subsets, serum cytokines, and EBV-DNA levels as well as the delayed-type hypersensitivity (DTH) responses were determined after vaccination combined with a radiotherapy/chemotherapy. The serum levels of interleukin-2 and interferon-γ (P<0.05) as well as the percentage of natural killer and CD4+T cells increased significantly (P<0.05) after the vaccination. Nine of 16 (56.25%) patients showed a positive skin response to the HLA-A2 restricted EBV LMP2A peptides in a DTH test. The serum EBV-DNA level decreased significantly from 1519 ± 384 to 1214 ± 211 copies/mL in the 9 DTH-positive patients (P=0.0310). No unanticipated or serious toxicity was observed and the vaccine was well tolerated. In conclusion, in NPC patients vaccinated after radiotherapy with autologous DCs, which were pulsed with EBV LMP2A peptides, Th1-specific immune responses were elicited particularly in DTH test positive individuals. The clinical results obtained are encouraging and the EBV-specific HLA-A2-restricted DC vaccination is a promising treatment for EBV-related NPCs.

  5. Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

    SciTech Connect

    Tan, Terence; Lim, Wan-Teck; Fong, Kam-Weng; Cheah, Shie-Lee; Soong, Yoke-Lim; Ang, Mei-Kim; Ng, Quan-Sing; Tan, Daniel; Ong, Whee-Sze; Tan, Sze-Huey; Yip, Connie; Quah, Daniel; Soo, Khee-Chee; Wee, Joseph

    2015-04-01

    Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.

  6. Circulating Epstein-Barr virus microRNAs miR-BART7 and miR-BART13 as biomarkers for nasopharyngeal carcinoma diagnosis and treatment.

    PubMed

    Zhang, Gaohong; Zong, Jingfeng; Lin, Shaojun; Verhoeven, Rob J A; Tong, Shuang; Chen, Yixin; Ji, Mingfang; Cheng, Weimin; Tsao, Sai-Wah; Lung, Maria; Pan, Jianji; Chen, Honglin

    2015-03-01

    More than 75% of nasopharyngeal carcinoma (NPC) patients have already developed local or regional spread at diagnosis, which hampers effective treatment and results in a poor prognosis. It is essential to characterize more sensitive and specific biomarkers for screening of high risk individuals and assessment of NPC treatment effectiveness. NPC is an Epstein-Barr virus (EBV) associated tumor in which only a few viral proteins but more than 20 BamHI A rightward transcripts (BART) microRNAs are detected, at abundant levels. We hypothesized that these BART microRNAs may be novel biomarkers for NPC. Systematic analysis of EBV BART microRNA expression profiles in EBV latently infected Mutu I and Mutu III cell lines, EBV-harboring NPC and noncancerous NP cells found that miR-BART3, miR-BART7 and miR-BART13 microRNAs are highly expressed and regularly secreted into the extracellular environment of NPC cells. These BART microRNAs were evaluated for used as potential NPC biomarkers. Analysis of plasma specimens obtained from NPC patients (n = 89), and healthy (n = 28) and non-NPC tumor patient controls (n = 18) found levels of both miR-BART7 and miR-BART13, but not miR-BART3, to be distinctly presence among NPC patients, with elevated levels being particularly apparent among patients with advanced disease. Receiver operating characteristic curve analysis combining miR-BART7 and miR-BART13 levels produces a 90% predictive value for the presence of NPC. Analysis of 41 NPC patients before and after radiotherapy showed that miR-BART7 and miR-BART13, but not miR-BART3, were diminished after treatment. These results indicate that EBV microRNAs, miR-BART7 and miR-BART13, may constitute useful new serological biomarkers for diagnosis of NPC and prediction of treatment efficacy.

  7. 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

  8. 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

  9. 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

  10. The correlation between the comprehensive nutrition index and quality of life of patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy.

    PubMed

    Ma, Liqin; Wu, Tingting; Pan, Jianji; Kong, Xiangquan; Guo, Qiaojuan; Yang, Ling; Zhang, Yu; Lin, Shaojun; Chen, Chuanben; Huang, Chaobin

    2014-01-01

    The purpose of this study was to compare the changing tendency of nutrition with 54 nasopharyngeal carcinoma patients during intensity-modulated radiation therapy (IMRT), and to investigate the correlation between comprehensive nutritional status and quality of life (QoL), which was assessed by the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire. The nutritional index, including body mass index, ideal body weight percentage, usual body weight percentage, albumin, hemoglobin, and total lymphocyte count (TLC), was evaluated at 2 time points: within 48 h after admission (T1) and at the end of treatment with IMRT (T2). A statistically significant downgrade of every index was observed during IMRT. A comprehensive nutritional model was established by principal components analysis at T2. QoL scores of functional (P = 0.002) and the global QoL scales (P = 0.001) existed a positive correlation with comprehensive nutritional status. QoL scores of symptom scales (P = 0.002) and 6 single items (P = 0.005) had a negative correlation with it. The scores of global QoL scales in comprehensive nutrition of normal (20.4%), moderate (55.6%), and severe malnutrition (24.1%) were 69.70 ± 17.98, 48.33 ± 19.25, and 37.18 ± 24.67, respectively. Patients with different nutritional status had different QoL (B = 10.405, SE = 2.828, t = 3.680, P = 0.001). Multiaspect nutritional supports should be enhanced to improve patients' comprehensive nutritional status during treatment.

  11. 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.

  12. Prognostic Correlations between ABO Blood Group and Pre-Treatment Plasma Epstein-Barr Virus DNA in Patients with Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy

    PubMed Central

    Li, Wen-Fei; Zhang, Yuan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2016-01-01

    Purpose The objective of this study is to assess the prognostic value of ABO blood group in nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). Patients and Methods We retrospectively reviewed the data on 1397 patients with non-metastatic, newly diagnosed NPC treated using IMRT. Patient survival between different ABO blood groups were compared using log-rank test. Cox hazards model was adopted to establish independent prognostic factors. Results In our study, the distribution of the A, B, AB and O blood groups was 26.6% (372/1397), 26.2% (366/1397), 5.2% (73/1397) and 42.0% (586/1397), respectively. The cut-off value of pre-treatment Epstein-Barr virus (EBV) DNA based on disease-free survival (DFS) was 1355 copies/ml (area under curve [AUC], 0.649; sensitivity, 0.76; specificity, 0.496) for the whole cohort. Estimated four-year DFS, overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) rates were 81.7%, 89.2%, 89.4% and 92.3% for blood group A; 82.1%, 89.3%, 89.0% and 92.0% for group B; 83.3%, 88.1%, 86.2% and 95.5% for group AB, 80.9%, 90.7%, 88.4% and 90.2% for group O (P > 0.05 for all rates). Multivariate analysis revealed ABO blood group was not an independent prognostic factor for DFS, OS, DMFS or LRRFS (P > 0.05 for all rates) after adjusting for plasma EBV DNA in either the whole cohort or subgroup analysis by gender. Conclusions The prognostic value of ABO blood group may be limited for patients with NPC in the era of IMRT, and no substantial correlation between ABO blood group and plasma EBV DNA was observed. PMID:27835689

  13. 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.

  14. High numbers of granzyme B/CD8-positive tumour-infiltrating lymphocytes in nasopharyngeal carcinoma biopsies predict rapid fatal outcome in patients treated with curative intent.

    PubMed

    Oudejans, Joost J; Harijadi, Hari; Kummer, J Alain; Tan, I Bing; Bloemena, Elizabeth; Middeldorp, Jaap M; Bladergroen, Belinda; Dukers, Danny F; Vos, Wim; Meijer, Chris J L M

    2002-12-01

    This study determined whether tumour-infiltrating lymphocytes (TILs) in nasopharyngeal carcinomas (NPCs) include activated cytotoxic T lymphocytes (CTLs) and whether the numbers of activated CTLs in these biopsies are related to clinical outcome. Moreover, the study investigated whether the numbers of activated CTLs are associated with the expression of MHC class I proteins and the granzyme B antagonist PI-9 in the tumour cells. Forty-three Indonesian NPC patients (T(1-3), N(1-3), M(0)), who were treated with curative intent by radiotherapy only, were studied. Tumour-infiltrating activated CTLs were detected using antibodies against granzyme B, CD8, and CD56. Expression of MHC class I proteins and PI-9 was also determined by immunohistochemistry. Granzyme B-positive TILs were detected in all NPC biopsies. The presence of a high percentage (>25%) of granzyme B-positive TILs appeared to be a very strong predictor of a rapid fatal clinical outcome, independent of stage. Complete absence of MHC class I heavy chain expression in tumour cells was observed in 11 of 31 evaluable cases and low levels were observed in seven additional cases. No association between MHC class I expression and the numbers of granzyme B-positive TILs was observed. Expression of the granzyme B antagonist PI-9 in tumour cells was detected in three cases. It is concluded that the presence of many granzyme B-positive TILs in a selected group of Indonesian NPC patients is a strong and stage-independent marker for a rapid fatal clinical outcome.

  15. The AQP-3 water channel and the ClC-3 chloride channel coordinate the hypotonicity-induced swelling volume in nasopharyngeal carcinoma cells.

    PubMed

    Zhang, Haifeng; Li, Huarong; Liu, Enqi; Guang, Yutao; Yang, Lili; Mao, Jianwen; Zhu, Linyan; Chen, Lixin; Wang, Liwei

    2014-12-01

    Cell volume regulation is a fundamental activity to maintain cell survival, and aquaporins and chloride channels play important roles in this process. However, the interactions between these channels are far from clear. In this study, the interactions between AQP-3 and ClC-3 were investigated in CNE-1 and CNE-2Z nasopharyngeal carcinoma cells, which are well and poorly differentiated, respectively. The correlation coefficient of AQP-3 and ClC-3 protein phylogenetic trees was 0.319. In CNE-1 cells, there are overlapping distributions of AQP-3 and ClC-3, mainly in the plasma membrane. This was confirmed by the co-immunoprecipitation of AQP-3 and ClC-3, showing that they could be interlinked and form complexes. AQP-3 over-expression had no significant effects on swelling-induced Cl(-) currents (ICl,swell); however, ICl,swell could be inhibited by aquaporin blockers, anti-AQP-3 antibodies and AQP-3-siRNAs. In addition, the AQP-3 expression was decreased by down-regulation of ClC-3 expression, indicating that ClC-3 can modulate the expression of AQP-3 proteins. The effects of aquaporin blockers, anti-AQP-3 antibodies and AQP-3 over-expression on ICl,swell in CNE-2Z cells were consistent with those in CNE-1 cells. In conclusion, AQP-3 and ClC-3 are functionally-related integral membrane channel proteins, and their interactions are involved in cell volume regulation in CNE-1 and CNE-2Z cells. The opening of ClC-3 transports Cl(-) across the cell membrane and then drives the efflux of water through AQP-3 channels and ion channels; AQP-3 may interact with ClC-3 in order to regulate the effluxes of chloride and water.

  16. The C-reactive Protein/Albumin Ratio Is an independent Prognostic Factor for Overall Survival in Patients with Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy.

    PubMed

    Tao, Chang-Juan; Chen, Yuan-Yuan; Jiang, Feng; Feng, Xing-Lai; Jin, Qi-Feng; Jin, Ting; Piao, Yong-Feng; Chen, Xiao-Zhong

    2016-01-01

    This study aims to investigate the prognostic value of the C-reactive protein/albumin (CRP/ALB) ratio in nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. A total of 719 patients with NPC treated between January 2007 and December 2012 were retrospectively reviewed. Serum albumin and CRP levels were measured before treatment. The associations between the CRP/ALB ratio and clinicopathological parameters were analyzed. Multivariate analyses using the Cox proportional hazards model were performed to identify significant prognostic factors associated with overall survival (OS). The prognostic value of the CRP/ALB ratio was determined using receiver operating characteristic (ROC) curve analysis. The optimal CRP/ALB ratio cutoff value was 0.141. High CRP/ALB ratio was significantly associated with older age (P < 0.001), more advanced T category (P < 0.001) and advanced TNM stage (P = 0.024). Patients with an elevated CRP/ALB ratio (≥ 0.141) had poorer OS than those with a CRP/ALB ratio < 0.141 (5-year OS rates: 91.9% vs. 78.1%; P < 0.001). Multivariate analysis suggested clinical T category [hazard ratio (HR) 2.284; 95% confidence interval (CI), 1.429-3.652; P = 0.001]; clinical N category (HR 1.575; 95% CI, 1.007-2.464; P = 0.047) and CRP/ALB ratio (HR 2.173; 95% CI, 1.128-3.059; P = 0.015) were independently associated with OS. In conclusion, pretreatment CRP/ALB ratio is an objective biomarker with significant prognostic value for OS in NPC. The CRP/ALB ratio can enhance conventional TNM staging to stratify patients and may help facilitate individualized treatment of high-risk cases.

  17. 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

  18. A new T staging system for nasopharyngeal carcinoma based on intensity-modulated radiation therapy: results from a prospective multicentric clinical study

    PubMed Central

    Kang, Min; Zhou, Pingting; Wei, Tingting; Zhao, Tingting; Long, Jianxiong; Li, Guisheng; Yan, Haolin; Feng, Guosheng; Liu, Meilian; Zhu, Jinxian; Wang, Rensheng

    2017-01-01

    Purpose: This prospective multicentric study aimed to establish a new clinical T staging standard for nasopharyngeal carcinoma (NPC) based on intensity-modulated radiotherapy (IMRT). Methods and materials: Between January 2006 and December 2009, four hundred and ninety-two NPC patients undergoing IMRT were staged according to the seventh edition of the UICC/AJCC staging system. The Kaplan-Meier method was used to calculate survival rates, and the log-rank test was used to compare survival differences. Results: The 5-year overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), and distant metastasis-free survival (DMSF) rates were 80.5%, 78.6%, 94.1%, and 84.3%, respectively. Univariate and multivariate analyses showed that the invasion of the nasal cavity, parapharyngeal space, oropharynx, skull base, internal pterygoid muscle, external pterygoid muscle, paranasal sinus, infratemporal fossa, orbit, cranial nerves, cavernous sinus, and intracalvarium were independent prognostic factors (P<0.05). According to the results of risk variety and survival curves, we suggest that the new T staging system for NPC based on magnetic resonance imaging and intensity modulated radiation therapy can be classified as T1 (nasopharynx, nasal cavity, parapharyngeal space, oropharynx, skull base and internal pterygoid muscle) and T2 (external pterygoid muscle, paranasal sinus, infratemporal fossa, orbit, cranial nerves, cavernous sinus and intracalvarium). Compared to the seventh edition of UICC/AJCC staging system, our new recommended staging system performs better in risk difference and distribution balance. Furthermore, the differences between the substages of 5-year curves of LRFS, DMFS and OS were all statistically significant in our new recommended staging system. Conclusions: Our new recommended staging system is more adaptable to IMRT and can predict the prognosis of NPC patient in a more objective and accurate manner.

  19. Investigation of long-term survival outcomes and failure patterns of patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: a retrospective analysis

    PubMed Central

    Zhao, Wei; Lei, Hao; Zhu, Xiaodong; Li, Ling; Qu, Song; Liang, Xia

    2016-01-01

    Intensity-modulated radiotherapy (IMRT) has replaced the conventional radiotherapy (2D-RT) and improved clinical efficacy in Nasopharyngeal Carcinoma (NPC) patients. In the present study, we retrospectively analyzed the clinical characteristics of patients with NPC treated with IMRT to assess the long-term survival outcomes and failure patterns. Of the 527 patients, One hundred and twenty-one patients experienced treatment failure, 86 patients developed distant metastases, and 12 patients developed a second primary tumor. The local and regional recurrence rates were 31.4% and 14.0%, respectively. The 5-year overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), regional relapse-free survival (RRFS), and distant metastatic relapse-free survival (DMFS) rates were 80.9%, 75.6%, 91.7%, 96.2%, and 83.0%, respectively. The 5-year LRFS rates of Stage T1-4 patients were 100.0%, 93.1%, 92.0%, and 85.8%, respectively. The 5-year DMFS rates of Stage N0-3 patients were 95.0%, 86.1%, 79.5%, and 67.2%, respectively. Multivariate analysis showed age and T-stage were independent predictors of OS, T-stage was an independent predictor of LRFS, and age and N-stage were independent predictors of PFS and DMFS. In summary, the improved treatment results with IMRT are primarily due to the achievement of a higher local tumor control rate and OS in NPC patients. However, distant metastasis was the most commonly observed failure pattern after treatment. These results provide deep insights about the value of IMRT in the treatment and prognosis of NPC patients. PMID:27894100

  20. The protein level and transcription activity of activating transcription factor 1 is regulated by prolyl isomerase Pin1 in nasopharyngeal carcinoma progression.

    PubMed

    Huang, Guo-Liang; Liao, Dan; Chen, Hua; Lu, Yan; Chen, Liyong; Li, Huahui; Li, Binbin; Liu, Weilong; Ye, Caiguo; Li, Tong; Zhu, Zhu; Wang, Jian; Uchida, Takafumi; Zou, Ying; Dong, Zigang; He, Zhiwei

    2016-12-29

    The function of activating transcription factor 1 (ATF1) and the mechanism about why ATF1 was over-phosphorylated in nasopharyngeal carcinoma (NPC) progression is completely undiscovered. In this study, a series of experiments both in vitro and in vivo were used to characterize a promotive function of ATF1 in NPC tumorigenesis and identify prolyl isomerase Pin1 as a novel regulator of ATF1 at post-transcription. First, we found that overexpression of ATF1 promoted colony formation in NPC. However, the high protein level of ATF1 in NPC was not resulted from high mRNA level. Then, a direct interaction between Pin1 and ATF1 at Thr184 was demonstrated using mammalian two-hybrid assay and coimmunoprecipitation. Cycloheximide (CHX) treatment indicated Pin1 stabilized the expression of ATF1 at post-transcription level. We confirmed that Pin1 upregulated ATF1 transcriptional activity of Bcl-2 using luciferase reporter assay, quantitative RT-PCR and western blot. Furthermore, the newly identified phosphorylation of ATF1 at Thr184 was suggested to have an important role in ATF1 function of transcription and tumor promotion. Finally, high expression of Pin1 in NPC tissue was found to be positively correlated with ATF1. The ATF1 promoted NPC tumorigenesis was regulated by Pin1 both in vitro and in vivo. All these findings clearly state that Pin1 is a novel regulator of ATF1 at Thr184 and thereby enhances ATF1 transcription activity and tumorigenesis promotive function in NPC.

  1. The protein level and transcription activity of activating transcription factor 1 is regulated by prolyl isomerase Pin1 in nasopharyngeal carcinoma progression

    PubMed Central

    Huang, Guo-Liang; Liao, Dan; Chen, Hua; Lu, Yan; Chen, Liyong; Li, Huahui; Li, Binbin; Liu, Weilong; Ye, Caiguo; Li, Tong; Zhu, Zhu; Wang, Jian; Uchida, Takafumi; Zou, Ying; Dong, Zigang; He, Zhiwei

    2016-01-01

    The function of activating transcription factor 1 (ATF1) and the mechanism about why ATF1 was over-phosphorylated in nasopharyngeal carcinoma (NPC) progression is completely undiscovered. In this study, a series of experiments both in vitro and in vivo were used to characterize a promotive function of ATF1 in NPC tumorigenesis and identify prolyl isomerase Pin1 as a novel regulator of ATF1 at post-transcription. First, we found that overexpression of ATF1 promoted colony formation in NPC. However, the high protein level of ATF1 in NPC was not resulted from high mRNA level. Then, a direct interaction between Pin1 and ATF1 at Thr184 was demonstrated using mammalian two-hybrid assay and coimmunoprecipitation. Cycloheximide (CHX) treatment indicated Pin1 stabilized the expression of ATF1 at post-transcription level. We confirmed that Pin1 upregulated ATF1 transcriptional activity of Bcl-2 using luciferase reporter assay, quantitative RT-PCR and western blot. Furthermore, the newly identified phosphorylation of ATF1 at Thr184 was suggested to have an important role in ATF1 function of transcription and tumor promotion. Finally, high expression of Pin1 in NPC tissue was found to be positively correlated with ATF1. The ATF1 promoted NPC tumorigenesis was regulated by Pin1 both in vitro and in vivo. All these findings clearly state that Pin1 is a novel regulator of ATF1 at Thr184 and thereby enhances ATF1 transcription activity and tumorigenesis promotive function in NPC. PMID:28032861

  2. 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.

  3. CD4 and CD8 T cell responses to tumour-associated Epstein-Barr virus antigens in nasopharyngeal carcinoma patients.

    PubMed

    Lin, Xiaorong; Gudgeon, Nancy H; Hui, Edwin P; Jia, Hui; Qun, Xue; Taylor, Graham S; Barnardo, Martin C N M; Lin, C Kit; Rickinson, Alan B; Chan, Anthony T C

    2008-07-01

    Nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated tumour common in Southern Chinese populations, is a potentially important target for T cell-based immunotherapy. The tumour cells are HLA class I- and II-positive and express a limited subset of EBV latent proteins, namely the nuclear antigen EBNA1 and the latent membrane proteins LMP2 and (in some cases) LMP1. To ask whether the tumour develops in the presence of a potentially protective host response or in its absence, we set out to determine the prevailing levels of CD4+ and CD8+ T cell memory to these proteins in NPC patients at tumour diagnosis. We first screened healthy Chinese donors against Chinese strain EBNA1, LMP1 and LMP2 sequences in Elispot assays of interferon-gamma release and identified the immunodominant CD4+ and CD8+ epitope peptides presented by common Chinese HLA alleles. Then, comparing 60 patients with >70 healthy controls on peptide epitope mini-panels, we found that T cell memory to CD4 epitopes in all three proteins was unimpaired in the blood of patients at diagnosis. In most cases NPC patients also showed detectable responses to CD8 epitopes relevant to their HLA type, the one consistent exception being the absence in patients of a B*4001-restricted response to LMP2. We infer that NPC arises in patients whose prevailing levels of T cell memory to tumour-associated EBV proteins is largely intact; the therapeutic goal must therefore be to re-direct the existing memory repertoire more effectively against antigen-expressing tumour cells.

  4. The Epstein-Barr Virus-Encoded MicroRNA MiR-BART9 Promotes Tumor Metastasis by Targeting E-Cadherin in Nasopharyngeal Carcinoma

    PubMed Central

    Hsu, Chung-Yuan; Yi, Yung-Hsiang; Chang, Kai-Ping; Chang, Yu-Sun; Chen, Shu-Jen; Chen, Hua-Chien

    2014-01-01

    MicroRNAs (miRNAs) are a family of small RNA molecules that negatively regulate the expression of protein-coding genes and play critical roles in orchestrating diverse cellular processes. This regulatory mechanism is also exploited by viruses to direct their life cycle and evade the host immune system. Epstein-Barr virus (EBV) is an oncogenic virus that is closely associated with multiple human diseases, including nasopharyngeal carcinoma (NPC), which is a highly metastatic type of tumor and is frequently reported in South Asia. Several viral proteins have been found to promote the migration and invasiveness of NPC cells. However, not all tumor tissues express these viral oncoproteins, suggesting that other mechanisms may contribute to the aggressive behavior of NPC tumor cells. A previous sequencing study by our group revealed that the EBV miRNA miR-BART9 was expressed at high levels in all EBV-positive NPC tissues. In the present study, we used gain- and loss-of-function approaches to investigate the effect of miR-BART9 in EBV-negative and EBV-positive NPC cells. We discovered that miR-BART9 promotes the migration and invasiveness of cultured NPC cells. The promigratory activity observed in vitro was manifested as an enhanced metastatic ability in vivo. Computational analysis revealed that miR-BART9 may target E-cadherin, a membrane protein that is pivotal in preserving cell-cell junctions and the epithelial phenotype. Through biochemical assays and functional rescue analysis, we confirmed that miR-BART9 specifically inhibits E-cadherin to induce a mesenchymal-like phenotype and promote the migration of NPC cells. These results indicated that miR-BART9 is a prometastatic viral miRNA and suggested that high levels of miR-BART9 in EBV-positive NPC cells may contribute to the aggressiveness of tumor cells. PMID:24586173

  5. Consistent high concentration of the viral microRNA BART17 in plasma samples from nasopharyngeal carcinoma patients - evidence of non-exosomal transport

    PubMed Central

    2013-01-01

    Background Because latent Epstein Barr (EBV)-infection is a specific characteristic of malignant nasopharyngeal carcinoma (NPC), various molecules of viral origin are obvious candidate biomarkers in this disease. In a previous study, we could show in a few clinical samples that it was possible to detect a category of EBV microRNAs called miR-BARTs in the plasma of at least a fraction of NPC patients. The first aim of the present study was to investigate the status of circulating miR-BART17-5p (one of the miR-BARTs hereafter called miR-BART17) and EBV DNA in a larger series of NPC plasma samples. The second aim was to determine whether or not circulating miR-BART17 was carried by plasma exosomes. Patients and methods Plasma samples were collected from 26 NPC patients and 10 control donors, including 9 patients with non-NPC Head and Neck squamous cell carcinoma and one healthy EBV carrier. Concentrations of miR-BART17 and two cellular microRNAs (hsa-miR-16 and -146a) were assessed by real-time quantitative PCR with spike-in normalization and absolute quantification. In addition, for 2 patients, exosome distributions of miR-BART17 and miR-16 were investigated following plasma lipoprotein fractionation by isopycnic density gradient ultrcentrifugation. Results The miR-BART17 was significantly more abundant in plasma samples from NPC patients compared to non-NPC donors. Above a threshold of 506 copies/mL, detection of miR-BART17 was highly specific for NPC patients (ROC curve analysis: AUC=0.87 with true positive rate = 0.77, false positive rate = 0.10). In this relatively small series, the concentration of plasma miR-BART17 and the plasma EBV DNA load were not correlated. When plasma samples were fractionated, miR-BART17 co-purified with a protein-rich fraction but not with exosomes. Conclusions Detection of high concentrations of plasma miR-BART17 is consistent in NPC patients. This parameter is, at least in part, independent of the viral DNA load. Circulating mi

  6. Alternative endpoints to the 5-year overall survival and locoregional control for nasopharyngeal carcinoma: A retrospective analysis of 2,450 patients.

    PubMed

    Chen, Chen; Yi, Wei; Gao, Jin; Li, Xiao-Hui; Shen, Lu-Jun; Li, Bo-Fei; Tu, Zi-Wei; Tao, Ya-Lan; Jiang, Chang-Bin; Xia, Yun-Fei

    2014-05-01

    The purpose of the present study was to investigate alternative endpoints to the 5-year overall survival (OS) and locoregional control (LRC) for nasopharyngeal carcinoma (NPC). A total of 2,450 NPC patients were enrolled in this study, including 1,842 patients treated with two-dimensional (2D) radiotherapy (RT), 451 treated with 3D conformal RT (CRT) and 157 treated with intensity-modulated RT (IMRT). We sequentially calculated the 1-, 2-, 3- and 4-year survival rates using a life table and compared these with the 5-year survival rate using the McNemar method, with the survival rate of the last indifferent comparison being considered as the alternative endpoint. For 2D RT, stage I patients exhibited similar survival rates at 1 and 5 years (98.9 vs. 94.4%, respectively; P=0.125 for both OS and LRC); stage N3 patients exhibited similar 4-year OS (55.2 vs. 53.5%; P=1.000) and 2-year LRC (78.3 vs. 71.2%; P=0.125) to the 5-year OS and LRC. For IMRT, the 1-, 2-, 3-, 4- and 5-year OS and LRC rates in stage I/II NPC patients were 100, 98, 96, 94 and 94% for OS and 100, 98, 96, 96 and 96% for LRC, respectively. No significant differences were observed for all the comparisons. For stage III/IV NPC patients treated with IMRT, the 1-, 2-, 3-, 4- and 5-year rates were 99.1, 96.3, 92.5, 88.8 and 85.0% for OS and 98.1, 97.2, 95.3, 90.7 and 89.7% for LRC, respectively. Only the 4-year OS and LRC rates were indifferent from those at 5 years (P=0.125 for OS and P=1.00 for LRC). In conclusion, the 1-year OS and LRC for stage I NPC patients treated with 2D RT or stage I/II NPC patients treated with IMRT, the 4-year OS and 2-year LRC for stage N3 NPC patients treated with 2D RT and the 4-year OS and LRC for stage III/IV NPC patients treated with IMRT were determined as the alternative endpoints to the 5-year OS and LRC for NPC patients.

  7. In vivo Molecular Imaging and Radionuclide (131I) Therapy of Human Nasopharyngeal Carcinoma Cells Transfected with a Lentivirus Expressing Sodium Iodide Symporter

    PubMed Central

    Shi, Shuo; Zhang, Min; Guo, Rui; Miao, Ying; Hu, Jiajia; Xi, Yun; Li, Biao

    2015-01-01

    Introduction Despite recent improvements in the survival rates for nasopharyngeal carcinoma (NPC), novel treatment strategies are required to improve distant metastasis-free survival. The sodium iodine symporter (NIS) gene has been applied for in vivo imaging and cancer therapy. In this study, we examined the potential of NIS gene therapy as a therapeutic approach in NPC by performing non-invasive imaging using 125I and 131I therapy in vivo. Methods We constructed a lentiviral vector expressing NIS and enhanced green fluorescent protein (EGFP) under the control of the human elongation factor-1α (EF1α) promoter, and stably transfected the vector into CNE-2Z NPC cells to create CNE-2Z-NIS cells. CNE-2Z and CNE-2Z-NIS tumor xenografts were established in nude mice; 125I uptake, accumulation and efflux were measured using micro-SPECT/CT imaging; the therapeutic effects of treatment with 131I were assessed over 25 days by measuring tumor volume and immunohistochemical staining of the excised tumors. Results qPCR, immunofluorescence and Western blotting confirmed that CNE-2Z-NIS cells expressed high levels of NIS mRNA and protein. CNE-2Z-NIS cells and xenografts took up and accumulated significantly more 125I than CNE-2Z cells and xenografts. In vitro, 131I significantly reduced the clonogenic survival of CNE-2Z-NIS cells. In vivo, 131I effectively inhibited the growth of CNE-2Z-NIS xenografts. At the end of 131I therapy, CNE-2Z-NIS xenograft tumor cells expressed higher levels of NIS and caspase-3 and lower levels of Ki-67. Conclusion Lentiviruses effectively delivered and mediated long-lasting expression of NIS in CNE-2Z cells which enabled uptake and accumulation of radioisotopes and provided a significant therapeutic effect in an in vivo model of NPC. NIS-mediated radioiodine treatment merits further investigation as a potentially effective, low toxicity therapeutic strategy for NPC. PMID:25621996

  8. EBV-miR-BART7-3p promotes the EMT and metastasis of nasopharyngeal carcinoma cells by suppressing the tumor suppressor PTEN.

    PubMed

    Cai, L-M; Lyu, X-M; Luo, W-R; Cui, X-F; Ye, Y-F; Yuan, C-C; Peng, Q-X; Wu, D-H; Liu, T-F; Wang, E; Marincola, F-M; Yao, K-T; Fang, W-Y; Cai, H-B; Li, X

    2015-04-23

    The epithelial-mesenchymal transition (EMT) is crucial to cancer progression and metastasis. Although multiple cellular miRNAs have been identified to regulate the EMT and metastasis in cancers, the role of viral miRNAs in cancer progression remains largely unknown. Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy typically characterized by its early metastasis. In the present study, we have discovered the involvement of a viral miRNA, EBV-miR-BART7-3p, in the EMT and metastasis of NPC cells. Initially, we observed that EBV-miR-BART7-3p was highly expressed in NPC and positively correlated with lymph node metastasis and clinical stage of NPC. Subsequently, we demonstrated that EBV-miR-BART7-3p