Downregulation of MUC1 Inhibits Proliferation and Promotes Apoptosis by Inactivating NF-κB Signaling Pathway in Human Nasopharyngeal Carcinoma

Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital.The expression of MUC1 was measured by real-time quantitative PCR(qPCR)in the patients with PNC.The 5-8F and HNE1 cells were transfected with siRNA control(si-control)or siRNA targeting MUC1(si-MUC1).Cell proliferation was analyzed by cell counting kit-8 and colony formation assay,and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells.The qPCR and ELISA were executed to analyze the levels of TNF-αand IL-6.Western blot was performed to measure the expression of MUC1,NFкB and apoptosis-related proteins(Bax and Bcl-2).Results The expression of MUC1 was up-regulated in the NPC tissues,and NPC patients with the high MUC1 expression were inclined to EBV infection,growth and metastasis of NPC.Loss of MUC1 restrained malignant features,including the proliferation and apoptosis,downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells.Conclusion Downregulation of MUC1 restrained biological characteristics of malignancy,including cell proliferation and apoptosis,by inactivating NF-κB signaling pathway in NPC.

3-Methyladenine potentiates paclitaxel-induced apoptosis and phosphorylation of cyclin-dependent kinase 1 at thr161 in nasopharyngeal carcinoma cell

Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.

Screening for nasopharyngeal carcinoma in high-incidence regions——Next steps

Epstein-Barr virus(EBV)infection is a well-established risk factor in the development of nonkeratinizing and undifferentiated forms of nasopharyngeal carcinoma(NPC)common in parts of China and Southeast Asia.Early detection of NPC can significantly improve survival rates,as the 5-year survival rate for patients diagnosed at an early stage can exceed 90%after treatment.Studies have demonstrated that screening for NPC using EBV markers is an effective tool for identifying individuals with the disease.Future efforts should focus on implementing screening programs in high-incidence populations,assessing and refining screening algorithms,and exploring new,potentially more cost-effective screening methods.It is crucial to ensure that any new approaches are validated as superior or non-inferior to existing protocol before being adopted on a wider scale.The success of these screening tools in reducing NPC-related morbidity and mortality will depend on their effective implementation and ensuring access for the populations most in need of preventive interventions.This opinion piece briefly summarizes the current evidence supporting EBV-based screening for NPC detection and discusses future steps,including:1)the implementation of effective NPC screening programs,2)the evaluation of improvements in screening methodologies,and 3)the consideration of novel approaches to screening.

Re-searching nasopharyngeal carcinoma

Nasopharyngeal carcinoma(NPC)has been a focus of medical research for more than 100 years,with significant interest emerging over the last 58 years following the identification of the link between the disease and Epstein-Barr virus(EBV)infection.NPC possesses several distinctive characteristics among human cancers,notably its well-documented global epidemiology,which reveals localized high-incidence regions primarily in Southeast Asia,particularly in the Southern provinces of China near the Pearl river,as well as in Greenland and North Africa.Epidemiological data indicate a marked male predominance,early disease onset,and a nearly 100%prevalence of latent EBV infection in the tumors.Due to lack of consistent pattern of cancer-related mutations in NPC genomes and excessive DNA-methylation in the tumor cells,NPC can be considered"an epigenetic cancer".Despite extensive researches,convincing biological explanations for these unique characteristics remain elusive.Recently,suggestive evidence has been published that specific local variants of EBV may represent major high risk factors.In spite of tumor and virus specific immunity,it has not been possible to use this for improved treatment.Ongoing studies on the role of the local microflora and tumor microenvironment are essential for a comprehensive understanding of host-EBV-tumor interactions.Ultimately,this knowledge aims to enhance diagnosis,disease fractionation,treatment strategies,and potentially prevention of NPC.

Treatment of nasopharyngeal carcinoma and prevention of nonalcoholic Wernicke’s disease:A case report and review of literature

BACKGROUND Wernicke encephalopathy is a neurological disorder caused by thiamine deficiency,commonly seen in alcoholic populations but also involving other circumstances that may lead to thiamine deficiency.The recognition of Wernicke encephalopathy often depends on clinicians’keen ability to detect its typical triad of features;however,most cases do not present with the full constellation of signs,which complicates the timely identification of Wernicke encephalopathy.CASE SUMMARY This case report describes a patient with nasopharyngeal carcinoma who developed abnormal ocular function and ataxia following concurrent chemoradiotherapy,without a history of alcohol abuse.With the aid of radiological examinations,he received a timely diagnosis and treatment;however,his symptoms did not fully resolve during follow-up.CONCLUSION For patients with malignant tumors exhibiting neurological symptoms,clinicians should consider the possibility of Wernicke encephalopathy and provide prophylactic thiamine therapy.

The role of glycoproteins in nasopharyngeal carcinoma pathogenesis

Nasopharyngeal carcinoma(NPC)is a malignant tumor arising from the nasopharyngeal epithelium.It consists of undifferentiated squamous cells in the nasopharynx.This type of epithelial cell neoplasm is globally distributed,with the highest prevalence observed in certain regions of the world.It has been known since ancient times.The incidence of NPC is steadily decreasing as data on the molecular factors involved in the pathogenesis of NPC accumulate.Glycoproteins are characterized by polymers of saccharides attached to the amino acid sequences of proteins during the process of glycosylation.They are present in all animal cells and are especially abundant on the surface of tumor cells.Alterations in expression of cellular glycoproteins have recently attracted attention as a key component of neoplastic progression.Tumor-associated glycoproteins may serve as a hallmark of cancer cells and thus represent novel diagnostic and even therapeutic targets.Interest in the role of glycoproteins in cancer in general and specifically in NPC pathology has steadily increased over the past fifty years,reaching over thousands and two hundred publications in the last five years,respectively.Here,data on a specific class of proteins,glycoproteins,involved in tumorigenesis of NPCs are summarized,with a focus on a few of the best-studied ones.Relevant studies performed mainly in the last five years were retrieved and collected through the PubMed system.

Predicting distant metastasis in nasopharyngeal carcinoma using gradient boosting tree model based on detailed magnetic resonance imaging reports

BACKGROUND Development of distant metastasis(DM)is a major concern during treatment of nasopharyngeal carcinoma(NPC).However,studies have demonstrated im-proved distant control and survival in patients with advanced NPC with the addition of chemotherapy to concomitant chemoradiotherapy.Therefore,precise prediction of metastasis in patients with NPC is crucial.AIM To develop a predictive model for metastasis in NPC using detailed magnetic resonance imaging(MRI)reports.METHODS This retrospective study included 792 patients with non-distant metastatic NPC.A total of 469 imaging variables were obtained from detailed MRI reports.Data were stratified and randomly split into training(50%)and testing sets.Gradient boosting tree(GBT)models were built and used to select variables for predicting DM.A full model comprising all variables and a reduced model with the top-five variables were built.Model performance was assessed by area under the curve(AUC).RESULTS Among the 792 patients,94 developed DM during follow-up.The number of metastatic cervical nodes(30.9%),tumor invasion in the posterior half of the nasal cavity(9.7%),two sides of the pharyngeal recess(6.2%),tubal torus(3.3%),and single side of the parapharyngeal space(2.7%)were the top-five contributors for predicting DM,based on their relative importance in GBT models.The testing AUC of the full model was 0.75(95%confidence interval[CI]:0.69-0.82).The testing AUC of the reduced model was 0.75(95%CI:0.68-0.82).For the whole dataset,the full(AUC=0.76,95%CI:0.72-0.82)and reduced models(AUC=0.76,95%CI:0.71-0.81)outperformed the tumor node-staging system(AUC=0.67,95%CI:0.61-0.73).CONCLUSION The GBT model outperformed the tumor node-staging system in predicting metastasis in NPC.The number of metastatic cervical nodes was identified as the principal contributing variable.

Changing Nasopharyngeal Carcinoma Survival in Southern China during 2000-2015: Results of a Retrospective Cohort Study

Objective: Around 50% of new nasopharyngeal carcinoma (NPC) cases come from China. The present study aimed to update the surveillance of NPC survival in southern China, and investigate the survival disparities between sexes within this patient population. Methods: Patients diagnosed with primary and invasive NPC between 2000 and 2015 were included in this study. Data on demographics, diagnosis, and follow-up to December 2020 were collected. Patients were stratified by diagnosis period, sex, and age at diagnosis. Survival analysis employed cohort and Life Table methods, Kaplan-Meier curves, log-rank tests, and Cox regression. Results: The study included 32,901 patients, of whom 69.6% were males. The overall 5-year survival rate rose from 69.6% in 2000-2003 to 83.3% in 2013-2015, with a consistent average increase of 3.3% every 3 years. For males, the 5-year survival rate increased from 66.3% to 82.0%, faster than females. Kaplan-Meier curves demonstrated a significantly higher survival rate for females than males, and subgroup analysis confirmed this advantage. The Cox proportional hazards model confirmed the lower mortality risk for females (HR 0.75, 95% CI: 0.71 - 0.78), patients with younger ages at diagnosis, and patients diagnosed in more recent years (All P Conclusions: The 5-year survival rate for NPC patients in southern China has significantly and steadily improved from 2000 to 2015, indicating the improved quality of cancer care in China. The survival advantage of female patients is not limited to younger patients but is also observed in postmenopausal patients, despite the gradual narrowing of the gender gap.

Clinical Analysis of Xerostomia in Patients with Nasopharyngeal Carcinoma after Radiation Therapy

Objective: To investigate the severity of xerostomia and its impact on the quality of life in patients with nasopharyngeal carcinoma after conventional radiation therapy. Methods: One hundred and thirty-six patients with nasopharyngeal carcinoma, treated by conventional radiation therapy in Cancer Center, Sun Yat-sen University, were surveyed by interview at the outpatient department. A questionnaire and a visual analog scale (VAS) were used to analyze xerostomia and xerostomia-related problems. Results: Of 136 patints, 73.5% experienced a moderate to severe degree of xerostomia; 82.4% had to sip water to facilitate speech; 92.6% had to sip water to facilitate chewing and swallowing; 91.2% changed their feeding pattern (eating only mashed food); 61.3% had to wake up to drink water because of dry mouth; 75.0% had dental lesions to varying degrees. Conclusion: 73.5% of the patients with nasopharyngeal carcinoma after conventional radiation therapy experienced a moderate to severe degree of xerostomia. Xerostomia has a significant impact on the patient's speech, deglutition, and sleep, and can increase the morbidity of the dental diseases.

Significance of the Expression of CyclinD1 and Ki67 Antigen in Nasopharyngeal Carcinoma

Objective: To detect the expression of cyclinD1 and Ki67 in nasopharyngeal carcinoma (NPC) and their correlation with the biological behaviors and prognosis. Methods: 56 cases of biopsy specimens of NPC which had been embedded with para?n in 1996 in our hospital were collected and immunostained with cyclinD1 and Ki67 monoclonal antibodies by means of the streptavidin peroxides method. The patients were followed up periodically, and then their biological behaviors and prognosis were statistically analyzed. Results: The percentage of cyclinD1 and Ki67 positive cells in the NPC specimens ranged from 0–54% and 0–31% respectively. The staining was nuclear. Of the 56 cases, 30 cases (56.6%) highly expressed cyclinD1 or Ki67 HPI and 26 cases (46.4%) lowly expressed cyclinD1, while only 16 cases (28.6%) showed Ki67 HPI (high proliferated index) and 40 cases (71.4%) showed Ki67 LPI (low proliferated index). Patients who lowly expressed cyclinD1 or highly expressed Ki67 had a higher radiosensitivity and a better prognosis. Conclusion: CyclinD1 and Ki67 immunohistochemical staining is considered to be useful, not only as an independent factor of radiosensitivity and prognosis respectively, but also as a means of determining the optimum treatment for each individual patient with NPC.

A Prospective Study on Therapeutic Gain by Concurrent Chemoradiotherapy for Stage Ⅱ-Ⅳa Nasopharyngeal Carcinoma

The benefit achieved by concurrent chemoradiotherapy（CCR） and sequential chemoradiotherapy（SCR） vs radiotherapy（RT） alone for patients with stage Ⅱ-Ⅳa nasopharyngeal carcinoma（NPC） was compared.A total of 113 patients with stage Ⅱ-Ⅳa NPC were allotted into CCR group（n=38）,SCR group（n=36） and RT alone group（n=39）.All patients were irradiated with the same RT technique to ≥66 Gy at 2 Gy per fraction,conventional 5 fractions/week in all groups.The CCR group received concurrent chemotherapy of weekly cisplatin for 7 weeks,and the SCR group received neoadjuvant and（or） adjuvant chemotherapy.The results showed that the 3-and 5-year overall survival rate was significantly higher in CCR group than in RT alone group（92.16% vs 61.54%,81.58% vs 51.28%,P〈0.005）.The median survival time was significantly longer in CCR group than in RT alone group（67.8 months vs 52.7 months,P〈0.005）.It was concluded that CCR could significantly improve overall survival rate,progression-free survival rate,and median survival time when compared with RT alone.

Application of Support Vector Machine to Predict 5-year Survival Status of Patients with Nasopharyngeal Carcinoma after Treatment

Objective： Support Vector Machine （SVM） is a machine-learning method, based on the principle of structural risk minimization, which performs well when applied to data outside the training set. In this paper, SVM was applied to predict 5-year survival status of patients with nasopharyngeal carcinoma （NPC） after treatment, we expect to find a new way for prognosis studies in cancer so as to assist right clinical decision for individual patient. Methods： Two modelling methods were used in the study; SVM network and a standard parametric logistic regression were used to model 5-year survival status. And the two methods were compared on a prospective set of patients not used in model construction via receiver operating characteristic （ROC） curve analysis. Results： The SVM1, trained with the 25 original input variables without screening, yielded a ROC area of 0.868, at sensitivity to mortality of 79.2% and the specificity of 94.5%. Similarly, the SVM2, trained with 9 input variables which were obtained by optimal input variable selection from the 25 original variables by logistic regression screening, yielded a ROC area of 0.874, at a sensitivity to mortality of 79.2% and the specificity of 95.6%, while the logistic regression yielded a ROC area of 0.751 at a sensitivity to mortality of 66.7% and gave a specificity of 83.5%. Conclusion： SVM found a strong pattern in the database predictive of 5-year survival status. The logistic regression produces somewhat similar, but better, results. These results show that the SVM models have the potential to predict individual patient＇s 5-year survival status after treatment, and to assist the clinicians for making a good clinical decision.

Clinical Effect of Biafine in Preventing and Treating Radioactive Skin Destruction of Nasopharyngeal Carcinoma Patients Caused by Concurrent Intensity- Modulated Radiotherapy and Chemotherapy

OBJECTIVE To observe the clinical effect of Biafine cream in preventing and treating radioactive skin destruction of nasopharyngeal carcinoma （NPC） patients induced by synchronized intensity-modulated radiotherapy and chemotherapy. METHODS The patients were treated with Varian-600CD 6 MV X-ray three-dimensional （3D） conformal intensity-modulation radiotherapy （IMRT）, with a 120-blade multiple leaf-blade grating and in combination with synchronal Capecitabine chemotherapy. Fifty-one patients undergoing radiotherapy and chemotherapy were randomized into 2 groups： 25 in the treatment group received a Biafine cream application following the first radiotherapy and / or chemotherapy, while the other 26, served as controls. They received no application of the cream, but only followed normal procedures for conventional radiotherapy and health education. RESULTS The rate of the skin-reaction was 100% in the patients of both groups. A mild radiation reaction （grade-Ⅰ and Ⅱ） occurred as follows： 88.0% （22/25 cases） in the treatment group and 57.7% （15/26 cases） in the control group. A grade-Ⅲ radiation reaction developed in 12.0% （3/25 cases） in the treatment group, and 42.3% （11/26 cases） in the controls. There was a significant difference, P〈0.01 between the two groups. Concerning the degree of the skin response before the patients received a dose of 40 Gy, the radiation reaction emerged in 32.0% （8/25） of the cases in the treatment group, and in 96.2% （25/26） of the cases of the control group. CONCLUSION Biafine cream can effectively reduce the acute irradiation or chemotherapy-induced dermal injury. It can alleviate the patients＇ suffering, improve their quality of life, and can ensure less injurious radiotherapy.

Magnetic Resonance Imaging Findings of Temporal Lobe Radiation Encephalopathy in Nasopharyngeal Carcinoma

Objective： To observe the magnetic resonance imaging （MRI） morphological features of radiation encephalopathy （REP） in nasopharyngeal carcinoma （NPC） and investigate their diagnostic value. Methods： The MRI data of 160 lesions from 104 NPC patients with the diagnosis of temporal lobe REP were retrospectively analyzed. The MRI was performed after radiation therapy of NPC with an interval ranged from 8 months to 13 years. The imaging sequences included T1-weighted imaging and T2-weighted imaging. Additionally T1-weighted imaging with injection of the contrast agent of Gd-DTPA was performed in 111 lesions and fluid attenuated inversion recovery （FLAIR） was performed on 37 lesions, and among them, 2 cases were subjected to MR perfusion weighted imaging （PWI）. Results： Unilateral temporal lobe was involved in 48 cases of REP, bilateral temporal lobe in 56 cases of REP respectively, with a total of 160 lesions. The REP in the white matter displayed hyper-intensity signal on T2-weighted imaging which could be homogenous, whereas areas with heterogeneous hypo-intensity signal could be seen in 59 of them otherwise with hyper-intensity signal, and 91 lesions of white matter were associated with gray matter lesions with an appearance of hypo-intensity signal on T1-weighted imaging and hyper-intensity signal on T2-weighted imaging. In 111 lesions with the Gd-DTPA enhanced T1-weigthed imaging, 91 showed the enhancement of brain parenchyma. Hemorrhage and hemosiderosis occurred in 5 lesions of REP. Conclusion： REP in NPC has a multiplicity of the imaging features on MRI, in addition to the common involvement of white matter, including other relatively frequent findings, such as the involvement of gray matter, hemorrhage, hemosiderosis and blood-brain barrier destruction, those could be clearly revealed on MRI.

Stereotactic radiotherapy for the treatment of nasopharyngeal carcinoma: a Meta-analysis of 1371 cases in China

Objective The aim of this study was to clarify the outcomes of stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma and to promote scientific clinical treatment and research on it in China and other countries by creating a large data resource.Methods This Meta-analysis conducted a literature search using the China National Knowledge Infrastructure database for all clinical research articles on stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma in China.Data on patient cohort numbers and other research factors were recorded for every relevant clinical research article.Calculated and analyzed these fact sheets to pave the way for the objective of this project.Results A total of 40 clinical research articles including 1,371 patients in China from 1998 to 2012 were identified.The average cohort size was 34 patients(range 9-98 patients).The average total radiation dose range was 16-33.6 Gy.The average study or treatment duration was 3.51 years.The calculated average follow-up time was 31.59 months.Conclusion The study provided the largest resource for further research and Meta-analyses to determine the clinical pathway of stereotactic radiotherapy for the treatment of local residual and(or) local recurrent nasopharyngeal carcinoma.The results indicated that variability in the total radiation dose,treatment or research time,and follow-up duration may have contributed to the complications and side effects of stereotactic radiotherapy for local residual and(or) local recurrent nasopharyngeal carcinoma in China.The calculated average total radiation dose,follow-up time,and treatment and research durations may be referenced for future treatment and research.This study also proposed worldwide cooperation for the metaanalysis of research articles on stereotactic radiotherapy for treating local residual and(or) local recurrent nasopharyngeal carcinoma.

Comparing Gross Tumor Volume of Delineation between CT and MRI for Nasopharyngeal Carcinoma

Objective: To study the accuracy between CT and MRI in delineating gross tumor volume (GTV) of nasopharyngeal carcinoma (NPC) in making radiotherapy plan. Methods: The clinical data of 39 cases pathologically proven as nasopharyngeal carcinoma selected from April 2003 to September 2004 were retrospectively analyzed. All were subjected to CT and MR examination one week before treatment. CT scanning was performed with GE Light speed 16, and axial scan was parallel to the OM line routinely from soft palate to the suprasellar cistern. MR scanning was performed by GE Signa super-conducting magnetic resonance imaging system (1.5 Tesla). The standard quadrature head coil was used. Routine axial, sagittal and coronal image with SE sequence were obtained, and FLAIR was used in 10 of 21 cases. Scanned field ranged from the soft palate to the suprasellar cistern. Part of all cases underwent enhanced scanned with Ultravist in CT group or/and GD-DTPA in MR group. All data were analyzed by using the paired-samples t test. Results: The media primary tumor volume (cm3) in CT group and MR group was 32.49±19.91, 29.06±18.75, respectively, and the difference between the two groups were significant (t=5.268, P=0.000). There was significant difference between the two groups in early stage (T1+T2) and advanced stage (T3+T4) by Fuzhou Staging System (t=5.677, P=0.000; t=3.310, P=0.005, respectively). There was significant difference in stage T1, T2, T3 (P=0.005, P=0.001, P=0.004, respectively), and not in stage T4 (P=0.146) between the two groups. Conclusion: MR was more accurate than CT in delineating GTV of NPC, so, is more valuable in making radiotherapy plan.

Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy

Background: The prognostic values of staging parameters require continual re?assessment amid changes in diag?nostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non?meta?static nasopharyngeal carcinoma(NPC) in the intensity?modulated radiotherapy(IMRT) era.Methods: We reviewed the data from 749 patients with newly diagnosed, biopsy?proven, non?metastatic NPC in our cancer center(South China, an NPC endemic area) between January 2003 and December 2007. All patients under?went magnetic resonance imaging(MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log?rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insigniicant explanatory variables.Results: The 5?year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5?year survival rates were as follows: local relapse?free survival, 94.6%; nodal relapse?free survival, 97.0%; distant metastasis?free survival, 82.6%; disease?free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only signiicant prognostic fac?tor for local failure(P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho's location of the cervical lymph nodes were signiicant prognostic factors for both distant failure and disease failure(all P < 0.05). Intracranial extension had signiicant prognostic value for distant failure(P = 0.040).Conclusions: The key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the signiicant prognostic parameters for local control have also been altered substantially.

Associations of lifestyle and diet with the risk of nasopharyngeal carcinoma in Singapore:a case–control study

Background: Nasopharyngeal carcinoma(NPC) is a commonly diagnosed cancer in Southeast Asia. Many studies have examined the risk factors for NPC, yet the roles of some risk factors remain inconclusive. The purpose of this study was to examine associations between modifiable lifestyle factors and the risk of NPC in the Singaporean population.Methods: We conducted a case–control study in Singapore with 300 patients and 310 controls who were recruited between 2008 and 2012. Each control was selected and individually matched to each patient based on sex, ethnicity, and age(±5 years). A total of 290 pairs of cases and controls were matched successfully. We examined lifestyle factors such as tobacco smoking, alcohol drinking, various salted and preserved food consumption, and weaning practices.Results: After adjusting for covariates, multivariate analysis showed that those participants who were current smokers and had ever smoked tobacco had a higher risk of NPC than participants who had never smoked, with odds ratios(ORs) of 4.50(95% confidence interval [CI] 2.58–7.86; P < 0.001) and 2.52(95% CI 1.54–4.12; P < 0.001), respectively. Those who consumed salted vegetables at least once a week also showed a significantly increased risk of NPC than those who never or rarely consumed salted vegetables, with an OR of 4.18(95% CI 1.69–10.38; P = 0.002).Conclusion: Smoking(currently and ever-smoked) and consuming salted vegetables once a week or more were lifestyle risk factors for NPC, and changes of these factors for the better may reduce the risk of NPC.

Biomarkers for enhancing the radiosensitivity of nasopharyngeal carcinoma

Nasopharyngeal carcinoma(NPC) is a common head and neck malignancy. The incidence of NPC is higher in Southern China and Southeast Asia compared with Western countries. Given its high radiosensitivity, the standard treatment for NPC is radiotherapy. However, radioresistance remains a serious obstacle to successful treatment. Radioresistance can cause local recurrence and distant metastases in some patients after treatment by radiation. Thus, special emphasis has been given to the discovery of effective radiosensitizers. This review aims to discuss the biomarkers, classified according to the main mechanisms of radiosensitization, which can enhance the sensitivity of NPC cells to ionizing radiation.

T cells expressing a LMP1-specific chimeric antigen receptor mediate antitumor effects against LMP1-positive nasopharyngeal carcinoma cells in vitro and in vivo

T cells modified with chimeric antigen receptor are an attractive strategy to treat Epstein-Barr virus（EBV） associated malignancies.The EBV latent membrane protein 1（LMP1） is a 66-KD integral membrane protein encoded by EBV that consists of transmembrane-spanning loops.Previously,we have identified a functional signal chain variable fragment（scFv） that specifically recognizes LMP1 through phage library screening.Here,we constructed a LMP1 specific chimeric antigen receptor containing anti-LMP1 scFv,the CD28 signalling domain,and the CD3ζchain（HELA/CAR）.We tested its functional ability to target LMP1 positive nasopharyngeal carcinoma cells.HELA/CAR cells were efficiently generated using lentivirus vector encoding the LMP1-specific chimeric antigen receptor to infect activated human CD3＋ T cells.The HELA/CAR T cells displayed LMP1 specific cytolytic action and produced IFN-γ and IL-2 in response to nasopharyngeal carcinoma cells overexpressing LMP1.To demonstrate in vivo anti-tumor activity,we tested the HELA/CAR T cells in a xenograft model using an LMP1 overexpressing tumor.Intratumoral injection of anti-LMP1 HELA/CAR-T cells significantly reduced tumor growth in vivo.These results show that targeting LMP1 using HELA/CAR cells could represent an alternative therapeutic approach for patients with EBV-positive cancers.