EB病毒膜潜伏蛋白LMP-1筛选鼻咽癌的初步结果

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% (104of 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.     

Current knowledge of Chlamydia pneumoniae and atherosclerosis

Tc-99m tetrofosmin SPECT imaging of the head and neck was performed on 10 patients with nasopharyngeal carcinoma (NPC) and 10 controls. There was no abnormal nasopharyngeal uptake of tetrofosmin in the 10 controls. In the patients with NPC, 3/10 (30%) of the cases had no abnormal uptake and 7/10 (70%) had increased nasopharyngeal uptake. Considering our preliminary study, we find that Tc-99m tetrofosmin SPECT of the head and neck may be helpful in the detection of NPC. However, further study with a larger number of patients is needed to ascertain the value of Tc-99m tetrofosmin SPECT in such cases.     

Immune thrombocytopenia due to Tranilast (Rizaben): detection of drug-dependent platelet-associated IgG

This study tried to assess the probability of nasopharyngeal carcinoma (NPC) being present in adults with only otitis media with effusion (OME) and evaluate the necessity of nasopharyngeal biopsy in Taiwanese adults with only OME. The clinical features of patients with known OME were analyzed and the incidence of nasopharyngeal carcinoma in adults with only OME was assessed. The clinical features of 36 adults with OME but without other symptoms and signs suggestive of NPC who presented to the Kaohsiung Medical College Hospital Department of Otorhinolaryngology between December 1995 and February 1997 were analyzed. Two of these patients had biopsy-proven non-keratinizing carcinomas. OME was caused by upper respiratory infection in 8 patients (22.2%), chronic paranasal sinusitis in 5 (13.9%), allergic rhinitis in 5 (13.9%), NPC in 2 (5.6%), other etiologies in 5 (13.9%) and by unknown etiologies in 11 (30.5%). The incidence of NPC in adults with OME but no other symptoms and signs suggestive of NPC was 5.6% (2 out of 36 patients). It was higher than other reports because NPC has a high prevalence in Taiwan. Therefore, biopsy of the post-nasal space in adults with only OME when NPC is strongly suspected is necessary for the early diagnosis of NPC in Taiwan. We conclude that Taiwanese adults with only OME for which the cause is unclear should be subjected to an examination and biopsy of the nasopharynx to exclude NPC.     

Isolation of bacterial endotoxins from Pseudomonas putida 36 and Escherichia coli (vulgaris)

A prospective analysis of 69 patients who had been treated for nasopharyngeal carcinoma (NPC) by external radiotherapy was carried out. Biopsies from the posterior nasopharynx were performed and analyzed by in situ hybridization using an antisense Epstein-Barr Early RNA (EBER) radio-labelled riboprobe. None of the patients had evidence of disease in the nasopharynx. One patient was found to have nasopharyngeal carcinoma detected only by in situ hybridization. In the subsequent 18-month follow-up of these clinically- and biopsy-negative patients, only one patient developed relapse in the nasopharynx. In situ hybridization is a valuable tool for the detection of NPC and should be routinely available in histopathology laboratories where NPC is regularly diagnosed.     

Prognostic features and treatment outcome in locoregionally advanced nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy

PURPOSE: Concurrent chemotherapy and radiotherapy (CCRT) are effective in treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the prognostic factors after CCRT have not been evaluated. We therefore attempt to evaluate factors that influence treatment outcomes following CCRT. METHODS AND MATERIALS: Seventy-four (5 in stage III and 69 in stage IV) patients with locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5-fluorouracil. Cox proportional-hazards model was used to analyze the prognostic factors which included age, gender, pathologic type, T, N, lactate dehydrogenase (LDH), and infiltration of the clivus. RESULTS: The primary tumor control rate at 3 years was 96.7% (95% confidence interval [CI]: 92.5-100), distant metastasis-free survival 81.1% (95% CI: 70.6-91.6), disease-free survival 77.0% (95% CI: 65.3-88.7), and overall survival 79.8% (95% CI: 69.2-90.4) with a median follow-up interval of 29 months (range 15-74 months). Cox proportional-hazards model revealed that infiltration of the clivus and serum level of LDH before treatment were the most two important factors that predict distant metastases. Infiltration of the clivus and the serum LDH level greater than 410 U/L were strongly associated with distant metastasis-free survival (p = 0.0004 and p = 0.0002, respectively). When these two risk factors were considered together, no distant metastasis was observed in 40 patients with both intact clivus and LDH < or = 410 U/L. On the contrary, 13 of the remaining 34 patients with at least one risk factor developed distant metastasis (p = 0.0001). CONCLUSION: Our study demonstrates that CCRT can improve the primary tumor control of 96.7% and disease-free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the major cause of failure. Infiltration of the clivus by the tumor and LDH greater than 410 U/L are the two independent and useful prognostic factors in patients with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk patients can be distinguished by virtue of their having both conditions.     

Evaluation of cervical nodal necrosis in nasopharyngeal carcinoma by computed tomography: incidence and prognostic significance

PURPOSE: The purpose was to study the prognostic value of contrast-enhanced computed tomography (CT) nodal necrosis in nasopharyngeal carcinoma. PATIENTS AND METHODS: One hundred sixty-one patients with newly diagnosed nasopharyngeal carcinoma and nodal metastases were reviewed. Forty patients also received cisplatin-based neoadjuvant chemotherapy in addition to radiotherapy. Nodal necrosis was defined as presence of hypodense areas in more than 33% of the node. Nodal response rate to chemotherapy, overall nodal control rate, local control rate, distant failure rate, overall relapse-free survival rate, and overall and cause-specific survival rates were compared between patients with and without nodal necrosis. Multivariate analysis was also performed. RESULTS: The incidence of nodal necrosis was 22.9%. Overall nodal response rates to chemotherapy were 88.9% (8/9) in patients with nodal necrosis and 74.2% (23/31) in those without. No significant differences in nodal control rate, local control rate, distant failure rate, and overall and cause-specific survival rates were found. Five-year overall relapse-free survival rate was lower in patients with cervical nodal necrosis (36%) as compared with those without (53%, p = .04). Multivariate analysis, however, did not confirm cervical nodal necrosis to be an independent prognostic factor. CONCLUSIONS: Presence of nodal necrosis in nasopharyngeal carcinoma does not affect nodal response to chemotherapy and nodal control by radiotherapy with or without chemotherapy. Cervical nodal necrosis does not appear to be an independent factor in predicting treatment outcome. Further studies to correlate nodal density with oxygenation status as well as tumor cell kinetics are warranted.     

Nasopharyngeal carcinoma research in Hong Kong in the past decade

OBJECTIVE: To review the research carried out in Hong Kong on nasopharyngeal carcinoma (NPC) over the past 10 years. METHODS: The literature published in Hong Kong over the past 10 years on nasopharyngeal carcinoma were reviewed in the light of other important international publications on the same subject. RESULTS: The research carried out in Hong Kong covers etiology, natural behavior, treatment and prognosis of NPC. These studies not only elucidated the different aspects of NPC, many of these new findings will also guide future directions of research. CONCLUSIONS: Major efforts have been made to research into the various aspects of NPC with important findings which will translate into better treatment results. As this tumor is uncommon in other parts of the world, continued efforts to improve the prevention, early diagnosis, treatment and care of this tumor are required in China.     

Establishment of partial gene expression map of 7q32 in nasopharyngeal carcinoma and primary culture normal nasopharyngeal epithelial cells

OBJECTIVE: To establish partial gene expression map of 7q32 in nasopharyngeal carcinoma (NPC) cell line, tissues and primary culture normal nasopharyngeal epithelial cells. METHODS: We detected the expression of 20 ESTs at 7q32 in NPC cell line HNE1,13 NPC biopsies and primary culture normal nasopharyngeal epithelial cells using differential RT PCR and Northern hybridization. RESULTS: 8 ESTs (AA188181, AA13079,N27556, AA031919, N22721, H20825, T91284, AA001936) expressed equally in both of HNE1 and primary culture normal nasopharyngeal epithelial cells; 7 ESTs (T64215, AA025822, R60014,R80002,H06688, R60192,R95096) expressed in neither of them; 3 ESTs (H19830,W72688,AA130630) overexpressed in HNE1 ; and 2 ESTs (AA070437, H90882) overexpressed in primary culture normal nasopharyngeal epithelial cells. W72688 and H19830 each overexpressed in 77%(10/13) of NPC biopsies; AA070437 down-expressed in 30.7% of NPC biopsies. CONCLUSION: Partial gene expression map of 7q32 in nasopharyngeal carcinoma cell line ,tissues and primary culture normal nasopharyngeal epithelial cells has been established. The up-regulation of W72688, H19830 and down-regulation of AA070437 may be related to the occurrence of NPC.     

Nasopharyngeal carcinoma: clinical trends

Nasopharyngeal carcinoma (NPC) is one of the most difficult diseases to diagnose at an early stage. The clinical presentation of 122 patients with confirmed NPC is described and the findings analysed. The common modes of presentation and cases where detailed nasopharyngeal examination need to be performed are highlighted. We emphasize the importance of health education and training for primary care physicians for early detection of these cases.     

Perspectives on the role of the lateral pterygoid muscle and the sphenomandibular ligament in temporomandibular joint function

This is a phase II study to evaluate the efficacy and toxicity of short-course carboplatin in advanced-stage nasopharyngeal carcinoma (NPC). Thirty-three previously untreated stage III-IV NPC patients were studied. Carboplatin was given as a rapid intravenous injection every 3 weeks. The dose of carboplatin was calculated according to the individual patient's creatinine clearance and desired platelet nadir of 75,000/microliter according to the Egorin formula. Response and toxicity were evaluated. Thirty-two patients were evaluated for response. The median age was 54 years, range 30-70 years. Twenty-four patients had local regional disease and 8 patients had metastatic disease. The median dose of carboplatin given was 415 mg/m2 (range 91-791 mg/m2). Fourteen (44%) patients had a partial response with a 95% confidence interval of 26-62%. Fifteen (47%) patients had stable disease and 3 (9%) progressive disease. The overall median survival rate was not reached at 43 months. Overall toxicity was tolerable. Grade III-IV myelosuppression occurred in 4 (12%) patients. There were no other major toxicity- or treatment-related deaths. We conclude that carboplatin has a significant anticancer effect in advanced NPC. Thus carboplatin combination chemotherapy for the treatment of NPC is worthy of future clinical investigations.     

Aerobic growth and survival of Campylobacter jejuni in food and stream water

OBJECTIVE: To search differentially expressed sequences correlated with pathogenesis of human nasopharyngeal carcinoma (NPC), including the candidates of tumor suppressor genes. METHODS: cDNA representational difference analysis (RDA) was performed to isolate differentially expressed sequences between cDNA from normal human primary cultures of nasopharyngeal epithelial cells and cDNA from NPC cell line HNE1. The sources of differentially expressed products were proved by Southern blot and Northern blot. The fragments were cloned with pGEM-T easy kit and sequenced by the chain termination reaction. RESULTS: Four differentially expressed cDNA fragments were isolated in the fourth subtractive hybridization using cDNA from normal human primary cultures of nasopharyngeal epithelial cells as tester amplicon and cDNA from NPC cell line HNE1 as driver amplicon by cDNA RDA. These differential cDNA fragments revealed that they really came from the tester amplicon and were not expressed or down-regulated in the NPC HNE1 cells. Of these obtained clones, some are the fragments of the human known genes including house-keeping genes, the others are novel genes. CONCLUSION: NPC involves alteration of multiple genes. Some of known genes matched with the differentially expressed sequences have an effective suppressive ability on the carcinoma.     

Human magnetic resonance imaging at 8 T

BACKGROUND: Antibodies to Epstein Barr Virus (EBV) antigens have been used for the diagnosis of nasopharyngeal carcinoma (NPC). While immunofluorescence assays (IFA) of IgA antiviral capsid and early antigens have been the mainstay of this diagnosis, enzyme immunoassays (ELISA) of various EBV antigens are now available. However in almost all of these assays, the sensitivities and specificities have been calculated using blood donors and normal hospital staff as controls, who may not be the most appropriate controls. We wanted to evaluate the usefulness of IFA and ELISA of various EBV antigens in a clinical setting to distinguish between patients with NPC and those suspected of NPC but being biopsy negative. METHODS: Between January 1987 and June 1988, 322 consecutive patients suspected of NPC and who had a post-nasal biopsy were studied. Blood was taken for EBV tests before diagnosis. Tests included IFA and ELISA IgA anti-VCA and anti-EA and ELISA IgA and IgG anti-ribonucleotide reductase, a cloned EA antigen. RESULTS: IFA IgA anti-VCA together with IFA IgA anti-EA both at a cut-off of 1:10 gave the best discrimination between patients with NPC and those suspected of NPC but were biopsy negative. CONCLUSION: The ELISA IgG anti-ribonucleotide reductase test is convenient to perform and looks very promising. An ELISA using a cocktail of cloned EA peptides may be even better.     

Primary study of neovasculature correlating with metastatic nasopharyngeal carcinoma using computer image analysis

The significance of neoangiogenesis in the metastasis of nasopharyngeal carcinoma (NPC) was investigated to clarify the role neovascularity in the prognosis of NPC and the probability of antiangiogenesis preventing NPC from distant metastasis. A group of 52 patients presenting with metastatic NPC were selected and strictly paired one-to-one, in sex, age, T stage, and N stage, with another 52 patients with non-metastatic NPC, who had survived for a long time after therapy. The tumor tissues of all 104 patients were retrieved for computer-assisted, immunohistochemical analysis of tumor vasculature. Counts of the microvessels and the relative area of all microvessels per image were significantly higher in metastatic NPC than they were in curable, non-metastatic NPC, while the average area of the microvessels and their average perimeter of in metastatic NPC were smaller than in non-metastatic disease. No significant difference in any microvessel parameter was found among the various types of metastasis. The alterations of microvessel parameters were significantly linked to the metastasis of NPC. Evaluation of neovascularity by computer image analysis may be helpful in estimating the prognosis of NPC and in determining the indicators for aggressive multimodal treatments.     

Sarcoidosis mimicking toxoplasmosis with severe hypercalcaemia and normal 1,25-dihydroxy vitamin D

In order to investigate the changes in glycoprotein structure between non-metastatic and metastatic cells of nasopharyngerl carcinoma (NPC), peanut agglutinin (PNA), ulex europeaus (UEA-I) and concanavalin ensifomis agglutinin (ConA) staining were used to examine 102 nasopharyngeal carcinoma tissues (84 primary tumors and 18 metastatic lymph nodes) with the avidin-biotinperoxidase complex method. PNA reaction was positive in most cells of nasopharyngeal carcinomas regardles of in histopathologic type, the degree of differentiation and metastasis. The levels of UEA-I receptors apparently increased during nasopharyngeal carcinoma progression from non-metastatic to metastatic tumors. The binding to ConA clearly decreased in the cells of metastatic cases and metastatic lymph node. So, the increased expression of UEA-I receptors and decrease of ConA receptors on tumor cells might have been implicated in the expression of metastatic potential.     

The role of chemotherapy in the management of nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a radiosensitive tumor for which there is a high local control rate after radical radiotherapy (RT). However, for patients with locoregionally advanced disease, the rate of distant metastasis is high and the 5-year overall survival rate is poor. METHODS: A review of retrospective and prospective clinical studies was performed to assess the role of chemotherapy in three settings: metastatic disease; neoadjuvant and/or adjuvant; and concurrent chemotherapy with radiotherapy. RESULTS: Cisplatin-based combination chemotherapy results in a high response rate in patients with metastatic NPC, and a subgroup may achieve long term disease free survival. The use of neoadjuvant and adjuvant chemotherapy to treat locoregionally advanced disease has resulted in consistently high response rates, but no randomized trial to date has demonstrated an improvement in overall survival. A recent Head and Neck Intergroup study randomized patients in the United States to receive concurrent chemotherapy (cisplatin) and radiotherapy or radiotherapy only. Although this approach demonstrated significant benefit in overall survival favoring the use of concurrent chemotherapy and radiotherapy, its applicability in geographic areas of high NPC incidence remains to be proven. CONCLUSIONS: NPC is a chemosensitive tumor, and patients with metastatic disease have a high response rate. Further prospective studies will define the standard approach to treating locoregionally advanced NPC, which is likely to incorporate into the primary treatment some form of systemic chemotherapy.     

Treatment of psoriasis with fumaric acid esters: results of a prospective multicentre study. German Multicentre Study

Nasopharyngeal carcinomas (NPC) are common in Hong Kong and southern China but rare in Western countries. Telomerase activation is common in human cancers but has not been reported previously in NPC. Telomerase activation in NPC was determined using the sensitive TRAP (telomerase rapid amplification protocol) assay in 45 nasopharyngeal biopsies (36 NPC, nine normal nasopharyngeal mucosae) in four xenografted NPC tumours established in nude mice and in five in vitro NPC cell lines. Telomerase activation is common in NPC and can be detected at high frequencies (85% in primary tumours and 100% in recurrent tumours). The frequency of telomerase activation was lowest in NPC biopsies without lymph node involvement (60%) compared with those with positive lymph node involvement (100%), and the difference is statistically significant (P < 0.05; Fisher exact test). All the xenografted NPC tumours and in vitro NPC cell lines were strongly positive for telomerase activity. Our results suggest that telomerase activation is common in NPC and it may be useful as a diagnostic marker in the detection of tumour cells in nasopharyngeal biopsies. The high frequency of telomerase activation in stage I NPC (80% positive) suggests that it is an early event in tumour progression.     

Pathogenesis of middle-ear effusion in nasopharyngeal carcinoma: a new perspective

The theory that middle-ear effusion (MEE) associated with nasopharyngeal carcinoma (NPC) is merely the result of tensor veli palatinus destruction is deficient because recent studies have shown that many patients with NPC have MEE but no tensor veli palatinus dysfunction. The present study evaluates the relationship between MEE and Eustachian cartilage erosion by NPC and examines the pathogenesis of NPC-associated MEE from a new perspective. Thirty-five patients with NPC were studied by magnetic resonance scans taken along the lengths of the Eustachian tubes. Twenty-four patients had tumour involvement of both sides of the nasopharynx so that 59 ears were available for study. Eighteen ears had MEE of which 12 had Eustachian cartilage erosion (p < 0.00001), Fischer's Exact Test). In ears with MEE, Eustachian cartilage erosion was frequently but not necessarily associated with tensor veli palatinus destruction. We postulate that altered Eustachian tubal compliance as a result of cartilage erosion by tumour is an important reason why middle-ear effusions develop in patients with NPC.     

Inhibition of sodium selenite on transformation of human B lymphocytes by Epstein-Barr virus

We detected the effect of non-toxic doses of sodium selenite (Se) on the expressing effect of nuclear antigen (EBNA) of Epstein-Barr virus (EBV) in Raji cell line by microfluorescence spectrophoto-quantitation (MFS) and studied the inhibing transformation in B lymphocytes from human umbilical cord blood (BL) with EBV in vitro by Se. We found that Se (0.01-0.50 microgram/ml) can lower EBNA-MFS value 8.4%-21.8% in Raji cell line. The transformation effect of BL with EBV was markedly inhibited by Se (0.1-1.0 microgram/ml) in pretreatment and cotreatment. The inhibition rates of BL transformation were 73.4%-92.1% and 60.3%-77.2% respectively. EBV is associated with nasopharyngeal carcinoma (NPC). The Se levels of serum and hair in NPC patients were markedly lower than those in healthy persons. The results suggest that supplement Se to persons for active expression of EBV gene and NPC patients may help protect againt and treat NPC and diseases associated with EBV.     

Adenovirus-mediated p16 transfer to glioma cells induces G1 arrest and protects from paclitaxel and topotecan: implications for therapy

This study evaluated Epstein-Barr virus (EBV) DNA in sera of 42 patients with nasopharyngeal carcinoma (NPC) and 82 healthy individuals who had been infected previously with EBV. Thirteen of 42 NPC samples were positive for EBV DNA in their sera, whereas all 82 normal controls were negative. In addition, EBV typing between primary tumors and sera showed identical results, suggesting that serum EBV DNA represented tumor DNA. To evaluate the importance of the serum NPC DNA, clinical data and tumor phenotypes including age, sex, WHO type, EBV type, stage, tumor invasion, metastasis, and apoptosis were correlated with serum EBV DNA, and only apoptosis was found statistically significant. In conclusion, EBV DNA was detectable in the serum of some patients with NPC, represented tumor DNA, and might have clinical implications in the future.