Abstract Background: Nasopharyngeal cancer (NPC) is a malignancy of the nasopharyngeal mucosal epithelium. Primary and secondary metastases in nasopharyngeal cancer are generally prevalent in the bones. Gene expression plays a critical role in regulating fundamental cellular processes in cancer cells, including metastasis. Methods: A total of 29 patients with non-metastatic NPC were included in the study. Results: The mean age of the participants was 48.45±9.98 years old. Most participants were male (75.9%). More than half of the participants had T4 and N2, 52.7% and 51.0% respectively). Secondary metastasis was observed in 9 of the 29 participants within two years. Patients with secondary metastases had a higher proportion of T4 (7/9) and N2 (4/9) disease. Bone was the first site of secondary metastasis (6/9 patients). The median time to secondary bone metastasis was 14.0 (6.8-21.2) months. Based on the differential expression gene (DEG) analysis, the MMP9 gene was upregulated 12.50 (4.18–37.40), adjusted p <0.01, and the ADNP gene was downregulated 0.141 (0.04–0.43), adjusted p 0.04, among patients with secondary bone metastasis. Conclusion: Bones are the first site of metastasis, with a time to metastasis of 14.0 (6.8-21,2) months. MMP9 was upregulated, and ANDP was downregulated in patients with bone metastasis compared to those without metastasis.
MMP-9 ; ADNP ; nasopharyngeal cancer ; secondary bone metastasis

Objective: To evaluate the safety and effectiveness of a vaccine based on latent membrane protein 2 (LMP2) modified dendritic cells (DCs) that boosts specific responses of cytotoxic T lymphocytes (CTLs) to LMP2 before and after intradermal injection in patients with nasopharyngeal carcinoma (NPC). Methods: DCs were derived from peripheral blood monocytes of patients with NPC. We prepared LMP2-DCs infected by recombinant adenovirus vector expressing LMP2 (rAd-LMP2). NPC patients were immunized with 2 × 10 Results: We demonstrated that DCs derived from monocytes displayed typical DC morphologies; the expression of LMP2 in the LMP2-DCs vaccine was confirmed by immunocytochemical assay. Twenty-nine patients with NPC were enrolled in this clinical trial. The LMP2-DCs vaccine was well tolerated in all of the patients. Boosted responses to LMP2 peptide sub-pools were observed in 18 of the 29 patients with NPC. The follow-up data of 29 immunized patients from April, 2010 to April 2015 indicated a five-year survival rate of 94.4% in responders and 45.5% in non-responders. Conclusion In this pilot study, we demonstrated that the LMP2-DCs vaccine is safe and effective in patients with NPC. Specific CTLs responses to LMP2 play a certain role in controlling and preventing the recurrence and metastasis of NPC, which warrants further clinical testing.
Adult ; Aged ; Cancer Vaccines/therapeutic use* ; China ; Dendritic Cells/immunology* ; Female ; Humans ; Immunotherapy/methods* ; Injections, Intradermal ; Male ; Middle Aged ; Nasopharyngeal Carcinoma/therapy* ; Nasopharyngeal Neoplasms/therapy* ; T-Lymphocytes, Cytotoxic/immunology* ; Viral Matrix Proteins/therapeutic use* ; Young Adult

OBJECTIVETo investigate the relationship between changes in high-risk populations and screening detected nasopharyngeal carcinoma (NPC) during the three-year follow-up of high-risk and moderate-risk groups at initial EB virus serology screening.

METHODSWe tested EB virus VCA-IgA and EBNA1-IgA antibody to identify the probability of suffering from NPC of the crowd. The high-risk and moderate-risk groups at initial screening in one county during 2009 to 2010 were followed-up once a year with EB virus serology testing. All the high-risk people during initial screening and follow-up were conducted with nasopharyngeal fiber endoscopy. Through the follow-up of three years, we analyzed changes in the number of high-risk group, detection rate of NPC in high-risk group, and tumor staging. Firstly detected NPC by screening was defined as screening group, and detected by following-up was defined as following-up group.

RESULTSA total of 404 participants were at high-risk and 1 041 participants were at moderate-risk group, 1 445 persons were in the group. All 404 persons were at high-risk at initial screening, the number of high-risk people during follow-up decreased from 371 to 187, 853 people of the all high-risk group were conducted with nasopharyngeal fiber endoscopy, and 38 cases of NPC were detected. NPC detection rate of high-risk group was 6.2% (25/404), 3.2% (12/371), 0.5% (1/188) and 0 (0/187) during the initial screening and three years follow-up respectively. The cumulative incidence of NPC in the high-risk and moderate-risk group were 7.7% (31/404) ,0.8% (8/1 041) . The early diagnosis rate of NPC in screening group and following-up group was 80% (20/25)and 11/13, respectively. With the primary tumor, the rate of T1 in screening group was higher than following-up group (80% to 38%, 20/25 to 5/13; P = 0.028). However, compared with following-up group, the rate of regional lymph node metastasis in screening group was higher (19/25 to 5/13; P = 0.035 ).

CONCLUSIONAlong with the high detection rate of early staging NPC in screening group and following-up group, the detection of NPC in high risk people is mainly at initial screening and the first year following-up and NPC detection rate thereafter is dropping significantly.

Antibodies, Viral ; Antigens, Viral ; Capsid Proteins ; Carcinoma ; Early Detection of Cancer ; Epstein-Barr Virus Nuclear Antigens ; Follow-Up Studies ; Herpesvirus 4, Human ; Humans ; Nasopharyngeal Neoplasms ; Neoplasm Staging ; Risk Factors

OBJECTIVETo evaluate the cost-effectiveness of different screening strategies for nasopharyngeal carcinoma (NPC) and recommend a preferable NPC screening strategy.

METHODSA Markov simulation model was constructed based on the natural history of NPC. Seven strategies (A. Annual screening; B. Annual screening for (Epstein-Barr virus, EBV) EBV-seropositive subjects, triennial screening for seronegative subjects; C. Biennial screening; D. Triennial screening; E. 4-year screening; F. 5-year screening; G. 6-year screening) were evaluated. The NPC-pickup rate, cost, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated.

RESULTSThe ICERs of the 7 strategies were 83 111.6, 47 768.9, 50 164.7, 40 016.2, 34 272.8, 32 215.6, and 32 248.0 Yuan/QALY, respectively. The discounted QALYs of the strategies were 23 079.9, 22 955.6, 22 810.4, 22 636.5, 22 522.7, 22 445.0, and 22 361.9 years, respectively. The ICERs of the strategies were less than three times of the average per capita gross domestic product (89 976 Yuan) in China in 2010. The strategy A achieved a highest NPC pick-up rate (81.7%), a highest discounted QALY and a smallest number of NPC death (681), but a highest discounted cost and a greatest ICER. Compared with the strategy A, the strategy B achieved a little smaller NPC pick-up rate (73.1%), a little smaller number of NPC death (707), however, the ICER of the strategy B decreased by 38.2%.

CONCLUSIONThe strategy B (annual screening for EB virus seropositive subjects and triennial screening for seronegative subjects) is a preferable option for NPC screening.

Adult ; Carcinoma ; China ; epidemiology ; Cost-Benefit Analysis ; Early Detection of Cancer ; economics ; methods ; Epstein-Barr Virus Infections ; diagnosis ; Female ; Herpesvirus 4, Human ; isolation & purification ; Humans ; Male ; Markov Chains ; Mass Screening ; economics ; methods ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnosis ; mortality ; Quality-Adjusted Life Years ; Survival Rate

OBJECTIVETo investigate the inhibitory effects of Pseudomonas aeruginosa vaccine (PA-MSHA) on the proliferation of human nasopharyngeal cancer cells and explore the possible mechanism.

METHODSMTT assay was used to determine the cell growth of human nasopharyngeal cancer cell line 5-8F and 6-10B in vitro treated with the vaccine. The cell cycle distribution of the cells was detected by flow cytometry, and the expression levels of apoptosis and cycle-related proteins were evaluated by Western blotting.

RESULTSPA-MSHA treatment significantly suppressed the proliferation of 5-8F and 6-10B cells in a time- and concentration-dependent manner compared with the control group (P<0.05). The cells with PA-MSHA treatment exhibited a decreased percentage of cells entering S phase and a corresponding increase in G(1) phase cells in FACS analysis. The expression of cyclin D(1), CDK4, and CDK6 was significantly up-regulated, Bax protein up-regulated, and the anti-apoptosis protein Bcl-2 down-regulated in PA-MSHA-treated cells.

CONCLUSIONPA-MSHA can suppress the proliferation of nasopharyngeal carcinoma cell in vitro by affecting the cell cycle and promoting cell apoptosis.

Apoptosis ; drug effects ; Cancer Vaccines ; immunology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Nasopharyngeal Neoplasms ; pathology ; Pseudomonas aeruginosa ; immunology

In a prospective study, 42 048 adults residing in Zhongshan City, Guangdong, China, were followed for 16 years, and 171 of them developed nasopharyngeal carcinoma (NPC). Although Epstein-Barr virus (EBV) antibody levels of the cohort fluctuated, the antibody levels of 93% of the patients with NPC were raised and maintained at high levels for up to 10 years prior to diagnosis. This suggests that the serologic window affords an opportunity to monitor tumor progression during the preclinical stage of NPC development, facilitating early NPC detection. We reviewed the clinical records of the 171 patients with NPC in the prospective study to assess the efficacy of early NPC detection by serologic screening and clinical examination. Of the 171 patients, 51 had Stage I tumor (44 were among the 73 patients detected by clinical examination and 7 were among the 98 patients presented to outpatient department). Initial serologic screening predicted 58 (95.1%) of the 61 patients detected within 2 years. The risk of the screened population (58/3093) raised 13 times relative to cohort (61/42 048) during this period. Clinical examination detected all the 58 predicted cases, and 35 (60.3%) of which were diagnosed with Stage I tumor. The serologic prediction rate fell to 33.6% (37/110) 2 to 16 years after screening. The proportion of cases detected by clinical examination fell to 40.5% (15/37). The proportion of Stage I tumors among the cases detected by clinical examination during both periods remained at about 60%. We concluded that early detection of NPC can be accomplished by repeated serologic screening to maintain high prediction rates and by promptly examining screened subjects to detect tumors before the symptoms develop.
Adult ; Aged ; Antibodies, Viral ; blood ; Antigens, Viral ; immunology ; Capsid Proteins ; immunology ; Carcinoma, Squamous Cell ; blood ; diagnosis ; pathology ; Chemotherapy, Adjuvant ; Cohort Studies ; Early Detection of Cancer ; methods ; Female ; Herpesvirus 4, Human ; immunology ; Humans ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; blood ; diagnosis ; pathology ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Remission Induction ; Survival Rate

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.
Age Factors ; Antibodies, Viral ; analysis ; Antigens, Viral ; analysis ; Asian Continental Ancestry Group ; genetics ; Capsid Proteins ; analysis ; Carcinoma ; China ; epidemiology ; Early Detection of Cancer ; methods ; Herpesvirus 4, Human ; immunology ; Humans ; Nasopharyngeal Neoplasms ; epidemiology ; genetics ; immunology ; prevention & control ; Prevalence

OBJECTIVE: Nasopharyngeal Carcinoma (NPC) can be successfully treated by radiotherapy, if the tumor is confined to nasopharynx, but clinical onset is usually delayed to more advanced stages, when prognosis is poor. The objective is to determine efficacy of a new program for early NPC detection, which entails stratification of the NPC risk of target population according to serum levels of 3 Epstein Barr Virus (EBV) antibodies. METHOD: The sera of 1373 healthy adult residents from Zhongshan were collected and analyzed in this study from Mar 16, 2007 to Dec 31, 2007. The levels of EBNA1/IgA, zta/IgG and EBNA1/IgG were tested by ELISA. To stratify the subjects of 1373 adults into high, moderate and normal NPC risk groups by regression analysis of the levels of the EBV antibody. The high-risk groups of nasopharyngeal carcinoma risk could be followed-up every 3-6 month. RESULT: NPC risk of 1379 adults was stratified according to serum levels of the 3 EBV antibodies. Eleven (0.8%) were identified to be of high risk for NPC, having high levels of all three antibodies and/or IgA EBNA level > 3 rod. Clinical examination of high risk subjects detected 5 NPC cases, 3 cases detected in the first instance and 2 in follow-up examination 3 to 6 months hence. Three cases were diagnosed with UICC Stage I tumor (60%), one in the first instance and 2 in follow-up, and the 5 cases account for all NPC cases detected from the entire cohort over 28 months(100%). CONCLUSION The new program affords an efficient and efficacious means for early NPC detection.
Antibodies, Viral ; blood ; China ; epidemiology ; Early Detection of Cancer ; methods ; Epstein-Barr Virus Nuclear Antigens ; immunology ; Humans ; Male ; Middle Aged ; Multiphasic Screening ; Nasopharyngeal Neoplasms ; blood ; diagnosis ; epidemiology ; virology ; Risk Assessment

OBJECTIVETo analyze the change of EB virus VCA/IgA and EA/IgA titer during the development of nasopharyngeal carcinoma (NPC), and the role in screening for NPC.

METHODSVCA/IgA and EA/IgA were monitored in a period of 12 years by immunoenzymatic titration from the sera of 54 NPC patients after primary serological screening.

RESULTSVCA/IgA and EA/IgA titer had shown gradual increment 1 - 7 years before NPC was pathologically diagnosed. The mean titer of VCA/IgA was 1:21.04, 7 - 4 years before diagnosis. VCA/IgA titer ascended quickly within 3 years before diagnosis. The geometric mean titer (GMT) of VCA/IgA and EA/IgA were 1:76.86 and 1:6.49 when NPC was diagnosed, which descended quickly after radiotherapy and, in 4 years, approached the average titer of VCA/IgA positive population.

CONCLUSIONVCA/IgA titer rises uninterruptedly 3 years before NPC is diagnosed pathologically in most patients but their EA/IgA titer rises slowly. The detection of VCA/IgA titer can be used to find early NPC, whereas EA/IgA can not. The pre-clinical phase of NPC is 3 years according to this dynamic study.

Adult ; Antibodies, Viral ; blood ; Antigens, Viral ; immunology ; Capsid Proteins ; immunology ; Early Detection of Cancer ; Humans ; Immunoglobulin A ; blood ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnosis ; virology

OBJECTIVETo investigate the effect of active immunotherapy with anti-idiotypic vaccine in patients with nasopharyngeal carcinoma (NPC).

METHODSAnti-idiotypic antibodies (2H4/5D3) bearing the internal image of the NPC antigen were used in active immunotherapy in NPC patients receiving radiotherapy. Antibodies and cytokine levels in patient sera were determined using ELISA before and after active immunotherapy. IL-2 mRNA expression in the peripheral blood mononuclear cells (PBMC) was measured by in situ hybridization.

RESULTSNineteen patients with NPC at stage IV were treated with alum-precipitated 2H4 or 5D3. Neither hypersensitivity nor adverse side effects were observed. The levels of anti-anti-idiotypic antibodies (Ab3) and anti-NPC antibodies (Ab1') were increased. Human anti-mouse antibodies (HAMA) were seen in 19 patients of the experimental group; the levels of Ab1' did not increase in the control group. Serum IL-2, IFN-gamma and TNF-alpha levels were increased in most patients in the experimental group, while no differences were observed in Ab1' and cytokine levels between pre- and post-therapy in the control group. In addition, IL-2 mRNA expression in PBMCs from NPC patients was closely related to serum IL-2 (r = + 0.8829) levels by in situ hybridization.

CONCLUSIONSAnti-idiotype vaccine is safe for clinical active immunotherapy. Anti-idiotypic vaccine might be able to enhance humoral and/or cellular immunity in NPC patients receiving radiotherapy.

Adult ; Antibodies, Anti-Idiotypic ; immunology ; therapeutic use ; Antibody Specificity ; Cancer Vaccines ; immunology ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunotherapy, Active ; Interferon-gamma ; blood ; Interleukin-2 ; blood ; genetics ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; blood ; drug therapy ; immunology ; RNA, Messenger ; genetics ; metabolism ; Treatment Outcome ; Tumor Necrosis Factor-alpha ; metabolism