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The aim of this study was to evaluate the association between prenatal and neonatal period exposures and the risk of childhood and adolescent nasopharyngeal carcinoma (NPC). From January 2009 to January 2016, a total of 46 patients with childhood and adolescent NPC (i.e., less than 18 years of age) who were treated at Sun Yat-sen University Cancer Center were screened as cases, and a total of 45 cancer-free patients who were treated at Sun Yat-sen University Zhongshan Ophthalmic Center were selected as controls. The association between maternal exposures during pregnancy and obstetric variables and the risk of childhood and adolescent NPC was evaluated using logistic regression analysis. Univariate analysis revealed that compared to children and adolescents without a family history of cancer, those with a family history of cancer had a significantly higher risk of childhood and adolescent NPC [odds ratios (OR) = 3.15, 95% confidence interval (CI) = 1.02-9.75, P = 0.046], and the maternal use of folic acid and/or multivitamins during pregnancy was associated with a reduced risk of childhood and adolescent NPC in the offspring (OR = 0.07, 95% CI = 0.02-0.25, P < 0.001). After multivariate analysis, only the maternal use of folic acid and/or multivitamins during pregnancy remained statistically significant. These findings suggest that maternal consumption of folic acid and/or multivitamins during pregnancy is associated with a decreased risk of childhood and adolescent NPC in the offspring.

Background: To have better prognostic outcomes and minimize deaths due to nasopharyngeal cancer, it is vital to understand factors that motivate the public to undertake cancer preventive measures. The study investigated determinants of intention to adopt measures to reduce nasopharyngeal cancer risk using the Theory of Planned Behavior., Method: A cross-sectional survey was conducted on Malaysians (n = 515) using a questionnaire on attitudes, subjective norm, perceived behavioral control, knowledge of nasopharyngeal cancer, past nasopharyngeal cancer preventive behavior, and intention to adopt preventive measures. The attitudes construct encompassed perceptions of susceptibility, severity, benefits and barriers. Hierarchical regression of mediation effect under structural equation model approach was used to test the theory. The model was re-estimated using the two-stage least square approach by instrumental approach. Next the Maximum Likelihood Estimation-Structural Equation Modeling was conducted to gauge the instrumentation and check the robustness of the model's simultaneity., Results: The respondents had moderate knowledge of nasopharyngeal cancer, and reported high levels of perceived risk, perceived severity and perceived behavioral control. The respondents were under little social pressure (subjective norm) to perform nasopharyngeal cancer preventive actions, marginally believed in the benefits of medical tests and reported few barriers. The Partial Least Squares-Structural Equation Modeling results show that the relationship between intention and four independent variables were significant (perceived behavioral control, perceived risk, perceived severity, marital status) at p < .05. Tests of Two-stage Least Square Approach and Maximum Likelihood Estimation-Structural Equation Modeling confirm the four key factors in determining the intention to reduce nasopharyngeal cancer risk. The variance explained by these factors is 33.01 and 32.73% using Two-stage Least Square Approach and Maximum Likelihood Estimation-Structural Equation Modeling respectively. Intention to undertake nasopharyngeal cancer risk-reducing behavior has no significant relationship with subjective norm, attitudes (perceived benefits and barriers to screening), knowledge of nasopharyngeal cancer and past behavior in enacting nasopharyngeal cancer preventive measures. The only demographic variable that affects intention is marital status. Gender, age, race, religion, education level, and income are not significantly associated with intention., Conclusions: In contexts where knowledge of nasopharyngeal cancer is moderate, the factors associated with the intention to reduce risk are perceived risk and severity, perceived behavioral control, and marital status., (© 2022. The Author(s).)

Objective: Lifestyle-induced nasopharyngeal carcinoma is a serious but preventable risk factor. This study serves to develop and validate a questionnaire that aims to predict the health behavioural intention on smoking cessation in Sarawak, Malaysia using the Health Belief Model (HBM)., Design: A cross-sectional study., Setting: Urban and suburban areas in Sarawak, Malaysia., Participants: The preliminary items of the instrument were developed after extensive literature review. The instrument was translated into the Malay language using the forward-backwards method before commencing with the content validity by a panel of 10 experts. Face validity was done both quantitatively and qualitatively by 10 smokers. The construct validity of the instrument was evaluated through exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). A total of 100 smokers participated in phase 1 for EFA, while 171 smokers participated in phase 2 for CFA. Internal consistency was measured using Cronbach's alpha coefficients to evaluate the reliability., Results: In the exploratory stage, the factor loading of each item remained within the acceptable threshold. The final revised CFA yielded appropriate fit of the seven-factor model with the following model fit indices: χ 2 =641.705; df=500; p<0.001; comparative fit index=0.953; Tucker-Lewis Index=0.948; root mean square error of approximation=0.041. Satisfactory convergent validity and divergent validity were shown, with the exception of one pairwise construct. The internal reliability of these scales was above the desirable threshold, with Cronbach's alpha coefficients ranging from 0.705 to 0.864 and 0.838 to 0.889 in phases 1 and 2, respectively., Conclusions: The study substantiated the instrument to be valid and reliable for predicting smokers' health behavioural intention to reduce cancer risk. The instrument is made up of 34 items, categorised into two sections, six HBM constructs and health behavioural intention. The instrument can be utilised for other smoking cessation-related cancers in different at-risk populations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: It has been studied that mesenchymal stem cells (MSCs)-derived exosomes could suppress tumor growth in nasopharyngeal carcinoma (NPC) and microRNA-181a (miR-181a) could mediate drug resistance in NPC. Focused on this work, the mechanism of human umbilical cord MSCs (hUC-MSCs)-derived exosomal miR-181a was explored in NPC cell progression., Methods: NPC tissues and normal tissues were obtained from patients, and miR-181a and KDM5C expression was examined. hUC-MSCs-derived exosomes were extracted, identified and co-cultured with NPC cells (C666-1 and SUNE1). C666-1 cell progression in vitro and/or tumor growth in vivo were examined after incubation with exosomes, miR-181a or lysine-specific demethylase 5C (KDM5C). miR-181a and KDM5C expression were examined in NPC., Results: miR-181a expression was reduced while KDM5C expression was elevated in NPC. hUC-MSCs-derived exosomes restrained NPC cell growth in vivo and in vitro. Depleting or restoring exosomal miR-181a promoted or delayed NPC cell progression. KDM5C silencing suppressed NPC cell progression., Conclusion: This study concluded that hUC-MSCs-derived exosomal miR-181a retards NPC development via negatively modulating KDM5C, serving as a candidate reference for the therapy of NPC., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Heated debates have been on-going about tea consumption and the incidence of cancer, especially in head and neck cancer types. This study aimed to review the association between tea consumption habits and nasopharyngeal cancer (NPC). Methods: This review was carried out in accordance with the PRISMA-P protocol. Literature search for journal articles that published studies on the relationship between tea consumption and NPC was performed via databases, such as Elsevier, PubMed, Science Direct, Springer Link, Google, and Google Scholar, for 10 years from 2008 to 2018. Relevant studies were obtained by applying the pre-determined keywords, such as nasopharyngeal cancer, tea consumption and NPC, risk factors of NPC and benefits of tea consumption. Results: A total of 126 articles was retrieved. These articles were subjected to eligibility assessment. Six articles remained after applying the inclusion criteria. Results suggest that habitual tea consumption reduces NPC. Tea consumption significantly reduces NPC with all the studies having a p-value ≤0.05. Meta-analysis showed statistical association between tea consumption and NPC risk with OR=0.865 at 95% CI (0.806-0.929). Conclusion: This study suggests that habitual tea consumption could be associated with prevention of NPC development. Additional studies are needed to further understand the molecular role of bioactive compound and potential health benefit of tea consumption in NPC prevention.

The worldwide burden of disease due to Epstein-Barr virus (EBV) infection is enormous. Diseases include endemic Burkitt lymphoma, infectious mononucleosis, cancers after transplantation, Hodgkin lymphoma, and nasopharyngeal carcinoma. A prophylactic EBV vaccine has the potential to significantly reduce the incidence and/or the severity of all these diseases. Infectious mononucleosis can be nasty and prolonged with a median duration of 17 days. Patients, especially children, undergoing bone marrow or solid organ transplantation may develop post-transplant lymphoproliferative disorder (PTLD). Preventing or modifying primary EBV infection could reduce the incidence PTLD, and also certain lymphomas and nasopharyngeal carcinoma. EBV is a major environmental risk factor for multiple sclerosis (MS). Contracting EBV is essential to getting MS, and having a childhood case of infectious mononucleosis increases that risk. Vaccinating against EBV could be vaccinating against MS.

Introduction: Epstein-Barr virus (EBV) infects more than 95% of the world's population and is associated with infectious mononucleosis as well as a number of cancers in various geographical locations. Despite its significant health burden, no licenced prophylactic or therapeutic vaccines are available. Areas covered: Over the last two decades, our understanding of the role of EBV infection in the pathogenesis and immune regulation of EBV-associated diseases has provided new lines of research to conceptualize various novel prophylactic and therapeutic approaches to control EBV-associated disease. In this review, we evaluate the prophylactic and therapeutic vaccine approaches against EBV and various immunotherapeutic strategies against a number of EBV-associated malignancies. This review also describes the existing and future prospects of improved EBV-targeted therapeutic strategies. Expert opinion: It is anticipated that these emerging strategies will provide answers for the major challenges in EBV vaccine development and help improve the efficacy of novel therapeutic strategies.

Background: Metformin has anticancer effects, but whether it can reduce the risk of nasopharyngeal cancer (NPC) is not known., Methods: A total of 15,486 ever-users and 15,486 never-users of metformin matched by propensity score were enrolled from among patients with new-onset type 2 diabetes mellitus diagnosed during the period 1999-2005 and who were found in the reimbursement database of Taiwan's National Health Insurance. The patients were followed until December 31, 2011. Hazard ratios were estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity scores., Results: NPC incidence was 33.41 and 106.04 per 100,000 person-years in ever-users and never-users, respectively. The overall hazard ratio (95% confidence interval) of 0.312 (0.197-0.494) favored a significantly lower risk among metformin ever-users than in never-users. Hazard ratios comparing the first (<26.03 months), second (26.03-58.03 months) and third (>58.03 months) tertiles of cumulative duration of metformin use to never-users were 0.690 (0.389-1.224), 0.187 (0.076-0.463) and 0.168 (0.068-0.415), respectively. A significantly lower risk of NPC was consistently observed among metformin users in subgroup analyses of age (<50 years and ≥50 years), sex (men and women), and patients with or without nephropathy, liver diseases or diseases of the esophagus, stomach, and duodenum, respectively., Conclusions: Metformin use is associated with a significantly lower risk of NPC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Once endemic in southern China, nasopharyngeal cancer is becoming less prevalent in Hong Kong. This is probably due to a better understanding of the risk factors associated with the disease, its genomic landscape, advances in radiotherapy technology, and development of effective systemic agents. More specifically, the close relationship between Epstein-Barr virus and nasopharyngeal cancer opens up the possibility of using Epstein-Barr virus DNA as a biomarker for early detection and monitoring of the disease. On the other hand, the looming genomic data for nasopharyngeal cancer aid in the development of powerful biomarkers and promising targeted therapy. Clinical use of a combination of radiotherapy and chemotherapy continues to increase, while the development of immunotherapy, such as checkpoint inhibitors, offers hope in improving treatment outcome.

MicroRNAs are important factors in the pathogenic processes of human types of cancers including nasopharyngeal carcinoma (NPC). In the present study, we confirmed that the microRNA-212 expression level was significantly decreased both in NPC tissues and NPC cell lines. Decreased expression of miR-212 was associated with advanced tumor-node-metastasis (TNM) stage and metastasis of NPC. Patients with a lower level of miR-212 had significantly decreased rates of overall and disease-free survival. Functional experiments showed that forced expression of miR-212 inhibited the migration and invasion of NPC cells while inhibition of miR-212 increased the migration and invasion of NPC cells. Furthermore, the results of luciferase assay, qRT-PCR and western blotting showed that SOX4 was the direct downstream target of miR-212 in NPC cells. In addition, we further confirmed that miR-212 exerted its inhibitory influence on the migration and invasion of NPC cells by targeting SOX4.

Introduction: Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with a number of clinical manifestations. Primary EBV infection in young adolescents often manifests as acute infectious mononucleosis and latent infection is associated with multiple lymphoid and epithelial cancers and autoimmune disorders, particularly multiple sclerosis. Areas covered: Over the last decade, our understanding of pathogenesis and immune regulation of EBV-associated diseases has provided an important platform for the development of novel vaccine formulations. In this review, we discuss developmental strategies for prophylactic and therapeutic EBV vaccines which have been assessed in preclinical and clinical settings. Expert commentary: Major roadblocks in EBV vaccine development include no precise understanding of the clinical correlates of protection, uncertainty about adjuvant selection and the unavailability of appropriate animal models. Recent development of new EBV vaccine formulations provides exciting opportunities for the formal clinical assessment of novel formulations.

Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

Virus infections are an important factor in the global burden of human cancer. The discovery and mode of action of human tumour viruses is briefly reviewed together with the promise of prevention through vaccination.

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.

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.

Aims: To clone and express Siva1 protein, and to investigate the role of Siva1 protein in proliferation, apoptosis, invasion, and migration of human nasopharyngeal carcinoma cell line CNE-2 in vitro and in vivo., Methods: The PCR fragment of Siva1 from human nasopharyngeal carcinoma cell line CNE-2 were double digested with BamHI and SalI and then induced into the pQE30 vector double digested by the same enzymes. The pQE30 vector harboring Siva1 was introduced into M15 competent cells and then induced by isopropyl β -D-1-thiogalactopyranoside (IPTG). The Siva1 fusion protein was identified by 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and then separated and purified by Ni-affinity chromatography. Subsequently, the effects of recombinant Siva1 protein on proliferation, apoptosis, invasion and migration were assayed in vitro and in vivo., Results: The transformed cells expressed Siva1 fusion protein with a molecular weight of approximately 12 kDa. Cell counting kit-8 (CCK-8) assay showed that the Siva1 protein significantly inhibited the proliferation of the CNE-2 cells at a concentration of 10 μ mol/L. In addition, compared to the control, the Siva1 protein promoted the apoptosis of the cancer cells. And, the Siva1 protein greatly suppressed the invasion and migration of the cancer cells. In vivo, the Siva1 protein significantly inhibited the tumor growth of the tumor-bearing mice. Further, the Siva1 treatment markedly upregulated Bax, caspase-3, and downregulated Bcl-2 protein levels in the transplanted tumor tissue., Conclusions: The Siva1 protein has a significant anticancer activity on human nasopharyngeal carcinoma cell line CNE-2 including inhibiting proliferation, invasion, migration and promoting apoptosis of the cancer cells.

Background: To analyze the mortality distribution of nasopharyngeal carcinoma in China from 1991 to 2013, to predict the mortality in the ensuing five years, and to provide evidence for prevention and treatment of nasopharyngeal carcinoma., Materials and Methods: Mortality data for Nasopharyngeal Carcinoma in China from 1991 to 2013 were used to describe its epidemiological characteristics, such as the change of the standardized mortality rate, sex and age differences, urban-rural differences. Trend-surface analysis was used to study the geographical distribution of the mortality. Curve estimation, time series, gray modeling, and joinpoint regression were used to predict the mortality for the ensuing five years in the future., Results: In China, the standardized mortality rate of Nasopharyngeal Carcinoma increased with time from 1996, reaching the peak values of 1.45 /105 at the year of 2002, and decreased gradually afterwards. With males being 1.51 times higher than females, and the city had a higher rate than the rural during the past two decades. The mortality rate increased from age 40. Geographical analysis showed the mortality rate increased from middle to southern China., Conclusions: The standardized mortality rate of Nasopharyngeal Carcinoma is falling. The regional disease control for Nasopharyngeal Carcinoma should be focused on Guangdong province of China, and the key targets for prevention and treatment are rural men, especially after the age of 40. The mortality of Nasopharyngeal Carcinoma will decrease in the next five years.

Objective: To retrospectively evaluate the association of MRI findings with local control of nasopharyngeal carcinoma (NPC) treated with radiation therapy and chemotherapy (chemoradiotherapy)., Methods: Pre-treatment MRIs of 101 patients (78 males and 23 females, 23-79 years of age) who had NPC treated with chemoradiotherapy were retrospectively reviewed to evaluate tumour involvement of nasopharyngeal anatomic subsites, tumour volume and MRI appearance. Local control rates were evaluated with respect to these MRI findings., Results: Univariate analysis (using the Kaplan-Meier method) showed that invasion of the skull base as determined by MRI was a significant predictor of local control. In terms of clinical characteristics, T stage and pathological subtype were significant predictors of local control. Multivariate analysis (Cox regression model) of the radiologic findings and clinical characteristics revealed that invasion of the skull base (p = 0.003) and pathological subtype (p < 0.001) were independent prognostic factors for local control., Conclusion: Invasion of the skull base as determined by MRI predicts the likelihood of local failure and may be helpful in identifying a subset of patients with tumours at risk of local recurrence within 3 years after primary chemoradiotherapy., Advances in Knowledge: It has now become common practice to use MRI for pre-treatment evaluation of patients with NPC. The potential role for MRI findings in predicting local control and prognosis in patients with NPC has implications for treatment planning.

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Nasopharyngeal carcinoma (NPC) is characterized by insidious progression and atypical early symptoms and mostly diagnosed in middle or late stages. The long-term prognosis is poor after conventional radiotherapy or chemotherapy, and the therapy often has strong toxic effects on normal tissue and organs. There were in vitro and in vivo preclinical evidences to support chemotherapeutic and chemopreventive effects of 3,3'-diindolylmethane (DIM), which was a natural compound extracted from cruciferous plants. The in vitro experiments showed that 100 µM DIM could induce remarkable apoptosis of NPC cells, and no obvious damage was observed in normal human bronchial epithelial cells and human liver cells (P < 0.01). DIM could simultaneously regulate several signaling pathways directly related to NPC, such as PI3K, MAPK, Akt and NF-κB. In animal model, the volume of transplanted tumor in animals raised by feed containing DIM was significantly less than that of control group (P < 0.01). The animals with 2 weeks of preventive feeding with feed containing DIM before inoculation had the smallest volume of transplanted tumor (P < 0.01). Intake of DIM had no toxic effects on vital organs such as heart, liver and kidney of experimental animals. In summary, the results of this study confirmed that the DIM effectively induced apoptosis of NPC cells, and had a preventive and curative role in the development and progression of NPC. The drug was safe and had no toxic effects on normal tissues and organs.

Purpose: The role of dietary habits in the etiology of nasopharyngeal carcinoma (NPC) has been extensively investigated in high-incidence areas, but evidence is scanty in low-incidence populations. This study aimed to investigate the relationship between NPC risk and a wide range of food groups in the Italian population., Methods: We conducted a hospital-based case-control study in Italy on 198, histologically confirmed, NPC cases of Caucasian ethnicity, aged 18-76 years. Controls were 594 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Odds ratios (ORs) and the corresponding confidence intervals (CIs) were estimated through logistic regression, adjusting for socio-demographic characteristics, tobacco smoking, alcohol drinking, and energy intake., Results: Elevated vegetable consumption was inversely related to NPC risk (OR for highest vs. lower quartile = 0.51; 95 % CI 0.29-0.90). The association was particularly strong for yellow- or red-pigmented vegetables (OR = 0.31; 95 % CI 0.18-0.54), and this effect was stronger among never smokers (OR = 0.18; 95 % CI 0.06-0.55) than among ever smokers (OR = 0.37; 95 % CI 0.19-0.71). Increased NPC risk emerged for elevated eggs consumption (OR = 2.50; 95 % CI 1.44-4.32; p-trend <0.01). No significant associations emerged between NPC risk and consumption of cereals, meat, fish, dairy products, and sweets., Conclusions: The study findings show that, also in low-risk populations, vegetable consumption is a protective factor against NPC. The stronger effect for yellow- or red-pigmented vegetables is in agreement with the inverse association reported for carotenoids intake.

Some studies examined the inverse relation between nasopharyngeal carcinoma (NPC) risk and dietary fibers in endemic populations. By means of a hospital-based case-control study, we verified whether this association was also present in Italy in connection with various types of dietary fibers. Cases were 198 patients with incident, histologically confirmed, NPC admitted to major teaching and general hospitals during 1992-2008. Controls were 594 patients admitted for acute, nonneoplastic conditions to the same hospital network of cases. Information was elicited using a validated food frequency questionnaire including 78 foods, food groups, or dishes. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated for quartiles of intake of different types of fiber after allowance for energy intake and other potential confounding factors. Total fiber intake was inversely related to risk of NPC (OR = 0.58 for the highest vs. the lowest quartile of intake; 95% CI: 0.34-0.96). We found an inverse association for total soluble (OR = 0.58; 95% CI: 0.35-0.96) and total insoluble fiber (OR = 0.56; 95% CI: 0.33-0.95), in particular cellulose (OR = 0.57; 95% CI: 0.33-0.96), and lignin (OR = 0.51; 95% CI: 0.31-0.85). In conclusion, this study suggests that dietary intake of soluble and insoluble fibers is inversely related to NPC risk in a nonendemic southern population.

Nasopharyngeal carcinoma is endemic in Asia and is etiologically associated with Epstein-Barr virus. Radiotherapy is the primary treatment modality. The role of systemic therapy has become more prominent. Based on multiple phase III studies and meta-analyses, concurrent cisplatin-based chemoradiotherapy is the current standard of care for locally advanced disease (American Joint Committee on Cancer manual [7th edition] stages II-IVb). The reported failure-free survival rates from phase II trials are encouraging for induction + concurrent chemoradiotherapy. Data from ongoing phase III trials comparing induction + concurrent chemoradiotherapy with concurrent chemoradiotherapy will validate the results of these phase II studies. Intensity-modulated radiotherapy techniques are recommended if the resources are available. Locoregional control exceeding 90% and reduced xerostomia-related toxicities can now be achieved using intensity-modulated radiotherapy, although distant control remains the most pressing research problem. The promising results of targeted therapy and Epstein-Barr virus-specific immunotherapy from early clinical trials should be validated in phase III clinical trials. New technology, more effective and less toxic chemotherapy regimens, and targeted therapy offer new opportunities for treating nasopharyngeal carcinoma.

We report on the application of photodynamic therapy in the management of recurrent advanced carcinoma of the nasopharynx. A selected cohort of 7 patients, only suitable for palliative therapy, was offered this modality to assess the palliative role of PDT. All 7 patients had at least 2 previous recurrences, which were managed with surgery and chemoradiotherapy but ultimately failed to respond. PDT was offered after careful discussion at a multidiscipline meeting. The photosensitiser "mTHPC" was introduced intravenously 96 h prior to delivering the light with nasoendoscopic guidance. Six patients' symptoms were reduced markedly post photodynamic therapy. Five patients have to had another round of treatment which was found to be as effective as the first round in terms of controlling disease progression as well as symptoms. Magnetic resonance images showed variable reduction of tumour volume with the majority of the patients having moderate to significant response. Photodynamic therapy was very successful palliative therapy for this small group of recurrent advanced nasopharyngeal cancer patients., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: A case-control study was conducted to evaluate the role of adult diet on nasopharyngeal carcinoma (NPC) in Taiwan., Methods: A total of 375 incident NPC cases and 327 controls matched to the cases on sex, age, and residence were recruited between July 1991 and December 1994. A structured questionnaire inquiring complete dietary history, socio-demographic characteristics, and other potential confounding factors was used in the personal interview. Unconditional logistic regression analysis was used to estimate multivariate-adjusted odds ratio (OR(adj)) with 95% confidence interval (CI) after accounting for known risk factors., Results: Fresh fish (OR(adj), 0.56; 95% CI, 0.38-0.83 for the highest vs. lowest tertile of intake), green tea (OR(adj), 0.61; 95% CI, 0.40-0.91 for drinking ≥1 times/week vs. never) and coffee (OR(adj), 0.56; 95% CI, 0.37-0.85 for drinking ≥0.5 times/week vs. never) were inversely associated with the NPC risk. No association with NPC risk was observed for the intake of meats, salted fish, fresh vegetables, fruits and milk. Intake of vitamin A from plant sources was associated with a decreased NPC risk (OR(adj), 0.62; 95% CI, 0.41-0.94 for the highest vs. lowest tertile)., Conclusion: The study findings suggest that certain adult dietary patterns might protect against the development of NPC.

Use of anti-idiotype antibody vaccines is a promising strategy against tumor, however, their immunogenicity still need to be improved. Heat shock proteins (HSPs) have been shown to act as adjuvants when coadministered with peptides or given as fusion proteins and enhance the vaccination efficiency. To evaluate the enhancement of the potency of anti-idiotype antibody immunogenicity by heat shock protein gp96, C57BL/6 mice were immunized with three intramuscular inoculations of the G22 DNA and/or gp96 DNA vaccine. Control was inoculated with empty plasmid pcDNA3.1. The levels of G22-specific antibody and lymphocyte phenotype were measured by ELISA, fluorescence activated cell sorter (FACS) analysis, respectively. In the tumor protection experiment, the immunized mice were then challenged with CMT-93-G22 cells. The tumor size and the survival time of the animals were compared among these groups. The results showed that the efficacy of G22 DNA vaccine could be enhanced by coadministrating with gp96 DNA which might be relevant with activating CD8(+)T cells. Furthermore, co-injection of G22 DNA with gp96 DNA could prolong the survival time and lessen the tumor size of the CMT-93-G22-bearing mice. Our study demonstrates for the first time that G22+gp96 DNA vaccine can induce comparable G22-specific CD8(+)T cell response and is a promising candidate DNA vaccine for nasopharyngeal carcinoma., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Cellular immune responses, particularly those associated with CD3(+)CD8(+) cytotoxic T lymphocytes (CTL), are critical factors in controlling viral infection. Nasopharyngeal carcinoma (NPC) is closely associated with persistent Epstein-Barr virus (EBV) infection. NPC vaccine studies have focused on enhancing specific antiviral CTL responses. In this study, three vaccines capable of expressing the EBV-latent membrane protein 2 (LMP2) (a DNA vector, an adeno-associated virus (AAV) vector, and a replication-defective adenovirus serotype 5 (Ad5) vector) were respectively used to immunize female Balb/c mice (4-6 weeks old) at weeks 0, 2 and 4, either alone or in combination. Our results suggest that combined immunization with DNA, AAV, and adenovirus vector vaccines induced specific cellular immunity more effectively than any of these vectors alone or a combination of two of the three, constituting a sound vaccine strategy for the prevention and treatment of NPC.

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.

Aim: To construct a prokaryotic expression vector expressing a fully human bivalent anti-idiotype antibody and identify the expression product., Methods: The genes of G22, I50 were subcloned into prokaryotic expression vector pET25b (+) in order and confirmed by colony PCR, restriction enzyme digestion, DNA sequencing.The positive construct was transformed into E.coli BL21 (DE3) and the protein was expressed after induction by IPTG. The identity of the expressed protein was confirmed by Western blot. The activity of the protein was analysed by ELISA and further by lymphocyte proliferation assay., Results: The recombinant vector was constructed successfully, the recombinant protein was successfully expressed and purified with a purification of about 90%. The molecular weight of the expressed protein was 42000 which was in accordance with expectation. The activity of expressed protein after renaturation had recovered and further confirmed by lymphocyte proliferation assay in vitro., Conclusion: We obtained an active bivalent anti-idiotype antibody which laid a foundation for the clinical immunotherapy of nasopharyngeal carcinoma.

G22, an anti-idiotype single chain antibody screened from human nasopharyngeal carcinoma phage anti-idiotype antibody library, has been already identified by He et al. G22 DNA vaccine was produced by cloning G22 gene and inserting the cloned gene into pcDNA3.1. To investigate the immunogenicity of pcDNA3.1-G22, C57BL/6 mice were immunized with the vaccine, pcDNA3.1 and PBS individually and the antibody response, T cell phenocyte at the 15th, 22th, 29th, 36th day after the last immunity were detected. In the tumor protection experiment, the immunized mice were then challenged with CMT-93-G22 cells or CMT-93-mock cells. The tumor size and the survival time of the animals were compared between these groups. The results showed that DNA vaccine pcDNA3.1-G22 could raise G22-specific humoral and cellular immune responses. Furthermore, pcDNA3.1-G22 could prolong the survival time and lessen the tumor size of the CMT-93-G22-bearing mice but had no protection effect on the mice attacked by CMT-93-mock cells. These results were expected to lay foundation for further studies on the clinical application of pcDNA3.1-G22 DNA vaccine., (Copyright 2010 Elsevier Ltd. All rights reserved.)

This study explored the effects of indole-3-carbinol on the proliferation of human nasopharyngeal carcinoma, both in vitro and in vivo, and the underlying mechanisms in inducing apoptosis of CNE1 cells. Proliferation, apoptosis, malondialdehyde, superoxide dismutase, glutathione peroxidase, expressions of caspase-9, and caspase-3 in human nasopharyngeal carcinoma cells CNE1 were examined. Indole-3-carbinol suppressed proliferation, induced apoptosis, decreased malondialdehyde level, increased the activity of superoxide dismutase and glutathione peroxidase, and up-regulated the expression of active fragments of caspase-9 and caspase-3 both in vitro and in vivo. It was concluded that indole-3-carbinol could inhibit proliferation and induce apoptosis of CNE1 cells and inhibit tumor growth in mice. Increased activity of superoxide dismutase and glutathione peroxidase and activated expression of caspase-9 and caspase-3 were also observed in indole-3-carbinol-treated tumors or tumor cells, suggesting that stress- and apoptosis-related molecules are involved in the indole-3-carbinol-induced apoptosis and inhibition of tumor growth.

Epstein-Barr virus (EBV) is associated with several malignant diseases including nasopharyngeal carcinoma (NPC), a common neoplasm throughout southeast Asia. Radiotherapy and chemotherapy can achieve remission, but a reemergence of disease is not uncommon. Therefore, there is a need for specific therapies that target the tumor through the recognition of EBV antigens. In NPC, latent membrane protein 1 (LMP1) and LMP2 offer the best opportunity for specific targeting since they are typically expressed and T-cell determinants in each of these proteins have been defined. We have attempted to maximize the opportunity of incorporating every possible CD4 and CD8 determinant in a single formulation. We have achieved this by generating a scrambled protein incorporating random overlapping peptide sets from EBNA1, LMP1, and LMP2, which was then inserted into a replication-deficient strain of adenovirus (adenovirus scrambled antigen vaccine [Ad-SAVINE]). This report describes the construction of this Ad-SAVINE construct, its utility in generating LMP1 and LMP2 responses in healthy individuals as well as NPC patients, and its capacity to define new epitopes. This formulation could have a role in NPC immunotherapy for all ethnic groups since it has the potential to activate all possible CD4 and CD8 responses within EBNA1 and LMPs.

The underlying mechanism of the protective and suppressive role of NKT cells in human tumor immunosurveillance remains to be fully elucidated. We show that the frequencies of CD8(+) NKT cells in patients with EBV-associated Hodgkin's lymphoma or nasopharyngeal carcinoma are significantly lower than those in healthy EBV carriers. These CD8(+) NKT cells in tumor patients are also functionally impaired. In human-thymus-severe combined immunodeficient (hu-thym-SCID) chimeras, EBV challenge efficiently promotes the generation of IFN-gamma-biased CD8(+) NKT cells. These cells are strongly cytotoxic, drive syngeneic T cells into a Th1 bias, and enhance T-cell cytotoxicity to EBV-associated tumor cells. Interleukin-4-biased CD4(+) NKT cells are predominately generated in unchallenged chimeras. These cells are noncytotoxic, drive syngeneic T cells into a Th2 bias, and do not affect T-cell cytotoxicity. In humanized xenogeneic tumor-transplanted hu-thym-SCID chimeras, adoptive transfer with EBV-induced CD8(+) NKT cells significantly suppresses tumorigenesis by EBV-associated malignancies. EBV-induced CD8(+) NKT cells are necessary and sufficient to enhance the T-cell immunity to EBV-associated malignancies in the hu-thym-SCID chimeras. CD4(+) NKT cells are synergetic with CD8(+) NKT cells, leading to a more pronounced T-cell antitumor response in the chimeras cotransferred with CD4(+) and CD8(+) NKT cells. Thus, immune reconstitution with EBV-induced CD8(+) NKT cells could be a useful strategy in management of EBV-associated malignancies.

Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC) is a high incidence tumor in Southeast Asia. Among EBV encoded proteins, latent membrane protein 2A (LMP2A) is an important antigen for T cell therapy of EBV. In this study, we predicted six HLA-A2 restricted CTL candidate epitopes of LMP2A by SYFPEITHI, NetMHC and MHCPred methods combined with the polynomial method. Subsequently, biological functions of these peptides were tested by experiments in vitro. In ELISPOT assay, the positive response of the LMP2A specific CTL stimulated by three (LMP2A(264-272), LMP2A(426-434) and LMP2A(356-364)) of six peptides respectively showed that the numbers of spots forming cells (SFC) ranged from 55.7 to 80.6 SFC/50,000 CD8(+) T cells and the responding index (RI) ranged from 5.4 to 7. These three epitope-specific CTLs could effectively kill specific HLA-A2-expressing target cells. As a result, LMP2A(264-272) (QLSPLLGAV), LMP2A(426-434) (CLGGLLTMV) and LMP2A(356-364) (FLYALALLL) were identified as LMP2A-specific CD8(+) T-cell epitopes. It would be useful to clarify immune response toward EBV and to develop a vaccine against EBV-correlative NPC.

Lactotransferrin (LTF) has been shown to regulate tumorogenesis. However, little is known about the role of LTF in regulating the development of human nasopharyngeal carcinoma (NPC). The aim of our study was to investigate whether LTF could regulate the development of NPC by characterizing the pattern of LTF expression in human NPC tissues using cDNA and tissue microarrays. Loss of LTF expression was observed in a significantly higher frequency of NPC tissues compared to that in nontumor nasopharyngeal epithelial tissues. While 61.25% of NPC tissues at the T1/T2 stage were positive for LTF expression, only 40.82% of NPC at the T3/T4 stage were stained by anti-LTF. Similarly, 41.58% of NPC with local lymph node metastasis displayed LTF expression, a value significantly lower than the 46.36% in primary tumors (p < 0.05). These findings suggest that LTF may negatively regulate the development and metastasis of NPC in vivo. Furthermore, overexpression of or treatment with LTF inhibited the proliferation of NPC cells and promoted cell cycle arrest at the G(0)/G(1) phase in vitro. While LTF treatment downregulated expression of cyclin D1 and phosphorylation of retinoblastoma protein (Rb), expression of p21 and p27 in 5-8F NPC cells was enhanced. Moreover, LTF treatment modulated the mitogen-activated protein kinase (MAPK) pathway, but did not affect p53 and STAT3 expression in 5-8F NPC cells. Thus LTF is likely to be a candidate tumor suppressor and downregulates the development of NPC by inhibiting NPC proliferation through induction of cell cycle arrest and modulation of the MAPK signaling pathway. Therefore, our findings provide new insights in understanding the mechanism(s) underlying the action of LTF in regulating the development of human NPC., ((c) 2008 Wiley-Liss, Inc.)

Vascular endothelial growth factor (VEGF) is up-regulated in the vast majority of human tumors. The up-regulation of VEGF not only plays important roles in tumor angiogenesis, but also provides a target for tumor treatment with small interfering RNA (siRNA) that targets VEGF; however, it is unclear whether a quite high up-regulation of VEGF will affect the efficiency of RNA interference strategies targeting VEGF. A high level expression of VEGF was found in CNE cells from a nasopharyngeal carcinoma cell line. In this study, we investigate whether VEGF-specific siRNAs can effectively suppress VEGF expression in CNE cells, and study the methods for the use of VEGF-specific siRNAs as potential therapeutic agents. CNE cells with high VEGF expression induced by hypoxia were transfected with VEGF-specific siRNAs. The expression of VEGF was effectively suppressed by VEGF-specific siRNAs, measured by ELISA, Western blot analysis and RT-PCR. Furthermore, experiments in nude mice bearing nasopharyngeal carcinoma xenograft were initiated 5 d after injection of CNE cells. VEGF-specific siRNAs were modified with 2'-deoxy, then injected into the tumors, and a liposome-mediated siRNA transfection system and ultrasound exposure were used to help delivery of the siRNAs. Tumor growth was reduced significantly after 3 weeks' treatment. These studies suggest that VEGF-specific siRNAs still can effectively suppress VEGF expression even in tumor cell lines with a relatively high level of VEGF expression, such as CNE, and VEGF-specific siRNAs modified with 2'-deoxy can be used as potential agents for tumor therapy.

Nasopharyngeal carcinoma (NPC) has a unique and complex etiology that is not completely understood. Although NPC is rare in most populations, it is a leading form of cancer in a few well-defined populations, including natives of southern China, Southeast Asia, the Arctic, and the Middle East/North Africa. The distinctive racial/ethnic and geographic distribution of NPC worldwide suggests that both environmental factors and genetic traits contribute to its development. This review aims to summarize the current knowledge regarding the epidemiology of NPC and to propose new avenues of research that could help illuminate the causes and ultimately the prevention of this remarkable disease. Well-established risk factors for NPC include elevated antibody titers against the Epstein-Barr virus, consumption of salt-preserved fish, a family history of NPC, and certain human leukocyte antigen class I genotypes. Consumption of other preserved foods, tobacco smoking, and a history of chronic respiratory tract conditions may be associated with elevated NPC risk, whereas consumption of fresh fruits and vegetables and other human leukocyte antigen genotypes may be associated with decreased risk. Evidence for a causal role of various inhalants, herbal medicines, and occupational exposures is inconsistent. Other than dietary modification, no concrete preventive measures for NPC exist. Given the unresolved gaps in understanding of NPC, there is a clear need for large-scale, population-based molecular epidemiologic studies to elucidate how environmental, viral, and genetic factors interact in both the development and the prevention of this disease.

The incidence rates of nasopharyngeal carcinoma (NPC) are dramatically higher in certain regions of Asia compared to the rest of the world. Few risk factors for NPC are known; however, in contrast to the hypothesized health benefits of nonpreserved vegetables, it is thought that preserved vegetable intake may play a role in contributing to the higher incidence of NPC in high-risk regions. Therefore, the purpose of this study was to systematically review the epidemiologic evidence on the associations between adulthood intake of preserved and nonpreserved vegetables and NPC risk. A search of the epidemiological literature from 1966 to 2004 was performed using several bibliographic databases, including PubMed and the Chinese Biomedical Literature Database System. There were no language restrictions. Meta-analysis was conducted to obtain pooled odds ratios (ORs) for the highest-versus-lowest categories of preserved and nonpreserved vegetable intake. A total of 16 case-control studies were identified in the search. Results showed that highest-versus-lowest preserved vegetable intake was associated with a 2-fold increase in the risk of NPC (Random Effects Odds Ratio (RE OR) 2.04; 95% Confidence Limits (CL) 1.43, 2.92). Conversely, high nonpreserved vegetable intake was associated with 36% decrease in the risk of NPC (RE OR 0.64; 95% CL 0.48, 0.85). Findings for both preserved and nonpreserved vegetables were consistent across vegetable type and by country of study. Further research in high-risk areas to gain insight into the risk associated with preserved vegetables and protection associated with nonpreserved vegetables may advance understanding of NPC and yield clues for prevention., (Copyright 2006 Wiley-Liss, Inc.)

Nasopharyngeal carcinoma (NPC) is a highly metastatic carcinoma characterized by consistent association with Epstein-Barr virus (EBV). Of the EBV-encoded product, latent membrane protein-1 (LMP-1) is considered to be an onco-protein playing an essential role in cell transformation and metastasis. In this study, we used a recombinant adeno-associated virus type 2 vector (rAAV-2) to deliver small hairpin RNA (shRNA) targeting EBV LMP-1 into the EBV-positive human NPC C666-1 cells and evaluated the effect of long-term suppression of LMP-1 on NPC growth and metastasis in vivo and in vitro. An NPC metastasis nude mouse model with NPC xenograft transplanted in liver was established. The NPC C666-1 cells infected with rAAV-shRNA-LMP-1 or rAAV-EGFP were inoculated in the livers of nude mice. Formation of liver and lung metastasis was evaluated at day 14 after tumor inoculation. Our results demonstrate that rAAV-shRNA-LMP-1 effectively infected C666-1 cells and suppressed LMP-1 expression. Such suppression, in turn, did not significantly inhibit tumor growth, but prevented NPC metastasis in the liver as well as in the lung. Consistent with in vivo data, the in vitro studies in NPC C666-1 cell cultures showed that suppression of LMP-1 by rAAV-shRNA-LMP-1 significantly reduced cell mobility and transmembrane invasion ability. These results demonstrated for the first time that long-term suppression of EBV-encoded LMP-1 in vivo is an effective means for preventing NPC metastasis.

Virus-associated malignancies are potential targets for immunotherapeutic vaccines aiming to stimulate T-cell responses against viral antigens expressed in tumor cells. Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma, a high-incidence tumor in southern China, expresses a limited set of EBV proteins, including the nuclear antigen EBNA1, an abundant source of HLA class II-restricted CD4(+) T-cell epitopes, and the latent membrane protein LMP2, a source of subdominant CD8(+) T-cell epitopes presented by HLA class I alleles common in the Chinese population. We used appropriately modified gene sequences from a Chinese EBV strain to generate a modified vaccinia virus Ankara recombinant, MVA-EL, expressing the CD4 epitope-rich C-terminal domain of EBNA1 fused to full-length LMP2. The endogenously expressed fusion protein EL is efficiently processed via the HLA class I pathway, and MVA-EL-infected dendritic cells selectively reactivate LMP2-specific CD8(+) memory T-cell responses from immune donors in vitro. Surprisingly, endogenously expressed EL also directly accesses the HLA class II presentation pathway and, unlike endogenously expressed EBNA1 itself, efficiently reactivates CD4(+) memory T-cell responses in vitro. This unscheduled access to the HLA class II pathway is coincident with EL-mediated redirection of the EBNA1 domain from its native nuclear location to dense cytoplasmic patches. Given its immunogenicity to both CD4(+) and CD8(+) T cells, MVA-EL has potential as a therapeutic vaccine in the context of nasopharyngeal carcinoma.

This article presents a review of the health effects of occupational exposure to wood dusts and of the data that could be used for setting occupational exposure limits for this nuisance. The causal role of wood dust in the onset of sinonasal cancers is solidly established by numerous epidemiological studies, and the magnitude of the risk is particularly high for adenocarcinoma induced by exposure to hardwood dust. However, no current data allows to rule out the carcinogenic role of softwood dusts and, in the view of protecting the health of the workers, it does not seem relevant to distinguish these two types of wood. Various impairments of the lung function have been frequently associated with exposure to both 'allergenic' and 'non-allergenic' wood dusts and may occur at very low concentrations. According to the SUMER 94 and CAREX studies, about 200 000 workers are currently exposed to wood dusts in France (about 1% of the working population between 1990 and 1994). When taking into account full professional careers, the percentage of workers having been occupationally exposed can be estimated to be about 15% for men and 5% for women. Measurements performed in France between 1987 and 2000 show that exposure levels are high, about 50% of the samplings being over 1mg/m(3) (actual TWA in France). Although the studies present limits, particularly for the quantitative assessment of individual exposure levels, it seems that nonmalignant effects are susceptible to arise at the level of 1mg/m(3); a limit value of 0.5mg/m(3) would credibly allow to protect exposed workers from most of the risks of nonmalignant pulmonary effects. However, it is impossible to assure that this value will avoid the induction of sinonasal cancer, even if this level is certainly lower than the levels to which the cases of sinonasal cancers published in the literature were exposed.

Nasopharyngeal carcinoma (NPC) is universally associated with EBV infection. We have shown that the phosphonated nucleoside analog, (S)-1-[3-hydroxy-2-(phosphonylmethoxy)-propyl]cytosine (HPMPC) strongly inhibits growth of NPC xenografts in nude mice by causing apoptosis (J. Neyts et al., Cancer Res., 58, 384-388, 1998). We, therefore, tested two additional members of this drug family that have different degrees of antiviral activity, 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) and 9-2-(R)-(phosphonomethoxy)propyladenine (PMPA). Intratumoral injection of PMEA (75 microl of 2% solution) in C15 NPC xenografts, which are latently infected with EBV, slowed tumor growth moderately, whereas PMPA (75 microl of 2% solution) slowed tumor growth only marginally. Compared with the previous results showing complete regression of tumor, PMEA had less antitumoral effect than HPMPC, and PMPA had the least. After 4 weeks of preventive treatment, tumors formed in 12.5, 50, and 100% of mice treated with HPMPC, PMEA, and PMPA, respectively, in contrast to the development of tumors in all of the PBS-treated control mice. We also investigated the effect of each drug on the EBV-positive epithelial cell line NPC-KT in vitro. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed inhibition of growth of NPC-KT cells by HPMPC and PMEA, but not by PMPA, which correlates with the results observed in tumor xenografts. Growth inhibition was attributable to induction of apoptosis in NPC-KT cells as indicated by a DNA fragmentation assay. Cleavage of poly(ADP-ribose) polymerase after treatment of NPC-KT cells with HPMPC was observed, which suggested that the apoptosis may be mediated by caspase(s). The apoptotic effects of the drugs are independent of any effects on EBV DNA polymerase, which is not expressed in these latently infected NPCs. These results suggest that HPMPC as well as PMEA could provide an adjunctive treatment for NPC.

Undifferentiated carcinoma is the most frequent nasopharyngeal cancer; it has a typical pathognomonic histological pattern, a close relationship to Epstein-Barr virus (EBV), a peculiar natural history and a good prognosis. It has an early tendency to locally spread to the parapharyngeal space. Nodal involvement is highly frequent (70-90%) and bulky regardless of the size of the primary. Literature reports up to 11% distant metastases at presentation and up to 87% at autoptic studies. Pretreatment work-up should include: personal history, clinical and fiberscopic examination, magnetic resonance imaging (MRI) or computed tomography (CT) scan of the base of the skull and neck, histology of the primary and cytology of neck lumps, bone marrow aspiration and biopsy, and EBV serological profile. Clinical and pathological factors predicting possible distant spread are primary tumor and node extension, and treatment failure. Up to now no reliable predictive biological markers have been identified. After treatment, distant metastases are found in about 30% of patients within 5 years and generally have a bad prognosis. Metastatic nodes above the clavicle, in absence of locoregional failure, aggressively treated with chemoradiotherapy, have a disease-free survival longer than 5 years. The following is the suggested posttreatment work-up for early diagnosis of these salvageable patients: clinical and fiberscopic evaluation every 3 months for 2 years and later on every 6 months; skull base and neck MRI or CT scan, and chest CT scan at 6, 12, 18, 24, 36, 48 and 60 months; EBV serological evaluation., (Copyright 2001 S. Karger AG, Basel)

Background: The aim of our work was to identify risk factors specific to populations in our region for primary prevention of risk behaviors, particularly eating habits., Methods: We conducted a case-control study on dietary factors of nasopharyngeal carcinoma in the Setif area in Algeria. The study included 72 cases and 72 controls matched for age, sex and area of residence. The variables analyzed were identified by an anthropological study., Results: Increased risk of disease was associated with consumption of traditionally preserved foods such as "harissa", pickled fruit and vegetables and dried and salted meat. These factors were commonly found in other endemic areas. Certain products appeared to be specific to the Setif area including dried and salted fat, especially after prolonged exposure. Rancid butter was related to a 4 to 7-fold increase in risk and use of pickling increased the risk of nasopharyngeal carcinoma 4 to 12-fold depending on the type of food., Conclusions: These data point to the need for biochemical analysis of food specimens to search for the carcinogenic agents and to the importance of an immediate information and education program on food habits for the populations living in this area.