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.

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.

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.

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.

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.

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.

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.

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.

Integrated strategies for chemotherapy cycles in nasopharyngeal carcinoma patients: Real-world data from two epidemic centers guiding decision-making

objective:Two cycles of induction chemotherapy(IC)followed by 2 cycles of platinum-based concurrent chemoradiotherapy(CCRT)(2IC+2CCRT)for locoregionally advanced nasopharyngeal carcinoma(LA-NPC)is widely adopted but not evidence-confirmed.This study aimed to determine the clinical value of 2IC+2CCRT regarding efficacy,toxicity and cost-effectiveness.Methods:This real-world study from two epidemic centers used propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)analyses.The enrolled patients were divided into three groups based on treatment modality:Group A(2IC+2CCRT),Group B(3IC+2CCRT or 2IC+3CCRT)and Group C(3IC+3CCRT).Long-term survival,acute toxicities and cost-effectiveness were compared among the groups.We developed a prognostic model dividing the population into high-and low-risk cohorts,and survivals including overall survival(OS),progression-free survival(PFS),distant metastasis-free survival(DMFS)and locoregional relapse-free survival(LRRFS)were compared among the three groups according to certain risk stratifications.Results:Of 4,042 patients,1,175 were enrolled,with 660,419,and 96 included in Groups A,B and C,respectively.Five-year survivals were similar among the three groups after PSM and confirmed by IPTW.Grade 3-4 neutropenia and leukocytopenia were significantly higher in Groups C and B than in Group A(52.1%vs.41.5%vs.25.2%;41.7%vs.32.7%vs.25.0%)as were grade 3-4 nausea/vomiting and oral mucositis(29.2%vs.15.0%vs.6.1%;32.3%vs.25.3%vs.18.0%).Cost-effective analysis suggested that 2IC+2CCRT was the least expensive,while the health benefits were similar to those of the other groups.Further exploration showed that 2IC+2CCRT tended to be associated with a shorter PFS in high-risk patients,while 3IC+3CCRT potentially contributed to poor PFS in low-risk individuals,mainly reflected by LRRFS.Conclusions:In LA-NPC patients,2IC+2CCRT was the optimal choice regarding efficacy,toxicity and costeffectiveness;however,2IC+2CCRT and 3IC+3CCRT probably shortened LRRFS in high-and low-risk populations,respectively.

KIF15, a key regulator of nasopharyngeal carcinoma development mediated by the P53 pathway

Background:Kinesin family member 15(KIF15)is a protein that regulates cell mitosis and plays an important role in the development and progression of several types of human cancers.However,the role of KIF15 in the development of nasopharyngeal cancer(NPC)is still unclear.Methods:The differential expression of KIF15 in NPC and para-carcinoma tissues was evaluated based on data collected from Gene Expression Omnibus(GEO)database and immunohistochemical analysis of clinical specimens collected from a patient cohort.Cell lines 5-8F and CNE-2Z were selected for the construction of KIF15‑knockdown cell models.CCK8 assay,flow cytometry,wound healing,Transwell and clone formation assays were used to detect the proliferation,apoptosis,migration,invasion and colony formation of NPC cells in vitro.A mouse xenograft model and the tail intravenous mouse distant transfer model were constructed for in vivo study.Furthermore,the potential molecular mechanisms underlying the effects of KIF15 were explored through western blot analysis,and several in vitro and in vivo functional assays were performed to explore its role in NPC.Results:The results revealed significantly higher expression of KIF15 in NPC tissues compared to para-carcinoma tissues.High levels of KIF15 expression were also associated with short overall survival(OS)and progression-free survival(PFS).Knockdown of the KIF15 gene led to a cell cycle arrest in the growth 2(G2)phase,inhibition of cell proliferation,migration,invasion,colony formation,and enhanced cell apoptosis.The in vivo murine xenograft experiments showed that down-regulation of the KIF15 gene could inhibit tumor growth and reduce the risk of liver and lung metastasis in NPC.Moreover,the evaluation of the molecular pathway showed that the mitogen-activated protein kinase/P53 pathways might be involved in the KIF15-induced regulation of NPC.Rescue assays indicated that Pifithrin-αcould counteract the pro-proliferative and pro-apoptotic effects mediated by KIF15.Conclusion:This work indicated that KIF15 overexpression accelerated the progression of NPC and promoted the development of distant metastases.Therefore,KIF15 may have an important role as a prognostic indicator and a potential drug target for the treatment of NPC.

SIRT2 interacts with DDX24 to promote nasopharyngeal carcinoma growth

Background:Nasopharyngeal carcinoma(NPC)is one of the most prevalent cancers in Southeast Asia.Sirtuin 2(SIRT2)is a member of the NAD+-dependent deacetylase family and has been shown to play important roles in numerous biological processes.However,Its function in NPC remains uncertain.The primary aim of this study is to clarify the role of SIRT2 in NPC.Methods:In this research,we examined the effect of SIRT2 silencing on NPC cell proliferation and colony formation using vitro NPC cell lines.Co-immunoprecipitation and mass spectrometry was applied to identify SIRT2-interacting proteins in NPC cells.Results:In comparison to nasopharyngeal epithelial NP69 cells,SIRT2 was up-regulated in multiple NPC cell lines,particularly in CNE2 cells.SIRT2 knockdown abrogated CNE2 cell proliferation and colony formation,whereas SIRT2 overexpression promoted HNE1 cell proliferation and colony formation.The SIRT2-interacting proteins were gathered in gene expression and regulation processes including RNA processing and translation.Among the SIRT2-interacting proteins,there were multiple DEAD-box(DDX)family members.Of note,silencing of DDX24 phenocopied the effect of SIRT2 knockdown on NPC growth.Overexpression of DDX24 restored SIRT2-depleted CNE2 cells to proliferative and colony formation.Conclusions:Our study indicates that SIRT2 can interact with DDX24 to enhance NPC growth.The clinical relevance of SIRT2 and DDX24 in NPC warrants further investigation.

Effects of Cisplatin and Metformin on Proliferation of Nasopharyngeal Carcinoma SUNE-1 Cells

[Objectives]This study was conducted to investigate the effects of different concentrations of cisplatin and metformin on the growth and proliferation of nasopharyngeal carcinoma SUNE-1 cells.[Methods]The concentrations of cisplatin were set as 2.5,5.0,10.0,25.0,40.0μg/mL,and those of metformin were set as 0.625,1.25,2.5,5,10,and 20 mmol/L.After 48 h of intervention in nasopharyngeal carcinoma SUNE-1 cells,the proliferation inhibitory rate and the median inhibitory concentration(IC_(50))of SUNE-1 cells were measured by the CCK-8 method.[Results]It was found that different concentrations of cisplatin and metformin all had an inhibitory effect on the proliferation of SUNE-1 cells,and the inhibitory effect became more significant with the increase of concentration.The IC_(50)values of cisplatin and metformin were 43.57μg/mL and 6.855 mmol/L,respectively.[Conclusions]Cisplatin and metformin inhibited the proliferation of SUNE-1 cells in a concentration-dependent manner,providing a theoretical guidance for the clinical treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma with synchronous breast metastasis:A case report

BACKGROUND Recent reports have described cases of metachronous breast metastasis in patients with nasopharyngeal carcinoma.However,no similar cases of synchronous breast metastasis have been reported,and evidence that can be used to support the clinical diagnosis of stage IV nasopharyngeal carcinoma in patients with concurrent breast metastasis remains lacking.Therefore,additional evidence is required to elucidate the clinical characteristics of this condition and aid in the development of optimal management strategies.CASE SUMMARY We report the case of a 46-year-old woman who visited our hospital with a right breast mass as the first symptom.The first pathological biopsy report suggested triple-negative breast invasive carcinoma.Subsequent imaging revealed a nasopharyngeal mass.Further puncture biopsy of the nasopharyngeal mass,molecular pathological Epstein–Barr virus in situ hybridization,and immunohistochemistry confirmed the diagnosis of nasopharyngeal carcinoma with breast metastasis.The patient did not undergo a mastectomy and achieved complete remission after chemotherapy and radiotherapy.She continued to receive oral chemotherapy as maintenance therapy and experienced no recurrence or metastasis during the 6-month follow-up period.CONCLUSION This case report suggests that breast specialists should carefully rule out secondary breast cancers when diagnosing and treating breast masses.Furthermore,clinicians should aim to identify the pathological type of the tumor to obtain the most accurate diagnosis and prevent excessive diagnosis and treatment.

Comparative Study between Patients Treated with Conventional Radiotherapy and IMRT with Chemotherapy for Stage III - IVA Nasopharyngeal Carcinoma: A Single Institution Retrospective Report

Introduction: Nasopharyngeal carcinomas are the most radiation-sensitive tumours, and radiotherapy alone provides better local control. Objectives: To evaluate the clinical efficacy and acute and late toxicities of two different treatment regimens for locally advanced nasopharyngeal carcinoma. Methods: From 2014 to 2017, 150 cases of stage III and 68 cases of stage IVA nasopharyngeal carcinoma were treated. Of these, 137 received conventional radiotherapy plus chemotherapy, and 81 received intensity-modulated radiotherapy plus chemotherapy. Chemotherapy was given either as induction, concurrent or adjuvant therapy. Survival rates were calculated according to Kaplan Meier and compared with the Log-rank test. The RTOG or EORTC criteria were used to assess acute and late toxicities. Results: The median follow-up time was 21.5 months, and the 2-year locoregional relapse-free survival, distant metastases-free survival, and overall survival rates in the conventional radiotherapy plus chemotherapy group were 76%, 71% and 77%, respectively;in the intensity-modulated radiotherapy plus chemotherapy group, they were 97%, 84%, and 100%, respectively. The difference in survival between the two groups was significant (χ2 = 5.06, P = 0.028). The incidence of grade 2 and 3 xerostomia one year after radiotherapy was 45.1% and 30.9% versus 33.3% and 0%. Conclusion: Compared with conventional radiotherapy plus chemotherapy, intensity-modulated radiotherapy plus chemotherapy offers better locoregional relapse-free survival and overall survival in patients with stage III and IVA nasopharyngeal carcinoma, and may significantly reduce the occurrence of radiation-induced xerostomia.

Predictive function of tumor burden-incorporated machine-learning algorithms for overall survival and their value in guiding management decisions in patients with locally advanced nasopharyngeal carcinoma

Objective:Accurate prognostic predictions and personalized decision-making on induction chemotherapy(IC)for individuals with locally advanced nasopharyngeal carcinoma(LA-NPC)remain challenging.This research examined the predictive function of tumor burden-incorporated machine-learning algorithms for overall survival(OS)and their value in guiding treatment in patients with LA-NPC.Methods:Individuals with LA-NPC were reviewed retrospectively.Tumor burden signature-based OS prediction models were established using a nomogram and two machine-learning methods,the interpretable eXtreme Gradi-ent Boosting(XGBoost)risk prediction model,and DeepHit time-to-event neural network.The models’prediction performances were compared using the concordance index(C-index)and the area under the curve(AUC).The patients were divided into two cohorts based on the risk predictions of the most successful model.The efficacy of IC combined with concurrent chemoradiotherapy was compared to that of chemoradiotherapy alone.Results:The 1221 eligible individuals,assigned to the training(n=813)or validation(n=408)set,showed significant respective differences in the C-indices of the XGBoost,DeepHit,and nomogram models(0.849 and 0.768,0.811 and 0.767,0.730 and 0.705).The training and validation sets had larger AUCs in the XGBoost and DeepHit models than the nomogram model in predicting OS(0.881 and 0.760,0.845 and 0.776,and 0.764 and 0.729,P<0.001).IC presented survival benefits in the XGBoost-derived high-risk but not low-risk group.Conclusion:This research used machine-learning algorithms to create and verify a comprehensive model inte-grating tumor burden with clinical variables to predict OS and determine which patients will most likely gain from IC.This model could be valuable for delivering patient counseling and conducting clinical evaluations.

The initial results of Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP-1) for screening nasopharyngeal carcinoma (NPC)

Objective: Early diagnosis of nasopharyngeal carcinoma (NPC) is an important method to improve the survival rate.However,the sensitivity and specificity of the screening protocols which was widely used in clinic now are considered to be unsatisfactory.Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP-1) is one of the proteins that have been suggested to be a classic oncogene with transformation properties.The current study set out to discuss the clinical significance of LMP-1 on the screening of NPC.Methods: Three hundred patients who visited our institution (Department of Radiation Oncology,Fujian Provincial Cancer Hospital,Fuzhou,China) with ENT symptoms between 2007 and 2008 were involved in this study,and all of them were agreed to be involved in this investigation.Not only did they undergo nasopharyngeal swab to obtain cells for the LMP-1 polymerase chain reaction (PCR) analysis,but also nasopharyngeal biopsy were taken to identify the diagnosis.Results: An amount of DNA that was sufficient for PCR was extracted from 243 (81%) swab samples,the positive rate of LMP-1 of those with non-nasopharyngeal carcinoma was 3.85% (4/108),which was much lower than those with nasopharyngeal carcinoma (P < 0.05).By detecting LMP-1 in nasopharyngeal swabs,NPC was diagnosed with a sensitivity of 88.15% (119 of 135 patients),specificity of 96.30% (104 of 108 patients),a positive predictive value of 95.2% (119 of 123 patients),a negative predictive value of 86.67% (104 of 120 patients),accuracy of 91.77%,and Youden index of 84.45%.Conclusion: The nasopharyngeal swab coupled with PCR-based EBV LMP-1 detection have high sensitivity and specificity,and also good repeatability,it could serve as part of the screening program for high-risk populations.

ESTABLISHMENT OF HIGH RISK POPULATION AND PRECANCEROUS LESION OF NASOPHARYNGEAL CARCINOMA(NPC)

A prospective study was done by the examination of nasopharyngoscope, reaction of EB virus's antigens and antibodies, nasopharyngofibroscope, pathological and EB virus's DNA, EBERs, etc. of about 100000 persons in high risk area of NPC in Guangdong Province, China from 1986 to 1995. If any one of the following four conditions is present in some persons, i.e., (1) EBV VCA/IgA titer>1:80, (2) EBV EDAb>60%, (3) Dual or triple positiveness in VCA/IgA, EA/IgA and EDAb, (4) Any one of VCA/IgA, EA/IgA and EDAb keeps high titer or going up, they should be regarded as in precancerosis of NPC. The moderate or severe heteroplasia and heterometaplasia of nasopharyngeal mucosa are the precancerous lesions of NPC. Some individual who is in precancerosis or with precancerous lesion should be regarded as the high risk population of NPC. The results are of important scientific basis for screening and second degree prevention of NPC.

POPULATION CHARACTERS IN HIGH RISK PEDIGREES OFNASOPHARYNGEAL CARCINOMA (NPC)

Objective: To investigate population characters in high risk pedigrees of NPC in Guangdong area and to explore the effect each other between tumor genetic susceptibility and infection of EB virus on pathogenic mechanism. Methods: Pedigree investigation, examination of DNA fingerprint, multi-antibodies of EB virus and nasopharyngeal cavity were done for all of the members in each high risk pedigree. Results: High positive rate of EBV VCA/IgA (23.22%), high percentage of high risk population of NPC (6.53–10.40%), high detected rate of malignant tumor (9552.59/105), and high detected rate of NPC (8464.32/105) were discovered and NPC was most common in first degree relative of a pedigree. Conclusion: Tumor genetic susceptibility, infection of EB virus might play a role in coordination of reinforced effect on occurrence of NPC.

THE IMPACT OF RADIOTHERAPY COURSE LENGTH ON THE TREATMENT RESULTS OF NASOPHARYNGEAL CARCINOMA(NPC)

Analyses made among four radiotherapy schedules for NPC in order to determine whether there is an impact of radiotherapy course length on treatment results.A series of 320 NPC patients were divided into four radiation treatment branches each with a schedule, this clinical trial was non-randomized.Radiotherapy course length factor was considered with a derivative LQ model formula that biological effective dose(BED)=nd[1 +d/(α/β)]-(T-28).The four branches were:1.split-course 103 cases, with an intermediary rest of 3-4 weeks,mean total dose 70Gy/35fx,73d, BED 51.6 Gy; 2.continuous 115 cases, 72Gy/36fx, 61d, BED 62.6 Gy;3.hyperfractionation I 52 cases, 1.5 Gy b.i.d.,time interval(Ti)≥6 hr, 75Gy/49fx,57d,BED 65.5Gy;4. hyperfractionation Ⅱ 50 cases, 1.2 Gy b.i.d., Ti≥6hr,76Gy/60fx,59d,BED 63.0 Gy.Treatment results were compared with 1-, and 3-year loco-regional recurrent rates,and 1-,and 3-year survival rates, and these rates were of a negative interrelation with prolonged course duration, but of a positive one with BED valas.Continuous branch was of a course mean 12 days shorter than the spilt-course one, its treatment results were nearly 10% higher in some subgroups;and hyperfractionation branches were slightly better than continuous one.

SERO-EPIDEMIOLOGICAL STUDIES OF EPSTEIN-BARR VIRUS(EBV) INFECTION BY TESTING ANTIBODIES AGAINST EBV SPECIFIC DNASE(EDAb) AS A METHOD FOR EARLY DETECTION OF NASOPHARYNGEAL CARCINOMA(NPC)

In 1987, a mass survey of EDAb was carried out in Sihui county of Gunagdong Province (the highest incidence area of NPC in China) and the city of Guangzhou using the methods previously established by our lab. In order to study the correlation between EDAb level and NPC, the titre of DEAb and their distribution in sera from 430 patients with NPC and 5030 normal persons were detected. It was found that the AER (level of EDAb was represented by the anti enzyme rate) of NPC patients gave a negative skew distribution and the Md=65.3% while the natural population (30 59 years old) gave a serious positive skew distribution and the Md is 7.9%. According to the pattern of EDAb distribution curve of 430 NPC patients and 2060 natural population. AER≥30% was defined as a cut off point between EDAb positive and negative. Using this value we got a rate of 90.7% (390/430) positive diagnosis in NPC patients, while in natural population the positive rate was 3.3% (68/2060), and in the IgA/VCA positive (1:5) normal person the positive rate was 6.0% (41/681). As to the other tumors including head and neck tumors the positive rate was 3.4% (7/204), similar to the natural population. After a period of 62 months of follow up surveillance, 15 of 224 EDAb positive normal persons found in the mass survey were diagnosed as NPC by histopathological examination. While in 4806 EDAb negative normal person only one case NPC patient was found in this period. 60% of these patients were diag nosed in their early stage of NPC. From these patients it was found that EDAb could appear in the sera of the patients as early as 62 months before NPC was definitely diagnosed. 2 of these patients were shown IgA/VCA negative and EDAb positive in mass survey. This suggested that in some of the precancerous patients EDAb could appear earlier than IgA/VCA. The signifi cance of the sera EDAb positivity of normal person was discussed.