同步放化疗治疗晚期鼻咽癌远期疗效评价

目的:研究同步放化疗对晚期鼻咽癌远期疗效的影响.方法:128例Ⅲ、Ⅳa期鼻咽癌随机分成两组(单放组和放化同步组).单放组64例,采用6MEV,直线加速器,以常规分割方式放疗,鼻咽部剂量68～70 GY,颈部根治量60～68 GY,预防量46～50 GY;同步放化组64例,除了按上述放疗外,并同步行DDP30mg+5-Fu0.75g+CF0.2 g连续静脉点滴5 d化疗,并在放疗结束前一周,再行同样化疗一周期.结果:单放组和同步放化组肿瘤消退率分别为81.25%、95.75%(P>0.05),颈部转移灶完全消退率分别为84.375%、90.625%(P>0.05).五年无瘤生存率分别为25%,39.06%(P<0.05).五年生存率分别为37.5%、56.25%(P<0.05).远处转移率分别为37.5%、12.5%(P<0.05).出现远处转移平均时间单放组16个月,放化同步组32个月(P<0.02).结论:同步放化组在三年、五年总生存率(OS)和无瘤生存率(DPS)方面及出现远处转移率和转移平均时间方面均要优于单放组,且有显著性差异.

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.

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.

Regulation of Survivin and CDK4 by Epstein-Barr virus encoded latent mem-brane protein 1 in nasopharyngeal carcinoma cell lines

Latent membrane protein 1 （LMP1）, an important protein encoded by Epstein Barr virus （EBV）, has been implied to link with the pathogenesis of nasopharyngeal carcinoma （NPC）. Its dual effects of increasing cell proliferation and inhibiting cell apoptosis have been confirmed. In this study, we showed that the expression of Survivin and CDK4 protein in CNE-LMP1, a LMP1 positive NPC epithelial cell line, is higher than in LMP1 negative NPC epithelial cell line- CNE1, and the expression is LMP1 dosage-dependent. Although it was reported that Survivin specifically expressed in cell cycle G2/M phase, our studies suggested that LMP1 could promote the expression of Survivin in G0/G1, S and G2/ M phase. It also showed that Survivin and CDK4 could be accumulated more in the nuclei triggered by LMP1. More interestingly, Survivin and CDK4 could form a protein complex in the nuclei of CNE-LMP1 rather than in that of CNE1, which demonstrated that the interaction between these two proteins could be promoted by LMPI. These results strongly suggested that the role of LMP1 in the regulation of Survivin and CDK4 may also shed some light on the mechanism research of LMP1 in NPC.

Involvement of regulatory volume decrease in the migration of nasopharyn-geal carcinoma cells

The transwell chamber migration assay and CCD digital camera imaging techniques were used to investigate the relationship between regulatory volume decrease (RVD) and cell migration in nasopharyngeal carcinoma cells (CNE-2Z cells). Both migrated and non-migrated CNE-2Z cells, when swollen by 47% hypotonic solution, exhibited RVD which was inhibited by extracellular application of chloride channel blockers adenosine 5’-triphosphate (ATP), 5-nitro-2-(3- phenylpropylamino) benzoic acid (NPPB) and tamoxifen. However, RVD rate in migrated CNE-2Z cells was bigger than that of non-migrated cells and the sensitivity of migrated cells to NPPB and tamoxifen was higher than that of non- migrated cells. ATP, NPPB and tamoxifen also inhibited migration of CNE-2Z cells. The inhibition of migration was positively correlated to the blockage of RVD, with a correlation coefficient (r) = 0.99, suggesting a functional relation- ship between RVD and cell migration. We conclude that RVD is involved in cell migration and RVD may play an important role in migratory process in CNE-2Z cells.

Mechanisms of cell immortalization mediated by EB viral activation of telomerase in nasopharyngeal carcinoma

Nasopharyngeal carcinoma （NPC） is a common cancer in Southern China and Southeast Asia. The disease is a poorly differentiated carcinoma without effective cure, and the mechanism underlying its development remains largely unknown. Of several factors identified in NPC aetiology in recent years, Epstein-Barr virus （EBV） infection has emerged to be most important. In almost all NPC cells, EBV uses several intracellular mechanisms to cause oncogenic evolution of the infected cells. One such mechanism by which EBV infection induces cellular immortalization is believed to be through the activation of telomerase, an enzyme that is normally repressed but becomes activated during cancer development. Studies show that greater than 85% of primary NPC display high telomerase activity by mechanisms involving EBV infection, consistent with the notion that EBV is commonly involved in inducing cell immortalization. More recently, different EBV proteins have been shown to activate or inhibit the human telomerase reverse transcriptase gene, by modulating intracellular signalling pathways. These findings suggest a new model with a number of challenges towards our understanding, molecular targeting and therapeutic intervention in NPC.

NASOPHARYNGEAL CARCINOMA RADIOSENSITIVITY PREDICTION BY CYTOKINESIS－BLOCK MICRONUCLEUS ASSAY

Cytokinesis-block micronucleus method is used to evaluate the radiosensitivity of a nasopharyngeal carcinoma cell line (CNE-1) and biopsies obtained from 31 patients with nasopharyngeal carcinoma. The number of micronuclei increases with theradiation dose. A good correlation was found between the radiosensitivity determined by the micro-nucleus assay and that measured by the colony-forming assay in CNE-1 cell line (r=-0.998). Moreover, the results of micronucleus assay for tumor cells from biopsies of patients with primary carcinoma look promising for the prediction of tumor radiosensitivity. These results are encouraging but fleed to be confirmed with a larger number of patients with a longer follow-up.

Comparison of efficacy between two boost treatments in residual tumor of nasopharyngeal carcinoma after radical radiotherapy

Objective： To compare the efficacy between stereotactic radiotherapy （SRT） and intracavitary brachytherapy （brachytherapy） in residual tumor of nasopharyngeal carcinoma （NPC） after treating with conventional external beam radiotherapy. Methods： 60 patients with residual tumor of NPC after radical external beam radiotherapy （range 68 to 72 Gy） were randomized into SRT group （27 patients） and brachytherapy group （33 patients）. Patients in SRT group received boost treatment of 10-20 Gy, 2-3 fractions, once every other day; patients in brachytherapy group were treated with boost 10-20 Gy, 5 Gy per fraction, twice a week. Results： Efficacy in the near future： in SRT group, the complete recession （CR）, partial recession （PR） and no change （NC） rates were 77.8% （21/27）, 18.5% （5/27）, 3.7% （1/27）, respectively and the efficacy rate was 96.3% （CR ＋ PR）; in brachytherapy group： the CR, PR and NC rates were 75.8% （25/33）, 18.2% （6/33）, 6.1% （2/33）, respectively and the efficacy rate was 93.9% （CR ＋ PR）. The efficacy rates of the above two groups were compared （x^2 = 0.032, P 〉 0.05）. Long term efficacy： in SRT group, 1-year and 3-year survival rates were 96.3%, 66.5% respectively and the median live time was 48 months; in brachytherapy group： 1-year and 3-year survival rates were 93.9%, 60.2% respectively and the median live time was 46 months. The survival rates of two groups were compared （x^2 = 0.172, P 〉 0.05）. Conclusion： Both boost techniques of SRT and brachytherapy had elevated efficacy in patients with residual tumor of NPC and there was no obvious difference between the efficacy of the near and long term in SRT and brachytherapy group.

Detection of Epstein-Barr virus DNA in plasma/serum:a useful serological indicator for diagnosis of nasopharyngeal carcinoma

OBJECTIVE: To compare the detection rates of Epstein-Barr virus (EBV) DNA in the serum/plasma between apparently healthy adults (AHAs) and nasopharyngeal carcinoma (NPC) patients in attempt to evaluate the efficiency of EBV DNA assay for serodiagnosis of NPC. METHODS: The plasma and serum were obtained from 58 AHAs and 66 untreated NPC patients. EBV DNA W-fragment was detected using nested ploymerase chain reaction (PCR). Immunoenzymatic assay for titration of IgA-VCA was also adopted. RESULTS: EBV DNA detection rate (84.85%) in the plasma/serum of 66 NPC patients was significantly higher than that (10.34%) in 58 AHAs. The sensitivity of plasma/serum EBV DNA assay (0.8485) was higher than that (0.8030) of titrating IgA-VCA (positive criterion >/= 1:40) though the specificities of these two tests were the same (0.8966). The correct rate, predictive value of a positive test, and Odds ratio of dual positivity (0.8387, 0.9792 and 141.0, respectively) were higher than those of single positivity either to plasma/serum EBV assay (0.5242, 0.7333 and 1.1423, respectively) or to IgA-VCA >/= 1:40 test (0.4839, 0.5385 and 1.0480, respectively). CONCLUSION: The EBV DNA detection in the plasma/serum using nested PCR may be a useful indicator for serodiagnosis of NPC.