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Sample records for advanced nasopharyngeal carcinoma

  1. INTERVENTION CHEMOTHERAPY IN COMPREHENSIVE TREATMENT OF ADVANCED NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the use of interventional chemotherapy in comprehensive treatment for advanced nasopharyngeal carcinoma. Methods: Interventional chemotherapy with multi-drugs including cisplatin (DDP) 100 mg, 5-fluorouracil (5-FU) 1000 mg and bleomycin (BLM) 16 mg was used to treat 30 cases with advanced nasopharyngeal carcinoma before radiotherapy. 50 cases that received radiotherapy alone were used as a control group. The methods, time and dose schedule of radiotherapy were similar in the two groups. Results: The primary lesions in 16 cases and the cervical lymph nodes in 12 cases were reduced in size after interventional chemotherapy. Radiation doses of those in complete response in their primary lesion and cervical lymph nodes were lower than that of the control group (P<0.05). The complete response rate of study group was 83.3% and that of control group was 72.0% (P<0.05). Conclusion: Interventional chemotherapy plus radiotherapy is a valuable treatment method in advanced nasopharyngeal carcinoma.

  2. Neoadjuvant chemotherapy and radiation therapy in advanced stage nasopharyngeal carcinoma

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    To assess the feasibility and the toxicity of the neoadjuvant chemotherapy on the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. We analyzed 77 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with neoadjuvant chemotherapy followed by radiation therapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows: AJCC stage 111-2, stage IV-75. Sixty-six patients received infusion of 5-FU (1000 mg/m2, on Day 1-5) and cisplatin (100 mg/m2, on Day 1), eleven patients received infusion of 5.FU (1000 mg/m2, on Day 1-5) and carboplatin (300 mg/m2, on Day 1) as neoadjuvant chemotherapy prior to radiation therapy. The median follow-up for surviving patients was 44 months. The overall chemotherapy response rates were 87%. The toxicities of chemotherapy were mild. Only 3 patients experienced Grade 3 toxicities (1 for cytopenia, 2 for nausea/vomiting). The degree of radiation induced mucositis was not severe, and ten patients developed Grade 2 mucositis. The 5-year overall survival rates were 68% and the 5-year disease free survival rates were 65%. The 5-year freedom from distant metastasis rates were 82% and 5-year locoregional control rates were 75%. This single institution experience suggests that neoadjuvant chemotherapy improves overall survival and disease free survival for patients with advanced stage nasopharyngeal carcinoma without increase of toxicity

  3. CHEMOTHERAPY FOR ADVANCED NASOPHARYNGEAL CARCINOMA WITH METHOTREXATE, VINCRISTINE, CISPLATIN AND ADRIAMYCIN

    Institute of Scientific and Technical Information of China (English)

    苏勇; 张锦明; 夏云飞; 朱荣; 钱朝南; 莫浩元

    2002-01-01

    Objective: To evaluate the efficacy and toxicity of M-VCA (methortrexate 30 mg/m2, vincristine 2 mg, cisplatin 70 mg/m2, adriamycin 30 mg/m2) combination chemotherapy for advanced nasopharyngeal carcinoma. Methods: Thirty-five patients with advanced nasopharyngeal carcinoma, including 11 patients with untreated local advanced nasopharyngeal carcinoma and 24 patients with local-regional recurrent or metastatic nasopharyngeal carcinoma, received the chemotherapy of M-VCA. The cycle was repeated on day 22 for two cycles. All patients completed the chemotherapy courses. Results: The overall response rate was 75%, with untreated local advanced nasopharyngeal carcinomas 11/11(100%), local-regional recurrent nasopharyngeal carcinomas 12/18(67%), lung metastases 8/9(89%), bone metastases 5/9(56%), and liver metastases 1/2(50%). The main side effects included mild to moderate degree alopecia, nausea/vomiting, and neutropenia. Conclusion: M-VCA is well tolerated and has good efficacy for advanced nasopharyngeal carcinoma and is worth investigating further.

  4. Nasopharyngeal carcinoma: Advances in genomics and molecular genetics

    Institute of Scientific and Technical Information of China (English)

    ZENG ZhaoYang; LI XiaoLing; XIONG Wei; LI GuiYuan; HUANG HongBin; ZHANG WenLing; XIANG Bo; ZHOU Ming; ZHOU YanHong; MA Jian; YI Mei; LI XiaYu

    2011-01-01

    Nasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma that arises in the epithelial lining of the nasopharynx [1].This neoplasm has a notable ethnic and geographic distribution,being of high prevalence in southern China but rare in other parts of the world [2].Familial clustering of NPC has been observed in diverse populations [3].Elevated levels of circulating free Epstein-Barr virus (EBV) DNA and EBV-related antibodies in sera,as well as EBV DNA in tumor cells,have been consistently detected in individuals with NPC [4,5].These studies have revealed that the risk factors of NPC are both environmental and genetic.How the risk factors interact,and the genes that are involved in the development of NPC,are not well understood [6].

  5. Bevacizumab plus cisplatin and helical tomotherapy in treatment of locally advanced nasopharyngeal carcinoma

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    Li JX

    2015-06-01

    Full Text Available Jianxiong Li,1,* Zhifei Zhao,1,* Xuan Wu,1,* Jie Yao,2,* Lin Ma,1 Rui Ye,1 Baolong Niu,1 Lanqing Liang,1 Xiao Zhao,1 Qianqian Wang1 1Radiology Department, Cancer Center, The General Hospital of the People’s Liberation Army, Beijing, People’s Republic of China; 2Department of Oncology, The People’s Liberation Army 161 Hospital, Wuhan, People’s Republic of China *These authors contributed equally to this work Background: In recent years, chemotherapy, radiotherapy, and targeted drugs have been respectively used in nasopharyngeal carcinoma. In our research, we combined all of them for better curative effects.Materials and methods: Thirty patients with histologically confirmed stage III~IV (without distant metastasis nasopharyngeal carcinoma were recruited between December 2013 and October 2014 with strict eligibility requirements and exclusion criteria. Bevacizumab 5 mg/kg, 80 mg/m2 cisplatin and 67.5 Gy radiotherapy (helical tomotherapy [TOMO] was given according to standard treatment protocols.Results: After 3 months, 24 complete responses (80% and six partial responses (40% were observed in our research. Twenty-four patients (80% experienced oropharyngeal mucositis, 26% patients experienced weight loss caused by pharyngeal pain and dysphagia caused by oropharyngeal mucositis.Conclusion: Bevacizumab plus cisplatin and TOMO in treatment of locally advanced nasopharyngeal carcinoma can increase curative effects with low side effects and toxicities. Keywords: bevacizumab, cisplatin, helical tomotherapy (TOMO, nasopharyngeal carcinoma

  6. A meta-analysis of neoadjuvant chemotherapy plus radiation in the treatment of locally advanced nasopharyngeal carcinoma

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    Xun He

    2015-01-01

    Conclusion: Neoadjuvant chemotherapy followed by radiation can decrease the risk of recurrence and metastasis but not improve the 5 years overall survival and 5 years disease free survival compared to radiotherapy alone in the patients with locally advanced nasopharyngeal carcinoma.

  7. Neoadjuvant chemotherapy and radiation therapy compared with radiation therapy alone in advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Purpose: To analyze the impact of neoadjuvant chemotherapy on the treatment of locoregionally advanced nasopharyngeal carcinoma and to assess the outcomes of patients receiving such treatment. Methods and Materials: We analyzed 137 previously untreated and histologically confirmed advanced stage nasopharyngeal carcinoma patients treated with either radiation therapy only or combined radiation therapy and chemotherapy at the Seoul National University Hospital between 1984 and 1996. The stage distribution was as follows: AJCC Stage III-21, Stage IV-61 in the radiation therapy group (RT group); AJCC Stage III-1, Stage IV-54 in neoadjuvant chemotherapy and radiation therapy group (CT/RT group). The median follow-up for surviving patients was 48 months. Results: The 5-year overall survival (OS) rates were 71% for the CT/RT group and 59% for the RT group (p = 0.04). The 5-year actuarial disease-free survival (DFS) rates were 63% for the CT/RT group and 52% for the RT group (p = 0.04). Distant metastasis (DM) incidence was significantly lower in the CT/RT group. The 5-year freedom from distant metastasis rates were 84% for the CT/RT group and 66% for the RT group (p 0.01). The incidence of locoregional failures was also lower in the CT/RT group, although this difference did not reach statistical significance (69% vs. 56%, p = 0.09) Conclusion: While not providing conclusive evidence, historical evidence from this institution suggests that neoadjuvant chemotherapy significantly improves both overall and the disease-free survival of patients with advanced stage nasopharyngeal carcinoma

  8. Comparing treatment outcomes of different chemotherapy sequences during intensity modulated radiotherapy for advanced N-stage nasopharyngeal carcinoma patients

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    Sun, Xueming; Zeng, Lei; Chen, Chunyan; Huang, Ying; Han, Fei; Xiao, WeiWei; Liu, Shuai; Lu, Taixiang

    2013-01-01

    Background N-stage is related to distant metastasis of nasopharyngeal carcinoma (NPC) patients. We performed this study to compare the efficacy of different chemotherapy sequences in advanced N-stage (N2 and N3) NPC patients treated with intensity modulated radiotherapy (IMRT). Methods From 2001 to 2008, 198 advanced N-stage NPC patients were retrospectively analyzed. Thirty-three patients received IMRT alone. Concurrent chemoradiotherapy (CCRT) was delivered to 72 patients, neoadjuvant chemo...

  9. The impact of smoking on the clinical outcome of locoregionally advanced nasopharyngeal carcinoma after chemoradiotherapy

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    Cigarette smoking is a common risk factor for developing nasopharyngeal carcinoma. However, the relationship between smoking and clinical outcomes remains uncertain. The patients who participated in this study were drawn from a randomized clinical trial, for which the purpose was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy with that of induction chemotherapy plus radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. The patients who ever smoked were divided into the following categories of cumulative smoking exposure based on the duration of smoking and the quantity of cigarettes smoked: light, short-term smokers; light, long-term smokers; heavy, short-term smokers; and heavy, long-term smokers. A log-rank test and Cox models were used to assess the association between smoking and the clinical outcomes of overall survival (OS), failure-free survival (FFS), locoregional recurrence failure-free survival (LRFFS) and distant failure-free survival (DFFS). We found that ever-smokers experienced significantly shorter LRFFS times than never-smokers (5-year LRFFS rates: 85.8% vs. 88.5%, P = 0.022). The amount of smoking was significantly associated with FFS (P = 0.046) and LRFFS (P = 0.001) in the different ever-smoker groups. The amount of smoking was associated with LRFFS [P = 0.002, HR = 2.069 (95% confident interval (CI), 1.298-3.299)] even after a multivariable adjustment. Smoking increases the risk of locoregional recurrence. Furthermore, the amount of smoking influences the prognosis of smokers, and these effects are dose-dependent

  10. Expression profiling of 21 biomolecules in locally advanced nasopharyngeal carcinomas of Caucasian patients

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    Krikelis Dimitrios

    2013-01-01

    Full Text Available Abstract Background Since scarce data exist on the pathogenesis of nasopharyngeal carcinoma in Caucasian patients, we attempted to elucidate the responsible molecular pathways in this patient population. Methods Formalin-fixed paraffin-embedded tumor tissue samples from 107 patients, diagnosed with locally-advanced nasopharyngeal carcinoma and treated with chemotherapy or chemo-radiotherapy, were analyzed by immunohistochemistry for the expression of the following proteins: E-cadherin, P-cadherin, Fascin-1, Cyclin D1, COX-2, EGFR, VEGF-A, VEGF-C, VEGFR-2, VEGFR-3, ERCC1, p53, p63, Ki67, MAPT, phospho-p44/42MAPK, PTEN, phospho-AKT, phospho-mTOR, and phospho-GSK-3β. EBER status was assessed by in situ hybridization. The majority of the cases were included in tissue microarray. All stains were performed and assessed centrally by two pathologists. The median follow-up time was 76.8 (42.3 – 99.2 months. Results Biomolecules expressed in >90% of cases were: p53, COX-2, P-cadherin, EBER, phospho-GSK-3β, and Fascin-1. WHO II+III tumors were more frequently EBER & PTEN positive and VEGF-A negative. Advanced age was significantly associated with positive phospho-GSK-3β and ERCC1 expression; male gender with positive phospho-AKT and phospho-p44/42MAPK; and worse performance status (1 or 2 with negative Ki67, ERCC1, PTEN, and phospho-mTOR expression. Earlier disease stage was closely associated with p63, MAPT, PTEN, and Cyclin D1 positivity. Univariate Cox regression analysis highlighted Cyclin D1 as a negative prognostic factor for disease-free survival (p=0.034 and EBER as a positive one for overall survival (p=0.048. In multivariate analysis, advanced age and stage, poor performance status, and positive ERCC1 emerged as predictors of worse disease-free and overall survival, as opposed to positive phospho-mTOR. Clustering analysis defined two protein-expression groups being predictive of better overall survival (p=0.043. Conclusions Our study is the

  11. Intensity-modulated radiotherapy with simultaneous integrated boost for locoregionally advanced nasopharyngeal carcinoma

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    To compare the treatment outcomes of intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) alone to concurrent chemoradiotherapy (CCRT) for locoregionally advanced nasopharyngeal carcinoma (NPC). From November 2001 to December 2009, 333 patients with pathologically diagnosed, locoregionally advanced NPC were treated by IMRT-SIB with or without weekly cisplatin concurrent chemotherapy at our institute. Among them, 62 patients received neo- or adjuvant chemotherapy or molecular target drugs were excluded from this analysis. There were 129 patients received IMRT-SIB alone, and 142 patients received IMRT-SIB with weekly cisplatin 30 mg/m2 for 7 weeks. The radiotherapy protocol was identical for each group. There were no significant differences in survival between CCRT and IMRT-SIB group in terms of gender, T/N classifications and concurrent chemoradiotherapy. The 5-year local control (LC), overall survival (OS), disease-free survival (DFS) and distant metastasis-free survival (DMFS) for the entire group were 87.0%, 79.4%, 69.7 and 83.3%, respectively. The LC, OS, DFS and DMFS for CCRT and IMRT-SIB alone groups were 80.6% vs. 90.8% (P = 0.10), 71.7% vs. 83.2% (P = 0.201), 63.9% vs. 74.6% (P = 0.07), and 79.6% vs. 86.0% (P = 0.27), respectively. Compared to CCRT, IMRT-SIB alone had demonstrated similar disease LC, OS, DFS and DMFS in locoregionally advanced NPC. Careful radiation target volume design and simultaneous integrated boost may play a role that overrides the benefit from concurrent chemotherapy. Further investigation with randomized study is necessary to determine whether IMRT-SIB alone can achieve similar outcomes of concurrent chemoradiotherapy

  12. Locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy plus concurrent weekly cisplatin with or without neoadjuvant chemotherapy

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    Wee, Chan Woo; Keam, Bhum Suk; Heo, Dae Seog; Sung, Myung Whun; Won, Tae Bin; Wu, Hong Gyun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    The outcomes of locoregionally advanced nasopharyngeal carcinoma patients treated with concurrent chemoradiation (CCRT) using intensity-modulated radiotherapy (IMRT) with/without neoadjuvant chemotherapy (NCT) were evaluated. Eighty-three patients who underwent NCT followed by CCRT (49%) or CCRT with/without adjuvant chemotherapy (51%) were reviewed. To the gross tumor, 67.5 Gy was prescribed. Weekly cisplatin was used as concurrent chemotherapy. With a median follow-up of 49.4 months, the 5-year local control, regional control, distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival rates were 94.7%, 89.3%, 77.8%, 68.0%, and 81.8%, respectively. In multivariate analysis, the American Joint Committee on Cancer stage (p = 0.016) and N stage (p = 0.001) were negative factors for DMFS and DFS, respectively. Overall, NCT demonstrated no benefit and an increased risk of severe hematologic toxicity. However, compared to patients treated with CCRT alone, NCT showed potential of improving DMFS in stage IV patients. CCRT using IMRT resulted in excellent local control and survival outcome. Without evidence of survival benefit from phase III randomized trials, NCT should be carefully administered in locoregionally advanced nasopharyngeal carcinoma patients who are at high-risk of developing distant metastasis and radiotherapy-related mucositis. The results of ongoing trials are awaited.

  13. Emerging treatment options for nasopharyngeal carcinoma

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    Zhang L

    2013-02-01

    Full Text Available Lu Zhang,1,2 Qiu-Yan Chen,1,2 Huai Liu,1,2 Lin-Quan Tang,1,2 Hai-Qiang Mai1,21State Key Laboratory of Oncology in South China, 2Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of ChinaAbstract: Nasopharyngeal carcinoma is endemic in Asia and is etiologically associated with Epstein–Barr virus. Radiotherapy is the primary treatment modality. The role of systemic therapy has become more prominent. Based on multiple phase III studies and meta-analyses, concurrent cisplatin-based chemoradiotherapy is the current standard of care for locally advanced disease (American Joint Committee on Cancer manual [7th edition] stages II–IVb. The reported failure-free survival rates from phase II trials are encouraging for induction + concurrent chemoradiotherapy. Data from ongoing phase III trials comparing induction + concurrent chemoradiotherapy with concurrent chemoradiotherapy will validate the results of these phase II studies. Intensity-modulated radiotherapy techniques are recommended if the resources are available. Locoregional control exceeding 90% and reduced xerostomia-related toxicities can now be achieved using intensity-modulated radiotherapy, although distant control remains the most pressing research problem. The promising results of targeted therapy and Epstein–Barr virus-specific immunotherapy from early clinical trials should be validated in phase III clinical trials. New technology, more effective and less toxic chemotherapy regimens, and targeted therapy offer new opportunities for treating nasopharyngeal carcinoma.Keywords: nasopharyngeal carcinoma, intensity-modulated radiotherapy, chemoradiotherapy, molecular targeted agents, immunotherapy, prognostic markers

  14. Radiation myelopathy in nasopharyngeal carcinoma

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    Enomoto, Hiroyuki; Tsukuda, Mamoru; Kono, Hidehiro; Omata, Toshiyuki; Mochimachi, Izumi; Hasegawa, Osamu [Yokohama City Univ. (Japan). School of Medicine

    1995-08-01

    A 36-year-old woman with nasopharyngeal carcinoma developed radiation myelopathy. She was treated with radiotherapy, a total dose of about 120 Gy to the cervical spinal cord at the C1 level, chemotherapy and immunotherapy. Nine months after the final radiation therapy, she complained of a paresthesia in the distal area of the right leg. Neurological examination revealed incomplete left Brown-Sequard syndrome below the level of C5. Neurological symptoms had been progressive. The spinal MRI showed an abnormal intramedullary high intensity area enhanced by Gd-DTPA. (author).

  15. Comparing treatment outcomes of different chemotherapy sequences during intensity modulated radiotherapy for advanced N-stage nasopharyngeal carcinoma patients

    International Nuclear Information System (INIS)

    N-stage is related to distant metastasis of nasopharyngeal carcinoma (NPC) patients. We performed this study to compare the efficacy of different chemotherapy sequences in advanced N-stage (N2 and N3) NPC patients treated with intensity modulated radiotherapy (IMRT). From 2001 to 2008, 198 advanced N-stage NPC patients were retrospectively analyzed. Thirty-three patients received IMRT alone. Concurrent chemoradiotherapy (CCRT) was delivered to 72 patients, neoadjuvant chemotherapy (NACT) + CCRT to 82 patients and CCRT + adjuvant chemotherapy (AC) to 11 patients. The 5-year overall survival rate, recurrence-free survival rate, distant metastasis-free survival rate and progress-free survival rate were 47.7% and 73.1%(p<0.001), 74.5% and 91.3% (p = 0.004), 49.2% and 68.5% (p = 0.018), 37.5% and 63.8% (p<0.001) in IMRT alone and chemoradiotherapy group. Subgroup analyses indicated that there were no significant differences among the survival curves of CCRT, NACT + CCRT and CCRT + AC groups. The survival benefit mainly came from CCRT. However, there was only an improvement attendency in distant metastasis-free survival rate of CCRT group (p = 0.107) when compared with RT alone group, and NACT + CCRT could significantly improve distant metastasis-free survival (p = 0.017). For advanced N-stage NPC patients, NACT + CCRT might be a reasonable treatment strategy

  16. Efficacy of the Additional Neoadjuvant Chemotherapy to Concurrent Chemoradiotherapy for Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: a Bayesian Network Meta-analysis of Randomized Controlled Trials

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    Chen, Yu-Pei; Guo, Rui; Liu, Na; Liu, Xu; Mao, Yan-Ping; Tang, Ling-Long; Zhou, Guan-qun; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2015-01-01

    Background: Due to the lack of studies, it remains unclear whether the additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) is superior to CCRT alone for locoregionally advanced nasopharyngeal carcinoma (NPC). The main objective of this Bayesian network meta-analysis was to determine the efficacy of NACT+CCRT as compared with CCRT alone. Methods: We comprehensively searched databases and extracted data from randomized controlled trials involving NPC patients who r...

  17. Evaluation of the dosimetric feasibility of hippocampal sparing intensity-modulated radiotherapy in patients with locally advanced nasopharyngeal carcinoma.

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    Guang Han

    Full Text Available PURPOSE: The objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC sparing intensity-modulated radiotherapy (IMRT in patients with locally advanced nasopharyngeal carcinoma (NPC. MATERIALS/METHODS: Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR per Radiation Therapy Oncology Group (RTOG 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs. RESULTS: All plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, D mean, D median, D98% and D min and volume (V5, V10, V15, V20, V30, V40 and V50 parameters for the HPC were significantly lower in the HPC sparing plans (p<0.05, except for D min (P = 0.06 and V5 (P = 0.12. CONCLUSIONS: IMRT for patients with locally advanced NPC exposes the HPC to a significant radiation dose. HPC sparing IMRT planning significantly decreases this dose, with minimal impact on the therapeutic targets and other OARs.

  18. Experience with combination of docetaxel, cisplatin plus 5-fluorouracil chemotherapy, and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma

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    Our aim was to evaluate the efficacy and toxicity of cisplatin, fluorouracil, and docetaxel chemotherapy plus intensity-modulated radiotherapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC). Sixty patients with locoregionally advanced NPC were enrolled. Patients received IMRT plus three courses of neoadjuvant chemotherapy and two courses of adjuvant chemotherapy consisting of docetaxel (60 mg/m2/day on day 1), cisplatin (25 mg/m2/day on days 1-3), and 5-fluorouracil (500 mg/m2/day on days 1-3). The overall response rate to neoadjuvant chemotherapy was 89%. Three months after the completion of radiotherapy, 53 (93%) patients achieved complete regression, 3 (5%) achieved partial response (PR), and 1 experienced liver metastasis. However, among the 3 PR patients, 2 patients had no evidence of relapse in the follow-up. With a median follow-up of 27 months (range, 6-43), the 2-year estimated locoregional failure-free survival, distant failure-free survival, progression-free survival, and overall survival were 96.6, 93.3, 89.9, and 98.3%, respectively. Leukopenia was the main adverse effect in chemotherapy; 14 patients experienced grade 3 or grade 4 neutropenia, and 1 patient developed febrile neutropenia. The nonhematological adverse events included alopecia, nausea, vomiting, anorexia, and diarrhea. The incidence of grade 3 acute radiotherapy-related mucositis was 28.3%; no grade 4 acute mucositis was observed. No grade 3 or grade 4 hematological toxicity occurred during radiotherapy. None of the patients had interrupted radiotherapy. The common late adverse effects included xerostomia and hearing impairment. Neoadjuvant-adjuvant chemotherapy using cisplatin, fluorouracil, plus docetaxel combined with IMRT was an effective and well-tolerated alternative for advanced NPC. (author)

  19. Concurrent image-guided intensity modulated radiotherapy and chemotherapy following neoadjuvant chemotherapy for locally advanced nasopharyngeal carcinoma

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    To evaluate the experience of induction chemotherapy followed by concurrent chemoradiationwith helical tomotherapy (HT) for nasopharyngeal carcinoma (NPC). Between August 2006 and December 2009, 28 patients with pathological proven nonmetastatic NPC were enrolled. All patients were staged as IIB-IVB. Patients were first treated with 2 to 3 cycles of induction chemotherapy with EP-HDFL (Epirubicin, Cisplatin, 5-FU, and Leucovorin). After induction chemotherapy, weekly based PFL was administered concurrent with HT. Radiation consisted of 70 Gy to the planning target volumes of the primary tumor plus any positive nodal disease using 2 Gy per fraction. After completion of induction chemotherapy, the response rates for primary and nodal disease were 96.4% and 80.8%, respectively. With a median follow-up after 33 months (Range, 13-53 months), there have been 2 primary and 1 nodal relapse after completion of radiotherapy. The estimated 3-year progression-free rates for local, regional, locoregional and distant metastasis survival rate were 92.4%, 95.7%, 88.4%, and 78.0%, respectively. The estimated 3-year overall survival was 83.5%. Acute grade 3, 4 toxicities for xerostomia and dermatitis were only 3.6% and 10.7%, respectively. HT for locoregionally advanced NPC is feasible and effective in regard to locoregional control with high compliance, even after neoadjuvant chemotherapy. None of out-field or marginal failure noted in the current study confirms the potential benefits of treating NPC patients by image-guided radiation modality. A long-term follow-up study is needed to confirm these preliminary findings

  20. Feasibility and efficacy of chemoradiotherapy for elderly patients with locoregionally advanced nasopharyngeal carcinoma: results from a matched cohort analysis

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    To clarify the feasibility and efficacy of chemoradiotherapy (CRT) in elderly (age≥65 years) patients with locoregionally advanced nasopharyngeal carcinoma (NPC). From January 2000 to December 2006, 101 newly diagnosed elderly non-metastatic NPC patients (age≥65 years) who received cisplatin 3-weekly or weekly concurrent CRT with/without sequential chemotherapy were recruited. Each patient from the CRT group was matched to another patient treated with radiotherapy (RT) alone based on age, gender, pathological type, performance status, overall stage, stage method, Adult Comorbidity Evaluation-27 (ACE-27) score and RT technique, from the same institute and time period. We also recruited 101 young patients (age<65 years) as the referent group, which had been matched to the CRT group based on patient characteristics and treatment parameters. Treatment tolerability and toxicity were clarified, and treatment outcomes were calculated and compared among groups. CRT was feasible in elderly NPC patients, while a concurrent regimen of weekly cisplatin was more tolerable. Grade≥3 acute toxicity in CRT group was similar with referent group, although it was significantly higher than the RT alone group (65.3% vs. 43.6%, P=0.002). Furthermore, patients with ACE-27 score≥2 in the CRT group had significantly higher severe acute toxicity and dose reduction. Survival was poorer in elderly patients than the referent group. Compared to RT alone, CRT significantly improved the 5-year overall survival (OS: 54.6% vs. 39.3%, P=0.009), cancer-specific survival (CSS: 56.6% vs. 42.7%, P=0.022), disease-free survival (DFS: 51.6% vs. 30.2%, P=0.028) and locoregional relapse-free survival (LRRFS: 78.4% vs. 52.2%, P=0.003), but not distant metastasis-free survival (DMFS: 69.6% vs. 63.6%, P=0.669). However, CRT did not significantly improve 5-year OS (43.6% vs. 27.3%, P=0.893) or CSS (43.6% vs. 34.1%, P=0.971) in elderly NPC patients with ACE-27 score≥2. CRT is feasible and effective in

  1. Role of chemotherapy in nasopharyngeal carcinoma

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    Fabiola Paiar

    2012-06-01

    Full Text Available Nasopharyngeal carcinoma (NPC is a unique malignant head and neck cancer with clinical, demographic, and geographic features distinct from other head and neck epithelial malignancies. Non-keratinizing, poorly differentiated, and undifferentiated WHO types 2 and 3 is the most common subtypes of NPC. NPC is also characterized by its relatively high sensitivity to radiation, so that in the last decades radiotherapy (RT has been the cornerstone of treatment. However, in the majority of cases NPC is discovered at locally advanced stage. The results are disappointing when RT alone is offered. The 5-year survival rates have been reported to be about 34-52%. The poor prognosis for advanced NPC led to increasing interests in exploring the use of chemotherapy (CT. NPC has been considered to be not only radiosensitive but also chemo-sensitive and has shown high response rate to various chemotherapeutic agents. Certainly, the treatment strategies for NPC will continue to change and evolve as a better understanding is gained of the molecular and immune mechanisms that drive this disease. We reviewed the current literature focusing on the role of CT and new-targeted agents.

  2. Nasopharyngeal carcinoma with metastases to colon

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    Yatiee Swany Lahuri

    2015-07-01

    Full Text Available Squamous cell carcinoma (SCC of the nasopharynx is amongst the most common head and neck cancers. The most common distant metastases are to the bone, liver and lung. Herein, we are reporting a rare case of a 61-year-old man with nasopharyngeal carcinoma (NPC who presented with 3 weeks history of blood streaked sputum, post nasal drip and blocked nose with no history of epistaxis, tinnitus and unilateral hearing loss. Almost 2 years upon completion of his concurrent chemotherapy and radiotherapy, he developed a right hypochondrium mass and underwent colonoscopy which revealed a mass in ascending colon and which was then subsequently resected via right hemicolectomy. Histological analyses from the resected specimen confirmed its nasopharyngeal origin.

  3. Nasopharyngeal carcinoma with bone marrow metastasis.

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    Zen, H G; Jame, J M; Chang, A Y; Li, W Y; Law, C K; Chen, K Y; Lin, C Z

    1991-02-01

    Five of 23 patients with recurrent nasopharyngeal carcinoma (NPC) were diagnosed to have bone marrow metastasis. They all had advanced local-regional disease, and were treated with neoadjuvant chemotherapy and definitive radiotherapy after the initial diagnosis. Bone marrow metastasis developed 4-24 months later. The clinical features were anemia (5 of 5), leukopenia (3 of 5), thrombocytopenia (4 of 5), sepsis (3 of 5), tenderness of the sternum (3 of 5), and fever (4 of 5). Patients frequently had elevation of serum lactic dehydrogenase (LDH), alkaline phosphatase (ALK-P), and IgG and IgA antibody titers to Epstein-Barr viral capsid antigen when bone marrow involvement was diagnosed. However, clinical manifestations and laboratory tests were not specific. It is important that three patients had normal bone scans. All five patients had a rapid downhill course; four patients died within 23 days, and the fifth 3 months after the diagnosis of bone marrow metastasis. We concluded that bone marrow was a common metastatic site in NPC patients. Bone marrow metastasis adversely affected patients' survival and required a high index of suspicion for diagnosis. We suggested that bone marrow biopsy should be considered as a routine staging procedure in NPC patients and indicated especially when patients presented with abnormal blood counts, sepsis, bone pain, or tenderness of the sternum. It may be positive in the face of a normal bone scan. PMID:1987743

  4. Comparison of concurrent chemoradiotherapy versus neoadjuvant chemotherapy followed by radiation in patients with advanced nasopharyngeal carcinoma in endemic area: experience of 128 consecutive cases with 5 year follow-up

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    Wu, Shang-Yin; Wu, Yuan-Hua; Yang, Ming-Wei; Hsueh, Wei-Ting; Hsiao, Jenn-Ren; Tsai, Sen-Tien; Chang, Kwang-Yu; Chang, Jeffrey S.; Yen, Chia-Jui

    2014-01-01

    Background Combined radiotherapy and chemotherapy is considered the standard of care for locally advanced nasopharyngeal carcinoma (LA-NPC) in Epstein-Barr virus infection endemic area. This study compared the long-term outcomes between LA-NPC patients treated with neoadjuvant chemotherapy followed by radiotherapy (NACT) and those treated with concurrent chemoradiotherapy (CCRT). Methods From 2003 to 2007, a total of 128 histopathologically proven LA-NPC patients receiving either NACT or CCRT...

  5. Comparison between nedaplatin and cisplatin plus docetaxel combined with intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma: a multicenter randomized phase II clinical trial

    Science.gov (United States)

    Tang, Chunyuan; Wu, Fang; Wang, Rensheng; Lu, Heming; Li, Guisheng; Liu, Meilian; Zhu, Haisheng; Zhu, Jinxian; Zhang, Yong; Hu, Kai

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is highly incident in southern China. Metastasis is the major cause of death in NPC patients. Concurrent chemoradiotherapy (CCRT) has been accepted as standard in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma (NPC). However, induction chemotherapy (IC) also has benefits in this disease, especially in the patients with certain high-risk factors such as bulky and/or extensive nodal disease. It has been presented that adding IC to CCRT might be a reasonable approach and need more work to confirm. The optimal chemotherapeutic regimen combined with radiotherapy has not been determined so far. It is important to explore high effective and low toxic chemotherapy for the patients. In the multicenter prospective study, 223 patients with locoregionally advanced untreated NPC were randomized into experimental group and control group. The patients received two cycles of induction chemotherapy (IC) with docetaxel (DOC) plus nedaplatin (NDP) in experimental group every 3 weeks, followed by IMRT concurrent with weekly NDP for six cycles, and NDP was replaced by cisplatin (CDDP) in control group. More patients in experimental group could receive full courses of IC and concurrent chemoradiotherapy (CCRT) (P=0.013). There was no significant difference between the two groups in the percentage of reduction of GTVnx and GTVnd after IC (P=0.207 and P=0.107) and CR rate three months after completion of chemoradiotherapy (P=0.565 and P=0.738). With a mean follow-up of 35.1 months, no statistically significant difference in the 3-year OS, LRFS, RRFS, DMFS, and PFS was found. During IC, more patients suffered vomiting in control group (P=0.001). During CCRT, grade 3/4 neutropenia/thrombocytopenia were more common in experimental group (P=0.028 and P=0.035); whereas, severe anemia and vomiting were more common in control group (P=0.0001 and P=0.023). In conclusions, patients with locoregionally advanced NPC showed good

  6. A PROPOPSAL CONCERNING THE HISTOLOGICAL TYPING OF PRIMARY NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    Zong; Yong-sheng

    2001-01-01

    [1]Liang PC, Chen CS, Chu CC, et al. The histopathological classification, biologic characteristics and histogenesis of nasopharyngeal carcinomas [J]. Chin Med J 1962; 81:629.[2]Van Hasselt CA, Gibb AG. Nasopharyngeal carcinoma [M]. 1st ed. Hong Kong, China: The Chinese University Press, 1991; 48.[3]Shanmugaratnam K, Sobin LH. Histological typing of tumors of the upper respiratory tract and ear [M]. 2nd Ed. Berlin: Springer-Verlag, 1991; 32.[4]Zong YS. Histological diagnosis of nasopharyngeal carcinoma [M]. In: Health Administrative Section of Health Ministry, P. R. of China, eds. The Standards of diagnosis and therapy of common malignancies in China, 5th section?nasopharyngeal carcinoma (in Chinese). 1st ed. Beijing: Beijing Medical University and China Union Medical University Publishing House, 1991; 4.[5]Svoboda DJ, Kirchiner FR, Shanmugaratnam K. The fine structure of nasopharyngeal carcinoma [M]. In: Muri CS, Shamugaratnam K. eds. Cancer of the nasopharynx. 1st ed. Copenhagen: UICC Monograph Series Publishing House, 1967; 163.[6]Zhang JX, Chen HL, Zong YS, et al. Epstein-Barr virus expression within keratinizing nasopharyngeal carcinoma [J]. J Med Virol 1998; 55:227.[7]Zong YS, Zhang JX, Chan KH et al. Association of Epstein-Barr virus with nasopharyngeal squamous cell carcinoma in the south of China [J]. Chin J Cancer 1999; 18: 9.[8]Rosai J. Ackerman's Surgical Pathology [M]. 8th ed. New York: Mosby, 1998; 293.[9]Zong YS, Lin H, Choy DT, et al. Nasopharyngeal carcinoma and lymphoinfiltration [J]. Oncology 1991; 48:290.[10]Zong YS, Zhang CQ, Zhang F, et al. Infiltrating lymphocytes and accessory cells in nasopharyngeal carcinoma [J]. Jpn J Cancer Res 1993; 84:900.[11]Yeung WM, Zong YS, Chiu CT, et al. Epstein-Barr virus carriage by nasopharyngeal carcinoma in situ [J]. Int J Cancer 1993; 53:746.[12]Zong YS, Sham JS, Ng MH, et al. Immunoglobulin A against viral capsid antigen of Epstein-Barr virus and indirect

  7. Clinics in diagnostic imaging (90). Childhood nasopharyngeal carcinoma.

    Science.gov (United States)

    Ng, B K; Chong, C L; Tan, A M; Hwang, W S

    2003-10-01

    An 11-year-old boy presented with a nasopharyngeal mass that was thought to represent a juvenile angiofibroma based on the initial clinical and radiological evaluation. Partial tumour resection was performed. Resected specimen revealed histological diagnosis of undifferentiated carcinoma. Further evaluation of the tumour including MR imaging, radioisotope bone scan, CT thorax and abdomen were performed. Differential diagnoses of childhood nasopharyngeal masses were discussed. The differences between childhood NPC and adult NPC, rhabdomyosarcoma, malignant lymphoma and juvenile nasopharyngeal angiofibroma were also discussed.

  8. MicroRNAs in nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jeff P Bruce; Fei-Fei Liu

    2014-01-01

    MicroRNAs (miRNAs) provide insight into both the biology and clinical behavior of many human cancers, including nasopharyngeal carcinoma (NPC). The dysregulation of miRNAs in NPC results in a variety of tumor-promoting effects. Furthermore, several miRNAs are prognostic markers for NPC. In addition to celular miRNAs, NPC samples also often contain miRNAs encoded by Epstein-Barr virus, and these miRNAs may impact NPC biology by targeting both celular and viral genes. Given their numerous putative roles in NPC development and progression, a thorough understanding of the impact of miRNA dysregulation in NPC is expected to shed light on useful biomarkers and therapeutic targets for the clinical management of this disease. In this review, we describe the efforts to date to identify and characterize such miRNAs in the context of NPC.

  9. Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Terence, E-mail: trdtwk@nccs.com.sg [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Lim, Wan-Teck [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Fong, Kam-Weng; Cheah, Shie-Lee; Soong, Yoke-Lim [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Ang, Mei-Kim; Ng, Quan-Sing; Tan, Daniel [Division of Medical Oncology, National Cancer Centre Singapore (Singapore); Ong, Whee-Sze; Tan, Sze-Huey [Division of Clinical Trial and Epidemiological Sciences, National Cancer Centre Singapore (Singapore); Yip, Connie; Quah, Daniel [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore); Soo, Khee-Chee [Division of Surgical Oncology, National Cancer Centre Singapore (Singapore); Wee, Joseph [Division of Radiation Oncology, National Cancer Centre Singapore (Singapore)

    2015-04-01

    Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma (NPC) treated with induction chemotherapy and concurrent chemo-radiation (CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP (3 cycles of gemcitabine 1000 mg/m{sup 2}, carboplatin area under the concentration-time-curve 2.5, and paclitaxel 70 mg/m{sup 2} given days 1 and 8 every 21 days) followed by CCRT (radiation therapy 69.96 Gy with weekly cisplatin 40 mg/m{sup 2}), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5-year overall survival (OS) with a 5% significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 (GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS (3-year OS 94.3% [GCP] vs 92.3% [control]; hazard ratio 1.05; 1-sided P=.494]), disease-free survival (hazard ratio 0.77, 95% confidence interval 0.44-1.35, P=.362), and distant metastases–free survival (hazard ratio 0.80, 95% confidence interval 0.38-1.67, P=.547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia (52% vs 37%) and neutropenia (24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo-irradiation did not improve survival in locally advanced NPC.

  10. Current and emerging treatment options for nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Spratt DE

    2012-10-01

    Full Text Available Daniel E Spratt, Nancy LeeDepartment of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USAAbstract: In this article, we focus on the current and emerging treatments in nasopharyngeal cancer (NPC. A detailed evolution of the current standard of care, and new techniques and treatment options will be reviewed. Intergroup 0099 established the role for chemoradiotherapy (chemo-RT in the treatment of nasopharyngeal carcinoma. Multiple randomized Phase III trials have shown the benefit of chemo-RT; however, none of these studies utilized modern radiotherapy (RT techniques of intensity-modulated radiation therapy (IMRT. IMRT has the ability to deliver high doses of radiation to the target structures while sparing adjacent bystander healthy tissues, and has now become the preferred RT treatment modality. Chemotherapy also has had a shifting paradigm of induction and/or adjuvant chemotherapy combined with RT alone, to the investigation with concurrent chemo-RT. New treatment options including targeted monoclonal antibodies and small molecule tyrosine kinase inhibitors are being studied in NPC. These new biologic therapies have promising in vitro activity for NPC, and emerging clinical studies are beginning to define their role. RT continues to expand its capabilities, and since IMRT and particle therapy, specifically intensity-modulated proton therapy (IMPT, has reports of impressive dosimetric efficacy in-silica. Adaptive RT is attempting to reduce toxicity while maintaining treatment efficacy, and the clinical results are still in their youth. Lastly, Epstein–Barr virus (EBV DNA has recently been studied for prediction of tumor response and its use as a biomarker is increasingly promising to aid in early detection as well as supplementing the current staging system. RT with or without chemotherapy remains the standard of care for nasopharyngeal carcinoma. Advances in RT technique, timing of chemotherapy, biologically

  11. A Rare Presentation of Primary Nasopharyngeal Carcinoma (NPC) in Mediastinum

    Science.gov (United States)

    Fathi, Afshin; Amani, Firuz; Davoodi, Mohammad; Bahadoram, Sara; Bahadoram, Mohammad

    2016-01-01

    Introduction Nasopharyngeal carcinoma among the children has been rare accounting for only 1% of all pediatric malignancies. Both genetic and environmental factors have contributed to the development of nasopharyngeal carcinoma. Among the children there was a higher rate of undifferentiated histology. The mean age of nasopharyngeal carcinoma diagnosis has been 11 years old age; and the most common site was nasopharynx. Palpable lymphadenopathy, dysphasia and neural defect were common associated signs. Case Presentation A 15-year-old boy has presented with a mass that located near by the heart in the left side of mediastinum with invasion to anterior mediastinum from two years ago. In biopsy, nasopharyngeal carcinoma, non-keratinizing type, has diagnosed while there was no involvement of nasopharyngeal region. Patient has treated by 70 Gy (2.0 Gy/fraction) radiotherapy plus concomitant chemotherapy with base of docetaxel. But the mass had no regression. Then, the patient has treated with Cisplatin 100 mg/m2 IV on days 1, 22, and 43 with radiation, then cisplatin 80 mg/m2 IV on day 1 plus fluorouracil (5-FU) 1000 mg/m2/day by continuous IV infusion on days 1 - 4 every 4wk for 3 cycles and after remission interferon beta has added to treatment for 6 months duration as a maintenance therapy. After 1 year follow up; the patient was in complete remission. In the course of therapy, only hypothyroidism has occurred. Conclusions Nasopharyngeal carcinoma in childhood, without nasopharyngeal involvement, initially could be detected in other sites such as pericardium. Also good results could be respected by cisplatin and 5-fluorouracil based neoadjuvant chemotherapy before radiotherapy plus interferon beta as a maintenance therapy in childhood aggressive nasopharyngeal carcinoma.

  12. Pro-apoptotic effect of cecropin AD on nasopharyngeal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    XIAO Ye-chen; HUANG Ya-dong; XU Pei-lin; ZHOU Zhen-qing; LI Xiao-kun

    2006-01-01

    @@ Nasopharyngeal carcinoma (NPC) is one of the highly prevalent malignancies in Southeast Asia.1 Chemotherapy and radiotherapy are commonly administrated to treat nasopharyngeal carcinoma, but these therapies can not prevent the recurrence and metastasis of tumor cells.

  13. The prognostic significance of parapharyngeal tumour involvement in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    From 1984 to 1989, 903 treatment-naive non-disseminated nasopharyngeal carcinomas (NPCs) were given primary radical radiotherapy. All patients had computed tomographic and endoscopic evaluation of the primary tumour. Potentially significant parameters were analysed by both univariate and multivariate methods for independent significance. In the whole group of patients, the male sex, skull base and cranial nerve(s) involvement, advanced Ho N-level, presence of fixed or partially fixed nodes and nodes contralateral to the side of the bulk of the nasopharyngeal primary, significantly determined survival and distant metastasis rates, whereas skull base and cranial nerve involvement, advanced age and male sex significantly worsened local control. However in the Ho T2No subgroup, parapharyngeal tumour involvement was the most significant prognosticator that determined distant metastasis and survival rates in the absence of the overriding prognosticators of skull base infiltration, cranial nerve(s) palsy, and cervical nodal metastasis. The local tumour control of the Ho T2No was adversely affected by the presence of oropharyngeal tumour extension. The administration of booster radiotherapy (20 Gy) after conventional radiotherapy (60-62.5 Gy) in tumours with parapharyngeal involvement has led to an improvement in local control, short of statistical significance

  14. Clinical role of18F-FDG PET/CT-based simultaneous modulated accelerated radiotherapy treatment plan-ning for locally advanced nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jianshe Wang; Tianyou Tang Co-first author; Jing Xu; Andrew Z Wang; Liang Li; Junnian Zheng; Longzhen Zhang

    2015-01-01

    Objective The aim of this study was to compare the long-term local control, overal survival, and late toxicities of positron emission tomography/computed tomography (PET/CT)-guided dose escalation radio-therapy versus conventional radiotherapy in the concurrent chemoradiotherapy treatment of local y ad-vanced nasopharyngeal carcinoma (NPC). Methods A total of 48 patients with stage III–IVa NPC were recruited and randomly administered PET/CT-guided dose escalation chemoradiotherapy (group A) or conventional chemoradiotherapy (group B). The dose-escalation radiotherapy was performed using the simultaneous modulated accelerated radiotherapy technique at prescribed doses of 77 gray (Gy) in 32 fractions (f) to the gross target volume (GTV): planning target volume (PTV) 1 received 64 Gy/32 f, while PTV2 received 54.4 Gy/32 f. Patients in group B received uniform-dose intensity-modulated radiotherapy, PTV1 received 70 Gy/35 f and PTV2 received 58 Gy/29 f. Concurrent chemotherapy consisted of cisplatin [20 mg/m2 intravenous (IV) on days 1–4] and docetaxel (75 mg/m2 IV on days 1 and 8) administered during treatment weeks 1 and 4. Al patients received 2–4 cycles of adjuvant chemotherapy of the same dose and drug regimen. Results The use of fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT significantly reduced the treat-ment volume delineation of the GTV in 83.3% (20/24) of patients. The 5-year local recurrence-free survival rates of the two groups were 100% and 79.2%, respectively (P = 0.019). The 5-year disease free survival (DFS) rates were 95.8% and 75.0%, respectively (P = 0.018). The 5-year local progression-free survival and DFS rates were significantly dif erent. The 5-year overal survival (OS) rates were 95.8% and 79.2%, re-spectively. Dif erences in OS improvement were insignificant (P = 0.079). Late toxicities were similar in the two groups. The most common late toxicities of the two arms were grade 1–2 skin dystrophy, xerostomia, subcutaneous fibrosis, and

  15. Bone scans in nasopharyngeal carcinoma: local experience

    International Nuclear Information System (INIS)

    Introduction: Nasopharyngeal carcinoma (NPC) tops the list of malignancy in Malaysia and ranks first in male malignancy in the state of Sarawak. The majority of the NPC patients presented in the advanced stages and often with distal metastasis usually to the bones. In our local hospital is the new practice of bone scan using Tc99 started last year. Over a period of 9 months from July 2003 to March 2004, 41 NPC patients had the bone scans and our experience in these are reviewed and presented. Method: The NPC patients are selected consecutively including both new and treated patients. The scanner used is Siemen E.cam plus and Technecium (Tc99) the radio-active isotope used. The scan images are read and reported by qualified and trained Radiologists. The bone scans are requested from the ENT Specialist of the ENT department of the Hospital. The bone scan reports are checked by the ENT Specialists and the decisions made as to clinical correlation and further definitive imaging studies. Results: 41 NPC patients were included in the studies, 29 newly diagnosed and bone-canned before treatment started and 12 treated of which 3 being diagnosed having recurrent NPC. Of the 29 newly diagnosed patients, one was found true positive bone scan having increased radio-tracer uptake and confirmed Xray imagings. 3 of the treated patients had true positive bone scan with increased radio-tracer uptake and confirmed Xray imagings. Hence a total of 4 out of the 41 patients (9.8%) had bone metastasis on positive bone scans. Of the 29 newly diagnosed patients, 14 were found false positive bone scan having increased radio-tracer uptake but no confirmed X ray imagings. 4 of the treated patients had false positive bone scan with increased radio-tracer uptake but no confirmed X ray imagings. Hence a total of 18 out of the 41 patients (44%) had no bone metastasis on positive bone scans. There were 6 patients with symptoms referable to the bones' distal to the head and 2 had true positive bone

  16. Volume and dosimetric variations during two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma.

    Science.gov (United States)

    Wang, Rui-hao; Zhang, Shu-xu; Zhou, Ling-hong; Zhang, Guo-qian; Yu, Hui; Lin, Xiao-dan; Lin, Shengqu

    2014-01-01

    The aims of this study were to evaluate the volume and dosimetric variations during IMRT for locally advanced NPC and to identify the benefits of a two-phase adaptive IMRT method. Twenty patients with locally advanced NPC having received IMRT treatment were included. Each patient had both an initial planning CT (CT-1) and a repeated CT scan (CT-2) after treatment at a dose of 40 Gy. Three IMRT planning scenarios were compared: (1) the initial plan on the CT-1 (plan-1); (2) the hybrid plan recalculated the initial plan on the CT-2 (plan-2); (3) the replan generated on the CT-2 being used to complete the course of IMRT (plan-3). The mean gross target volume and mean volumes of the positive neck lymph nodes, high-risk clinical target volume, and the left and right parotid glands significantly decreased by 30.2%, 45.1%, 21.1%, 14.7% and 18.2%, respectively on the CT-2. Comparing plan-2 with plan-1, the dose coverage of the targets remained unchanged, whereas the dose delivered to the parotid glands and spinal cord increased significantly. These patients with locally advanced NPC might benefit from replanning because of the sparing of the parotid glands and spinal cord. PMID:24212016

  17. Oncogene mutational profile in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang ZC

    2014-03-01

    Full Text Available Zi-Chen Zhang,1,* Sha Fu,1,* Fang Wang,1 Hai-Yun Wang,1 Yi-Xin Zeng,2 Jian-Yong Shao11Department of Molecular Diagnostics, 2Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, People's Republic of China *These authors contributed equally to this work Abstract: Nasopharyngeal carcinoma (NPC is a common tumor in Southern China, but the oncogene mutational status of NPC patients has not been clarified. Using time-of-flight mass spectrometry, 238 mutation hotspots in 19 oncogenes were examined in 123 NPC patients. The relationships between mutational status and clinical data were assessed with a χ2 or Fisher's exact test. Survival analysis was performed using the Kaplan–Meier method with the log-rank test. In 123 patients, 21 (17.1% NPC tumors were positive for mutations in eight oncogenes: six patients had PIK3CA mutations (4.9%, five NRAS mutations (4.1%, four KIT mutations (3.3%, two PDGFRA mutations (1.6%, two ABL mutations (1.6%, and one with simultaneous mutations in HRAS, EGFR, and BRAF (1%. Patients with mutations were more likely to relapse or develop metastasis than those with wild-type alleles (P=0.019. No differences or correlations were found in other clinical characteristics or in patient survival. No mutations were detected in oncogenes AKT1, AKT2, CDK, ERBB2, FGFR1, FGFR3, FLT3, JAK2, KRAS, MET, and RET. These results demonstrate an association between NPC and mutations in NRAS, KIT, PIK3CA, PDGFRA, and ABL, which are associated with patient relapse and metastasis. Keywords: NPC, oncogene, mutation

  18. Prevertebral muscle involvement in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study is to evaluate the prevalence and prognostic significance of prevertebral muscle involvement in patients with nasopharyngeal carcinoma (NPC). Methods and Materials: Between July 1990 and December 2001, 521 newly diagnosed patients with NPC treated at Koo Foundation Sun Yat-Sen Cancer Center (KF-SYSCC) were examined with magnetic resonance imaging (MRI) for evidence of prevertebral muscle involvement before treatment. Patients were staged according to the 1997 American Joint Committee on Cancer staging classification of NPC based on the physical exams and MRI findings. All patients received radiotherapy with or without chemotherapy. The association between clinical prevertebral muscle involvement and posttreatment outcomes (overall survival, locoregional recurrence, and distant metastasis) were evaluated using Cox regression model to adjust for other prognostic factors. Results: Of 521 patients treated at KF-SYSCC, 181 (35%) patients were found to have prevertebral muscle involvement, one-third in those with Stage II/III tumors and two-thirds in those with Stage IV tumor. In multivariate analysis accounting for all previously known prognostic factors, prevertebral muscle invasion was associated with an increased risk for any recurrence (adjusted relative risk, 2.01; p < 0.001), locoregional recurrence (adjusted relative risk, 2.69; p < 0.001), and distant metastasis (adjusted relative risk, 2.25; p < 0.001), and with a borderline significant increased risk for overall survival (adjusted relative risk, 1.44; p = 0.10). Conclusions: Prevertebral muscle involvement is an independent prognostic factor for NPC recurrence

  19. Dosimetry Comparison between Volumetric Modulated Arc Therapy with RapidArc and Fixed Field Dynamic IMRT for Local-Regionally Advanced Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Bao-min Zheng; Xiao-xia Dong; Hao Wu; You-jia Duan; Shu-kui Han; Yan Sun

    2011-01-01

    Objective:A dosimetric study was performed to evaluate the performance of volumetric modulated arc radiotherapy with RapidArc on locally advanced nasopharyngeal carcinoma (NPC).Methods:The CT scan data sets of 20 patients of locally advanced NPC were selected randomly.The plans were managed using volumetric modulated arc with RapidArc and fixed nine-field coplanar dynamic intensity-modulated radiotherapy (IMRT) for these patients.The dosimetry of the planning target volumes (PTV),the organs at risk (OARs) and the healthy tissue were evaluated.The dose prescription was set to 70 Gy to the primary tumor and 60 Gy to the clinical target volumes (CTV) in 33 fractions.Each fraction applied daily,five fractions per week.The monitor unit (MU) values and the delivery time were scored to evaluate the expected treatment efficiency.Results:Both techniques had reached clinical treatment's requirement.The mean dose (Dmean),maximum dose (Dmax) and minimum dose (Dmin) in RapidArc and fixed field IMRT for PTV were 68.4±0.6 Gy,74.8±0.9 Gy and 56.8±1.1 Gy; and 67.6±0.6 Gy,73.8±0.4 Gy and 57.5±0.6 Gy (P<0.05),respectively.Homogeneity index was 78.85±1.29 in RapidArc and 80.34±0.54 (P<0.05) in IMRT.The conformity index (CI:95%) was 0.78±0.01 for both techniques (P>0.05).Compared to IMRT,RapidArc allowed a reduction of Dmean to the brain stem,mandible and optic nerves of 14.1% (P<0.05),5.6% (P<0.05) and 12.2% (P<0.05),respectively.For the healthy tissue and the whole absorbed dose,Dmean of RapidArc was reduced by 3.6% (P<0.05),and 3.7% (P<0.05),respectively.The Dmean to the parotids,the spinal cord and the lens had no statistical difference among them.The mean MU values of RapidArc and IMRT were 550 and 1,379.The mean treatment time of RapidArc and IMRT was 165 s and 447 s.Compared to IMRT,the delivery time and the MU values of RapidArc were reduced by 63% and 60%,respectively.Conclusion:For locally advanced NPC,both RapidArc and IMRT reached

  20. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma. A matched-pair multicenter analysis of outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Yi-Yuan [Affiliated Hospital of Guilin Medical University, Department of Radiation Oncology, Guilin (China); Guilin Medical University Affiliated Hospital, Department of Otorhinolaryngology, Guilin (China); Xiang, Chun [Nan Xishan Hospital, Department of Otorhinolaryngology, Guilin (China); Lu, Jian-Xun [Affiliated Hospital of Youjiang Medical University for Nationalities, Department of Oncology, Baise (China); Su, Yi-Xin [Lingshan People' s Hospital, Department of Radiation Oncology, Lingshan (China); Pan, Yu-Fei [Nan Xishan Hospital, Department of Radiation Oncology, Guilin (China); Cai, Rui; Zhang, Rong-Jun; He, Zhuo-Kai; Liu, Mei-Lian; Huang, Hui; Bai, Xue; Tang, Hua-Ying; Shi, Yun-Hua; Wang, Yan; Jiang, Wei [Affiliated Hospital of Guilin Medical University, Department of Radiation Oncology, Guilin (China)

    2016-06-15

    The benefit of adjuvant chemotherapy (AC) in locoregionally advanced nasopharyngeal carcinoma (NPC) is controversial. This study compared concurrent chemoradiotherapy plus AC (CCRT/AC) with CCRT. Pair-matched analysis based on eight clinicopathological features of 244 patients treated with platinum-based CCRT/AC or CCRT alone was performed. Survival outcomes were assessed using the Kaplan-Meier method and log-rank test. Toxicities and response rates were compared using Fisher's exact test. Four-year overall survival, progression-free survival, distant failure-free survival, and locoregional failure-free survival were 72 %, 61 %, 71 %, and 81 %, respectively, for the CCRT arm, compared to 74 % (hazard ratio, HR 0.89; 95 % confidence interval, CI 0.64-1.23; P = 0.474), 62 % (HR 0.91, 95 % CI 0.68-1.20, P = 0.489), 73 % (HR 0.84, 95 % CI 0.59-1.18, P = 0.316), and 84 % (HR 0.84, 95 % CI 0.52-1.24, P = 0.323), respectively, for the CCRT/AC arm. Cox multivariate regression analysis demonstrated AC was not an independent prognostic factor. Overall, there was a higher incidence of grade 3-4 toxicities in the CCRT/AC arm. The most common grade 3-4 adverse events in the CCRT/AC arm were vomiting (27 %), nausea (43 %), leukopenia/neutropenia (23 %), thrombocytopenia (8.8 %), and anemia (6.2 %). Addition of AC to CCRT increased toxicities but did not improve survival in locoregionally advanced NPC. (orig.) [German] Der Nutzen der adjuvanten Chemotherapie (AC) bei lokoregional fortgeschrittenem nasopharyngealem Karzinom (NPC) ist kontrovers. In dieser Studie wurde die simultane Radiochemotherapie (''concurrent chemoradiotherapy'', CCRT) plus adjuvante Chemotherapie (AC) mit einer alleinigen CCRT verglichen. Die Matched-pair-Analyse basiert auf acht klinisch-pathologischen Merkmalen von 244 Patienten, die mit platinbasierter CCRT/AC oder alleiniger CCRT behandelt wurden. Die Ueberlebensendpunkte wurden mit der Kaplan-Meier-Methode und dem Log

  1. EBV-associated gastric carcinoma in high- and low-incidence areas for nasopharyngeal carcinoma

    DEFF Research Database (Denmark)

    Boysen, T.; Mohammadi, M.; Melbye, M.;

    2009-01-01

    BACKGROUND: Approximately 10% of gastric carcinomas are associated with Epstein-Barr virus (EBV). The Inuit in Greenland have a high incidence of EBV-associated nasopharyngeal carcinoma. METHODS: We conducted a population-based case-control study comparing gastric carcinomas in Greenland and in D...

  2. NASOPHARYNGEAL CARCINOMA RADIOSENSITIVITY PREDICTION BY CYTOKINESIS—BLOCK MICRONUCLEUS ASSAY

    Institute of Scientific and Technical Information of China (English)

    杨星; 史剑慧; 等

    1995-01-01

    Cytokinesis-block micronucleus method is used to evaluate the radiosensityvity of a nasopharyngeal carcinoma cell line(CNE-1) and biopsies obtained from 31 patients with nasopharyngeal carcinoma,The number of micronuclei increases with the radiation 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 need to be confirmed with a larger number of patients with a longer follow-up.

  3. Chemotherapy in nasopharyngeal carcinoma: review of results at University Hospital, Kuala Lumpur.

    Science.gov (United States)

    Khanijow, V K; Prasad, U; Chang, C M

    1989-12-01

    Nasopharyngeal carcinoma (NPC) is one of the commonest presentation of head and neck cancers in Malaysia, especially in the Chinese. The standard treatment is radical radiotherapy to the post-nasal space and the neck. Chemotherapy is given to patients with primary advanced disease and to patients with recurrence. The study reviews results of chemotherapy given to 33 patients at the University Hospital, Kuala Lumpur, over the last four years.

  4. Nasopharyngeal carcinoma--a review of radiotherapy techniques.

    Science.gov (United States)

    Tsao, S Y

    1993-07-01

    With modern megavoltage external X-ray treatment for nasopharyngeal carcinoma, results have improved but late sequelae, which are more often associated with the treatment of advanced tumours or multiple courses of external treatment, have also surfaced. Life-threatening complications include temporal lobe necrosis and hypothalamic-pituitary dysfunction. As CT scanning is superior to conventional radiography in tumour mapping, a new dedicated working staging system, catering for cross-sectional imaging parameters, is proposed for a prospective, multi-centre exercise to finalise on a badly needed common system. With it, case selection for more conservative (to minimise complications) or intensified treatments is facilitated. Intracavitary radiation has now been developed well enough for the nasopharynx. For earlier cases, based on the new staging system, this method has the potential to complement a "sub-radical" external treatment dose designed to minimise complications. A multi-centre trial is indicated. To reach cancericidal doses for the more advanced tumours coming very close to vital structures, extra machine time, though precious, is fully justified so that smaller treatment fractions delivered with facial shells for accurate reproduction of precise machine geometry and field geography can be implemented. Otherwise, subsequent management of possible serious treatment complications may cost more than the treatment itself. Various possible complications of radiotherapy and avoidance and management are outlined. PMID:8257075

  5. Correlative study on anemia and radiotherapy effects in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Objective: To study the effect of oxygen-carrying ability of blood efficacy of radiotherapy for patients with nasopharyngeal carcinoma. Methods: Altogether 161 cases of patients with nasopharyngeal carcinoma were classified according to severity of anemia, and Hb, RBC, MCH, HCT, MCV, MCHC and RDW were tested before, during and after radiotherapy. The patients were followed-up for up to 5 years, the relationship and mechanism among anemia, radiotherapy effects and survival rate was discussed. Results: The survival rate between anemia group and non-anemia group was different significantly (P<0.05). Anemia before radiotherapy, anemia appearance or anemia deterioration during radiotherapy were sensitive factors affecting radiotherapy results. The anemia more severe, the radiotherapy worse. Conclusion: Anemia-hypohemoglobinemia leads to decrease of oxygen-carrying capacity of blood, resulting in oxygen deficiency of tumor cells and their radiotherapy resistance. Therefore this method is worthy of further studies

  6. Temporal lobe necrosis in nasopharyngeal carcinoma: Pictorial essay

    International Nuclear Information System (INIS)

    Nasopharyngeal carcinoma (NPC) shows a high frequency of skull base erosion and intracranial spread. This tumour is usually treated with radiation therapy. The medial and inferior portions of both temporal lobes are included within the radiation portals. These areas are therefore potential sites of radiation-induced necrosis. It is important to recognize this complication and separate it from intracranial tumour recurrence because the treatments of these entities are different. (authors)

  7. Mesenchymal stem cell-derived exosomes facilitate nasopharyngeal carcinoma progression

    OpenAIRE

    Shi, Si; Zhang, Qicheng; Xia, Yunfei; You, Bo; Shan, Ying; Bao, Lili; Li, Li; You, Yiwen; Gu, Zhifeng

    2016-01-01

    Mesenchymal stem cells (MSCs), which are capable of differentiating into multiple cell types, are reported to exert multiple effects on tumor development. However, the relationship between MSCs and nasopharyngeal carcinoma (NPC) cells remains unclear. Exosomes are small membrane vesicles that can be released by several cell types, including MSCs. Exosomes, which can carry membrane and cytoplasmic constituents, have been described as participants in a novel mechanism of cell-to-cell communicat...

  8. Comparison of Treatment Results Between Adult and Juvenile Nasopharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Purpose: Nasopharyngeal carcinoma (NPC) has a bimodal age distribution. In contrast to the adult variant, little is known about the juvenile form. This study examined the treatment results between adult (aNPC) and juvenile NPC (jNPC) patients for future treatment considerations in jNPC. Methods and Materials: The jNPC population included 53 patients treated at two institutions between 1972 and 2004. The aNPC population included 84 patients treated at one institution. The patients had received a median dose of 66 Gy of external beam radiotherapy and 72% underwent chemotherapy. The mean follow-up for surviving patients was 12.6 years for jNPC and 6.6 years for aNPC. Results: The jNPC patients presented with more advance stages than did the aNPC patients (92% vs. 67% Stage III-IV, p = .006). However, jNPC patients had significantly better overall survival (OS) than did aNPC patients. The 5-year OS rate was 71% for jNPC and 58% for aNPC (p = .03). The jNPC group also demonstrated a trend for greater relapse-free survival than the aNPC group (5-year relapse-free survival rate, 69% vs. 49%; p = .056). The pattern of failure analysis revealed that the jNPC patients had greater locoregional control and freedom from metastasis but the differences were not statistically significant. Univariate analysis for OS revealed that age group, nodal classification, and chemotherapy use were significant prognostic factors. Age group remained significant for OS on multivariate analysis, after adjusting for N classification and treatment. Conclusion: Despite more advance stage at presentation, jNPC patients had better survival than did aNPC patients. Future treatment strategies should take into consideration the long-term complications in these young patients.

  9. Profiling gene expression patterns of nasopharyngeal carcinoma and normal nasopharynx tissues with cDNA microarray

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    5 μg of total RNAs from normal nasopharynx and nasopharyngeal carcinoma tissue have been labeled with α-32P-dCTP during reverse transcription. The synthesized cDNA probes have been hybridized to high-density cDNA microarray containing 5184 genes or expression sequence tags (ESTs). Then image analysis software has been applied to comparing their expression profiles. Results show that 187 ESTs were of density value above 200 in nasopharyngeal carcinoma tissue while there were 307 such ESTs in normal nasopharynx tissue; 38 ESTs were strongly expressed in nasopharynx, but weakly expressed in nasopharyngeal carcinoma; 48 ESTs were strongly expressed in nasopharyngeal carcinoma, but weakly expressed in normal nasopharynx. These results suggest that there may exist some new differentially expressed genes involved in nasopharyngeal carcinoma development. Furthermore, the results strongly indicate that high-density cDNA microarray is a powerful and efficient tool for large-scale screening differentially expressed genes.

  10. Comparison of rapidArc and fixed field intensity-modulated radiation therapies for advanced nasopharyngeal carcinoma%晚期鼻咽癌RapidArc与固定野调强放疗的比较研究

    Institute of Scientific and Technical Information of China (English)

    庄名赞; 张拓丹; 彭逊; 陈志坚; 林志雄; 李德锐

    2013-01-01

      目的:近年RapidArc的临床应用已引起越来越多的关注,本研究比较RapidArc与固定野调强放射治疗(IMRT)两种放疗技术在晚期鼻咽癌治疗计划中的差异.方法:随机选取10例晚期鼻咽癌患者,采用RapidArc与IMRT两种技术进行计划设计与剂量验证,比较计划的靶区剂量、危及器官与正常组织剂量、机器跳数、治疗时间与剂量验证结果.结果:两种计划的剂量分布基本一致,均能提供足够的靶区剂量.RapidArc的PTVnx最小剂量,PTVnd、PTV60、喉、腮腺的平均剂量低于IMRT,PTV60的HI值高于 IMRT,机器跳数比 IMRT 减少约58%,治疗时间减少约70%.以3%/3mm 为界,RapidArc 验证的γ指数通过率为(98.75±0.50)%,IMRT的通过率为(98.86±0.67)%.结论:两种放疗技术均能够满足临床治疗需要,剂量验证结果能够较好的符合计划计算结果.RapidArc比IMRT有着更多的优势,不仅可以减少机器跳数,缩短治疗时间,而且可以减少喉、腮腺的受照剂量.%Objective: This study compares volumetric-modulated arc therapy (RapidArc) and fixed field intensity-modulated radiation therapy (IMRT) for advanced nasopharyngeal carcinoma. Methods: Ten advanced nasopharyngeal carcinoma patients were randomly selected for this study. Two treatment plans were completed for each patient, i.e., the RapidArc and IMRT schemes. Dosimetric verification was conducted for each scheme. The doses for the planning target volumes (PTVs), organs at risk (OARs), and normal tissues were compared. The technical delivery parameters, including monitor units (MUs), time of therapy, and results of dosimetric verification, were analyzed. Results: No significant differences were found in dose distribution between the two schemes. Both techniques delivered adequate doses for the PTVs. For RapidArc planning, the minimal dose of PTVnx, mean dose of PTVnd, PTV60, larynx, and parotid were lower compared with those of IMRT schemes, whereas the

  11. Statistical analysis of 32 patients with nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    In order to assess the clinical outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) who were initially treated in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine between 1997 and 2006, statistical analyses were performed based on the patient medical records. Cause-specific survival (CSS) and disease-free survival (DFS) in all cases (stage I to IV, n=32) and advanced cases (stage III and IV, n=22) were estimated using the Kaplan-Meier method. The independent prognostic values of the clinical and therapeutic factors were determined using multivariate Cox proportional hazards models. The 5-year CSS/DFS were 43.4%/34.8% in all cases and 34.5%/29.8% in advanced cases. Multivariate analysis revealed that, in all cases, the independent prognostic factors for CSS were age (≥61 vs. ≤60, risk ratio (RR)=5.717, p=0.006), T-stage (3/4 vs. 1/2, RR=6.957, p=0.004), and the use of platinum agents (unused vs. used, RR=3.911, p=0.012), whereas those for DFS were T-stage (3/4 vs. 1/2, RR=3.499, p=0.019) and the use of platinum agents (unused vs. used, RR=2.947, p=0.028). In advanced cases, the use of platinum agents alone was significant for both CSS (RR=4.503, p=0.023) and DES (RR=4.218, p=0.014). The patients who received neoadjuvant chemotherapy (NAC) showed better CSS and DFS than the patients who did not (p=0.066 and p=0.025, respectively) in a univariate analysis (Log-rank test), although no significant difference was seen between these groups in the multivariate analysis. The advantage of the administration of platinum agents in the treatment of NPC was statistically corroborated even in our study with its small sample size. As agents combined with chemoradiotherapy, the efficacy of docetaxel alone did not seem comparable to that of platinum agents. The docetaxel-CDDP-5-FU regimen applied as NAC was suggested to be possibly beneficial for advanced cases of NPC. (author)

  12. Epigenetic disruption of cell signaling in nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Li-Li Li; Xing-Sheng Shu; Zhao-Hui Wang; Ya Cao; Qian Tao

    2011-01-01

    Nasopharyngeal carcinoma (NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia. Alternative to genetic changes, aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/ or histone modifications. These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC. In this review, we summariye the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research. Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.

  13. Three cases of temporal bone osteoradionecrosis after nasopharyngeal carcinoma treatment

    International Nuclear Information System (INIS)

    Osteoradionecrosis is most commonly caused by radiation-induced injury. We report on 3 cases of temporal bone necrosis that occurred after chemoradiotherapy for nasopharyngeal carcinoma performed more than 10 years previously. Case 1 was a 42-year-old woman who had nasopharyngeal carcinoma in 1991. The patient underwent chemoradiotherapy (70 Gy total) in 1991, and gamma knife irradiation (20 Gy) in 1998 for local recurrence. The bone in the posterior wall of the left external auditory canal began to be exposed in 2003. Otorrhea from the left ear increased and we found a skin defect and ulcer formation in the postauricular region. We performed radical mastoidectomy and debridement on April, 2010. The area of the defect was covered and filled in with a pedicle musculoperiosteal flap. The intra-aural skin became dry in 6 months, however, she lost consciousness due to a temporal lobe abscess and underwent an emergency operation on April, 2011. After operation, the patient recovered with no neurological symptoms and infections up to the present date. Case 2 was a 58-year-old man who had nasopharyngeal carcinoma in 2001. The patient underwent chemoradiotherapy (66 Gy total) in 2001, and X knife irradiation (15 Gy) 3 months later due to the remaining tumor. The left posterior ear canal wall collapsed and the tympanic membrane retracted with pooling epithelial debris appearing in 2007. Left facial nerve palsy was seen in December 2010. We performed a mastoidectomy on January, 2011. Cholesteatoma and necrotic granuloma with fragile bone filled the mastoid cavity, and a facial canal bone defect was seen. Bone necrosis with cholesteatoma and inflammatory granuloma was revealed by the pathological examination. The facial palsy improved after the operation. Case 3 was a 59-year-old man who had left abducens palsy with nasopharyngeal carcinoma invading the clivus. The patient underwent chemoradiotherapy (60 Gy total) in 2001, and X knife irradiation (24 Gy) 4 months later for

  14. Role of chemotherapy in stage llb nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xin-Bin Pan; Xiao-Dong Zhu

    2012-01-01

    The efficacy of neoadjuvant chemotherapy and adjuvant chemotherapy on stage lib nasopharyngeal carcinoma(NPC) remains unclear.Conventional two-dimensional radiotherapy combined with concurrent chemotherapy can improve the overall survival,progression-free survival,recurrence-free survival,and distant metastasis-free survival of patients with stage lib NPC.Intensity-modulated radiotherapy without concurrent chemotherapy also provides good outcomes for patients with stage lib NPC.This article summarizes the features of stage lib NPC and reviews the role of chemotherapy in this subgroup of NPC.

  15. Simultaneous nasopharyngeal carcinoma with laryngeal squamous cell carcinoma and review of literature

    Directory of Open Access Journals (Sweden)

    Kasim S. Kasim

    2015-03-01

    Full Text Available The occurrence of second primary carcinomas (SPC in aerodigestive tract is well recognized in the literature especially the lung and esophagus. The tumors are described according to the chronological presentation as simultaneous, synchronous and metachronous. Occurrence of second primary malignancy can be missed in early examination if they are not actively looked for. We are reporting the first and extremely rare presentation of nasopharyngeal carcinoma (NPC presented simultaneously with laryngeal carcinoma with literature review and stress on the importance of pan-endoscopy in the management.

  16. Evaluation of Body Mass Index and Survival of Nasopharyngeal Carcinoma by Propensity-Matched Analysis

    OpenAIRE

    OuYang, Pu-Yun; Zhang, Lu-Ning; Jie TANG; Lan, Xiao-Wen; Xiao, Yao; Gao, Yuan-Hong; Jun MA; Xie, Fang-Yun

    2016-01-01

    Abstract The effect of pretreatment body mass index on survival of nasopharyngeal carcinoma remains contradictory. All patients (N = 1778) underwent intensity-modulated radiotherapy with or without chemotherapy. Body mass index was categorized as underweight (

  17. MiR-634 sensitizes nasopharyngeal carcinoma cells to paclitaxel and inhibits cell growth both in vitro and in vivo

    OpenAIRE

    Peng, Xiaowei; Cao, Peiguo; He, Dong; Han, Shuang; Zhou, Jianda; Tan, Guolin; Li, Wei; Yu, Fenghui; Yu, Jianjun; Li, Zan; Cao, Ke

    2014-01-01

    Resistance to chemotherapy is one of the key causal factors in cancer death and increasing evidence has revealed that microRNAs (miRNAs) are involved in chemoresistance in many kinds of human cancers. Paclitaxel has been used for treatment of advanced nasopharyngeal carcinoma (NPC); however, treatment failure often occurs due to development of acquired paclitaxel resistance. In this study, based on miRNA microarray screening and qRT-PCR validation, we found six differentially expressed miRNAs...

  18. Mathematical modeling of the cells repair regulations in Nasopharyngeal carcinoma.

    Science.gov (United States)

    Adi-Kusumo, Fajar; Wiraya, Ario

    2016-07-01

    Nasopharyngeal Carcinoma (NPC) is a malignant cancer which is caused by the activation of Epstein-Barr Virus (EBV) via some external factors. In the cells repair regulations, the p53 gene mutation can be used as the early indication of the NPC growth. The NPC growth is due to the DNA damage accumulation caused by the EBV infection. In this paper we construct the cells repair regulations model to characterize the NPC growth. The model is a 15 dimensional of first order ODE system and consists the proteins and enzymes reactions. We do some numerical simulations to show the inactivation of the phosphorylated and acetylated p53, and the chromosomal instability of p53 gene, which can be used as the earlier stage detection of NPC. PMID:27140528

  19. Role of plasma EBV DNA levels in predicting recurrence of nasopharyngeal carcinoma in a western population

    Directory of Open Access Journals (Sweden)

    Ferrari Daris

    2012-05-01

    Full Text Available Abstract Background Loco-regionally advanced nasopharyngeal carcinomas can be cured by the combination of chemotherapy and radiotherapy. In Eastern countries, plasma levels of viral Epstein-Barr deoxyribonucleic acid (DNA are accurate in predicting recurrence, but few data are available in Western populations. The aim of this prospective study was to evaluate the relationship between viral Epstein-Barr DNA copy numbers in plasma and the response rate, progression-free survival and overall survival in a cohort of Western patients with stage IIb-IVb nasopharyngeal cancer. Methods We evaluated plasma samples from 36 consecutive patients treated with induction chemotherapy followed by chemoradiation. EBV copy numbers were determined after DNA extraction using real-time quantitative polymerase chain reaction. Survival curves were estimated using the Kaplan–Meier method. Results Circulating Epstein-Barr virus DNA levels were measured before treatment, at the end of concomitant chemo- and radiotherapy, and during the follow-up period. Pre-treatment levels significantly correlated with the initial stage and probability of relapse. Their increase was 100% specific and 71.3% sensitive in detecting loco-regional or metastatic recurrence (an overall accuracy of 94.4%. Three-year progression-free and overall survival were respectively 78.2% and 97.1%. Conclusions The results of this study confirm that patients from a Western country affected by loco-regionally advanced nasopharyngeal carcinoma have high plasma Epstein-Barr virus DNA levels at diagnosis. The monitoring of plasma levels is sensitive and highly specific in detecting disease recurrence and metastases.

  20. 新辅助化疗治疗晚期鼻咽癌的系统评价%A systematic review of neoadjuvant chemotherapy in the treatment of advanced nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    余林; 沈艾; 刘锐; 魏续福; 吴忠均

    2013-01-01

    Objective:To evaluate the efficacy and safety of neoadjuvant chemotherapy(NACT) in the treatment of advanced nasopharyngeal carcinoma.Methods:Literature was searched online in Pubmed,Embase,Cochrane Library before April 1st,2013.Only randomized controlled trials(RCTs) with regard to NACT were included.Results:A total of 7 trials with 1 463 cases were included.Meta analyses demonstrated that NACT significantly improved the recurrence-free survival(HR:0.74,95%CI:0.64,0.86,P<0.001) and overall survival (HR:0.81,95 % CI:0.68,0.96,P=0.013),decreased the locoregional recurrence (RR:0.80,95 % CI:0.67,0.97,P=0.022) and the distant metastasis(RR:0.70,95%CI:0.58,0.85,P<0.001).During NACT,the common grade 3-4 adverse events were hair loss (46.4%),nausea/vomiting (20.1%),neutropenia (35.9%).However,NACT didn' t increased the treatment-related death (P=0.806) and grade 3-4 adverse events after treatments.Conclusions:NACT is an effective and safe modality for patients with advanced nasopharyngeal carcinoma.%目的:新辅助化疗(neoadjuvant chemotherapy,NACT)被广泛应用于晚期鼻咽癌的治疗,但其疗效却受到争议.因此,本系统评价旨在评估NACT的有效性及安全性.方法:计算机检索Pubmed,Emabse,Cochrane Library数据库2013年4月1日之前的数据.只纳入以NACT为变量的随机对照试验.结果:7篇随机对照试验共1 463名患者进入本系统评价.Meta分析显示NACT能明显延长患者的无瘤生存期[风险比(hazard ratio,HR):0.74,95%置信区间(confidence interval,CI)(0.64,0.86),P<0.001]及总生存期[HR:0.81,95%CI(0.68,0.96),P=0.013],降低肿瘤局部复发率[相对风险比(relative risk,RR):0.80,95%CI(0.67,0.97),P=0.022]及远处转移率[RR:0.70,95%CI(0.58,0.85),P<0.001].但NACT不明显增加治疗相关的死亡率(P=0.806).NACT过程中3~4级并发症发生率较高的是脱发(46.4%)、恶心/呕吐(20.1%)、中性粒细胞减少(35.9%),但NACT并不明显增加放疗或同

  1. 多西紫杉醇在局部晚期鼻咽癌同期放化疗中的临床应用研究%Clinical application of docetaxel on concurrent chemo- radiotherapy in locally advanced nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    秦继勇; 夏耀雄; 蒋美萍; 黄华; 丁祥; 李岚; 李文辉

    2012-01-01

    目的 研究1次/同多西紫杉醇单药在局部晚期鼻咽癌同期放化疗的剂量递增耐受性试验中,多西紫杉醇的剂量限制性毒性和最大耐受剂量.方法 局部晚期鼻咽癌初治患者10例,常规放疗+后程适形放疗同期使用多两紫杉酵1次/周剂量递增方案进行化疗,评价治疗相关不良反应.结果 12.5 mg/(m2·w)剂量水平3例患者中,1例出现Ⅲ级吞咽疼痛、放射皮肤炎14d.17.5 mg/(m2·w)剂量水平5例患者中,1例患者出现Ⅱ级口干、吞咽疼痛、食欲减退、恶心、呕吐、乏力,致使放疗中断;1例出现Ⅲ级放射皮肤炎14d.22.5 mg/(m2·w)剂量水平2例患者中,1例出现Ⅱ~Ⅲ级食欲减退、黏膜损伤、吞咽疼痛、放射皮肤炎持续18 d;1例同期放化疗3周后出现Ⅲ级黏膜损伤、存咽疼痛,停化疗后完成放疗.结论 食欲减退、黏膜损伤、吞咽疼痛、放射皮肤炎是本试验观察到的主要剂量限制性毒性.%Objective To explore the dose limit toxicity (DLT) and maximum tolerated dose of docetaxel once a week in the concurrent chemo - radiotherapy in locally advanced nasopha-ryngeal carcinoma. Methods Ten patients with locally advanced nasopharyngeal carcinoma received conventional radiotherapy plus conformal radiotherapy with dose escalation chemotherapy of docetaxel once a week. The adverse reactions related to treatment were evaluated. Results Among 3 patients with 12.5 mg/(m2

  2. Comparison of long-term efficacy between intensity-modulated radiotherapy with concurrent chemotherapy and neoadjuvant chemotherapy followed by intensity-modulated radiotherapy with concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Objective: To compare the long-term efficacy between two radiochemotherapy regimens for locally advanced nasopharyngeal carcinoma (NPC): intensity-modulated radiotherapy with concurrent chemotherapy (CCRT) versus neoadjuvant chemotherapy (NACT) followed by CCRT. Methods: A retrospective analysis was performed on the clinical data of 278 patients with locally advanced NPC who were admitted to our hospital from 2001 to 2008. Of the 278 patients, 133 received CCRT, and 145 received NACT followed by CCRT (NACT + CCRT). Results: The follow-up rate was 96.6%. The 5-year overall survival (OS),distant metastasis-free survival (DMFS), recurrence-free survival (RFS), and progression-free survival (PFS) were 78.1%, 78.0%, 90.6%, and 72.0%, respectively. There were no significant differences between the CCRT group and NACT + CCRT group in 5-year OS (79.9% vs. 76.4%, P=0.443), DMFS (77.1% vs. 78.9%, P=0.972), RFS (91.6% vs. 89.8%, P=0.475), and PFS (71.6% vs. 72.2%, P=0.731). Subgroup analysis showed that compared with CCRT, NACT + CCRT did not significantly improve 5-year RFS in T3-4N0-1 patients (90.7% vs. 86.9%, P=0.376) and did not significantly improve 5-year DMFS in patients with advanced N-stage disease (57.6% vs. 69.7%, P=0.275). There were significantly higher numbers of individuals with neutropenia,decrease in hemoglobin, and upper gastrointestinal reactions in patients treated with NACT + CCRT than in those treated with CCRT (100 vs. 52, P=0.000; 64 vs. 35, P=0.010; 90 vs. 63, P=0.044). Conclusions: Compared with CCRT,NACT + CCRT does not significantly improve the prognosis in patients with locally advanced NPC and leads to significant increases in grade ≥ 3 toxicities (neutropenia, decrease in hemoglobin, and upper gastrointestinal reactions). The role of NACT in the treatment of locally advanced NPC needs further study. (authors)

  3. BRCC3 acts as a prognostic marker in nasopharyngeal carcinoma patients treated with radiotherapy and mediates radiation resistance in vitro

    International Nuclear Information System (INIS)

    BRCC3 has been found to be aberrantly expressed in breast tumors and involved in DNA damage response. The contribution of BRCC3 to nasopharyngeal carcinoma prognosis and radiosensitivity is still unclear. Immunohistochemical analysis of BRCC3 was carried out in 100 nasopharyngeal carcinoma tissues, and the protein level was correlated to patient survival. BRCC3 expression of nasopharyngeal carcinoma cell lines was determined by Western-blotting and real-time PCR. Additionally, the effects of BRCC3 knockdown on nasopharyngeal carcinoma cell clongenic survival, DNA damage repair, and cell cycle distribution after irradiation was assessed. The BRCC3 protein level was inversely correlated with nasopharyngeal carcinoma patient overall survival (P < 0.001) and 3-year loco-regional relapse-free survival (P = 0.034). Multivariate analysis demonstrated that BRCC3 expression was an independent prognostic factor (P = 0.010). The expression of BRCC3 was much higher in radioresistant nasopharyngeal carcinoma cells than in radiosensitive cells. Knockdown of BRCC3 increased the cell survival fraction, attenuated DNA damage repair and resulted in G2/M cell cycle arrest in radioresistant NPC cells. High BRCC3 expression in nasopharyngeal carcinoma patients is associated with poor survival. BRCC3 knockdown could abate the radioresistance in nasopharyngeal carcinoma cells. These findings suggest the utility of BRCC3 as a prognostic biomarker and novel target for nasopharyngeal carcinoma

  4. Clinical Characteristics of Recurrent Nasopharyngeal Carcinoma in High-Incidence Area

    Directory of Open Access Journals (Sweden)

    Jia-Xin Li

    2012-01-01

    Full Text Available Background. To describe the clinical characteristics of the patients who suffered from relapse after conventional irradiation for nasopharyngeal carcinoma (NPC. Methods. Three hundred and fifty-one consecutive patients with first-time recurrent NPC between January 1999 and July 2005 were included. The patients’ clinical data were reviewed, including recurrent interval time, symptoms, signs, imaging characteristics, pathologic features, and restaging. Results. The median interval of relapse was 26.0 months. The most common symptoms in symptomatic patients were nasal bloody discharge (37.9% and headache (31.1%. Local recurrence alone accounted for 73.5%. Most patients were restaged as stage III (23.1% and stage IV (51.1%. Subgroup analysis suggested a significantly higher proportion of the long-latent relapses originated from early primary. A series of postreirradiation complications were more frequent in patients with longer latency at reception. Conclusions. Most recurrent nasopharyngeal carcinoma is advanced disease. Patients with different recurrent interval time show different nature behavior.

  5. Present situation and development of chemotherapy of nasopharyngeal carcinoma%鼻咽癌化疗现状及进展

    Institute of Scientific and Technical Information of China (English)

    冼献清; 谢民强; 江刚

    2013-01-01

    Chemotherapy is one of main treatments for nasopharyngeal carcinoma (NPC) except radiation therapy. Improving and optimizing chemotherapeutic regimen are helpful to improve the therapeutic effects and reduce side effects. At present, concurrent chemoradiotherapy still is the standard treatment for advanced nasopharyngeal carcinoma. Induced chemotherapy has been shown superiority, but the effect of adjuvant chemotherapy needs further study. This paper analyzed the superior and inferior, effect and side effect of all kinds of chemotherapeutic methods or scheme including induced chemotherapy,concurrent chemotherapy, adjuvant chemotherapy and palliative chemotherapy and introduced simply the mechanism and clinical effect of new drugs of anticancer. It was hoped to offer some reference for the selection of chemotherapy for NPC.

  6. Nasopharyngeal carcinoma as a paradigm of cancer genetics

    Institute of Scientific and Technical Information of China (English)

    Malcolm J. Simons

    2011-01-01

    The unusual incidence patterns for nasopharyngeal carcinoma (NPC) in China, Northeast India, Arctic Inuit, Peninsular and island Southeast Asia, Polynesian Islanders, and North Africans indicate a role for NPC risk genes in Chinese, Chinese-related, and not-obviously Chinese-related populations. Renewed interest in NPC genetic risk has been stimulated by a hypothesis that NPC population patterns originated in Bai-Yue / pre-Austronesian-speaking aborigines and were dispersed during the last glacial maximum by Sundaland submersion. Five articles in this issue of the Chinese Journal of Cancer, first presented at a meeting on genetic aspects of NPC [National Cancer Center of Singapore (NCCS), February 20-21, 2010], are directed towards incidence patterns, to early detection of affected individuals within risk populations, and to the application of genetic technology advances to understanding the nature of high risk. Turnbull presents a general framework for understanding population migrations that underlie NPC and similar complex diseases, including other viral cancers. Trejaut et al. apply genetic markers to detail migration from East Asia through Taiwan to the populating of Island Polynesia. Migration dispersal in a westward direction took mongoloid peoples to modem day Northeast India adjacent to Western China (Xinjiang). NPC incidence in mongoloid Nagas ranks amongst the highest in the world, whereas elsewhere in India NPC is uncommon. Cao et al. detail incidence patterns in Southeast China that have occurred over recent decades. Finally, Ji et al. describe the utility of Epstein-Barr virus serostatus in early NPC detection. While genetic risk factors still remain largely unknown, human leukocyte antigen (HLA) genes have been a focus of attention since the discovery of an HLA association with NPC in 1973 and, two years later, that NPC susceptibility in highest-risk Cantonese involved the co-occurrence of multi-HLA locus combinations of HLA genes as chromosome

  7. CXCL12 genetic variants as prognostic markers in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Chen RW

    2015-10-01

    Full Text Available Ruiwan Chen,1,* Yafei Xu,2,* Xiaojing Du,2,* Na Liu,2 Yingqin Li,2 Qingmei He,2 Linglong Tang,2 Yanping Mao,2 Ying Sun,2 Lei Chen,2,* Jun Ma2,* 1Department of Radiotherapy, The First Affiliated Hospital, Sun Yat-sen University, 2Department of Radiation Oncology, State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: The chemokine receptor 4/chemokine ligand 12 (CXCR4/CXCL12 axis plays an important role in tumorigenesis, metastasis, and recurrence of tumors. Its single nucleotide polymorphisms (SNPs are associated with patient survival in several types of cancer. However, the prognostic value of SNPs in nasopharyngeal carcinoma (NPC has not been fully investigated. This retrospective study assessed the relationships between CXCR4 rs2228014 and CXCL12 rs1801157 polymorphisms and patient outcome in 222 patients newly diagnosed with NPC. The analysis found no significant correlation between the presence of both SNPs and clinicopathological factors. However, univariate analysis showed that N classification, clinical stage, and the CXCL12 rs1801157 polymorphism were significantly associated with distant metastasis-free survival (P=0.018, 0.028, and 0.013, respectively and progression-free survival (P=0.007, 0.046, and 0.021, respectively. After adjusting clinicopathological factors, multivariate analysis identified CXCL12 rs1801157 as an independent prognostic factor for distant metastasis-free survival and progression-free survival (hazard ratio: 3.332; 95% confidence interval: 1.597–6.949; P=0.001 and hazard ratio: 2.665 95% confidence interval: 1.387–5.119; P=0.003, respectively. Our results suggest that CXCL12 rs1801157 AA genotype might serve as a potential prognostic factor in patients with NPC. Keywords: nasopharyngeal carcinoma, CXCR4, CXCL12, polymorphism

  8. BZLF1 Expression of EBV is correlated with PARP1 Regulation on Nasopharyngeal Carcinoma Tissues

    OpenAIRE

    Wahyu nur laili fajri, Ahmad Rofi'i, Fatchiyah Fatchiyah

    2013-01-01

    Nasopharyngeal carcinomas (NPC) is a cancer that arises in the epithelial tissue that covers the inside of the nasopharyngeal mucosa and nasopharynx. Infected Epstein Barr Virus (EBV) cell in a latent infection associated with the expression of nine latent proteins. Latent Membrane Protein 1 (LMP1) is one of latent proteins, and mayor EBV oncoprotein, with functions including virus growth, and to activate BamHI-Z Leftward Reading Frame 1 (BZLF1)-EBV, which can inhibit p53 to induce apoptotic ...

  9. Neoadjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: Defining high-risk patients who may benefit before concurrent chemotherapy combined with intensity-modulated radiotherapy

    OpenAIRE

    Xiao-Jing Du; Ling-Long Tang; Lei Chen; Yan-Ping Mao; Rui Guo; Xu Liu; Ying Sun; Mu-Sheng Zeng; Tie-Bang Kang; Jian-Yong Shao; Ai-Hua Lin; Jun Ma

    2015-01-01

    The purpose of this study was to create a prognostic model for distant metastasis in patients with locally advanced NPC who accept concurrent chemotherapy combined with intensity-modulated radiotherapy (CCRT) to identify high-risk patients who may benefit from neoadjuvant chemotherapy (NACT). A total of 881 patients with newly-diagnosed, non-disseminated, biopsy-proven locoregionally advanced NPC were retrospectively reviewed; 411 (46.7%) accepted CCRT and 470 (53.3%) accepted NACT followed b...

  10. Classification of progression free survival with nasopharyngeal carcinoma tumors

    Science.gov (United States)

    Farhidzadeh, Hamidreza; Kim, Joo Y.; Scott, Jacob G.; Goldgof, Dmitry B.; Hall, Lawrence O.; Harrison, Louis B.

    2016-03-01

    Nasopharyngeal carcinoma (NPC) is an abnormal growth of tissue which arises from the back of the nose. At the time of diagnosis, detection of tumor features with prognostic significance, including patient demographics, imaging characteristics and molecular characteristics, can enable the treating clinician to select a treatment that is optimized for the individual patient. At present, the analysis of tumor imaging features is limited to size criteria and macroscopic textural semantic descriptors, but computerized quantification of intratumoral heterogeneity and their temporal evolution may provide another metric for predicting prognosis. We propose medical imaging feature analysis methods and radiomics machine learning methods to predict failure of treatment. NPC tumors on contrast-enhanced T1 (T1Gd) sequences of 25 NPC patients' diagnostic magnetic resonance images (MRI) were manually contoured. Otsu segmentation was applied to segment the tumor into highly enhancing vs. weakly enhancing signal intensity subregions. Within these subregions, texture features were extracted to numerically quantify the intraregional heterogeneity. Patients were divided into two prognostic groups; a progression-freesurvival group (those without locoregional recurrence or distant metastases), and the disease progression group (those with locoregional recurrence or distant metastases). We used Support Vector Machines (SVM) to perform classification (prediction of prognosis). The features from the highly enhancing subregion classify prognosis with 80% predictive accuracy with AUC=0.60, while the captured features from the weakly enhancing subregion classify prognosis with 76% accuracy with AUC= 0.76.

  11. ASSOCIATION OF pIgR POLYMORPHISMS WITH NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    FAN Qin; JIA Wei-hua; ZHANG Ru-hua; YU Xing-juan; CHEN Li-zhen; FENG Qi-sheng; ZENG Yi-xin

    2006-01-01

    Objective: Epstein-Barr virus (EBV) associated nasopharyngeal carcinoma (NPC) is an important squamous cell cancer endemic in southern China and Southeast Asia. pIgR (polymeric immunoglobulin receptor) gene plays central roles during immune responses and EBV inflammatory and therefore is a good candidate susceptibility gene for NPC. This study is to evaluated potential associations between pIgR gene and NPC susceptibility. Methods: Sequencing was used to identify multiple single nucleotide polymorphisms (SNPs) within the exon regions of pIgR in Guangdong population. Four SNPs were genotyped in 528 NPC patients and 408 normal individuals to perform case-control study. Results: There was no statistical difference in the allele frequencies of each SNP (P>0.05). After categorized into 2 groups by age of 45 y, in the group of age below 45 the minor allele T frequency of C888oT was 7%, whereas 4% in controls, with significant difference (P<0.05). The Odds Ratio (OR=1.84) also showed higher risk of NPC with individuals carried the minor alleles. Conclusion: The result has proved that SNP C8880T is associated with NPC susceptibility and pIgR gene might play a certain role in oncogenesis and development of NPC.

  12. Multiple oncogenic mutations related to targeted therapy in nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jian-Wei Zhang; Hong-Yuan Zhao; Yu-Xiang Ma; Zhi-Huang Hu; Pei-Yu Huang; Li Zhang; Tao Qin; Shao-Dong Hong; Jing Zhang; Wen-Feng Fang; Yuan-Yuan Zhao; Yun-Peng Yang; Cong Xue; Yan Huang

    2015-01-01

    Introduction:An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma (NPC). However, targeted therapy-related oncogenic mutations have not been fully evaluated. This study aimed to detect targeted therapy-related oncogenic mutations in NPC and to determine which targeted therapy might be potentially effective in treating NPC. Methods:By using the SNaPshot assay, a rapid detection method, 19 mutation hotspots in 6 targeted therapy-related oncogenes were examined in 70 NPC patients. The associations between oncogenic mutations and clinicopathologic factors were analyzed. Results:Among 70 patients, 12 (17.1%) had mutations in 5 oncogenes:7 (10.0%) had v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutation, 2 (2.8%) had epidermal growth factor receptor (EGFR) mutation, 1 (1.4%) had phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation, 1 (1.4%) had Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and 1 (1.4%) had simultaneous EGFR and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations. No significant differences were observed between oncogenic mutations and clinicopathologic characteristics. Additionally, these oncogenic mutations were not associated with tumor recurrence and metastasis. Conclusions:Oncogenic mutations are present in NPC patients. The efficacy of targeted drugs on patients with the related oncogenic mutations requires further validation.

  13. The prevalence and prevention of nasopharyngeal carcinoma in China

    Institute of Scientific and Technical Information of China (English)

    Su-Mei Cao; Malcolm J. Simons; Chao-Nan Qian

    2011-01-01

    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.

  14. Hearing disability before and after radiotherapy for nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    This paper evaluates post-irradiation hearing changes in patients with nasopharyngeal carcinoma (NPC) from a disability orientated approach, which takes into account binaural hearing. Newly diagnosed patients with NPC were studied before radiotherapy, and at four months (mean 9.2 months) after radiotherapy, provided they remained disease-free. Each patient was examined clinically and with pure tone audiograms. Tympanometry was used to confirm middle ear effusion. Averaged hearing thresholds over 0.5, 1 and 2 kHz were evaluated. If abnormal (> 30 dB), the resultant hearing disability was illustrated by a modified Glasgow Plot. Twenty-three males and 10 females completed the study. Middle ear effusions resulted in 39.3 per cent (binaural in two patients) and 33.3 per cent (binaural in five patients) of patients having hearing disability pre- and post-irradiation respectively. No patient had hearing disability as a result of a sensoineural loss. It is recommended that future reporting of post-irradiation hearing changes in patients with NPC, as in middle ear surgery, be considered from a disability-orientated approach. (author)

  15. Pregnancy associated nasopharyngeal carcinoma: A retrospective case-control analysis of maternal survival outcomes

    International Nuclear Information System (INIS)

    Background: Pregnancy-associated nasopharyngeal carcinoma (PANPC) has been associated with poor survival. Recent advances in radiation technology and imaging techniques, and the introduction of chemotherapy have improved survival in nasopharyngeal carcinoma (NPC); however, it is not clear whether these changes have improved survival in PANPC. Therefore, the purpose of this study was to compare five-year maternal survival in patients with PANPC and non-pregnant patients with NPC. Methods: After adjusting for age, stage and chemotherapy mode, we conducted a retrospective case-control study among 36 non-metastatic PANPC patients and 36 non-pregnant NPC patients (control group) who were treated at our institution between 2000 and 2010. Results: The median age of both groups was 30 years (range, 23–35 years); median follow-up for all patients was 70 months. Locoregionally-advanced disease accounted for 83.3% of all patients with PANPC and 92.9% of patients who developed NPC during pregnancy. In both the PANPC and control groups, 31 patients (86.1%) received chemotherapy and all patients received definitive radiotherapy. The five-year rates for overall survival (70% vs. 78%, p = 0.72), distant metastasis-free survival (79% vs. 76%, p = 0.77), loco-regional relapse-free survival (97% vs. 91%, p = 0.69) and disease-free survival (69% vs. 74%, p = 0.98) were not significantly different between the PANPC and control groups. Multivariate analysis using a Cox proportional hazards model revealed that only N-classification was significantly associated with five-year OS. Conclusion: This study demonstrates that, in the modern treatment era, pregnancy itself may not negatively influence survival outcomes in patients with NPC; however, pregnancy may delay the diagnosis of NPC

  16. Salted fish and inhalants as risk factors for nasopharyngeal carcinoma in Malaysian Chinese.

    Science.gov (United States)

    Armstrong, R W; Armstrong, M J; Yu, M C; Henderson, B E

    1983-06-01

    We conducted a case-control study of nasopharyngeal carcinoma among Malaysian Chinese to test inhalants, salted fish consumption, and use of tobacco, alcohol, and nasal ointments as risk factors for the disease. Interviews with 100 cases and 100 controls indicated that salted fish consumption during childhood was a significant risk factor (relative risk, 3.0; p = 0.04); childhood daily consumption of this food item compared to nonconsumption carried a relative risk of 17.4 [95% confidence interval = (2.7, 111.1)]. Occupational exposure to smokes (relative risk, 6.0; p = 0.006) and to dusts (relative risk, 4.0; p less than 0.001) was also significantly associated with nasopharyngeal carcinoma. The two risk factors (consumption of salted fish and exposure to smoke and/or dust) were independent of each other. There was no association between nasopharyngeal carcinoma and tobacco, alcohol, or nasal ointments.

  17. Neoadjuvant chemotherapy in locally advanced nasopharyngeal carcinoma: Defining high-risk patients who may benefit before concurrent chemotherapy combined with intensity-modulated radiotherapy

    Science.gov (United States)

    Du, Xiao-Jing; Tang, Ling-Long; Chen, Lei; Mao, Yan-Ping; Guo, Rui; Liu, Xu; Sun, Ying; Zeng, Mu-Sheng; Kang, Tie-Bang; Shao, Jian-Yong; Lin, Ai-Hua; Ma, Jun

    2015-01-01

    The purpose of this study was to create a prognostic model for distant metastasis in patients with locally advanced NPC who accept concurrent chemotherapy combined with intensity-modulated radiotherapy (CCRT) to identify high-risk patients who may benefit from neoadjuvant chemotherapy (NACT). A total of 881 patients with newly-diagnosed, non-disseminated, biopsy-proven locoregionally advanced NPC were retrospectively reviewed; 411 (46.7%) accepted CCRT and 470 (53.3%) accepted NACT followed by CCRT. Multivariate analysis demonstrated N2–3 disease, plasma Epstein–Barr virus (EBV) DNA > 4000 copies/mL, serum albumin ≤46 g/L and platelet count >300 k/cc were independent prognostic factors for distant metastasis in the CCRT group. Using these four factors, a prognostic model was developed, as follows: 1) low-risk group: 0–1 risk factors; and 2) high-risk group: 2–4 risk factors. In the high-risk group, patients who accepted NACT + CCRT had significantly higher distant metastasis-free survival and progression-free survival rates than the CCRT group (P = 0.001; P = 0.011). This simple prognostic model for distant metastasis in locoregionally advanced NPC may facilitate with the selection of high-risk patients who may benefit from NACT prior to CCRT. PMID:26564805

  18. 尼妥珠单抗联合同步放化疗治疗进展期鼻咽癌的临床研究%Nimotuzumab combined with concurrent chemoradiotherapy in treatment of advanced nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    李斌; 胡福军; 陈晓钟; 姜锋; 秦卫丰; 冯星来; 包婺安

    2011-01-01

    目的 观察尼妥珠单抗联合放化疗治疗进展期鼻咽癌的近期疗效和不良反应.方法 对初治进展期鼻咽癌患者40例(治疗组)进行同步放化疗+尼妥珠单抗同步增敏治疗.所有鼻咽癌患者均接受调强放疗(IMRT),鼻咽部GTVnx处方剂量7 200cGy/30F;同步化疗采用DDP或NDP,80mg/m2,与放疗同时开始,每3周重复1次;28例每次采用尼妥珠单抗100mg,12例每次200mg,于放疗前静脉滴注,放疗期间1次/周,共6~8次.观察患者的治疗效果及急性皮肤、黏膜反应、皮疹反应、骨髓功能抑制、疼痛和体重变化.并与同期行同步放化疗的患者(对照组)对比.结果 所有患者均完成治疗计划.局部控制情况治疗组完全缓解38例(95.0%),部分缓解1例(2.5%),疾病稳定1例(2.5%).对照组完全缓解36例(90.0%),部分缓解4例(10.0%).治疗组和对照组3级以上的皮肤反应、黏膜反应、骨髓功能抑制发生率分别为20.0%、30.0%、37.5%和5.0%、7.5%、7.5%,两组皮肤反应和体重减轻差异无统计学意义(P >0.05),黏膜炎、骨髓功能抑制和疼痛治疗组较对照组明显,皮疹反应治疗组(15.0%)较对照组(0)增加.结论 尼妥珠单抗联合放化疗治疗晚期鼻咽癌安全有效,黏膜反应和骨髓功能抑制加重但未影响治疗,未增加严重毒副反应,部分患者出现皮疹反应但不影响放化疗进行.%Objective To evaluate the efficacy and acute toxicity of nimotuzumab combined with concurrent chemoradiotherapy in treatment of advanced nasopharyngeal carcinoma (NPC). Methods Forty patients with advanced NPC were treated with nimotuzumab combined with concurrent chemoradiotherapy (NC group). Nimotuzumab was given intravenously with a dosage of 100mg or 200mg weekly before the radiation throughout the course. Another 40 patients treated with concurrent chemoradiotherapy only in the same period served as control group. All cases received intensity modulated

  19. Nasopharyngeal carcinoma in children and adolescents - a single institution experience of 158 patients

    International Nuclear Information System (INIS)

    To evaluate the clinical features, treatment results, prognostic factors and late toxicities of nasopharyngeal carcinoma in children and adolescents. Between January 1990 and January 2011, 158 NPC patients younger than 20 years old were treated in our institution, and the patient’s clinical characteristics, treatment modalities, outcomes and prognostic factors were retrospectively analyzed. There were 9 (5.7%) patients in stage II, 60 (38.0%) in stage III and 89 (56.3%) in stage IV according to the UICC2002 staging system. Neck mass (32.3%), headache (21.5%) and nasal obstruction (15.2%) were the most common chief complaints. With a median follow-up time of 62.5 months (range 2.0-225.0 months), the 5-year overall survival (OS) rate, local-regional control (LRC) rate and distant metastasis-free survival (DMFS) rate were 82.6%, 94.9% and 76.4%, respectively. There were 43 (27.2%) patients failed during the follow up, with seven local-regional recurrences and 38 distant metastases. In univariate analysis, the 5-year OS of T4 and T1-3 were 75% and 87.9%, p = 0.01, stage IV and stage II-III were 77.1% and 90%, p = 0.04, respectively. In multivariate analysis, T4 (p = 0.02) and stage IV (p = 0.04) were the independent adverse prognostic factors for OS. Significant reduction in trismus (27.3% v 3.6%, p = 0.03) and G2 xerostomia (37.9% v 10.3%, p = 0.02) was observed in patients treated by IMRT. Most childhood and adolescence nasopharyngeal carcinoma patients were locally advanced diseases at first diagnosed. The treatment results of radiotherapy, with or without chemotherapy, are excellent in our institution. Reducing distant metastasis with new strategies and late toxicities with intensity-modulated radiotherapy are the future directions for the treatment of adolescent nasopharyngeal carcinoma

  20. The role of Epstein-Barr virus infection in the pathogenesis of nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chi; Man; Tsang; Sai; Wah; Tsao

    2015-01-01

    Nasopharyngeal carcinoma(NPC) is closely associated with Epstein-Barr virus(EBV) infection. EBV episomes are detected in almost all NPC cells. The role of EBV in NPC pathogenesis has long been postulated but remains enigmatic. In contrast to infection of B lymphocytes, EBV infection does not directly transform nasopharyngeal epithelial cells into proliferative clones with malignant potential. EBV infection of normal pharyngeal epithelial cells is predominantly lytic in nature. Genetic alterations in premalignant nasopharyngeal epithelium, in combination with inflammatory stimulation in the nasopharyngeal mucosa, presumably play essential roles in the establishment of a latent EBV infection in infected nasopharyngeal epithelial cells during the early development of NPC. Establishment of latent EBV infection in premalignant nasopharyngeal epithelial cells and expression of latent viral genes, including the BART transcripts and BART-encoded micro RNAs, are crucial features of NPC. Expression of EBV genes may drive further malignant transformation of premalignant nasopharyngeal epithelial cells into cancer cells. The difficulties involved in the establishment of NPC cell lines and the progressive loss of EBV epsiomes in NPC cells propagated in culture strongly implicate the contribution of host stromal components to the growth of NPC cells in vivo and maintenance of EBV in infected NPC cells. Defining the growth advantages of EBV-infected NPC cells in vivo will lead to a better understanding of the contribution of EBV infection in NPC pathogenesis, and may lead to the identification of novel therapeutic targets for NPC treatment.

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

    Institute of Scientific and Technical Information of China (English)

    TANGXi; HUGuoqing; QIUHong; CUIWei

    2005-01-01

    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.

  2. Treatment results for nasopharyngeal carcinoma in the modern era: The Hong Kong experience

    International Nuclear Information System (INIS)

    Purpose: To analyze the treatment results achievable for nasopharyngeal carcinoma in the modern era to identify the key failures for future improvement and to provide an updated baseline for future trials. Methods and materials: The results of 2687 consecutive patients treated at all public oncology centers in Hong Kong during 1996-2000 were retrospectively analyzed. The stage distribution (by American Joint Committee on Cancer and International Union Against Cancer staging system, 1997) was 7% Stage I, 41% Stage II, 25% Stage III, and 28% Stage IVA-B. All patients were irradiated with 6-MV photons and the median total dose was 66 Gy. Only 23% of patients had additional treatment with chemotherapy. Results: The 5-year local, nodal, and distant failure-free rates were 85%, 94%, and 81%, respectively; patients with local failure had significantly higher risk of nodal and distant failures. The 5-year progression-free, overall, and cancer-specific survival rates were 63%, 75%, and 80%, respectively. The presenting stage was the most important prognostic factor for all endpoints: with overall survival decreasing from 90% for Stage I to 58% for Stage IVA-B. The results achieved by the 2070 patients treated by radiotherapy alone were almost identical to that of the whole series, the distant failure-free rate among patients with locoregional control was 89% for Stage I-II and 75% for Stage III-IVB. The 860 patients (32%) staged with magnetic resonance imaging achieved significantly better results than those staged by computed tomography, the overall survival being 93% vs. 83% for Stages I-II, and 72% vs. 63% for Stages III-IVB (p = 0.001). Conclusions: Treatment results for nasopharyngeal carcinoma have substantially improved in the modern era; future trials should be based on updated baseline results. Further reduction of distant failure is important for future breakthrough, particularly for patients with advanced disease

  3. Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis

    Energy Technology Data Exchange (ETDEWEB)

    Stenmark, Matthew H., E-mail: stenmark@med.umich.edu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); McHugh, Jonathan B. [Department of Pathology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Walline, Heather M.; Komarck, Christine [Department of Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Feng, Felix Y. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Worden, Francis P. [Department of Medical Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Wolf, Gregory T.; Chepeha, Douglas B.; Prince, Mark E.; Bradford, Carol R. [Department of Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Mukherji, Suresh K. [Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Eisbruch, Avraham [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Carey, Thomas E. [Department of Head and Neck Surgery, University of Michigan Medical Center, Ann Arbor, Michigan (United States)

    2014-03-01

    Purpose: To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials: Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results: Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001). Conclusion: In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings.

  4. Inhibitory effects of 3-bromopyruvate in human nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Zou, Xue; Zhang, Mengxiao; Sun, Yiming; Zhao, Surong; Wei, Yingmei; Zhang, Xudong; Jiang, Chenchen; Liu, Hao

    2015-10-01

    Tumor cells depend on aerobic glycolysis for adenosine triphosphate (ATP) production, which is therefore targeted by therapeutic agents. The compound 3-bromopyruvate (3-BrPA), a strong alkylating agent and hexokinase inhibitor, inhibits tumor cell glycolysis and the production of ATP, causing apoptosis. 3-BrPA induces apoptosis of nasopharyngeal carcinoma (NPC) cell lines HNE1 and CNE-2Z, which may be related to its molecular mechanisms. In the present study, we investigated the effects of 3-BrPA on the viability, reactive oxygen species (ROS), apoptosis and other types of programmed cell death in NPC cells in vitro and in vivo. PI staining showed significant apoptosis in NPC cells accompanied by the overproduction of ROS and downregulation of mitochondrial membrane potential (MMP, ΔΨm) by 3-BrPA. However, the ROS scavenger N-acetyl-L-cysteine (NAC) significantly reduced 3-BrPA-induced apoptosis by decreasing ROS and facilitating the recovery of MMP. We elucidated the molecular mechanisms underlying 3-BrPA activity and found that it caused mitochondrial dysfunction and ROS production, leading to necroptosis of NPC cells. We investigated the effects of the caspase inhibitor z-VAD-fmk, which inhibits apoptosis but promotes death domain receptor (DR)-induced NPC cell necrosis. Necrostatin-1 (Nec-1) inhibits necroptosis, apparently via a DR signaling pathway and thus abrogates the effects of z-VAD‑fmk. In addition, we demonstrated the effective attenuation of 3-BrPA-induced necrotic cell death by Nec-1. Finally, animal studies proved that 3-BrPA exhibited significant antitumor activity in nude mice. The present study is the first demonstration of 3-BrPA-induced non-apoptotic necroptosis and ROS generation in NPC cells and provides potential strategies for developing agents against apoptosis‑resistant cancers. PMID:26239511

  5. Nasopharyngeal carcinoma incidence and mortality in China in 2009

    Institute of Scientific and Technical Information of China (English)

    Zhi-Jian Xu; Rong-Shou Zheng; Si-Wei Zhang; Xiao-Nong Zou; Wan-Qing Chen

    2013-01-01

    Nasopharyngeal carcinoma (NPC) is rare globally but common in China and exhibits a distinct ethnic and geographic distribution.In 2009,the National Central Cancer Registry in China provided real-time surveillance information on NPC.Individual NPC cases were retrieved from the national database based on the ICD-10 topography code C11.The crude incidence and mortality of NPC were calculated by sex and location (urban/rural).China's population in 1982 and Segi's world population structures were used to determine age-standardized rates.In regions covered by the cancer registries in 2009,the crude incidence of NPC was 3.61/100,000 (5.08/100,000 in males and 2.10/100,000 in females; 4.19/100,000 in urban areas and 2.42/100,000 in rural areas).Age-standardized incidences by Chinese population (ASIC) and Segi's world population (ASIW) were 2.05/100,000 and 2.54/100,000,respectively.The crude mortality of NPC was 1.99/100,000 (2.82/100,000 in males and 1.14/100,000 in females; 2.30/100,000 in urban areas and 1.37/100,000 in rural areas).The age-standardized mortalities by Chinese population (ASMC) and world population (ASMW) were 1.04/100,000 and 1.35/100,000,respectively.The incidence and mortality of NPC were higher in males than in females and higher in urban areas than in rural areas.Both agespecific incidence and mortality were relatively low in persons younger than 30 years old,but these rates dramatically increased.Incidence peaked in the 60-64 age group and mortality peaked in the over 85 age group.Primary and secondary prevention,such as lifestyle changes and early detection,should be carried out in males and females older than 30 years of age.

  6. Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

    International Nuclear Information System (INIS)

    Purpose: Radiation/chemoradiotherapy-induced carotid stenosis and cerebrovascular events in patients with nasopharyngeal carcinoma (NPC) can cause severe disability and even death. This study aimed to estimate the risk of ischemic stroke in this patient population over more than 10 years of follow-up. Methods and Materials: The study cohorts consisted of all patients hospitalized with a principal diagnosis of NPC (n = 1094), whereas patients hospitalized for an appendectomy during 1997 and 1998 (n = 4376) acted as the control group and surrogate for the general population. Cox proportional hazard model was performed as a means of comparing the stroke-free survival rate between the two cohorts after adjusting for possible confounding and risk factors. Results: Of the 292 patients with ischemic strokes, 62 (5.7%) were from the NPC cohort and 230 (5.3%) were from the control group. NPC patients ages 35–54 had a 1.66 times (95% CI, 1.16–2.86; p = 0.009) higher risk of ischemic stroke after adjusting for patient characteristics, comorbidities, geographic region, urbanization level of residence, and socioeconomic status. There was no statistical difference in ischemic stroke risk between the NPC patients and appendectomy patients ages 55–64 years (hazard ratio = 0.87; 95% CI, 0.56–1.33; p = 0.524) after adjusting for other factors. Conclusions: Young NPC patients carry a higher risk for ischemic stroke than the general population. Besides regular examinations of carotid duplex, different irradiation strategies or using new technique of radiotherapy, such as intensity modulated radiation therapy or volumetric modulated arc therapy, should be considered in young NPC patients.

  7. Nasopharyngeal carcinoma incidence and mortality in China in 2010

    Institute of Scientific and Technical Information of China (English)

    Kuang-Rong Wei; Rong-Shou Zheng; Si-Wei Zhang; Zhi-Heng Liang; Zhi-Xiong Ou; Wan-Qing Chen

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is common in South China. Although regional epidemiological data on NPC in China is available, national epidemiological data have been unavailable up to now. The goal of this study was to analyze the NPC incidence and mortality data in some domestic cancer registries, estimate these rates in China in 2010, and provide scientific information that can be harnessed for NPC control and prevention. To accomplish this goal, NPC incidence and mortality data for 2010 were col ected from 145 Chinese cancer registries from which data were included in the 2013 National Cancer Registry Annual Report. Such indices as its incident and death numbers, crude rates, age-standardized rates and truncated rates were calculated and analyzed. The incidence and mortality in China and constituent areas were estimated according to the national population in 2010. An estimated 41,503 new cases and 20,058 deaths were attributed to NPC in China in 2010, accounting for 1.34%of al new cancer cases and 1.03% of all cancer-related deaths that year in China. Crude incidence and mortality were 3.16/100,000 and 1.53/100,000, respectively. World age-standardized incidence and mortality were 2.44/100,000 and 1.18/100,000, respectively. Incidence and mortality were higher among males than among females and slightly higher in urban areas than in rural areas. Among seven Chinese administrative regions, NPC incidence and mortality were obviously higher in South China than in other regions and lowest in North China. The male and female age-specific incidence and mortality both rose quickly from age 25-29 years, but peaked at different ages and varied by location. These results demonstrated that NPC incidence and mortality in China especially in South China were at high levels in the world, and suggested that control and prevention efforts should be enhanced.

  8. Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis

    International Nuclear Information System (INIS)

    Purpose: To investigate the relationship between human papillomavirus (HPV) and Epstein-Barr virus (EBV) in nonendemic nasopharyngeal carcinoma (NPC) and assess the prognostic implications of viral status. Methods and Materials: Paraffin-embedded tumor specimens from 62 patients with primary NPC diagnosed between 1985 and 2011 were analyzed for EBV and high-risk HPV. EBV status was determined by the use of in situ hybridization for EBV encoded RNA. HPV status was assessed with p16 immunohistochemistry and multiplex polymerase chain reaction MassArray for determination of HPV type. Proportional hazards models were used to compare the risk of death among patients as stratified by viral status. Results: Of 61 evaluable tumors, 26 (43%) were EBV-positive/HPV-negative, 18 (30%) were HPV-positive/EBV-negative, and 17 (28%) were EBV/HPV-negative. EBV and HPV infection was mutually exclusive. HPV positivity was significantly correlated with World Health Organization grade 2 tumors, older age, and smoking (all P<.001). The racial distribution of the study population was 74% white, 15% African American, and 11% Asian/Middle Eastern. Among HPV-positive patients, 94% were white. At a median follow-up time of 7 years, HPV-positive and EBV/HPV-negative tumors exhibited worse outcomes than did EBV-positive tumors, including decreased overall survival (hazard ratio [HR] 2.98, P=.01; and HR 3.89, P=.002), progression-free survival (HR 2.55, P=.02; and HR 4.04, P<.001), and locoregional control (HR 4.01, P=.03; and HR 6.87, P=.001). Conclusion: In our Midwestern population, high-risk HPV infection may play an etiologic role in the development of nonendemic, EBV-negative NPC. Compared with EBV-positive NPC, HPV-positive and EBV/HPV-negative NPC are associated with worse outcomes. A larger confirmatory study is needed to validate these findings

  9. Significant prognosticators after primary radiotherapy in 903 nondisseminated nasopharyngeal carcinoma evaluated by computer tomography

    International Nuclear Information System (INIS)

    Purpose: To evaluate the significant prognosticators in nasopharyngeal carcinoma (NPC). Methods and Materials: From 1984 to 1989, 903 treatment-naive nondisseminated (MO) NPC were given primary radical radiotherapy to 60-62.5 Gy in 6 weeks. All patients had computed tomographic (CT) and endoscopic evaluation of the primary tumor. Potentially significant parameters (the patient's age and sex, the anatomical structures infiltrated by the primary lesion, the cervical nodal characteristics, the tumor histological subtypes, and various treatment variables were analyzed by both monovariate and multivariate methods for each of the five clinical endpoints: actuarial survival, disease-free survival, free from distant metastasis, free from local failure, and free from regional failure. Results: The significant prognosticators predicting for an increased risk of distant metastases and poorer survival included male sex, skull base and cranial nerve(s) involvement, advanced Ho's N level, and presence of fixed or partially fixed nodes or nodes contralateral to the side of the bulk of the nasopharyngeal primary. Advanced patient age led to significantly worse survival and poorer local tumor control. Local and regional failures were both increased by tumor infiltrating the skull base and/or the cranial nerves. In addition, regional failure was increased significantly by advancing Ho's N level. Parapharyngeal tumor involvement was the strongest independent prognosticator that determined distant metastasis and survival rates in the absence of the overriding prognosticators of skull base infiltration, cranial nerve(s) palsy, and cervical nodal metastasis. Conclusions: The significant prognosticators are delineated after the advent of CT and these should form the foundation of the modern stage classification for NPC

  10. Effect of inducing chemotherapy + chrono-chemotherapy + intensity-modulated radiation therapy on the survival and tumor malignancy in patients with nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hui Liu

    2016-01-01

    Objective:To analyze the effect of inducing chemotherapy + chrono-chemotherapy + intensity-modulated radiation therapy on the survival and tumor malignancy in patients with nasopharyngeal carcinoma.Methods: A total of 60 patients with locally advanced nasopharyngeal carcinoma were divided into observation group and control group according to different treatment, observation group received inducing chemotherapy + chrono-chemotherapy + intensity-modulated radiation therapy and control group received conventional treatment. Differences in the survival and tumor malignancy were compared between two groups.Results:miR-143 and miR-218 expression levels in nasopharyngeal carcinoma tissue of observation group after treatment were higher than those of control group, and miR-7 expression level was lower than that of control group; caspase-3, GRP-78 and Bax protein expression levels in tumor tissue of observation group after treatment were higher than those of control group, and Bcl-2 protein expression level was lower than that of control group;serum VEGF, -HBDH, CYFRA21-1 and PCⅢ levels of observation group after treatment were lower than those of control group.Conclusion:Inducing chemotherapy + chrono-chemotherapy + intensity-modulated radiation therapy can reduce the tumor malignancy and optimize the quality of life in patients with nasopharyngeal carcinoma.

  11. The Efficacy of Palonosetron for Prevention of Concurrent Radiochemotherapy Induced Nausea and Vomit in Patients with Locally Advanced Nasopharyngeal Carcinoma%帕洛诺司琼在局部晚期鼻咽癌同步放化疗中止吐作用研究

    Institute of Scientific and Technical Information of China (English)

    童琴; 何振宇; 孙家媛; 李凤岩; 管迅行

    2012-01-01

    [目的]观察帕洛诺司琼在局部晚期鼻咽癌同步放化疗中的止吐疗效.[方法] 54例采用每周顺铂方案进行同步放化疗的局部晚期鼻咽癌患者随机分为帕洛诺司琼组和托烷司琼组,比较两组患者恶心、呕吐及其他不良反应的发生情况.[结果]帕洛诺司琼组和托烷司琼组急性恶心和急性呕吐发生率无明显差异(P>0.05);而延迟性恶心和呕吐发生率帕洛诺司琼组(78.91% 、62.50%)均低于托烷司琼组(88.37% 、80.62%)( P<0.05).其他不良反应包括便秘、腹胀、头痛及头晕,两组无明显差异(P>0.05).[结论]帕洛诺司琼能有效预防局部晚期鼻咽癌同步放化疗引起的恶心呕吐,尤其对迟发性呕吐有较好的治疗效果.%[Purpose] To investigate the efficacy of palonosetron for prevention of concurrent ra-diochemotherapy induced nausea and vomit in patients with locally advanced nasopharyngeal carcinoma. [Methods] Fifty-four cases with locally advanced nasopharyngeal carcinoma were randomly divided into palonosetron group and tropisetron group. The incidence rates of nausea, vomit and other side effects were observed and calculated.[Results] Incidence rates of acute nausea and acute vomit had no significant difference between palonosetron group and tropisetron group (P>0.05), while the incidence rates of chronic nausea and chronic vomit were lower in palonosetron group (78.91% and 62.50%) than that in tropisetron group(88.37% and 80.62%)(P0.05). [Conclusion] Palonosetron is effective for prevention of nausea and vomit induced by concurrent ra-diochemotherapy in patients with locally advanced nasopharyngeal carcinoma, especially for prevention of chronic nausea and vomit.

  12. Incidence of nasopharyngeal carcinoma in Belgrade during the period 1991-2005

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    Nešić Vladimir

    2009-01-01

    Full Text Available Background/Aim. Nasopharyngeal carcinoma (NPC is a relatively rare malignant disease, of which 80 000 individuals become ill around the world annually, which amounts to 0.7% of all carcinomas. The aim of this descriptive study was to analyze NPC incidence in Belgrade (the capital city of Serbia, with about 1.6 million inhabitants during the period 1991-2005. Methods. In data analysis, crude rates age and sex specific rates, and standardized incidence rates were used. Standardization was performed by a direct method, using world population as the standard. Results. In Belgrade, during the observed 15-year-period, the number of new NPC patients totaled 118, of which 86 (72.9% were male and 32 (27.1% were female. The average standardized incidence rate for men was 0.52 per 100 000 and for women 0.16 per 100 000. In both sexes the incidence was very low before 40 years of age. In men, the greatest incidence rate of NPC was in the 50-59 years age group, and in women in those 60 and more years old. Furthermore, undifferentiated carcinoma of nasopharyngeal type was 3.6 times more often in comparison to squamous cell carcinoma. Conclusion. Belgrade belongs to a region with a low incidence rate of NPC. Further investigations are needed to explain higher frequency of undifferentiated carcinoma of nasopharyngeal type than squamous cell carcinoma.

  13. The HLA-DRB1 allele polymorphisms and nasopharyngeal carcinoma.

    Science.gov (United States)

    Yang, Huimin; Yu, Kaihui; Zhang, Ruoheng; Li, Jiatong; Wei, Xiaomou; Zhang, Yuening; Zhang, Chengdong; Xiao, Feifan; Zhao, Dong; Lin, Xuandong; Wu, Huayu; Yang, Xiaoli

    2016-06-01

    Human leukocyte antigen (HLA)-DRB1 has been reported to influence individual's susceptibility to nasopharyngeal carcinoma (NPC) by many studies in recent years; however, these studies provided controversial results. The meta-analysis was thus conducted here to estimate the relationship between HLA-DRB1 polymorphisms and NPC. After an extensive review of journals from various databases (PubMed, the Web of Science, Embase, China National Knowledge Internet (CNKI), and Wanfang Database), 8 out of 69 case-control studies, including 778 cases and 1148 controls, were extracted. The results showed that 4 of 13 polymorphisms allele are statistically significantly associated with NPC, among them, HLA-DRB1*3, HLA-DRB1*9, and HLA-DRB1*10 may increase the risk of NPC while HLA-DRB1*01 has the opposite effect. The pooled odds ratio and 95 % confidence interval (CI) were 1.702 [95 % CI (1.047, 2.765)], 1.363 [95 % CI (1.029, 1.806)], 1.989 [95 % CI (1.042, 3.799)], and 0.461 [95 % CI (0.315, 0.676)], respectively. In a further ethnicity-based subgroup analysis, HLA-DRB1*08, HLA-DRB1*11, and HLA-DRB1*16 were found to be linked with NPC in Asian, Tunisian, and Caucasian, respectively. In Asian, HLA-DRB1*03, 08, and 10 may elevate the risk whereas HLA-DRB1*09 could lower it. In Tunisian, HLA-DRB1*01 and 11 are the protective factors while HLA-DRB1*03 is the only risk factor. In Caucasian, HLA-DRB1*01 and 03 increase the risk and HLA-DRB1*16 lowers it. The most frequent statistically associated gene is found to be HLA-DRB1*03 which has protective influence on Asian and Tunisian. In conclusion, HLA-DRB1*01, DRB1*03, DRB1*09, and DRB1*10 are related with NPC susceptibility, and the association of HLA-DRB1*08, DRB1*11, and DRB1*16 with NPC risk are significantly different in different ethnicities. PMID:27059731

  14. Nosocomial infection during chemoradiotherapy for advanced nasopharyngeal carcinoma: a clinical investigation%同步放化疗治疗局部晚期鼻咽癌并医院感染的临床分析

    Institute of Scientific and Technical Information of China (English)

    林坤花; 江少娜; 李艺江; 黄建丽; 谢源福; 林凤村; 陈伟霖; 卓延红; 陈贵平; 林艺娜; 陈丽民

    2011-01-01

    目的 调查分析局部晚期鼻咽癌行同步放化疗患者医院感染情况,探讨有效的防治措施.方法 回顾性分析55例行同步放化疗鼻咽癌住院患者的医院感染病原体及药物敏感试验.结果 55例患者中发生医院感染38例,感染率为69.01%;医院感染出现的时间为放疗开始后10~49 d,中位时间为29.5 d;感染部位为口咽及鼻咽部黏膜36例,占94.73%,肺部1 例,占2.63%,败血症1例,占2.63%;共分离病原菌47株及带状疱疹病毒1株,以革兰阴性菌最多见,共27株,占56.25%,其次为真菌,共18株,占37.50%;革兰阳性菌2株,占4.17%;革兰阴性菌耐药现象多见,主要对青霉素类、第一二代头孢类抗菌药物耐药;医院感染高危因素为口咽黏膜炎、白细胞减少、激素不合理使用.结论同期放化疗医院感染以革兰阴性菌口咽黏膜感染发生率最高,重视咽拭子培养及药敏检测,加强口腔护理、预防白细胞下降、合理应用糖皮质激素.%OBJECTIVE To investigate the risk factors of nosocomial infection in patients with advanced nasopharyngeal cancer during chemoradiotherapy.METHODS Fifty five cases of advanced nasopharyngeal cancer patients in our hospital were analyzed retrospectively.RESULTS 38 inpatients occured nosocomial infection.The infection rate was 69.01% and isolates of bacteria were found, of which Gram-negative organisms were 56.25 %,epiphyte were 37.50%, Gram-positive ones were 4.17%.The drug susceptibility reports showed that Gramnegative organisms were high drug resistance to penicillins, the first generation cephalosporins and the second generation cephalosporins.The main risk factors were oropharynx mucosal lesion, leukocytopenia, improper application of glucocorticoids.CONCLUSION It is Gram-negative bacteria oropharyngeal mucosal which is the highest rate of nosocomial infection in patients with advanced nasopharyngeal cancer during chemoradiotherapy.It is very important for us to test

  15. Treatment of nasopharyngeal carcinoma using simultaneous modulated accelerated radiation therapy via helical tomotherapy: a phase II study

    Directory of Open Access Journals (Sweden)

    Du Lei

    2016-06-01

    Full Text Available The aim of the study was to evaluate short-term safety and efficacy of simultaneous modulated accelerated radiation therapy (SMART delivered via helical tomotherapy in patients with nasopharyngeal carcinoma (NPC.

  16. A Survey of Researches on Synergy and Toxicity Abatement of Traditional Chinese Medicine in Radiotherapy of Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    刘城林; 刘丽萍; 李佩文

    2001-01-01

    @@ Even though radiotherapy is a therapy of first choice in the treatment of nasopharyngeal carcinoma, its radiotoxicity is often difficult to bear for patients in addition to the unsatisfactory effect in some patients. Therefore, an important problem in the treatment of nasopharyngeal carcinoma is to abate radiotherapeutic toxicity and improve its effect. Some progresses in promoting the effect of radiotherapy and abating its toxicity have been made through application of traditional Chinese medicine (TCM) which is briefly reviewed as follows.

  17. NRP-1 gene expression in nasopharyngeal carcinoma tissue and regulating effect of targeted inhibition of gene expression on cell function

    Institute of Scientific and Technical Information of China (English)

    Xin-Ming Ma

    2016-01-01

    Objective:To studyNRP-1 gene expression in nasopharyngeal carcinoma tissue and the regulating effect of targeted inhibition of gene expression on cell function.Methods:Nasopharyngeal carcinoma tissue, adjacent tissue and normal tissue were collected, and NRP-1 expression levels were detected; nasopharyngeal carcinoma CNE-2 cells were cultured and transfected with NRP-1 siRNA and negative control (NC) siRNA, and the contents of angiogenesis molecules, proliferation-related proteins and invasion-related proteins were detected.Results:NRP-1 protein content, positive cell rate, staining intensity and IHC score in nasopharyngeal carcinoma tissue were higher than those in adjacent tissue and normal tissue; VEGF, bFGF, EGF and ANG-1 contents in culture medium of NRP1-siRNA group were lower than those in NC-siRNA group; Tie-2, EGFR, Livin, Bmi-1, CDK6, CDK4, CCND1, E2F1, LMP1, FN1, MT1-MMP and Fascin expression levels in cells of NRP1-siRNA group were lower than those in NC-siRNA group.Conclusions:NRP-1 expression level significantly increases in nasopharyngeal carcinoma tissue, and NRP-1 can promote nasopharyngeal carcinoma angiogenesis, cell proliferation and invasion.

  18. Target volume and position variations during intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Tan W

    2013-11-01

    Full Text Available Wenyong Tan,* Yanping Li,* Guang Han, Jiaozhen Xu, Xiaohong Wang, Ying Li, Desheng HuDepartment of Radiation Oncology, Hubei Cancer Hospital, Wuhan, People's Republic of China*These authors contributed equally to this workPurpose: Considerable anatomical changes occur during intensity-modulated radiotherapy (IMRT for nasopharyngeal carcinoma (NPC. This study aimed to quantify volumetric and positional variations of the target volume during IMRT.Materials and methods: Twenty patients with locally advanced NPC who received concurrent (13 patients or sequential (seven patients chemoradiotherapy were prospectively recruited and underwent planning computed tomography (CT and six repeat CTs (every five fractions. Each repeat CT was rigidly registered to the planning CT. Gross tumor volume (GTV and elective clinical target volume (CTV were manually delineated on each axial CT image. CTVs of the primary tumor and lymph nodes were expanded with 5 mm margins to corresponding GTVs, with necessary modifications. Volume loss, system and random errors, and the mean and three-dimensional vector displacements were calculated and compared statistically.Results: Volumes of the primary tumor and small (>1 cm, ≤3 cm and large (>3 cm positive neck lymph nodes decreased at a rate of 2.6%, 3.7%, and 3.9% per treatment day, respectively. CTVs of the primary tumor, lymph nodes, and elective region decreased 1.5%, 2.3%, and 0.3% per treatment day, respectively. Average displacements of the GTVs and CTVs were <1.3 mm in all directions. GTVs and CTVs of the large and small lymph nodes shifted medially by 0.8–1.3 and 0.6–1.2 mm, respectively, on average. Average three-dimensional displacements of the GTVs and CTVs were 3.4–4.3 mm and 2.5–3.7 mm, respectively. Volume loss and displacements in most directions were significantly larger in patients receiving concurrent chemoradiotherapy than in those receiving sequential therapy. Volume loss and displacements of the

  19. CASE-CONTROL ASSOCIATION STUDIES OF THE UBAP1 GENE AND NASOPHARYNGEAL CARCINOMA IN SOUTHERN CHINESE

    Institute of Scientific and Technical Information of China (English)

    曾朝阳; 熊炜; 熊芳; 李小玲; 王蓉; 李伟芳; 钱骏; 李桂源

    2003-01-01

    Objective: To identify the relation between nasopharyngeal carcinoma and the human novel gene UBAP1, which is located in the region of minimal heterozygosity deletion at 9pl3.2 and down-expressed in NPC. Methods: Five single nucleotide polymorphisms (SNPs) within UBAP1 gene were analysed by sequencing in 105 NPC patients and 183 control subjects which matched to the NPC cases on age, sex and residence. Results: Significant association was found between NPC with one SNP mark (rs1049557), which is located at 3' non-region of UBAP1 gene; the relative risk of this SNP mark is 1.64 (genotype GG) and 1.31 (genotype CG). Conclusion: The result has proved again that UBAP1 gene may play a certain role in the occurrence and development of nasopharyngeal carcinoma. The SNP mark rs1049557, considering its location, may influence the expression of UBAP1 gene.

  20. Early changes of auditory brain stem evoked response after radiotherapy for nasopharyngeal carcinoma - a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Lau, S.K.; Wei, W.I.; Sham, J.S.T.; Choy, D.T.K.; Hui, Y. (Queen Mary Hospital, Hong Kong (Hong Kong))

    1992-10-01

    A prospective study of the effect of radiotherapy for nasopharyngeal carcinoma on hearing was carried out on 49 patients who had pure tone, impedance audiometry and auditory brain stem evoked response (ABR) recordings before, immediately, three, six and 12 months after radiotherapy. Fourteen patients complained of intermittent tinnitus after radiotherapy. We found that 11 initially normal ears of nine patients developed a middle ear effusion, three to six months after radiotherapy. There was mixed sensorineural and conductive hearing impairment after radiotherapy. Persistent impairment of ABR was detected immediately after completion of radiotherapy. The waves I-III and I-V interpeak latency intervals were significantly prolonged one year after radiotherapy. The study shows that radiotherapy for nasopharyngeal carcinoma impairs hearing by acting on the middle ear, the cochlea and the brain stem auditory pathway. (Author).

  1. Andrographolide Suppresses Proliferation of Nasopharyngeal Carcinoma Cells via Attenuating NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Tao Peng

    2015-01-01

    Full Text Available Andrographolide (Andro has been reported to have anticancer activity in multiple types of cancer due to its capacity to inactivate NF-κB pathway. Previous studies showed the therapeutic potential of targeting NF-κB pathway in nasopharyngeal carcinoma (NPC. However, the anticancer activity of Andro in NPC has not been reported. In this study, we defined the anticancer effects of Andro in NPC and elucidated its potential mechanisms of action. Our results showed that Andro significantly inhibited the proliferation and invasion of NPC cells (P<0.05, resp.. These anticancer activities were associated with cell apoptosis, cell death and induction of cell cycle arrest, and the downregulation of NF-κB target genes. This work provides evidence that NF-κB pathway is a potential therapeutic target and may also be indispensable in the Andro-mediated anticancer activities in nasopharyngeal carcinoma.

  2. Hearing Assessment after Treatment of Nasopharyngeal Carcinoma with CRT and IMRT Techniques

    Directory of Open Access Journals (Sweden)

    Chung-Feng Hwang

    2015-01-01

    Full Text Available Objectives. This study analyzed the long-term hearing loss after treatment of primary nasopharyngeal carcinoma to elucidate its causal factors. Methods. Ninety-two nasopharyngeal carcinoma patients were treated with radiotherapy or chemoradiotherapy. Pure tone audiometry was performed before the therapy and annually up to 9 years after completing treatment. The hearing thresholds were corrected for age-related deterioration and compared to the results without adjusting for age. Results. The mean air and bone conduction threshold with and without correction for age-related deterioration differed significantly 2–9 years after completing radiotherapy p72 cGy resulted in more severe hearing loss than <72 cGy p<0.05. Conclusion. Hearing loss after completing therapy should be corrected for age-related hearing deterioration to reveal the true extent to which the loss is a therapeutic complication. Both the radiation modality used and the dose were significantly associated with hearing loss.

  3. Detecting plasma Epstein-Barr virus DNA to diagnose postradiation nasopharyngeal skull base lesions in nasopharyngeal carcinoma patients: a prospective study

    Institute of Scientific and Technical Information of China (English)

    Fa-Ya Liang; Wei Sun; Ping Han; Xing Lu; Ying-Ni Lian; Xiao-Ming Huang

    2012-01-01

    The diagnosis of postradiation nasopharyngeal skull base lesions in petients with nasopharyngeal carcinoma (NPC) is still a tough problem in clinical practice.An early and accurate diagnosis is important for subsequent management.We prospectively evaluated the diagnostic value of plasma Epstein-Barr virus (EBV) DNA in detecting postradiation nasopharyngeal skull base lesions in NPC patients.From July 2006 to September 2010,90 patients with postradiation NPC (34 women and 56 men; median age:42years) met the selection criteria and were recruited in this study.All postradiation nasopharyngeal skull base lesions were found in the latest magnetic resonance imaging (MRI) examinations before endoscopic surgery,and the nasopharyngeal cavity was normal under flexible nasopharyngoscopy.Plasma EBV DNA detection was performed within 2 weeks before endoscopic surgery.A total of 90 endoscopic operations were successfully performed without any postoperative complications. Recurrences confirmed by postoperative pathology were found in 30 patients.The specificity,positive and negative predictive values of plasma EBV DNA detection were better than those of MRI.In addition,combining plasma EBV DNA detection with MRI improved the specificity and positive predictive values of MRI.Plasma EBV DNA detection followed by MRI would help to diagnose recurrence whereas MRI was unable.These results indicate that plasma EBV DNA is an effective and feasible biomarker for detecting postradiation nasopharyngeal skull base lesions in NPC patients.

  4. Diagnostic imaging in staging, results and follow-up of nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Ninety-seven patients affected with nasopharyngeal carcinoma (NPC) were examined with both conventional and Computed Tomography (CT) to evaluate the involved sites with both methods. CT staging was more accurate, showing involvement in more locations than conventional tomography, so that staging was modified in 23 of 97 patients. Two hundred and seventeen patients treated from 1970 to 1985 were subdivided into group A (111 patients who underwent conventional tomography only) and group B (106 patients examined with CT, from 1978 on). A trend toward more advanced stages at presentation was observed in group B; nevertheless, local control at 5 years was higher in group B (59%) than in group A (42%). The role of Magnetic Resonance (MR) imaging in NPC staging was also evaluated in 30 patients: there was disagreement in 2 cases. Involvement of different structures was shown in 10 of 28 cases with the same CT and MR staging. MR imaging proved a valuable tool in the follow-up as well: in fact, it clarified 12 questionable opacities on CT in a group of 35 followed patients as inflammatory lesions in 10 patients and tumors in 2

  5. Trismus, xerostomia and nutrition status in nasopharyngeal carcinoma survivors treated with radiation.

    Science.gov (United States)

    Chen, Y-J; Chen, S-C; Wang, C-P; Fang, Y-Y; Lee, Y-H; Lou, P-J; Ko, J-Y; Chiang, C-C; Lai, Y-H

    2016-05-01

    The aims of the study were to: (1) examine levels of trismus, xerostomia and nutritional status; (2) compare levels of trismus, xerostomia and nutritional status in patients with nasopharyngeal carcinoma (NPC) receiving different types of radiation modalities; and (3) identify factors related to NPC survivors' risk status for malnutrition and existing malnutrition. A cross-sectional study with consecutive sampling was conducted. NPC survivors were recruited from otolaryngology/oncology outpatient clinics in a medical centre in Northern Taiwan. Study measures included (1) Mandibular Function Impairment Questionnaire, (2) Xerostomia Questionnaire, (3) Mini Nutrition Assessment, (4) Hospital Anxiety and Depression Scale - Depression subscale, and (5) Symptom Severity Scale. A total of 110 subjects were recruited. Those receiving intensity-modulated radiation therapy had less trismus and xerostomia than patients receiving two-dimensional radiation therapy. Patients with female gender, advanced stage, completion of treatments within 1 year, higher levels of depression, more severe trismus and higher symptom severity tended to have malnutrition or were at risk of malnutrition. Trismus and xerostomia are long-term problems in some NPC survivors and may contribute to malnutrition. To better manage a patient's trismus and xerostomia and to enhance nutritional status, clinicians should develop a patient-specific care programme based on careful assessment and targeted measures to improve oral function and insure adequate nutritional intake. PMID:25495287

  6. Clinical Seminar/114th Congress of the Otorhinolaryngological Society of Japan. Advances in diagnosis and treatment of nasopharyngeal carcinoma. History of a half century from the discovery of EB virus

    International Nuclear Information System (INIS)

    The title subject is explained about the carcinoma on anatomical characteristics, its diagnosis/relation to Epstein-Barr virus (EBV) infection, EBV gene expression, and treatment. The cancer, because of its location, easily invades the internal carotid artery and parapharyngeal space through Rosenmuller fossa, resulting in the rapid and extensive metastasis. Diagnosis is based on the histological examination and classified in WHO type-I (keratinized), -II (poorly differentiated) and -III (undifferentiated). The stage is decided by CT and MRI. Type I is minor (several %). Type-II and -III express EBERs (EBV-encoded small RNAs) in their nuclei, which is a mean of diagnosis as well as the serum EBV antibody value. Although 50 years have passed since the discovery of the virus, the cause of its dominant carcinogenesis in rather restricted regions of the world and the pathway of its infection in the nasopharyngeal epithelium are not fully elucidated yet. Authors have shown that an oncogene latent membrane protein-1 (LMP1) is important at the latent phase of EBV infection. EBV-positive types are susceptible to both chemo- and radio-therapy, and the linac is generally used for the latter. Machines for intensity modulated radiotherapy (IMRT) and tomotherapy have been introduced recently, of which efficacy is under examination by a multicenter study. The present standard regimen is radiotherapy+cisplatin/booster fluorouracil (5-FU) in Western countries. In Japan, alternating or simultaneous chemoradiotherapy with cisplatin/5-FU (+docetaxel) is spreading with an improved survival rate. Use of cetuximab against this cancer is awaited for examination, and treatment targeting EBV is also promising. (T.T.)

  7. Development and External Validation of Nomograms for Predicting Survival in Nasopharyngeal Carcinoma Patients after Definitive Radiotherapy

    OpenAIRE

    Lin Yang; Shaodong Hong; Yan Wang; Haiyang Chen; Shaobo Liang; Peijian Peng; Yong Chen

    2015-01-01

    The distant metastasis free survival (DMFS) and overall survival (OS) differ significantly among individuals even within the same clinical stages. The purpose of this retrospective study was to build nomograms incorporating plasma EBV DNA for predicting DMFS and OS of nasopharyngeal carcinoma (NPC) patients after definitive radiotherapy. A total of 1168 non-metastatic NPC patients from two institutions were included to develop the nomograms. Seven and six independent prognostic factors were i...

  8. Identification of epigenetic biomarkers for diagnosis of nasopharyngeal carcinoma and determination of WIF1 functional relevance

    OpenAIRE

    Yang, Xuesong; 楊雪松

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr Virus (EBV).Early diagnosis of NPC will improve the overall survival. However, traditional EBV markers do not perform well in high-risk individuals or for early detection of NPC. Aberrant promoter hypermethylation of tumor suppressor genes (TSGs) is an important epigenetic change in early tumorigenesis. This study identified a promising panel of methylation markers for early detection of NPC and assessed the clinical usefu...

  9. Prognostic value of wait time in nasopharyngeal carcinoma treated with intensity modulated radiotherapy: a propensitymatched analysis

    OpenAIRE

    Chen, Yu-Pei; Mao, Yan-Ping; Zhang, Wen-Na; Chen, Lei; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Zhou, Guan-qun; Guo, Rui; Sun, Ying; Kang, Tie-Bang; Zeng, Mu-Sheng; Ma, Jun

    2016-01-01

    The aim of this study was to determine the prognostic value of wait time from histological diagnosis to primary treatmen for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Between October 2009 and February 2012, a total of 1672 NPC patients were retrospectively analyzed. A cutoff value of > 4 weeks was used to define prolonged wait time. Matched patients according to the wait time were identified using propensity score matching (PSM), which was also used ...

  10. Integrated analysis of microRNA regulatory network in nasopharyngeal carcinoma with deep sequencing

    OpenAIRE

    Wang, Fan; Lu, Juan; Peng, Xiaohong; Jie WANG; LIU, XIONG; Chen, Xiaomei; Jiang, Yiqi; LI, XIANGPING; Zhang, Bao

    2016-01-01

    Background MicroRNAs (miRNAs) have been shown to play a critical role in the development and progression of nasopharyngeal carcinoma (NPC). Although accumulating studies have been performed on the molecular mechanisms of NPC, the miRNA regulatory networks in cancer progression remain largely unknown. Laser capture microdissection (LCM) and deep sequencing are powerful tools that can help us to detect the integrated view of miRNA-target network. Methods Illumina Hiseq2000 deep sequencing was u...

  11. The mechanism of Epstein-Barr virus infection in nasopharyngeal carcinoma cells.

    OpenAIRE

    Lin, C T; Lin, C. R.; Tan, G. K.; Chen, W.; Dee, A. N.; Chan, W Y

    1997-01-01

    To investigate the relationship between Epstein-Barr virus (EBV) and nasopharyngeal carcinoma (NPC) cells, we examined the pathway of EBV infection in NPC cell lines. We used immunolocalization to investigate the EBV receptor (C3d-R) and polymeric immunoglobulin receptor [secretory component (SC) protein]. We incubated IgA anti-EBV and EBV particles with NPC cells and observed the EBV DNA signal by in situ polymerase chain reaction hybridization and polymerase chain reaction plus Southern blo...

  12. Andrographolide Suppresses Proliferation of Nasopharyngeal Carcinoma Cells via Attenuating NF-κB Pathway

    OpenAIRE

    Tao Peng; Min Hu; Ting-Ting Wu; Cen Zhang; Zhe Chen; Shuo Huang; Xu-Hong Zhou

    2015-01-01

    Andrographolide (Andro) has been reported to have anticancer activity in multiple types of cancer due to its capacity to inactivate NF-κB pathway. Previous studies showed the therapeutic potential of targeting NF-κB pathway in nasopharyngeal carcinoma (NPC). However, the anticancer activity of Andro in NPC has not been reported. In this study, we defined the anticancer effects of Andro in NPC and elucidated its potential mechanisms of action. Our results showed that Andro significantly inhibi...

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

    Institute of Scientific and Technical Information of China (English)

    LIUXuekui; ZENGZongyuan; HONGMinghuang; ZHANGAllan; CUINianji; CHENFujing

    2005-01-01

    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.

  14. Radioresistance related genes screened by protein-protein interaction network analysis in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Objective: To discover radioresistance associated molecular biomarkers and its mechanism in nasopharyngeal carcinoma by protein-protein interaction network analysis. Methods: Whole genome expression microarray was applied to screen out differentially expressed genes in two cell lines CNE-2R and CNE-2 with different radiosensitivity. Four differentially expressed genes were randomly selected for further verification by the semi-quantitative RT-PCR analysis with self-designed primers. The common differentially expressed genes from two experiments were analyzed with the SNOW online database in order to find out the central node related to the biomarkers of nasopharyngeal carcinoma radioresistance. The expression of STAT1 in CNE-2R and CNE-2 cells was measured by Western blot. Results: Compared with CNE-2 cells, 374 genes in CNE-2R cells were differentially expressed while 197 genes showed significant differences. Four randomly selected differentially expressed genes were verified by RT-PCR and had same change trend in consistent with the results of chip assay. Analysis with the SNOW database demonstrated that those 197 genes could form a complicated interaction network where STAT1 and JUN might be two key nodes. Indeed, the STAT1-α expression in CNE-2R was higher than that in CNE-2 (t=4.96, P<0.05). Conclusions: The key nodes of STAT1 and JUN may be the molecular biomarkers leading to radioresistance in nasopharyngeal carcinoma, and STAT1-α might have close relationship with radioresistance. (authors)

  15. Effect of Yupingfeng granules on HA and Foxp3~+ Treg expression in patients with nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ji-Hong; Huang; Zhong-Lin; Mu; Xue-Jun; Zhou; Qiong-Lian; Huang; Feng; Gao; Xi; Chen

    2015-01-01

    Objective: To investigate the effect of Yupingfeng on hyaluronic acid(HA) and Foxp3+ Treg in patients with nasopharyngeal carcinoma. Methods: A total of 58 cases of nasopharyngeal carcinoma were divided into two groups, 30 cases in the treatment group, 28 cases in the control group. Patients in two groups were treated with synchronous radiotherapy and chemotherapy treatment, the treatment group was treated with the Yupingfeng granules through oral administration, 10 g/time, tid for 2 courses. The serum Foxp3+ Treg markers of each group were detected by flow cytometry assay before treatment and after treatment, and the level of HA in serum was detected by radio immunoassay. Results: After radiotherapy and chemotherapy, the contents of Foxp3+ Treg and HA were significantly decreased in two groups(P<0.05), and the decrease of treatment group was more significantly(P<0.01). Correlation analysis showed positive correlation between Foxp3+ Treg and HA(P<0.05). After treatment, the incidence of side effects in two groups was significantly decreased. And there was significant difference between two groups(P<0.05). Conclusions: Combined chemotherapy and radiotherapy with Yupingfeng treatment can decrease the levles of Foxp3+ Treg and HA in nasopharyngeal carcinoma patients. Yupingfeng can also effectively reduce the side effect due to radiation and chemotherapy.

  16. Effect of Yupingfeng granules on HA and Foxp3+ Treg expression in patients with nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ji-Hong Huang; Zhong-Lin Mu; Xue-Jun Zhou; Qiong-Lian Huang; Feng Gao; Xi Chen

    2015-01-01

    Objective:To investigate the effect of Yupingfeng on hyaluronic acid (HA) and Foxp3+Treg in patients with nasopharyngeal carcinoma.Methods:A total of 58 cases of nasopharyngeal carcinoma were divided into two groups, 30 cases in the treatment group, 28 cases in the control group. Patients in two groups were treated with synchronous radiotherapy and chemotherapy treatment, the treatment group was treated with the Yupingfeng granules through oral administration, 10 g/time, tid for 2 courses. The serum Foxp3+ Treg markers of each group were detected by flow cytometry assay before treatment and after treatment, and the level of HA in serum was detected by radio immunoassay.Results:After radiotherapy and chemotherapy, the contents of Foxp3+ Treg and HA were significantly decreased in two groups (P<0.05), and the decrease of treatment group was more significantly (P<0.01). Correlation analysis showed positive correlation between Foxp3+ Treg and HA (P<0.05). After treatment, the incidence of side effects in two groups was significantly decreased. And there was significant difference between two groups (P<0.05).Conclusions:Combined chemotherapy and radiotherapy with Yupingfeng treatment can decrease the levles of Foxp3+ Treg and HA in nasopharyngeal carcinoma patients. Yupingfeng can also effectively reduce the side effect due to radiation and chemotherapy.

  17. Smoking is a poor prognostic factor for male nasopharyngeal carcinoma treated with radiotherapy

    International Nuclear Information System (INIS)

    Background and Purpose: To evaluate the effect of smoking on prognosis of male nasopharyngeal carcinoma by comparing the treatment outcomes between smokers and non-smokers. Materials and Methods: A total of 2450 nasopharyngeal carcinoma patients were enrolled, including 1865 male patients. Matching was performed between smokers and non-smokers in male patients according to age, UICC clinical stage, T stage, N stage and treatment. Survival outcomes were compared using Kaplan–Meier analysis and Cox regression. Smoking index was calculated by multiplying cigarette packs per day and smoked time (year). Results: In male patients, smokers had significantly lower 5-year overall survival (70.1% vs. 77.5%, P < 0.001) and locoregional recurrent free survival (76.8% vs.82.4%, P = 0.002) compared with non-smokers. Matched-pair analysis showed that smokers kept a high risk of death compared with non-smokers (HR = 2.316, P < 0.001). High degree of smoking index (>15 pack-years) had a poor effect on overall survival (HR = 1.225, P = 0.016). When smoking index was more than 45 and 60 pack-years, the risk for death increased to 1.498 and 1.899 fold compared with non-smokers (P = 0.040, 0.001), respectively. Conclusions: Smoking was a poor prognostic factor for male nasopharyngeal carcinoma. The heavier the patients smoked, the poorer prognosis they suffered

  18. Glutamate Decarboxylase 1 Overexpression as a Poor Prognostic Factor in Patients with Nasopharyngeal Carcinoma

    Science.gov (United States)

    Lee, Yi-Ying; Chao, Tung-Bo; Sheu, Ming-Jen; Tian, Yu-Feng; Chen, Tzu-Ju; Lee, Sung-Wei; He, Hong-Lin; Chang, I-Wei; Hsing, Chung-Hsi; Lin, Ching-Yih; Li, Chien-Feng

    2016-01-01

    Background: Glutamate decarboxylase 1 (GAD1) which serves as a rate-limiting enzyme involving in the production of γ-aminobutyric acid (GABA), exists in the GABAergic neurons in the central nervous system (CNS). Little is known about the relevance of GAD1 to nasopharyngeal carcinoma (NPC). Through data mining on a data set derived from a published transcriptome database, this study first identified GAD1 as a differentially upregulated gene in NPC. We aimed to evaluate GAD1 expression and its prognostic effect on patients with early and locoregionally advanced NPC. Methods: We evaluated GAD1 immunohistochemistry and performed an H-score analysis on biopsy specimens from 124 patients with nonmetastasized NPC receiving treatment. GAD1 overexpression was defined as an H score higher than the median value. The findings of such an analysis are correlated with clinicopathological behaviors and survival rates, namely disease-specific survival (DSS), distant-metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) rates. Results: GAD1 overexpression was significantly associated with an increase in the primary tumor status (p < 0.001) and American Joint Committee on Cancer (AJCC) stages III-IV (p = 0.002) and was a univariate predictor of adverse outcomes of DSS (p = 0.002), DMeFS (p < 0.0001), and LRFS (p = 0.001). In the multivariate comparison, in addition to advanced AJCC stages III-IV, GAD1 overexpression remained an independent prognosticator of short DSS (p = 0.004, hazard ratio = 2.234), DMeFS (p < 0.001, hazard ratio = 4.218), and LRFS (p = 0.013, hazard ratio = 2.441) rates. Conclusions: Our data reveal that GAD1 overexpression was correlated with advanced disease status and may thus be a critical prognostic indicator of poor outcomes in NPC and a potential therapeutic target to facilitate the development of effective treatment modalities. PMID:27698909

  19. Endoscopic Coblation for the treatment of advanced juvenile nasopharyngeal angiofibroma.

    Science.gov (United States)

    Pierson, Brandon; Powitzky, Rosser; Digoy, G Paul

    2012-10-01

    We present 2 cases of advanced juvenile nasopharyngeal angiofibroma (JNA) to illustrate the advantages of endoscopic Coblation-assisted resection of intranasal extensions of these masses. Both patients-an 11-year-old boy and a 14-year-old boy-presented with a large, extensive mass (Radkowski stage IIIb and Fisch stage IVb in both cases). After embolization was performed on each patient, his JNA was partially ablated via an endoscopic approach with the Coblator II Surgery System with an EVac Xtra Plasma Wand in conjunction with an image-guided navigation system. Both patients experienced resolution of their nasal obstruction with removal of the intranasal extension of the tumor. Coblation allowed for a controlled debulking of the tumors with less blood loss and without the need for multiple instruments. To the best of our knowledge, our report is one of the first to describe image-guided endoscopic Coblation of advanced JNA tumors. Future studies in adequately sized populations are needed to determine the safety and effectiveness of Coblation-assisted endoscopic removal of both advanced and lower-stage JNAs.

  20. Identification of a recurrent transforming UBR5–ZNF423 fusion gene in EBV-associated nasopharyngeal carcinoma

    OpenAIRE

    Chung, Grace TY; Lung, Raymond WM; Hui, Angela BY; Yip, Kevin YL; Woo, John KS; Chow, Chit; Tong, Carol YK; Lee, Sau-Dan; Yuen, Jessie WF; Lun, Samantha WM; Tso, Ken KY; Wong, Nathalie; Tsao, Sai-Wah; Yip, Timothy TC; Busson, Pierre

    2013-01-01

    Nasopharyngeal carcinoma (NPC) is a distinct type of head and neck cancer which is prevalent in southern China, south-east Asia and northern Africa. The development and stepwise progression of NPC involves accumulation of multiple gross genetic changes during the clonal expansion of Epstein–Barr virus (EBV)-infected nasopharyngeal epithelial cell population. Here, using paired-end whole-transcriptome sequencing, we discovered a number of chimeric fusion transcripts in a panel of EBV-positive ...

  1. Hyperfractionated radiation therapy for locoregionally advanced nasopharyngeal cancer

    International Nuclear Information System (INIS)

    The purpose of this study is to clarify the efficacy and toxicity of hyperfractionated radiation therapy (RT) for patients with nasopharyngeal cancer (NPC). Twenty-two patients with NPC treated at our hospital between April 1994 and December 2002 were the subjects of this study. They received hyperfractionated RT with a fraction size of 1.2 Gy, with a median tumor dose of 72 Gy (range 64.8-80.4). During this study period, our institutional strategy for locoregionally advanced NPC included neoadjuvant or concurrent chemotherapy combined with hyperfractionated RT, and 17 patients received some forms of cisplatin-containing chemotherapy. With a median follow-up of 59 months, the estimated 5-year disease-free survival rate and overall survival rate were 72.7 and 85.2%, respectively. Acute hematological toxicities were acceptable and manageable. However, >50% of patients required nutritional support, and experienced severe pharyngitis, skin reaction and body weight loss. With regard to late sequelae, one patient developed grade 3 osteomyelitis, and one patient each developed grade 4 passage disturbance and laryngeal edema. No patients experienced any grades of optic nerve injury or temporal lobe necrosis. Hyperfractionated RT using 1.2 Gy per fraction, for a total dose of 72 Gy, produces a comparable treatment outcome. Although deleterious neurological sequelae were not observed in this study, caution should be exercised regarding other late sequelae, such as osteomyelitis and passage disturbance. (author)

  2. Habitual consumption of soy products and risk of nasopharyngeal carcinoma in Chinese adults: a case-control study.

    Directory of Open Access Journals (Sweden)

    Yuan-ting Liu

    Full Text Available BACKGROUND AND OBJECTIVES: Many studies have shown a negative association between the consumption of soy products and the risk of some cancers, but little is known about the effect of soy consumption on nasopharyngeal carcinoma. We assessed the association between the consumption of soy products on nasopharyngeal carcinoma risk in Chinese individuals. METHODS: This case-control study included 600 (448 males and 152 females incident cases of nasopharyngeal carcinoma, and an equal number of controls, matched according to gender, age (± 3 y and household type to the nasopharyngeal carcinoma cases. All subjects were recruited from hospitals in Guangzhou, China. A face-to-face interview was conducted with each study individual to collect general information and habitual dietary intake using a 78-item quantitative food-frequency questionnaire. Odds ratios and their 95% confidence intervals were estimated using conditional logistic regression analyses. RESULTS: The median intakes of soy foods (in protein were 0.5/0.5, 1.4/1.7, 2.7/3.3 and 6.1/7.7 (male/female g/d in the quartiles 1 to 4. Both univariate and multivariate analyses showed no significant association between the consumption of soy proteins or soy isoflavones and the risk of nasopharyngeal carcinoma. The adjusted odds ratios (95% confidence intervals between extreme quartiles were 0.97 (0.66-1.45 for soy proteins and 0.97 (0.66-1.42 for total isoflavones. Null associations were also observed between intake of the individual isoflavones daidzein, genistein and glycitein and NPC risk, with adjusted odds ratios for the extreme quartiles ranging between 0.73 and 1.23. CONCLUSION: Habitual consumption of soy products had no significant effect on the risk of nasopharyngeal carcinoma in Chinese adults with a relatively low intake.

  3. Matrix metalloproteinase 13-containing exosomes promote nasopharyngeal carcinoma metastasis.

    Science.gov (United States)

    You, Yiwen; Shan, Ying; Chen, Jing; Yue, Huijun; You, Bo; Shi, Si; Li, Xingyu; Cao, Xiaolei

    2015-12-01

    Nasopharyngeal cancer (NPC) is an endemic type of head and neck cancer with a high rate of cervical lymph node metastasis. Metastasis is the major cause of death in NPC patients. Increasing evidence indicates that exosomes play a pivotal role in promoting cancer metastasis by enhancing angiogenesis and ECM degradation. Matrix metalloproteinase 13 is an important kind of matrix proteinase that is often overexpressed in various tumors and increases the risk of metastasis. However, little is known about the potential role of MMP13-containing exosomes in NPC. In this study, we found that MMP13 was overexpressed in NPC cells and exosomes purified from conditioned medium (CM) as well as NPC patients' plasma. Transwell analysis revealed that MMP13-containing exosomes facilitated the metastasis of NPC cells. Furthermore, siRNA inhibited the effect of MMP13-containing exosomes on tumor cells metastasis as well as angiogenesis. The current findings provided novel insight into the vital role of MMP13-containing exosomes in NPC progression which might offer unique insights for potential therapeutic strategies for NPC progressions.

  4. Nasopharyngeal carcinoma in the Northeastern states of India

    Institute of Scientific and Technical Information of China (English)

    Amal Chandra Kataki; Malcolm J. Simons; Ashok Kumar Das; Kalpana Sharma; Narinder Kumar Mehra

    2011-01-01

    Nasopharyngeal cancer (NPC) is a rare disease in most parts of the world, except for Southeast Asia, some parts of North Africa and the Arctic. It is mostly seen in people of Chinese origin. In India, NPC is also rare, except for the Hill States of Northeast India, particularly Nagaland, Manipur, and Mizoram. The striking feature of NPC in Northeast India is that the incidence ranges over the complete spectrum from the lowest (as 0.5/100 000 to 2.0/100 000 among Caucasoid) to the highest (as ~20/100 000 among Cantonese/Zhongshan dialect Chinese). The age-adjusted rate of NPC in Kohima district of Nagaland State is 19.4/100000, which is among the highest recorded rates. By contrast, in Assam, one of the so called Hill States but not itself a hilly state, NPC is much less common. The Northeastem region is distinguished by a preponderance of the Tibeto-Burman languages and by variable mongoloid features among peoples of the region. The nature of the migratory populations who are presumed to be bearers of the mongoloid risk is unknown, but these NPC occurrence features provide an outstanding opportunity for NPC risk investigation, such as that of the hypothesis of Wee et al. for westward displacement of Chinese aborigines following the last glacial maximum.

  5. Prognostic significance of tumor volume in locally recurrent nasopharyngeal carcinoma treated with salvage intensity-modulated radiotherapy.

    Directory of Open Access Journals (Sweden)

    WeiWei Xiao

    Full Text Available INTRODUCTION: To evaluate the prognostic value of gross tumor volume (TV in patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma. METHODS: Between 2001 and 2012, 291 consecutive patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma underwent salvage IMRT were retrospectively reviewed. The correlations between TV and recurrent T classification were analyzed. Survival analyses were performed. Receiver operating characteristic (ROC curves were calculated to identify cut-off point of TV. The Akaike information criterion and Harrell's concordance index (c-index were utilized to test the prognostic value. RESULTS: The median TV significantly increased with advancing recurrent T classification (P<0.001. The 5-year overall survival rate was 33.2% for the entire cohort. On multivariate analysis, TV was an independent negative prognostic factor for distant metastasis-free survival (hazard ratio =1.013, P =0.003, overall survival (hazard ratio = 1.015, P<0.001 and toxicity-related death (hazard ratio = 1.014, P<0.001. The 5-year overall survival rates were 63.1% and 20.8% for patients with a TV < 22 cm3 and TV ≥22 cm3, respectively (P < 0.001. In patient with TV <22 cm3, locoregional failure is the leading cause of death. In patients with TV≥22 cm3, distant metastasis rate is higher and occurred within short term after local recurrence; meanwhile, radiation-induced injuries became more common and led to half of deaths in this group. The Akaike information criterion and c-index analyses indicated that the predictive ability of recurrent T classification improved when combined with TV. CONCLUSIONS: Our data suggests TV is a significant prognostic factor for predicting the distant metastasis, overall survival and toxicity-related death of patients with locally recurrent, nonmetastatic nasopharyngeal carcinoma after salvage IMRT. TV should be considered when designing personalized salvage treatments for these patients

  6. Intensity-Modulated Radiation Therapy in the Salvage of Locally Recurrent Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Qiu Sufang [Department of Radiation Oncology, Cancer Hospital of Fujian Medical University, Fuzhou, Fujian (China); Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore (Singapore); Lin Shaojun [Department of Radiation Oncology, Cancer Hospital of Fujian Medical University, Fuzhou, Fujian (China); Tham, Ivan W.K. [Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore (Singapore); Pan Jianji; Lu Jun [Department of Radiation Oncology, Cancer Hospital of Fujian Medical University, Fuzhou, Fujian (China); Lu, Jiade J., E-mail: mdcljj@nus.edu.sg [Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore (Singapore)

    2012-06-01

    Purpose: Local recurrences of nasopharyngeal carcinoma (NPC) may be salvaged by reirradiation with conventional techniques, but with significant morbidity. Intensity-modulated radiation therapy (IMRT) may improve the therapeutic ratio by reducing doses to normal tissue. The aim of this study was to address the efficacy and toxicity profile of IMRT for a cohort of patients with locally recurrent NPC. Methods and Materials: Between August 2003 and June 2009, 70 patients with radiologic or pathologically proven locally recurrent NPC were treated with IMRT. The median time to recurrence was 30 months after the completion of conventional radiation to definitive dose. Fifty-seven percent of the tumors were classified asrT3-4. The minimum planned doses were 59.4 to 60 Gy in 1.8- to 2-Gy fractions per day to the gross disease with margins, with or without chemotherapy. Results: The median dose to the recurrent tumor was 70 Gy (range, 50-77.4 Gy). Sixty-five patients received the planned radiation therapy; 5 patients received between 50 and 60 Gy because of acute side effects. With a median follow-up time of 25 months, the rates of 2-year locoregional recurrence-free survival, disease-free survival, and overall survival were 65.8%, 65.8%, and 67.4%, respectively. Moderate to severe late toxicities were noted in 25 patients (35.7%). Eleven patients (15.7%) had posterior nasal space ulceration, 17 (24.3%) experienced cranial nerve palsies, 12 (17.1%) had trismus, and 12 (17.1%) experienced deafness. Extended disease-free interval (relative risk 2.049) and advanced T classification (relative risk 3.895) at presentation were adverse prognostic factors. Conclusion: Reirradiation with IMRT provides reasonable long-term control in patients with locally recurrent NPC.

  7. A clinical staging system and treatment guidelines for maxillary osteoradionecrosis in irradiated nasopharyngeal carcinoma patients

    International Nuclear Information System (INIS)

    Purpose: To develop a clinical staging system for maxillary osteoradionecrosis (ORN) in irradiated nasopharyngeal carcinoma (NPC) patients. Methods and Materials: The data of maxillary ORN cases among 1,758 irradiated NPC patients were analyzed. A staging system based on the degrees of bone exposure (E), infection (I), and bleeding (B) was developed. Correlations between various clinical parameters and stages of maxillary ORN and relationships between treatment modalities and outcomes at each stage were evaluated. Cumulative success of treatment and risk factors that affect treatment outcomes were analyzed. Results: The incidence of maxillary ORN was 2.7% (48/1,758). TNM stage of NPC (p < 0.001), radiation dose (p = 0.029), and tooth extraction (p < 0.001) appeared to have significant influences on disease severity. Success rates between conservative therapy and surgical treatment were not significantly different for Stage I ORN but differed significantly for Stage II (p = 0.013) and Stage III (p = 0.008) lesions. Grade 3 infection and bleeding significantly jeopardized treatment success (p = 0.043 and 0.015, respectively). The risk ratios of treatment failure for Grade 3 infection and bleeding were 2.523 (p = 0.034) and 3.141 (p = 0.027), respectively. Conclusions: More serious maxillary ORN tended to occur in cases with more advanced NPC, higher radiation dose, and history of tooth extraction. Surgical treatment was usually required in Stage II and III ORN. The grades of infection and bleeding are important factors in guidance of treatment and prediction of outcomes

  8. FREQUENT ALLELIC IMBALANCE AND CYTOGENETIC DELETION ON THE SHORT ARM OF CHROMOSOME 1 IN NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    黄铁军; 黄必军; 张林杰; 梁启万; 方燕

    2004-01-01

    Objective: To construct a fine map of the loss of chromosome lpter-p36.11 region in nasopharyngeal carcinoma (NPC) using PCR-LOH technique. Methods:DNA extracted from separated cancerous cells and their mated noncancerous lymphocytes from 47 cases of NPC biopsies were analyzed by means of PCR-LOH to detect 20loci spanning chromosome lpter-p36.11 region in NPC.Results: In 47 NPC cases, 37 (82.2%) cases showed at least one loci LOH. The highest frequency of less of heterozygosity (LOH) at all 20 loci was found at loci DIS234(50. 0%) on lp36.13 and loci DIS2644 (37.5%) on lp36.22.There was a statistically significant difference betweenDIS234 LOH frequency (60%, 9/15) in early stage and that (50. 0%, 8/16) in advanced stage (P>0.05). Of all 20 STSs (sequence tqgged-site, STS), DIS243 (37.5%) and DIS199(30.2%) showed the highest frequency of MI (microsatellite instability) on lp36.33 and lp36.21, respectively. In addition,several cases showed a contiguous stretch of allelic loss in a different level. Conclusion: Two minimal deletion regions (MDR) on the short arm of chromosome 1 were seated at lp36.13 (DIS234, 2.0 cm) and lp36.22 (DIS436-DIS2644, 6.3cm) respectively, indicating that one or more candidate tumor suppressor gene (TSG) in the two regions may be involved in NPC pathogenesis in an early clinical stage.

  9. Local failure patterns for patients with nasopharyngeal carcinoma after intensity-modulated radiotherapy

    International Nuclear Information System (INIS)

    To investigate the clinical feature and the local failure patterns after intensity-modulated radiotherapy for nasopharyngeal carcinoma. Between March 2007 and July 2009, 710 patients with nasopharyngeal carcinoma were treated with intensity-modulated radiotherapy. The magnetic resonance imagings obtained at recurrence were registered with the original planning computed tomography for dosimetry analysis. With a median follow-up of 38 months, 34 patients have developed local recurrence (32 cases valid). The incidence of invasion to nasopharynx, parapharyngeal space and the retropharyngeal space by the primary tumors was 100%, 75.0% and 62.5%, respectively, but 78.1%, 34.4% and 21.9% at recurrence, respectively. The rate of invasion to ethmoid sinus was 3.1% by the primary tumors but 28.1% at recurrence (p = 0.005). The topographic analysis of the local failure patterns showed 'central' in 16 patients; 'marginal' in 9; and 'outside' in 7. The median volumes of primary gross tumor were 45.84 cm3 in the central failure group, 29.44 cm3 in the marginal failure group, and 21.52 cm3 in the outside failure group, respectively (p = 0.012), and the median volumes of primary clinical target1 were 87.28 cm3, 61.90 cm3 and 58.74 cm3 in the three groups, respectively (p = 0.033). In patients with nasopharyngeal carcinoma treated with intensity-modulated radiotherapy, the recurrent tumors had their unique characteristic and regularity of invasion to adjacent structures. 'Central' failure was the major local failure pattern. The volumes of primary gross tumor and clinical target1 were significantly correlated with recurrent patterns. Employ more aggressive approaches to tumor cells which will be insensitive to radiotherapy may be an effective way to reduce the central failure

  10. 鼻咽癌放疗后大出血43例%Clinical analysis of 43 cases nasopharyngeal massive hemorrhage with nasopharyngeal carcinoma after radiotherapy

    Institute of Scientific and Technical Information of China (English)

    蒋军; 张宁

    2010-01-01

    目的 探讨鼻咽癌放疗后大出血的相关因素及预防措施.方法 回顾性分析43例鼻咽癌放疗后大出血的临床资料.结果 43例中,肿瘤广泛侵及颅底39例(90.7%),继往曾接受高剂量放疗36例(83.7%),接受后程大分割放疗10例(23.3%),伴有糖尿病者13例(30.2%).结论 肿瘤发生部位是鼻咽癌大出血最主要的因素;放疗剂量、分割方式、糖尿病则是次要的相关因素.对于伴有上述高危因素的患者,应尽量采用超分割,控制总剂量、血糖等.积极地预防比抢救更重要.%Objective To investigate the related factors and preventive measures of nasopharyngeal massive hemorrhage in patients with nasopharyngeal carcinoma after radiotherapy. Methods Clinical data of 43 nasopharyngeal massive hemorrhage patients with nasopharyngeal carcinoma after radiotherapy were analyzed retrospectively. Results Thirty-nine cases(90.7 %) had abroad skull base invasion due to tumor, 36 cases (83.7%) received high dose of radiation, and 13 cases (30.2 %) were accompanied by diabetes. Conclusion Tumor location is the major factor for nasopharyngeal massive hemorrhage, while radiation dosage, fractionation patterns and diabetes are the secondary factors. The measures in cluding hyperfractionation, overall dose control and blood sugar regulation should be taken for the high risk patients. Prevention is more important than salvage.

  11. Reirradiation as therapeutical choice in the local failure of nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    In the local failure of nasopharyngeal carcinoma, on previouysly irradiated patients, reirradiation is a therapeutical choice. Different techniques of external irradiation and brachitherapy that have been used have brought about satisfactory results. We set out our results in 10 cases of salvage treatment using external or intracavitary radiotherapy on their own or combinated. In intracavitary radiotherapy groups (alone or combinated with external beam irradiation) there has been no local failure. In the exclusively external radiotherapy groups local failure has been registrated in 2 of 4 patients. Nowadays after an average control period of 5.5 years, 6 of 10 patients are alive and free of disease. (Author)

  12. Relation between parthenolideinduced cytotoxicity and COX—2 expression in nasopharyngeal carcinoma cell

    Institute of Scientific and Technical Information of China (English)

    LinYL; OngCN

    2002-01-01

    To investigate the potential anti-tumor effects and its relative its relative mechanism of active component in chrysanthemum,on human nasopharyngeal carcinoma(NPC).Parthenolide(PN) was used as tested substance and exposed to NPC cell lines,CNE1 and CNE2.Cell toxicity indexes and cyclooxygenase-2(COX-2) expression were determined.Results showed that in CNE1 cells,with high level COX-2,there were significant cytotoxicities after PN-treated.However,there were not inducible effects on CNE2 cells with low level COX-2.It was indicated that PN could induce cytotoxicity in NPC cell,which correlated with its intracellular COX-2 expression.

  13. Dose escalated radiotherapy for T1 and T2 nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Nasopharyngeal carcinoma (NPC) is most prevalent in the Guangzhou province in southern China, in Hong Kong and in Singapore. It also occurs in Europe and North America, partly due to its epidemiological association with the woodworking and shoe manufacturing industry. Because of its anatomical location, i.e. so close to vital organs at risk, such as the brain stem and eyes, the technique of radiotherapy and dose/fractionation prescription is of extreme importance. This communication describes our experience with dose escalation radiotherapy for stages T1 and T2 of NPC. (author)

  14. Mitochondrial DNA Haplogroup Confers Genetic Susceptibility to Nasopharyngeal Carcinoma in Chaoshanese from Guangdong, China

    OpenAIRE

    Sheng-Ping Hu; Ju-Ping Du; De-Rui Li; Yong-Gang Yao

    2014-01-01

    Recent studies have shown association of mtDNA background with cancer development. We analyzed mitochondrial DNA (mtDNA) control region variation of 201 patients with nasopharyngeal carcinoma (NPC) and of 201 normal controls from Chaoshan Han Chinese to discern mtDNA haplogroup effect on the disease onset. Binary logistic regression analysis with adjustment for gender and age revealed that the haplogroup R9 (P = 0.011, OR = 1.91, 95% CI = 1.16-3.16), particularly its sub-haplogroup F1 (P = 0....

  15. Expression of Human Leukocyte Antigen G is associated with Prognosis in Nasopharyngeal Carcinoma

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    Man-Bo Cai, Hui-Qiong Han, Jin-Xin Bei, Chao-Chun Liu, Jin-Ju Lei, Qian Cui, Qi-Sheng Feng, Hai-Yun Wang, Jia-Xing Zhang, Yi Liang, Li-Zhen Chen, Tie-Bang Kang, Jian-Yong Shao, Yi-Xin Zeng

    2012-01-01

    Full Text Available Human leukocyte antigen G (HLA-G has multiple immune regulatory functions including the induction of immune tolerance in malignancies. The roles of HLA-G have not been investigated in nasopharyngeal carcinoma (NPC. This study is aimed to evaluate the role of HLA-G as prognostic factor for NPC patients as well as its role in the immune regulation. Western assays showed high HLA-G expression in NPC cell lines, but low in the immortalized nasopharyngeal epithelial cell line NP69. HLA-G protein was further detected in 79.2% of 552 NPC specimens with immunohistochemistry (IHC, but not in normal nasopharyngeal epithelium tissue. Moreover, high expression of HLA-G predicted poor survival of NPC patients and positively correlated with tumor N classification and recurrence or metastasis. Multivariate analysis indicated that HLA-G was an independent and unfavorable prognostic factor. Furthermore, the presence of CD68+macrophages and IL-10 were also examined, which are two prognostic markers of NPC and important factors for regulating immune surveillance. The correlations of HLA-G with these two immune factors were revealed in NPC tissues. Taken together, our results suggest that HLA-G is an independent biomarker for NPC prognosis, and HLA-G might contribute to NPC progression, which might jointly regulate immune surveillance in NPC together with macrophages and IL-10.

  16. Induction of cytotoxic T lymphocyte respones in vivo after immunotherapy with dendritic cells in patients with nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    JIAN MIN ZUO; LING ZHOU; ZHI JIAN CHEN; DE RUI LI; QI WANG; JIONG YU CHEN; ZHAN WANG; SHU QING YE; YI ZENG

    2006-01-01

    The aim of the present study was to determine the efficacy of immunotherapy with dendritic cells to elicit EBV-specific CTL-immunity in advanced cases of EBV-positive patients with nasopharyngeal carcinoma (NPC) and to determine the safety and toxicity of this preparation. Nine cases of histologically confirmed patients with NPC undergoing treatment with radiological therapy were enrolled in this study. Dendritic cells, generated in vitro from blood monocytes of patients were cultured and matured with cytokines and then infected with recombinant adenovirus vaccine containing EBV-latent membrane protein-2 (Ad-LMP2). On 9 days' cultivation of cells, the matured DCs were harvested, irradiated with 60Co and then injected intradermally to patients with NPC. The injections were performed 3 times totally. After immunization, the CTL responses were assayed by means of cytotoxicity and epitope-specific IFN-γ production. The results of this trial showed that all patients could tolerate this kind of treatment without any side effect, during which marked increase of LMP2-specific CTL-responses could be demonstrated in 5 patients of this group. And the level of IgA/VCA antibody decreased in 8 of 9 patients, thus accounting for a better prognosis for these patients. All patients will be followed up for another one year. At least, the present work shows that intradermal vaccination with autologous DCs infected with recombinant Ad-LMP2 adenovirus is a safe procedure in NPC patients, in which this procedure can enhance the LMP2-specific CTL responses in patients. These data are encouraging to develop more effective vaccine strategies for the treatment of nasopharyngeal carcinoma.

  17. Curcumin treatment alters ERK-1/2 signaling in vitro and inhibits nasopharyngeal carcinoma proliferation in mouse xenografts.

    Science.gov (United States)

    Xie, Yi-Qiang; Wu, Xian-Bo; Tang, Song-Qi

    2014-01-01

    Curcumin, a plant phenol, has been used for centuries in traditional medicines for its anti-inflammatory and anti-neoplastic properties. The compound is believed to act on a range of proteins involved in cell cycle regulation. In this study, the effect of curcumin on ERK-1/2 pathway protein expression and on proliferation of nasopharyngeal carcinoma cells was investigated. CNE-2Z nasopharyngeal carcinoma cells were cultured with 10, 20, 40, or 80 μM curcumin for 24 h before proliferation was assessed by MTT colorimetry. Cell proliferation was increasingly inhibited as the concentration of curcumin increased (PERK-1/2, MMP-9, and TIMP-1 was altered following curcumin treatment, also in a dose-dependent manner. Expression of p-ERK-1/2 and MMP-9 decreased, while expression of TIMP-1 increased (PERK-1/2 signaling pathway. Therefore, curcumin warrants further investigation as a potential treatment for nasopharyngeal cancer.

  18. DNA COPY PROFILE IN NASOPHARYNGEAL CARCINOMA AND ITS CORRELATION WITH CLINICAL STAGING

    Institute of Scientific and Technical Information of China (English)

    鄢践; 方嬿; 梁启万; 曾益新

    2001-01-01

    To detect genetic alterations in nasopharyngeal carcinoma (NPC) in Cantonese, the population with the highest incidence of NPC, and to correlate the findings with clinical staging. Methods: Comparative genomic hybridization (CGH) was performed on 35 primary nasopharyngeal carcinomas and a nonparametric χ2 test was used to analyze relationship between chromosome changes and clinical staging. Results: The identified common chromosomal alterations in NPC included gain of chromosomes 12q (21 cases, 60%), 4q (19cases, 43%), 3q (18 cases, 51%), 1q (15 cases, 43%),8q (14 cases, 40%), and 2q (12 cases, 30%). The most frequently detected loss of chromosomal materials involved chromosome 1p (24 cases, 69%), chromosome 3p (21 cases, 60%), 11q (20 cases, 57%), 14q (18 cases, 51%), 16q (14 cases, 40%), 13(12 cases, 34%), and 9p(11 cases, 31%). The high frequency (>50%) 4q gain and 1p loss were novel findings. Compared by nonparametric χ2 test, gains on 12q and 8q were found mainly in stages Ⅲ/Ⅳ and there were significant differences between two clinical stage groups ( stagesⅠ/Ⅱvs stages Ⅲ/Ⅳ). Conclusions: Current analysis has revealed a comprehensive profile of the chromosomal regions showing DNA copy number changes, which may harbor oncogenes or tumor suppressor genes involved in the development of primary NPC.

  19. Effect of Quercetin on Proliferation and Apoptosis of Human Nasopharyngeal Carcinoma HEN1 Cells

    Institute of Scientific and Technical Information of China (English)

    Feng ZHANG; Yonghua CUI; Pingping CAO

    2008-01-01

    The effect of quercetin (Que) on proliferation and apoptosis of human nasopharyngeal carcinoma HEN1 cells was investigated. Inhibition rate of quercetin on HEN1 was assayed by MTT method, apoptosis by flow cytometry (FCM), and the caspase-3 expression of each group by colorimetry set respectively. Quercetin inhibited HEN1 cells in in a dose-(r=0.709,P<0.01) and time-dependent manner (r=0.703,P<0.01). The ratio of apoptotic and necrosis cells was increased in the cells treated with quercetin. Cell cycle was specificly arrested in G2/M phase. Apoptosis cusp was revealed by FCM. The activity of caspase-3 was significantly up-regulated in 5 groups treated with quecetin as compared with control group (P<0.05). It was concluded that the growth inhibition of quercetin was highly related to cell cycle arrest at the G2/M phase and induction of caspase-dependent apoptosis in human nasopharyngeal carcinoma HEN1 cells.

  20. Indole-3-carbinol inhibits nasopharyngeal carcinoma growth through cell cycle arrest in vivo and in vitro.

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    Zhe Chen

    Full Text Available Nasopharyngeal carcinoma is a common malignant tumor in the head and neck. Because of frequent recurrence and distant metastasis which are the main causes of death, better treatment is needed. Indole-3-carbinol (I3C, a natural phytochemical found in the vegetables of the cruciferous family, shows anticancer effect through various signal pathways. I3C induces G1 arrest in NPC cell line with downregulation of cell cycle-related proteins, such as CDK4, CDK6, cyclin D1 and pRb. In vivo, nude mice receiving I3C protectively or therapeutically exhibited smaller tumors than control group after they were inoculated with nasopharyngeal carcinoma cells. The expression of CDK4, CDK6, cyclin D1 and pRb in preventive treatment group and drug treatment group both decreased compared with the control group. We conclude that I3C can inhibit the growth of NPC in vitro and in vivo by suppressing the expression of CDK and cyclin families. The drug was safe and had no toxic effects on normal tissues and organs.

  1. Expression of matrix metalloproteinase-9 in nasopharyngeal carcinoma and association with Epstein-Barr virus infection

    Institute of Scientific and Technical Information of China (English)

    汤建国; 李旋; 陈萍

    2004-01-01

    Objective: To evaluate the expression of matrix metalloproteinase-9 (MMP9) in nasopharyngeal carcinoma and the association between MMP9 and Epstein-Barr virus infection. Methods: The MMP9 expression was studied by immunohistochemical analysis; and Epstein-Barr virus encoded small nuclear mRNA-1 (EBER-1) produced by in situ hybridization were examined in 41 nasopharyngeal carcinoma sections, and the relation between them, and the associations of MMP9 with clinical features were statistically analyzed. Results: Positive expression rate of MMP9 was 73.17%. The expression of MMP9 showed significant positive correlation with the expression of EBER-1(γ=0.483, P=0.001 ). There was significant association of MMP9 expression with lymph nodes metastasis and clinical stage (P<0.001), non-significant association with age, gender, pathological classification and T classification. Conclusions: The highly pronounced expression of MMP9 is associated with cervical lymph nodes metastasis. Epstein-Barr virus can enhance NPC metastasis by up-regulating the expression of MMP9.

  2. Expression of matrix metalloproteinase-9 in nasopharyngeal carcinoma and association with Epstein-Barr virus infection

    Institute of Scientific and Technical Information of China (English)

    汤建国; 李旋; 陈萍

    2004-01-01

    Objective: To evaluate the expression of matrix metalloproteinase-9 (MMP9) in nasopharyngeal carcinoma and the association between MMP9 and Epstein-Barr virus infection. Methods: The MMP9 expression was studied by immunohistochemical analysis; and Epstein-Barr virus encoded small nuclear mRNA-1 (EBER-1) produced by in situ hybridization were examined in 41 nasopharyngeal carcinoma sections, and the relation between them, and the associations of MMP9 with clinical features were statistically analyzed. Results: Positive expression rate of MMP9 was 73.17%. The expression of MMP9 showed significant positive correlation with the expression of EBER- 1 (γ=0.483, P=0.001). There was significant association of MMP9 expression with lymph nodes metastasis and clinical stage (P<0.001), non-significant association with age, gender, pathological classification and T classification. Conclusions: The highly pronounced expression of MMP9 is associated with cervical lymph nodes metastasis. Epstein-Barr virus can enhance NPC metastasis by up-regulating the expression of MMP9.

  3. Risk factors for the occurrence of undifferentiated carcinoma of nasopharyngeal type: A case-control study

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    Nešić Vladimir

    2010-01-01

    Full Text Available Introduction. The incidence rate of nasopharyngeal carcinoma in Serbia is less than one per 100,000 citizens, which classifies it as a region with low incidence for this disease. Objective. The aim of this study was to test some hypotheses of the risk factors for undifferentiated carcinoma of nasopharyngeal type (UCNT in the low incidence population. Methods. A case-control study was used for the research. The study included 45 cases with histopathological diagnosis of UCNT and 90 controls. Cases and the controls were individually matched by sex, age (±3 years, and place of residence (city-village. Data were gathered about sociodemographic characteristics, occupational exposure to harmful agents, habits, diet, personal history, and family history. In the analysis of the data, conditional univariate and multivariate logistic regression analyses were applied. Results. According to the results of multivariate logistic regression analysis UCNT was significantly positively associated with 'passive smoking' of tobacco in the family during childhood, frequent consumption of industrially manufactured food additives for enhancing flavour and frequent consumption of white bread. UCNT was significantly negatively associated with frequent consumption of margarine, olive oil and cornbread. Conclusion. In our low incidence population, an independent risk factor for the occurrence of UCNT was 'passive smoking' of tobacco in the family during childhood, use of industrially manufactured food with additives for enhancing flavour and consumption of white bread. Multicentric study enrolling a greater number of cases would be desirable.

  4. miR-421 induces cell proliferation and apoptosis resistance in human nasopharyngeal carcinoma via downregulation of FOXO4

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Liang [Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282 (China); Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010 (China); Tang, Yanping [Neurosurgery Institute, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Zhujiang Hospital of Southern Medical University, Guangzhou 510282 (China); Wang, Jian [Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010 (China); Yan, Zhongjie [Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA,The Bayi Clinical Medical Institute of Southern Medical University, Beijing 100700 (China); Xu, Ruxiang, E-mail: RuxiangXu@yahoo.com [Affiliated Bayi Brain Hospital, The Military General Hospital of Beijing PLA,The Bayi Clinical Medical Institute of Southern Medical University, Beijing 100700 (China)

    2013-06-14

    Highlights: •miR-421 is upregulated in nasopharyngeal carcinoma. •miR-421 induces cell proliferation and apoptosis resistance. •FOXO4 is a direct and functional target of miR-421. -- Abstract: microRNAs have been demonstrated to play important roles in cancer development and progression. Hence, identifying functional microRNAs and better understanding of the underlying molecular mechanisms would provide new clues for the development of targeted cancer therapies. Herein, we reported that a microRNA, miR-421 played an oncogenic role in nasopharyngeal carcinoma. Upregulation of miR-421 induced, whereas inhibition of miR-421 repressed cell proliferation and apoptosis resistance. Furthermore, we found that upregulation of miR-421 inhibited forkhead box protein O4 (FOXO4) signaling pathway following downregulation of p21, p27, Bim and FASL expression by directly targeting FOXO4 3′UTR. Additionally, we demonstrated that FOXO4 expression is critical for miR-421-induced cell growth and apoptosis resistance. Taken together, our findings not only suggest that miR-421 promotes nasopharyngeal carcinoma cell proliferation and anti-apoptosis, but also uncover a novel regulatory mechanism for inactivation of FOXO4 in nasopharyngeal carcinoma.

  5. High expression of p300 is linked to aggressive features and poor prognosis of Nasopharyngeal Carcinoma

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    Liao Zhi-Wei

    2012-05-01

    Full Text Available Abstract Background Increased expression of transcriptional coactivator p300 has been observed in a variety of human cancers. However, the expression status of p300 protein/mRNA in nasopharyngeal carcinoma (NPC tissues and its clinicopathologic/prognostic implication are poorly understood. Methods In our study, mRNA and protein expression levels of p300 was explored by reverse transcription-polymerase chain reaction (RT-PCR, Western blotting (WB and immunohistochemistry (IHC in nasopharyngeal mucosal and NPC tissues. The data were analyzed by receiver operating characteristic (ROC curve analysis, spearman’s rank correlation, Kaplan-Meier plots and Cox proportional hazards regression model. Results Up-regulated expression of p300 mRNA/p300 protein was detected in NPC tissues by RT-PCR and WB, when compared to nasopharyngeal mucosal tissues. Based on ROC curve analysis, the cutoff score for p300 high expression was defined when more than 35% of the tumor cells were positively stained. High expression of p300 was observed in 127/209 (60.7% of NPCs. In NPCs, high expression of p300 was positively associated with later T classification, later N classification, distant metastasis and later clinical stage (P P = 0.002 and overall survival (P = 0.001 in NPCs. More importantly, p300 expression was evaluated as an independent prognostic factor for NPC in multivariate analysis (P = 0.036. Conclusions Our findings support that high expression of p300 protein might be important in conferring a more aggressive behavior, and is an independent molecular marker for shortened survival time of patients with NPC.

  6. Radiation-Guided Peptide Delivery in a Mouse Model of Nasopharyngeal Carcinoma

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    Pei-cheng Lin

    2016-01-01

    Full Text Available Purpose. This study aimed to evaluate the characteristics of the HVGGSSV peptide, exploring radiation-guided delivery in a mouse model of nasopharyngeal carcinoma. Methods. Mice with CNE-1 nasopharyngeal carcinoma were assigned to two different groups treated with Cy7-NHS and Cy7-HVGGSSV, respectively. Meanwhile, each mouse received a single dose of 3 Gy radiation. Biological distribution of the recombinant peptide was assessed on an in vivo small animal imaging system. Results. The experimental group showed maximum fluorescence intensity in irradiated tumors treated with Cy7-labeled HVGGSSV, while untreated (0 Gy control tumors showed lower intensity levels. Fluorescence intensities of tumors in the right hind limbs of experimental animals were 7.84×107±1.13×107, 1.35×108±2.66×107, 4.05×108±1.75×107, 5.57×108±3.47×107, and 9.26×107±1.73×107 photons/s/cm2 higher compared with left hind limb values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence intensities of tumor in the right hind limbs of the experimental group were 1.66×108±1.71×107, 1.51×108±3.23×107, 5.38×108±1.96×107, 5.89×108±3.57×107, and 1.62×108±1.69×107 photons/s/cm2 higher compared with control group values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence was not specifically distributed in the control group. Compared with low fluorescence intensity in the heart, lungs, and tumors, high fluorescence distribution was found in the liver and kidney at 48 h. Conclusions. HVGGSSV was selectively bound to irradiated nasopharyngeal carcinoma, acting as a targeting transport carrier for radiation-guided drugs that are mainly metabolized in the kidney and liver.

  7. Radiation-Guided Peptide Delivery in a Mouse Model of Nasopharyngeal Carcinoma

    Science.gov (United States)

    Lin, Pei-cheng; He, Jun-yan; Le, Yu-yin; Du, Kai-xin; Zhu, Wei-feng; Peng, Qing-qin; Dong, Ya-ping

    2016-01-01

    Purpose. This study aimed to evaluate the characteristics of the HVGGSSV peptide, exploring radiation-guided delivery in a mouse model of nasopharyngeal carcinoma. Methods. Mice with CNE-1 nasopharyngeal carcinoma were assigned to two different groups treated with Cy7-NHS and Cy7-HVGGSSV, respectively. Meanwhile, each mouse received a single dose of 3 Gy radiation. Biological distribution of the recombinant peptide was assessed on an in vivo small animal imaging system. Results. The experimental group showed maximum fluorescence intensity in irradiated tumors treated with Cy7-labeled HVGGSSV, while untreated (0 Gy) control tumors showed lower intensity levels. Fluorescence intensities of tumors in the right hind limbs of experimental animals were 7.84 × 107 ± 1.13 × 107, 1.35 × 108 ± 2.66 × 107, 4.05 × 108 ± 1.75 × 107, 5.57 × 108 ± 3.47 × 107, and 9.26 × 107 ± 1.73 × 107 photons/s/cm2 higher compared with left hind limb values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence intensities of tumor in the right hind limbs of the experimental group were 1.66 × 108 ± 1.71 × 107, 1.51 × 108 ± 3.23 × 107, 5.38 × 108 ± 1.96 × 107, 5.89 × 108 ± 3.57 × 107, and 1.62 × 108 ± 1.69 × 107 photons/s/cm2 higher compared with control group values at 1, 2, 15, 24, and 48 h, respectively. Fluorescence was not specifically distributed in the control group. Compared with low fluorescence intensity in the heart, lungs, and tumors, high fluorescence distribution was found in the liver and kidney at 48 h. Conclusions. HVGGSSV was selectively bound to irradiated nasopharyngeal carcinoma, acting as a targeting transport carrier for radiation-guided drugs that are mainly metabolized in the kidney and liver.

  8. Phase II trial of docetaxel combined with nedaplatin for patients with recurrent and metastatic nasopharyngeal carcinoma

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    Peng PJ

    2015-12-01

    Full Text Available Pei-Jian Peng,1,* Bao-Jun Lv,2,* Con Tang,2,* Hai Liao,3 Zhong Lin,1 Yu-Meng Liu,4 Zhi-Hui Wang,1 Si-Yang Wang,5 Zhi-Bin Cheng5 1Department of Medical Oncology, 2Department of Surgical Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 3Department of Medical Oncology, Cancer Centre, Sun Yat-sen University, Guangzhou, 4Department of Oncology, People’s Hospital of Zhongshan City, Zhongshan, 5Department of Radiation Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Purpose: This Phase II trial was designed to evaluate the efficacy and safety of docetaxel combined with nedaplatin as first-line treatment for patients with recurrent or metastatic nasopharyngeal carcinoma. Methods: In this multicenter Phase II trial, the patients were treated with intravenous docetaxel (75 mg/m2, day 1 and nedaplatin (80 mg/m2, day 1, each cycle repeated every 3 weeks for two cycles at least. Results: From January 2010 to November 2013, a total of 78 patients were recruited in this trial. Among them, 73 patients were assessable for response. The treatment was well tolerated. The main hematological adverse event was neutropenia. A total of 12 patients (15.4% had grade 3 or grade 4 neutropenia. Grade 3 anemia was observed in six patients (7.7% and no grade 3/4 thrombocytopenia was observed. No Grade 3/4 non-hematological toxicity was observed. There were five complete response (6.8%, 43 partial responses (58.9%, and the overall response rate was 65.8% (95% confidence interval [CI], 48.7%–81.2%. With a median follow-up period of 18.6 months, the median time to progression was 7.9 months (95% CI, 4.2–10.8 months, median overall survival was 15.7 months (95% CI, 11.6–18.5 months. Conclusion: Docetaxel combined with nedaplatin offers a satisfactory clinical activity and an acceptable safety profile as first

  9. Dinitrosopiperazine-Mediated Phosphorylated-Proteins Are Involved in Nasopharyngeal Carcinoma Metastasis

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    Gongjun Tan

    2014-11-01

    Full Text Available N,N'-dinitrosopiperazine (DNP with organ specificity for nasopharyngeal epithelium, is involved in nasopharyngeal carcinoma (NPC metastasis, though its mechanism is unclear. To reveal the pathogenesis of DNP-induced metastasis, immunoprecipitation was used to identify DNP-mediated phosphoproteins. DNP-mediated NPC cell line (6-10B motility and invasion was confirmed. Twenty-six phosphoproteins were increased at least 1.5-fold following DNP exposure. Changes in the expression levels of selected phosphoproteins were verified by Western-blotting analysis. DNP treatment altered the phosphorylation of ezrin (threonine 567, vimentin (serine 55, stathmin (serine 25 and STAT3 (serine 727. Furthermore, it was shown that DNP-dependent metastasis is mediated in part through ezrin at threonine 567, as DNP-mediated metastasis was decreased when threonine 567 of ezrin was mutated. Strikingly, NPC metastatic tumors exhibited a higher expression of phosphorylated-ezrin at threonine 567 than the primary tumors. These findings provide novel insight into DNP-induced NPC metastasis and may contribute to a better understanding of the metastatic mechanisms of NPC tumors.

  10. [Genetic polymorphism of cytochrome P450 2E1 and the risk of nasopharyngeal carcinoma].

    Science.gov (United States)

    Ben Chaaben, Arij; Abaza, Hajer; Douik, Hayet; Chaouch, Leila; Ayari, Fayza; Ouni, Nesrine; Mamoghli, Tasnim; Ben Guezella, Dorra; Mejri, Rachida; Harzallah, Latifa; Guemira, Fethi

    2015-12-01

    Cytochrome P450 2E1 (CYP2E1) is a detoxifying enzyme that belongs to the phase I metabolism of xenobiotics. This enzyme is encoded by a highly polymorphic gene whose common polymorphism corresponds to the substitution of cytosine (C) and thymine (T) at position -1019 (rs2031920). This polymorphism has been identified in several cancers including nasopharyngeal cancer (NPC). The study involved 124 patients with nasopharyngeal carcinoma, compared with 166 healthy controls. The presence or absence of the polymorphism is determined by PCR-RFLP. The frequency comparison between the two groups is determined by the χ(2) test. The analysis of our results showed a significant difference between the two groups regarding the mutant genotype (C2/C2) (5% vs. 0.5%, P=0.04) and has a risk factor for NPC in Tunisia (OR=8.39; CI 95% [0.99-388.1]). Also, the C2 allele was significantly associated with the group of patients than the control group (6% vs. 2%, P=0.016) and increased three times the risk of NPC in Tunisia (OR=2.99, CI 95% [1.12-8.79]). Our results confirm the results reported in other populations and emphasize the importance of the involvement of this gene in the development of detoxification of the NPC, which seems more and more strongly associated with environmental factors.

  11. Expression of the Pokemon proto-oncogene in nasopharyngeal carcinoma cell lines and tissues.

    Science.gov (United States)

    Jiao, Wei; Liu, Fei; Tang, Feng-Zhu; Lan, Jiao; Xiao, Rui-Ping; Chen, Xing-Zhou; Ye, Hui-Lan; Cai, Yong-Lin

    2013-01-01

    To study the differentiated expression of the proto-oncogene Pokemon in nasopharyngeal carcinoma (NPC) cell lines and tissues, mRNA and protein expression levels of CNE1, CNE2, CNE3 and C666-1 were detected separately by reverse transcription polymerase chain reaction (RT-PCR), real-time PCR and Western-blotting. The immortalized nasopharyngeal epithelial cell line NP69 was used as a control. The Pokemon protein expression level in biopsy specimens from chronic rhinitis patients and undifferentiated non keratinizing NPC patients was determined by Western-blotting and arranged from high to low: C666-1>CNE1>CNE2> CNE3>NP69. The Pokemon mRNA expression level was also arranged from high to low: CNE1>CNE2>NP69>C666-1>CNE3. Pokemon expression of NP69 and C666-1 obviously varied from mRNA to protein. The Pokemon protein level of NPC biopsy specimens was obviously higher than in chronic rhinitis. The data suggest that high Pokemon protein expression is closely associated with undifferentiated non-keratinizing NPC and may provide useful information for NPC molecular target therapy. PMID:24377524

  12. Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma

    Science.gov (United States)

    Hu, Li-Fu; Moumad, Khalid; Pavlova, Tatiana V.; Kashuba, Vladimir; Almgren, Malin; Zabarovsky, Eugene R.; Ernberg, Ingemar

    2015-01-01

    Epigenetic silencing of tumor suppressor genes (TSGs) by promoter methylation can be an early event in the multi-step process of carcinogenesis. Human chromosome 3 contains clusters of TSGs involved in many cancer types including nasopharyngeal carcinoma (NPC), the most common cancer in Southern China. Among ten candidate TSGs identified in chromosome 3 using NotI microarray, ITGA9 and WNT7A could be validated. 5′-aza-2′ deoxycytidine treatment restored the expression of ITGA9 and WNT7A in two NPC cell lines. Immunostaining showed strong expression of these genes in the membrane and cytoplasm of adjacent control nasopharyngeal epithelium cells, while they were weakly expressed in NPC tumor cells. The ITGA9 promoter showed marked differentially methylation between tumor and control tissue, whereas no differentially methylation could be detected for the WNT7A promoter. The expression level of ITGA9 in NPC tumors was downregulated 4.9-fold, compared to the expression in control. ITGA9 methylation was detected by methylation specific PCR (MSP) in 56% of EBV positive NPC- cases with 100% specificity. Taken together, this suggests that ITGA9 might be a TSG in NPC that is involved in tumor cell biology. The possibility of using ITGA9 methylation as a marker for early detection of NPC should further be explored. PMID:26372814

  13. Cancer stem-like cells in Epstein-Barr virus-associated nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Samantha Wei-Man Lun; Siu-Tim Cheung; Kwok-Wai Lo

    2014-01-01

    Although the Epstein-Barr virus (EBV) has spread to all populations in the world, EBV-associated nasopharyngeal carcinoma (NPC) is prevalent only in South China and Southeast Asia. The role of EBV in the malignant transformation of nasopharyngeal epithelium is the main focus of current researches. Radiotherapy and chemoradiotherapy have been successful in treating early stage NPC, but the recurrence rates remain high. Unfortunately, local relapse and metastasis are commonly unresponsive to conventional treatments. These recurrent and metastatic lesions are believed to arise from residual or surviving cells that have the properties of cancer stem cels. These cancer stem-like cels (CSCs) have the ability to self-renew, differentiate, and sustain propagation. They are also chemo-resistant and can form spheres in anchorage-independent environments. This review summarizes recent researches on the CSCs in EBV-associated NPC, including the findings regarding cell surface markers, stem cell-related transcription factors, and various signaling pathways. In particular, the review focuses on the roles of EBV latent genes [latent membrane protein 1 (LMP1) and latent membrane protein 2A (LMP2A)], cellular microRNAs, and adenosine triphosphate (ATP)-binding cassette chemodrug transporters in contributing to the properties of CSCs, including the epithelial-mesenchymal transition, stem-like transition, and chemo-resistance. Novel therapeutics that enhance the efficacy of radiotherapy and chemoradiotherapy and inhibitors that suppress the properties of CSCs are also discussed.

  14. Reduced CTGF expression promotes cell growth, migration, and invasion in nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Yan Zhen

    Full Text Available BACKGROUND: The role of CTGF varies in different types of cancer. The purpose of this study is to investigate the involvement of CTGF in tumor progression and prognosis of human nasopharyngeal carcinoma (NPC. EXPERIMENTAL DESIGN: CTGF expression levels were examined in NPC tissues and cells, nasopharynx (NP tissues, and NP69 cells. The effects and molecular mechanisms of CTGF expression on cell proliferation, migration, invasion, and cell cycle were also explored. RESULTS: NPC cells exhibited decreased mRNA expression of CTGF compared to immortalized human nasopharyngeal epithelial cell line NP69. Similarly, CTGF was observed to be downregulated in NPC compared to normal tissues at mRNA and protein levels. Furthermore, reduced CTGF was negatively associated with the progression of NPC. Knocking down CTGF expression enhanced the colony formation, cell migration, invasion, and G1/S cell cycle transition. Mechanistic analysis revealed that CTGF suppression activated FAK/PI3K/AKT and its downstream signals regulating the cell cycle, epithelial-mesenchymal transition (EMT and MMPs. Finally, DNA methylation microarray revealed a lack of hypermethylation at the CTGF promoter, suggesting other mechanisms are associated with suppression of CTGF in NPC. CONCLUSION: Our study demonstrates that reduced expression of CTGF promoted cell proliferation, migration, invasion and cell cycle progression through FAK/PI3K/AKT, EMT and MMP pathways in NPC.

  15. 中晚期鼻咽癌新辅助化疗联合放疗前瞻性 临床试验的长期结果%Long-Term Results of a Prospective Randomized Trial Comparing Neoadjuvant Chemotherapy Plus Radiotherapy with Radiotherapy Alone for Patients with Locoregionally Advanced Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    马骏; 麦海强; 洪明晃; 闵华庆; 毛志达; 崔念基

    2001-01-01

    目的:评价新辅助化疗联合放疗在中晚期鼻咽癌治疗中的价值。方法:前瞻性临床试验采用化疗方案: Cisplatin 20 mg/m2, 1~ 5天, 5-FU 500 mg/m2, 1~ 5天, BLM 7 mg/m2,第 1、 5天,化疗 2~ 3个疗程。放射治疗鼻咽剂量: 66~ 74 Gy/33~ 37次,共 7~ 9周;颈部淋巴结剂量: 60~ 70 Gy/30~ 35次,共 7~ 8.5周;颈部预防量: 48~ 50 Gy。结果: 1992~ 1993年 457例鼻咽癌病人进入研究, 17例因各种原因退出队列, 440例进入分析(化疗+放疗组 219例、单纯放疗组 221例)。 5年生存率及无瘤生存率实验组及对照组分别为 62% vs 55% (P=0.1335)及 58% vs 48% (P=0.0539)。 5年无局部复发生存率及无远处转移生存率两组分别为 82% vs 74% (P=0.0412)及 79% vs 75%( P=0.4177)。亚组分析显示新辅助化疗能明显提高 T3~ 4期的局控率;对 N2~ 3病人的远处转移率无影响。结论:新辅助化疗未能提高中晚期鼻咽癌病人的总生存率,亦未能降低远处转移率,有提高无瘤生存率的趋势。新辅助化疗的指征: T3~ 4期病人。%Objective: A prospective randomized trial was performed to evaluate the contribution of neoadjuvant chemotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma. Methods: The patients with locoregionally advanced nasopharyngeal carcinoma were treated with either radiotherapy alone (RT group) or neoadjuvant chemotherapy plus radiotherapy (CT/RT group). Neoadjuvant chemotherapy consisting of 2-3 cycles of cisplatin (20 mg/m2 on Day 1 to Day 5), bleomycin (7 mg/m2 on Day 1 and Day 5), and 5-FU (500 mg/m2 on Day 1 to Day 5) followed by radiotherapy was given to CT/RT group. All patients were treated in a uniform definitive-intent radiation therapy in two groups. Results: From 1992 to 1993, 457 patients were enrolled and 440 patients (221 in RT group, 219 in CT/RT group) were assessable. The 5

  16. Effects of Concurrent Chemoradiotherapy for EB Virus DNA Levels in Plasma of Patients with Advanced Nasopharyngeal Carcinoma%同期放化疗对晚期鼻咽癌患者血浆 EB 病毒 DNA 水平的影响

    Institute of Scientific and Technical Information of China (English)

    矫德馨; 龚智强; 贾鑑慧

    2015-01-01

    目的:探讨同期放化疗对晚期鼻咽癌患者血浆EB病毒DNA水平的影响。方法选取98例晚期鼻咽癌患者作为研究对象,采用放疗联合紫杉醇化疗进行治疗,并对98例患者血浆EBV-DNA 水平采用荧光定量PCR 技术进行测定,并与其影像学检查及病理结果进行比较分析。结果放化疗后鼻咽癌患者52例缓解,21例稳定,25例进展。三组鼻咽癌患者血浆EB-DNA水平测定阳性率缓解组为0、稳定组为4.76%,进展组最高为88.00%,缓解组与稳定组比较,差异无统计学意义(P>0.05),进展组分别与缓解组、稳定组比较,差异均具有统计学意义(P<0.05);3组敏感性分别为0、4.76%、88.00%,特异性分别为100.00%、95.24%、12.00%,阴性预测值分别为69.33%、26.67%、4.00%,阳性预测值分别为0、4.35%、95.65%;缓解组特异性和阴性预测值最高,与进展组比较,差异有统计学意义( P<0.05);进展组敏感性和阳性预测值最高,与缓解组和稳定组比较,差异有统计学意义(P<0.05)。结论晚期鼻咽癌患者同期放化疗后血浆EB病毒DNA水平,可作为监测和反映鼻咽癌患者放化疗后转移、复发的重要指标。%Objective To investigate the effect of concurrent chemoradiotherapy for EB virus DNA levels in plasma of patients with advanced nasopharyngeal carcinoma .Methods 98 patients with advanced nasopharyngeal carcinoma received radia-tion therapy combined with paclitaxel chemotherapy , and plasma EBV-DNA level of 98 patients were measured by quantitative PCR and was compared with imaging and pathology results .Results After chemoradiotherapy ,there were 52 cases of remission , 21 cases of stable and 25 cases of progress.Positive rate of plasma EB-DNA level in remission group was 0,stable group was 4.76%,progressive group was 88.00%,the difference was not statistically significant

  17. Nasopharyngeal carcinoma. Treatment planning with IMRT and 3D conformal radiotherapy

    DEFF Research Database (Denmark)

    Kristensen, Claus A; Kjaer-Kristoffersen, Flemming; Sapru, Wendy;

    2007-01-01

    -CRT plans were made and compared to the IMRT plans with respect to doses to the planning target volumes (PTVs) and to organs at risk (OARs). For comparison of the conformation of dose to defined target volumes the conformity index (CI) was used. Target volume coverage and critical organ protection were......The study was undertaken in order to compare dose plans for intensity-modulated radiotherapy (IMRT) with 3D conformal radiotherapy (3D-CRT) dose plans in patients with nasopharyngeal carcinoma (NPC). Clinical data from 20 consecutive patients treated with IMRT are presented. For 11 patients 3D...... significantly improved with IMRT compared to 3D-CRT. One-year loco-regional control, distant metastasis-free survival, and overall survival were 79%, 72%, and 80%. Two patients have had recurrence in the clinical target volume (CTV) only and seven patients have relapsed in distant organs and/or in head...

  18. Chromosomal imbalances in nasopharyngeal carcinoma: a meta-analysis of comparative genomic hybridization results

    Directory of Open Access Journals (Sweden)

    Jin Ping

    2006-01-01

    Full Text Available Abstract Nasopharyngeal carcinoma (NPC is a highly prevalent disease in Southeast Asia and its prevalence is clearly affected by genetic background. Various theories have been suggested for its high incidence in this geographical region but to these days no conclusive explanation has been identified. Chromosomal imbalances identifiable through comparative genomic hybridization may shed some light on common genetic alterations that may be of relevance to the onset and progression of NPC. Review of the literature, however, reveals contradictory results among reported findings possibly related to factors associated with patient selection, stage of disease, differences in methodological details etc. To increase the power of the analysis and attempt to identify commonalities among the reported findings, we performed a meta-analysis of results described in NPC tissues based on chromosomal comparative genomic hybridization (CGH. This meta-analysis revealed consistent patters in chromosomal abnormalities that appeared to cluster in specific "hot spots" along the genome following a stage-dependent progression.

  19. ISG15 predicts poor prognosis and promotes cancer stem cell phenotype in nasopharyngeal carcinoma

    Science.gov (United States)

    Han, Ping; Wang, Hong-Bo; Liang, Fa-Ya; Feng, Guo-Kai; Zhou, Ai-Jun; Cai, Mu-Yan; Zhong, Qian; Zeng, Mu-Sheng; Huang, Xiao-Ming

    2016-01-01

    Interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, is known for its anti-viral capacity. However, its role in tumorigenesis remains controversial. Here, using RNA-seq profiling analysis, we identified ISG15 as a differentially expressed gene in nasopharyngeal carcinoma (NPC) and validated its overexpression in NPC samples and cells. High ISG15 levels in NPC tissues were correlated with more frequent local recurrence and shorter overall survival and disease-free survival. ISG15 overexpression promoted a cancer stem cell phenotype in NPC cells, including increased colony and tumorsphere formation abilities, pluripotency-associated genes expression, and in vivo tumorigenicity. By contrast, knockdown of ISG15 attenuated stemness characteristics in NPC cells. Furthermore, overexpression of ISG15 increased NPC cell resistance to radiation and cisplatin (DDP) treatment. Our study demonstrates a protumor role of ISG15, and suggests that ISG15 is a prognostic predictor and a potential therapeutic target for NPC. PMID:26919245

  20. The Criteria to Confirm the Role of Epstein-Barr Virus in Nasopharyngeal Carcinoma Initiation

    Directory of Open Access Journals (Sweden)

    Ai-Di Gu

    2012-10-01

    Full Text Available Epstein-Barr virus (EBV is associated with nasopharyngeal carcinoma (NPC, but it remains obscure whether EBV is a viral cause of, or only an accompaniment of, NPC. We will discuss the accumulated evidence pointing to the relationship between EBV infection and NPC initiation from epidemiologic, pathogenic, molecular oncogenic, and experimental animal studies. We believe that convincing evidence from these perspectives must be provided before we can ascertain the causal role of EBV infection in NPC. Specifically, (1 epidemiological studies should reveal EBV infection as a risk factor; (2 the introduction of EBV into an animal model should produce NPC; (3 in the animal model NPC, the main molecular event(s or the involved signaling pathway(s should be identical to that in human NPC; and (4 finally and most importantly, prevention of EBV infection or clearance of EBV from infected individuals must be able to reduce the incidence rate of NPC.

  1. Surgical resection of a solitary liver metastasis from nasopharyngeal carcinoma:a case report

    Institute of Scientific and Technical Information of China (English)

    Spiros Delis; Ioannis Biliatis; Antonia Bourli; Nikolaos Kapranos; Christos Dervenis

    2006-01-01

    BACKGROUND: Nasopharyngeal carcinoma (NPC) has a propensity to develop distant metastases at a high rate and with poor prognosis. Metastatic sites are usually multifocal and involve bones, lungs, liver and distant lymph nodes. Management of metastatic disease is essentially palliative and is based on chemotherapy. METHODS:A 50-year-old man with a solitary liver metastasis from a newly diagnosed NPC was treated by segmentectomy. Prior to surgery, neoadjuvant chemo-therapy followed by concurrent chemoradiotherapy was administered. RESULTS:Complete remission of the primary disease was achieved, although the size of the hepatic lesion was increased. After resection of the liver metastasis, no signs of local or distant recurrence was noted during the 6-month follow up. CONCLUSION:Although surgical treatment has a limited role in metastatic NPC, there are rare cases of localized disease with a reasonable outcome after resection.

  2. Temporal lobe and hypothalmic-pituitary dysfunctions after radiotherapy for nasopharyngeal carcinoma: a distinct clinical syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Woo, E.; Lam, K.; Yu, Y.L.; Ma, J.; Wang, C.; Yeung, R.T.T.

    1988-10-01

    Eleven patients with combined neurological and endocrine complications after external radiotherapy for nasopharyngeal carcinoma are described. Memory disturbance, complex partial seizures and hypodense areas in one or both temporal lobes on CT were typical features. Endocrinologically, hypopituitarism was the prominent manifestation. This constellation of clinical features in a patient with previous radiotherapy to the nasopharynx characterises radiation injury to the inferomedial aspects of the temporal lobes and the hypothalamic-pituitary axis. While parenchymal brain lesions may mimic metastases or glioma on CT, associated endocrine disturbance would betray the correct diagnosis. The importance of recognising hypo-pituitarism which may be clinically asymptomatic and which is amenable to therapy is emphasised, as is the need for a proper fractionation of radiation dose to minimise the incidence of these disabling complications.

  3. Clinical study on external carotid artery infusion (trans-femoral) treatment of recurrent nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the effect and safety of external carotid artery infusion treatment of recurrent nasopharyngeal carcinoma (NPC). Methods: 20 cases of recurrent NPC (13 male and 7 female, age 36-65 years, mean 50 years) diagnosed by clinical examination (including nasopharyngoscope), serology (VCA-IgA) and imaging (CT, MR) and treated by external carotid artery infusion (trans-femoral) with adriamycin (or epi-adriamycin), cisplatin (or carboplatin), Pingyangmycin and 5-Fluorouracil. Results: Of all the patients, 8 cases (40%) had a complete response (CR), 7 cases (35%) had a partial response (PR). The overall response rate (CR + PR) was 75%. Cumulative survival rates at 1, 3 years were 90% (18/20), 50%(10/20) respectively. No severe side-effects and complications found. Conclusion: External carotid artery infusion (trans-femoral) should be effective and safe in the treatment of recurrent NPC

  4. Symptomatic hypothalamic-pituitary dysfunction in nasopharyngeal carcinoma patients following radiation therapy: a retrospective study

    International Nuclear Information System (INIS)

    Endocrine assessment was performed in 32 relapse-free southern Chinese patients 5-17 years following radiation therapy (RT) alone for early nasopharyngeal carcinoma (NPC). Initial screening was done using questionnaires emphasizing impaired sexual function and menstrual disturbance plus measurement of serum levels of thyroxine, free thyroxine index, thyrotropic hormone, prolactin, and additionally testosterone for males only. Those showing abnormalities were subjected to detailed pituitary function tests. Hypothalamic-pituitary dysfunction was found in 7 female patients and only 1 male patient. A delayed TSH response to thyrotropin releasing hormone suggesting a hypothalamic disorder was seen in 6 of the affected female patients, and hyperprolactinaemia in also 6. None of the patients had evidence of diabetes insipidus. Hypopituitarism became symptomatic 2-5 years after RT with a mean latent interval of 3.8 years. A practical protocol for regular endocrine assessment for NPC patients after RT has been proposed. Multiple linear regression analysis of the radiotherapeutic data from the 11 female patients indicates that the likelihood of late occurrence of symptomatic hypothalamic-pituitary dysfunction following RT is dependent on the TDF of the target dose to the nasopharyngeal region and the height of the upper margin of the opposed lateral facial fields above the diaphragma sellae (coefficient of multiple correlation = 0.9025). Except when the sphenoid sinus or the middle cranial fossa is involved, it is advisable to set the height of the upper margin of the lateral facial field at a level no higher than the diaphragma sellae. The hypothalamus and possibly the pituitary stalk as well may sustain permanent damage by doses of radiation within the conventional radiotherapeutic range for carcinomas

  5. A nomogram for predicting survival of nasopharyngeal carcinoma patients with metachronous metastasis.

    Science.gov (United States)

    Zeng, Zixun; Shen, Lujun; Wang, Yue; Shi, Feng; Chen, Chen; Wu, Ming; Bai, Yutong; Pan, Changchuan; Xia, Yunfei; Wu, Peihong; Li, Wang

    2016-07-01

    Patients with metachronous metastatic nasopharyngeal carcinoma (NPC) differ significantly in survival outcomes. The aim of this study is to build a clinically practical nomogram incorporating known tumor prognostic factors to predict survival for metastatic NPC patients in epidemic areas.A total of 860 patients with metachronous metastatic nasopharyngeal carcinoma were analyzed retrospectively. Variables assessed were age, gender, body mass index, Karnofsky Performance Status (KPS), Union for International Cancer Control (UICC) T and N stages, World Health Organization (WHO) histology type, serum lactate dehydrogenase (sLDH) level, serum Epstein-Barr virus (EBV) level, treatment modality, specific metastatic location (lung/liver/bone), number of metastatic location(s) (isolated vs multiple), and number of metastatic lesion(s) in metastatic location(s) (single vs multiple). The independent prognostic factors for overall survival (OS) by Cox-regression model were utilized to build the nomogram.Independent prognostic factors for OS of metastatic NPC patients included age, UICC N stage, KPS, sLDH, number of metastatic locations, number of metastatic lesions, involvement of liver metastasis, and involvement of bone metastasis. Calibration of the final model suggested a c-index of 0.68 (95% confidence interval [CI], 0.65-0.69). Based on the total point (TP) by nomogram, we further subdivided the study cohort into 4 groups. Group 1 (TP Discrimination was visualized by the differences in survival between these 4 groups (group 2/group 1: hazard ratio [HR] = 1.61, 95%CI: 1.24-2.09; group 3/group 1: HR = 2.20, 95%CI: 1.69-2.86; and group 4/group 1: HR = 3.66, 95%CI: 2.82-4.75).The developed nomogram can help guide the prognostication of patients with metachronous metastatic NPC in epidemic areas. PMID:27399084

  6. Association between genetic polymorphisms and carotid atherosclerosis in patients treated with radiotherapy for nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Radiotherapy (RT) of the neck is commonly given to nasopharyngeal carcinoma (NPC) patients for preventing cervical lymph node metastasis. However, neck RT may induce the development of carotid atherosclerosis. The mechanisms of radiation-induced carotid atherosclerosis are still unclear and no previous study has investigated the genetic involvement of radiation-induced carotid atherosclerosis. The present study aims to determine the association between genetic polymorphisms and carotid atherosclerosis in patients treated with RT for nasopharyngeal carcinoma. The present study recruited 128 post-RT NPC patients. Carotid plaque score was assessed using ultrasonography. Thirteen single nucleotide polymorphisms (SNPs) that affect the function of anti-atherosclerotic genes, including SOD2, SOD3, CAT, PON1, PPARG, ADIPOQ, IL10, TGFB1 and NOS3, were genotyped. Association between the 13 SNPs and carotid atherosclerosis was evaluated using multiple regression after adjustment for covariates (PLINK). Multiple testing was corrected using Benjamini-Hochberg step-up false discovery rate controlling procedure. rs662 and rs705379 of PON1 were close to be significantly associated with carotid plaque score (Corrected P value, Pcor = 0.0528 and Pcor = 0.0842). When the two SNPs were combined together, TC haplotype in rs662-rs705379 of PON1 was significantly associated with higher carotid plaque score (Pcor < 0.05). None of the other SNPs showed significant association with carotid plaque score. TC haplotype in rs662-rs705379 of PON1 is likely to be a genetic risk factor of carotid plaque score. Post-RT NPC patients with the TC haplotype may need earlier and more frequent carotid ultrasound examinations for early detection of carotid atherosclerosis

  7. The effects of combining ionizing radiation and adenoviral p53 therapy in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Purpose: Nasopharyngeal carcinoma (NPC) is a malignant disease of the head/neck region, with a 5-year survival level of approximately 65%. To explore gene therapy as a novel approach which might improve outcome, we have shown previously that introduction of human recombinant wild-type p53 mediated by the adenoviral vector (Ad5CMV-p53) was cytotoxic in two human nasopharyngeal carcinoma (NPC) cell lines (CNE-1 and CNE-2Z). The current work was designed to determine whether this strategy, combined with ionizing radiation (XRT), was more effective than either treatment alone. Methods and Materials: CNE-1, CNE-2Z, and a normal human nasopharyngeal fibroblast strain, KS1, were infected with 2- and 6-plaque-forming units (pfu)/cell of Ad5CMV-p53, respectively. These doses were iso-effective for β-galactosidase activity in the CNE-1 and CNE-2Z cells. XRT was administered 24 h post-infection, and Western blot analyses were conducted for p53, p21WAF1/CIP1, bax, and bcl-2 2 days after XRT. Cell survival was assessed using a clonogenic assay. Presence of DNA ladders reflecting apoptosis was detected using DNA agarose gel electrophoresis, and cell cycle was analyzed using flow cytometry. Results: The combination of Ad5CMV-p53 plus XRT (2, 4, and 6 Gy) resulted in an approximately 1-log greater level of cytotoxicity compared to that observed with XRT alone for both NPC cell lines. The two modalities appear to be interacting in a synergistic manner in cancer cells, but not in KS1 fibroblasts. XRT alone stimulated minimal p53 expression in control cells; Ad5CMV-p53 alone induced significant recombinant p53 expression, which was not further enhanced by the addition of XRT. Similar observations were made for p21WAF1/CIP1expression. No changes were observed for bax or bcl-2 expression with any of these treatments. Apoptosis was induced following 4 Gy of XRT alone, but was observed after only 2 Gy when combined with Ad5CMV-p53. Cell cycle analysis indicated that Ad5CMV-p53 infection

  8. Choanal stenosis: a rare complication of radiotherapy for nasopharyngeal carcinoma; Stenose choanale post-radique: une complication rare de la radiotherapie des carcinomes nasopharynges

    Energy Technology Data Exchange (ETDEWEB)

    Bonfils, P.; Preobrajenski, N. de [Universite Rene-Descartes, Hopital Europeen Georges-Pompidou, Service d' ORL et de Chirurgie Cervicofaciale, Faculte de Medecine Paris-Descartes, 75 - Paris (France); Florent, A. [Cabinet d' ORL, 75 - Paris (France); Bensimon, J.L. [Cabinet de radiologie, 75 - Paris (France)

    2007-05-15

    Choanal stenosis is usually a congenital anomaly in children. Acquired choanal stenosis after radiotherapy for nasopharyngeal carcinoma is a very rare pathology; only two publications report seven cases in the literature. We describe the clinical history, preoperative evaluation, surgical treatment and outcome of a case of acquired choanal stenosis after radiotherapy. The patient, a 56-year-old woman, presented with a history of nasopharyngeal carcinoma (T2- NO-MO) one year before that had been successful treated with radiotherapy (68 Gy). At the end of radiotherapy, she complained of complete nasal obstruction, anosmia and hearing loss due to a bilateral serous otitis media. Bilateral complete choanal stenosis was confirmed by endoscopy and CT scan. Functional endoscopic surgery was performed, and nasal stents were left in place for 3 weeks. One year after, the patient have good airflow, and a patent nasopharynx without choanal stenosis. In conclusion, choanal stenosis is an unusual complication of radiotherapy that can be successfully treated with trans-nasal endoscopic resection. (authors)

  9. 局部晚期鼻咽癌同期放化疗顺铂单药每周方案剂量递增临床研究%Radiation therapy concurrent with weekly cisplatin therapy for Ioco-regionally advanced nasopharyngeal carcinoma: outcomes of a clinical trial

    Institute of Scientific and Technical Information of China (English)

    Daiyuan Ma; Chunqiao Fu; Bangxian Tan; Mi Liu; Xianfu Li; Yeqin Zhou

    2011-01-01

    Objective: The purpose of this study was to define the maximum tolerated dose (MTD) by describing the doselimiting toxicity (DLT) of weekly cisplatin concurrently with conventional plus 3-dimensional conformal radiotherapy (CT +3DCRT) in patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). Methods: Patients with loco-regionally advanced NPC (Ⅲ/Ⅳa stage) were enrolled into a dose-escalating study. Toxicity was graded according to Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0). MTD was defined when 2 of 6 patients developed DLT. The starting dose of cisplatin was 15 mg/m2/w, with a subsequent dose escalation of 5 mg/m2/w in cohorts of 3 new patients. CT +3DCRT was given to the nasopharynx and the upper neck; the lower neck was treated by a single anterior field irradiation. The prescription dose was 70-80 Gy by 35-40 fractions to the nasopharynx gross tumor, and 66-70 Gy by 33-35 fractions to the positive neck lymph nodes. Results: From Jun. 2008 to Sep. 2009, 24 patients received complete chemoradiotherapy, and all of them were eligible for toxicity evaluation. On the first five dose levels of 15 mg/m2/w and 35 mg/m2/w, no patient experienced DLT. On the next dose level of 40 mg/m2/w, 1 patient experienced DLT of grade 3 myelosuppression for 1.4 weeks, and among the additional 3 patients, no one developed DLT. On the seventh dose level of 45 mg/m2/w, all the patients developed grade 3 myelosuppression for more than 1 weeks, and the dose-escalating trial stopped. The 23 (95.8%) patients achieved clinicai complete remission (CR) in the local site; 22 (91.7%) achieved CR in the regional site, and all patients got CR 3 months later. After a median follow-up of 16.4 months, 1 patient developed liver metastases 2 months later, 1 patient developed bone metastases 10 months later and 22 kept disease-free survival. Conclusion: The MTD of cisplatin weekly with concurrent CT + 3DCRT for local advanced NPC is 40 mg/m2/w, with

  10. An analysis of factors affecting local control and survival in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    This study was performed to find out the prognostic factors affecting local control, survival and disease free survival rate in nasopharyngeal carcinomas treated with chemotherapy and radiation therapy. We analysed 47 patients of nasopharyngeal carcinomas, histologically confirmed and treated at Chonnam University Hospital between July 1986 and June 1996, retrospectively. Range of patients' age were from 16 to 80 years (median; 52 years). Thirty three (70%) patients was male. Histological types were composed of 3 (6%) keratinizing, 30 (64%) nonkeratinizing squamous cell carcinoma and 13 (28%) undifferentiated carcinoma. Histological type was not known in 1 patient (2%). We restaged according to the staging system of 1997 American Joint Committee on Cancer. Forty seven patients were recorded as follows:T1; 11 (23%), T2a; 6 (13%), T2b; 9 (19%), T3; 7 (15%), T4; 14 (30%), and NO; 7 (15%), N1; 14 (30%), N2; 21 (45%), N3; 5 (10%). Clinical staging was grouped as follows: Stage 1; 2 (4%), IIA; 2 (4%), IIB; 10 (21%), III; 14 (30%), IVA; 14 (30%) and IVB; 5 (11%). Radiation therapy was done using 6 MV and 10 MV X-ray of linear accelerator. Electron beam was used for the lymph nodes of posterior neck after 4500 cGy. The range of total radiation dose delivered to the primary tumor was from 6120 to 7920 cGy (median; 7020 cGy). Neoadjuvant chemotherapy was performed with cisplatin+5-fluorouracil (25 patients) or cisplatin+pepleomycin (17 patients) with one to three cycles. Five patients did not received chemotherapy. Local control rate, survival and disease free survival rate were calculated by Kaplan-Meier method. Generalized Wilcoxon test was used to evaluate the difference of survival rates between groups. Multivariate analysis using Cox proportional hazard model was done for finding prognostic factors. Local control rate was 81% in 5 year. Five year survival rate was 60% (median survival; 106 months). We included age, sex, cranial nerve deficit, histologic type, stage

  11. Suppression of bcl-2 Gene by RNA Interference Increases Chemosensitivity to Cisplatin in Nasopharyngeal Carcinoma Cell Line CNE1

    Institute of Scientific and Technical Information of China (English)

    Zhi-Hua YIN; Cai-Ping REN; Feng LI; Xu-Yu YANG; Hui LI; Ming ZHAO; Kai-Tai YAO

    2004-01-01

    To explore the effect of suppressing BCL-2 expression using RNA interference (RNAi) technique in nasopharyngeal carcinoma cell line CNE1. CNE1 cell lines stably expressing shRNAs targeted bcl-2 and GL3 gene were established and gene expression inhibition was assessed by Western blotting analysis. The effect of suppressing bcl-2 by RNAi on cell growth was studied, the apoptosis induction and the sensitization of CNE 1 cells to cisplatin were quantified by MTT assay and flow cytometry. The results showed that: stable transfection of CNE 1 cells with vectors expressing shRNAs against bcl-2 decreased the expression of BCL-2 protein; suppression of BCL-2 expression did not affect cell proliferation but could increase the chemosensitivity to cisplatin in CNE1 cells. This will help physicians to make some clinical trials of gene therapy on nasopharyngeal carcinoma by RNAi.

  12. Effects of holistic nursing on protection and control of nasopharyngeal carcinoma patient' oral mucosa damage during radiotherapy

    International Nuclear Information System (INIS)

    Objective: To explore if the overall care can effectively control nasopharyngeal carcinoma patients' oral mucosa damage during radiotherapy. Method: Forty-seven nasopharyngeal carcinoma patients were randomly divided into test group (24 cases) and control group (23 cases). Patients in test group received mental nursing,oral care and health guidance plus the routine nursing, and patients in control group just given routine nursing. Result: The damaged degree of oral mucosal was lighter in test group than that in control group, and the difference was statistically significant (χ2=5.181 and 4.449, both P<0.05). Conclusion: The damage of oral mucosa can controlled effectively by holistic nursing during radiotherapy. (authors)

  13. Proteomic analysis of docetaxel resistance in human nasopharyngeal carcinoma cells using the two-dimensional gel electrophoresis method.

    Science.gov (United States)

    Peng, Xingchen; Gong, Fengming M; Ren, Min; Ai, Ping; Wu, ShaoYong; Tang, Jie; Hu, XiaoLin

    2016-09-01

    Docetaxel-based chemotherapy has been recommended for advanced nasopharyngeal carcinoma (NPC). However, treatment failure often occurs because of acquired drug resistance. In this study, a docetaxel-resistant NPC cell line CNE-2R was established with increasing doses of docetaxel for more than 6 months. Two-dimensional gel electrophoresis and ESI-Q-TOF-MS were used to compare the differential expression of docetaxel-resistance-associated proteins between human NPC CNE-2 cells and docetaxel-resistant CNE-2R cells. As a result, 24 differentially expressed proteins were identified, including 11 proteins with increased expression and 13 proteins with decreased expression. These proteins function in diverse biological processes such as metabolism, signal transduction, calcium ion binding, immune response, proteolysis, and so on. Among these, α-enolase (ENO1), significantly upregulated in CNE-2R, was selected for detailed analysis. Inhibition of ENO1 by shRNA restored CNE-2R cells' sensitivity to docetaxel. Moreover, overexpression of ENO1 could facilitate the development of acquired resistance of docetaxel in CNE-2 cells. Western blot and reverse-transcription PCR data of clinical samples confirmed that α-enolase was upregulated in docetaxel-resistant human NPC tissues. Finding such proteins might improve interpretation of the molecular mechanisms leading to the acquisition of docetaxel chemoresistance. PMID:27333594

  14. EphA2 silencing in nasopharyngeal carcinoma leads to decreased proliferation, invasion and increased sensitization to paclitaxel.

    Science.gov (United States)

    Tan, Pingqing; Liu, Yong; Yu, Changyun; Su, Zhongwu; Li, Guo; Zhou, Xiaojuan; Huang, Donghai; Zhang, Xin; Qiu, Yuanzheng; Tian, Yongquan

    2012-09-01

    EphA2 is frequently overexpressed and functionally altered in a variety of human cancers. However, its roles in human nasopharyngeal carcinoma (NPC) remain unclear. To investigate the roles of EphA2 in the development and progression of NPC, we initially evaluated the expression pattern of EphA2 protein in NPC tissues using western blotting and CCK-8 assay. Fluorescence-activated cell sorting analysis and invasion assay were conducted to observe the effects of EphA2 inhibition in vivo. Our results demonstrated that EphA2 was overexpressed in NPC specimens and the expression of EphA2 was significantly associated with T classification, advanced clinical stage and lymph node metastasis. Moreover, human NPC 5-8F cells were infected with lentiviral vector-mediated EphA2-specific shRNA, which resulted in the significant inhibition of cell growth, invasion of 5-8F cells and markedly enhanced the sensitivity of 5-8F cells to the chemotherapeutic agent paclitaxel in vitro. Collectively, our results demonstrate that EphA2 is involved in malignant cell behavior and is a potential therapeutic target in human NPC. PMID:23741245

  15. Prognostic score models for survival of nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy and chemotherapy

    OpenAIRE

    Zeng, Lei; Guo, Pi; Li, Jin-Gao; Han, Fei; Li, Qiang; Lu, Yong; Deng, Xiao-wu; Zhang, Qing-Ying; Lu, Tai-xiang

    2015-01-01

    Purpose To establish accurate prognostic score models to predict survival for patients with nasopharyngeal carcinoma (NPC), treated with intensity-modulated radiotherapy (IMRT) and chemotherapy. Materials and methods Six hundred and seventy-five patients with newly diagnosed, nonmetastatic and histologically proven NPC who were treated with IMRT and chemotherapy were analyzed retrospectively. Samples were split randomly into a training set (n = 338) and a test set (n = 337) to analyze. All da...

  16. Enhanced inhibitory effect of curcumin via reactive oxygen species generation in human nasopharyngeal carcinoma cells following purple-light irradiation

    OpenAIRE

    Wang, Dujuan; Hu, Jiang; LV, Lin; XIA, XIUWEN; Liu, Jianzhong; Li, Xiaoyuan

    2013-01-01

    Curcumin, a traditional medicine, exhibits anti-carcinogenic properties in various cell lines and animals. As a phenolic compound, curcumin is light-sensitive and photoactived curcumin exhibits a greater anticancer effect compared with curcumin alone. However, the mechanisms by which curcumin inhibits tumor cell growth in human nasopharyngeal carcinoma (NPC) cells following purple light (PL) irradiation remains unclear. In the present study, CNE1 and CNE2 cells were treated with curcumin and ...

  17. Effect of heparin on apoptosis in human nasopharyngeal carcinoma CNE2 cells

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In order to study the mechanism of the effect of heparin on apoptosis in carcinoma cells, the nasopharyngeal carcinoma cell line CNE2 was used to identify the effect of heparin on apoptosis associated with the expression of c-myc, bax, bcl-2 proteins by use of Hoechst 33258 staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), agarose gel electrophoresis, and flow cytometry, as well as Western blot analysis. The results showed that heparin induced apoptosis of CNE2 cells including the morphologic changes such as reduction in the volume, and the nuclear chromatin condensation, as well as the “ladder pattern” revealed by agarose gel electrophoresis of DNA in a concentration-dependent manner.The number of TUNEL-positive cells was dramatically increased to 33.6±1.2% from 2.8±0.3% by treat ment with heparin in different concentrations (10~40 kU/L). The apoptotic index was increased to 32.5% from 3.5% by detecting SubG1 peaks on flow cytometry. Western blot analysis showed that levels of bcl-2,bax and c-myc were significantly overexpressed by treatment with the increase of heparin concentrations.These results suggest that heparin induces apoptosis of CNE2 cells, which may be regulated by differential expression of apoptosis-related genes.

  18. 68Ga-DOTA0-Tyr3-octreotide positron emission tomography in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    PET/CT with 68Ga-labelled [DOTA0,Tyr3]-octreotide (68Ga-DOTA-TOC PET/CT) is a routinely used imaging modality for neuroendocrine tumours expressing somatostatin receptors (SSTR). Recent studies have shown SSTR expression in head and neck squamous cell carcinoma, albeit lower than in highly differentiated neuroendocrine tumours. We sought to determine whether nasopharyngeal carcinoma (NPC) positive for Epstein-Barr virus (EBV), a rare subtype of head and neck cancer, shows increased 68Ga-DOTA-TOC uptake indicating expression of SSTR. Five patients with untreated, histologically proven EBV-positive NPC were referred for 68Ga-DOTA-TOC PET/CT. Tracer uptake in tumour lesions was assessed visually and semiquantitatively measuring maximum standardized uptake values (SUVmax) and tumour to background ratios. Increased tumour-specific uptake was detected in all five patients with a median SUVmax of 10.6 (range 3.6 - 17.1) in the primary tumour and 13.2 (range 6.1 - 14.5) in cervical lymph node metastases. 68Ga-DOTA-TOC PET/CT demonstrated tracer uptake in EBV-positive NPC comparable to that in highly differentiated neuroendocrine tumours. This observation is consistent with increased SSTR expression in EBV-positive NPC and may open new diagnostic and therapeutic windows in NPC. (orig.)

  19. Nuclear overexpression of metastasis-associated protein 1 correlates significantly with poor survival in nasopharyngeal carcinoma

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    Li Wen-Fei

    2012-04-01

    Full Text Available Abstract Background Metastasis-associated protein 1 (MTA1 has been associated with poor prognosis in several malignant carcinomas. The purpose of this study was to investigate the expression and prognostic value of MTA1 in nasopharyngeal carcinoma (NPC. Methods MTA1 expression was assessed using immunohistochemistry in paraffin-embedded tumor specimens from 208 untreated NPC patients. Cox regression analysis was used to calculate the hazard ratio (HR, 95% confidence interval (CI and identify independent prognostic factors, and recursive partitioning analysis was used to create a decision tree. Results Nuclear overexpression of MTA1 was observed in 48.6% (101/208 of the NPC tissues. Nuclear overexpression of MTA1 correlated positively with N classification (P = 0.02, clinical stage (P = 0.04, distant metastasis (P P = 0.01. Additionally, nuclear overexpression of MTA1 correlated significantly with poorer distant metastasis-free survival (DMFS; P P P = 0.02 and poorer OS (HR, 1.98; 95% CI, 1.09–3.59; P = 0.03. Using recursive partitioning analysis, the NPC patients could be classified with a low, intermediate or high risk of distant metastasis and death, on the basis of clinical stage, age and MTA1 expression. Conclusion The results of this study suggest that nuclear overexpression of MTA1 correlates significantly with poorer DMFS and poorer OS in NPC. MTA1 has potential as a novel prognostic biomarker in NPC.

  20. Epstein-Barr virus genomes in undifferentiated and squamous cell nasopharyngeal carcinomas in Italian patients.

    Science.gov (United States)

    Della Torre, G; Pilotti, S; Donghi, R; Pasquini, G; Longoni, A; Grandi, C; Salvatori, P; Pierotti, M A; Rilke, F

    1994-03-01

    Although undifferentiated carcinoma (UC) and squamous cell carcinoma (SCC) of the nasopharynx are regarded as two distinct histopathologic and clinical entities, it is unclear whether, like UC, SCC carries Epstein-Barr virus (EBV) genomes. We used the polymerase chain reaction (PCR) on paraffin-embedded biopsy specimens to test for the presence of EBV DNA in 20 cases of UC and 9 cases of SCC. Multiple copies of the viral genome were regularly detected in all UCs; however, of the nine cases of SCC, seven had no detectable EBV DNA and two contained viral genomes in a low copy number. In parallel, a marked difference in the serum levels of anti-EBV antibodies between patients with UC and SCC was found. Our findings provide evidence for the specific association of EBV with UC in Italian patients and prove by means of a highly sensitive molecular technique that SCC is occasionally related to EBV DNA. Because of the absence of EBV DNA in most cases of SCC and the minimal viral DNA copy number in the few EBV-associated cases of SCC, a different pathway of oncogenic transformation and growth of the nasopharyngeal epithelium is suggested for SCC and UC.

  1. An Analysis on Prognosis of Locoregionally Advanced Nasopharyngeal Carcinoma Treated with IMRT and Platinum-based Chemotherapy%调强放射治疗联合铂类化疗治疗局部晚期鼻咽癌预后分析

    Institute of Scientific and Technical Information of China (English)

    郭文杰; 许建华; 卞秀华; 姜雪松; 郭业松; 王雪; 宗丹; 何侠

    2012-01-01

    [目的]评价调强放射治疗联合铂类化疗治疗不同亚组局部晚期鼻咽癌的预后.[方法]将181例连续收治经病理学确诊的初治局部晚期鼻咽癌分为3组,以局部扩展为主要特征的T3~4N0~1M066例,以区域淋巴结转移为主要特征的T1~2N2~3M0 42例及混合型T3~4N2~3M0 73例,均采用调强放射治疗合并以铂类为基础的诱导化疗及同步化疗.中位随访24个月.[结果]局部扩展型、区域淋巴结转移型和混合型2年局部区域控制率分别为92.3%、100%及97.2% (P=0.32);2年无远处转移生存率分别为91.1%,78.2%和76.3% (P=0.016);2年无进展生存率分别为86.7%,78.2%和77.0%(P=0.095).COX多因素分析示N分期是局部晚期鼻咽癌远处转移及疾病相关死亡的独立的危险因素(HR=2.99,95 %CI:1.65~5.44;HR=3.20,95%CI:1.58~6.49).[结论]在调强放疗联合铂类化疗的治疗背景下,局部及区域晚期鼻咽癌中N2~3亚组预相对较差,远处转移率及疾病相关死亡率上升.%[Purpose] To investigate the prognosis of locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy (IMRT) and platinum-based chemotherapy. [Methods] One hundred eighty-one patients with locally advanced nasopharyngeal carcinoma were retrospectively divided into three subgroups: locally advanced (T3-4N0-1M0) group(n =66), regionally advanced (T1-2N2-3M0)group (n= 42) and the mixed group(T3-4V2-3,M0)(n=73). The patients were all treated with definitive intensity-modulated radiotherapy and platinum-based chemotherapy with median follow-up of 24 months. [Results] The 2-year locoregional control (LRC) rate for locally advanced group,regionally advanced group,and the mixed type group was 92.3%, 100% and 97.2% respectively(P=0.32),the 2-year distant metastasis free survival(DMFS) rate was 91.1%,78.2% and 76.3% repectively (P=0.016),the 2-year progress free survival (PFS) rate was 86.7%,78.2% and 77

  2. Can Intensity-Modulated Radiotherapy Preserve Oral Health-Related Quality of Life of Nasopharyngeal Carcinoma Patients?

    International Nuclear Information System (INIS)

    Purpose: To investigate the changes in salivary function and oral health-related quality of life for patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy (IMRT). Methods and Materials: A total of 57 patients with early-stage nasopharyngeal carcinoma received IMRT. The parotid and whole saliva flow was measured, and the Medical Outcomes Study 36-item short form, European Organization for Research and Treatment of Cancer Quality of Life questionnaire-C30, European Organization for Research and Treatment of Cancer Quality of Life questionnaire 35-item head-and-neck module, and Oral Health Impact Profile questionnaires were completed at baseline and 2, 6, 12, 18, and 24 months after IMRT. Results: Parotid saliva flow recovered fully after 1 year and maintained. Whole saliva flow recovered partially to 40% of baseline. A general trend of deterioration in most quality of life scales was observed after IMRT, followed by gradual recovery. Persistent oral-related symptoms were found 2 years after treatment. Conclusion: IMRT for early-stage nasopharyngeal carcinoma could only partially preserve the whole salivary function and oral health-related quality of life.

  3. Can Intensity-Modulated Radiotherapy Preserve Oral Health-Related Quality of Life of Nasopharyngeal Carcinoma Patients?

    Energy Technology Data Exchange (ETDEWEB)

    Pow, Edmond H.N., E-mail: ehnpow@hku.hk [Oral Rehabilitation, University of Hong Kong Faculty of Dentistry, Hong Kong Special Administrative Region (China); Kwong, Dora L.W.; Sham, Jonathan S.T.; Lee, Victor H.F.; Ng, Sherry C.Y. [Department of Clinical Oncology, University of Hong Kong Li Ka Shing Faculty of Medicine, Hong Kong Special Administrative Region (Hong Kong)

    2012-06-01

    Purpose: To investigate the changes in salivary function and oral health-related quality of life for patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy (IMRT). Methods and Materials: A total of 57 patients with early-stage nasopharyngeal carcinoma received IMRT. The parotid and whole saliva flow was measured, and the Medical Outcomes Study 36-item short form, European Organization for Research and Treatment of Cancer Quality of Life questionnaire-C30, European Organization for Research and Treatment of Cancer Quality of Life questionnaire 35-item head-and-neck module, and Oral Health Impact Profile questionnaires were completed at baseline and 2, 6, 12, 18, and 24 months after IMRT. Results: Parotid saliva flow recovered fully after 1 year and maintained. Whole saliva flow recovered partially to 40% of baseline. A general trend of deterioration in most quality of life scales was observed after IMRT, followed by gradual recovery. Persistent oral-related symptoms were found 2 years after treatment. Conclusion: IMRT for early-stage nasopharyngeal carcinoma could only partially preserve the whole salivary function and oral health-related quality of life.

  4. Hypertrophic adenoids in patients with nasopharyngeal carcinoma:appearance at magnetic resonance imaging before and after treatment

    Institute of Scientific and Technical Information of China (English)

    Yao-Pan Wu; Pei-Qiang Cai; Li Tian; Jie-Hua Xu; Richard Alan Mitteer Jr; Yi Fan; Zhenfeng Zhang

    2015-01-01

    Introduction:Patients with nasopharyngeal carcinoma (NPC) sporadically develop abnormal adenoids. Nasopharyngeal adenoids are usually included in the gross tumor volume (GTV) but may have different therapeutic responses than tumor tissue. Therefore, distinguishing adenoids from tumor tissue may be required for precise and efficient chemoradiotherapy and radiotherapy. We characterized nasopharyngeal adenoids and investigated the therapeutic responses of NPC and nasopharyngeal adenoids using magnetic resonance imaging (MRI). Methods:MRI data from 40 NPC patients with a coexisting adenoid mass before and after treatment were analyzed. The features of the adenoid masses, including location, striped appearance, size, interface, symmetry/asymmetry, and cysts, were evaluated. Treatment response were scored according to the World Health Organization guidelines. Results:A striped appearance was observed in 36 cases before treatment and in all cases after treatment. In these 36 cases, the average GTVs including and excluding the uninvolved adenoids were 19.8 cm3 and 14.8 cm3, respectively. The average percentage change after excluding the uninvolved adenoids from the GTV was 31.0%. Stable disease in the adenoids was identified in 27 (96.4%) of 28 patients after neoadjuvant chemotherapy, while NPC clearly regressed. Partial adenoid responses were identified in 33 (82.5%) of 40 patients at 3 months after chemoradiotherapy or radiotherapy, whereas complete tumor responses were achieved in all patients. Six months after treatment, the adenoids continued to atrophy but did not disappear, and tumor recurrence was not found. Conclusions:Nasopharyngeal adenoids and carcinoma tissue in NPC patients can be distinguished by using MRI and have different responses to chemoradiotherapy and radiotherapy. These findings contribute to better delineating the GTV of NPC, based on which spatially optimized strategies can be developed to render precise and efficient chemoradiotherapy and

  5. Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China

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    Li Zuguo

    2008-06-01

    Full Text Available Abstract Background The pathogenesis of nasopharyngeal carcinoma (NPC is a complicated process involving genetic predisposition, Epstein-Bar Virus infection, and genetic alterations. Although some oncogenes and tumor suppressor genes have been previously reported in NPC, a complete understanding of the pathogenesis of NPC in the context of global gene expression, transcriptional pathways and biomarker assessment remains to be elucidated. Methods Total RNA from 32 pathologically-confirmed cases of poorly-differentiated NPC was divided into pools inclusive of four consecutive specimens and each pool (T1 to T8 was co-hybridized with pooled RNA from 24 normal non-cancerous nasopharyngeal tissues (NP to a human 8K cDNA array platform. The reliability of microarray data was validated for selected genes by semi-quantitative RT-PCR and immunohistochemistry. Results Stringent statistical filtering parameters identified 435 genes to be up-regulated and 257 genes to be down-regulated in NPC compared to NP. Seven up-regulated genes including CYC1, MIF, LAMB3, TUBB2, UBE2C and TRAP1 had been previously proposed as candidate common cancer biomarkers based on a previous extensive comparison among various cancers and normal tissues which did not, however, include NPC or NP. In addition, nine known oncogenes and tumor suppressor genes, MIF, BIRC5, PTTG1, ATM, FOXO1A, TGFBR2, PRKAR1A, KLF5 and PDCD4 were identified through the microarray literature-based annotation search engine MILANO, suggesting these genes may be specifically involved in the promotion of the malignant conversion of nasopharyngeal epithelium. Finally, we found that these differentially expressed genes were involved in apoptosis, MAPK, VEGF and B cell receptor signaling pathways and other functions associated with cell growth, signal transduction and immune system activation. Conclusion This study identified potential candidate biomarkers, oncogenes/tumor suppressor genes involved in several

  6. BZLF1 Expression of EBV is correlated with PARP1 Regulation on Nasopharyngeal Carcinoma Tissues

    Directory of Open Access Journals (Sweden)

    Wahyu nur laili fajri, Ahmad Rofi'i, Fatchiyah Fatchiyah

    2013-04-01

    Full Text Available Nasopharyngeal carcinomas (NPC is a cancer that arises in the epithelial tissue that covers the inside of the nasopharyngeal mucosa and nasopharynx. Infected Epstein Barr Virus (EBV cell in a latent infection associated with the expression of nine latent proteins. Latent Membrane Protein 1 (LMP1 is one of latent proteins, and mayor EBV oncoprotein, with functions including virus growth, and to activate BamHI-Z Leftward Reading Frame 1 (BZLF1-EBV, which can inhibit p53 to induce apoptotic resistance, metastasis, and immune modulation. The body will respond to the expansion of EBV infection with activation of Poly(ADP-ribosePolymerase-1 (PARP1. The objective of study is to observe the expression of BZLF1 and determine PARP1 regulation in nasopharyngeal tissues. NPC-T2, NPC-T3 and polyp tissues slides are from Ulin Hospital, Banjarmasin. To characterize the necrotic cells such as pyknosis, karyorrhexsis, and karyolysis, histological slides were stained by HE that the necrotic cells measured by using a BX-53 microscope (Olympus with CellSens Standard software. Tissues slides were stained by using immunofluorohistochemistry with EBV-BZLF1 antibody-Mouse anti-EBV monoclonal antibody against Goat anti-mouse IgG-FITC and anti-PARP1 antibody (MC-10 against Goat anti-mouse IgG labeled Rhodamin. The expression intensities were measured by Confocal Laser Scanning Microscope (Olympus. The percentage number of necrotic cells and BZLF1 and PARP1 expression intensity were analyzed using SPSS 16.0 by one-way ANOVA test with α = 0.05, beside that we use correlate and regression analyze. The research showed that the amount of karryorhexis higher than pyknosis and karyolysis in both tissues. BZLF1 expression 1.79 INT/sel (in polyp, 2.76 INT/sel (NPC Type 2 and 4.36 INT/sel (NPC Type 3, PARP1 expression 2.25 INT/sel (in polyp, 3.31 INT/sel (NPC Type 2, dan 5.93 INT/sel (NPC Type 3.The high of intensity of expression BZLF1 induced the increasing of PARP1 expression

  7. Osteoradionecrosis of the upper cervical spine: MR imaging following radiotherapy for nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    King, Ann D. [Department of Diagnostic Radiology and Organ Imaging, Faculty of Medicine, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong (China)], E-mail: king2015@cuhk.edu.hk; Griffith, James F.; Abrigo, Jill M. [Department of Diagnostic Radiology and Organ Imaging, Faculty of Medicine, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong (China); Leung Singfai [Department of Clinical Oncology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong (China); Yau Fungkwai [Department of Orthopaedics and Traumatology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong (China); Tse, Gary M.K. [Department of Anatomical and Cellular Pathology, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong (China); Ahuja, Anil T. [Department of Diagnostic Radiology and Organ Imaging, Faculty of Medicine, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong (China)

    2010-03-15

    Purpose: To document the MRI appearances of radiation-induced abnormalities in the cervical spine following treatment for nasopharyngeal carcinoma (NPC). Methods: Patients with radiation-induced abnormalities in the upper cervical spine were identified from a retrospective analysis of reports from patients undergoing MRI follow-up. Imaging and clinical records of these patients were reviewed. Symmetrical distribution of abnormalities at C1 (anterior arch {+-} adjacent aspect of the lateral masses) and C2 (dens {+-} body especially with a characteristic horizontal rim of marrow preservation above the inferior endplate) were considered typical for osteoradionecrosis (ORN). Results: Abnormalities of C1/2 were identified in 9/884 (1%) patients. The MRI distribution of abnormalities was typical for ORN in four and atypical in five patients. Abnormal soft tissue was present in the atlantoaxial joint in eight patients, forming a florid mass in six. This soft tissue was in direct continuity with the posterior nasopharyngeal wall ulceration via the retropharyngeal region. The final clinical diagnosis was ORN in eight, five of whom had clinical factors which suggested infection could have played a contributory role, and osteomyelitis in one patient. All patients had undergone additional radiotherapy treatment comprising of brachytherapy (7), stereotactic radiotherapy (1) or radiotherapy boost (2) and three had undergone nasopharyngectomy. Conclusion: ORN of the upper cervical spine following radiotherapy for NPC is more common than previously suspected and is seen in patients with additional treatment, especially brachytherapy. MRI features are often atypical and a contributory role of infection in the development of some cases of ORN is postulated.

  8. Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins.

    Science.gov (United States)

    Chan, Yuk-Kit; Zhang, Huoming; Liu, Pei; Tsao, Sai-Wah; Lung, Maria Li; Mak, Nai-Ki; Ngok-Shun Wong, Ricky; Ying-Kit Yue, Patrick

    2015-10-15

    Exosomes, a group of secreted extracellular nanovesicles containing genetic materials and signaling molecules, play a critical role in intercellular communication. During tumorigenesis, exosomes have been demonstrated to promote tumor angiogenesis and metastasis while their biological functions in nasopharyngeal carcinoma (NPC) are poorly understood. In this study, we focused on the role of NPC-derived exosomes on angiogenesis. Exosomes derived from the NPC C666-1 cells and immortalized nasopharyngeal epithelial cells (NP69 and NP460) were isolated using ultracentrifugation. The molecular profile and biophysical characteristics of exosomes were verified by Western blotting, sucrose density gradient and electron microscopy. We showed that the C666-1 exosomes (10 and 20 μg/ml) could significantly increase the tubulogenesis, migration and invasion of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Subsequently, an iTRAQ-based quantitative proteomics was used to identify the differentially expressed proteins in C666-1 exosomes. Among the 640 identified proteins, 51 and 89 proteins were considered as up- and down-regulated (≥ 1.5-fold variations) in C666-1 exosomes compared to the normal counterparts, respectively. As expected, pro-angiogenic proteins including intercellular adhesion molecule-1 (ICAM-1) and CD44 variant isoform 5 (CD44v5) are among the up-regulated proteins, whereas angio-suppressive protein, thrombospondin-1 (TSP-1) was down-regulated in C666-1 exosomes. Further confocal microscopic study and Western blotting clearly demonstrated that the alteration of ICAM-1 and TSP-1 expressions in recipient HUVECs are due to internalization of exosomes. Taken together, these data strongly indicated the critical roles of identified angiogenic proteins in the involvement of exosomes-induced angiogenesis, which could potentially be developed as therapeutic targets in future.

  9. Upregulation of KLHDC4 Predicts a Poor Prognosis in Human Nasopharyngeal Carcinoma.

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    Yi-Fan Lian

    Full Text Available Kelch proteins are implicated in the pathogenesis of many human diseases, including cancer. Nasopharyngeal carcinoma (NPC is a rare malignancy in most countries, but prevalent in southern China and certain areas of Southeast Asia. In this study, we identified Kelch Domain Containing 4 (KLHDC4, an orphan member of the kelch repeat superfamily, as a prognosis marker for NPC. We examined the expression of KLHDC4 in 168 NPC cases by immunohistochemical staining and found a substantially higher level of KLHDC4 in NPC biopsies compared to adjacent normal nasopharyngeal mucosa. KLHDC4 expression was significantly related to the T classification (P <0.05, N classification (P <0.05 and total staging (P <0.01 in NPC, and patients with higher KLHDC4 expression had poorer overall (P <0.01 and metastasis-free survival (P <0.05 rates. Knockout (KO of KLHDC4 via CRISPR/Cas9-mediated gene editing in NPC cell line dramatically inhibited cell proliferation, colony formation in soft agar and tumor formation in nude mice. In addition, cell migration and invasion were also impaired by KLHDC4 depletion as revealed by wound healing and Transwell assay. Mechanically, loss of KLHDC4 markedly induced spontaneous apoptosis in NPC cells, as evidenced by increased levels of cleaved caspase-3 and cleaved PARP. Consistently, KLHDC4 knockout cell-derived xenografts also showed elevated cleaved caspase-3 and PARP but reduced Ki-67 staining. In conclusion, our results suggest that KLHDC4 promotes NPC oncogenesis by suppressing cellular apoptosis. Thus, KLHDC4 may serve as a prognosis biomarker and a potential therapeutic target for NPC.

  10. Causes of interruption of radiotherapy in nasopharyngeal carcinoma patients in Taiwan

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    Chen, Yu P.; Tsang, Ngan M.; Tseng, Chen K.; Lin, Shinn Y. [Chang Gung Memorial Hospital, Taiwan (China)

    2000-05-01

    Nasopharyngeal cancer (NPC) is now curable with early diagnosis and radiotherapy treatment. In the past several decades, few studies have investigated why some patients fail to complete the recommended full course of radiotherapy. A total of 3273 nasopharyngeal carcinoma patients were treated at the Radiation Oncology Department of Linkou Chang Gung Memorial Hospital in a span of 18 years from 1979 to 1996. Among these patients, 276 did not complete the full course of treatment of radiation therapy. The medical records of these patients were reviewed to determine the factors contributing to treatment interruption. Of the 276 patients whose treatment was interrupted, 120 (43.5%) were unable to endure the acute side effects of radiation therapy and were afraid of the possible complications resulting from the treatment; 57 (20.7%) had doubts about the diagnosis or had the subjective perception that the treatment offered would be ineffective in view of the severity of their disease; 50 (18.1%) resorted to folk prescriptions; 17 (6.2%) were faced with socioeconomic problems; 15 (5.4%) sought treatment at another hospital owing to transport considerations; 10 (3.6%) stopped radiation therapy and switched to chemotherapy for palliative management; seven (2.5%) resorted to praying, god worshipping and taking incense powder and magic elixirs because their families were against any established therapy. The acute side effects and complications caused by radiation therapy were the major factors influencing patients' decisions to discontinue treatment. This finding suggests that more attention should be paid to providing care with regard to the acute side effects of radiotherapy and to reinforcing pretreatment education. (author)

  11. Proteomic analysis of exosomes from nasopharyngeal carcinoma cell identifies intercellular transfer of angiogenic proteins

    KAUST Repository

    Chan, Yuk-kit

    2015-04-01

    Exosomes, a group of secreted extracellular nanovesicles containing genetic materials and signaling molecules, play a critical role in intercellular communication. During tumorigenesis, exosomes have been demonstrated to promote tumor angiogenesis and metastasis while their biological functions in nasopharyngeal carcinoma (NPC) are poorly understood. In this study, we focused on the role of NPC-derived exosomes on angiogenesis. Exosomes derived from the NPC C666-1 cells and immortalized nasopharyngeal epithelial cells (NP69 and NP460) were isolated using ultracentrifugation. The molecular profile and biophysical characteristics of exosomes were verified by Western blotting, sucrose density gradient, and electron microscopy. We showed that the C666-1 exosomes (10 and 20 μg/ml) could significantly increase the tubulogenesis, migration and invasion of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. Subsequently, an iTRAQ-based quantitative proteomics was used to identify the differentially expressed proteins in C666-1 exosomes. Among the 640 identified proteins, 51 and 89 proteins were considered as up- and down-regulated (≥ 1.5-fold variations) in C666-1 exosomes compared to the normal counterparts, respectively. As expected, pro-angiogenic proteins including intercellular adhesion molecule-1 (ICAM-1) and CD44 variant isoform 5 (CD44v5) are among the up-regulated proteins, whereas angio-suppressive protein, thrombospondin-1 (TSP-1) was down-regulated in C666-1 exosomes. Further confocal microscopic study and Western blotting clearly demonstrated that the alteration of ICAM-1, and TSP-1 expressions in recipient HUVECs are due to internalization of exosomes. Taken together, these data strongly indicated the critical roles of identified angiogenic proteins in the involvement of exosomes-induced angiogenesis, which could potentially be developed as therapeutic targets in future. This article is protected by copyright. All rights reserved.

  12. Methylation Inactivation Mechanism of Parkin Gene mRNA Expression in Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ni Haifeng; Jiang Bo; Zhou Zhen; Li Yong; Huang Guangwu

    2014-01-01

    Objective:To investigate the methylation inactivation and the clinical signiifcance of Parkin gene mRNA expression in nasopharyngeal carcinoma (NPC). Methods: The methylation-speciifc PCR (MSP) and semi-quantitative reverse transcription PCR (RT-PCR) were used to detect methylation and the mRNA expression level of Parkin gene in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues.The mRNA expression of Parkin gene in two NPC cell lines (CNE1 and CNE2) were detected before and after treatment with the methyltransferase inhibitor 5-aza-2-deoxycytidine so as to analyze the effects of Parkin gene methylation and demethylation on Parkin gene mRNA expression and the relationship between Parkin gene mRNA expression and clinical factors. Results: The methylation frequency of Parkin gene in human NPC tissues was 62.96% (34/54), but didn’t happen in any of 16 cases of NNE tissues. The mRNA expression level was (0.3430±0.4947) in 54 cases of NPC tissues and (1.0052±0.4911) in NNE tissues, showing that the mRNA expression level of NPC tissues was significantly down-regulated (P0.05), but was closely related to lymph node metastasis (P<0.05). Conclusion:Parkin gene mRNA expression, serving as a cancer suppressor gene in the occurrence and development of NPC, is inactivated and regulated by methylation, which also has a negative correlation with lymph node metastasis and could be considered as the judgment of predictive index of clinical prognosis of NPC.

  13. Evaluation of salivary function by sialoscintigraphy in locally advanced nasopharyngeal cancer patients after intensity modulated radiotherapy

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    T. L. Chuang; Y.F. Wang; C H Tsai; J E Chiu; Lee, M. S.; W Y Chiou; Lin, H Y; W T Tsai; S K Hung

    2015-01-01

    Purpose: This study aimed to evaluate the salivary gland function changes by sialoscintigraphy in locally advanced nasopharyngeal cancer (NPC) after intensity modulated radiotherapy (IMRT). Materials And Methods: Salivary function was assessed by sialoscintigraphy. Quantitative sialoscintigraphy was performed in 24 NPC patients prior to and after IMRT. Results were categorized in four groups according to the duration of treatment. The sialoscintigraphy parameters were examined. Results: Sialo...

  14. Prognostic value of wait time in nasopharyngeal carcinoma treated with intensity modulated radiotherapy: a propensity matched analysis.

    Science.gov (United States)

    Chen, Yu-Pei; Mao, Yan-Ping; Zhang, Wen-Na; Chen, Lei; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Zhou, Guan-Qun; Guo, Rui; Sun, Ying; Kang, Tie-Bang; Zeng, Mu-Sheng; Ma, Jun

    2016-03-22

    The aim of this study was to determine the prognostic value of wait time from histological diagnosis to primary treatmen for nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Between October 2009 and February 2012, a total of 1672 NPC patients were retrospectively analyzed. A cutoff value of > 4 weeks was used to define prolonged wait time. Matched patients according to the wait time were identified using propensity score matching (PSM), which was also used to identify matched patients for subsequent stratified analyses. Differences in progression-free survival (PFS), overall survival (OS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS) were estimated using the Kaplan-Meier method and Cox proportional hazards models. In total, 407 pairs of NPC patients were selected by PSM. The 3-year PFS rate was significantly lower for patients with a prolonged wait time (> 4 weeks) than for those with an acceptable wait time (P = 0.035). Stratified analyses revealed that the negative effects of a prolonged wait time occurred primarily in patients with advanced NPC without neoadjuvant chemotherapy (NACT; PFS:P = 0.040; DMFS:P = 0.028). In multivariate analysis, a prolonged wait time was found to be an independent unfavorable prognostic factor for PFS and DMFS in advanced-staged patients without NACT. These results suggest that a prolonged time (> 4 weeks) between diagnosis and primary radical radiotherapy is a disadvantage for NPC patients, particularly those with advanced disease receiving no NACT. Thus, it is necessary to optimize resources for decreasing this wait time, although additional studies are warranted to further clarify our findings. PMID:26942870

  15. The outcome and prognosis factors of adolescent nasopharyngeal carcinoma treated in a single institute-analysis of 148 patients

    International Nuclear Information System (INIS)

    Objective: To evaluate the clinical characteristics, outcome and prognostic factors of adolescent nasopharyngeal carcinoma. Methods: Between Jan 1990 and Dec 2009, totally 148 pathological confirmed nasopharyngeal carcinoma (NPC) patients with age ≤20 years were treated in our hospital, including stage II 8, stage III 58, stage IV 81, and unknown 1 when restaged by TNM system (UICC 2002), ninety-four (63.5%) patients were treated with radiotherapy alone, 54 (36.5%)patients were treated with radiotherapy combined with cisplatin-based chemotherapy. Results: The median follow-up time for all patients was 44.5 months. The 5-year overall survival (OS), local-regional control (LRC) and distant metastasis-free survival (DMFS) rates were 82.9%, 85.1% and 78.6%. There were 42 patients (28.4%) failed with 16 regional recurrence and 29 distant metastasis, and 3 with both; bone metastasis was the most common site of distant metastasis(22/29). In univariate analysis,the adverse prognostic factors for OS were stage T4(χ2=5.61, P=0.018), radiation dose 2=5.30, P=0.021), for LRC was radiation dose 2=4.24, P=0.039). In multivariate analysis, radiation dose 4 were the independent prognostic factors for OS (χ2=5.73, 5.56, P=0.017, 0.018), for LRC was radiation dose 2=5.81, P=0.016). Conclusions: The outcome of the present series was excellent, total nasopharyngeal radiation dose less than 70 Gy is inappropriate. Reduce the distant metastasis and late toxicities were the future direction for the treatment of adolescent nasopharyngeal carcinoma. (authors)

  16. Prognostic significance of pretreated serum lactate dehydrogenase level in nasopharyngeal carcinoma among Chinese population

    Science.gov (United States)

    Zhang, Mingwei; Wei, Shushan; Su, Li; Lv, Wenlong; Hong, Jinsheng

    2016-01-01

    Abstract Background: A large number of studies have investigated the prognostic value of pretreated lactate dehydrogenase (LDH) level in nasopharyngeal carcinoma (NPC) patients while the role of it was inconsistent and inconclusive. Hence, the aim of the current study was to conduct a meta-analysis of all published studies to quantify the prognostic impact of pretreated serum LDH in NPC for Chinese population. Objectives: The aim of the current study was to conduct a meta-analysis of all published studies to quantify the prognostic impact of pretreated serum lactate dehydrogenase (LDH) in nasopharyngeal carcinoma (NPC) for Chinese population. Methods: The PubMed, Medline, Embase, and Web of Science databases were searched for studies that assessed survival outcome and LDH in NPC. Overall survival (OS) was the primary survival outcome. Distant metastasis-free survival (DMFS) and disease-free survival (DFS) were secondary outcomes. The pooled hazard ratios (HRs), associated with 95% confidence intervals (95% CIs), were combined to calculate overall effects. The Cochran Q and I2 statistics were used to assess heterogeneity. When apparent heterogeneity was observed, sensitivity and meta-regression analyses were performed to explore its origin. Results: Sixteen studies, which included 14,803 patients, were enrolled in the current meta-analysis to yield statistics. Overall, the pooled HR for OS in 11 eligible studies with high LDH level was 1.79 (95% CI = 1.47–2.12), and the pooled HR for DMFS in 9 eligible studies with high LDH level was 1.85 (95% CI = 1.48–2.22). Meanwhile, the pooled HR for DFS in 5 eligible studies with high LDH level was 1.63 (95% CI = 1.34–1.91). Egger test and funnel plots revealed that the publication bias in the current meta-analysis was insignificant. Conclusions: The present meta-analysis demonstrated that high pretreated LDH level is significantly associated with poorer OS, DMFS, and DFS, suggesting that pretreated LDH could

  17. Upregulation of metastasis-associated gene 2 promotes cell proliferation and invasion in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Wu MH

    2016-03-01

    Full Text Available Minhua Wu,1,2,* Xiaoxia Ye,2,* Xubin Deng,3,* Yanxia Wu,4 Xiaofang Li,4 Lin Zhang11Department of Histology and Embryology, Southern Medical University, Guangzhou, 2Department of Histology and Embryology, Guangdong Medical University, Zhanjiang, 3Affiliated Cancer Hospital of Guangzhou Medical University, Cancer Center of Guangzhou Medical University, Guangzhou, 4Pathological Diagnosis and Research Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China*These authors contributed equally to this workAims: Metastasis-associated gene 2 (MTA2 is reported to play an important role in tumor progression, but little is known about the role of MTA2 in nasopharyngeal carcinoma (NPC. The aim of the study was to explore the expression and function of MTA2 in NPC.Methods: Expression of MTA2 in NPC tissues and cell lines was detected by immunohistochemistry and Western blotting. Relationship between MTA2 expression and clinicopathological features was analyzed. Stable MTA2-overexpressing and MTA2-siliencing NPC cells were established by transfection with plasmids encoding MTA2 cDNA and lentivirus-mediated short hairpin RNA, respectively. Cell viability was determined by Cell Counting Kit-8 and colony formation assay. Cell migration ability was evaluated by wound healing and transwell invasion assay. The impact of MTA2 knockdown on growth and metastasis of CNE2 cells in vivo was determined by nude mouse xenograft models. Expression of several Akt pathway proteins was detected by Western blotting.Results: MTA2 was upregulated in NPC tissues and three NPC cell lines detected (CNE1, CNE2, and HNE1. MTA2 expression was related to clinical stage and lymph node metastasis of patients with NPC. MTA2 upregulation promoted proliferation and invasion of CNE1 cells, while MTA2 depletion had opposite effects on CNE2 cells. Moreover, MTA2 depletion suppressed growth and metastasis of CNE2 cells in vivo. MTA2 overexpression

  18. Dose-response relationship of nasopharyngeal carcinoma above conventional tumoricidal level: A study by the Hong Kong nasopharyngeal carcinoma study group (HKNPCSG)

    International Nuclear Information System (INIS)

    Background and purpose: To define the dose-response relationship of nasopharyngeal carcinoma (NPC) above the conventional tumoricidal dose level of 66 Gy when the basic radiotherapy (RT) course was given by the 2D Ho's technique. Patients and methods: Data from all five regional cancer centers in Hong Kong were pooled for this retrospective study. All patients (n=2426) were treated with curative-intent RT with or without chemotherapy between 1996 and 2000 with the basic RT course using the Ho's technique. The primary endpoint was local control. The prognostic significance of dose-escalation ('boost') after 66 Gy, T-stage, N-stage, use of chemotherapy, sex and age (≤40 years vs >40 years) was studied. Both univariate and multivariate analyses were performed. Results: On multivariate analysis, T-stage (P< 0.01; hazard ratio [HR], 1.58) and optimal boost (P=0.01; HR, 0.34) were the only significant factors affecting local failure for the whole study population, and for the population of patients treated by radiotherapy alone, but not for patients who also received chemotherapy. The following were independent determinants of local failure for patient groups with different T-stages treated by radiotherapy alone: use of a boost in T1/T2a disease (P=0.01; HR, 0.33); use of a boost (P<0.01; HR, 0.60) and age (P=0.01; HR, 1.02) in T3/T4 tumors. Among patients with T2b tumors treated by radiotherapy alone and given a boost, the use of a 20 Gy-boost gave a lower local failure rate than a 10 Gy-boost. There was no apparent excess mortality attributed to RT complications. Conclusions: Within the context of a multi-center retrospective study, dose-escalation above 66 Gy significantly improved local control for T1/T2a and T3/4 tumors when the primary RT course was based on the 2D Ho's technique without additional chemotherapy. 'Boosting' in NPC warrants further investigation. Caution should be taken when boosting is considered because of possible increase in radiation toxicity

  19. Reversal of chemo-resistance in advanced nasopharyngeal carcinoma by injection of recombinant human p53 adenovirus%重组人p53腺病毒注射液逆转鼻咽癌化疗耐药的研究

    Institute of Scientific and Technical Information of China (English)

    张政; 翁敬锦; 兰桂萍; 韦海明; 覃扬达; 覃颖; 孙金杰; 司勇锋

    2012-01-01

    目的:探讨重组人p53腺病毒(rAd-p53)瘤内注射前后的鼻咽癌原发灶中P糖蛋白(P-glycoprotein,P-gp)、多药耐药相关蛋白(multi-drug resistance-associated protien,MRP)和肺耐药蛋白(lung resistance-related protein,LRP)的表达情况及其意义.方法:71例确诊中晚期鼻咽癌的患者随机分为3组:基因治疗组(27例,行-rAd-p53瘤内注射+同步放化疗)、常规放化疗组(24例)和单纯放疗组(20例).12例同期门诊活检病理为鼻咽黏膜慢性炎患者作为对照.分别收集治疗前、治疗中鼻咽部瘤体组织标本.采用免疫组化法检测鼻咽癌组织中P-gp、MRP和LRP的表达情况.结果:鼻咽癌组中P-gp、MRP及LRP阳性表达率分别为57.7%(41/71)、57.7%(41/71)、53.5%(38/71),黏膜慢性炎组未见P-gp、MRP及LRP表达.基因治疗组治疗前、后原发灶P-gp、MRP和LRP蛋白阳性表达率分别为55.6%和25.9%、63.0%和33.3%、59.3%和25.9%,差异有统计学意义.常规放化疗组治疗前、后鼻咽癌原发灶P-gp、MRP和LRP蛋白阳性表达率分别为62.5%和79.2%、58.3%和70.8%、50%和58.3%,差异无统计学意义.单纯放疗组治疗前、后鼻咽癌原发灶P-gp、MRP和LRP蛋白阳性表达率分别为55.0%和55.O%、50%和40%、50%和55%,差异无统计学意叉.结论:P-gp、MRP和LRP与鼻咽癌的内源性耐药相关;p53基因治疗可一定程度逆转鼻咽癌耐药,可能是其治疗鼻咽癌的作用机制之一.%Objective To investigate the expressions of P-glycoprotein (P-gp), multi-drug resistance-associated protein (MRP), and lung resistance-related protein (LRP) in advanced nasopharyngeal carcinoma (NPC) before and after the intratumoral injection with recombinant human p53 adenovirus (rAd-p53). Methods Seventy-one patients who were diagnosed as advanced NPC were randomly divided into 3 groups: the gene therapy group (n = 27) received intratumoral injection of rAd-p53 and concurrent chemo-radiotherapy, the conventional group (n = 24), and the

  20. Secondary mandibular fibrosarcoma after chemoradiotherapy for undifferentiated nasopharyngeal carcinoma. Report of a case and literature review; Fibrosarcome secondaire de la mandibule apres chimioradiotherapie pour carcinome indifferencie du nasopharynx. A propos d'une observation et revue de la litterature

    Energy Technology Data Exchange (ETDEWEB)

    Kochbati, L.; Besbes, M.; Benna, F.; Maalej, M. [Institut Salah Azaiz, Service de Radiotherapie, Tunis (Tunisia); Boussen, H.; Ben Ayed, F. [Institut Salah Azaiz, Service de Medecine, Tunis (Tunisia); Gritli, S.; Ladgham, A. [Institut Salah Azaiz, Service de Chirurgie ORL, Tunis (Tunisia); Saadi, A. [Institut Salah Azaiz, Service de Radiodiagnostic, Tunis (Tunisia); El May, A. [Institut Salah Azaiz, Service d' Anatomopathologie, Tunis (Tunisia)

    2001-06-01

    Secondary mandibular fibrosarcoma after chemoradiotherapy for undifferentiated nasopharyngeal carcinoma. Report of a case and literature review. Secondary tumours to radio- and/or chemotherapy have rarely been reported after treatment for head and neck cancers. We report a case of mandibular fibrosarcoma observed 7 years after chemoradiotherapy for undifferentiated nasopharyngeal carcinoma in a patient treated when 20 years old. (authors)

  1. Quantitative expression analysis and prognostic significance of the BCL2-associated X gene in nasopharyngeal carcinoma: a retrospective cohort study

    International Nuclear Information System (INIS)

    Nasopharyngeal carcinoma (NPC) is a highly metastatic epithelial malignancy showing high prevalence in Southeast Asia and North Africa. The BCL2-associated X (BAX) gene encodes the most important pro-apoptotic member of the BCL2 family. We have recently shown that BCL2 and BCL2L12, two other members of the same apoptosis-related family, possess significant prognostic value in NPC. The objective of the current study was to analyze BAX mRNA expression in nasopharyngeal biopsies of NPC patients, and to assess its prognostic potential in this disease. Total RNA was isolated from 88 malignant and 9 hyperplastic nasopharyngeal biopsies, resected from Tunisian patients. After cDNA synthesis by reverse transcription of polyadenylated RNA, BAX mRNA expression was analyzed using a highly sensitive quantitative real-time polymerase chain reaction (qRT-PCR) method. Lower BAX mRNA levels were detected in NPC biopsies than in hyperplastic nasopharyngeal samples. BAX mRNA expression status was associated with low tumor extent, negative regional lymph node status, and absence of distant metastases. Kaplan-Meier survival analysis demonstrated that patients with BAX mRNA-positive NPC have significantly longer disease-free survival (DFS) and overall survival (OS). In accordance with these findings, Cox regression analysis revealed that BAX mRNA expression can be considered as a favorable prognostic indicator of DFS and OS in NPC, independent of their gender, age, tumor histology, tumor extent, and nodal status. Furthermore, NPC patients without distant metastases are less likely to relapse when their primary tumor is BAX mRNA-positive, compared to metastasis-free patients with a BAX-negative nasopharyngeal malignancy. This is the first study examining the potential clinical utility of BAX as a prognostic tumor biomarker in NPC. We provide evidence that BAX mRNA expression can be considered as an independent favorable prognostic indicator of DFS and OS in NPC

  2. Evaluation of screening for nasopharyngeal carcinoma: trial design using Markov chain models.

    Science.gov (United States)

    Chen, H H; Prevost, T C; Duffy, S W

    1999-04-01

    In this paper, we develop a Markov chain model to estimate parameters pertaining to the natural history of nasopharyngeal carcinoma (NPC). The model is of progression from no disease to Epstein-Barr virus (EBV) infection, preclinical screen-detectable tumour and clinical tumour. We derive tentative estimates of the parameters of the model, based on limited published data, to assess the efficacy of serum screening in conjunction with clinical assessment (indirect mirror examination for NPC), for example the average duration of the preclinical screen-detectable phase is estimated as 3.1 years. We further apply these parameters to a hypothetical screening trial in the Hong Kong population to assess the efficacy of serum screening with clinical assessment by different combinations of screening regime. Results suggest: (1) there is no substantial difference between 3-yearly and 6-yearly serum screening; and (2) within the same serum screening regime annual and 3-yearly clinical assessment can prevent 33% and 28% of deaths from NPC respectively. Prediction of deaths and surrogate end points can be used to estimate the required sample size and duration for designing a randomized trial of screening for NPC. Based on these findings and power projections, we suggest a design for a randomized trial in a high incidence area such as Hong Kong. PMID:10206310

  3. Late Toxicities after Conventional Radiotherapy for Nasopharyngeal Carcinoma: Incidence and Risk Factors

    Directory of Open Access Journals (Sweden)

    Wicem Siala

    2014-01-01

    Full Text Available Background. To determine the incidence and analyze the factors affecting late toxicity for nasopharyngeal carcinoma patients treated with conventional radiotherapy. Patients and Methods. Retrospective analysis was performed on 239 NPC patients treated between 1993 and 2004 in our institution. One hundred and fifty-seven patients were treated with conventional fractionation (2 Gy per fraction, 5 fractions per week and eighty-two patients with hyperfractionated radiotherapy (1.6 Gy per fraction twice a day, 5 days per week. One hundred fifty nine patients underwent neoadjuvant cisplatin based chemotherapy. Late toxicity was evaluated according to the RTOG/EORTC score. Results. Xerostomia was the most common related complication (98.7%. Neoadjuvant chemotherapy and hyperfractionated radiotherapy did not increase late toxicities. Multivariate analyses showed that radiation dose was a significant factor for hearing impairment, younger age for trismus, initial node status for neck fibrosis, and initial dental hygiene for dental complications. Female gender was associated with significantly higher incidence of trismus and hearing impairment. Conclusion. Conventional radiotherapy was associated with a high rate of late toxicities which affect patients’ quality of life. With the development of three-dimensional conformal radiotherapy and intensity modulated radiotherapy, a reduced incidence of radiation related complications could be expected.

  4. Thallium-201 single-photon emission tomography in the treatment follow-up of nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    In order to assess the usefulness of thallium-201 single-photon emission tomography (SPET) in the treatment follow-up of nasopharyngeal carcinoma (NPC), a total of 75 201Tl SPET studies were performed in 18 patients with histologically proven NPC. The findings were compared with those of magnetic resonance imaging (MRI) before and after therapy. Four patients received radiotherapy alone while the other 14 received concurrent chemo-radiotherapy. Treatment response was classified as complete (CR) or partial (PR) based on the findings of MRI and 201Tl SPET. Intense 201Tl uptake by the tumour was seen in all 18 patients before treatment. After treatment, MRI showed seven CRs and 11 PRs, whereas 201Tl SPET showed 13 CRs and five PRs. In 12 patients, the results of 201Tl SPET were in agreement with those of MRI. In six patients MRI showed PR but 201Tl showed CR. Follow-up (mean 10.6 months) MRI and 201Tl SPET studies of these six patients revealed that tumour gradually decreased and finally vanished in three patients. This preliminary study indicates that 201Tl SPET has potential in the assessment of early response to treatment of patients with NPC when compared with MRI. (orig.)

  5. Prognostic Evaluation of Nasopharyngeal Carcinoma with Bone-Only Metastasis after Therapy

    Science.gov (United States)

    Lu, Tianzhu; Guo, Qiaojuan; Cui, Xiaofei; Chen, Zhuhong; Lin, Shaojun; Xu, Luying; Lin, Jin; Zong, Jingfeng

    2016-01-01

    Purpose To evaluate the prognosis of nasopharyngeal carcinoma (NPC) patients who developed bone-only metastasis after primary treatment and the stratification of these patients into different risk groups based on independent prognostic factors. Materials and Methods Eighty NPC patients who developed bone-only metastasis after definitive radiotherapy from October 2005 to December 2010 were enrolled. All these patients received palliative treatment for bone metastasis, including chemotherapy and/or radiotherapy. Clinical features, treatment modality, and laboratory parameters were examined with univariate and multivariate analyses. Results The median follow-up time was 15.5 months (range, 2–67 months) for the whole cohort. The median overall metastatic survival (OMS) time and the 2-year estimate OMS rate were 26.5 months and 52%, respectively. Multivariate analysis indicated that patients with short metastases-free interval, multiple bone metastases sites, high serum lactic dehydrogenase levels, and treated with radiotherapy or chemotherapy alone had significantly worse outcomes. Patients were stratified into three different risk groups based on the number of adverse factors present. The OMS curves of the three groups were all significantly different (pnumber of adverse factors present, bone-only metastasis patients can be stratified into three risk groups with significantly different prognoses. Such grouping may help in improving the design of clinical trials and in guiding individualized treatment for NPC patients with bone-only metastasis. PMID:27189275

  6. Cetuximab in combination with chemoradiotherapy in the treatment of recurrent and/or metastatic nasopharyngeal carcinoma.

    Science.gov (United States)

    Xu, Tingting; Ou, Xiaomin; Shen, Chunying; Hu, Chaosu

    2016-01-01

    The aim of the study was to assess the efficacy and toxicity of cetuximab in the combined treatment for patients with recurrent and/or metastatic nasopharyngeal carcinoma (R/M NPC). Between March 2007 and November 2011, a total of 30 R/M NPC patients treated with comprehensive therapy including cetuximab were retrospectively enrolled. Intensity-modulated radiation therapy was delivered in recurrent disease with a median dose of 60 Gy. Chemotherapy regimens included TP/TPF (docetaxel 60-75 mg/m d1+DDP 25 mg/m d1-3±5-FU 500 mg/m/day with 120-h infusion), GP (gemcitabine 1.0 g/m d1, d8+DDP 25 mg/m d1-3), and PC (paclitaxel 60 mg/m/week d1+carboplatin AUC 2/week d1). Acute and late toxicities were documented by the radiation oncologists. The median age of the patients was 44 years (range 26-62). A total of 21 patients (70%) achieved response (CR+PR). The median survival time, time to progression, and 2-year overall survival were 23.6, 12.2 months, and 53.3%, respectively. Cetuximab appears to be effective and well tolerated when combined with chemoradiation therapy for the treatment of R/M NPC. PMID:26352217

  7. Ex vivo expansion of tumor-infiltrating lymphocytes from nasopharyngeal carcinoma patients for adoptive immunotherapy

    Institute of Scientific and Technical Information of China (English)

    Jia He; Xiao-Feng Tang; Qiu-Yan Chen; Hai-Qiang Mai; Zhou-Feng Huang; Jiang Li; Yi-Xin Zeng

    2012-01-01

    Establishing Epstein-Barr virus (EBV)-specific cytolytic T lymphocytes (EBV-CTLs) from peripheral blood mononuclear cells (PBMCs) for adoptive immunotherapy has been reported in EBV-associated malignancies including Hodgkin's lymphoma and nasopharyngeal carcinoma (NPC).In the current study,we performed ex vivo expansion of tumor-infiltrating lymphocytes (TILs) obtained from NPC biopsy specimens with a rapid expansion protocol using anti-CD3 monoclonal antibody (OKT3),recombinanthuman interleukin (IL)-2,and irradiated PBMCs from healthy donors to initiate the growth of TILs.Young TIL cultures comprised of more than 90% of CD3+ T cells,a variable percentage of CD3+CD8+ and CD3+CD4+ T cells,and less than 10% of CD3-CD16+ natural killer cells,a similar phenotype of EBV-CTL cultures from PBMCs.Interestingly,TIL cultures secreted high levels of the Th1 cytokines,interferon gamma (IFNγ) and tumor necrosis factor-alpha (TNF-α),and low levels of the Th2 cytokines,IL-4 and IL10.Moreover,young TILs could recognize autologous EBV-transformed B lymphoblast cell lines,but not autologous EBV-negative blast cells or allogeneic EBV-negative tumor cells.Taken together,these data suggest that ex vivo expansion of TILs from NPC biopsy tissue is an appealing alternative method to establish T cell-based immunotherapy for NPC.

  8. Inhibition of Pim-1 attenuates the proliferation and migration in nasopharyngeal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Wei Jie; Qi-Yi He; Bo-Tao Luo; Shao-Jiang Zheng; Yue-Qiong Kong; Han-Guo Jiang; Ru-Jia Li; Jun-Li Guo; Zhi-Hua Shen

    2012-01-01

    Objective:To explore the role of proto-oncogenePim-1 in the proliferation and migration of nasopharyngeal carcinoma(NPC) cells.Methods:Pim-1 expressions inNPC cell lines CNE1,CNE1-GL,CNE-2Z andC666-1 were examined byRT-PCR, western blotting and immunoflucesence, respectively.AfterCNE1,CNE1-GL andC666-1 cells were treated with different concentrations ofPim-1 special inhibitor, quercetagetin, the cell viability, colony formation rate and migration ability were analyzed.Results:Pim-1 expression was negative in well-differentiatedCNE1 cells, whereas expressed weakly positive in poor-differentiated CNE-2Z cells and strongly positive in undifferentiatedC666-1 cells.Interestingly,CNE1-GL cells that derived fromCNE1 transfected with anEpsteinBarr virus latent membrane protein-1 over-expression plasmid displayed stronger expression ofPim-1.Treatment ofCNE1-GL and C666-1 cells with quercetagetin significantly decreased the cell viability, colony formation rate and migration ability but not theCNE1 cells.Conclusions:These findings suggest thatPim-1 overexpression contributes toNPC proliferation and migration, and targetingPim-1 may be a potential treatment for anti-Pim-1-expressedNPCs.

  9. Comorbidity predicts poor prognosis in nasopharyngeal carcinoma: Development and validation of a predictive score model

    International Nuclear Information System (INIS)

    Background and purpose: The impact of comorbidity on prognosis in nasopharyngeal carcinoma (NPC) is poorly characterized. Material and methods: Using the Adult Comorbidity Evaluation-27 (ACE-27) system, we assessed the prognostic value of comorbidity and developed, validated and confirmed a predictive score model in a training set (n = 658), internal validation set (n = 658) and independent set (n = 652) using area under the receiver operating curve analysis. Results: Comorbidity was present in 40.4% of 1968 patients (mild, 30.1%; moderate, 9.1%; severe, 1.2%). Compared to an ACE-27 score ⩽1, patients with an ACE-27 score >1 in the training set had shorter overall survival (OS) and disease-free survival (DFS) (both P < 0.001), similar results were obtained in the other sets (P < 0.05). In multivariate analysis, ACE-27 score was a significant independent prognostic factor for OS and DFS. The combined risk score model including ACE-27 had superior prognostic value to TNM stage alone in the internal validation set (0.70 vs. 0.66; P = 0.02), independent set (0.73 vs. 0.67; P = 0.002) and all patients (0.71 vs. 0.67; P < 0.001). Conclusions: Comorbidity significantly affects prognosis, especially in stages II and III, and should be incorporated into the TNM staging system for NPC. Assessment of comorbidity may improve outcome prediction and help tailor individualized treatment

  10. Matrine inhibits the migratory and invasive properties of nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Sun, Bin; Xu, Min

    2015-06-01

    Matrine is a widely used Chinese herbal medicine that has historically been used in the treatment of inflammation and cancer. However, the antimetastatic effects and associated molecular mechanisms of matrine on nasopharyngeal carcinoma (NPC) remain to be elucidated. Therefore, the aims of the present study were to assess the antimetastatic effects of matrine on NPC, and identify the underlying mechanisms. Matrine inhibited the proliferation of NPC cells in vitro and in vivo. Furthermore, matrine inhibited the migration and invasion of NPC tumor cells at doses below the toxic range. Following treatment with matrine for 24 h, there was a decrease in the protein expression levels and activities of matrix metalloproteinase (MMP)‑2 and MMP‑9 in NPC‑039 cells. In addition, matrine markedly reduced the expression levels of p65 and p50 in the nuclei. Combined treatment of matrine with helenalin, a nuclear factor‑κB (NF‑κB) inhibitor resulted in a synergistic reduction in MMP‑2 and MMP‑9 expression levels, and the invasive capabilities of the NPC‑039 cells were also reduced. In conclusion, matrine inhibits NPC cell migration and invasion by suppressing the NF‑κB pathway. These results suggest that matrine may be a potential therapeutic agent for NPC.

  11. Ex vivo expansion of tumor-infiltrating lymphocytes from nasopharyngeal carcinoma patients for adoptive immunotherapy

    Directory of Open Access Journals (Sweden)

    Jiang Li

    2012-06-01

    Full Text Available Establishing Epstein-Barr virus(EBV-specific cytolytic T lymphocytes(EBV-CTLs from peripheral blood mononuclear cells(PBMCs for adoptive immunotherapy has been reported in EBV-associated malignancies including Hodgkin's lymphoma and nasopharyngeal carcinoma(NPC. In the current study, we performed ex vivo expansion of tumor-infiltrating lymphocytes(TILs obtained from NPC biopsy specimens with a rapid expansion protocol using anti-CD3 monoclonal antibody(OKT3, recombinant human interleukin(IL-2, and irradiated PBMCs from healthy donors to initiate the growth of TILs. Young TIL cultures comprised of more than 90% of CD3+ T cells, a variable percentage of CD3+CD8+ and CD3+CD4+ T cells, and less than 10% of CD3-CD16+ natural killer cells, a similar phenotype of EBV-CTL cultures from PBMCs. Interestingly, TIL cultures secreted high levels of the Th1 cytokines, interferon gamma (IFNγ and tumor necrosis factor-alpha (TNF-α, and low levels of the Th2 cytokines, IL-4 and IL-10. Moreover, young TILs could recognize autologous EBV-transformed B lymphoblast cell lines, but not autologous EBV-negative blast cells or allogeneic EBV-negative tumor cells. Taken together, these data suggest that ex vivo expansion of TILs from NPC biopsy tissue is an appealing alternative method to establish T cell-based immunotherapy for NPC.

  12. Functional inactivation of EBV-specific T-lymphocytes in nasopharyngeal carcinoma: implications for tumor immunotherapy.

    Directory of Open Access Journals (Sweden)

    Jiang Li

    Full Text Available Nasopharyngeal carcinoma (NPC is an Epstein-Barr virus (EBV associated malignancy with high prevalence in Southern Chinese. In order to assess whether defects of EBV-specific immunity may contribute to the tumor, the phenotype and function of circulating T-cells and tumor infiltrating lymphocytes (TILs were investigated in untreated NPC patients. Circulating naïve CD3+CD45RA+ and CD4+CD25- cells were decreased, while activated CD4+CD25+ T-cells and CD3-CD16+ NK-cells were increased in patients compared to healthy donors. The frequency of T-cells recognizing seven HLA-A2 restricted epitopes in LMP1 and LMP2 was lower in the patients and remained low after stimulation with autologous EBV-carrying cells. TILs expanded in low doses of IL-2 exhibited an increase of CD3+CD4+, CD3+CD45RO+ and CD4+CD25+ cells and 2 to 5 fold higher frequency of LMP1 and LMP2 tetramer positive cells compared to peripheral blood. EBV-specific cytotoxicity could be reactivated from the blood of most patients, whereas the TILs lacked cytotoxic activity and failed to produce IFNgamma upon specific stimulation. Thus, EBV-specific rejection responses appear to be functionally inactivated at the tumor site in NPC.

  13. THE INTRACELLULAR FORM OF EPSTEIN-BARR VIRUS GENOME IN NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    Wang Huimin; Chen Jun; Zeng Musheng; Li Manzhi; Jian Shaowen; Pan Wentong; Zhang Ling; Wu Yintang

    1998-01-01

    Object: To study the existent form of EBV genome in nasopharyngeal carcinoma (NPC) biopsies, in a transplanted NPC tumor SUNT-1 and its corresponding epithelial cell line SUNE-1. Methods: By using polymerase chain reaction (PCR) amplification of Epstein-Barr virus (EBV) BamHI W fragment, EBV DNA was detected in 20/20 biopsy specimens of poorlydifferentiated, as well as in a nude mouse xenografted NPC tumor (SUNT-1, from passage 1 to 34) and in the corresponding epithelial cell line (SUNE-1, from passage 1 to 62). The intracellular form of EBV genome was studied by analyzing the terminal structure using a LMP2A probe and an "in situ lysing gel" technique.Results: A single EBV fused terminal DNA fragment was detected in 19 biopsy specimens, two hybridized bands were seen in one specimen. These results indicate that an episomal form of EBV genome is predominantly present in most NPC biopsy specimens, but insertion of the genome into the host chromosome could not be excluded. Conclusion: The finding suggests that EBV infection precedes clonal amplification of transformed cells, or in a rare case, that a single EBV infected clone is predominant in the development of NPC. Linear form of EBV DNA was detected in the 20th passage of SUNE-1;this may imply the in vitro activation of the productive cycle of EBV.

  14. Late Toxicities after Conventional Radiotherapy for Nasopharyngeal Carcinoma: Incidence and Risk Factors

    International Nuclear Information System (INIS)

    Background. To determine the incidence and analyze the factors affecting late toxicity for nasopharyngeal carcinoma patients treated with conventional radiotherapy. Patients and Methods. Retrospective analysis was performed on 239 NPC patients treated between 1993 and 2004 in our institution. One hundred and fifty-seven patients were treated with conventional fractionation (2 Gy per fraction, 5 fractions per week) and eighty-two patients with hyperfractionated radiotherapy (1.6 Gy per fraction twice a day, 5 days per week). One hundred fifty nine patients underwent neoadjuvant cisplatin based chemotherapy. Late toxicity was evaluated according to the RTOG/EORTC score. Results. Xerostomia was the most common related complication (98.7%). Neoadjuvant chemotherapy and hyperfractionated radiotherapy did not increase late toxicities. Multivariate analyses showed that radiation dose was a significant factor for hearing impairment, younger age for trismus, initial node status for neck fibrosis, and initial dental hygiene for dental complications. Female gender was associated with significantly higher incidence of trismus and hearing impairment. Conclusion. Conventional radiotherapy was associated with a high rate of late toxicities which affect patients’ quality of life. With the development of three-dimensional conformal radiotherapy and intensity modulated radiotherapy, a reduced incidence of radiation related complications could be expected.

  15. Genetic and Epigenetic Alterations of DLC-1, a Candidate Tumor Suppressor Gene, in Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Dan PENG; Cai-Ping REN; Hong-Mei YI; Liang ZHOU; Xu-Yu YANG; Hui LI; Kai-Tai YAO

    2006-01-01

    The DLC-1 gene, located at the human chromosome region 8p22, behaves like a tumor suppressor gene and is frequently deleted in diverse tumors. The deletion of 8p22 is not an uncommon event in nasopharyngeal carcinoma (NPC), therefore we explored the expression levels of the DLC-1 gene in NPCs and NPC cell lines by reverse transcription-polymerase chain reaction. The results showed the mRNA level of DLC-1 was downregulated. To identify the mechanism of DLC-1 downregulation in NPC, we investigated the methylation status of the DLC-1 gene using methylation-specific PCR, and found that 79% (31 of 39) of the NPC tissues and two DLC-1 nonexpressing NPC cell lines, 6-10B and 5-8F, were methylated in the DLC-1 CpG island. Microsatellite PCR was also carried out, and loss of heterozygosity was found at four microsatellite sites (D8S552, D8S1754, D8S1790 and D8S549) covering the whole DLC-1 gene with ratios of 33% (4 of 12 informative cases), 18% (2 of 11), 5% (1 of 18), and 25% (3 of 12), respectively. Taken together, our results suggest that DLC-1 might be an NPC-related tumor suppressor gene affected by aberrant promoter methylation and gene deletion.

  16. Houttuynia cordata Thunb extract induces cytotoxicity in human nasopharyngeal carcinoma cells: Raman spectroscopic studies

    Science.gov (United States)

    Chen, Weiwei; Li, Zuanfang; Yu, Yun; Lin, Duo; Huang, Hao; Shi, Hong

    2016-01-01

    The molecular mechanisms of cytotoxicity induced by Houttuynia cordata Thunb (HCT) in nasopharyngeal carcinoma (NPC) cells was investigated by Raman spectroscopy (RS). The average Raman spectra of cell groups treated with HCT (0, 62.5, 125, 250, and 500 μg ml-1) for 24 h were measured separately. Compared to the control group, the intensities of the selected bands (1002, 1338, and 1448 cm-1) related to protein, DNA, and lipid in the treatment groups decreased obviously as the concentration of HCT increased. Both cell groups treated with 250 and 500 μg ml-1 of HCT could be differentiated from the control group by principal component analysis (PCA) combined with linear discriminate analysis (LDA) with a diagnostic accuracy of 100%, suggesting that cytotoxicity occurred and that 250 μg ml-1 was the proper dose for treatment. Simultaneously, the Raman spectra of cells treated with different treatment times with 250 μg ml-1 of HCT were obtained. We can get that treatment with HCT decreased cell viability in a dose and time-dependent fashion. The results indicated that the RS combined with PCA-LDA can be used for pharmacokinetics studies of HCT in NPC cells, which could also provide useful data for clinical dosage optimization for HCT.

  17. Domestic incense burning and nasopharyngeal carcinoma: a case-control study in Hong Kong Chinese.

    Science.gov (United States)

    Xie, Shao-Hua; Yu, Ignatius Tak-sun; Tse, Lap Ah; Au, Joseph Siu Kie; Wang, Feng; Lau, June Sze Man; Zhang, Bo

    2014-12-01

    Incense burning is a powerful producer of carcinogens and has been considered as a risk factor for nasopharyngeal carcinoma (NPC). We conducted a case-control study and case-only analyses to investigate the effect of incense burning and its interaction with genetic background on NPC risk among Hong Kong Chinese. Between June 2010 and December 2012, we recruited 352 incident cases of NPC and 410 controls. We collected information on lifelong practice of domestic incense burning via interviews and genotyped 80 single nucleotide polymorphisms (SNPs) in DNA repair genes. We observed an increased NPC risk associated with daily burning in women [Adjusted OR = 2.49, 95% confidence interval (CI): 1.33, 4.66] but not in men. The adjusted OR for daily burning with poor ventilation was 2.08 (95% CI: 1.02, 4.24), while that with good ventilation was 1.35 (95% CI: 0.92, 1.98). Interactions between 2 SNPs (rs2074517 and rs4771436) and incense burning were significantly associated with NPC risk and tended to have a SNP exposure-response effect. Evidence for gene-environment interactions supported the knowledge that NPC is a multi-factorial disease resulting from the joint effects of environmental exposures and inherited susceptibility.

  18. Involvement of regulatory volume decrease in the migration of nasopharyngeal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Jian Wen MAO; Li Xin CHEN; Li Wei WANG; Tim JACOB; Xue Rong SUN; Hui LI; Lin Yan ZHU; Pan LI; Ping ZHONG; Si Huai NIE

    2005-01-01

    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 nonmigrated 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 relationship 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.

  19. Locoregional radiotherapy in patients with distant metastases of nasopharyngeal carcinoma at diagnosis

    Institute of Scientific and Technical Information of China (English)

    Ming-Yuan Chen; Li Zhang; Ming-Huang Hong; Hai-Qiang Mai; Chao-Nan Qian; Rou Jiang; Ling Guo; Xiong Zou; Qing Liu; Rui Sun; Fang Qiu; Zhong-Jun Xia; Hui-Qiang Huang

    2013-01-01

    Systemic chemotherapy is the basic palliative treatment for metastatic nasopharyngeal carcinoma (NPC); however, it is not known whether locoregional radiotherapy targeting the primary tumor and regional lymph nodes affects the survival of patients with metastatic NPC. Therefore, we aimed to retrospectively evaluate the benefits of locoregional radiotherapy. A total of 408 patients with metastatic NPC were included in this study. The mortality risks of the patients undergoing supportive treatment and those undergoing chemotherapy were compared with that of patients undergoing locoregional radiotherapy delivered alone or in combination with chemotherapy. Univariate and multivariate analyses were conducted. The contributions of independent factors were assessed after adjustment for covariates with significant prognostic associations (P<0.05). Both locoregional radiotherapy and systemic chemotherapy were identified as significant independent prognostic factors of overall survival (OS). The mortality risk was similar in the group undergoing locoregional radiotherapy alone and the group undergoing systemic chemotherapy alone [multi-adjusted hazard ratio (HR) = 0.9, P = 0.529]; this risk was 60% lower than that of the group undergoing supportive treatment (HR = 0.4, P = 0.004) and 130% higher than that of the group undergoing both systemic chemotherapy and locoregional radiotherapy (HR = 2.3, P < 0.001). In conclusion, locoregional radiotherapy, particularly when combined with systemic chemotherapy, is associated with improved survival of patients with metastatic NPC.

  20. Therapy effects of gold nanorods on the CNE-1 nasopharyngeal carcinoma cell line

    Directory of Open Access Journals (Sweden)

    Shao J

    2012-10-01

    Full Text Available Jinyan Shao,1 Jianguo Tang,1 Jian Ji,2 Wenbo Zhou21Department of Otolaryngology, Head and Neck Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 2Department of Polymer Science, Ministry of Education Key Laboratory of Macromolecule Synthesis and Functionalization, Zhejiang University, Hangzhou, People's Republic of ChinaAbstract: The use of nanocarriers to deliver drugs to tumor tissue is one of the most important strategies in cancer therapeutics. Recently, gold nanorods (GNRs have begun to be used in cancer therapy because of their unique properties. The purpose of this study was to show the potential that GNRs have against human nasopharyngeal carcinoma CNE-1 cells, using near-infrared (NIR laser light. Transmission electron microscopic and ultraviolet-visible spectroscopic investigations confirmed the efficient uptake of the GNRs by CNE-1 and human rhinal epithelia cells. The in vitro NIR photothermal therapy for the CNE-1 and rhinal epithelia cells was designed in three groups: (1 control, (2 laser alone, and (3 GNRs with laser. Fluorescence microscopy images indicated that, at some GNR concentrations and some intensities of NIR laser, GNRs with laser therapy could induce cell death for CNE-1 cells while keeping the rhinal epithelia cells healthy. Therefore, the results of this study suggest that using GNRs with NIR laser therapy can selectively destruct CNE-1 cells while having no effect on normal (rhinal epithelia cells.Keywords: photothermal therapy, near-infrared laser, rhinal epithelia cells, cell uptake

  1. Nasopharyngeal carcinoma in Malaysian Chinese: salted fish and other dietary exposures.

    Science.gov (United States)

    Armstrong, R W; Imrey, P B; Lye, M S; Armstrong, M J; Yu, M C; Sani, S

    1998-07-17

    We interviewed 282 histologically confirmed cases of nasopharyngeal carcinoma (NPC) in Chinese residents of Selangor and the Federal Territory, Malaysia, and an equal number of Chinese age-, sex-, and length-of-residence-matched controls sampled from the general population. Consumption of 55 dietary items during childhood, and 5 years pre-diagnosis of NPC, was analyzed by univariate and multivariate methods. Four salted preserved foods (fish, leafy vegetables, egg and root), fresh pork/beef organ meats and beer and liquor consumption exhibited strong positive associations, and 4 vegetable/fruit combinations strong negative associations with NPC. Factor analysis and multivariable modeling using estimated factor scores strongly supported separate effects on NPC of vegetables/fruits, salted preserved foods, pork/beef organ meats and beer/liquor consumption. Multivariable modeling associated NPC most clearly with high consumption of salted fish, salted eggs, pork/beef liver and beer and low consumption of Chinese flowering cabbage, oranges/tangerines and shrimp. A strong residual association of social class with NPC remained after adjustment for diet, which is consistent with a substantial role for non-dietary environmental factors.

  2. Diet Quality Scores and Risk of Nasopharyngeal Carcinoma in Chinese Adults: A Case-Control Study.

    Science.gov (United States)

    Wang, Cheng; Lin, Xiao-Ling; Fan, Yu-Ying; Liu, Yuan-Ting; Zhang, Xing-Lan; Lu, Yun-Kai; Xu, Chun-Hua; Chen, Yu-Ming

    2016-03-01

    Many studies show that dietary factors may affect the risk of nasopharyngeal carcinoma (NPC). We examined the association between overall diet quality and NPC risk in a Chinese population. This case-control study included 600 NPC patients and 600 matched controls between 2009 and 2011 in Guangzhou, China. Habitual dietary intake and various covariates were assessed via face-to-face interviews. Diet quality scores were calculated according to the Healthy Eating Index-2005 (HEI-2005), the alternate Healthy Eating Index (aHEI), the Diet Quality Index-International (DQI-I), and the alternate Mediterranean Diet Score (aMed). After adjustment for various lifestyle and dietary factors, greater diet quality scores on the HEI-2005, aHEI, and DQI-I-but not on the aMed-showed a significant association with a lower risk of NPC (p-trends, 2005), 0.48 (0.33-0.70) (aHEI), and 0.43 (0.30-0.62) (DQI-I). In gender-stratified analyses, the favorable association remained significant in men but not in women. We found that adherence to the predefined dietary patterns represented by the HEI-2005, aHEI, and DQI-I scales predicted a lower risk of NPC in adults from south China, especially in men. PMID:26927167

  3. Nasopharyngeal carcinoma in Malaysian Chinese: salted fish and other dietary exposures.

    Science.gov (United States)

    Armstrong, R W; Imrey, P B; Lye, M S; Armstrong, M J; Yu, M C; Sani, S

    1998-07-17

    We interviewed 282 histologically confirmed cases of nasopharyngeal carcinoma (NPC) in Chinese residents of Selangor and the Federal Territory, Malaysia, and an equal number of Chinese age-, sex-, and length-of-residence-matched controls sampled from the general population. Consumption of 55 dietary items during childhood, and 5 years pre-diagnosis of NPC, was analyzed by univariate and multivariate methods. Four salted preserved foods (fish, leafy vegetables, egg and root), fresh pork/beef organ meats and beer and liquor consumption exhibited strong positive associations, and 4 vegetable/fruit combinations strong negative associations with NPC. Factor analysis and multivariable modeling using estimated factor scores strongly supported separate effects on NPC of vegetables/fruits, salted preserved foods, pork/beef organ meats and beer/liquor consumption. Multivariable modeling associated NPC most clearly with high consumption of salted fish, salted eggs, pork/beef liver and beer and low consumption of Chinese flowering cabbage, oranges/tangerines and shrimp. A strong residual association of social class with NPC remained after adjustment for diet, which is consistent with a substantial role for non-dietary environmental factors. PMID:9650558

  4. Replanning Criteria and Timing Definition for Parotid Protection-Based Adaptive Radiation Therapy in Nasopharyngeal Carcinoma

    Science.gov (United States)

    Yao, Wei-Rong; Xu, Shou-Ping; Liu, Bo; Cao, Xiu-Tang; Ren, Gang; Du, Lei; Zhou, Fu-Gen; Feng, Lin-Chun; Qu, Bao-Lin; Xie, Chuan-Bin; Ma, Lin

    2015-01-01

    The goal of this study was to evaluate real-time volumetric and dosimetric changes of the parotid gland so as to determine replanning criteria and timing for parotid protection-based adaptive radiation therapy in nasopharyngeal carcinoma. Fifty NPC patients were treated with helical tomotherapy; volumetric and dosimetric (Dmean, V1, and D50) changes of the parotid gland at the 1st, 6th, 11th, 16th, 21st, 26th, 31st, and 33rd fractions were evaluated. The clinical parameters affecting these changes were studied by analyses of variance methods for repeated measures. Factors influencing the actual parotid dose were analyzed by a multivariate logistic regression model. The cut-off values predicting parotid overdose were developed from receiver operating characteristic curves and judged by combining them with a diagnostic test consistency check. The median absolute value and percentage of parotid volume reduction were 19.51 cm3 and 35%, respectively. The interweekly parotid volume varied significantly (p < 0.05). The parotid Dmean, V1, and D50 increased by 22.13%, 39.42%, and 48.45%, respectively. The actual parotid dose increased by an average of 11.38% at the end of radiation therapy. Initial parotid volume, initial parotid Dmean, and weight loss rate are valuable indicators for parotid protection-based replanning. PMID:26793717

  5. Replanning Criteria and Timing Definition for Parotid Protection-Based Adaptive Radiation Therapy in Nasopharyngeal Carcinoma

    Directory of Open Access Journals (Sweden)

    Wei-Rong Yao

    2015-01-01

    Full Text Available The goal of this study was to evaluate real-time volumetric and dosimetric changes of the parotid gland so as to determine replanning criteria and timing for parotid protection-based adaptive radiation therapy in nasopharyngeal carcinoma. Fifty NPC patients were treated with helical tomotherapy; volumetric and dosimetric (Dmean, V1, and D50 changes of the parotid gland at the 1st, 6th, 11th, 16th, 21st, 26th, 31st, and 33rd fractions were evaluated. The clinical parameters affecting these changes were studied by analyses of variance methods for repeated measures. Factors influencing the actual parotid dose were analyzed by a multivariate logistic regression model. The cut-off values predicting parotid overdose were developed from receiver operating characteristic curves and judged by combining them with a diagnostic test consistency check. The median absolute value and percentage of parotid volume reduction were 19.51 cm3 and 35%, respectively. The interweekly parotid volume varied significantly (p<0.05. The parotid Dmean, V1, and D50 increased by 22.13%, 39.42%, and 48.45%, respectively. The actual parotid dose increased by an average of 11.38% at the end of radiation therapy. Initial parotid volume, initial parotid Dmean, and weight loss rate are valuable indicators for parotid protection-based replanning.

  6. Identification of Genes Related to Nasopharyngeal Carcinoma with the Help of Pathway-based Networks

    Institute of Scientific and Technical Information of China (English)

    Hui LI; Cai-Ping REN; Xiao-Jun TAN; Xu-Yu YANG; Hong-Bo ZHANG; Wen ZHOU; Kai-Tai YAO

    2006-01-01

    cDNA microarray is a powerful tool to analyze simultaneously the expression levels of tens of thousands of genes. Compared with normal nasopharynx (NP) tissues, 2210 genes were highly differentially expressed in nasopharyngeal carcinoma (NPC) tissues detected by cDNA microarray. Since signal pathway is widely used to describe the complex relationship between genes, a pathway-based network was constructed to visualize the connection between the genes obtained from microarray data in this report. We analyzed the targeted genes that may have more important influence on this gene network with statistical methods and found that some genes might have significant influence on this network, especially Ras-related nuclear protein (RAN), carboxyl ester lipase (CEL), v-rel reticuloendotheliosis viral oncogene homolog A (RELA) genes. To verify the results from pathway-based selection, reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR were performed to detect the expression levels of RAN, CEL and RELA genes and it was found that the RAN and CEL genes were significantly up-regulated in more than 80%of NPC tissues. To further elucidate the function of the RAN gene, RAN expression was specifically suppressed in a 5-8F NPC cell line by RNA interference (RNAi). As expected, the depletion of RAN could effectively block the proliferation of tumor cells. Therefore, our study may open up a new way to analyze the vast microarray data.

  7. Activation of multiple apoptotic pathways in human nasopharyngeal carcinoma cells by the prenylated isoflavone, osajin.

    Directory of Open Access Journals (Sweden)

    Tsung-Teng Huang

    Full Text Available Osajin is a prenylated isoflavone showing antitumor activity in different tumor cell lines. The underlying mechanism of osajin-induced cancer cell death is not clearly understood. In the present study, the mechanisms of osajin-induced cell death of human nasopharyngeal carcinoma (NPC cells were explored. Osajin was found to significantly induce apoptosis of NPC cells in a dose- and time-dependent manner. Multiple molecular effects were observed during osajin treatment including a significant loss of mitochondrial transmembrane potential, release of cytochrome c into the cytosol, enhanced expression of Fas ligand (FasL, suppression of glucose-regulated protein 78 kDa (GRP78, and activation of caspases-9, -8, -4 and -3. In addition, up-regulation of proapoptotic Bax protein and down-regulation of antiapoptotic Bcl-2 protein were also observed. Taken together, osajin induces apoptosis in human NPC cells through multiple apoptotic pathways, including the extrinsic death receptor pathway, and intrinsic pathways relying on mitochondria and endoplasmic reticulum stress. Thus, osajin could be developed as a new effective and chemopreventive compound for human NPC.

  8. 2-Methoxyestradiol induces cell cycle arrest and apoptosis of nasopharyngeal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Ning-ning ZHOU; Xiao-feng ZHU; Jun-ming ZHOU; Man-zhi LI; Xiao-shi ZHANG; Peng HUANG; Wen-qi JIANG

    2004-01-01

    AIM: To investigate 2-methoxyestradiol induced apoptosis and its mechanism of action in CNE2 cell lines.METHODS: CNE2 cells were cultured in RPMI-1640 medium and treated with 2-methoxyestradiol in different concentrations. MTT assay was used to detect growth inhibition. Flow cytometry and DNA ladders were used to detect apoptosis. Western blotting was used to observe the expression of p53, p21WAF1, Bax, and Bcl-2 protein.RESULTS: 2-methoxyestradiol inhibited proliferation of nasopharyngeal carcinoma CNE2 cells with IC50 value of2.82 μrnol/L. The results of flow cytometry showed an accumulation of CNE2 cells in G2/M phase in response to2-methoxyestradiol. Treatment of CNE2 cells with 2-methoxyestradiol resulted in DNA fragmentation. The expression levels of protein p53 and Bcl-2 decreased following 2-methoxyestradiol treatment in CNE2 cells, whereas Bax and p21WAF1 protein expression were unaffected after treatment with 2-methoxyestradiol. CONCLUSION:These results suggest that 2-methoxyestradiol induced cell cycle arrest at G2/M phase and apoptosis of CNE2 cells which was associated to Bcl-2 down-regulation.

  9. Rad51 Expression in Nasopharyngeal Carcinoma and Its Association with Tumor Reduction: A Preliminary Study in Indonesia

    Science.gov (United States)

    Cahyanti, Dian; Rachmadi, Lisnawati; Wulani, Vally; Adham, Marlinda

    2016-01-01

    Background: Overexpression of Rad51 protein in many tumor cells has been proven to increase radioresistance and can be related to the resistance of chemosensitivity of tumor cells. This preliminary study was conducted to determine the relationship between the Rad51 expression level in nasopharyngeal carcinoma and the response of the treatment based on the measurement of the tumor reduction. Methods: Thirteen cases of the NPCs were analyzed. The expression levels of the Rad51 were examined from the pretreatment biopsies. Furthermore, tumor reductions were determined based on the change in sum longest diameter of the nasopharyngeal CT-scan before and after therapy. Results: The expression level of the Rad51 was associated with the reduction of tumor mass. The P value was 0.049 and the correlation coefficient was 0.479. Conclusion: The tumor cells Rad51 expression levels may affect the tumor reduction of NPC after the therapy.

  10. Integrated pathway analysis of nasopharyngeal carcinoma implicates the axonemal dynein complex in the Malaysian cohort.

    Science.gov (United States)

    Chin, Yoon-Ming; Tan, Lu Ping; Abdul Aziz, Norazlin; Mushiroda, Taisei; Kubo, Michiaki; Mohd Kornain, Noor Kaslina; Tan, Geok Wee; Khoo, Alan Soo-Beng; Krishnan, Gopala; Pua, Kin-Choo; Yap, Yoke-Yeow; Teo, Soo-Hwang; Lim, Paul Vey-Hong; Nakamura, Yusuke; Lum, Chee Lun; Ng, Ching-Ching

    2016-10-15

    Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma on the mucosal lining of the nasopharynx. The etiology of NPC remains elusive despite many reported studies. Most studies employ a single platform approach, neglecting the cumulative influence of both the genome and transcriptome toward NPC development. We aim to employ an integrated pathway approach to identify dysregulated pathways linked to NPC. Our approach combines imputation NPC GWAS data from a Malaysian cohort as well as published expression data GSE12452 from both NPC and non-NPC nasopharynx tissues. Pathway association for GWAS data was performed using MAGENTA while for expression data, GSA-SNP was used with gene p values derived from differential expression values from GEO2R. Our study identified NPC association in the gene ontology (GO) axonemal dynein complex pathway (pGWAS-GSEA  = 1.98 × 10(-2) ; pExpr-GSEA  = 1.27 × 10(-24) ; pBonf-Combined  = 4.15 × 10(-21) ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (pAmpliSeq-GSEA  = 6.56 × 10(-4) ). Loss of function in the axonemal dynein complex causes impaired cilia function, leading to poor mucociliary clearance and subsequently upper or lower respiratory tract infection, the former of which includes the nasopharynx. Our approach illustrates the potential use of integrated pathway analysis in detecting gene sets involved in the development of NPC in the Malaysian cohort. PMID:27236004

  11. Concurrent chemoradiotherapy comparison of taxanes and platinum versus 5-fluorouracil and platinum in nasopharyngeal carcinoma treatment

    Institute of Scientific and Technical Information of China (English)

    Chen Xichuang; Hong Yuan; Feng Jinhua; Ye Jianlin; Zheng Panpan; Guan Xiyin; You Xiaohong

    2014-01-01

    Background Nasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma especially prevailing among the natives of southern China.The regimen of concurrent chemoradiotherapy (CCRT) that include platinum and 5-fluorouracil (5-FU)is considered to be the standard treatment for NPC.However,its clinical use is limited by its toxicity.Our purpose was to evaluate the efficacy and safety of the regimen of CCRT with taxanes and platinum versus the regimen of CCRT with 5-FU and platinum in NPC treatment.Methods Medline,the Cochrane library,and the Chinese medical literature database were searched for eligible studies.Meta-analysis was performed using Review Manager (Version 5.2).Results Six random controlled trials (RCTs) including 514 patients met our criteria.Meta-analysis showed that the regimen of CCRT with taxanes and platinum had an improved significant difference in complete remission (CR) and less incidence rate in adverse reactions such as gastrointestinal impairment grades Ⅲll-Ⅳ,liver and kidney impairment grades Ⅰ-Ⅱ,and radiodermatitis grades Ⅲ-Ⅳ versus the conventional regimen of CCRT with 5-FU and platinum,while the long-term effectiveness rate of overall survival,Iocoregional failure-free survival,or distant metastasis failure-free survival between the two groups was therapeutic equivalence.Conclusions The regimen of CCRT with taxanes and platinum in NPC therapy may be more efficient and safe compared to the conventional modality of 5-FU and platinum in CCRT.However,we need more high-quality studies of multi-center and randomized double-blind clinical trials to further compare,analyze,and confirm the findings.

  12. Knowledge-based optimization in external radiation therapy: association of an expert-system and a numerical optimization technique in the treatment of nasopharyngeal carcinomas

    International Nuclear Information System (INIS)

    Knowledge-based optimization in external radiation therapy: association of an expert-system and a numerical optimization technique in the treatment of nasopharyngeal carcinomas. Optimization of radiation therapy in nasopharyngeal carcinoma is particularly complex due to both the proximity of at risk organs and the high dose that has to be delivered. To obtain an optimal dose distribution, a knowledge-based optimization technique has been designed that associates an expert-system, named CAVCAV, with numeric optimization (gradient projection method). Based on clinical and physical criteria, CAVCAV determines the geometric characteristics of the radiation fields (beam direction, location and shape of the shielding blocks) for the three stages of radiation therapy of nasopharyngeal carcinomas. Stage 2-treatment fields proposed by CAVCAV, though not perfectly adapted to the patient, are mathematically (beam weights, beam directions, isocenter position) and geometrically (adaptation of fields and shape of blocks by virtual simulation) optimized. (author)

  13. Reticular and myxoid non-keratinizing nasopharyngeal carcinoma: an unusual case mimicking a salivary gland carcinoma.

    Science.gov (United States)

    Petersson, Fredrik; Vijayadwaja, Desai; Loh, Kwok Seng; Tan, Kong-Bing

    2014-01-01

    We present a case of non-keratinizing carcinoma of the nasopharynx (NK-NPC) with an unusual histopathological pattern. The neoplastic cells were arranged in anastomosing cords embedded in a stroma which contained a significant component of alcian blue-positive myxoid substance forming a reticular pattern. These histopathological features gave an initial impression of a salivary gland-type carcinoma. On immunohistochemistry the tumor cells were strongly and diffusely positive for cytokeratins (AE1-3 and 5/6) and p63 and there was strong and diffuse nuclear positivity for Epstein-Barr virus-encoded small RNA on in situ hybridization. This case highlights the histomorphological variability of NK-NPC. Awareness of the histological spectrum of NK-NPC is important in clinical practice and this is not always adequately highlighted in currently used standard textbooks of Head and Neck Pathology.

  14. Reticular and myxoid non-keratinizing nasopharyngeal carcinoma: an unusual case mimicking a salivary gland carcinoma.

    Science.gov (United States)

    Petersson, Fredrik; Vijayadwaja, Desai; Loh, Kwok Seng; Tan, Kong-Bing

    2014-01-01

    We present a case of non-keratinizing carcinoma of the nasopharynx (NK-NPC) with an unusual histopathological pattern. The neoplastic cells were arranged in anastomosing cords embedded in a stroma which contained a significant component of alcian blue-positive myxoid substance forming a reticular pattern. These histopathological features gave an initial impression of a salivary gland-type carcinoma. On immunohistochemistry the tumor cells were strongly and diffusely positive for cytokeratins (AE1-3 and 5/6) and p63 and there was strong and diffuse nuclear positivity for Epstein-Barr virus-encoded small RNA on in situ hybridization. This case highlights the histomorphological variability of NK-NPC. Awareness of the histological spectrum of NK-NPC is important in clinical practice and this is not always adequately highlighted in currently used standard textbooks of Head and Neck Pathology. PMID:24323539

  15. Fractionated stereotactic radiotherapy with vagina carotica protection technique for local residual nasopharyngeal carcinoma after primary radiotherapy

    Institute of Scientific and Technical Information of China (English)

    LIU Feng; HUAN Fu-kui; FANG Hao; WAN Bao; LI Ye-xiong; XIAO Jian-ping; XU Ying-jie; ZHANG Ye; XU Guo-zhen; GAO Li; YI Jun-lin; LUO Jing-wei; HUANG Xiao-dong

    2012-01-01

    Background Local failure of nasopharyngeal carcinoma (NPC) after radiotherapy (RT) remains one of the major treatment failures.This study aimed to evaluate the clinical efficacy and complications of fractionated stereotactic radiotherapy (FSRT) with vagina carotica protection technique for local residual of NPC patients after the primary RT.Methods From August 2006 to August 2010,FSRT with vagina carotica protection technique was applied to 36 patients in our department,the patients aged between 13 and 76 years with a median of 41.3 years,25 of them were male and 11were female.According to 2002 Union for International Cancer Control (UICC) Staging System,the stages before primary radiotherapy were:Ⅱa 2,Ⅱb 5,Ⅲ 18,Ⅳa 7,Ⅳb 4.In the first course of radiotherapy,9 patients received conventional RT,27 patients received intensity modulated radiotherapy (IMRT) and 20 out of the 36 patients received concurrent chemoradiotherapy.The total dose in the first course of RT was 69.96-76.90 Gy (median,72.58 Gy).The intervals between the primary RT and FSRT ranged from 12 to 147 days (median,39.8 days).Target volumes ranged from 1.46 to 32.98 cm3 (median,14.94 cm3).The total FSRT doses were 10.0-24.0 Gy (median,16.5 Gy) with 2.0-5.0Gy per fraction.The most common regimen was 15 Gy in 5 fractions of 3 Gy,the irradiation dose to vagina carotica was less than 2 Gy per fraction.Results The median follow-up time was 34 months (range,12-59 months).The 3-year local control rate was 100%;the 3-year overall survival rate was 94.4%;the 3-year disease-free survival rate was 77.8%.In this study,we had one case of cranial nerve injury,two cases of temporal lobe necrosis,and no nasopharyngeal massive hemorrhage was observed.Conclusion FSRT with vagina carotica protection technique is an effective and safe RT regimen for local residual of NPC with reduction of radiation-related neurovascular lesions.

  16. Influence of the Application of MRI on the T, N Staging System of Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    ChuanmiaoXie; BilingLiang; HaogaoUn; PeihongWu

    2004-01-01

    OBJECTIVE To investigate the influence of utilizing MRI on the T, N staging system (the 5th edition, UICC) and on the 1992 China staging systems (Fuzhou-Guangzhou,China) by comparing the results of CT and MRI examinations of nasopharyngeal carcinoma (NPC).METHODS All 56 NPC patients, which were confirmed by histology,accepted both CT and MRI examinations. CT system scans were obtained by using an Elscient CT Twin Flash with the conventional axial scan. Three cases were examined by an additional coronary scan and 16 patients received an enhanced CT. The MR imaging was performed with a 0.5T MR system (Philips T5- II Ultra-Magnetic). The conventional axial, sagittal and coronary sections with SE sequences were obtained. The scan field was from the supra sellar cistern to the inferior border of C2. Most patients (50/56) accepted contrast enhanced MRI.RESULTS The pharyngobasilar fascia can clearly be seen on MRI but not on CT, so MRI can accurately determine the lesion in the nasopharyngeal cavity. MRI is more sensitive for evaluation of tumor involvement of soft tissue such as the Iongus colli muscle (14 cases by CT and 26 by MRI), tensor veli patalini muscle and levator veli palatini muscle (17 cases by CT and 23 by MRI), and skull-base bone marrow invasion (15 cases by CT and 42 by MRI). MRI can also demonstrate the invasion of the carotid sheath area and the enlargement of retropharyngeal lymph nodes more definitely than CT.The involvement of the trigeminal nerve can be detected on MRI, which may influence the clinical staging directly.CONCLUSION Of the 56 cases examined, 16 (28.6%) changed the staging based on UICC staging; while 33.9% (19/56) cases changed based on the 1992 China-stagin9 system. The major influence of MRI examinations on the 1992 staging was to differentiate the involvement of the carotid sheath area from metastasis of the retropharyngeal lymph nodes. There also was a significant difference in finding early invasion of the skull base.

  17. Phase Ⅰ / Ⅱ clinical trial of docetaxel, cisplatin, and fluorouracil induction chemotherapy followed by intensity-modulated radiotherapy and concomitant chemotherapy in locally advanced nasopharyngeal carcinoma%局部晚期鼻咽癌调强放疗同期化疗前TPF诱导化疗Ⅰ和Ⅱ期临床研究

    Institute of Scientific and Technical Information of China (English)

    张群; 何妨; 康德华; 王振宇; 文碧秀; 罗伟

    2013-01-01

    Objective To investigate the maximum-tolerated dose (MTD) of cisplatin in docetaxel,cisplatin,and fluorouracil (TPF) induction chemotherapy followed by intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy as well as the safety and short-term efficacy of TPF induction chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma (NPC).Methods Thirtythree patients with locally advanced NPC were enrolled in this trial.The MTD of cisplatin was determined by dose escalation study,and the short-term efficacy and toxicities were evaluated.Results When the doses of docetaxel and fluorouracil were 60 mg/m2 d1 and 550 mg/m2 d1-5,respectively,the MTD of cisplatin was 65 mg/m2 d1.In this regimen (repeated every 3 weeks),grade 3-4 toxicities included neutropenia (67%),febrile neutropenia (9%),diarrhea (21%),and oral mucositis (6%).Except those who experienced dose-limited toxicity,other patients completed the whole treatment schedule.After TPF induction chemotherapy,the overall response rate was 97%,and the complete response rate was 21%.Conclusions In the endemic areas of NPC,induction chemotherapy with docetaxel (60 mg/m2 d1),cisplatin (65 mg/m2 d1),and fluorouracil (550 mg/m2 d1-5),which is repeated every 3 weeks,is proved safe and effective for Asian patients with locally advanced NPC.%目的 探讨局部晚期鼻咽癌调强放疗同期化疗前多西泰索加顺铂加氟尿嘧啶方案诱导化疗中顺铂最大耐受剂量(MTD)及方案安全性、有效性.方法 选取33例局部晚期鼻咽癌患者,通过剂量递增试验确立顺铂MTD并评价临床疗效及不良反应.结果 多西泰索60 mg/m2第1天、氟尿嘧啶550 mg/m2第1~5天剂量下顺铂MTD为65 mg/m2第1天,每3周重复下3、4级不良反应发生率分别为中性粒细胞降低67%,粒细胞缺乏性发热9%,腹泻21%,口腔黏膜炎6%.除剂量限制性毒性患者外,其余均完成了治疗.诱导化疗后有效率为97%,其中完

  18. Detection of bone metastasis in nasopharyngeal carcinoma by bone scintigraphy: A retrospective study in perspective of limited resource settings

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor

    2015-01-01

    Full Text Available Background: Nasopharyngeal carcinoma (NPC is an aggressive tumor with a significant proportion of patients presenting with distant metastasis. The skeleton is one of the most common sites of distant failure. This retrospective study was performed to analyze the incidence and patterns of skeletal metastasis in NPC detected by bone scintigraphy in resource-poor settings. Materials and Methods: We analyzed records of 301 NPC patients attending our oncology outpatient department from January 2002 to December 2012. Of these, 33 patients who presented with bony pain underwent bone scan (BS for suspect of skeletal metastasis. In patients with positive scans, histological diagnosis to confirm metastasis was attempted. Results: Bone metastasis (BM was found in 19 patients (57.6% of patients undergoing BS, 6.3% of total NPC patients. About 36.8% and 15.8% of BM cases were in the age group 20-29 and 30-39 years, respectively (P = 0.27. 63.1% of metastatic cases were of World Health Organization type-II histology (P = 0.021. Of the patients diagnosed with BM, 52.6% belonged to stage IV at presentation (P = 0.022. Spine was involved in 56% of the positive cases, followed by the pelvis (32%, and ribs (24%. On univariate analysis, histology (P < 0.001, stage at diagnosis (P = 0.007 and age group (P = 0.001 were identified as significant factors affecting BM. However, on multivariate analysis, only stage (P = 0.001 was a significant factor. Conclusion: Bone scintigraphy can be considered in limited resource settings for the evaluation of distant metastasis in the patients of advanced NPC.

  19. Indication of lower neck irradiation in nasopharyngeal carcinoma without nodal metastasis: the potential impact of tumor volume

    Institute of Scientific and Technical Information of China (English)

    FU Jie; ZHOU Jia-yin; Vincent FH CHONG; James BK Khoo

    2013-01-01

    Background Elective radiation of lower neck is controversial for nasopharyngeal carcinoma (NPC) without lymph node metastasis (N0 disease).Tumor volume is an important prognostic indicator.The objective of this study is to explore the potential impact of tumor volume on the indication of the lower neck irradiation for N0-NPC,by a qualitative evaluation of the relationship between tumor volume and nodal metastasis.Methods Magnetic resonance (MR) images of 99 consecutive patients with NPC who underwent treatment were retrospectively reviewed.Primary tumor volumes of NPC were semi-automatically measured,nodal metastases were N-classified and neck level involvements were examined.Distributions of tumor volumes among N-category-based groups and distributions of N-categories among tumor volume-based groups were analyzed,respectively.Results The numbers of patients with N0 to N3 disease were 12,39,32,and 16,respectively.The volumes of primary tumor were from 3.3 to 89.6 ml,with a median of 17.1 ml.For patients with nodal metastasis,tumor volume did not increase significantly with the advancing of N-category (P >0.05).No significant difference was found for the distribution of N1,N2,and N3 categories among tumor volume-based groups (P >0.05).Nevertheless patients with nodal metastasis had significantly larger tumor volumes than those without metastasis (P <0.05).Patients with larger tumor volumes were associated with an increased incidence of nodal metastasis.Conclusions Certain positive correlations existed between tumor volume and the presence of nodal metastasis.The tumor volume (>10 ml) is a potential indicator for the lower neck irradiation for N0-NPC.

  20. Preliminary assessment of nasopharyngeal carcinoma incidence in the Philippines:a second look at published data from four centers

    Institute of Scientific and Technical Information of China (English)

    Mario Paulus Cesar B. Sarmiento; Michael Benedict A. Mejia

    2014-01-01

    In endemic regions such as southern China and Southeast Asia, the annual incidence of nasopharyngeal carcinoma (NPC) ranges from 3 to 30 per 100,000. In the Philippines, the estimated incidence in 2010 was 1.2 per 100,000. However, this rate is based on data collected from registries covering only two regions in the country. Here, we report the findings from our study to better approximate the incidence of NPC in the Philippines. Between September 1, 2011 and August 31, 2012, data were col ected from 49 patients from 4 different institutions-University of Santo Tomas, Makati Medical Center, Philippine Oncology Center Corporation, and Cardinal Santos Memorial Medical Center-using a NPC screening questionnaire. Crude incidence was 0.09 per 100,000. Age-standardized incidences using Segi and WHO standards were 2.08 and 1.79 per 100,000, respectively. Of the 49 patients, 31 were males and 18 were females, and 71% of patients were between 30 and 59 years old. WHO types II and III represented 22% and 78% of the subjects, respectively, and 75.5% of cases were locally advanced (stages III-IVB). Although the age-standardized incidence from the 4 institutions was numerically higher than the published age-standardized incidence (2.07 per 100,000 vs. 1.2 per 100,000), two-proportion z-test showed no significant difference between them (P=0.68). A more concerted effort is needed for a better approximation of the country’s NPC disease burden.

  1. Silencing Fibronectin Extra Domain A Enhances Radiosensitivity in Nasopharyngeal Carcinomas Involving an FAK/Akt/JNK Pathway

    International Nuclear Information System (INIS)

    Purpose: Fibronectin extra domain A (EDA) is known to play important roles in angiogenesis, lymphangiogenesis, and metastasis in malignant tumors. The present study examined the effect of EDA on the radioresistance potential of nasopharyngeal carcinoma (NPC). Methods and Materials: EDA expression levels in blood samples and tumor tissues of NPC patients were tested by enzyme-linked immunosorbent assay and immunohistochemistry. Radiosensitivity was tested by colony survival assay. Apoptosis was determined by flow cytometry. The expressions of EDA, cleaved caspase 9, cleaved caspase 3, cleaved PARP, Bcl-2, and the levels of phosphorylated FAK, Akt, and JNK were measured by Western blot. Xenografts were used to confirm the effect of EDA on radiosensitivity in vivo. Results: EDA levels in blood samples of advanced NPC patients were much higher than those in early-stage patients. In tumor tissues, the positive expressions of EDA in NPC tumor tissues were shown to be correlated with the differentiation degrees of cancer cells and lymph node metastases. Additionally, the expression of EDA is positively correlated with the expression of antiapoptotic gene (Bcl2), but negatively correlated with the expressions of apoptotic genes (cleaved caspase-3, cleaved caspase-9, cleaved PARP). In vitro, EDA-silenced NPC cells CNE-2 shows substantially enhanced radiosensitivity with lower colony survival and more apoptosis in response to radiation. In vivo, EDA-silenced xenografts were more sensitive to radiation. At the molecular level, FAK/Akt/JNK signaling was demonstrated to be inactivated in EDA-silenced CNE-2 cells. Conclusions: EDA strongly affected the radiosensitivity of NPC cells. FAK/Akt/JNK signaling was found to be a potential signaling mediating EDA function.

  2. Clinical characteristics and changes in living quality of patients with radiation encephalopathy induced by radiation therapy for treating nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yamei Tang; Yi Li; Fusheng Zhang; Yunlin Liu; Haihong Zhou; Jianhong Ye; Yigang Xing

    2007-01-01

    BACKGROUND: Radiation encephalopathy (RE) caused by radiation therapy of nasopharyngeal carcinoma severely influences patients' quality of life (QOL). The factors, which influence such patients' QOL, have not been confirmed.OBJECTIVE: To observe the clinical and imageological characteristics of patients with radiation therapy of nasopharyngeal carcinoma-induced RE and the changes in QOL, and analyze QOL influencing factors.DESIGN: Retrospective case analysis.SETTING: Department of Neurology, the Second Affiliated Hospital of Sun Yat-sen University.PARTICIPANTS: Eighty-nine inpatients or outpatients with RE induced by radiation therapy of nasopharyngeal carcinoma admitted to Sun Yat-sen University Cancer Center and Department of Neurology,the Second Affiliated Hospital of Sun Yat-sen University from March 1994 to August 2004 were involved in this experiment. They all met the diagnosis criteria of RE from MERRITT'S neurology (10th edition).Thirty-three involved patients were randomly chosen as RE group. Another 34 concurrent inpatients or outpatients with nasopharyngeal carcinoma who received radiation therapy but without RE were chosen as control group. Informed consents of detected items were obtained from all the involved subjects.Quality of Life Questionnaire abbreviated version (WHOQOL-BREF) was used for on-the-spot evaluation.High points of WHOQOL-BREF indicated better QOL. The Late Effects on Normal Tissues - Subjective,Objective, Management and Analytic (LENT-SOMA) scale for evaluating radiation injury was used to evaluate headache and neurologic disorder of patients with RE induced by radiation therapy of nasopharyngeal carcinoma. The evaluation was graded into 5 degrees. High degrees indicted severer clinical therapy ending to onset), initial symptoms, common symptoms, imageological characteristics, QOL and other software.MAIN OUTCOME MEASURES: QOL and clinical characteristics of patients with RE induced by radiation therapy of nasopharyngeal carcinoma as

  3. Examestane in advanced or recurrent endometrial carcinoma

    DEFF Research Database (Denmark)

    Lindemann, Kristina; Malander, Susanne; Christensen, René dePont;

    2014-01-01

    We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma.......We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma....

  4. Challenges of advanced hepatocellular carcinoma.

    Science.gov (United States)

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-09-14

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  5. Development and validation of quality of life scale of nasopharyngeal carcinoma patients: the QOL-NPC (version 2)

    OpenAIRE

    Su, Yong; Mo, Chuan-wei; Cheng, Wan-qin; Wang, Lei; Xu, Qian; Wu, Zu-chun; Wu, Zhe-li; Liu, Li-Zhi; Chen, Xin-lin

    2016-01-01

    Background The aim was to develop and validate the quality of life scale for nasopharyngeal carcinoma (NPC) patients, the QOL-NPC (version 2), a specific instrument to measure quality of life for NPC patients. Methods The QOL-NPC was developed and validated according to standard procedures. The patients were assessed using the QOL-NPC, FACT-G, and FACT-H&N. Classical test theory was used to evaluate the reliability, validity, and responsiveness of the QOL-NPC. Results A total of 487 patients ...

  6. 3D-image-guided high-dose-rate intracavitary brachytherapy for salvage treatment of locally persistent nasopharyngeal carcinoma

    OpenAIRE

    Ren, Yu-Feng; Cao, Xin-Ping; Xu, Jia; Ye, Wei-Jun; Gao, Yuan-Hong; Teh, Bin S.; Wen, Bi-Xiu

    2013-01-01

    Background To evaluate the therapeutic benefit of 3D-image-guided high-dose-rate intracavitary brachytherapy (3D-image-guided HDR-BT) used as a salvage treatment of intensity modulated radiation therapy (IMRT) in patients with locally persistent nasopharyngeal carcinoma (NPC). Methods Thirty-two patients with locally persistent NPC after full dose of IMRT were evaluated retrospectively. 3D-image-guided HDR-BT treatment plan was performed on a 3D treatment planning system (PLATO BPS 14.2). The...

  7. PET/CT imaging of delayed radiation encephalopathy following radiotherapy for nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Xin-lu; YIN Ji-lin; LI Hua; LI Xiang-dong; QUAN Jiang-tao

    2007-01-01

    Background With the significant improvement in the survival of patients with nasopharyngeal carcinoma (NPC)undergoing radiotherapy and the growing availability of the sophisticated imaging modalities, the number of radiation encephalopathy (RE) cases relating to NPC radiotherapy is increasing. In this study, we investigated the metabolic and density changes of the compromised brain tissues during delayed RE using a positron-emission tomography-computed tomography (PET/CT) to provide clinical evidences for the diagnosis of delayed RE following radiotherapy for NPC.Methods The PET/CT manifestations and the clinical data of 53 pathologically confirmed NPC patients with delayed RE following radical radiotherapy and 15 healthy volunteers were investigated. The standardized uptake values (SUV) of the bilateral temporal lobes, the occipital lobe and the brain stem were measured respectively; and then the metabolic reduction rate of 88 temporal lobes and 13 brain stems were calculated for a statistical comparison between the two groups.Results The earliest case of delayed RE in the investigated patients occurred 1.5 years after radiotherapy. Delayed RE frequently involved the inferior temporal lobe. For patients with delayed RE confirmed by clinical symptoms and imaging findings, PET maintained a 100% coincidence rate with CT; however, in the 25 temporal lobes of the 35 delayed RE patients, PET revealed obvious hypometabolic changes whereas CT displayed normal density. The incidence of brain stem metabolic reductions was 24.5% (13/53) in the investigated patients, including 4 patients with hypometabolic changes shown by PET and negative finding shown by CT. The incidence of granuloma adjacent to the hypometabolic region in the temporal lobe was 12.5% (11/88).Conclusion Delayed RE patients exhibit significant hypometabolic changes in the inferior temporal lobe, captured by PET much earlier than by CT. PET/CT offers a valuable means for the diagnosis of delayed RE in

  8. Replanning During Intensity Modulated Radiation Therapy Improved Quality of Life in Patients With Nasopharyngeal Carcinoma

    International Nuclear Information System (INIS)

    Purpose: Anatomic and dosimetric changes have been reported during intensity modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the effects of replanning on quality of life (QoL) and clinical outcomes during the course of IMRT for NPC patients. Methods and Materials: Between June 2007 and August 2011, 129 patients with NPC were enrolled. Forty-three patients received IMRT without replanning, while 86 patients received IMRT replanning after computed tomography (CT) images were retaken part way through therapy. Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Head and Neck Quality of Life Questionnaire 35 were completed before treatment began and at the end of treatment and at 1, 3, 6, and 12 months after the completion of treatment. Overall survival (OS) data were compared using the Kaplan-Meier method. Results: IMRT replanning had a profound impact on the QoL of NPC patients, as determined by statistically significant changes in global QoL and other QoL scales. Additionally, the clinical outcome comparison indicates that replanning during IMRT for NPC significantly improved 2-year local regional control (97.2% vs 92.4%, respectively, P=.040) but did not improve 2-year OS (89.8% vs 82.2%, respectively, P=.475). Conclusions: IMRT replanning improves QoL as well as local regional control in patients with NPC. Future research is needed to determine the criteria for replanning for NPC patients undergoing IMRT.

  9. Locoregional extension patterns of nasopharyngeal carcinoma and suggestions for clinical target volume delineation

    Institute of Scientific and Technical Information of China (English)

    Wen-Fei Li; Jun Ma; Ying Sun; Mo Chen; Ling-Long Tang; Li-Zhi Liu; Yan-Ping Mao; Lei Chen; Guan-Qun Zhou; Li Li

    2012-01-01

    Clinical target volume (CTV) delineation is crucial for tumor control and normal tissue protection.This study aimed to define the Iocoregional extension patterns of nasopharyngeal carcinoma (NPC) and to improve CTV delineation.Magnetic resonance imaging scans of 2366 newly diagnosed NPC patients were reviewed.According to incidence rates of tumor invasion,the anatomic sites surrounding the nasopharynx were classified into high-risk (>30%),medium-risk (5%-30%),and low-risk (<5%) groups.The lymph node (LN) level was determined according to the Radiation Therapy Oncology Group guidelines,which were further categorized into the upper neck (retropharyngeal region and level Ⅱ),middle neck (levels Ⅲ and Va),and lower neck (levels IV and Vb and the supraclavicular fossa).The high-risk anatomic sites were adjacent to the nasopharynx,whereas those at medium-or low-risk were separated from the nasopharynx.If the high-risk anatomic sites were involved,the rates of tumor invasion into the adjacent medium-risk sites increased; if not,the rates were significantly lower (P < 0.01).Among the 1920 (81.1%) patients with positive LN,the incidence rates of LN metastasis in the upper,middle,and lower neck were 99.6%,30.2%,and 7.2%,respectively,and skip metastasis happened in only 1.2% of patients.In the 929 patients who had unilateral upper neck involvement,the rates of contralateral middle neck and lower neck involvement were 1.8% and 0.4%,respectively.Thus,local disease spreads stepwise from proximal sites to distal sites,and LN metastasis spreads from the upper neck to the lower neck.Individualized CTV delineation for NPC may be feasible.

  10. Pharmacokinetic and pharmacodynamic studies with 4'-epi-doxorubicin in nasopharyngeal carcinoma patients.

    Science.gov (United States)

    Hu, O Y; Chang, S P; Jame, J M; Chen, K Y

    1989-01-01

    The plasma pharmacokinetic profile of 4'-epidoxorubicin (epirubicin) was investigated in 28 patients with nasopharyngeal carcinoma (NPC) after single i.v. rapid infusions. All patients had normal liver and renal functions. Plasma concentrations of the parent compound were specifically determined by a high-performance liquid chromatographic (HPLC) method, with UV detection at 254 nm. Plasma levels of the compound were fitted to a three-compartment open model; a triexponential decrease in plasma concentrations with a long terminal plasma half-life (44.8 +/- 21.2 h) was observed in 27 patients. The respective mean (+/- SD) serum concentration at 72 h and the AUC, plasma clearance, and terminal elimination rate constant in complete responders were 7.67 +/- 1.98 ng/ml, 4,002 +/- 3,080 ng.h/ml, 26.6 +/- 12.9 l/h.m2, and 0.009 +/- 0.007 l/h, whereas those in nonresponders were 4.96 +/- 1.8 ng/ml, 1.88 +/- 652.8 ng.h/ml, 44.4 +/- 15 l/h.m2, and 0.017 +/- 0.006 l/h, respectively; these differences were significant (P less than 0.05). Epirubicin produced a 52% response rate, including 6 patients with a complete response, 8 with a partial response, 11 with no change, and 2 with progressive disease. No relationship could be found between the various pharmacokinetic parameters and either leukopenia, age, or sex. These observations strongly suggest that plasma clearance may be one of the determining factors affecting the response or nonresponse of NPC patients to epirubicin, and a dose adjustment according to plasma clearance would probably increase the response rate. PMID:2758564

  11. Radiation-induced brachial plexopathy in patients with nasopharyngeal carcinoma: a retrospective study

    Science.gov (United States)

    Fu, Ruying; Rong, Xiaoming; Wu, Rong; Cheng, Jinping; Huang, Xiaolong; Luo, Jinjun; Tang, Yamei

    2016-01-01

    Radiation-induced brachial plexopathy (RIBP) is one of the late complications in nasopharyngeal carcinoma (NPC) patients who received radiotherapy. We conducted a retrospective study to investigate its clinical characteristics and risk factors. Thirty-onepatients with RIBP after radiotherapy for NPC were enrolled. Clinical manifestations of RIBP, electrophysiologic data, magnetic resonance imaging (MRI), and the correlation between irradiation strategy and incidence of RIBP were evaluated. The mean latency at the onset of RIBP was 4.26 years. Of the symptoms, paraesthesia usually presented first (51.6%), followed by pain (22.6%) and weakness (22.6%). The major symptoms included paraesthesia (90.3%), pain (54.8%), weakness (48.4%), fasciculation (19.3%) and muscle atrophy (9.7%). Nerve conduction velocity (NCV) and electromyography (EMG) disclosed that pathological changes of brachial plexus involved predominantly in the upper and middle trunks in distribution. MRI of the brachial plexus showed hyper-intensity on T1, T2, post-contrast T1 and diffusion weighted whole body imaging with background body signal suppression (DWIBS) images in lower cervical nerves. Radiotherapy with Gross Tumor volume (GTVnd) and therapeutic dose (mean 66.8±2.8Gy) for patients with lower cervical lymph node metastasis was related to a significantly higher incidence of RIBP (P<0.001). Thus, RIBP is a severe and progressive complication of NPC after radiotherapy. The clinical symptoms are predominantly involved in upper and middle trunk of the brachial plexus in distribution. Lower cervical lymph node metastasis and corresponding radiotherapy might cause a significant increase of the RIBP incidence. PMID:26934119

  12. Technical and Dosimetric Study of Four Facio-cervical Fields Conformal Radiotherapy for Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    WANG Fang-zheng; FU Zhen-fu; WANG Lei; PIAO Yong-feng; HUA Yong-hong; CHEN Wei-jun; XU Min

    2015-01-01

    Objective: The aim of this study is to establish the methods of four facio-cervical field's conformal radiotherapy (4F-CRT) for nasopharyngeal carcinoma (NPC), and to optimize the methods for clinical practiceMaterials and Methods:40 patients with untreated NPC of T1-T4 (1997 AJCC Staging System) were rolled into this study.Conventional and four facio-cervical fields conform plans were designed for each patient using Pinnacle 8.0 three-dimension treatment planning system (3D-TPS) as follows:1Improved plan, four facio-cervical field's conform plan, anterior, posterior facio-cervical and two lateral opposing facio-cervical fields; 2Conventional plan, two lateral opposing facio-cervical fields delivered to the target in each plan, only with the same dose dose volume histograms (DVHs) of the targets and normal organs, brain stem, spinal cord, parotid glands, and temporal mandibular joints (TMJs) were compared and the dose distribution were evaluatedResults: 1.The dose distribution of the improved plan could meet the requirements for the target volume2There was not any significant difference in the dose of spinal cord between the two plans.The mean doses of D max for brain stem in conventional plan were much lower than those in the improved plan, though both were within safety limits3Compared with the conventional plans, the improved plan significantly decreased the hotspot areas in the target volume and had better parotid glands and temporal mandibular joints sparing effectConclusion:Compared with the conventional plan, the improved plan provides satisfactory dose coverage to the tumor volume and better sparing of the parotid gland, TMJs and other normal tissues in external beam radiotherapy of NPC.

  13. Prognostic Nomogram for Patients with Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy.

    Directory of Open Access Journals (Sweden)

    Shixiu Wu

    Full Text Available This study was aimed to define possible predictors of overall survival in nasopharyngeal carcinoma (NPC. Patients were treated with intensity-modulated radiation therapy (IMRT, to establish an effective prognostic nomogram that could provide individualized predictions of treatment outcome in this setting. We reviewed the records of 533 patients with non-metastatic NPC who underwent IMRT with or without concurrent chemotherapy at the Department of Radiation Oncology of Sun Yat-Sen University from 2002 to 2009; none of these patients received induction or adjuvant chemotherapy. These data sets were used to construct a nomogram based on Cox regression. Nomogram performance was determined via a concordance index (C-index and a calibration curve which was compared with the TNM staging system for NPC. The results were validated in an external cohort of 442 patients from the Department of Radiation Oncology of Wenzhou Medical College who were treated during the same period. Results showed that the greatest influence on survival were primary gross tumor volume, age, tumor stage and nodal stage (2002 Union for International Cancer Control [UICC] staging system, which were selected into the nomogram. The C-index of the nomogram for predicting survival was 0.748 (95%CI, 0.704-0.785, which was statistically higher than that of TNM staging system (0.684, P<0.001. The calibration curve exhibited agreement between nomogram-predicted and the actual observed probabilities for overall survival. In the validation cohort, the nomogram discrimination was superior to the TNM staging system (C-index: 0.768 vs 0.721; P = 0.026. In conclusion, the nomogram proposed in this study resulted in more-accurate prognostic prediction for patients with NPC after IMRT and compared favorably to the TNM staging system; this individualized information will aid in patient counseling and may be used for de-escalation trials in the future.

  14. Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma.

    Science.gov (United States)

    Fåhraeus, R; Fu, H L; Ernberg, I; Finke, J; Rowe, M; Klein, G; Falk, K; Nilsson, E; Yadav, M; Busson, P

    1988-09-15

    Expression of the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNA 1 to 6) and membrane-associated protein (LMP) was investigated by immunoblotting in 83 nasopharyngeal carcinoma (NPC) biopsies and 25 other tumor and normal tissue specimens from the head and neck region. Fifty-eight of the 83 NPC biopsies were large enough to yield parallel data on virus DNA and viral expression. All 16 cases of clinically diagnosed and histologically confirmed NPCs from North Africa contained EBV DNA and expressed EBNA-1. Of 31 clinically diagnosed NPCs from China, 29 contained EBV DNA and 25 of these expressed EBNA-1. One control tissue biopsy from the oropharynx of NPC patients contained EBV DNA, but none expressed EBNA-1. The latent membrane protein (LMP) was detected in 22/31 of the Chinese and in 10/16 of the North African NPC biopsies. None of the NPC biopsies or control tissues expressed detectable amounts of EBNA 2 or any of the other 4 nuclear antigens which are invariably expressed in EBV-transformed B cells. A smaller number of tumors from Malaysia and East Africa exhibited a similar pattern of expression. EBV was rescued from a nude-mouse-passaged North African NPC tumor by co-cultivation of the tumor cells with umbilical cord blood lymphocytes. The tumor expressed EBNA 1 and LMP, but not EBNA 2 or the other 4 EBNAs. The resulting LCLs expressed all 6 nuclear antigens, EBNA 1 to 6 and LMP. Our data suggest that expression of the EBV genome is regulated in a tissue-specific fashion. PMID:2843473

  15. Multicenter study of radiotherapy combined with sarcandra glabra for nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Objective: To observe the clinical effect of Sarcandra Glabra. Methods: 100 patients with non-metastatic nasopharyngeal carcinoma in stage III ∼ IVa and untreated before accepted the treatment plan of Sarcandra Glabra combined with chemoradiation in June 2006 to August 2008. Oral intake Sarcandra 3 days before the radiation therapy, once 10g, three times a day, until the end of treatment. Radiotherapy with conventional radiotherapy protocol, chemotherapy with PF program, 100 cases were chosen who were staging III ∼ IVa and received intensity modulated radiotherapy combined with concomitant chemotherapy for the program PF as the control study. Results: (1)Two groups of primary and cervical lymph node metastases, efficience rate are 100%, the test group primary and cervical lymph nodes CR is 69%, 73%, and the control group is 80%, 81%. There is no significant difference between them. (2)Two groups of acute radiation reactions, leukopenia, and xerostomia are of no difference. The incidence and severity of oral mucositis and skin reaction in control group were lower than test group. (3)In test group,the 1 year and 2 years, overall survival, disease-free survival, recurrence rate and distant metastasis rates were: 97%, 86%, 92%, 70%, 3%, 11%, 6%, 19%; control group was 100%, 93%, 97%, 81%, 1%, 5%, 2%, 12%. The difference was not statistically significant. (4)There is no statistically difference between two groups of xerostomia and the rate of radioactive tooth decay. There is statistically difference between two groups of difficulty in opening mouth and skin fibrosis, the control group is lower than the test group. Conclusion: Intensity-modulated radiation therapy in normal organ tissue protection still has an absolute advantage. But combined chemoradiation plus sarcandra has a significant remission effect on the xerostomia and radioactive tooth decay caused by the deficiency of saliva secretion and it can improve the quality of patients' lives. It can protect

  16. Optimization of magnetic resonance sequences in lymph node staging of nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    CHEN Yun-bin; HU Chun-miao; PAN Jian-ji; MAO Yu; WEI Wei

    2010-01-01

    Background Detection rate of retropharyngeal lymph node metastasis in patients with nasopharyngeal carcinoma (NPC) needs to be improved. The purpose of this study was to compare three magnetic resonance (MR) sequences for detecting lymph nodes in patients with NPC.Methods Between July 2007 and March 2008, MR staging of pre-treated tumor was conducted on 120 patients with pathologically confirmed NPC. The outcome of three different sequences for MR NPC staging were compared: coronal short TI inversion recovery (STIR), axial proton density fat-suppressed (PDWl fs), and coronal contrast enhanced fast spin echo T1 weighted fat-suppressed (CE FSE T1WI fs). Nodal classification method (1999) was applied to count the number of retropharyngeal and cervical lymph nodes discovered by each MR sequence. Paired t tests were used for statistical analysis.Results A total of 2575 lymph nodes were found using coronal STIR sequence; 1816 lymph nodes for coronal CE FSE T1WI fs sequence and 2638 lymph nodes for axial PDWI fs sequence. Significant differences existed in the number of lymph nodes detected by axial PDWI fs and coronal CE FSE T1WI fs sequence (paired t test, P 0.05).Conclusions For the detection of retropharyngeal and cervical lymph nodes, coronal STIR sequence and axial PDWI fs sequence have similar performance and both sequences showed better detection than CE FSE T1WI fs sequence. Furthermore, by combining coronal STIR sequence and axial PDWI fs sequence, we can improve the detection of lymph nodes in NPC N-staging before treatment, especially for lymph nodes located in the thoracic entrance.

  17. Cytochrome P450 2E1 polymorphism and nasopharyngeal carcinoma development in Thailand: a correlative study

    International Nuclear Information System (INIS)

    Nasopharyngeal carcinoma (NPC) is a rare tumor in most parts of the world but occurs at relatively high frequency among people of Chinese descent. The cytochrome P450 2E1 enzyme (CYP2E1) is responsible for the metabolic activation of nitrosamines, and has been shown to be a susceptibility gene for NPC development in Taiwan [RR = 2.6; 95%CI = 1.2-5.7]. Since there has been only one report of this link, it was decided to investigate the susceptibility of CYP2E1 to NPC development in other populations. Therefore, the correlation between the RsaI polymorphism of this gene and NPC was studied in-patients including Thai and Chinese in Thailand. The present study comprised 217 cases diagnosed with NPC and 297 healthy controls. Similar to the result found in Taiwanese, a homozygous uncut genotype demonstrated a higher relative risk both when all cases were analyzed [RR = 2.19; 95%CI = 0.62-8.68] or individual racial groups, Thai [RR = 1.51; 95%CI = 0.08-90.06] or Chinese [RR = 1.99; 95%CI = 0.39-10.87]. The ethnicity-adjusted odds ratio is 2.39 with 95%CI, 0.72-7.89. Though our finding was not statistically significant due to the moderate sample size of the study, similarity to the study in Taiwan with only a slight loss in precision was demonstrated. The higher RR found for the same genotype in distinct populations confirmed that CYP2E1 is one of several NPC susceptibility genes and that the RsaI minus variant is one mutation that affects phenotype

  18. Prognostic value of pretreatment and recovery duration of cranial nerve palsy in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the prognostic value of cranial nerve (CN) palsy in nasopharyngeal carcinoma (NPC) patients. A retrospective analysis was performed on CN involvement using medical records of 178 consecutive patients with histologically diagnosed, non-disseminated NPC. In 178 NPC patients with CN palsy, the 5-year survival rates were as follows: overall survival (OS), 61.0%; disease-specific survival (DSS), 69.6%; local relapse-free survival (LRFS), 75.2%; distant metastasis-free survival (DMFS), 73.4%; and disease-free survival (DFS), 55.3%. Significant differences were observed in the 5-year OS rates between patients with single and multiple CN palsy (69.8% vs. 54.3%; P = 0.033) and the OS rates between patients with different pretreatment durations (68.7% vs. 43.3%, P = 0.007). However, no significant differences were observed in OS, DSS, LRFS and DFS rates between patients with upper and lower CN palsy (P = 0.581, P = 0.792, P = 0.729 and P = 0.212, respectively). The results showed that recovery duration was an independent prognostic factor for OS (HR = 2.485; P < 0.001), DSS (HR = 2.065; P = 0.016), LRFS (HR = 3.051; P = 0.001) and DFS (HR = 2.440; P < 0.001). Recovery duration is an independent prognostic factor for NPC patients with CN palsy and is related to recurrence, which leads to poor survival. Recovery duration requires close surveillance and different treatment regimens

  19. Prognostic Value of Prevertebral Space Involvement in Nasopharyngeal Carcinoma Based on Intensity-Modulated Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: To investigate the prognostic significance of prevertebral space involvement (PSI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: A retrospective review of data from 506 biopsy-proven, nonmetastatic NPCs was performed. Patients underwent magnetic resonance imaging examinations and received IMRT as their primary treatment. Results: In this series, 161 NPC patients (31.8%) had PSI. Parapharyngeal space (p < 0.001), skull base (p < 0.001), and paranasal sinuses (p = 0.009) were associated with PSI after multivariate analysis. The 4-year overall survival (OS), local relapse-free survival (LRFS), distant metastasis–free survival (DMFS) for NPC patients with and without PSI was 69.1% and 89.2% (p < 0.0001), 83.9% and 96.4% (p < 0.0001), and 71.6% and 89.6% (p < 0.0001), respectively. Multivariate analysis identified PSI as an independent negative prognostic factor for both OS (HR = 1.478–4.380; p = 0.001) and DMFS (HR = 1.389–4.174; p = 0.002). Patients with PSI had similar survival rates in OS and DMFS (p = 0.241 and p = 0.493, respectively) to that of T4 disease, while the differences between PSI and T3 disease in both OS and DMFS were distinctly significant (p = 0.029 and p = 0.029, respectively). Conclusions: For NPC patients treated with IMRT, PSI was found to be an independent prognostic factor for both OS and DMFS. It seems reasonable that PSI should be classified as a T4 disease on the basis of the current American Joint Committee on Cancer staging classification criteria.

  20. The combination of suicide gene therapy and radiation enhances the killing of nasopharyngeal carcinoma xenographs

    International Nuclear Information System (INIS)

    Nasopharyngeal carcinoma (NPC) is very common in Southern China and Southeast Asian countries. To explore a novel and more effective approach to NPC therapy, a combined strategy of suicide genes and radiation was designed in this study. Five suicide gene expression cassettes, yeast cytosine deaminase (CD), yeast CD/uracil phosphoribosyl-transferase (UPRT), and yeast CDglyTK gene controlled by CMV, and Egr-1 and a synthetic CMV-enhanced Egr-1 promoter (CE) were constructed in an expression vector p11MS. The expression of suicide genes in NPC CNE-2 cells were detected by reverse transcription polymerase chain reaction (RT-PCR) and Western blot. The cytotoxicity of suicide gene therapy and radiation were analyzed by MTT assay. An animal study in which yeast CD/UPRT-expressing CNE-2 tumors in nude mice were treated with 5-fluorocytosine (5-FC) and radiation was also developed. Our results revealed that p11MSCEyCD/UPRT and p11MSCEyCDglyTK are superior over three other constructs in the killing of NPC cells in vitro. We combined suicide gene-expressing tumors, 5-FC treatment, and radiation in vivo and found that the tumors greatly regressed, some disappeared completely in 3 nude mice in the yCD/UPRT group, and a significant difference of tumor volumes was observed between this group and the other four groups (p<0.05). Our results indicated that suicide gene therapy and radiation have a synergic effect on NPC therapy, and the combined strategy of radiogene therapy is of great potential as a substitute for the traditional method, radiation alone, in NPC therapies. (author)

  1. Analysis of EGFR signaling pathway in nasopharyngeal carcinoma cells by quantitative phosphoproteomics

    Directory of Open Access Journals (Sweden)

    He Qiu-Yan

    2011-06-01

    Full Text Available Abstract Background The epidermal growth factor receptor (EGFR is usually overexpressed in nasopharyngeal carcinoma (NPC and is associated with pathogenesis of NPC. However, the downstream signaling proteins of EGFR in NPC have not yet been completely understood at the system level. The aim of this study was identify novel downstream proteins of EGFR signaling pathway in NPC cells. Results We analyzed EGFR-regulated phosphoproteome in NPC CNE2 cells using 2D-DIGE and mass spectrometry analysis after phosphoprotein enrichment. As a result, 33 nonredundant phosphoproteins including five known EGFR-regulated proteins and twenty-eight novel EGFR-regulated proteins in CNE2 were identified, three differential phosphoproteins were selectively validated, and two differential phosphoproteins (GSTP1 and GRB2 were showed interacted with phospho-EGFR. Bioinformatics analysis showed that 32 of 33 identified proteins contain phosphorylation modification sites, and 17 identified proteins are signaling proteins. GSTP1, one of the EGFR-regulated proteins, associated with chemoresistance was analyzed. The results showed that GSTP1 could contribute to paclitaxel resistance in EGF-stimulated CNE2 cells. Furthermore, an EGFR signaling network based on the identified EGFR-regulated phosphoproteins were constructed using Pathway Studio 5.0 software, which includes canonical and novel EGFR-regulated proteins and implicates the possible biological roles for those proteins. Conclusion The data not only can extend our knowledge of canonical EGFR signaling, but also will be useful to understand the molecular mechanisms of EGFR in NPC pathogenesis and search therapeutic targets for NPC.

  2. Preliminary results of phase I/II study of simultaneous modulated accelerated (SMART) for nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin Hong; Lee, Sang Wook; Back, Geum Mun [College of Medicine, University of Ulsan, Asan Medical Center, Seoul (Korea, Republic of)] (and others)

    2006-03-15

    To present preliminary results of intensity-modulated radiotherapy (IMRT) using the simultaneous modulated accelerated radiation therapy (SMART) boost technique in patients with nasopharyngeal carcinoma (NPC). Twenty patients who underwent IMRT for non-metastatic NPC at the Asan Medical Center between September 2001 and December 2003 were prospectively evaluated. IMRT was delivered using the 'step and shoot' SMART technique at prescribed doses of 72 Gy (2.4 Gy/day) to the gross tumor volume (GTV), 60 Gy (2 Gy/day) to the clinical target volume (CTV) and metastatic nodal station, and 46 Gy (2 Gy/day) to the clinically negative neck region. Eighteen patients also received concurrent chemotherapy using cisplatin once per week. The median follow-up period was 27 months. Nineteen patients completed the treatment without interruption; the remaining patient interrupted treatment for 2 weeks owing to severe pharyngitis and malnutrition. Five patients (25%) had RTOG grade 3 mucositis, whereas nine (45%) had grade 3 pharyngitis. Seven patients (35%) lost more than 10% of their pretreatment weight, whereas 11 (55%) required intravenous fluids and/or tube feeding. There was no grade 3 or 4 chronic xerostomia. All patients showed complete response. Two patients had distant metastases and loco-regional recurrence, respectively. IMRT using the SMART boost technique allows parotid sparing, as shown clinically and by dosimetry, and may also be more effective biologically. A larger population of patients and a longer follow-up period are needed to evaluate ultimate tumor control and late toxicity.

  3. Picropodophyllin inhibits tumor growth of human nasopharyngeal carcinoma in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Shu-Cheng [Department of Otolaryngology – Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Department of Otolaryngology – Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Guo, Wei [Department of Otolaryngology – Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Tao, Ze-Zhang, E-mail: zezhangtao@gmail.com [Department of Otolaryngology – Head and Neck Surgery, Renmin Hospital of Wuhan University, Wuhan 430060 (China)

    2013-09-13

    Highlights: •We identified that PPP inhibits IGF-1R/Akt pathway in NPC cells. •PPP dose-dependently inhibits NPC cell proliferation in vitro. •PPP suppresses tumor growth of NPC in nude mice. •PPP have little effect on microtubule assembly. -- Abstract: Insulin-like growth factor-1 receptor (IGF-1R) is a cell membrane receptor with tyrosine kinase activity and plays important roles in cell transformation, tumor growth, tumor invasion, and metastasis. Picropodophyllin (PPP) is a selective IGF-1R inhibitor and shows promising antitumor effects for several human cancers. However, its antitumor effects in nasopharyngeal carcinoma (NPC) remain unclear. The purpose of this study is to investigate the antitumor activity of PPP in NPC using in vitro cell culture and in vivo animal model. We found that PPP dose-dependently decreased the IGF-induced phosphorylation and activity of IGF-1R and consequently reduced the phosphorylation of Akt, one downstream target of IGF-1R. In addition, PPP inhibited NPC cell proliferation in vitro. The half maximal inhibitory concentration (IC50) of PPP for NPC cell line CNE-2 was ⩽1 μM at 24 h after treatment and ⩽0.5 μM at 48 h after treatment, respectively. Moreover, administration of PPP by intraperitoneal injection significantly suppressed the tumor growth of xenografted NPC in nude mice. Taken together, these results suggest targeting IGF-1R by PPP may represent a new strategy for treatment of NPCs with positive IGF-1R expression.

  4. PET/CT for staging and follow-up of pediatric nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cheuk, Daniel K.L. [St Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); The University of Hong Kong, Department of Paediatrics and Adolescent Medicine, Pokfulam (China); Sabin, Noah D.; Hossain, Moinul; Krasin, Matthew J.; Shulkin, Barry L. [St Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Wozniak, Amy [St Jude Children' s Research Hospital, Department of Biostatistics, Memphis, TN (United States); Naik, Mihir [St Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); University of Texas Health Science Center, Department of Radiation Oncology, San Antonio, TX (United States); Rodriguez-Galindo, Carlos [St Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Hematology/Oncology, Dana-Farber Cancer Institute, Boston, MA (United States)

    2012-07-15

    While FDG PET/CT for the evaluation of nasopharyngeal carcinoma (NPC) in adult patients has documented advantages and disadvantages compared with conventional imaging, to our knowledge, no studies of FDG PET/CT for the evaluation of NPC in pediatric patients have been performed. In this investigation, we studied the utility of FDG PET/CT in children with NPC. The study group comprised 18 children with biopsy-proven NPC who underwent FDG PET/CT and MRI (total 38 pairs of images). All baseline and follow-up FDG PET/CT and MRI studies were independently reviewed for restaging of disease. The concordance between FDG PET/CT and MRI in T, N, and overall staging was 29%, 64%, and 43%, respectively. Compared with MRI, FDG PET/CT yielded lower T and overall staging and showed less cervical and retropharyngeal lymphadenopathy. The concordance between follow-up FDG PET/CT and MRI was 79% overall and 100% 9 months after therapy. In patients who achieved complete remission, FDG PET/CT showed disease clearance 3-6 months earlier than MRI. There were no false-positive or false-negative FDG PET/CT scans during follow-up. FDG PET/CT may underestimate tumor extent and regional lymphadenopathy compared with MRI at the time of diagnosis, but it helps to detect metastases and clarify ambiguous findings. FDG PET/CT is sensitive and specific for follow-up and enables earlier determination of disease remission. FDG PET/CT is a valuable imaging modality for the evaluation and monitoring of NPC in pediatric patients. (orig.)

  5. Patterns of failure after the reduced volume approach for elective nodal irradiation in nasopharyngeal carcinoma

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    Seol, Ki Ho; Lee, Jeong Eun [Dept. of Radiation Oncology, Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

    2016-03-15

    To evaluate the patterns of nodal failure after radiotherapy (RT) with the reduced volume approach for elective neck nodal irradiation (ENI) in nasopharyngeal carcinoma (NPC). Fifty-six NPC patients who underwent definitive chemoradiotherapy with the reduced volume approach for ENI were reviewed. The ENI included retropharyngeal and level II lymph nodes, and only encompassed the echelon inferior to the involved level to eliminate the entire neck irradiation. Patients received either moderate hypofractionated intensity-modulated RT for a total of 72.6 Gy (49.5 Gy to elective nodal areas) or a conventional fractionated three-dimensional conformal RT for a total of 68.4-72 Gy (39.6-45 Gy to elective nodal areas). Patterns of failure, locoregional control, and survival were analyzed. The median follow-up was 38 months (range, 3 to 80 months). The out-of-field nodal failure when omitting ENI was none. Three patients developed neck recurrences (one in-field recurrence in the 72.6 Gy irradiated nodal area and two in the elective irradiated region of 39.6 Gy). Overall disease failure at any site developed in 11 patients (19.6%). Among these, there were six local failures (10.7%), three regional failures (5.4%), and five distant metastases (8.9%). The 3-year locoregional control rate was 87.1%, and the distant failure-free rate was 90.4%; disease-free survival and overall survival at 3 years was 80% and 86.8%, respectively. No patient developed nodal failure in the omitted ENI site. Our investigation has demonstrated that the reduced volume approach for ENI appears to be a safe treatment approach in NPC.

  6. Grape seed proanthocyanidins induce apoptosis through the mitochondrial pathway in nasopharyngeal carcinoma CNE-2 cells.

    Science.gov (United States)

    Yao, Kai; Shao, Jingjing; Zhou, Keyuan; Qiu, Haitao; Cao, Fengxiang; Li, Caihong; Dai, De

    2016-08-01

    Although modern radiotherapy offers excellent local control in the treatment of nasopharyngeal carcinoma (NPC), current therapeutic decisions remain burdensome due to the frequency of local recurrence and treatment failure at distant sites. One potential and promising strategy for the prevention or treatment of cancers is the use of bioactive components of plant origin, including dietary plant products. Herein, we studied one class of these bioactive compounds, grape seed proanthocyanidins (GSPs), and explored their effect on NPC CNE-2 cells, as well as the primary mechanism underlying this effect. Our results revealed that treatment of human NPC CNE-2 cells with GSPs reduced cell viability in a dose- and time-dependent manner, and moreover, markedly induced cell cycle arrest at the G2/M phase, leading to induction of apoptosis. In addition, we found that the underlying mechanism was associated with increased expression of the pro-apoptotic protein Bax, decreased expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, upregulation of cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PRAP) protein, and the loss of mitochondrial membrane potential (MMP) (Δψm). Furthermore, GSPs upregulated the Bcl-2 homology 3 (BH3)-only proteins, Bim and Bad, in a concentration-dependent manner. Taken together, these data supported our hypothesis that, in human NPC CNE-2 cells, GSPs could induce apoptosis through the mitochondrial pathway and ultimately reduce cell viability. Collectively, the results discussed above provide substantive evidence for the potential of GSPs as an effective bioactive phytochemical for the treatment of NPC. PMID:27277418

  7. Replanning During Intensity Modulated Radiation Therapy Improved Quality of Life in Patients With Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Yang Haihua [Department of Radiation Oncology, Laboratory of Cellular and Molecular Radiation Oncology, Taizhou Hospital, Wenzhou Medical College, Taizhou, Zhejiang Province (China); Hu Wei, E-mail: huw@enzemed.com [Department of Radiation Oncology, Laboratory of Cellular and Molecular Radiation Oncology, Taizhou Hospital, Wenzhou Medical College, Taizhou, Zhejiang Province (China); Wang Wei; Chen Peifang; Ding Weijun [Department of Radiation Oncology, Laboratory of Cellular and Molecular Radiation Oncology, Taizhou Hospital, Wenzhou Medical College, Taizhou, Zhejiang Province (China); Luo Wei [Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky (United States)

    2013-01-01

    Purpose: Anatomic and dosimetric changes have been reported during intensity modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the effects of replanning on quality of life (QoL) and clinical outcomes during the course of IMRT for NPC patients. Methods and Materials: Between June 2007 and August 2011, 129 patients with NPC were enrolled. Forty-three patients received IMRT without replanning, while 86 patients received IMRT replanning after computed tomography (CT) images were retaken part way through therapy. Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Head and Neck Quality of Life Questionnaire 35 were completed before treatment began and at the end of treatment and at 1, 3, 6, and 12 months after the completion of treatment. Overall survival (OS) data were compared using the Kaplan-Meier method. Results: IMRT replanning had a profound impact on the QoL of NPC patients, as determined by statistically significant changes in global QoL and other QoL scales. Additionally, the clinical outcome comparison indicates that replanning during IMRT for NPC significantly improved 2-year local regional control (97.2% vs 92.4%, respectively, P=.040) but did not improve 2-year OS (89.8% vs 82.2%, respectively, P=.475). Conclusions: IMRT replanning improves QoL as well as local regional control in patients with NPC. Future research is needed to determine the criteria for replanning for NPC patients undergoing IMRT.

  8. Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10−9), but was less obvious in other types of solid tumors except for prostate and Epstein–Barr virus (EBV)-positive gastric cancer (FDR<10−3). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection

  9. Intensity-modulated radiation therapy for T4 nasopharyngeal carcinoma. Treatment results and locoregional

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    Chen, J.L.Y.; Tsai, C.L.; Chen, W.Y.; Wang, C.W. [National Taiwan Univ. Hospital, Taipei (China). Div. of Radiation Oncology; Huang, Y.S.; Chen, Y.F. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Medical Imaging; Kuo, S.H. [National Taiwan Univ. Hospital, Taipei (China). Div. of Radiation Oncology; National Taiwan Univ. College of Medicine, Taipei (China). Graduate Inst. of Clinical Medicine; Hong, R.L. [National Taiwan Univ. Hospital, Taipei (China). Div. of Medical Oncology; Ko, J.Y.; Lou, P.J. [National Taiwan Univ. Hospital, Taipei (China). Dept. of Otolaryngology

    2013-12-15

    Purpose: The purpose of this work was to examine outcomes in patients with T4 nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). Methods and materials: Between 2007 and 2010, 154 patients with nonmetastatic T4 NPC were treated with IMRT to a total dose of 70 Gy in 33-35 fractions. In addition, 97 % of patients received concurrent platinum-based chemotherapy. The median follow-up time was 52.8 months. Results: The rates of 5-year actuarial locoregional control, distant metastasis-free survival, progression free-survival, and overall survival (OS) were 81.2, 72.2, 61.9, and 78.1 %, respectively. A total of 27 patients had locoregional recurrence: 85.2 % in-field failures, 11.1 % marginal failures, and 3.7 % out-of-field failures. Fourteen patients with locoregional recurrence received aggressive treatments, including nasopharyngectomy, neck dissection, or re-irradiation, and the 5-year OS rate tended to be better (61.9 %) compared to those receiving conservative treatment (32.0 %, p = 0.051). In patients treated with 1 course of radiotherapy, grade {>=} 3 toxicities of ototoxicity, neck fibrosis, xerostomia, epistaxis, and radiographic temporal lobe necrosis occurred in 18.2, 9.8, 6.3, 2.1, and 5.6 % of patients, respectively. Increased ototoxicity, osteonecrosis, severe nasal bleeding, and temporal necrosis were observed in patients treated by re-irradiation. Conclusion: IMRT offers good locoregional control in patients with T4 NPC. For patients with locoregional recurrence after definitive radiotherapy, aggressive local treatment may be considered for a better outcome. (orig.)

  10. A prospective study: current problems in radiotherapy for nasopharyngeal carcinoma in yogyakarta, indonesia.

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    Sharon D Stoker

    Full Text Available INTRODUCTION: Nasopharyngeal carcinoma (NPC has a high incidence in Indonesia. Previous study in Yogyakarta revealed a complete response of 29% and a median overall survival of less than 2 years. These poor treatment outcome are influenced by the long diagnose-to-treatment interval to radiotherapy (DTI and the extended overall treatment time of radiotherapy (OTT. This study reveals insight why the OTT and DTI are prolonged. METHOD: All patients treated with curative intent radiotherapy for NPC between July 2011 until October 2012 were included. During radiotherapy a daily diary was kept, containing information on DTI, missed radiotherapy days, the reason for missing and length of OTT. RESULTS: Sixty-eight patients were included. The median DTI was 106 days (95% CI: 98-170. Fifty-nine patients (87% finished the treatment. The median OTT for radiotherapy was 57 days (95% CI: 57-65. The main reason for missing days was an inoperative radiotherapy machine (36%. Other reasons were patient's poor condition (21%, public holidays (14%, adjustment of the radiation field (7%, power blackout (3%, inoperative treatment planning system (2% and patient related reasons (9%. Patient's insurance type was correlated to DTI in disadvantage for poor people. CONCLUSION: Yogyakarta has a lack of sufficient radiotherapy units which causes a delay of 3-4 months, besides the OTT is extended by 10-12 days. This influences treatment outcome to a great extend. The best solution would be creating sufficient radiotherapy units and better management in health care for poor patients. The growing economy in Indonesia will expectantly in time enable these solutions, but in the meantime solutions are needed. Solutions can consist of radiation outside office hours, better maintenance of the facilities and more effort from patient, doctor and nurse to finish treatment in time. These results are valuable when improving cancer care in low and middle income countries.

  11. High expression of Sox10 correlates with tumor aggressiveness and poor prognosis in human nasopharyngeal carcinoma

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    Zhao Y

    2016-03-01

    Full Text Available Yu Zhao,1,* Zhi-gang Liu,1,* Jiao Tang,1 Ren-fang Zou,1 Xiao-yan Chen,2 Guan-min Jiang,3 Yan-fang Qiu,1 Hui Wang11Key Laboratory of Translational Radiation Oncology, Department of Radiation Oncology, 2Department of Pathology, 3Department of Clinical Laboratory, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, People’s Republic of China*These authors contributed equally to this workPurpose: The aim of the study was to detect the expression of Sox10 in human nasopharyngeal carcinoma (NPC and investigate the relationship between its expression and the clinicopathological characteristics of NPC patients.Patients and methods: Tumor specimens (n=105 were retrospectively collected from patients with NPC diagnosed between 2004 and 2005 who presented at Hunan Cancer Hospital. Immunohistochemistry analyses were performed to characterize the expression of Sox10 in NPC. Kaplan–Meier survival and Cox regression analyses were employed to evaluate the prognosis of 105 NPC patients.Results: The results showed that Sox10 was markedly overexpressed in human NPC tissues. Analysis of clinicopathological parameters showed that high Sox10 expression was significantly correlated with the clinical stage (P=0.032, T classification (P=0.034, and lymph node metastasis (P=0.03. Cox regression analyses further showed that Sox10 expression was an independent prognostic factor for overall survival (P=0.005. This is the first time Sox10 has shown its importance in predicting NPC progressiveness and survival outcomes.Conclusion: Sox10 serves as a potential biomarker for NPC patients. It may hopefully become a novel therapeutic target for NPC patients.Keywords: Sox10, NPC, prognosis

  12. Clinical Dosimetric Comparison among Different Intensity-Modulated Radiotherapy Plans for Nasopharyngeal Carcinoma

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    Changjiang Sun

    2014-03-01

    Full Text Available Objective: To compare the dosimetric differences of different intensity-modulated radiation therapy (IMRT plans for nasopharyngeal carcinoma (NPC. Methods: 5-, 7- and 9-fields of IMRT plans in 16 NPC patients were respectively designed and synchronous dimention technology was applied to compare the dosimetric differences in target areas and involved organs. Results: The recovery rate in target area was 95% while the plan was evidently worse in 5-field than in 7- and 9-fields (P < 0.05. Whereas the maximum dosage (Dmax, mean dosage (Dmean and minimum dosage (Dmin were similar between 7- and 9-fields (P > 0.05, which were obviously lower in 5-field, and the differences were both significant (P < 0.05. In addition, the conformity and homogeneity indexes in target area had no significant difference between 7- and 9-fields, but were markedly better than in 5-field (P < 0.05. Indexes in each involved organs were the lowest in 5-field than in other fields (P < 0.05, but were similar between 7- and 9-fields (P > 0.05, which were all lower than tolerant dosage. As for BODY, there were significant differences in V10 - V20 between 5-field and other fields (P < 0.05, but were similar in V25 - V30 (P > 0.05. However, 7- and 9-fields were similar in V10 - V20 (P > 0.05. Conclusion: 7-field IMRT plan is the optimal one for NPC on both clinical dosimetric requirements and field-establishment principles.

  13. Influence of MRI abnormality in skull base bone on prognosis of nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Purpose. To evaluate the influence of skull base bone (SBB) abnormality showed by MRI on prognosis of nasopharyngeal carcinoma (NPC). Patients and methods. From March 1993 to December 1998, 122 NPC patients received prime radiotherapy treatment. All of them were proved pathologically and checked by magnetic resonance imaging (MRI). Every patient received radiation through conjoint facio-cervical field and conventional dose-fractionation schedules. The total dose to the primary tumor was 60 5 Gy (median, 70 Gy). The Kaplan Meier method, the Log-rank test and the Cox regression model were used to evaluate the significance of prognostic factors on NPC patient survival. Results. The overall median survival period was 50 (6 2) months, and the 1, 3 and 5 year-survival rates were, respectively, 99.2%, 87.9%, and 73.3%. The 1, 3, and 5 year-survival rates of abnormality and normality of the SBB on MRI were 98.9%, 87.2%, 71.9%, and 100.0%, 89.8%, 77.0%, respectively (P 0.4233). Gender, age, head pain, SBB abnormality, cranial nerve palsy, cervical lymphadenopathy and primary tumor extent were analyzed with the Cox regression model and SBB abnormality on MRI did not prove to have statistical significance (P = 0.6934). According to the analysis of regrouping, patients with SBB abnormalities ≥ sites have a worse prognosis (P = 0.0427). Then. the above seven factors are analyzed by Cox regression model and the result had statistical significance (P = 0.0385). Conclusion. The SBB abnormality on MRI is of no obvious influence on prognosis of NPC. However, when SBB abnormality sites were ≥ 2, there is obvious statistical significance on the prognosis. (author)

  14. High expression of ubiquitin-conjugating enzyme 2C (UBE2C) correlates with nasopharyngeal carcinoma progression

    International Nuclear Information System (INIS)

    Overexpression of ubiquitin-conjugating enzyme 2C (UBE2C) has been detected in many types of human cancers, and is correlated with tumor malignancy. However, the role of UBE2C in human nasopharyngeal carcinoma (NPC) is unclear. In this study, we investigated the role of aberrant UBE2C expression in the progression of human NPC. Immunohistochemical analysis was performed to detect UBE2C protein in clinical samples of NPC and benign nasopharyngeal tissues, and the association of UBE2C expression with patient clinicopathological characteristics was analyzed. UBEC2 expression profiles were evaluated in cell lines representing varying differentiated stages of NPC and immortalized nasopharyngeal epithelia NP-69 cells using quantitative RT-PCR, western blotting and fluorescent staining. Furthermore, UBE2C was knocked down using RNA interference in these cell lines and proliferation and cell cycle distribution was investigated. Immunohistochemical analysis revealed that UBE2C protein expression levels were higher in NPC tissues than in benign nasopharyngeal tissues (P<0.001). Moreover, high UBE2C protein expression was positively correlated with tumor size (P=0.017), lymph node metastasis (P=0.016) and distant metastasis (P=0.015) in NPC patients. In vitro experiments demonstrated that UBE2C expression levels were inversely correlated with the degree of differentiation of NPC cell lines, whereas UBE2C displayed low level of expression in NP-69 cells. Knockdown of UBE2C led to significant arrest at the S and G2/M phases of the cell cycle, and decreased cell proliferation was observed in poorly-differentiated CNE2Z NPC cells and undifferentiated C666-1 cells, but not in well-differentiated CNE1 and immortalized NP-69 cells. Our findings suggest that high expression of UBE2C in human NPC is closely related to tumor malignancy, and may be a potential marker for NPC progression

  15. THREE-DIMENSIONAL CONFORMAL RADIATION THERAPY FOR LOCALLY RECURRENT NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To investigate the safety and effectiveness of three-dimensional conformal radiation therapy (3-D CRT) for locally recurrent nasopharyngeal carcinoma (NPC). Methods: From April 1998 to March 2000, 34 patients who had undergone previous external beam radiation therapy were retreated with 3-D CRT for locally recurrent NPC (33 poorly differentiated squamous cell carcinomas, 1 adenoma). The patients were re-staged according to Huaqing staging system with the following distribution: T1N0M0 in 5 cases, T2N0M0 in 11 cases, T3N0M0 in 12 cases, T4N0M0 in 6 cases. The maximal dimension of the gross tumor volume (GTV) ranged from 1.0 cm to 5.0 cm (median: 2.9 cm). CT simulation and 3-D planning were used to ensure full and conformal coverage of the planning target volume (PTV) by treated volume, while minimizing the absorbed dose of the adjacent normal tissue. 5-7 static conformal coplanar or noncoplanar portals were delivered for each fraction irradiation. The total dose delivered ranged from 65-70 Gy, with 2.5 Gy per fractionation, one fractionation per day, 5 days a week. Median follow-up time from 3-D CRT was 25 months (range: 12-36 months). Results: Over the follow-up period, local recurrence was observed in 3 patients, regional failure in 3, distant metastasis in 3, and six patients died; 88.2% (30/34) of the patient maintained local control, 82.4% (28/34) survived, and 76.5% (26/34) survived with no evidence of tumor. Acute complications were minor and few. The overall incidence of late complication was 20.6% (7/34), and severe complication was 14.7% (5/34), after re-irradiation with 3-D CRT. Conclusion: 3-D CRT is safety and effectiveness for most of the patients with locally recurrent NPC. Our preliminary results indicate a high local control rate and a low complication rate. The long-term curative effect and sequelae await further study.

  16. Long-Term Outcomes of Nasopharyngeal Carcinoma in 148 Children and Adolescents

    Science.gov (United States)

    Lu, Suying; Chang, Hui; Sun, Xiaofei; Zhen, Zijun; Sun, Feifei; Zhu, Jia; Wang, Juan; Huang, Junting; Liao, Ru; Guo, Xiaofang; Lu, Lixia; Gao, Yuanhong

    2016-01-01

    Abstract The aim of this study was to investigate the survival and long-term morbidities of nasopharyngeal carcinoma (NPC) in children and adolescents. We retrospectively reviewed children and adolescents with NPC treated at Sun Yat-sen University Cancer Center from February 1991 to October 2010, where the prognostic factors and long-term effects of therapy were analyzed. A total of 148 patients were identified. The median age was 15 years old (range, 5–18 years) and the male to female ratio was 3.6:1. Most of the tumor histopathology was undifferentiated nonkeratinizing carcinoma (97.3%). The number of patients staged with IVa, IVb, IVc, III, and II were 45 (30.4%), 12 (8.1%), 5 (3.4%), 70 (47.3%), and 16 (10.8%), respectively. For the whole series with a median follow-up of 81 months (range, 6–282 months), the 5-year overall survival (OS) and disease-free survival (DFS) ratios were 79.3% and 69.7%, respectively. We observed significant differences in the 5-year OS (81.1% vs 25.0%, P = 0.002) and the DFS rates (72.2% vs 0.0%, P = 0.000) between patients with stage II to IVb disease and stage IVc disease. For patients with stage II, III, IVa, and IVb disease, we found a high radiation dose (dose > 66 Gy to the primary lesion) would not significantly improve the survival compared to the sub-high radiation dose group (dose = 60–66 Gy to the primary lesion), even considering the type of radiation therapy technologies. However, the incidences of sequelae (grades I–IV) in patients with high radiation dose were apparently higher than those in patients with low radiation dose. Considering the late sequelae, a dose of 60 to 66 Gy to the primary lesions seems to be enough for children and adolescents with NPC. PMID:27124036

  17. CDK2在鼻咽癌中的表达及意义%The Expression and Significance of CDK-2 in Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    官树雄; 蒋月荷; 王继群; 山艳春

    2011-01-01

    目的 探讨细胞周期蛋白依赖性激酶2(CDK2)在鼻咽癌和慢性鼻咽炎黏膜组织中的表达水平,及其与鼻咽癌的临床病理关系.方法 免疫组化SP法检测CDK2蛋白在鼻咽癌和慢性鼻咽炎黏膜组织中的表达情况.结果 CDK2蛋白阳性表达主要定位于细胞核,少数有胞浆着色,呈棕黄色或棕褐色不同强度的染色.62例鼻咽癌组织中阳性表达率为69.4%(43/62),慢性鼻咽炎黏膜组织中阳性率为32.0%(9/28),两组间差异有统计学意义(P<0.05).CDK2蛋白表达与鼻咽癌分化程度,淋巴结转移范围,TNM分期有关(P<0.05).结论 CDK2在鼻咽癌组织中的表达明显高于慢性鼻咽炎黏膜组织中的表达,提示CDK2与鼻咽癌的发生、发展有关.CDK2与鼻咽癌分化程度,淋巴结转移范围,TNM分期有关.%Objective The propose of the research was focused on the expression levels of CDK2 in the tissues of nasopharyngeal carcinoma and chronic inflammation nasopharyngeal membrane. And it may relate to the pathogenesis and clinical significance of nasopharyngeal carcinoma which had been observed in the field of cell cycle. Methods Immunohistochemistry.(sp) was used to examine the expression levels of CDK2 protein in the tissues of nasopharyngeal carcinoma and chronic inflammation nasopharyngeal membrane. Results Most of the CDK2 protein positive expression was found in cell nucleus,but some was found in the kytoplasm and its color was brown yellow or dark brown. The positive expression rate of nasopharyngeal carcinoma from 62 patients was 69.40% (43/62), and that of the chronic inflammation nasopharyngeal membrane was 32.0% (9/28). The difference of the two groups was found statistical significance( P < 0.05 ) ;the expression levels of CDK2 were related to the differential degree, the range of lymph node metastases and clinical staging of nasopharyngeal carcinoma, the difference was been found statistical significance( P < 0.05 ). Conclusion The expression

  18. Conformal Radiotherapy in the Treatment of Advanced Juvenile Nasopharyngeal Angiofibroma With Intracranial Extension: An Institutional Experience

    International Nuclear Information System (INIS)

    Purpose: To describe the results of conformal radiotherapy in advanced juvenile nasopharyngeal angiofibroma in a tertiary care institution. Methods and Materials: Retrospective chart review was conducted for 8 patients treated with conformal radiotherapy between 2006 and 2009. The median follow-up was 17 months. All patients had Stage IIIB disease with intracranial extension. Radiotherapy was considered as treatment because patients were deemed inoperable owing to extensive intracranial/intraorbital extension or proximity to optic nerve. All but 1 patient were treated with intensity-modulated radiotherapy using seven coplanar fields. Median (range) dose prescribed was 39.6 (30-46) Gy. Actuarial analysis of local control and descriptive analysis of toxicity profile was conducted. Results: Despite the large and complex target volume (median planning target volume, 292 cm3), intensity-modulated radiotherapy achieved conformal dose distributions (median van't Reit index, 0.66). Significant sparing of the surrounding organs at risk was obtained. No significant Grade 3/4 toxicities were experienced during or after treatment. Actual local control at 2 years was 87.5%. One patient died 1 month after radiotherapy secondary to massive epistaxis. The remaining 7 patients had progressive resolution of disease and were symptom-free at last follow-up. Persistent rhinitis was the only significant toxicity, seen in 1 patient. Conclusions: Conformal radiotherapy results in good local control with minimal acute and late side effects in juvenile nasopharyngeal angiofibromas, even in the presence of advanced disease.

  19. Increased treatment-related mortality with additional cisplatin-based chemotherapy in patients with nasopharyngeal carcinoma treated with standard radiotherapy

    International Nuclear Information System (INIS)

    Background and purposes: We performed a meta-analysis of randomized controlled trials (RCTs) to determine the overall risk of treatment-related death associated with additional cisplatin-based chemotherapy in patients with nasopharyngeal carcinoma treated with standard radiotherapy. Material and methods: Eligible studies included RCTs in which cisplatin-based chemotherapy in combination with radiotherapy was compared with radiotherapy alone. Statistical analyses were conducted to calculate the summary incidence rates, relative risks (RRs), and 95% confidence intervals (CIs) using fixed- or random-effects models based on the heterogeneity of included studies. Results: A total of 2829 patients from 13 RCTs were included in this study. The overall incidence for treatment-related death in chemoradiotherapy and radiotherapy treated patients was 1.7% and 0.8%. Compared to radiotherapy alone, radiotherapy plus cisplatin-based chemotherapy significantly increased the risk of treatment-related mortality. On subgroup analyses, no difference was found in treatment-related mortality between different timings of chemotherapy and chemotherapeutic agents. Adding cisplatin-based chemotherapy was associated with higher incidences of severe acute toxicity. Conclusions: Cisplatin-based chemotherapy plus radiotherapy increased the risk of treatment-related death and severe acute toxicity, compared with radiotherapy alone. Better management of treatment toxicity might improve the therapeutic gain in patients with nasopharyngeal carcinoma.

  20. Salinomycin inhibits proliferation and induces apoptosis of human nasopharyngeal carcinoma cell in vitro and suppresses tumor growth in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Danxin; Zhang, Yu; Huang, Jie; Fan, Zirong; Shi, Fengrong; Wang, Senming, E-mail: wsenming@126.com

    2014-01-10

    Highlight: •We first evaluated the effect of salinomycin on nasopharyngeal carcinoma (NPC). •Salinomycin could inhibit Wnt/β-catenin signaling and induce apoptosis in NPC. •So salinomycin may be a good potential candidate for the chemotherapy of NPC. -- Abstract: Salinomycin (Sal) is a polyether ionophore antibiotic that has recently been shown to induce cell death in various human cancer cells. However, whether salinomycin plays a functional role in nasopharyngeal carcinoma (NPC) has not been determined to date. The present study investigated the chemotherapeutic efficacy of salinomycin and its molecular mechanisms of action in NPC cells. Salinomycin efficiently inhibited proliferation and invasion of 3 NPC cell lines (CNE-1, CNE-2, and CNE-2/DDP) and activated a extensive apoptotic process that is accompanied by activation of caspase-3 and caspase-9, and decreased mitochondrial membrane potential. Meanwhile, the protein expression level of the Wnt coreceptor lipoprotein receptor related protein 6 (LRP6) and β-catenin was down-regulated, which showed that the Wnt/β-catenin signaling was involved in salinomycin-induced apoptosis of NPC cells. In a nude mouse NPC xenograft model, the anti-tumor effect of salinomycin was associated with the downregulation of β-catenin expression. The present study demonstrated that salinomycin can effectively inhibit proliferation and invasion, and induce apoptosis of NPC cells in vitro and inhibit tumor growth in vivo, probably via the inhibition of Wnt/β-catenin signaling, suggesting salinomycin as a potential candidate for the chemotherapy of NPC.

  1. Preparation of polyclonal antibody specific for NOR1 and detection of its expression pattern in human tissues and nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Bo Xiang; Mei Yi; Li Wang; Wei Liu; Wenling Zhang; Jue Ouyang; Ya Peng; Wenjuan Li; Ming Zhou; Huaying Liu; Minghua Wu; Rong Wang; Xiaoling Li; Guiyuan Li

    2009-01-01

    Oxidored-nitro domain containing protein 1 (NORI)gene is a novel nitroreductase gene first isolated from nasopharyngeal carcinoma (NPC). It plays an important role in the formation of chemical carcinogen and the carcinogenesis of NPC for its nitrosation function. Overexpression of the wild-type NOR1 gene in naso-pharyngeal carcinoma cells is effective to inhibit cell growth and proliferation. In this study, for the first time, we generated a highly specific NOR1 antibody and ana-lyzed NOR1 distribution in the human tissues and NPC biopsies. The results showed that NOR1 protein is predominantly expressed in human nasopharynx and tracheal tissues. Human heart, liver, spleen, stomach, colon, kidney, skeletal muscle, thymus, and pancreas are aH deficient of NORI protein. More importantly, we per-formed immunohistochemistry assay of NOR1 protein expression in the NPC tissues, and the result showed that NOR1 protein is frequently down-expressed in NPC. These data shed light on the selectivity of potential physiological functions of NOR1 and provides an indis-pensable reference to the carcinogenesis process of NPC and to identify or validate tissue-specific drug targets.

  2. Haplotype of gene Nedd4 binding protein 2 associated with sporadic nasopharyngeal carcinoma in the Southern Chinese population

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    Feng Qi-Sheng

    2007-07-01

    Full Text Available Abstract Background Bcl-3 as an oncoprotein is overexpressed in nasopharyngeal carcinoma (NPC. Nedd4 binding protein 2 (N4BP2, which is located in the NPC susceptibility locus, is a Bcl-3 binding protein. This study is aimed to explore the association between N4BP2 genetic polymorphism and the risk of NPC. Methods We performed a hospital-based case-control study, including 531 sporadic NPC and 480 cancer-free control subjects from southern China. PCR-sequencing was carried out on Exons, promoter region and nearby introns of the N4BP2 gene. The expression pattern of N4BP2 and Bcl-3 was also analyzed. Results We observed a statistically significant difference in haplotype blocks ATTA and GTTG between cases and controls. In addition, three novel SNPs were identified, two of which were in exons (loc123-e3l-snp2, position 39868005, A/G, Met171Val; RS17511668-SNP2, position 39926432, G/A, Glu118Lys, and one was in the intron6 (RS794001-SNP1, position 39944127, T/G. Moreover, N4BP2 was at higher levels in a majority of tumor tissues examined, relative to paired normal tissues. Conclusion These data suggest that haplotype blocks ATTA and GTTG of N4BP2 is correlation with the risk of sporadic nasopharyngeal carcinoma in the Southern Chinese population and N4BP2 has a potential role in the development of NPC.

  3. Angiogenesis, Inflammation, Platelets Count, and Metastatic Status as a Predictor for Thrombosis Risk in Nasopharyngeal Carcinoma Patients

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    Aru W Sudoyo

    2015-03-01

    Full Text Available Aim: to assess the use of of angiogenesis, inflammation, platelets count, and metastatic status as predictors for thrombosis risk represented by soluble P-selectin level in nasopharyngeal carcinoma (NPC patients. Methods: a cross sectional study was conducted on NPC patients at the Hematology and Oncology Clinic of Cipto Mangunkusumo Hospital, Jakarta, during Mei to October 2012. Data regarding angiogenesis (CD105 and VEGFR-2, inflammation (IL-6, platelets count, and metastatic status were assessed at enrollment, as well as soluble P-selectin levels in all eligible patients. Bivariate analysis continued with multiple linear regression analysis were done to identify independent predictors for soluble P-selectin levels. Results: sixty NPC patients were enrolled in the study. There was correlation between platelet counts (r=0.389; p=0.002, IL-6 (r=0.595; p<0.001 and number of metastatic sites (r=0.542; p<0.001 with soluble P-selectin level, and a linear regression analysis showed that these three variables can predict soluble P-selectin levels with adjusted R-square 65%. There was no correlation between VEGFR-2 and CD105 levels with soluble P-selectin levels.Conclusion: platelet counts, IL-6 level, and number of sites of metastasis can be used as predictors of soluble P-selectin level as parameter of thrombosis risk in NPC patients. Key words: nasopharyngeal carcinoma (NPC, thrombosis risk, soluble P-selectin.

  4. Evaluation of Body Mass Index and Survival of Nasopharyngeal Carcinoma by Propensity-Matched Analysis: An Observational Case-Control Study.

    Science.gov (United States)

    OuYang, Pu-Yun; Zhang, Lu-Ning; Tang, Jie; Lan, Xiao-Wen; Xiao, Yao; Gao, Yuan-Hong; Ma, Jun; Xie, Fang-Yun

    2016-01-01

    The effect of pretreatment body mass index on survival of nasopharyngeal carcinoma remains contradictory.All patients (N = 1778) underwent intensity-modulated radiotherapy with or without chemotherapy. Body mass index was categorized as underweight (support for early nutritional intervention during the long waiting time before treatment. PMID:26765414

  5. 鼻咽癌病人自我效能感的研究进展%Research progress on self efficacy of patients with nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    沈慧; 杨丽; 沈丽

    2016-01-01

    综述国内外鼻咽癌病人自我效能感的研究现状,探讨鼻咽癌病人自我效能感研究存在的不足,为自我效能感在鼻咽癌领域中的进一步研究发展提供参考。提出应将自我效能感研究应用到鼻咽癌病人的各个阶段还需进一步探究完善。%It summarized the research status quo of self efficacy of patients with nasopharyngeal carcinoma both at home and abroad and probe into the shortcomings in research of self efficacy in patients with nasopha-ryngeal carcinoma.It provided that reference for the further research and development of self efficacy in the field of nasopharyngeal carcinoma.It put forward that the study of self efficacy applied to each stage of pa-tients with nasopharyngeal carcinoma need to be further explored and improved.

  6. Induction of c-Met Proto-Oncogene by Epstein-Barr Virus Latent Membrane Protein-1 and the Correlation with Cervical Lymph Node Metastasis of Nasopharyngeal Carcinoma

    OpenAIRE

    Horikawa, Toshiyuki; Sheen, Tzung-Shiahn; Takeshita, Hajime; Sato, Hiroshi; Furukawa, Mitsuru; Yoshizaki, Tomokazu

    2001-01-01

    Nasopharyngeal carcinoma (NPC) is distinctive in head and neck carcinomas for its close association with Epstein-Barr virus and its highly metastatic nature. Up-regulation of cell motility is essential for enhancement of metastatic potential. The expression of c-Met proto-oncogene, a high-affinity receptor for hepatocyte growth factor/scatter factor, has been reported to correlate with metastatic ability of the tumor cell. We observed close association of c-Met expression with cervical lymph ...

  7. Influence of gender and age on the survival of patients with nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    The prognostic value of gender and age in the survival of nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT) is unclear. Several studies have suggested a female advantage in the prognosis of solid tumors. We investigated the relationship between gender differences and disease outcome in NPC patients treated with IMRT in South China. A total of 299 patients with non-disseminated NPC were analyzed retrospectively. IMRT was delivered with a simultaneous modulated, accelerated radiotherapy boost technique at prescribed doses of 70 Gy/30 fractions/6 weeks to the primary tumor (GTVp) and positive neck nodes (GTVn), 60Gy (2.0 Gy/day) to the clinical target volume (CTV) and upper neck region and 54 Gy (1.8 Gy/day) to the clinically negative low neck. A median boost dose of 9.2 Gy (4–20 Gy) was administered to patients with persistent disease at the primary site. With a median follow-up of 52 months, the male patients had a significantly unfavorable 5-year OS (70.7% compared to 94.1%, P < 0.001), DPFS (71.5% compared to 87.3%, P = 0.029) and DMFS (77.2% compared to 89.7%, P = 0.036) than the female patients. In patients younger than 45, the male patients had a poorer 5-year OS (66.8% compared to 91.2%, P = 0.008), DPFS (59.9% compared to 91.2%, P = 0.005) and DMFS (66.4% compared to 94.0%, P = 0.004) than the female patients. For patients older than 45, only the 5-year OS (72.2% compared to 96.0%, P = 0.001) was significantly different. Gender and age are strong independent prognostic factors for NPC in this study. We are the first to report that younger male patients were more likely to have distant metastases and exhibited inferior overall survival and disease progression-free survival rates compared to other patients

  8. An oncolytic adenovirus in combination with radiation treatment (RT) for nasopharyngeal carcinoma (NPC)

    International Nuclear Information System (INIS)

    We have succeeded in regulating gene expression in nasopharyngeal carcinoma (NPC) by exploiting the exclusive presence of the Epstein Barr virus (EBV) genome in the cancer cells. When the latently expressed EBV-gene product, EBNA-1, binds to a family of repeats (FR) sequence, located in the oriP of the EBV genome (oriP-FR), this results in transcriptional activation of downstream genes. Based on these observations we designed a transcriptional targeting strategy that now allows for the construction of a conditionally replicating adenovirus under the control of the oriP-FR promoter. Results: Cloning the E1A transcriptional unit downstream of the EBV-responsive, oriP-FR promoter sequence generated the novel adenovirus adv.oriP.E1A. E1A protein expression using Western blot analysis demonstrated a time-dependent increase in expression in the EBV-positive C666-1 cells, in contrast to minimal expression in EBV-negative NPC cells. The MTT assay showed a dose-dependent cytotoxic effect of adv.oriP.E1A in the C666-1 cells, and the combination with 6 Gy of ionizing radiation resulted in an additive cytotoxic effect. In contrast, no evidence of cytotoxicity was observed in a panel of four other human cell lines after adv.oriP.E1A treatment. Western blotting for adenoviral fiber knob protein demonstrated a time-dependent increase in expression, consistent with viral replication; this was confirmed using quantitative real-time PCR. Ex-vivo infection of C666-1 cells with adv.oriP.E1A inhibited tumor formation for at least 100 days after intramuscular injection as compared to control cells that established palpable tumors one week after injection. Treatment of established C666-1 tumours with six intratumoral injections of 2 x 109 pfu adv.oriP.E1A in combination with 2 x 4 Gy radiation therapy (RT) resulted in complete regression for 3-weeks. Conclusion: We have successfully constructed a novel selectively oncolytic virus for EBV-positive NPC cells, demonstrating significant

  9. EFFECTS OF p53 OVEREXPRESSION ON NEOPLASTIC CELL MITOSIS AND APOPTOSIS IN NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To investigate the p53 overexpression and its correlation withneoplastic cell mitosis and apoptosis in 43 nasopharyngeal carcinomas (NPCs). Methods: Forty-three pretreated NPC biopsy samples were randomly collected in the year 1997 for this study. p53 overexpression was detected by LSAB immunohistochemistry using DO-7 primary antibody. Mitotic figures were counted on H&E stained slides, and apoptotic cells on TUNEL-stained slides by use of in-situ cell death detection kit. Both of mitotic and apoptotic cells were quantitated by cell numbers per one high power field (5′ 40) averagely in terms of mitotic index (MI) and TUNEL index (TI), respectively. To compare the mean MIs of two groups categorized by different percentages of positive p53 positive cells found in NPC specimens was taken for the purpose of designating the criterion of p53 overexpression. And then, the correlation of p53 overexpression with MI and TI was made by statistical analysis. Results: Because statistically significant difference appeared at the criterion of 20%, the p53 overexpression of NPC was defined as≥20% of positive cells found. The p53 overexpression thus could be detected in 37 out of 43 NPCs, reaching 86.05% (37/43). The mean MI (1.87± 1.78/HPF) of 37 NPCs with p53 overexpression was significantly higher than that (0.76± 0.63/HPF) of 6 NPCs without p53 overexpression, the P value being <0.05. However, there was no statistical difference between the mean TI (24.50± 26.66HPF) of 37 NPCs with p53 overexpression and TI (23.17± 25.30/HPF) of 6 NPCs without p53 overexpression. Conclusions: p53 overexpression of NPC could be designated by ≥20% of positive neoplastic cells found in pretreated NPC specimens, and the rate of which reached 86.05% (37/43). The overexpressed p53 could enhance cell proliferative activity in pretreated NPCs represented by increasing of MI, but showed no effect on neoplastic cell apoptosis.

  10. Nasopharyngeal carcinoma in Indonesia: epidemiology, incidence,signs, and symptoms at presentation

    Institute of Scientific and Technical Information of China (English)

    Marlinda Adham; Antonius N.Kuniawan; Arina Ika Muhtadi; Averdi Roezin; Bambang Hermani; Soehartati Gondhowiardjo; I Bing Tan; Jaap M.Middeldorp

    2012-01-01

    Among all head and neck (H&N) cancers,nasopharyngeal carcinoma (NPC) represents a distinct entity regarding epidemiology,clinical presentation,biological markers,carcinogenic risk factors,and prognostic factors.NPC is endemic in certain regions of the world,especially in Southeast Asia,and has a poor prognosis.In Indonesia,the recorded mean prevalence is 6.2/100 000,with 13 000 yearly new NPC cases,but otherwise little is documented on NPC in Indonesia.Here,we report on a group of 1121 NPC patients diagnosed and treated at Dr.Cipto Mangunkusumo Hospital,Jakarta,Indonesia between 1996 and 2005.We studied NPC incidence among all H&N cancer cases (n=6000) observed in that period,focusing on age and gender distribution,the ethnic background of patients,and the disease etiology.We also analyzed most prevalent signs and symptoms and staging of NPC patients at first presentation.In this study population,NPC was the most frequent H&N cancer (28.4%),with a male-tofemale ratio of 2.4,and was endemic in the Javanese population.Interestingly,NPC appeared to affect patients at a relatively young age (20% juvenile cases) without a bimodal age distribution.Mostly,NPC initiated in the fossa of Rosenmuller and spreaded intracranially or locally as a mass in the head.Occasionally,NPC developed at the submucosal level spreading outside the anatomic limits of the nasopharynx.At presentation,NPC associated with hearing problems,serous otitis media,tinnitus,nasal obstruction,anosmia,bleeding,difficulty in swallowing and dysphonia,and even eye symptoms with diplopia and pain.The initial diagnosis is difficult to make because early signs and symptoms of NPC are not specific to the disease.Early-age Epstein-Barr virus (EBV) infection combined with frequent exposure to environmental carcinogenic co-factors is suggested to cause NPC development.Undifferentiated NPC is the most frequent histological type and is closely associated with EBV.Expression of the EBV-encoded latent membrane

  11. Prognostic value of MRI-derived masticator space involvement in IMRT-treated nasopharyngeal carcinoma patients

    International Nuclear Information System (INIS)

    This retrospective study reassessed nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT), to determine the significance how magnetic resonance imaging (MRI)-derived masticator space involvement (MSI) affected patients’ prognosis. One thousand one hundred ninety seven NPC patients who had complete set of MRI and medical records were enrolled. Basing on their MRI findings, the T-categories of tumors were identified according to the seventh edition of American Joint Committee on Cancer staging system, which considers MSI a prognostic indicator for NPCs. Rates of overall survival (OS), local relapse-free survival (LRFS), regional relapse-free survival (RRFS) and distant metastasis-free survival (DMFS) were analyzed by the Kaplan-Meier method, and the Log-Rank test compared their differences. Cox regression analysis was employed to evaluate various prognostic factors systematically. Statistical analyses were conducted with SPSS 18.0 software, P value < 0.05 was considered statistically significant. Medial pterygoid muscle (MPM) was involved in 283 (23.64 %) cases, of which lateral pterygoid muscle (LPM) was concurrently affected in 181 (15.12 %) and infratemporal fossa (ITF) in 19 (1.59 %). Generally, MSI correlated with an OS, LRFS, and DMFS consistent with a T4-stage diagnosis (P > 0.05). Although different degrees of MSI presented a similar OS and DMFS (P > 0.1), tumors involving LPM had a relatively poorer LRFS than those affected the MPM only (P = 0.027), even for subgroup of patients composed of T3 and T4 classifications (P = 0.035). A tumor involving MPM brought an LRFS consistent with a T2 or T3-stage disease (P > 0.1). If the tumor affected LPM or ITF concurrently, the survival outcomes were more consistent with a T4-stage disease (P > 0.1). Nevertheless, compared to tumor infiltrating MPM, those invading LPM or ITF more frequently spread into other concurrent sites that earned higher T-staging categories. Moreover

  12. Analysis of late toxicity in nasopharyngeal carcinoma patients treated with intensity modulated radiation therapy

    International Nuclear Information System (INIS)

    To observe the late toxicities in nasopharyngeal carcinoma (NPC) patients who achieved long-term survival after intensity modulated radiation therapy (IMRT). 208 untreated NPC patients who received IMRT and survived more than five years with locoregional disease control and no metastasis were evaluated in this study. The prescription dose to the gross target volume of nasopharynx (GTVnx), positive neck lymph nodes (GTVnd), clinical target volume 1 (CTV1) and 2 (CTV2) was 68Gy/30f, 60-66Gy/30f, 60 Gy/30f and 54Gy/30f, respectively. The nasopharynx and upper neck targets were irradiated using IMRT, and the lower neck and supraclavicular fossae targets were irradiated using the half-beam technique with conventional irradiation. The late toxicities were evaluated according to the LENT/SOMA criteria of 1995. The median follow-up time was 78 months (60–96 months). The occurrence rates of cervical subcutaneous fibrosis, hearing loss, skin dystrophy, xerostomia, trismus, temporal lobe injury, cranial nerve damage, cataract, and brain stem injury induced by radiotherapy were 89.9%, 67.8%, 47.6%, 40.9%, 7.21%, 4.33%, 2.88%, 1.44%, and 0.48%, respectively. No spinal cord injury and mandible damage were found. Grade 3–4 late injuries were observed as follows: 1 (0.48%) skin dystrophy, 4 (1.92%) cervical subcutaneous fibrosis, 2 (0.96%) hearing loss, 2 (0.96%) cranial nerve palsy, and 1 (0.48%) temporal lobe necrosis. No grade 3–4 late injuries occurred in parotid, temporomandibular joints and eyes. Xerostomia decreased gradually over time and then showed only slight changes after 4 years. The change in the incisor distance stabilised by 1 year after RT, however, the incidence of hearing loss, skin dystrophy, subcutaneous fibrosis and nervous system injuries increased over time after RT. The late injuries in most NPC patients who had long-term survivals after IMRT are alleviated. Within the 5 years of follow-up, we found xerostomia decreased gradually; The change in the

  13. Is there a sexual function decline in nasopharyngeal carcinoma survivors treated with radiotherapy?

    International Nuclear Information System (INIS)

    Objective: The want of study about the effect of definitive radiotherapy (RT) on sexual function for nasopharyngeal carcinoma (NPC) led to this investigation. This was designed as a pilot study to assess the patterns of sexual dysfunction and its prevention. Methods: Based on the SOMA/LENT toxicity criteria, a standardized questionnaire was designed to investigate the following sexual performances: desire, satisfaction, erectability, orgasm and frequency of sex in the two years before and after radiotherapy with each patient serving as his or her own control. Ninety patients (66 male, 24 female) were included into this study. Reduction of libido, satisfaction with sex, erectability, resumption of sex after radiotherapy, intensity of orgasm, frequency of sex and the subjective assumption of sex dysfunction by the patient were all entered and analyzed by the SOMA/LENT. Occupation: 27 workers, 39 farmers, 10 civil servants and 14 businessmen. Thirteen patients had had high school education or above, while the other 77 were on lower level. Results: All patients could remember the time of first sexual activity after treatment, 45 of them after 3 months, 71 after one year and 4 patients ceased sex at all. Fifteen patients were able to resume sex one year after radiotherapy. As for the quality of the sexual activity, 34 (37.8%) patients noted a decline in libido, 36 (40.0%) were dissatisfied with their sex and 5(7.6%) of the 66 male patients developed new impotence and 27 (30.0%) complained of lowered intensity of orgasm. The sexual frequency in this cohort was (1.271±0.877) times/ week before and (0.691±0.854) times/ week after the treatment. Sixty-four (71.1%) patients experienced a frequency diminution. Only 15 experienced no change in their sex. Statistical analysis did not show any significant relation between kinds of profession, education level or economic status and sexual dysfunction, subjective perception. However, subjective perception had a significant

  14. Quality of life in patients with nasopharyngeal carcinoma after intensity modulated radiotherapy

    International Nuclear Information System (INIS)

    Objective: To analyze the status of quality of life (QOL) and the related factors in patients with nasopharyngeal carcinoma (NPC) after radiotherapy, and to explore the significance of intensity modulated radiotherapy (IMRT) in decreasing side effects and improving QOL. Methods: A questionnaire including 35 items was designed according to EORTC QLQ-30 and the related symptoms and side effects of NPC. 142 NPC patients surviving with disease-free after radiotherapy were surveyed for the evaluation of QOL. The median follow-up was 25 months. The information of social demography and clinical details were collected. The patients were divided into IMRT group (75 patients) and conventional radiotherapy (CRT) group (67 patients). A statistical software package SAS 8.1 was used to compare the marks of QOL between the groups and analyze the influencing factors. Results: In IMRT group and CRT group, the marks of affective cognitive domain were 82.8 ± 14.7 and 77.5 ± 16.0 (t=2.07, P=0.040); and the marks of disease and treatment-related symptoms, and reactive domain were 78.9 ± 10.3 and 69.8 ± 13.3 (t=4.59, P= 0.000). The marks were significantly different in xerostomia, trismus, deglutitoy choke, hoarseness, restriction of neck movement and dysphagia (P<0.05). Of the influencing factors of QOL, the domain of body function was sex (regression coefficient was -4.692), the self-evaluation of total QOL were follow-up time and educational background (regression coefficients were -0.618 and 12.316, respectively), the financial status was family monthly income per capita (regression coefficient was -11.133), and the disease and treatment-related symptoms and reactive domain were group (techniques of radiation) and age (regression coefficients were -9.384 and -5.853, respectively). Conclusions: IMRT could improve the QOL through decreasing the side effects of patients with NPC including xerostomia, trismus, restriction of neck movement and dysphagia. Sex, age, family monthly

  15. Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Tao HM

    2016-03-01

    Full Text Available Hengmin Tao,1,2 Yumei Wei,1 Wei Huang,1 Xiujuan Gai,1,2 Baosheng Li11Department of 6th Radiation Oncology, Shandong Cancer Hospital and Institute, 2School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaAim: In recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF have been involved in the treatment of nasopharyngeal carcinoma (NPC. However, the potential clinical effects and toxicities are still controversial.Methods: Here, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS, 5-year progression-free survival (PFS, 5-year locoregional recurrence-free survival (LRFS, and relevant toxicities were analyzed.Results: In the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8–126 months. The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568. In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773 and 5-year LRFS (88.1% vs 90.8%, P=0.903. Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all P<0.05.Conclusion: Both IMRT-SIB and IMRT-CF techniques are effective in treating locally advanced NPC, with similar OS, PFS, and LRFS. However, IMRT-CF has more advantages than IMRT-SIB in protecting spinal cord, brainstem, and parotid gland from acute and late toxicities, such as xerostomia. Further prospective study is warranted to confirm our findings.Keywords: intensity

  16. Baseline Serum Lactate Dehydrogenase Levels for Patients Treated With Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: A Predictor of Poor Prognosis and Subsequent Liver Metastasis

    International Nuclear Information System (INIS)

    Purpose: To evaluate the prognostic value of baseline serum lactate dehydrogenase (LDH) levels in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). Methods and Materials: Cases of NPC (n = 465) that involved treatment with IMRT with or without chemotherapy were retrospectively analyzed. Results: The mean (±SD) and median baseline serum LDH levels for this cohort were 172.77 ± 2.28 and 164.00 IU/L, respectively. Levels of LDH were significantly elevated in patients with locoregionally advanced disease (p = 0.016). Elevated LDH levels were identified as a prognostic factor for rates of overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS), with p values <0.001 in the univariate analysis and p < 0.001, p = 0.004, and p = 0.003, respectively, in the multivariate analysis. Correspondingly, the prognostic impact of patient LDH levels was found to be statistically significant for rates of OS, DFS, and DMFS (p = 0.028, 0.024, and 0.020, respectively). For patients who experienced subsequent liver failure after treatment, markedly higher pretreatment serum LDH levels were detected compared with patients experiencing distant metastasis events at other sites (p = 0.032). Conclusions: Elevated baseline LDH levels are associated with clinically advanced disease and are a poor prognosticator for OS, DFS, and DMFS for NPC patients. These results suggest that elevated serum levels of LDH should be considered when evaluating treatment options.

  17. The interplay of host genetic factors and Epstein-Barr virus in the development of nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Maria Li Lung; Arthur Kwok Leung Cheung; Josephine Mun Yee Ko; Hong Lok Lung; Yue Cheng; Wei Dai

    2014-01-01

    The interplay between host cell genetics and Epstein-Barr virus (EBV) infection contributes to the development of nasopharyngeal carcinoma (NPC). Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as wel as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen (HLA) complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify the genes and pathways driving its molecular pathogenesis.

  18. Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting NF-κB and COX-2 signaling.

    Directory of Open Access Journals (Sweden)

    Mingzhu Zhuang

    Full Text Available Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-κB proteins. Moreover, effusanin E abrogated the binding of NF-κB to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-κB-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-κB/COX-2 (lipopolysaccharides abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-κB and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma.

  19. Enhancer of Zeste Homolog 2 Overexpression in Nasopharyngeal Carcinoma: An Independent Poor Prognosticator That Enhances Cell Growth

    International Nuclear Information System (INIS)

    Purpose: As a key component of polycomb-repressive complex 2, enhancer of zeste homolog 2 (EZH2) represses target genes through histone methylation and is frequently overexpressed and associated with poor prognosis in common carcinomas. For the first time, we reported EZH2 expression and its biological and clinical significance in nasopharyngeal carcinoma (NPC). Methods and Materials: In NPC cell lines and specimens, endogenous expression of EZH2 mRNA and protein was determined by semiquantitative reverse transcription–polymerase chain reaction and immunoblotting, respectively. To analyze the effect on cell growth, stable silencing of EZH2 was established in EZH2-expressing TW02 NPC cells with RNA interference. EZH2 immunolabeling was assessable for 89 primary NPC biopsy samples and correlated with clinicopathological variables, disease-specific survival (DSS), and overall survival (OS). Results: Growth activity of TW02 cells was significantly suppressed (p < 0.001) with stable EZH2 silencing. Compared with normal nasopharyngeal tissue, expression levels of EZH2 transcript and protein were apparently upregulated in NPC specimens. As a continuous variable, higher EZH2 expression preferentially occurred in NPCs of T3 to T4 stages (p = 0.03) and significantly predicted inferior DSS (p = 0.0010) and OS (p = 0.004). The prognostic implications for DSS (p = 0.010) and OS (p = 0.006) still remained valid when using the median (≥60%) of EZH2 immunolabeling index to dichotomize the cohort. In the multivariate model, higher EZH2 expression was an independent adverse factor of both DSS (p = 0.012) and OS (p = 0.011), along with American Joint Committee on Cancer Stages III to IV (p = 0.024 for DSS, p = 0.017 for OS). Conclusion: At least partly through promoting cell growth, EZH2 implicates disease progression, confers tumor aggressiveness, and represents an independent adverse prognosticator in patients with NPC.

  20. The role of Magnetic resonance sialography in evaluating radiation-induced xerostomia for patients with early stage nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Objective: To investigate the value of magnetic resonance sialography (MRS) as a noninvasive tool in evaluating major salivary gland function before and after radiotherapy (RT) for nasopharyngeal carcinoma patients. Methods: From August 2009 to June 2010, patients with stage I and IIa (AJCC/UICC 2002) nasopharyngeal carcinoma were enrolled. All the patients were treated with intensity modulated radiation therapy alone. MRS with salivary stimulation was performed in patients before and after RT on a 3.0T MR scanner. An MRS categorical scoring system was used to compare the visibility of ducts pre-RT and post-RT. The relationship between MRS score and EORTC Core QOL and EORTC Head and Neck QOL was analyzed. Spearman rank correlation test was performed to analyze the non-stimulated and stimulated MRS findings and the clinical severity of xerostomia. Results: All 10 enrolled patients completed planned treatment.The mean dose of the parotid glands and submandibular glands were (37.99 ± 3.70) Gy and (55.65 ± 2.99) Gy, respectively. Good-quality MRS images were obtained. The visibility scores of both the parotid and submandibular ducts were increased after secretion stimulation. Irradiation decreased the visualization of the salivary ducts and attenuated the response to secretion stimulation. There were specific correlations between post-RT secretion response of the parotid gland and EORTC QLQ scales (global QOL scale in QLQ-C30 (rs =0.636, P =0.048) and xerostomia scale in QLQ H and N35 (rs =- 0.694, P =0.026)). Conclusions: MRS can be used as a non-invasive way to evaluated of the functional changes of major salivary glands before and after RT and as a promising approach for investigating radiation-induced xerostomia. (authors)

  1. 鼻咽癌临床靶区定义%Definition of clinical target volume (CTV) for nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    林少俊; 潘建基; 郭巧娟

    2011-01-01

    Radiation therapy is the mainstay treatment modality for nasopharyngeal carcinoma (NPC), and the outcome is well associated to radiation dose. As a precise radiation technology, intensity-modulated radiotherapy (IMRT) offers the possibility of improving survival and simultaneously protect the surrounding normal tissue. The improvement of local control by IMRT has been well confirmed by a number of studies form domestic and abroad. However, the selection and definition of clinical target volume (CTV) for nasopharyngeal carcinoma has not yet reached a consensus. This article aimed to discovery the direction and mode for future research of reducing the treatment volume by reviewing the domestic and international development of CTV.%鼻咽癌为放射剂量相关性恶性肿瘤,放射治疗是鼻咽癌的首选治疗方法.调强放射治疗作为精确的放疗技术为提高剂量、保护周围正常组织提供了可能,国内外多家放疗中心的研究结果己证实调强放疗可提高鼻咽癌局部控制率.然而,当前对鼻咽癌的亚临床靶区(clinical target volume,CTV)的界定尚未达成共识,本文通过回顾国内外鼻咽癌CTV定义的发展过程,探讨未来缩小鼻咽癌靶区定义的发展方向和模式.

  2. Nasopharyngeal carcinoma: comparison of diffusion and perfusion characteristics between different tumour stages using intravoxel incoherent motion MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Vincent; Li, Xiao; Huang, Bingsheng; Khong, Pek Lan [University of Hong Kong, Queen Mary Hospital, Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, Hong Kong (China); Lee, Victor Ho Fun; Lam, Ka On [University of Hong Kong, Queen Mary Hospital, Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, Hong Kong (China); Fong, Daniel Yee Tak [University of Hong Kong, School of Nursing, Li Ka Shing Faculty of Medicine, Hong Kong (China); Chan, Queenie [Philips Healthcare, Hong Kong, New Territories (China)

    2014-01-15

    To explore intravoxel incoherent motion (IVIM) characteristics of nasopharyngeal carcinoma (NPC) and relationships with different tumour stages. We prospectively recruited 80 patients with newly diagnosed undifferentiated NPC. Diffusion-weighted MR imaging was performed and IVIM parameters (D, pure diffusion; f, perfusion fraction; D*, pseudodiffusion coefficient) were calculated. Patients were stratified into low and high tumour stage groups based on American Joint Committee on Cancer (AJCC) and TNM staging for determination of the predictive powers of IVIM parameters using t test, multiple logistic regression and ROC curve analyses. D, f and D* were all statistically significantly lower in high-stage groups in AJCC, T and N staging. D, f and D* were all independent predictors of AJCC staging, f and D* were independent predictors of T staging, and D was an independent predictor of N staging. D was most powerful for AJCC and N staging, whereas f was most powerful for T staging. Optimal cut-off values (area under the curve, sensitivity, specificity, positive likelihood ratio, negative likelihood ratio) were as follows: AJCC stage, D = 0.782 x 10{sup -3} mm{sup 2}/s (0.915, 93.3 %, 76.2 %, 3.92, 0.09); T staging, f = 0.133 (0.905, 80.5 %, 92.5 %, 10.73, 0.21); N staging, D = 0.761 x 10{sup -3} mm{sup 2}/s (0.848, 87.5 %, 66.7 %, 2.62, 0.19). Multivariate analysis showed no diagnostic improvement. Nasopharyngeal carcinoma has distinctive intravoxel incoherent motion characteristics parameters in different tumour staging, potentially helping pretreatment staging. (orig.)

  3. Expression of Aurora-B and FOXM1 predict poor survival in patients with nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Pei-Yu; Luo, Dong-Hua; Mai, Hai-Qiang [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Sun Yat-sen University Cancer Center, Department of Nasopharyngeal Carcinoma, Guangzhou (China); Li, Yan; Zeng, Ting-Ting; Li, Meng-Qing [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Hou, Xue; Zhang, Li [State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Sun Yat-sen University Cancer Center, Department of Medical Oncology, Guangzhou (China)

    2015-08-15

    The purpose of this work was to investigate the relationship between Aurora-B, FOXM1, and clinical outcomes in patients with nasopharyngeal carcinoma (NPC) who were treated with a combination of induction chemotherapy and radiotherapy. The expression of Aurora-B and FOXM1 were investigated by immunohistochemistry using a tissue microarray (TMA) containing samples from 166 NPC patients who were treated with cisplatin (DDP) + fluorouracil (5-FU) induction chemotherapy and radiotherapy between 1999 and 2005. The relationship of Aurora-B, FOXM1, and survival of these NPC patients was analyzed. Informative TMA results were obtained in 91 tumor cases for Aurora-B and 93 tumor cases for FOXM1. The 8-year failure-free survival rate (FFS) for the Aurora-B-negative and Aurora-B-positive group was 65.6 and 37.3 %, respectively (p = 0.024), and the 8-year distant FFS (D-FFS) rate was 65.6 and 41.5 %, respectively (p = 0.047). The 8-year overall survival (OS) in the FOXM1-negative group was moderately higher than in the FOXM1-positive group (58.4 vs 39.1 %, p = 0.081). Cox regression analysis revealed that for FFS, Aurora-B expression was a significant prognostic factor (p = 0.025), while for D-FFS, Aurora-B expression was a marginally significant prognostic factor (p = 0.056). When FOXM1 expression was analyzed, the Cox regression analyses showed that FOXM1 expression was a marginally significant prognostic factor (p = 0.056) for OS. Correlation analysis showed that Aurora-B and FOXM1 expression had no significant correlation. Aurora-B and FOXM1 were both adverse prognostic markers for NPC patients treated with chemoradiotherapy. However, the two markers had no significant correlation. (orig.) [German] Ziel war die Untersuchung der Beziehung zwischen Aurora-B, FOXM1 und den klinischen Ergebnissen bei Patienten mit nasopharyngealem Karzinom (NPC), die mit einer Kombinationstherapie aus Induktionschemotherapie und Radiotherapie behandelt wurden. Die Expression von Aurora-B und

  4. Met tyrosine kinase inhibitor, PF-2341066, suppresses growth and invasion of nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Zhao Y

    2015-08-01

    Full Text Available Yuanyuan Zhao,1,* Jing Zhang,2,* Ying Tian,1,* Cong Xue,1 Zhihuang Hu,1 Li Zhang1,3 1Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, 2Department of Medical Oncology, the First Affiliated Hospital of Guang Zhou Traditional Chinese Medicine University, 3National Anti-Cancer Drug Research Centre, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, People’s Republic of China*These authors contributed equally to this work Purpose: We explored the effect of hepatocyte growth factor (HGF/Met signaling pathway on nasopharyngeal carcinoma (NPC cells in vitro and in vivo, and investigated the ability of Met tyrosine kinase inhibitor (TKI to block HGF-induced biological signaling.Experimental design: Met TKI inhibitor PF-2341066 alone, or in combination with cisplatin, was investigated for its ability to block HGF-induced signaling and biological effects in vitro and in vivo. HGF/Met expression and activation of signaling in NPC cells were detected by using Western blot and immunohistochemistry. Biological evaluation, including wound healing, cell proliferation, and invasion of NPC cells, was also examined, and the correlation between HGF/Met expression of primary and metastatic tumor in NPC patients and clinical prognosis were also analyzed.Results: Met TKI inhibitor, PF-2341066, inhibited growth of NPC cells in vivo with half maximal inhibitory concentration of 0.79±0.21 µmol/L, and suppressed invasion and migration of NPC cells; also, the inhibition of PF-2341066 was synergized with cisplatin treatment. Compared with the control group, Met TKI inhibited metastasis of transplanted NPC in nude mice (the number of live metastases [mean ± SD]: 5.8±2.2 versus 11.8±2.2, P=0.03; the number of lung metastases: 2.3±1.5 versus

  5. Radionuclide imaging and therapy mediated by hNIS gene transfection in nasopharyngeal carcinoma xenograft model

    International Nuclear Information System (INIS)

    Objective: To explore the feasibility of 131I radiotherapy mediated by hNIS gene transfection in nasopharyngeal carcinoma (NPC). Methods: NPC xenograft models were established with CNE-2-hNIS cells (experimental group) and CNE-2 cells (control group). Radioactivity of different organs of nude mice was counted at 0.5,1,2,6 and 24 h after intraperitoneal injection of 125I using a gamma counter. 99TcmO4- imaging was also performed in nude mice. Changes in the xenograft tumor volume were observed after 131I treatment in the experimental group and control group. Cell apoptosis was detected after 131I treatment by the terminal oxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) method and caspase 3 and Ki67 expressions measured with immunohistochemistry of the tumor tissue. Statistical analysis was performed using SPSS 13.0 software, and the mean values between groups were compared using t test. Results: CNE-2-hNIS and CNE-2 NPC xenografts were established successfully in nude mice. Biodistribution of 125I in tumor-bearing nude mice showed enhanced tumor uptake of 125I in the experimental group, with peak uptake at 1 h ((20.28 ± 0.15)%). The biological half-life of 125I in the tumors transfected with hNIS was about 1.56 h. Imaging studies showed that the tumors in the experimental group accumulated 99TcmO4- with a peak at 1.5-2 h, whereas the control tumors were not visualized. The mean volume of the experimental xenograft tumors was (0.44 ±0.04) cm3 before 131I treatment and increased to (0.97 ±0.08) cm3 after 131I treatment. However, the volume of the control xenografts was (0.45 ± 0.06) cm3 before 131I treatment and (2.98 ±0.16) cm3 after 131I treatment. The tumor volume of the experimental group was significantly smaller compared with that of the control group after 131I treatment (t=19.46, P<0.01). A higher apoptotic index and caspase 3 positive rate as well as lower Ki67 proliferation index were observed in the experimental group after

  6. On the trails of markers and proxies: the socio-cognitive technologies of human movement, knowledge assemblage, and their relevance to the etiology of nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    David Turnbull

    2011-01-01

    Bacteria, pigs, rats, pots, plants, words, bones, stones, earrings, diseases, and genetic indicators of all varieties are markers and proxies for the complexity of interweaving trails and stories integral to understanding human movement and knowledge assemblage in Southeast Asia and around the world.Understanding human movement and knowledge assemblage is central to comprehending the genetic basis of disease, especially of a cancer like nasopharyngeal carcinoma. The problem is that the markers and trails, taken in isolation, do not all tell the same story. Human movement and knowledge assemblage are in constant interaction in an adaptive process of co-production with genes, terrain, climate, sea level changes, kinship relations, diet, materials, food and transport technologies, social and cognitive technologies, and knowledge strategies and transmission. Nasopharyngeal carcinoma is the outcome of an adaptive process involving physical, social, and genetic components.

  7. Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma

    Science.gov (United States)

    Tao, Hengmin; Wei, Yumei; Huang, Wei; Gai, Xiujuan; Li, Baosheng

    2016-01-01

    Aim In recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF) have been involved in the treatment of nasopharyngeal carcinoma (NPC). However, the potential clinical effects and toxicities are still controversial. Methods Here, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS), 5-year progression-free survival (PFS), 5-year locoregional recurrence-free survival (LRFS), and relevant toxicities were analyzed. Results In the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8–126 months). The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568). In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773) and 5-year LRFS (88.1% vs 90.8%, P=0.903). Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland) in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all Pxerostomia. Further prospective study is warranted to confirm our findings. PMID:27099518

  8. Epstein-Barr virus-encoded microRNA BART1 induces tumour metastasis by regulating PTEN-dependent pathways in nasopharyngeal carcinoma.

    Science.gov (United States)

    Cai, Longmei; Ye, Yanfen; Jiang, Qiang; Chen, Yuxiang; Lyu, Xiaoming; Li, Jinbang; Wang, Shuang; Liu, Tengfei; Cai, Hongbing; Yao, Kaitai; Li, Ji-Liang; Li, Xin

    2015-01-01

    Epstein-Barr virus (EBV), aetiologically linked to nasopharyngeal carcinoma (NPC), is the first human virus found to encode many miRNAs. However, how these viral miRNAs precisely regulate the tumour metastasis in NPC remains obscure. Here we report that EBV-miR-BART1 is highly expressed in NPC and closely associated with pathological and advanced clinical stages of NPC. Alteration of EBV-miR-BART1 expression results in an increase in migration and invasion of NPC cells in vitro and causes tumour metastasis in vivo. Mechanistically, EBV-miR-BART1 directly targets the cellular tumour suppressor PTEN. Reduction of PTEN dosage by EBV-miR-BART1 activates PTEN-dependent pathways including PI3K-Akt, FAK-p130(Cas) and Shc-MAPK/ERK1/2 signalling, drives EMT, and consequently increases migration, invasion and metastasis of NPC cells. Reconstitution of PTEN rescues all phenotypes generated by EBV-miR-BART1, highlighting the role of PTEN in EBV-miR-BART-driven metastasis in NPC. Our findings provide new insights into the metastasis of NPC regulated by EBV and advocate for developing clinical intervention strategies against NPC. PMID:26135619

  9. Long-term outcome and late toxicities of simultaneous integrated boost-intensity modulated radiotherapy in pediatric and adolescent nasopharyngeal carcinoma

    OpenAIRE

    Li-Zhi Liu; Xiao-Li Yu; Wen-Fei Li; Lei Chen; Yan-Ping Mao; Ling-Long Tang; Xu Liu; Chang-Juan Tao; Rong Zhang; Ai-Hua Lin; Jun Ma; Ying Sun

    2013-01-01

    The application of simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in pediatric and adolescent nasopharyngeal carcinoma (NPC) is underevaluated. This study aimed to evaluate long-term outcome and late toxicities in pediatric and adolescent NPC after SIB-IMRT combined with chemotherapy. Thirty-four patients (aged 8-20 years) with histologically proven, non-disseminated NPC treated with SIB-IMRT were enrolled in this retrospective study. The disease stage distribution ...

  10. Long-term outcome and late toxicities of simultaneous integrated boost-intensity modulated radiotherapy in pediatric and adolescent nasopharyngeal carcinoma

    OpenAIRE

    Tao, Chang-Juan; Liu, Xu; Tang, Ling-Long; Mao, Yan-Ping; Chen, Lei; Li, Wen-Fei; Yu, Xiao-Li; Liu, Li-Zhi; Zhang, Rong; Lin, Ai-Hua; Ma, Jun; Sun, Ying

    2013-01-01

    The application of simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in pediatric and adolescent nasopharyngeal carcinoma (NPC) is underevaluated. This study aimed to evaluate long-term outcome and late toxicities in pediatric and adolescent NPC after SIB-IMRT combined with chemotherapy. Thirty-four patients (aged 8–20 years) with histologically proven, non-disseminated NPC treated with SIB-IMRT were enrolled in this retrospective study. The disease stage distribution ...

  11. Analysis of the Prognosis for Patients with Stage T3N0~1M0 Nasopharyngeal Carcinoma Treated by Chemotherapy Combined with Radiotherapy

    Institute of Scientific and Technical Information of China (English)

    Guorong Zou; Fangyun Xie; Jianming Gao; Shaoxiong Wu; Shunan Qi; Miao Peng

    2006-01-01

    OBJECTIVE To investigate the relationship between the therapeutic modality and prognostic factors for the patients with T3N0~1M0 nasopharyngeal carcinoma.METHODS The clinical data from 127 cases of T3N0~1M0 nasopharyngeal carcinoma patients with initial treatment, during the period from January 4th, 2000 to November 12th, 2001, were retrospectively analyzed. The cases were divided into Group A with simple radiotherapy (90) and Group B with the radiation therapy combined with chemotherapy (37), based on various patients' conditions. In group B, inductive chemotherapywas conducted for 18 cases, inductive chemotherapy plus homochronous chemotherapy for 5 and homochronous chemotherapy for 14.RESULTS The 5-year overall survival (OS) in the groups A and B was 73.4% and 72.3% respectively (P>0.05); the cancer-correlated survival (CCS) in the 2 groups was 76.4% and 72.3% respectively (P>0.05); the disease-free survival (DFS) in group A and B was 65.5% and 71.7% respectively (P<0.05). A multiple analysis showed that the mode of radiation therapy plus chemotherapy was a favorable independent impact factor for DFS.CONCLUSION Chemotherapy plus radiotherapy can improve the DFS of patients with T3N0~1M0 nasopharyngeal carcinoma, but fails to prolong the survival time of the patients. The modality of chemotherapy plus radiotherapy is not the necessary choice in treatment of patients with T3N0~ 1M0 nasopharyngeal carcinoma.

  12. Patient- and therapy-related factors associated with the incidence of xerostomia in nasopharyngeal carcinoma patients receiving parotid-sparing helical tomotherapy

    OpenAIRE

    Tsair-Fwu Lee; Ming-Hsiang Liou; Hui-Min Ting; Liyun Chang; Hsiao-Yi Lee; Stephen Wan Leung; Chih-Jen Huang; Pei-Ju Chao

    2015-01-01

    We investigated the incidence of moderate to severe patient-reported xerostomia among nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT) and identified patient- and therapy-related factors associated with acute and chronic xerostomia toxicity. The least absolute shrinkage and selection operator (LASSO) normal tissue complication probability (NTCP) models were developed using quality-of-life questionnaire datasets from 67 patients with NPC. For acute toxicity, the do...

  13. Ancient migration routes of Austronesian-speaking populations in oceanic Southeast Asia and Melanesia might mimic the spread of nasopharyngeal carcinoma

    OpenAIRE

    Trejaut, Jean; Lee, Chien-Liang; Yen, Ju-Chen; Loo, Jun-Hun; Lin, Marie

    2011-01-01

    Mitochondrial DNA (mtDNA) and non-recombining Y chromosome (NRY) are inherited uni-parentally from mother to daughter or from father to son respectively. Their polymorphism has initially been studied throughout populations of the world to demonstrate the “Out of Africa” hypothesis. Here, to correlate the distribution of nasopharyngeal carcinoma (NPC) in different populations of insular Asia, we analyze the mtDNA information (lineages) obtained from genotyping of the hyper variable region (HVS...

  14. {sup 68}Ga-DOTA{sup 0}-Tyr{sup 3}-octreotide positron emission tomography in nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Schartinger, Volker H.; Dudas, Jozsef; Url, Christoph; Riechelmann, Herbert [Medical University Innsbruck, Department of Otorhinolaryngology, Innsbruck (Austria); Reinold, Susanne [Medical University Innsbruck, Institute of Pathology, Innsbruck (Austria); Virgolini, Irene J.; Kroiss, Alexander; Uprimny, Christian [Medical University Innsbruck, Department for Nuclear Medicine, Innsbruck (Austria)

    2015-01-15

    PET/CT with {sup 68}Ga-labelled [DOTA{sup 0},Tyr{sup 3}]-octreotide ({sup 68}Ga-DOTA-TOC PET/CT) is a routinely used imaging modality for neuroendocrine tumours expressing somatostatin receptors (SSTR). Recent studies have shown SSTR expression in head and neck squamous cell carcinoma, albeit lower than in highly differentiated neuroendocrine tumours. We sought to determine whether nasopharyngeal carcinoma (NPC) positive for Epstein-Barr virus (EBV), a rare subtype of head and neck cancer, shows increased {sup 68}Ga-DOTA-TOC uptake indicating expression of SSTR. Five patients with untreated, histologically proven EBV-positive NPC were referred for {sup 68}Ga-DOTA-TOC PET/CT. Tracer uptake in tumour lesions was assessed visually and semiquantitatively measuring maximum standardized uptake values (SUVmax) and tumour to background ratios. Increased tumour-specific uptake was detected in all five patients with a median SUVmax of 10.6 (range 3.6 - 17.1) in the primary tumour and 13.2 (range 6.1 - 14.5) in cervical lymph node metastases. {sup 68}Ga-DOTA-TOC PET/CT demonstrated tracer uptake in EBV-positive NPC comparable to that in highly differentiated neuroendocrine tumours. This observation is consistent with increased SSTR expression in EBV-positive NPC and may open new diagnostic and therapeutic windows in NPC. (orig.)

  15. FDG-PET, CT, MRI for diagnosis of local residual or recurrent nasopharyngeal carcinoma, which one is the best? A systematic review

    International Nuclear Information System (INIS)

    Purpose: To perform a systematic review to compare FDG-PET, CT, and MRI imaging for diagnosis of local residual or recurrent nasopharyngeal carcinoma. Materials and methods: MEDLINE, EMBASE, the CBMdisc databases and some other databases were searched for relevant original articles published from January 1990 to June 2007. Inclusion criteria were as follows: Articles were reported in English or Chinese; FDG-PET, CT, or MRI was used to detect local residual or recurrent nasopharyngeal carcinoma; histopathologic analysis and/or close clinical and imaging follow-up for at least 6 months were the reference standard. Two reviewers independently extracted data. A software called 'Meta-DiSc' was used to obtain pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curves, and the Q* index. Results: Twenty-one articles fulfilled all inclusion criteria. The pooled sensitivity estimates for PET (95%) were significantly higher than CT (76%) (P 0.05). Conclusion: FDG-PET was the best modality for diagnosis of local residual or recurrent nasopharyngeal carcinoma. The type of analysis for PET imaging and the section thickness for CT would affect the diagnostic results. Dual-section helical and multi-section helical CT were better than nonhelical and single-section helical CT

  16. Tumor suppressor BLU inhibits proliferation of nasopharyngeal carcinoma cells by regulation of cell cycle, c-Jun N-terminal kinase and the cyclin D1 promoter

    Directory of Open Access Journals (Sweden)

    Zhang Xiangning

    2012-06-01

    Full Text Available Abstract Background Tumor suppressor genes function to regulate and block tumor cell proliferation. To explore the mechanisms underlying the tumor suppression of BLU/ZMYND10 gene on a frequently lost human chromosomal region, an adenoviral vector with BLU cDNA insert was constructed. Methods BLU was re-expressed in nasopharyngeal carcinoma cells by transfection or viral infection. Clonogenic growth was assayed; cell cycle was analyzed by flow cytometry-based DNA content detection; c-Jun N-terminal kinase (JNK and cyclin D1 promoter activities were measured by reporter gene assay, and phosphorylation was measured by immunoblotting. The data for each pair of groups were compared with Student t tests. Results BLU inhibits clonogenic growth of nasopharyngeal carcinoma cells, arrests cell cycle at G1 phase, downregulates JNK and cyclin D1 promoter activities, and inhibits phosphorylation of c-Jun. Conclusions BLU inhibits growth of nasopharyngeal carcinoma cells by regulation of the JNK-cyclin D1 axis to exert tumor suppression.

  17. The efficacy and toxicity of individualized intensity-modulated radiotherapy based on the tumor extension patterns of nasopharyngeal carcinoma

    Science.gov (United States)

    Zhou, Guan-Qun; Guo, Rui; Zhang, Fan; Zhang, Yuan; Xu, Lin; Zhang, Lu-Lu; Lin, Ai-Hua; Ma, Jun; Sun, Ying

    2016-01-01

    Background To evaluate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) using individualized clinical target volumes (CTVs) based on the loco-regional extension patterns of nasopharyngeal carcinoma (NPC). Methods From December 2009 to February 2012, 220 patients with histologically-proven, non-disseminated NPC were prospectively treated with IMRT according to an individualized delineation protocol. CTV1 encompassed the gross tumor volume, entire nasopharyngeal mucosa and structures within the pharyngobasilar fascia with a margin. CTV2 encompassed bilateral high risk anatomic sites and downstream anatomic sites adjacent to primary tumor, bilateral retropharyngeal regions, levels II, III and Va, and prophylactic irradiation was gave to one or two levels beyond clinical lymph nodes involvement. Clinical outcomes and toxicities were evaluated. Results Median follow-up was 50.8 (range, 1.3–68.0) months, four-year local relapse-free, regional relapse-free, distant metastasis-free, disease-free and overall survival rates were 94.7%, 97.0%, 91.7%, 87.2% and 91.9%, respectively. Acute severe (≥ grade 3) mucositis, dermatitis and xerostomia were observed in 27.6%, 3.6% and zero patients, respectively. At 1 year, xerostomia was mild, with frequencies of Grade 0, 1, 2 and 3 xerostomia of 27.9%, 63.3%, 8.3% and 0.5%, respectively. Conclusions IMRT using individualized CTVs provided high rates of local and regional control and a favorable toxicity profile in NPC. Individualized CTV delineation strategy is a promising one that may effectively avoid unnecessary or missed irradiation, and deserve optimization to define more precise individualized CTVs. PMID:26980744

  18. Secreted protein acidic and rich in cysteine (SPARC is associated with nasopharyngeal carcinoma metastasis and poor prognosis

    Directory of Open Access Journals (Sweden)

    Wang Hai-Yun

    2012-02-01

    Full Text Available Abstract Background The aim of the present study was to analyse the expression of Secreted protein acidic and rich in cysteine (SPARC in nasopharyngeal carcinoma (NPC specimens, and to evaluate its correlation with clinicopathologic features, including survival of patients with NPC Methods NPC tissue microarrays (TMAs were constructed from Sun Yat-sen University Cancer Center (SYSUCC, another three centers on mainland China, Singapore and Hong Kong. Using quantitative RT-PCR and Western-blotting techniques, we detected mRNA and protein expression of SPARC in NPC cell lines and immortalized nasopharyngeal epithelial cells (NPECs induced by Bmi-1 (NPEC2 Bmi-1. The difference of SPARC expression in the cell lines was tested using a t-test method. The relationship between the SPARC expression and clinicopathological data was assessed by chi-square. Survival analysis was estimated using the Kaplan-Meier approach with log-rank test. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Results The expression levels of SPARC mRNA and protein were markedly higher in NPC cell lines than in NPEC2 Bmi-1. Especially, the expression levels of SPARC mRNA and protein were much lower in the 6-10B than in the 5-8 F (P = 0.002, P = 0.001. SPARC immunostaining revealed cytoplasmic localization in NPC cells and no staining in the stroma and epithelium. In addition, high level of SPARC positively correlated with the status of distant metastasis (P = 0.001 and WHO histological classification (P = 0.023. NPC patients with high SPARC expression also had a significantly poorer prognosis than patients with low SPARC expression (log-rank test, P P P Conclusions SPARC expression is common in NPC patients. Our data shows that elevated SPARC expression is a potential unfavorable prognostic factor for patients with NPC.

  19. Comparison of narrow-band imaging and conventional nasopharyngoscopy for the screening of unaffected members of families with nasopharyngeal carcinoma.

    Science.gov (United States)

    Ho, Ching-Yin; Chan, Kee-Tak; Chu, Pen-Yuan

    2013-09-01

    Familial aggregation of nasopharyngeal carcinoma (NPC) has been widely reported. The excess risk is about 4-8-fold among first-degree relatives of NPC patients compared with those without a family history of the disease. We used nasopharyngoscopy and a narrow-band image system (NBI) to screen NPC high-risk patients and identify a good tool for the early detection of NPC in these high-risk groups. We recruited all available, affected blood relations of the patients. When NPC patients were more distant relatives, such as cousins, we recruited their shared second-degree relatives, such as unaffected aunts and uncles, to genetically connect the NPC cases. We performed transnasal endoscopy, first in white-light mode, then under the NBI system. There were two NBI patterns in NPC: microvascular proliferation and engorged blood vessels. The NBI pattern in normal nasopharyngeal mucosa was a regular cobblestone pattern. A prospective study included 211 asymptomatic members from 154 NPC families. We found four cases of NPC, all with a tumor stage of T1. In one patient (1/4), MRI revealed a 2-cm-diameter neck lymphadenopathy (N1). The correlation between conventional nasopharyngoscopy and NBI was very high (κ = 0.798, P = 0.000). In conclusions, NBI is not superior to conventional nasopharyngoscopy for the early detection of NPC in unaffected members of families with NPC history. The long-term follow-up is necessary in high-risk NPC patients. Further studies will be needed to determine which screening tool-conventional nasopharyngoscopy, NBI, or EB virus titer-is most effective.

  20. Clinical study on the changes of the tumor target volume and organs at risk in helical tomotherapy for nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    LU Na; FENG Lin-chun; CAI Bo-ning; HOU Jun; WANG Yun-lai; XIE Chuan-bin

    2012-01-01

    Background Helical tomotherapy (HT) is a new image-guided intensity-modulated radiation therapy (IMRT).The aim of this study was to evaluate the changes in the target volume and organs at risk (OARs) of patients with nasopharyngeal carcinoma (NPC) during helical tomotherapy.Methods Forty-three patients with NPC and treated via HT from March 2008 to January 2010 were reviewed retrospectively.Repeated CT scanning and plan adaptation were conducted at the 20th fraction during radiotherapy.The volumetric differences between the two scans were evaluated for nasopharyngeal tumor and retro- pharyngeal lymph nodes (GTVnx),neck lymph nodes (GTVnd),and parotid glands,as well as the axial diameter of the head.Results The median interval between the two scans was 25 days (23-28 days).The volumetric decrease in GTVnx was 30.1% (median,29.8%) and in GTVnd 41.6% (median,45.9%).The variation in the GTVnd volume was correlated with the weight loss of the patient.The volume of the left parotid gland decreased by 35.5% (median,33.4%) and of the right parotid glands decreased by 36.8% (median,33.5%).The axial diameter of the head decreased by 9.39% (median,9.1%).Conclusions The target volume and OARs of patients with NPC varied considerably during HT.These changes may have potential dosimetric effects on the target volume and/or OARs and influence the clinical outcome.Repeated CT scanning and replanning during the HT for NPC patients with a large target volume or an obvious weight loss are recommended.

  1. The Research Status and the Clinical Significance between VEGF and Nasopharyngeal Carcinoma%VEGF与鼻咽癌的研究现况及其临床意义

    Institute of Scientific and Technical Information of China (English)

    王晓雪; 王光明; 潘云; 丁跃明

    2014-01-01

    Nasopharyngeal carcinoma is one of the common malignant tumor in southern China,that 5-year survival rate is in the range of 50%-60%and the prognosis is poor. Vascular endothelial growth factor(VEGF)belongs to the family of platelet-derived growth factors and so far as the only known specific factor acts to vascular endothelial cells. It expresses lower in most tissues of the human with nonspecific manner and higher abnormally in most tumor tissues. The fact that it is related closely to tumor’s occurrence,development,treatment and prognosis suggests that VEGF is a potentially valuable tumor marker and also expected to become an ideal new target for targeted cancer therapy. Some studies found that the phenomenon of high expression of VEGF is also occurs in nasopharyngeal carcinoma and gene silence with VEGF siRNA can inhibit the proliferation of nasopharyngeal carcinoma cell lines. Hence,the treatment using VEGF as the target may open new avenues for the clinical treatment of nasopharyngeal carcinoma. In this paper,it is reviewed about the research status of VEGF and nasopharyngeal carcinoma.%鼻咽癌是我国南方常见的恶性肿瘤之一,5年生存率持续在50%~60%之间,预后较差。血管内皮生长因子属于血小板源生长因子家族,是目前所知唯一特异作用于血管内皮细胞的因子。它非特异性的低表达于人类大部分组织中,但是在大多数肿瘤组织中异常高表达。VEGF与肿瘤的发生、发展、治疗、预后密切相关,是一个具有潜在价值的肿瘤标志物,有望成为肿瘤靶向治疗的理想新靶点。研究发现,VEGF在鼻咽癌组织中同样存在高表达现象,细胞水平利用VEGF基因沉默技术可以抑制鼻咽癌细胞的增殖,因此以VEGF为靶点的治疗方法可能为临床鼻咽癌治疗开辟新途径。本文就VEGF与鼻咽癌的研究现状作一综述。

  2. Clinical observation of submandibular gland transfer for the prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma: a prospective randomized controlled study of 32 cases

    International Nuclear Information System (INIS)

    The aim of this study was to evaluate the clinical efficacy of submandibular gland transfer for the prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma. Using the randomized controlled clinical research method, 65 patients with nasopharyngeal carcinoma were randomly divided into an experimental group consisting of 32 patients and a control group consisting of 33 patients. The submandibular glands were averted to the submental region in 32 patients with nasopharyngeal carcinoma before they received conventional radiotherapy; a lead block was used to shield the submental region during therapy. Prior to radiotherapy, the function of the submandibular glands was assessed using imaging. Submandibular gland function was measured using 99mTc radionuclide scanning at 60 months after radiotherapy. The data in the questionnaire regarding the degree of xerostomia were investigated and saliva secretion was measured at 3, 6, 12, and 60 months after radiotherapy. In addition, the 5-year survival rate was calculated. After follow-up for 3, 6, and 12 months, the incidence of moderate to severe xerostomia was significantly lower in the experimental group than in the control group. The average amount of saliva produced by the experimental and control groups was 1.60 g and 0.68 g, respectively (P < 0.001). After follow-up for 60 months, the uptake and secretion functions of the submandibular glands in the experimental group were found to be significantly higher than in the control group (P < 0.001 and P < 0.001, respectively). The incidence of moderate or severe xerostomia was significantly lower than in the control group (15.4% and 76.9%, respectively; P < 0.001). The 5-year survival rates of the experimental group and the control group were 81.3% and 78.8%, respectively, and there was no significant difference between the two groups (P = 0.806). After a 5 year follow-up period involving 32 patients who had their submandibular glands transferred for the

  3. Nasopharyngeal Case-Control Study

    Science.gov (United States)

    A case-control study conducted in Taiwan between 1991-1994 among approximately 1,000 individuals to examine the role of viral, environmental, and genetic factors associated with the development of nasopharyngeal carcinoma

  4. Tumor volume is an independent prognostic indicator of local control in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy

    International Nuclear Information System (INIS)

    To retrospectively analyze whether primary tumor volume and primary nodal volume could be considered independent prognostic factors for nasopharyngeal carcinoma treated with intensity-modulated radiation therapy. Three hundred sixty-three consecutive nasopharyngeal carcinoma (NPC) patients who were stage I-IVa+b and treated with intensity-modulated radiotherapy (IMRT) in our center from October 2003 to October 2005 were analyzed retrospectively. The predictive ability of gender, age, T and N stage, combined chemotherapy, primary tumor and nodal volume for the 5-year local control (LC), distant-metastasis free survival (DMFS) and overall survival (OS) rate were investigated. Primary tumor and nodal volume were measured based on registration of magnetic resonance imaging (MRI) with contrast-enhanced computed tomography (CT) images. The Kaplan–Meier method was used for survival analysis, the log-rank test was used for univariate analyses and the Cox proportional hazard model was used for multivariate prognostic analyses. The mean value of primary tumor and nodal volume were 31.5 ml and 9.7 ml. The primary tumor and nodal volume were respectively divided into four groups for analysis (primary tumor volume: TV1≤20 ml, 2040 ml; primay nodal volume: NV1≤5 ml, 520 ml). In univariate analysis, the 5-year LC and DMFS rate for TV4 was significantly decreased compared to the other groups (LC: p<0.001, DMFS: p=0.001), the 5-year OS rate for TV3 and TV4 were significantly decreased compared to other two subgroups (p=0.002) and the 5-year regional control (RC), DMFS and OS rate for NV3 and NV4 were significantly less than NV1 and NV2 (RC: p=0.002, DMFS: p=0.01, OS: p=0.014). Multivariate analysis showed that TV>40 ml was an adverse prognostic factor for the 5-year local regional control (LRC) rate (RR 2.454, p=0.002). Primary nodal volume had no statistical significance in predicting 5-year LRC, DMFS and OS

  5. Dosimetric verification of volumetric modulated arc therapy in nasopharyngeal carcinoma using COMPASS 3D patient anatomy based system

    International Nuclear Information System (INIS)

    Objective: To investigate the dosimetric performance of COMPASS system, a novel 3D quality assurance system for the verification of nasopharyngeal carcinoma volumetric modulated therapy (VMAT) treatment plan. Methods: Eight VMAT treatment plans of nasopharyngeal carcinoma patients were performed with MasterPlan, a treatment planning system (TPS), and then these treatment plans were sent to the COMPASS and MOSAIQ system, a coherent control system, respectively. Comparison of the COMPASS reconstructed dose versus TPS dose was conducted by using the dose volume-based indices:dose received by 95% volume of target (D95%), mean dose (Dmean) and γ pass rate, dose to the 1% of the spinal cord and brain stem volume (D1%), mean dose of leaf and right parotid (Dmean), and the volume received 30 Gy for left and right parotid (V30). COMPASS can reconstruct dose with the real measured delivery fluence after detector commissioning. Results: The average dose difference for the target volumes was within 1%, the difference for D95 was within 3% for most treatment plans, and the γ pass rate was higher than 95% for all target volumes. The average differences for the D1% values of spinal cord and brain stem were (4.3 ± 3.0)% and (5.9± 2.9)% respectively, and the average differences for the Dmean values of spinal cord and brain stem were (5.3 ± 3.0)% and (8.0 ± 3.5)% respectively. In general the COMPASS measured doses were all smaller than the TPS calculated doses for these two organs. The average differences of the Dmean values of the left and right parotids were (6.1± 3.1)% and (4.7 ± 4.4)% respectively, and the average differences of the V30 values of the left and right parotids were (9.4 ± 7.5 )% and (9.4 ± 9.9)% respectively. Conclusions: An ideal tool for the VMAT verification, the patient anatomy based COMPASS 3D dose verification system can check the dose difference between the real delivery and TPS calculation directly for each individual organ, either target volumes

  6. Sorafenib in advanced hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Køstner, Anne Helene; Sørensen, M; Olesen, René Krøjgaard;

    2013-01-01

    Advanced HCC is a clinical challenge with limited treatment options. The multikinase inhibitor sorafenib is the first and only agent showing a survival benefit in these patients. In this study we evaluate the efficacy and tolerability of sorafenib in an unselected patient population. Furthermore we...

  7. Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Li Xin

    2010-04-01

    Full Text Available Abstract Background The aim of the present study was to analyze the expression of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1 in nasopharyngeal carcinoma (NPC and its correlation with clinicopathologic features, including patients' survival time. Methods Using real-time PCR, we detected the expression of EIF4G1 in normal nasopharyngeal tissues, immortalized nasopharyngeal epithelial cell lines NP69, NPC tissues and cell lines. EIF4G1 protein expression in NPC tissues was examined using immunohistochemistry. Survival analysis was performed using Kaplan-Meier method. The effect of EIF4G1 on cell invasion and tumorigenesis were investigated. Results The expression levels of EIF4G1 mRNA were significantly greater in NPC tissues and cell lines than those in the normal nasopharyngeal tissues and NP69 cells (P EIF4G1 protein was higher in NPC tissues than that in the nasopharyngeal tissues (P EIF4G1 protein in tumors were positively correlated with tumor T classification (P = 0.039, lymph node involvement (N classification, P = 0.008, and the clinical stages (P = 0.003 of NPC patients. Patients with higher EIF4G1 expression had shorter overall survival time (P = 0.019. Multivariate analysis showed that EIF4G1 expression was an independent prognostic indicator for the overall survival of NPC patients. Using shRNA to knock down the expression of EIF4G1 not only markedly inhibited cell cycle progression, proliferation, migration, invasion, and colony formation, but also dramatically suppressed in vivo xenograft tumor growth. Conclusion Our data suggest that EIF4G1 can serve as a biomarker for the prognosis of NPC patients.

  8. Sequence analysis of EBV immune evasion gene BNLF2a in EBV associated tumors and healthy individuals from nasopharyngeal carcinoma endemic and non-endemic regions of China.

    Science.gov (United States)

    Liu, Song; Wang, Xiaofeng; Shu, Jun; Zhao, Zhenzhen; Sun, Zhifu; Luo, Bing

    2015-11-01

    BNLF2a is an Epstein-Barr virus (EBV) immune evasion gene. Its protein is located in the endoplasmic reticulum (ER) membrane, and can inhibit the antigen transporting function of TAP, thereby perturbing the immune response to EBV in lytic and prelatent phase. In order to explore whether the polymorphism of BNLF2a gene has a role in different types of EBV associated tumors, we conducted complete sequencing of the gene BNLF2a in 408 cases of EBV positive tumors (76 lymphomas, 45 gastric carcinomas, and 85 nasopharyngeal carcinomas in northern China and 27 lymphomas, 30 gastric carcinomas, and 57 nasopharyngeal carcinomas in southern China) and throat washings from healthy individuals (39 in northern China and 49 in southern China). Two main variant types of BNLF2a were identified. Type BNLF2a-A, which was similar to B95-8, was dominant in all sub-populations (66.7-100%) in this study. Type BNLF2a-B was characterized by the mutations at position 8 and 40. The variation patterns of BNLF2a were significantly different between samples from northern and southern China (P China (P China (33.3%), and the proportion of this type was higher in the northern than in the southern NPCs. These data demonstrate that the BNLF2a gene is highly conserved, and its polymorphism is geographically restricted. Type BNLF2a-B is more prevalent in northern China and may be less tumor transformative.

  9. An analysis of the efficacy of serial screening for familial nasopharyngeal carcinoma based on Markov chain models.

    Science.gov (United States)

    Choi, Cheuk Wai; Lee, Michael C H; Ng, Wai Tong; Law, Lai Yau; Yau, Tsz Kok; Lee, Anne W M

    2011-03-01

    Treatment of nasopharyngeal carcinoma (NPC) can be improved by early detection of the disease as treatment outcome worsens with disease's progression. This can be achieved with a mass screening program using Epstein Barr virus (EBV) serology and nasopharyngoscopy. The efficacy of any screening strategy should be evaluated before putting it into practice. Such evaluation is ideally performed with simulation as time and cost often preclude the evaluation by randomized trial. This study simulated and compared the outcomes of 4 screening strategies over a period of 12 years: (A) Annual screening, (B) biennial screening, (C) triennial screening, and (D) triennial screening for participants tested EBV negative and annual screening once the participants are tested EBV positive. Progression of the disease was divided into 4 phases and calculated by applying Markov chain model. Parameters of the transition matrix and probabilities were estimated using data from previous screening results of 1,072 family members of NPC patients. The early detection rates with strategies A, B, C and D are 88, 79, 71 and 87% respectively. The 5-year overall survival with screening is 10-12% higher than that without and is the highest with strategies A and D. Strategy D, however, requires only 64% screening tests compared with strategy A and has almost identical resultant disease stage distribution to strategy A. We concluded that strategy D offered the highest efficacy for NPC screening of family members of NPC patients among the four strategies studied. PMID:21052850

  10. Homozygous Wildtype of XPD K751Q Polymorphism Is Associated with Increased Risk of Nasopharyngeal Carcinoma in Malaysian Population.

    Directory of Open Access Journals (Sweden)

    Munn-Sann Lye

    Full Text Available The xeroderma pigmentosum group D (XPD gene encodes a DNA helicase, an important component in transcription factor IIH (TFIIH complex. XPD helicase plays a pivotal role in unwinding DNA at the damaged region during nucleotide excision repair (NER mechanism. Dysfunctional XPD helicase protein from polymorphic diversity may contribute to increased risk of developing cancers. This study aims to determine the association between XPD K751Q polymorphism (rs13181 and risk of nasopharyngeal carcinoma (NPC in the Malaysian population. In this hospital-based matched case-control study, 356 controls were matched by age, gender and ethnicity to 356 cases. RFLP-PCR was used to genotype the XPD K751Q polymorphism. A significant association was observed between XPD K751Q polymorphism and the risk of NPC using conditional logistic regression. Subjects with homozygous Lys/Lys (wildtype genotype have 1.58 times higher odds of developing NPC compared to subjects with recessive combination of heterozygous Lys/Gln and homozygous Gln/Gln genotypes (OR = 1.58, 95% CI = 1.05-2.38 p = 0.028 adjusted for cigarette smoking, alcohol and salted fish consumption. Our data suggests that Lys/Lys (wildtype of XPD K751Q contributes to increased risk of NPC in the Malaysian population.

  11. Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan

    Directory of Open Access Journals (Sweden)

    Chou Pesus

    2011-08-01

    Full Text Available Abstract Background Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC. Methods Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads. Results As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p p = 0.001 after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p Conclusions Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate.

  12. The cytological diagnosis of nasopharyngeal carcinoma from exfoliated cells collected by suction method. An eight-year experience.

    Science.gov (United States)

    Hanji, D; Shujing, S; Shuwei, H; Gohao, L

    1983-08-01

    A specially designed metallic tube, which is connected to a suction-pump and passed through the oral cavity into the nasopharynx for collecting exfoliative cells by negative pressure suction, is recommended in the diagnosis of nasopharyngeal carcinoma (NPC). From the beginning of 1973 through October 1976, among 458 cases of NPC, 405 cases were cytologically positive (with a positive rate of 88.4 per cent), and 433 cases were biopsy positive (with a positive rate of 94.3 per cent). In 1977, from January to October, among 116 cases of NPC, 103 cases were cytologically positive (with a positive rate of 88.8 per cent), and 108 cases were biopsy positive (with a positive rate of 93.1 per cent). The cytopathological features of the exfoliative NPC cells were correlated with the histopathological types of NPC. The degree of lymphocytic infiltration among the cancer cells in smears was compared with that in biopsies. They coincided roughly with each other. It indicates that one might interpret the immunological lymphocytic reaction by the number and typing of lymphocytes in smears too. The authors conclude that this cytological method is fairly dependable, less traumatic to the mucosa, convenient, and easily managed. A large number of tumor cells can be collected. It can also reflect the histologic typing of cancer cells. It can be used as a routine procedure in the clinico-pathological diagnosis of NPC, as well as in a mass screening program. PMID:6350514

  13. The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT.

    Science.gov (United States)

    Xu, Tingting; Shen, Chunying; Ou, Xiaomin; He, Xiayun; Ying, Hongmei; Hu, Chaosu

    2016-04-12

    Nasopharyngeal carcinoma (NPC) patients with N2-3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2-3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194-0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187-0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation. PMID:26942700

  14. Inhibition of autophagy by 3-MA enhances endoplasmic reticulum stress-induced apoptosis in human nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Song, Lele; Liu, Hao; Ma, Linyan; Zhang, Xudng; Jiang, Zhiwen; Jiang, Chenchen

    2013-10-01

    Radiotherapy and adjuvant cisplatin chemotherapy are the mainstream treatments for nasopharyngeal carcinoma (NPC), which effectively improve the outcome and reduce tumor recurrence. However, the resistance mechanism(s) involved in radiotherapy and chemotherapy, which is the main barrier in NPC treatment, remains undefined. Therefore, there is an urgent requirement for the identification of new therapeutic strategies or adjuvant drugs. In the present study, the effects of autophagy inhibitors on endoplasmic reticulum (ER) stress-induced autophagy was investigated. Combining 3-methyladenine (3-MA) with cisplatin (DDP), ionizing radiation (IR), 2-deoxy-D-glucose (2-DG) or tunicamycin (TM) resulted in enhanced cell death, as revealed by MTT and colony formation assays. Flow cytometry results demonstrated that the sensitivity of NPC cells to DDP- and IR-induced apoptosis was not significant. DDP, IR, 2-DG and TM induced ER stress and autophagy. Using fluorescence microscopy, 3-MA was identified to increase the apoptotic cell death induced by DDP, IR, 2-DG or TM. In addition, 3-MA inhibited the increased autophagy induced by DDP, IR, 2-DG or TM, as demonstrated by western blot analysis and immunocytochemistry results. Results of the present study indicate that autophagy acts as a protective mechanism response to the apoptosis induced by DDP, IR, 2-DG or TM.

  15. RNA interference by expression of short hairpin RNAs suppresses bcl-xL gene expression in nasopharyngeal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Fang LIU; Cheng-wei HE; Yue-fei ZHANG; Ke-yuan ZHOU

    2005-01-01

    Aim: To evaluate a new plasmid mediated RNA interference (RNAi) system and investigate whether knock-down of bcl-xL by short hairpin RNA (shRNA) can induce apoptosis of human nasopharyngeal carcinoma (NPC) cell line CNE-2Z in vitro. Methods: The plasmid containing mU6 promoter was subcloned to yield the pmU6 plasmid, recombinant plasmid expressing shRNA targeting bcl-xL gene was designed and constructed, and were co-transfected cells with green fluorescence protein expressing plasmid. Flow cytometry was used to evaluate transfection efficiency, and RT-PCR and Western blot were applied to analyze bcl-xL mRNA and protein levels, respectively. Results: The shRNA expressed by the recombi nant plasmid efficiently suppressed bcl-xL gene expression and induced apoptosis .of NPC cells in vitro. Conclusion: The recombinant plasmid can sufficiently mediate RNAi in CNE-2Z cells, and knock-down of the bcl-xL expression by shRNA significantly induced apoptosis in CNE-2Z cells. The results suggest this new system, mediated RNAi can be used as a tool for the study of gene function and gene therapy.

  16. Neurosurgery and prognosis in patients with radiation-induced brain injury after nasopharyngeal carcinoma radiotherapy: a follow-up study

    International Nuclear Information System (INIS)

    Radiotherapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) and may cause radiation-induced brain injury (RI). Treatment for RI remains a challenge. We conducted this study to investigate the indications of neurosurgery, operation time and prognosis of patients with RI after NPC radiotherapy who underwent neurosurgical management. This was a follow-up study between January 2005 and July 2011. Fifteen NPC cases of RI who underwent neurosurgery were collected. Brain Magnetic resonance imaging (MRI), surgery and histology were studied. The outcome was assessed by LENT/SOMA scales and modified Rankin scale. Brain lesion resection (86.7%) was more common than decompressive craniotomy (13.3%). According to LENT/SOMA scale before and six months after surgery, 13 of 15, 12 of 15, 14 of 15, and 14 of 15 cases showed improvement at subjective, objective, management and analytic domains, respectively. 12 of 15 patients showed improvement of modified Rankin scale after surgery. Three patients who underwent emergency surgery showed significant improvement (average score increment of 2, 2.7, 2.7, 3 and 2 at LENT/SOMA scale subjective, objective, management, analytic, and modified Rankin scale, respectively), as compared with 12 cases underwent elective surgery (average score increment of 1, 1, 1.4, 1.8 and 1 at LENT SOMA scale subjective, objective, management, analytic, and modified Rankin scale, respectively). Neurosurgery, including brain necrotic tissue resection and decompressive craniotomy, improves the prognosis for RI patients, especially for those with indications of emergency surgery

  17. The impact of time factors on overall survival in patients with nasopharyngeal carcinoma: a population-based study

    International Nuclear Information System (INIS)

    Nasopharyngeal carcinoma (NPC) is most common in Southeast Asia. The purpose of this study is to investigate the correlation between wait time and length of radiotherapy and overall survival (OS) of NPC patients in Taiwan. From Taiwan’s National Health Insurance Research Database, this nationwide population-based cohort study identified 3605 NPC patients who received radiotherapy between 2008 and 2011. The impact of time factors on NPC survival rates was estimated with Kaplan-Meier survival curves. A multivariable Cox hazards regression model tested the significance of results after adjustment for other covariables. In all, 317 patients had wait times >4 weeks, 1404 patients had longer duration of radiotherapy (i.e., >10 weeks) and 499 died. Patients with wait times > 4 weeks and length of radiotherapy ≤ 10 weeks didn’t have significantly inferior survival. Patients with wait times >4 weeks and length of radiotherapy >10 weeks had significantly lower OS than other groups, with an adjusted hazard ratio of 1.7 (95 % CI, 1.10–2.60). Time was a significant prognostic factor for NPC patients who had both >4 weeks wait times and length of radiotherapy >10 weeks. Patients with wait time > 4 weeks and length of radiotherapy ≤ 10 weeks had a trend toward an inferior survival

  18. Construction of a nasopharyngeal carcinoma 2D/MS repository with Open Source XML Database – Xindice

    Directory of Open Access Journals (Sweden)

    Li Jianling

    2006-01-01

    Full Text Available Abstract Background Many proteomics initiatives require integration of all information with uniformcriteria from collection of samples and data display to publication of experimental results. The integration and exchanging of these data of different formats and structure imposes a great challenge to us. The XML technology presents a promise in handling this task due to its simplicity and flexibility. Nasopharyngeal carcinoma (NPC is one of the most common cancers in southern China and Southeast Asia, which has marked geographic and racial differences in incidence. Although there are some cancer proteome databases now, there is still no NPC proteome database. Results The raw NPC proteome experiment data were captured into one XML document with Human Proteome Markup Language (HUP-ML editor and imported into native XML database Xindice. The 2D/MS repository of NPC proteome was constructed with Apache, PHP and Xindice to provide access to the database via Internet. On our website, two methods, keyword query and click query, were provided at the same time to access the entries of the NPC proteome database. Conclusion Our 2D/MS repository can be used to share the raw NPC proteomics data that are generated from gel-based proteomics experiments. The database, as well as the PHP source codes for constructing users' own proteome repository, can be accessed at http://www.xyproteomics.org/.

  19. Assessment of ERCC1 and XPF Protein Expression Using Quantitative Immunohistochemistry in Nasopharyngeal Carcinoma Patients Undergoing Curative Intent Treatment

    International Nuclear Information System (INIS)

    Purpose: We sought to evaluate the prognostic/predictive value of ERCC1 and XPF in patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with curative intent. Methods and Materials: ERCC1 and XPF protein expression was evaluated by immunofluorescence combined with automated quantitative analysis (AQUA) using the FL297 and 3F2 antibodies, respectively. ERCC1 and XPF protein expression levels were correlated with clinical outcomes. Results: Patient characteristics were as follows: mean age 52 years (range, 18-85 years), 67% male, 72% Karnofsky performance status (KPS) ≥90%, World Health Organization (WHO) type 1/2/3 = 12%/28%/60%, stage III/IV 65%. With a median follow-up time of 50 months (range, 2.9 to 120 months), the 5-year overall survival (OS) was 70.8%. Median standardized nuclear AQUA scores were used as cutpoints for ERCC1 (n=138) and XPF (n=130) protein expression. Agreement between dichotomized ERCC1 and XPF scores was high at 79.4% (kappa = 0.587, P<.001). Neither biomarker predicted locoregional recurrence, DFS, or OS after adjustment for age and KPS, irrespective of stratification by stage, WHO type, or treatment. Conclusions: Neither ERCC1 nor XPF, analyzed by quantitative immunohistochemistry using the FL297 and 3F2 antibodies, was prognostic or predictive in this cohort of NPC patients

  20. Survival rate in nasopharyngeal carcinoma improved by high caseload volume: a nationwide population-based study in Taiwan

    International Nuclear Information System (INIS)

    Positive correlation between caseload and outcome has previously been validated for several procedures and cancer treatments. However, there is no information linking caseload and outcome of nasopharyngeal carcinoma (NPC) treatment. We used nationwide population-based data to examine the association between physician case volume and survival rates of patients with NPC. Between 1998 and 2000, a total of 1225 patients were identified from the Taiwan National Health Insurance Research Database. Survival analysis, the Cox proportional hazards model, and propensity score were used to assess the relationship between 10-year survival rates and physician caseloads. As the caseload of individual physicians increased, unadjusted 10-year survival rates increased (p < 0.001). Using a Cox proportional hazard model, patients with NPC treated by high-volume physicians (caseload ≥ 35) had better survival rates (p = 0.001) after adjusting for comorbidities, hospital, and treatment modality. When analyzed by propensity score, the adjusted 10-year survival rate differed significantly between patients treated by high-volume physicians and patients treated by low/medium-volume physicians (75% vs. 61%; p < 0.001). Our data confirm a positive volume-outcome relationship for NPC. After adjusting for differences in the case mix, our analysis found treatment of NPC by high-volume physicians improved 10-year survival rate

  1. Cellular Redox Status Regulates Emodin-Induced Radiosensitization of Nasopharyngeal Carcinoma Cells In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Huaxin Hou

    2013-01-01

    Full Text Available Here, we report that regulation of cellular redox status is required for radiosensitization of nasopharyngeal carcinoma (NPC cells by emodin. We evaluated emodin’s radiosensitivity-enhancing ability by using NPC cells in vitro and xenografts in vivo. A clonogenic assay was performed to evaluate NPC cell survival and to determine dose modification factors. Flow cytometry, western blot analysis, and in vivo radiation-induced tumor regrowth delay assays were performed to characterize emodin’s effects. Exposure of CNE-1 NPC cells to emodin enhanced their radiosensitivity. HIF-1α expression significantly increased under hypoxic conditions but did not change after treatment with emodin alone. Emodin downregulated mRNA and protein expression of HIF-1α. Cells exposed to radiation and emodin underwent significant cell cycle arrest at the G2/M phase. The percentage of apoptotic cells and reactive oxygen species (ROS levels were significantly higher in the group exposed to emodin and radiation hypoxic group than in the other groups. Compared to the CNE-1 xenografts exposed to radiation alone, CNE-1 xenografts exposed to radiation with emodin showed significantly enhanced radiation effects. Our data suggest that emodin effectively enhanced the radiosensitivity of CNE-1 cells in vitro and in vivo. The mechanism appears to involve ROS generation and ROS-mediated inhibition of HIF-1α expression.

  2. Homozygous Wildtype of XPD K751Q Polymorphism Is Associated with Increased Risk of Nasopharyngeal Carcinoma in Malaysian Population.

    Science.gov (United States)

    Lye, Munn-Sann; Visuvanathan, Shaneeta; Chong, Pei-Pei; Yap, Yoke-Yeow; Lim, Chin-Chye; Ban, Eng-Zhuan

    2015-01-01

    The xeroderma pigmentosum group D (XPD) gene encodes a DNA helicase, an important component in transcription factor IIH (TFIIH) complex. XPD helicase plays a pivotal role in unwinding DNA at the damaged region during nucleotide excision repair (NER) mechanism. Dysfunctional XPD helicase protein from polymorphic diversity may contribute to increased risk of developing cancers. This study aims to determine the association between XPD K751Q polymorphism (rs13181) and risk of nasopharyngeal carcinoma (NPC) in the Malaysian population. In this hospital-based matched case-control study, 356 controls were matched by age, gender and ethnicity to 356 cases. RFLP-PCR was used to genotype the XPD K751Q polymorphism. A significant association was observed between XPD K751Q polymorphism and the risk of NPC using conditional logistic regression. Subjects with homozygous Lys/Lys (wildtype) genotype have 1.58 times higher odds of developing NPC compared to subjects with recessive combination of heterozygous Lys/Gln and homozygous Gln/Gln genotypes (OR = 1.58, 95% CI = 1.05-2.38 p = 0.028) adjusted for cigarette smoking, alcohol and salted fish consumption. Our data suggests that Lys/Lys (wildtype) of XPD K751Q contributes to increased risk of NPC in the Malaysian population.

  3. Identification of nasopharyngeal carcinoma metastasis-related biomarkers by iTRAQ combined with 2D-LC-MS/MS

    Science.gov (United States)

    Chen, Zhen; Long, Lu; Wang, Kun; Cui, Facai; Zhu, Lepan; Tao, Ya; Wu, Qiong; Xiang, Manlin; Liang, Yunlai; Qiu, Shiyang; Xiao, Zhiqiang; Yi, Bin

    2016-01-01

    To identify metastasis-related proteins in nasopharyngeal carcinoma (NPC), iTRAQ-tagging combined with 2D LC-MS/MS analysis was performed to identify the differentially expressed proteins (DEPs) in high metastatic NPC 5-8F cells and non-metastatic NPC 6-10B cells, and qRT-PCR and Western blotting were used to confirm DEPs. As a result, 101 DEPs were identified by proteomics, and 12 DEPs were selectively validated. We further detected expression of three DEPs (RAN, SQSTM1 and TRIM29) in a cohort of NPC tissue specimens to assess their value as NPC metastatic biomarkers, and found that combination of RAN, SQSTM1 and TRIM29 could discriminate metastatic NPC from non-metastatic NPC with a sensitivity of 88% and a specificity of 91%. TRIM29 and RAN expression level were closely correlated with lymph node and distant metastasis and clinical stage (P <0.05) in NPC patients. Finally, a combination of loss-of-function and gain-of-function approaches was performed to determine the effects of TRIM29 on NPC cell proliferation, migration, invasion and metastasis. The results showed that TRIM29 knockdown significantly attenuated while TRIM29 overexpression promoted NPC cell in vitro proliferation, migration and invasion and in vivo metastasis. The present data first time show that SQSTM1, RAN and TRIM29 are novel potential biomarkers for predicting NPC metastasis, demonstrate that TRIM29 is a metastasis-promoted protein of NPC. PMID:27145374

  4. Impact of primary tumor volume and location on the prognosis of patients with locally recurrent nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yun-Ming Tian; Wei-Wei Xiao; Li Bai; Xue-Wen Liu; Chong Zhao; Tai-Xiang Lu; Fei Han

    2015-01-01

    Introduction:The properties of a tumor itself were considered the main factors determining the survival of patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). However, recurrent tumors were mainly evaluated by using the American Joint Committee on Cancer staging system, which was modeled on primary tumors and did not incorporate the tumor volume. This study aimed to investigate the prognostic values of the primary tumor location and tumor volume, and to determine whether evaluating these parameters could improve the current staging system. Methods:Magnetic resonance (MR) images for 229 patients with local y recurrent NPC who underwent IMRT were analyzed retrospectively. Results:The skul base, parapharyngeal space, and intracranial cavity were the most common sites of tumors. There was a difference in the survival between patients with T1 and T2 diseases (77.6%vs. 50.0%, P38 cm3 (48.7%vs. 15.2%, P<0.01). Conclusions:A new staging system has been proposed, with T3 tumors being down-staged to T2 and with the tumor volume being incorporated into the staging, which may lead to an improved evaluation of these tumors. This new system can be used to guide the treatment strategy for different risk groups of recurrent NPC.

  5. 3D-image-guided high-dose-rate intracavitary brachytherapy for salvage treatment of locally persistent nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    To evaluate the therapeutic benefit of 3D-image-guided high-dose-rate intracavitary brachytherapy (3D-image-guided HDR-BT) used as a salvage treatment of intensity modulated radiation therapy (IMRT) in patients with locally persistent nasopharyngeal carcinoma (NPC). Thirty-two patients with locally persistent NPC after full dose of IMRT were evaluated retrospectively. 3D-image-guided HDR-BT treatment plan was performed on a 3D treatment planning system (PLATO BPS 14.2). The median dose of 16 Gy was delivered to the 100% isodose line of the Gross Tumor Volume. The whole procedure was well tolerated under local anesthesia. The actuarial 5-y local control rate for 3D-image-guided HDR-BT was 93.8%, patients with early-T stage at initial diagnosis had 100% local control rate. The 5-y actuarial progression-free survival and distant metastasis-free survival rate were 78.1%, 87.5%. One patient developed and died of lung metastases. The 5-y actuarial overall survival rate was 96.9%. Our results showed that 3D-image-guided HDR-BT would provide excellent local control as a salvage therapeutic modality to IMRT for patients with locally persistent disease at initial diagnosis of early-T stage NPC

  6. THE ROLE OF MRI IN THE ILLUSTRATION OF METASTATIC LYMPHATIC PATHWAYS AND CLINICAL N-STAGING OF NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    Wei Xiong; Li Jianjun; Tang Qixin

    1998-01-01

    Subject: To study the role of MRI in the illustration of metastatic lymphatic pathways and clinical N-staging of nasopharyngeal carcinoma (NPC). Methods: Eighty NPC patients were examined with MRI before radiotherapy from Mar. 1994 to Jun. 1996. MRI were performed using T1 weighted image (T1WI) and T2 weighted image (T2WI) in transverse, and using T1WI in sagittal and coronal sections. Results: 1. NpC chief metastatic lymphatic pathways are: primary foci → Rouviere's node (RN), or retrostyloid space nodes (RSN) secondarily →deep cervical nodes; 2. The superior border of neck fields should be moved upward to the level of external acoustic meatus; 3. The authors suggested that in Nstaging for NPC, N0 and N1 be divided into N0a and N0b,and N1a and N1b. Conclusion: MRI is very useful in clinical N-staging of NPC, especially for the reflection of the influance of RN and/or RSN tumefaction on N-staging.

  7. Volumetric modulation arc radiotherapy with flattening filter-free beams compared with conventional beams for nasopharyngeal carcinoma: a feasibility study

    Institute of Scientific and Technical Information of China (English)

    Mingzan Zhuang; Tuodan Zhang; Zhijian Chen; Zhixiong Lin; Derui Li; Xun Peng; Qingchun Qiu

    2013-01-01

    There is increasing interest in the clinical use of flattening filter-free (FFF) beams.In this study,we aimed to investigate the dosimetric characteristics of volumetric modulated arc radiotherapy (VMAT) with FFF beams for nasopharyngeal carcinoma (NPC).Ten NPC patients were randomly selected to undergo a RapidArc plan with either FFF beams (RA-FFF) or conventional beams (RA-C).The doses to the planning target volumes (PTVs),organs at risk (OARs),and normal tissues were compared.The technical delivery parameters for RapidArc plans were also assessed to compare the characteristics of FFF and conventional beams.Both techniques delivered adequate doses to PTVs.For PTVs,RA-C delivered lower maximum and mean doses and improved conformity and homogeneity compared with RA-FFF.Both techniques provided similar maximum doses to the optic nerves and lenses.For the brain stem,spinal cord,larynx,parotid glands,oral cavity,and skin,RA-FFF showed significant dose increases compared to RA-C.The dose to normal tissue was lower in RA-FFF.The monitor units (MUs) were (536 ± 46) MU for RA-FFF and (501 ± 25) MU for RA-C.The treatment duration did not significantly differ between plans.Although both treatment plans could meet clinical needs,RA-C is dosimetrically superior to RA-FFF for NPC radiotherapy.

  8. GENETIC DELETION OF DETOXIFIC ENZYME GSTM1 AND GSTT1 AS A HOST SUSCEPTIBLE FACTOR FOR NASOPHARYNGEAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    邓卓霖; 韦义萍; 马韵

    2004-01-01

    Objective: To study the gene polymorphisms of GSTT1 and GSTM1 in nasopharyngeal carcinoma (NPC) patients and controls in an incidental area to evaluate the relationship between specific genotype and genotype combinations of these polymorphisms with the risk of NPC.Methods: Cases and controls all came from the Southwestern Guangxi. DNAs were extracted from their WBC. PCR technique was used to calculate the deletion rate of the two detoxific enzyme genes. Results: In this high risk area of NPC, the residents had high level deletion rates of 47.4% (64/135) M1 and T1 40.7% (55/135). The deletion rates were even higher in NPC patients, 61.5% (56/91) for M1 and 59.3% (54/91) for T1 respectively. There were statistical significances compared with control, P<0.05 and P<0.01 for M1 and T1 respectively. The difference was more significant in terms of combined M1 and T1 deletion between patients and controls x2=12.533, P=0.002.Conclusion: The combined deletion of detoxific enzyme genes GSTM1 and GSTT1 may be an important genetic susceptible factor for NPC in Guangxi.

  9. Comparison of the prognostic impact of serum anti-EBV antibody and plasma EBV DNA assays in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Purpose: Nasopharyngeal carcinoma (NPC) has been proven as an Epstein-Barr virus (EBV)-associated cancer. Serum anti-EBV antibodies and plasma EBV DNA have been investigated as surrogate markers for NPC. A comparison of the prognostic impacts of both assays has never been reported. Methods and Materials: Paired serum and plasma samples from 114 previously untreated NPC patients were collected and subjected to an immunofluorescence assay for immunoglobulin (Ig)A and IgG antibodies against the viral capsid antigen (VCA) and a real-time quantitative polymerase chain reaction assay for EBV DNA measurement. The effects of both assays on patient prognosis were thoroughly investigated. Results: Relapsed patients had significantly higher pretreatment EBV DNA concentration than patients without relapse (p 0.0006). No associations of VCA-IgA (p = 0.9669) or VCA-IgG (p = 0.6125) were observed between patients with and without relapse. The 4-year overall survival (60.3% vs. 93.1%, p 0.1). Cox multivariate analyses also showed the same results. Conclusion: Plasma EBV DNA is superior to serum EBV VCA antibodies in prognostic predictions for NPC

  10. The impact of reduced-volume, intensity-modulated radiation therapy on disease control in nasopharyngeal carcinoma.

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    Yu-Wei Lin

    Full Text Available To investigate the feasibility of using intensity-modulated radiotherapy (IMRT with reduced, high-dose target volumes for nasopharyngeal carcinoma (NPC.The first 57 patients (admitted from October 2005 to May 2008 were treated with large-target-volume IMRT (LV-IMRT. For the LV-IMRT group, the CTV at 70 Gy (CTV70 was delineated as the gross target volume (GTV plus 7mm, with or without the first-echelon lymph-node region. The next 56 patients (admitted from June 2008 to November 2011 were treated with reduced-target-volume IMRT (RV-IMRT. For the RV-IMRT group, the CTV70 was delineated as the GTV alone.The 4-year local recurrence-free, regional recurrence-free, distant metastasis-free, progression-free, and overall survival rates were 77.2%, 80.1%, 83.2%, 61.2%, and 74.4% for the LV-IMRT group and 83.5%, 92.6%, 89.1%, 78.5, and 91.0% for the RV-IMRT group, respectively. Late toxicity scoring of xerostomia was lesser in the RV-IMRT group than the LV-IMRT group (P < 0.001.The use of RV-IMRT for the treatment of NPC did not negatively affect survival rates but did reduce the late xerostomia events compared to LV-IMRT.

  11. Pretreatment 18 F-FDG uptake heterogeneity can predict survival in patients with locally advanced nasopharyngeal carcinoma——a retrospective study

    International Nuclear Information System (INIS)

    Intratumoural heterogeneity has been demonstrated to be a strong indicator of malignant transformation. Our study was to investigate pretreatment 18 F-FDG parameters, including 18 F-FDG based heterogeneity for predicting survival in patients with locally advanced nasopharyngeal carcinoma (NPC). Forty newly diagnosed, biopsy-proven locally advanced NPC patients who underwent 18 F-FDG PET/CT were retrospectively included. The following PET parameters were assessed: maximum and mean standardised uptake value (SUVmax and SUVmean), metabolic tumour volume (MTV), total lesion glycolysis (TLG) and intratumoral heterogeneity index (HI). The previous parameters were recorded both for the primary tumor (-T) and neck lymph nodes (-N). The following endpoints were evaluated: local control (LC), progression-free survival (PFS) and overall survival (OS). The survival analyses were performed using the Kaplan–Meier method. Univariate analysis was performed using the log-rank test. Patients with a lower HI-T, SUVmax-T, SUVmean-T and TLG-T had significantly better 2-year LC. In predicting PFS, we found that both lower HI-T and HI-N had significantly better prognosis. However, the OS was only statistically associated with HI-T. 18 F-FDG based heterogeneity appears to be an potential predicator of patient survival after treatment

  12. An in silico analysis of dynamic changes in microRNA expression profiles in stepwise development of nasopharyngeal carcinoma

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    Luo Zhaohui

    2012-01-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are small non-coding RNAs that participate in the spatiotemporal regulation of messenger RNA (mRNA and protein synthesis. Recent studies have shown that some miRNAs are involved in the progression of nasopharyngeal carcinoma (NPC. However, the aberrant miRNAs implicated in different clinical stages of NPC remain unknown and their functions have not been systematically studied. Methods In this study, miRNA microarray assay was performed on biopsies from different clinical stages of NPC. TargetScan was used to predict the target genes of the miRNAs. The target gene list was narrowed down by searching the data from the UniGene database to identify the nasopharyngeal-specific genes. The data reduction strategy was used to overlay with nasopharyngeal-specifically expressed miRNA target genes and complementary DNA (cDNA expression data. The selected target genes were analyzed in the Gene Ontology (GO biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG biological pathway. The microRNA-Gene-Network was build based on the interactions of miRNAs and target genes. miRNA promoters were analyzed for the transcription factor (TF binding sites. UCSC Genome database was used to construct the TF-miRNAs interaction networks. Results Forty-eight miRNAs with significant change were obtained by Multi-Class Dif. The most enriched GO terms in the predicted target genes of miRNA were cell proliferation, cell migration and cell matrix adhesion. KEGG analysis showed that target genes were significantly involved in adherens junction, cell adhesion molecules, p53 signalling pathway et al. Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-29a/c, miR-34b, miR-34c-3p, miR-34c-5p, miR-429, miR-203, miR-222, miR-1/206, miR-141, miR-18a/b, miR-544, miR-205 and miR-149 may play important roles on the development of NPC. We proposed an integrative strategy for identifying the mi

  13. Incidence trend of nasopharyngeal carcinoma from 1987 to 2011 in Sihui County, Guangdong Province, South China:an age-period-cohort analysis

    Institute of Scientific and Technical Information of China (English)

    Li-Fang Zhang; Yan-Hua Li; Shang-Hang Xie; Wei Ling; Sui-Hong Chen; Qing Liu; Qi-Hong Huang; Su-Mei Cao

    2015-01-01

    Introduction:In the past several decades, declining incidences of nasopharyngeal carcinoma (NPC) have been observed in Chinese populations in Hong Kong, Taiwan, Los Angeles, and Singapore. A previous study indicated that the incidence of NPC in Sihui County, South China remained stable until 2002, but whether age, diagnosis period, and birth cohort affect the incidence of NPC remains unknown. Methods:Age-standardized rates (ASRs) of NPC incidence based on the world standard population were examined in both males and females in Sihui County from 1987 to 2011. Joinpoint regression analysis was conducted to quantify the changes in incidence trends. A Poisson regression age-period-cohort model was used to assess the effects of age, diagnosis period, and birth cohort on the risk of NPC. Results:The ASRs of NPC incidence during the study period were 30.29/100,000 for males and 13.09/100,000 for females. The incidence of NPC remained stable at a non-significant average annual percent change of 0.2%for males and−1.6%for females throughout the entire period. A significantly increased estimated annual percent change of 6.8%(95%confidence interval, 0.1%–14.0%) was observed from 2003 to 2009 for males. The relative risk of NPC increased with advancing age up to 50–59 and decreased at ages>60 years. The period effect curves on NPC were nearly flat for males and females. The birth cohort effect curve for males showed an increase from the 1922 cohort to the 1957 cohort and a decrease thereafter. In females, there was an undulating increase in the relative risk from the 1922 cohort to the 1972 cohort. Conclusions:The incidence trends for NPC remained generally stable in Sihui from 1987 to 2011, with an increase from 2003 to 2009. The relative risks of NPC increased in younger females.

  14. Intensity-modulated radiotherapy for stage IVA/IVB nasopharyngeal carcinoma. Clinical outcomes and patterns of failure in an endemic area in China

    International Nuclear Information System (INIS)

    The purpose of this study was to analyze the mode of relapse patterns and survival of 209 patients with stage IVA and IVB nasopharyngeal carcinoma (NPC). A total of 209 patients who underwent magnetic resonance imaging (MRI) and were subsequently histologically diagnosed with nondisseminated stage IV NPC received intensity-modulated radiotherapy (IMRT) as their primary treatment and were included in this retrospective study. Median follow-up time was 65 months (range, 3-108 months). The 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates for patients with stage IVA and stage IVB NPC were 72.7 vs. 60.0 % (p = 0.319), 62.9 vs. 51.3 % (p = 0.070), 82.9 vs. 93.1 % (p = 0.070), 82.9 vs. 82.9 % (p = 0.897), 76.4 vs. 58.5 % (p = 0.003), respectively. Age older than 44 years was found to be a statistically significant adverse independent prognostic factor for OS. Patients with advanced N status had worse OS, DFS, and DMFS rates. Patients with a primary gross tumor volume (GTV-P) ≥ 55.11 ml had worse OS, DFS, and LRRFS rates. The results of treating stage IVA NPC with IMRT were excellent. Distant metastasis remains the most difficult treatment challenge for patients with stage IVA and IVB NPC, and more effective systemic chemotherapy should be explored. (orig.)

  15. 鼻咽癌患者抑郁症影响因素研究%Study on Influencing Factors of Depression in Patients with Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    陈梅英; 肖水源; 刘萼莲; 刘晓红

    2012-01-01

    目的 探讨鼻咽癌患者抑郁症发病的影响因素,以便及时有效解决癌症患者的心理问题. 方法 应用Zung抑郁自评量表(SDS)及自制鼻咽癌患者抑郁症影响因素调查问卷进行调查. 结果 调查456例鼻咽癌患者抑郁症发生率为40.35%.年龄≤50岁者抑郁症发生率高于>50岁患者(x2=4.02,P<0.05).家庭经济状况条件越差,抑郁症发生也越高(x2=20.15,P<0.05).癌症发生转移患者和副反应程度越重患者,抑郁症发生率也越高(x2=19.19、21.81,P均<0.05),而鼻咽癌患者抑郁症发生率与性别、文化程度无关(P>0.05). 结论 影响鼻咽癌抑郁发病因素主要是年龄、经济状况、癌症有无转移及副反应程度等,对鼻咽癌患者应进行适当的心理疏导,让患者树立战胜疾病的信心是降低鼻咽癌患者抑郁症发生率的重要措施.%Objective To explore the factors influencing the development of depression among patients with nasopharyngeal carcinoma so as to solve the patients' psychological problems timely and effectively. Methods The survey was conducted using Zung Self - rating Depression Scale (SDS) and the self - designed questionnaire about factors associated with depression in patients with nasopharyngeal carcinoma. Results Among 456 patients with nasopharyngeal carcinoma, the incidence rate of depression was 40.35 %. The incidence rate of the patients aged ≤50 years was higher than that of the patients aged >50 years (X2=4.02, P0.05). Conclusions The main factors associated with the development of depression in patients with nasopharyngeal carcinoma are age, economic condition, the metastasis of nasopharyngeal carcinoma, the degree of side effects, etc. Giving proper psychological guidance and setting up the patient's confidence of overcoming the disease are the important measures to reduce the incidence rate of depression in patients with nasopharyngeal carcinoma.

  16. Comparative study on risk factors and family history of familial and sporadic nasopharyngeal carcinoma patients%家族性和散发性鼻咽癌患者的危险因素及肿瘤家族史的比较

    Institute of Scientific and Technical Information of China (English)

    罗翔宇; 刘稳升; 陈丽珍; 冯启胜; 曾益新; 贾卫华

    2009-01-01

    Familial nasopharyngeal carcinoma was 9. 64% in the observed subjects. In the familial nasopharyngeal carcinoma, the time interval at diagnosis was shorter between proband and siblings as compared with parents. Most of the patients were at advanced stage. So, we recommend the first-degree relatives of nasopharyngeal carcinoma patients, especially siblings, should be screened regularly according to the specific conditions.%目的 研究广东地区家族性鼻咽癌患者与散发性鼻咽癌患者发病因素间存在的差异及其一级亲属恶性肿瘤发病情况,为鼻咽癌患者家庭成员的遗传咨询和筛查策略提供依据.方法 选取2005年10月至2007年10月中山大学肿瘤防治中心收治的广东籍新发鼻咽痛患者作为研究对象,共收集1877例鼻咽痛患者,包括181例家族性鼻咽痛患者和1696例散发病例.对两组患者的人口学特征、临床特征、危险因素及一级亲属肿瘤家族史进行比较分析,并对家族性鼻咽癌患者受累一级亲属的分布及其与先证者发病的时间间隔进行分析.结果 1877例鼻咽癌患者中181例(9.64%)有一级亲属受累;在受累的一级亲属中有58.49%(124/212)为同胞,41.51%(88/212)为父母.同胞与先证者发病的时间间隔为(7.40±5.41)年,而父母与先证者发病的平均时间间隔为(15.55±10.61)年,两者间差异有统计学意义(t=-5.78,P0.05).两组患者在吸烟(OR=0.99;95%CI:0.68~1.45)及其一级亲属患其他肿瘤的风险方面(OR=0.85;95%CI:0.56~1.28)差异也无统计学意义(P值均>0.05).结论 在中国广东地区的鼻咽癌患者中,家族性鼻咽癌约占9.64%.在高发家系中,同胞与先证者发病的时间间隔短于父母与先证者发病的时间间隔.大多数患者就诊时已到晚期,建议确诊的鼻咽癌患者的一级亲属,特别是同胞,应根据具体情况定期进行鼻咽癌筛查.

  17. Proteomics-based Identification of Proteins with Altered Expression Induced by 12-O-Tetradecanoylphorbol 13-acetate in Nasopharyngeal Carcinoma CNE2 Cells

    Institute of Scientific and Technical Information of China (English)

    Pei-Zhou JIANG; Ming GAN; Hua HUANG; Xin-Ming SHEN; Shuang WANG; Kai-Tai YAO

    2005-01-01

    Nasopharyngeal carcinoma (NPC) is a malignancy with high incidence in Southern China and South-East Asia. Etiology studies indicate that chemical carcinogen promoters, such as 12-Otetradecanoylphorbol-13-acetate (TPA), are important factors causing NPC development. However, the mechanism of the TPA effect on NPC remains unclear. In the present study, cells from a poorly differentiated squamous cell carcinoma NPC cell line, CNE2, were stimulated by TPA and proteomics technology was carried out to find protein discrepancies between control and TPA-treated cells. Results revealed that TPA treatment in CNE2 cells could upregulate the expression of "triosephosphate isomerase" and "14-3-3 protein sigma" and downregulate the expression of "reticulocalbin 1 precursor", "nucleophosmin", "mitochondrial matrix protein pl precursor", and "stathmin". The changes in the expression of these genes suggested that TPA induced CNE2 cells to antiproliferation and to apoptosis, which was confirmed by subsequent apoptosis detection. Therefore, the effects of TPA on nasopharyngeal carcinoma cells were distinct from the effects on primary epithelial cells and we suggest reasons for these differences.

  18. Involvement of Difference in Decrease of Hemoglobin Level in Poor Prognosis of Stage I and II Nasopharyngeal Carcinoma: Implication in Outcome of Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: To investigate the effect of hemoglobin (Hb) concentration and the difference in its decrease during treatment on outcome of radiotherapy (RT) alone for patients with Stage I and II nasopharyngeal carcinoma. Methods and Materials: A total of 572 patients with Stage I-II nasopharyngeal carcinoma with RT alone between January 2001 and December 2004 were retrospectively analyzed. Patient characteristics, tumor variables, and Hb level, including pre-RT Hb, mid-RT Hb, and dynamic change of Hb between pre- and post- RT and its difference in decrease (▵Hb) were subjected to univariate and multivariable analysis to identify factors that predict disease-specific survival (DSS), local regional recurrence-free survival (LRFS), and metastases-free survival (MFS). Results: The 5-year DSS was poorer in the Hb continuous decrease group than in the Hb noncontinuous decrease group (84% vs. 89%; p = 0.008). There was poorer 5-year DSS in patients with ▵Hb of >11.5 g/L than in those with ▵Hb of ≤11.5 g/L (82% vs. 89%; p = 0.001), and poorer LRFS (79% vs. 83%; p = 0.035). Univariate and multivariate analysis showed that Hb decrease difference with greater than 11.5 g/L was an independent prognostic factor for DSS and LRFS. Conclusions: The difference in decrease of Hb level during the course of radiation treatment appeared as a poor prognostic factor in Stage I and II nasopharyngeal carcinoma patients.

  19. Can Epstein-Barr virus DNA load in nasopharyngeal brushings or whole blood predict recurrent nasopharyngeal carcinoma in a non-endemic region? A prospective nationwide study of the Dutch Head and Neck Oncology Cooperative Group.

    Science.gov (United States)

    Stoker, Sharon D; Wildeman, Maarten A; Novalic, Zlata; Fles, Renske; van der Noort, Vincent; de Bree, Remco; Braunius, Weibel W; van den Broek, Guido B; Kreike, Bas; Kross, Kenneth W; Juwana, Hedy; Ramayanti, Octavia; Verkuijlen, Sandra A W M; de Boer, Jan Paul; Greijer, Astrid E; Middeldorp, Jaap M; Tan, I Bing

    2016-06-01

    This study estimated the value of quantitative measurements of EBV markers in the clinical management of nasopharyngeal carcinoma in a non-endemic area. The aim was to predict prognosis and detect recurrent and residual disease. In 72 patients, EBV DNA load in blood and nasopharyngeal brushes, and IgA VCA-p18 and EBNA1 in plasma were measured at different time points. At diagnosis and post-treatment, a cut-off value was used for detecting disease [positive (PPV) and negative (NPV) predictive value]. The markers were correlated as a continuous variable with tumor stage, disease-free survival (DFS) and overall survival (OS). The Cox hazard ratio model assessed hazard ratios. At diagnosis, the markers were above the COV in 45, 92, 85 and 83 % of the patients, respectively. Post-treatment, DNA load test in blood and brush had the best discriminating power (blood DNA load test: PPV 39 % and NPV 97 %, brush for local disease: PPV 75 % and NPV 99 %). Post-treatment, DNA load in blood was the best predictor for OS and DFS [hazard ratio 3.2 (95 % CI 1.51-3.5) and 2.3 (95 % CI 1.72-5.8)]. Assessing the EBV DNA load in blood has significant prognostic value, although the clinical value is for discussion. The EBV DNA load in the brush might improve early detection of local failures post-treatment. PMID:25929413

  20. Clinical Study on Effect of Shenlong Oral Liquid (神龙口服液)Combined with Radiotherapy in Treating Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    朱小东; 王安宇; 王绍丰; 王仁生; 陈龙; 李龄; 陆海杰

    2001-01-01

    To observe the effect of Shenlong Oral Liquid(SLOL)combined with radiotherapy in treating nasopharyngeal carcinoma (NPC). Methods: Effects of the combined therapy, including clinical effects, changes of cellular immunity and side effects, in treating 60 NPC patients (in the treated group) were observed and compared with those of the other 60 patients treated with radiotherapy alone (in the control group). Results: (1)The side effects of radiation in the treated group were lower than those in the control group significantly (P<0.05). (2) The short-term remission rate of nasopharyngeal and neck metastatic tumor in the two groups was not significantly different (P>0.05). (3) The dose for complete remission of nasopharyngeal and neck tumor in the treated group was lower than that in the control group (P<0.01). (4) No change of T-lymphocyte subsets was found in the treated group after treatment, but in the control group , OKT3,OKT4,and OKT4/OKT8 ratio were markedly decreased (P<0.05). (5) The survival rate in the treated group was higher than that in the control group, but with no statistical significance (P=0.0518). Conclusion: The combined therapy of NPC with SLOL and radiotherapy is able to reduce side-effect of radiotherapy, improve the cellular immunity, reduce the dose of radiation for tumor remission and enhance the therapeutic effect of radiotherapy. It showed a trend of raising the long-term survival rate of NPC patients.

  1. Increased SHP-1 expression results in radioresistance, inhibition of cellular senescence, and cell cycle redistribution in nasopharyngeal carcinoma cells

    International Nuclear Information System (INIS)

    Radioresistance is the main limit to the efficacy of radiotherapy in nasopharyngeal carcinoma (NPC). SHP-1 is involved in cancer progression, but its role in radioresistance and senescence of NPC is not well understood. This study aimed to assess the role of SHP-1 in the radioresistance and senescence of NPC cells. SHP-1 was knocked-down and overexpressed in CNE-1 and CNE-2 cells using lentiviruses. Cells were irradiated to observe their radiosensitivity by colony forming assay. BrdU incorporation assay and flow cytometry were used to monitor cell cycle. A β-galactosidase assay was used to assess senescence. Western blot was used to assess SHP-1, p21, p53, pRb, Rb, H3K9Me3, HP1γ, CDK4, cyclin D1, cyclin E, and p16 protein expressions. Compared with CNE-1-scramble shRNA cells, SHP-1 downregulation resulted in increased senescence (+107 %, P < 0.001), increased radiosensitivity, higher proportion of cells in G0/G1 (+33 %, P < 0.001), decreased expressions of CDK4 (−44 %, P < 0.001), cyclin D1 (−41 %, P = 0.001), cyclin E (−97 %, P < 0.001), Rb (−79 %, P < 0.001), and pRb (−76 %, P = 0.001), and increased expression of p16 (+120 %, P = 0.02). Furthermore, SHP-1 overexpression resulted in radioresistance, inhibition of cellular senescence, and cell cycle arrest in the S phase. Levels of p53 and p21 were unchanged in both cell lines (all P > 0.05). SHP-1 has a critical role in radioresistance, cell cycle progression, and senescence of NPC cells. Down-regulating SHP-1 may be a promising therapeutic approach for treating patients with NPC

  2. Quercetin-induced inhibition and synergistic activity with cisplatin – a chemotherapeutic strategy for nasopharyngeal carcinoma cells

    Directory of Open Access Journals (Sweden)

    Daker Maelinda

    2012-07-01

    Full Text Available Abstract Background Nasopharyngeal carcinoma (NPC is a unique tumour of epithelial origin with a distinct geographical distribution, genetic predisposition and environmental as well as dietary influence as aetiological factors. Standard NPC treatment regimes, such as radiotherapy and concurrent chemotherapy with cytotoxic drugs, can produce undesirable complications often associated with significant toxicity. Here, we report the effects of a widely distributed flavonoid, quercetin, on cell proliferation, apoptosis and cell cycle arrest. The effects of combining quercetin and cisplatin on human NPC cells were explored. Methods Cell proliferation was monitored by the dynamic, impedance-based cell analyzer (xCELLigence system and the MTS assay. Ki67 proliferation antigen and fatty acid synthase (FASN level was examined by Western blotting. Flow cytometry was also carried out to study the effects of quercetin on cell cycle and apoptosis status. Results At 100 μM, quercetin inhibited cell proliferation and decreased expression of FASN and Ki67 antigen. Cell cycle analysis revealed a substantial increase in the proportion of cells in the G2/M phase. We also demonstrated the enhanced cytotoxic effects of quercetin treatment in concomitant with the chemotherapeutic drug, cisplatin, in cultured NPC cells. The combination index (CI value of quercetin-cisplatin combination was  Conclusions Our study showed that quercetin exhibited synergistic effects with cisplatin against NPC cells. Dose-reduction index (DRI values > 1 implied the possibility of reducing the cisplatin dosage required to treat NPC, with the addition of quercetin. In turn, this could reduce the risk of cisplatin-associated toxicity. The potential of combining quercetin with cisplatin as a chemotherapeutic strategy for treatment of NPC should be explored further.

  3. Prognostic factors in nasopharyngeal carcinoma with synchronous liver metastasis: a retrospective study for the management of treatment

    International Nuclear Information System (INIS)

    To retrospectively analyze the prognosis of patients with nasopharyngeal carcinoma (NPC) initially presenting with liver metastasis, in order to identify independent prognostic factors to facilitate management of treatment. Eighty-five patients with untreated NPC and synchronous liver metastasis, initially diagnosed between January 2000 and December 2009, were selected for this retrospective study. Seventy-eight received systemic chemotherapy, 32 underwent subsequent radiotherapy of the primary tumor, and 18 received local therapy for metastatic lesions. Clinical features, laboratory parameters and treatment modalities were compared by univariate and multivariate analyses. The median survival time was 19.0 months and the 3-year overall survival rate was 14.1%. The overall response and disease control rates were 70.4% and 86.4%, respectively. Significant predictors of short survival were KPS ≤ 70 (P = 0.03), serum lactate dehydrogenase levels >245 IU/l (P = 0.01) and poor response to chemotherapy (P < 0.01). In contrast, significantly longer survival rates were achieved by patients having at least six chemotherapy cycles compared to those receiving <6 cycles (3-year OS: 18.3% vs. 7.1%; P < 0.01), and patients receiving radiotherapy of the primary tumor following complete or partial response to chemotherapy (3-year OS: 30.8% vs. 3.8%, P < 0.01). Five key independent factors were identified and sub-classified as potential prognostic indicators for NPC with liver metastases. Progressive treatments of systemic chemotherapy and radiotherapy at the primary tumor could prolong survival in the subset of patients having fewer negative prognosticators

  4. Long-term effects on carotid intima-media thickness after radiotherapy in patients with nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Vascular abnormalities are the predominant histologic changes associated with radiation in nasopharyngeal carcinoma (NPC). This study examined if the duration after radiotherapy correlates with the progression of carotid intima-media thickness (IMT) and investigated its relationship with inflammatory markers. One hundred and five NPC patients post-radiotherapy for more than one year and 25 healthy control subjects were examined by B-mode ultrasound for IMT measurement at the far wall of the common carotid artery (CCA). Surrogate markers including lipid profile, HbA1c, and high sensitive C-reactive protein (hs-CRP) were assessed. The IMT of CCA was significantly increased in NPC patients and carotid plaque was detected in 38 NPC patients (38/105, 36.2%). Significant risk factors for carotid plaques included age, duration after radiotherapy, and HbA1c levels. Age, duration after radiotherapy, hs-CRP, HbA1c, and platelet count positively correlated with IMT. The cut-off value of age and duration after radiotherapy for the presence of plaque was 52.5 years and 42.5 months, respectively. In NPC subjects, multiple linear regression analysis revealed that age, gender, duration after radiotherapy and platelet counts were independently associated with CCA IMT. After adjustments for age, gender and platelet counts, IMT increased in a linear manner with duration after radiotherapy. Radiation-induced vasculopathy is a dynamic and progressive process due to late radiation effects. Extra-cranial color-coded duplex sonography can be part of routine follow-up in NPC patients aged ≥50 years at 40 months post-radiotherapy

  5. A rare polymorphism of the COX7B2 gene in a Cantonese family with nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    Nasopharyngeal carcinoma(NPC)is the most common head and neck cancer in southern China,and the genetic susceptibility is believed to play an important role in the aetiology of this malignancy.In our previous studies,one candidate susceptibility locus has been mapped to chromosome 4p11-p14 in a subset of NPC families.In the present study,we screened the cytochrome oxidase VIIb2(COX7B2)gene which resides in this region and investigated the relationship of single nucleotide polymorphisms(SNPs)of this gene with these familial NPC patients.We identified five novel SNPs in this gene,among them -158101G>T and -157322G>A in promoter region,-109602A>G in intron 2,78T>A in exon 3,and 354T>A in 3'-untranslational region.The change 78T>A at codon 26 which leads to CAT26CAA(His26GIn)was shared by patients from family 31 that carried the susceptibility haplotype,but not found in cases from other NPC families nor in sporadic cases.However,the frequency of allele A was relatively Iow in normal controls both from Guangdong and eastern China(0.45% and 0.26%,respectively),and this variant was not found in pooled DNA samples from the white and the black population.Protein sequence alignment showed that the 26His of COX7B2 protein is consistent among different species.Our results suggested that the codon 26 of COX7B2 gene might be conservative during the process of evolution,and the rare variation His26GIn was probably associated with the high risk in NPC pedigree 31.

  6. The principal genetic determinants for nasopharyngeal carcinoma in China involve the HLA class I antigen recognition groove.

    Directory of Open Access Journals (Sweden)

    Minzhong Tang

    Full Text Available Nasopharyngeal carcinoma (NPC is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS, independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa variants across the major histocompatibility complex-HLA-A, HLA -B, and HLA -C class I genes (P(HLA-A-aa-site-62 = 7.4 × 10(-29; P (HLA-B-aa-site-116 = 6.5 × 10(-19; P (HLA-C-aa-site-156 = 6.8 × 10(-8 respectively. Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9 as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China.

  7. Cognitive Function Before and After Intensity-Modulated Radiation Therapy in Patients With Nasopharyngeal Carcinoma: A Prospective Study

    International Nuclear Information System (INIS)

    Purpose: To evaluate the effects of radiation therapy (RT) on neurocognitive function in patients with nasopharyngeal carcinoma (NPC). Methods and Materials: Thirty patients with NPC treated with intensity-modulated RT were included. Dose-volume histograms of the temporal lobes were obtained in every patient. Neurocognitive tests were administered individually to each patient 1 day before initiation of RT and at least 12 months after completion of RT. Cognitive functioning status was evaluated as change in scores over time. Results: Among the total of 30 patients, 23 patients (76.7%) had significantly lower post-RT cognitive functioning scores compared with their pre-RT scores (p = 0.033). The cognitive functioning scores had significantly declined in the domains of short-term memory, language abilities, and list-generating fluency (p = 0.020, 0.023, and 0.001, respectively). Compared with patients with a mean dose to the temporal lobes of 36 Gy or less, patients with a mean dose of greater than 36 Gy had a significantly greater reduction in cognitive functioning scores (p = 0.017). Patients in whom V60 of the temporal lobes (i.e., the percentage of the temporal lobe volume that had received >60 Gy) was greater than 10% also had a greater reduction in cognitive functioning scores than those in whom V60 was 10% or less (p = 0.039). Conclusions: The results of our study indicated that RT could have deleterious effects on cognitive function in patients with NPC. Efforts should be made to reduce the radiation dose and irradiated volume of temporal lobes without compromising the coverage of target volume.

  8. MicroRNA-200a mediates nasopharyngeal carcinoma cell proliferation through the activation of nuclear factor-κB.

    Science.gov (United States)

    Shi, Zhuliang; Hu, Zhiqiang; Chen, Delu; Huang, Jie; Fan, Jie; Zhou, Subo; Wang, Xin; Hu, Jiandao; Huang, Fei

    2016-02-01

    In nasopharyngeal carcinoma (NPC), the nuclear factor-κB (NF-κB) signaling pathway is highly active. The constitutive activation of NF-κB prompts malignant cell proliferation, and microRNAs are considered an important mediator in regulating the NF-κB signaling pathway. The current study investigated the effect of microRNA-200a (miR-200a) on NF-κB activation. Reverse transcription-quantitative polymerase chain reaction was used to quantify the relative level of miR-200a in NPC tissue samples and CNE2 cells. An MTT assay was used to investigate the effect of miR-200a on cell proliferation. To investigate the activation of NF-κB, western blotting was used to measure the protein levels of NF-κB and its downstream targets. To identify the target genes of miR-200a, a luciferase reporter assay was used. The current study demonstrated that miR-200a was upregulated in NPC tissue samples and cell lines. Overexpression of miR-200a resulted in the proliferation of CNE2 cells. Western blot analysis indicated that the protein levels of p65 increased when CNE2 cells were transfected with miR-200a mimics. Additionally, the downstream targets of miR-200a were upregulated, including vascular cell adhesion molecule, intercellular adhesion molecule and monocyte chemoattractant protein-1. The luciferase assay indicated that IκBα was the target gene of miR-200a. In conclusion, miR-200a was demonstrated to enhance NPC cell proliferation by activating the NF-κB signaling pathway.

  9. Using neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy for nasopharyngeal carcinoma with intracranial invasion to protect critical normal tissue

    International Nuclear Information System (INIS)

    To investigate the feasibility of neoadjuvant chemotherapy and replanning intensity-modulated radiotherapy (IMRT) for intracranial invasion nasopharyngeal carcinoma (NPC). From June 2007 to January 2012, 32 patients with intracranial invasion NPC treated with TPF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, 5-FU 2500 mg/m2 every 3 weeks for 3 cycles) neoadjuvant chemotherapy, and replanning IMRT with concurrent chemotherapy were retrospectively studied. The first IMRT plan for each patient was generated based on the original planning CT scan acquired before the start of treatment. Because of tumor shrinkage during radiotherapy, modified gross tumor volume of primary tumor (GTV-P) and high risk clinical target volume (CTV-H), and a new plan was generated and used to complete the course of IMRT. The DVHs of IMRT plan with or without replanning were compared. There weren’t statistically significant differences in the V95, D-mean, D-95, and D-99 to the modified PTVGTV-P and PTVCTV-H with and without replanning IMRT. Replanning reduced the doses to the brain stem, optic nerve, optic chiasm and temporal lobe. Objective responses were 100.0% 3 months after completion of radiotherapy. Acute toxicities were well tolerated, except for the relatively high incidence of neutropenia. The 2-year local control rates and distant-metastasis free survival were 88.2% (95% CI, 72.9% to 100.0%) and 89.6% (95% CI, 75.9% to 100.0%). Neoadjuvant chemotherapy and replanning IMRT according to tumor shrinkage during the treatment is essential to ensure safe doses to normal tissues, and produces encouraging outcome for intracranial invasion NPC

  10. Curcumin analogue T83 exhibits potent antitumor activity and induces radiosensitivity through inactivation of Jab1 in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus–associated malignancy that is most common in East Asia, Africa, and Alaska. Radiotherapy is the main treatment option; unfortunately, disease response to concurrent radiotherapy and chemotherapy varies among patients with NPC, and in many cases, NPC becomes resistant to radiotherapy. Our previous studies indicated that Jab1/CSN5 was overexpressed and plays a role in the pathogenesis and radiotherapy resistance in NPC. Therefore, it is important to seek for innovative therapeutics targeting Jab1/CSN5 for NPC. In this study, we explored the antitumor effect of a curcumin analogue T83 in NPC, and found T83 exhibits antitumor activity and induces radiosensitivity through inactivation of Jab1 in NPC. NPC cell viability and proliferation were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. Cell cycle distribution was detected with use of flow cytometry. Apoptosis was examined by using the Annexin V/propidium iodide staining assay and cleavage poly(ADP-ribose polymerase (PARP) and cleavage caspase-3 expression. Jab1 expression was examined by Western blotting. A growth inhibitory effect was observed with T83 treatment in a dose- and time-dependent manner. T83 significantly induced G2/M arrest and apoptosis in NPC. In addition, T83 inhibited Jab1 expression and sensitized NPC cells to radiotherapy. Our data indicate that T83 exhibits potent inhibitory activity in NPC cells and induces radiotherapy sensitivity. Thus, T83 has translational potential as a chemopreventive or therapeutic agent for NPC

  11. Correlation of a hypoxia based tumor control model with observed local control rates in nasopharyngeal carcinoma treated with chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Avanzo, Michele; Stancanello, Joseph; Franchin, Giovanni; Sartor, Giovanna; Jena, Rajesh; Drigo, Annalisa; Dassie, Andrea; Gigante, Marco; Capra, Elvira [Department of Medical Physics, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Research and Clinical Collaborations, Siemens Healthcare, Erlangen 91052 (Germany); Department of Radiation Oncology, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Department of Medical Physics, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Oncology Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ (United Kingdom); Department of Medical Physics, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Department of Radiation Oncology, Centro di Riferimento Oncologico, Aviano 33081 (Italy); Department of Medical Physics, Centro di Riferimento Oncologico, Aviano 33081 (Italy)

    2010-04-15

    Purpose: To extend the application of current radiation therapy (RT) based tumor control probability (TCP) models of nasopharyngeal carcinoma (NPC) to include the effects of hypoxia and chemoradiotherapy (CRT). Methods: A TCP model is described based on the linear-quadratic model modified to account for repopulation, chemotherapy, heterogeneity of dose to the tumor, and hypoxia. Sensitivity analysis was performed to determine which parameters exert the greatest influence on the uncertainty of modeled TCP. On the basis of the sensitivity analysis, the values of specific radiobiological parameters were set to nominal values reported in the literature for NPC or head and neck tumors. The remaining radiobiological parameters were determined by fitting TCP to clinical local control data from published randomized studies using both RT and CRT. Validation of the model was performed by comparison of estimated TCP and average overall local control rate (LCR) for 45 patients treated at the institution with conventional linear-accelerator-based or helical tomotherapy based intensity-modulated RT and neoadjuvant chemotherapy. Results: Sensitivity analysis demonstrates that the model is most sensitive to the radiosensitivity term {alpha} and the dose per fraction. The estimated values of {alpha} and OER from data fitting were 0.396 Gy{sup -1} and 1.417. The model estimate of TCP (average 90.9%, range 26.9%-99.2%) showed good correlation with the LCR (86.7%). Conclusions: The model implemented in this work provides clinicians with a useful tool to predict the success rate of treatment, optimize treatment plans, and compare the effects of multimodality therapy.

  12. HLA class II alleles and the presence of circulating Epstein-Barr virus DNA in greek patients with nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Background and purpose: nasopharyngeal carcinoma (NPC) represents a seldom malignancy in most developed countries. Nevertheless, NPC receives an endemic form in concrete racial entities. The aims of this study were to detect the presence of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood of NPC patients, to molecularly define human leukocyte antigens (HLA) DRB1*, DQA1* and DQB1* allele frequencies, and, finally, to determine whether the genetic predisposition of an individual to NPC depends on the liability to EBV infection. Patients and methods: a total of 101 patients of Hellenic origin and nationality, with histologically proven NPC, participated in this study. EBV-DNA detection was also applied in 66 patients with EBV-related malignancies (Hodgkin's [HL] and non-Hodgkin's lymphoma [NHL]) and infectious mononucleosis (IM), as well as in 80 healthy EBV-seropositive controls. Results: 81% of the NPC patients, 77.8% with HL, 72.2% with NHL, and 66.7% with IM were EBV-DNA positive, whereas the EBV genome was detected only in 15% of the healthy controls. These differences were statistically significant in all cases. Analysis of HLA class II antigens showed decreased frequency of the DRB1*07 (p 0.003), DQA1*0103 (p = 0.002), and DQA1*0201 (p = 0.003) alleles among NPC patients. A significant association between the HLA-DR/DQ alleles and the presence of EBV-DNA in peripheral whole blood was not established. Conclusion: circulating EBV-DNA and specific HLA class II alleles may predispose to or protect from NPC. However, the results of this study suggest that the genetic predisposition of an individual to NPC is independent of the liability to EBV infection. (orig.)

  13. Plasma uric acid and tumor volume are highly predictive of outcome in nasopharyngeal carcinoma patients receiving intensity modulated radiotherapy

    International Nuclear Information System (INIS)

    The combined predictive value of plasma uric acid and primary tumor volume in nasopharyngeal carcinoma (NPC) patients receiving intensity modulated radiation therapy (IMRT) has not yet been determined. In this retrospective study, plasma uric acid level was measured after treatment in 130 histologically-proven NPC patients treated with IMRT. Tumor volume was calculated from treatment planning CT scans. Overall (OS), progression-free (PFS) and distant metastasis-free (DMFS) survival were compared using Kaplan-Meier analysis and the log rank test, and Cox multivariate and univariate regression models were created. Patients with a small tumor volume (<27 mL) had a significantly better DMFS, PFS and OS than patients with a large tumor volume. Patients with a high post-treatment plasma uric acid level (>301 μmol/L) had a better DMFS, PFS and OS than patients with a low post-treatment plasma uric acid level. Patients with a small tumor volume and high post-treatment plasma uric acid level had a favorable prognosis compared to patients with a large tumor volume and low post-treatment plasma uric acid level (7-year overall OS, 100% vs. 48.7%, P <0.001 and PFS, 100% vs. 69.5%, P <0.001). Post-treatment plasma uric acid level and pre-treatment tumor volume have predictive value for outcome in NPC patients receiving IMRT. NPC patients with a large tumor volume and low post-treatment plasma uric acid level may benefit from additional aggressive treatment after IMRT

  14. Prognosticators and Risk Grouping in Patients with Lung Metastasis from Nasopharyngeal Carcinoma: A more accurate and appropriate assessment of prognosis

    International Nuclear Information System (INIS)

    Lung metastases arising from nasopharyngeal carcinomas (NPC) have a relatively favourable prognosis. The purpose of this study was to identify the prognostic factors and to establish a risk grouping in patients with lung metastases from NPC. A total of 198 patients who developed lung metastases from NPC after primary therapy were retrospectively recruited from January 1982 to December 2000. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Actuarial survival rates were plotted against time using the Kaplan-Meier method, and log-rank testing was used to compare the differences between the curves. The median overall survival (OS) period and the lung metastasis survival (LMS) period were 51.5 and 20.9 months, respectively. After univariate and multivariate analyses of the clinical variables, age, T classification, N classification, site of metastases, secondary metastases and disease-free interval (DFI) correlated with OS, whereas age, VCA-IgA titre, number of metastases and secondary metastases were related to LMS. The prognoses of the low- (score 0-1), intermediate- (score 2-3) and high-risk (score 4-8) subsets based on these factors were significantly different. The 3-, 5- and 10-year survival rates of the low-, intermediate- and high-risk subsets, respectively (P < 0.001) were as follows: 77.3%, 60% and 59%; 52.3%, 30% and 27.8%; and 20.5%, 7% and 0%. In this study, clinical variables provided prognostic indicators of survival in NPC patients with lung metastases. Risk subsets would help in a more accurate assessment of a patient's prognosis in the clinical setting and could facilitate the establishment of patient-tailored medical strategies and supports

  15. A study of radiation-induced cerebral vascular injury in nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis.

    Directory of Open Access Journals (Sweden)

    Jianhong Ye

    Full Text Available PURPOSE: To investigate radiation-induced carotid and cerebral vascular injury and its relationship with radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma (NPC patients. METHODS AND MATERIALS: Fifty eight NPC patients with radiation-induced temporal lobe necrosis (TLN were recruited in the study. Duplex ultrasonography was used to scan bilateral carotid arterials to evaluate the intima-media thickness (IMT and occurrence of plaque formation. Flow velocities of bilateral middle cerebral arteries (MCAs, internal carotid arteries (ICAs and basal artery (BA were estimated through Transcranial Color Doppler (TCD. The results were compared with data from 33 patients who were free from radiation-induced temporal lobe necrosis after radiotherapy and 29 healthy individuals. RESULTS: Significant differences in IMT, occurrence of plaques of ICAs and flow velocities of both MCAs and ICAs were found between patients after radiotherapy and healthy individuals (p<0.05. IMT had positive correlation with post radiation interval (p = 0.049. Compared with results from patients without radiation-induced TLN, the mean IMT was significantly thicker in patients with TLN (p<0.001. Plaques were more common in patients with TLN than patients without TLN (p = 0.038. In addition, flow velocities of MCAs and ICAs in patients with TLN were much faster (p<0.001, p<0.001. Among patients with unilateral TLN, flow velocity of MCAs was significantly different between ipsilateral and contralateral sides to the lesion (p = 0.001. CONCLUSION: Thickening of IMT, occurrence of plaque formation and hemodynamic abnormality are more common in patients after radiotherapy, especially in those with TLN, compared with healthy individuals.

  16. Cytokine and immunoglobulin production by PWM-stimulated peripheral and tumor-infiltrating lymphocytes of undifferentiated nasopharyngeal carcinoma (NPC patients

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    Bouzouita Kamel

    2004-09-01

    Full Text Available Abstract Background Undifferentiated Nasopharyngeal Carcinoma (NPC patients show a characteristic pattern of antibody responses to the Epstein-Barr virus (EBV which is regularly associated with this tumor. However, no EBV-specific cytotoxic activity is detectable by the standard chromium-release assay at both peripheral and intratumoral levels. The mechanisms underlying this discrepancy between the humoral and cellular immune responses in NPC are still unknown, but might be related to an imbalance in immunoregulatory interleukin production. In this report, we investigated the ability of peripheral (PBL and tumor- infiltrating (TIL lymphocytes of undifferentiated NPC patients to produce in vitro three interleukins (IL-2, IL-6, IL-10 and three immunoglobulin isotypes (IgM, IgG, IgA. Methods Lymphocytes from 17 patients and 17 controls were cultured in the presence of Pokeweed mitogen (PWM for 12 days and their culture supernatants were tested for interleukins and immunoglobulins by specific enzyme-linked immunosorbent assays (ELISA. Data were analysed using Student's t-test and probability values below 5% were considered significant. Results The data obtained indicated that TIL of NPC patients produced significantly more IL-2 (p = 0,0002, IL-10 (p = 0,020, IgM (p= 0,0003 and IgG (p Conclusion Taken together, our data reinforce the possibility of an imbalance in immunoregulatory interleukin production in NPC patients. An increased ability to produce cytokines such as IL-10 may underlie the discrepancy between humoral and cellular immune responses characteristic of NPC.

  17. Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts

    International Nuclear Information System (INIS)

    Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented. In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models. Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R. Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC

  18. Elevated peripheral blood lymphocyte-to-monocyte ratio predicts a favorable prognosis in the patients with metastatic nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Rou Jiang; Pei-Yu Huang; Yan-Qun Xiang; Xing Lu; Lin Wang; Wei-Xiong Xia; Hai-Qiang Mai; Ming-Yuan Chen; Xiu-Yu Cai; Zhong-Han Yang; Yue Yan; Xiong Zou; Ling Guo; Rui Sun; Dong-Hua Luo; Qiu-Yan Chen

    2015-01-01

    Introduction:Patients with metastatic nasopharyngeal carcinoma (NPC) have variable survival outcomes. We have previously shown that an elevated peripheral blood lymphocyte-to-monocyte ratio (LMR) is associated with an increased metastatic risk in patients with primary NPC. The present study aimed to investigate the prognostic value of pretreatment LMR in a large cohort of metastatic NPC patients. Methods:Clinical data of 672 patients with metastatic NPC diagnosed between January 2003 and December 2009 were analyzed. The peripheral lymphocyte and monocyte counts were retrieved, and LMR was calculated. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate COX proportional hazards analyses were performed to evaluate the association of LMR with overall survival (OS). Results:Univariate analysis revealed that an elevated absolute lymphocyte count (≥1.390 × 109/L) and LMR (≥2.475) as well as a decreased monocyte count (<0.665 × 109/L) were significantly associated with prolonged OS. Multivariate Cox proportional hazard analysis showed that LMR (hazard ratio [HR]=0.50, 95%confidence interval [CI]=0.41–0.60, P<0.001), absolute lymphocyte count (HR=0.77, 95%CI=0.64–0.93, P=0.007), and monocyte count (HR=1.98, 95%CI=1.63–2.41, P<0.001) were independent prognostic factors. By stratification analyses, only LMR remained a significant predictor of prognosis. Conclusion:We identified pretreatment LMR as an independent prognostic factor for patients with metastatic NPC. Independent validation of our findings is needed.

  19. Telephone information-memory-concentration test used in evaluating cognitive function of patients with nasopharyngeal carcinoma after radiotherapy

    International Nuclear Information System (INIS)

    Objective: To investigate the telephone information-memory-concentration test (TIMCT) in evaluating the cognitive function of patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Methods: The cognitive function were evaluated by TIMCT and mini mental state examination (MMSE) in 2 weeks for 30 normal persons and 90 NPC patients. And the 90 NPC patients were divided into the 3 months, 2 years and 5 years after radiotherapy groups. All patients were carried out firstly face to face interview and telephone interview 1 time after 2 weeks. Results: The correlation coefficient of all groups between TIMCT(telephone) and TIMCT (face to face) were bigger (R=0.850) when MMSE wasn't control variable. And the correlation coefficients between TIMCT (telephone) and TIMCT (face to face) were lower (R=0.366) when MMSE was control variable. As for examining time was classification factor, TIMCT (telephone) and TIMCT (face to face) were analyzed by partial correlation analysis. Only normal group was correlated with group of 3 months after radiotherapy and group of 2 years after radiotherapy wasn't correlated with group of 5 years after radiotherapy (R=0.447,0.970,0.200 and 0.062). In addition, the difference plot of TIMCT(telephone) and TIMCT (face to face) indicated that telephone was consistent with face to face interview (MMSE≥28). Both telephone and face to face interview reflected the cognitive function downtrend of research objects. Conclusions: TIMCT (telephone), TIMCT(face to face) and MMSE (face to face) can reflect cognitive function downterend of patients with NPC after radiotherapy. But TIMCT(telephone) used in clinical screening cognitive function impairment of patients with NPC after radiotherapy should be improved further. (authors)

  20. Type 2 Diabetic Mellitus Is a Risk Factor for Nasopharyngeal Carcinoma: A 1:2 Matched Case–Control Study

    Science.gov (United States)

    Qiu, Wen-Ze; Tian, Yun-Hong; Zhang, Wei-Jun; Cao, Ka-Jia

    2016-01-01

    Background Diabetes has been identified as an adverse prognostic variable which associated with an increased mortality in various cancers, including colorectal, lung, and breast cancers. However, previous studies provided inconsistent results on the association between diabetes and nasopharyngeal carcinoma (NPC). The main aim of this study was to investigate the associations between diabetes mellitus and the survival of NPC patients. Methods This study was designed as a 1:2 matched case–control study. Cases were patients who met the criteria for the diagnosis of type 2 diabetic mellitus (DM) below. Controls, matched 1:2, were patients who were normoglycemic (NDM). The survival rates were assessed by Kaplan–Meier analysis, and the survival curves were compared using a log-rank test. Multivariate analysis was conducted using the Cox proportional hazard regression model. Results Both locoregional relapse-free survival (LRRFS) and disease-free survival (DFS) in the NDM group were higher than that in the DM group (p = 0.001 and p = 0.033). Additionally, subset analyses revealed that the differences in OS, LRRFS, and DFS were all significant between the two groups in the N0-N1 subset (p = 0.007, p =.000 and p = 0.002). The LRRFS was higher in the NDM group in the III-IV, T3-T4 and N0-N1 subsets (p = 0.004, p = 0.002 and p =.000). In T3-T4 subset, the NDM group experienced higher DFS than the DM group (p = 0.039). In multivariate analysis, T stage and N stage were found to be independent predictors for OS, DMFS and DFS; chemotherapy was a significant prognostic factor for DMFS and DFS, age for OS, and diabetes for LRRFS and DFS. Conclusions Type 2 diabetic mellitus is associated with poorer prognosis among patients with NPC. PMID:27760202

  1. HLA class II alleles and the presence of circulating Epstein-Barr virus DNA in greek patients with nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Karanikiotis, C. [424 Army General Hospital, Thessaloniki (Greece); Daniilidis, M.; Karyotis, N.; Nikolaou, A. [AHEPA Hospital, Aristotle Univ. of Thessaloniki School of Medicine (Greece); Bakogiannis, C. [Hygeia Hospital, Athens (Greece); Economopoulos, T. [' Attikon' Univ. Hospital, Athens (Greece); Murray, S. [Metropolitan Hospital, Athens (Greece); Papamichael, D. [Bank of Cyprus Oncology Center, Nicosia, Cyprus (Greece); Samantas, E. [' Agii Anargiri' Cancer Hospital, Athens (Greece); Skoura, L. [' Hippokration' Hospital, Thessaloniki (Greece); Tselis, N.; Zamboglou, N. [Dept. of Radiotherapy, Offenbach Hospital (Germany); Fountzilas, G. [' Papageorgiou' Hospital, Aristotle Univ. of Thessaloniki School of Medicine (Greece)

    2008-06-15

    Background and purpose: nasopharyngeal carcinoma (NPC) represents a seldom malignancy in most developed countries. Nevertheless, NPC receives an endemic form in concrete racial entities. The aims of this study were to detect the presence of Epstein-Barr virus DNA (EBV-DNA) in peripheral blood of NPC patients, to molecularly define human leukocyte antigens (HLA) DRB1*, DQA1* and DQB1* allele frequencies, and, finally, to determine whether the genetic predisposition of an individual to NPC depends on the liability to EBV infection. Patients and methods: a total of 101 patients of Hellenic origin and nationality, with histologically proven NPC, participated in this study. EBV-DNA detection was also applied in 66 patients with EBV-related malignancies (Hodgkin's [HL] and non-Hodgkin's lymphoma [NHL]) and infectious mononucleosis (IM), as well as in 80 healthy EBV-seropositive controls. Results: 81% of the NPC patients, 77.8% with HL, 72.2% with NHL, and 66.7% with IM were EBV-DNA positive, whereas the EBV genome was detected only in 15% of the healthy controls. These differences were statistically significant in all cases. Analysis of HLA class II antigens showed decreased frequency of the DRB1*07 (p = 0.003), DQA1*0103 (p = 0.002), and DQA1*0201 (p = 0.003) alleles among NPC patients. A significant association between the HLA-DR/DQ alleles and the presence of EBV-DNA in peripheral whole blood was not established. Conclusion: circulating EBV-DNA and specific HLA class II alleles may predispose to or protect from NPC. However, the results of this study suggest that the genetic predisposition of an individual to NPC is independent of the liability to EBV infection. (orig.)

  2. Combination of autoantibodies against NY-ESO-1 and viral capsid antigen immunoglobulin A for improved detection of nasopharyngeal carcinoma.

    Science.gov (United States)

    Peng, Yu-Hui; Xu, Yi-Wei; Qiu, Si-Qi; Hong, Chao-Qun; Zhai, Tian-Tian; Li, En-Min; Xu, Li-Yan

    2014-09-01

    Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Southern China and Southeast Asia, and early detection remains a challenge. Autoantibodies have been found to precede the manifestations of symptomatic cancer by several months to years, making their identification of particular relevance for early detection. In the present study, the diagnostic value of serum autoantibodies against NY-ESO-1 in NPC patients was evaluated. The study included 112 patients with NPC and 138 normal controls. Serum levels of autoantibodies against NY-ESO-1 and classical Epstein-Barr virus marker, viral capsid antigen immunoglobulin A (VCA-IgA), were measured by enzyme-linked immunosorbent assay. Measurement of autoantibodies against NY-ESO-1 and VCA-IgA demonstrated a sensitivity/specificity of 42.9/94.9% [95% confidence interval (CI), 33.7-52.6/89.4-97.8%] and 55.4/95.7% (95% CI, 45.7-64.7/90.4-98.2%), respectively. The area under receiver operating characteristic curve for autoantibodies against NY-ESO-1 (0.821; 95% CI, 0.771-0.871) was marginally lower than that for VCA-IgA (0.860; 95% CI, 0.810-0.910) in NPC. The combination of autoantibodies against NY-ESO-1 and VCA-IgA yielded an enhanced sensitivity of 80.4% (95% CI, 71.6-87.0%) and a specificity of 90.6% (95% CI, 84.1-94.7%). Moreover, detection of autoantibodies against NY-ESO-1 could differentiate early-stage NPC patients from normal controls. Our results suggest that autoantibodies against NY-ESO-1 may serve as a potential biomarker, as a supplement to VCA-IgA, for the screening and diagnosis of NPC.

  3. Integrative Medicine Therapy in Treatment of Nasopharyngeal Carcinoma%鼻咽癌的中西医结合诊治

    Institute of Scientific and Technical Information of China (English)

    周洪建

    2015-01-01

    Objective To explore the clinical effect of combining traditional Chinese and Western medicine in the treatment of na-sopharyngeal carcinoma. Methods Clinical data of 70 patients with nasopharyngeal carcinoma between January 2005 and January 2015 in our hospital were retrospective analyzed. According to the different ways of treatment the patients were divided into obser-vation group and the control group two groups. The reference group of 35 patients received radiotherapy or chemotherapy alone, while patients in the observation group of 35 cases were treated with the therapy of combination of Chinese traditional and Western medicine. The clinical curative effect of the two groups were compared. Results The total number of effective cases of observation group patients was 34 cases, the total efficiency of 94.29%, the total number of valid reference cases were 28 cases, the total effec-tive rate was 80%, the observation of patients in the treatment group the total efficiency was higher than that of the reference group;to observe the toxic and side effects of radiotherapy group were(2.1±0.4)score, referring to the side reaction of radiothera-py patients score was (2.9±0.3) points, the toxic reaction and side effect of radiotherapy in patients group was significantly lower than that in the reference group score. The observation group lymph node extinction rate was 95.83%, a reference group of lymph node response rate was 85.71% in the observation group, the extinction rate of lymph node should be significantly higher than the reference group. Conclusion The combination of traditional Chinese and Western medicine clinical effect in the treatment of na-sopharyngeal carcinoma was obviously, is superior to simple radiotherapy and chemotherapy, and the toxic and side effect of radio-therapy of small, good treatment effect, worth in clinical application.%目的:探究中西医结合治疗鼻咽癌的的临床效果,为临床提供参考。方法回顾性分析2005年1

  4. High-Sensitivity C-Reactive Protein Complements Plasma Epstein-Barr Virus Deoxyribonucleic Acid Prognostication in Nasopharyngeal Carcinoma: A Large-Scale Retrospective and Prospective Cohort Study

    International Nuclear Information System (INIS)

    Purpose: To evaluate the effects of combining the assessment of circulating high-sensitivity C-reactive protein (hs-CRP) with that of Epstein-Barr virus DNA (EBV DNA) in the pretherapy prognostication of nasopharyngeal carcinoma (NPC). Patients and Methods: Three independent cohorts of NPC patients (training set of n=3113, internal validation set of n=1556, and prospective validation set of n=1668) were studied. Determinants of disease-free survival, distant metastasis–free survival, and overall survival were assessed by multivariate analysis. Hazard ratios and survival probabilities of the patient groups, segregated by clinical stage (T1-2N0-1M0, T3-4N0-1M0, T1-2N2-3M0, and T3-4N2-3M0) and EBV DNA load (low or high) alone, and also according to hs-CRP level (low or high), were compared. Results: Elevated hs-CRP and EBV DNA levels were significantly correlated with poor disease-free survival, distant metastasis–free survival, and overall survival in both the training and validation sets. Associations were similar and remained significant after excluding patients with cardiovascular disease, diabetes, and chronic hepatitis B. Patients with advanced-stage disease were segregated by high EBV DNA levels and high hs-CRP level into a poorest-risk group, and participants with either high EBV DNA but low hs-CRP level or high hs-CRP but low EBV DNA values had poorer survival compared with the bottom values for both biomarkers. These findings demonstrate a significant improvement in the prognostic ability of conventional advanced NPC staging. Conclusion: Baseline plasma EBV DNA and serum hs-CRP levels were significantly correlated with survival in NPC patients. The combined interpretation of EBV DNA with hs-CRP levels led to refinement of the risks for the patient subsets, with improved risk discrimination in patients with advanced-stage disease

  5. High-Sensitivity C-Reactive Protein Complements Plasma Epstein-Barr Virus Deoxyribonucleic Acid Prognostication in Nasopharyngeal Carcinoma: A Large-Scale Retrospective and Prospective Cohort Study

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Lin-Quan [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou (China); Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou (China); Li, Chao-Feng [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou (China); Department of Information Technology, Sun Yat-sen University, Guangzhou (China); Chen, Qiu-Yan; Zhang, Lu [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou (China); Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou (China); Lai, Xiao-Ping; He, Yun; Xu, Yun-Xiu-Xiu; Hu, Dong-Peng; Wen, Shi-Hua; Peng, Yu-Tuan [ZhongShan School of Medicine, Sun Yat-sen University, Guangzhou (China); Chen, Wen-Hui [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou (China); Liu, Huai; Guo, Shan-Shan; Liu, Li-Ting [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou (China); Department of Nasopharyngeal Carcinoma, Sun Yat-sen University, Guangzhou (China); Li, Jing [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou (China); Zhang, Jing-Ping [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou (China); Department of Clinical Laboratory, Sun Yat-sen University, Guangzhou (China); and others

    2015-02-01

    Purpose: To evaluate the effects of combining the assessment of circulating high-sensitivity C-reactive protein (hs-CRP) with that of Epstein-Barr virus DNA (EBV DNA) in the pretherapy prognostication of nasopharyngeal carcinoma (NPC). Patients and Methods: Three independent cohorts of NPC patients (training set of n=3113, internal validation set of n=1556, and prospective validation set of n=1668) were studied. Determinants of disease-free survival, distant metastasis–free survival, and overall survival were assessed by multivariate analysis. Hazard ratios and survival probabilities of the patient groups, segregated by clinical stage (T1-2N0-1M0, T3-4N0-1M0, T1-2N2-3M0, and T3-4N2-3M0) and EBV DNA load (low or high) alone, and also according to hs-CRP level (low or high), were compared. Results: Elevated hs-CRP and EBV DNA levels were significantly correlated with poor disease-free survival, distant metastasis–free survival, and overall survival in both the training and validation sets. Associations were similar and remained significant after excluding patients with cardiovascular disease, diabetes, and chronic hepatitis B. Patients with advanced-stage disease were segregated by high EBV DNA levels and high hs-CRP level into a poorest-risk group, and participants with either high EBV DNA but low hs-CRP level or high hs-CRP but low EBV DNA values had poorer survival compared with the bottom values for both biomarkers. These findings demonstrate a significant improvement in the prognostic ability of conventional advanced NPC staging. Conclusion: Baseline plasma EBV DNA and serum hs-CRP levels were significantly correlated with survival in NPC patients. The combined interpretation of EBV DNA with hs-CRP levels led to refinement of the risks for the patient subsets, with improved risk discrimination in patients with advanced-stage disease.

  6. Sequence analysis of the Epstein-Barr virus (EBV BRLF1 gene in nasopharyngeal and gastric carcinomas

    Directory of Open Access Journals (Sweden)

    Jing Yongzheng

    2010-11-01

    Full Text Available Abstract Background Epstein-Barr virus (EBV has a biphasic infection cycle consisting of a latent and a lytic replicative phase. The product of immediate-early gene BRLF1, Rta, is able to disrupt the latency phase in epithelial cells and certain B-cell lines. The protein Rta is a frequent target of the EBV-induced cytotoxic T cell response. In spite of our good understanding of this protein, little is known for the gene polymorphism of BRLF1. Results BRLF1 gene was successfully amplified in 34 EBV-associated gastric carcinomas (EBVaGCs, 57 nasopharyngeal carcinomas (NPCs and 28 throat washings (TWs samples from healthy donors followed by PCR-direct sequencing. Fourteen loci were found to be affected by amino acid changes, 17 loci by silent nucleotide changes. According to the phylogenetic tree, 5 distinct subtypes of BRLF1 were identified, and 2 subtypes BR1-A and BR1-C were detected in 42.9% (51/119, 42.0% (50/119 of samples, respectively. The distribution of these 2 subtypes among 3 types of specimens was significantly different. The subtype BR1-A preferentially existed in healthy donors, while BR1-C was seen more in biopsies of NPC. A silent mutation A/G was detected in all the isolates. Among 3 functional domains, the dimerization domain of Rta showed a stably conserved sequence, while DNA binding and transactivation domains were detected to have multiple mutations. Three of 16 CTL epitopes, NAA, QKE and ERP, were affected by amino acid changes. Epitope ERP was relatively conserved; epitopes NAA and QKE harbored more mutations. Conclusions This first detailed investigation of sequence variations in BRLF1 gene has identified 5 distinct subtypes. Two subtypes BR1-A and BR1-C are the dominant genotypes of BRLF1. The subtype BR1-C is more frequent in NPCs, while BR1-A preferentially presents in healthy donors. BR1-C may be associated with the tumorigenesis of NPC.

  7. MR analysis of nasopharyngeal carcinoma: correlation of the pattern of tumor extent at the primary site with the distribution of metastasized cervical lymph nodes. Preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Wakisaka, M.; Mori, H. [Dept. of Radiology, Oita Medical University, Hasama-machi (Japan); Fuwa, N. [Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya (Japan); Matsumoto, A. [Dept. of Radiology, Oita Medical University, Hasama-machi (Japan); Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya (Japan)

    2000-06-01

    The purpose of this study was to correlate the pattern of tumor extent of nasopharyngeal carcinoma at the primary site on magnetic resonance (MR) imaging with the distribution of cervical lymph node metastasis. MR images of 32 patients with biopsy-proven nasopharyngeal carcinoma were reviewed and classified into five patterns of tumor extent in correlation with the distribution of cervical lymphadenopathy. The assessment of cervical lymph node metastasis was done on the basis of the computed tomography (CT) findings. The tumor volume was also correlated with the occurrence of contralateral lymphadenopathy. Of the 32 patients, five (16 %) presented as type 1, tumor limited to the nasopharyngeal mucosa; 12 (38 %) as type 2 a, tumor which had invaded either lateral side but did not extend over the roof of nasopharynx; three (9 %) as type 2 b, tumor which had invaded bilaterally across the midline but did not extend over the roof of nasopharynx; three (9 %) as type 2 c, tumor which had invaded mainly the skull base but did not cross the midline; and nine (28 %) as type 3, tumor which had extended anteriorly to the nasal cavity without invasion. Twenty-five patients (78 %) demonstrated cervical lymphadenopathy. Patients with type 1, type 2 b and type 3 spread had frequent bilateral cervical lymphadenopathy; those with type 2 a had only ipsilateral lymphadenopathy. There was statistical significance (P < 0.005) regarding the existence of contralateral lymphadenopathy with midline tumors as well as the absence of contralateral cervical lymphadenopathy with non-midline tumors. This study therefore suggests that the distribution of metastasized lymph nodes depends on the pattern of tumor extent at the primary site. (orig.)

  8. 2β-(Isobutyryloxyflorilenalin, a Sesquiterpene Lactone Isolated from the Medicinal Plant Centipeda minima, Induces Apoptosis in Human Nasopharyngeal Carcinoma CNE Cells

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    Miaoxian Su

    2009-06-01

    Full Text Available Centipeda minima is a medicinal plant reputed in China as a remedy for nasopharyngeal carcinoma (NPC. In this study, bioactivity-guided fractionation of the anti-NPC compound(s from C. minima led to the isolation of 2β-(isobutyryloxyflorilenalin (IF, a sesquiterpene lactone. IF showed significant dose- and time- dependent inhibition on the growth of the human nasopharyngeal carcinoma epithelia cells (CNE. It induced apoptosis in CNE cells, as shown by the accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation, caspase-3 activation and PARP cleavage. Such induction was associated with the depletion of mitochondrial membrane potential (ΔΨm and the release of cytochrome c to cytosol to regulate the expression of Bcl-2 family proteins. These activities led to the cleavage of caspases and the trigger of cell death process. Overall, IF in C. minima showed potent antiproliferative effect of C. minima on NPC cells, suggesting that the plant deserves more extensive investigation for its potential medicinal application.

  9. Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fogg, Mark [Department of Medicine, Brigham and Women' s Hospital (United States); Murphy, John R. [Departments of Medicine and Microbiology, Boston University School of Medicine, Boston, MA 02118 (United States); Lorch, Jochen; Posner, Marshall [Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Wang, Fred, E-mail: fwang@research.bwh.harvard.edu [Department of Medicine, Brigham and Women' s Hospital (United States); Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 (United States)

    2013-07-05

    Epstein–Barr virus (EBV) is associated with multiple malignancies including nasopharyngeal carcinoma (NPC). In nasopharynx cancer, CD8+ T cells specific for EBV Nuclear Antigen-1 (EBNA-1) and Latent Membrane Protein 2 (LMP2) are important components of anti-tumor immunity since both are consistently expressed in NPC. We have previously shown that EBNA-1-specific CD8+ T cell responses were suppressed in NPC patients compared to healthy controls. We now find that CD8+ T cell responses specific for LMP2 are also abnormal in NPC patients, and both EBNA-1- and LMP2-specific responses are suppressed by regulatory T cells (Treg). EBNA-1 and LMP2-specific CD8+ T cell responses, as well as immune control of EBV-infected cells in vitro, could be restored by the depletion of Tregs and by use of a clinically approved drug targeting Tregs. Thus, in vivo modulation of Tregs may be an effective means of enhancing these anti-tumor immune responses in NPC patients. - Highlights: • Viral proteins are tumor antigens in Epstein–Barr virus associated Nasopharyngeal Carcinoma. • CD8+ T cell responses against EBV proteins EBNA-1 and LMP2 are suppressed in NPC patients. • T regulatory cells are responsible for suppressing EBV immunity in NPC patients. • Depletion of Tregs with Ontak can rescue EBV-specific CD8+ T cell responses in NPC patients. • This clinically approved drug may be effective for enhancing anti-tumor immunity in NPC patients.

  10. A novel multifunctional nanocomposite C225-conjugated Fe3O4/Ag enhances the sensitivity of nasopharyngeal carcinoma cells to radiotherapy

    Institute of Scientific and Technical Information of China (English)

    Di Zhao; Xinchen Sun; Jinglong Tong; Jun Ma; Xiaodong Bu; Ruizhi Xu; Renhua Fan

    2012-01-01

    Radiotherapy is the major treatment for nasopharyngeal carcinoma,a malignant tumor of epithelial origin.In this process,a tracer with high sensitivity is pivotal for diagnostic imaging in radiotherapy.Here,we designed a novel muitifunctional magnetic silver nanocomposite,Fe3O4/Ag conjugated to an epidermal growth factor receptor-specific antibody (C225),which can be potentially used for synchronous cancer therapy and diagnosis via magnetic resonance imaging.Characteristics of Fe3O4/Ag/C225 were determined by transmission electron microscopy,energy dispersive X-ray spectroscopy,ultraviolet spectra,and dynamic light scattering.The results demonstrated that Fe3O4/Ag/C225 nanoparticles were spherical and dispersed well in water.The activity of C225 was preserved~80% in the Fe3O4/Ag/C225 nanoparticles.Futhermore,we tested the cytotoxicity and radiosensitivity of the nanocomposite for human nasopharyngeal carcinoma cell lines (CNEs) in vitro.MTT analysis revealed that Fe3O4/Ag/C225 could inhibit the proliferation of CNEs in a dose-and timedependent manner.The clonogenic assay indicated that Fe3O4/Ag/C225 combined with X-ray treatment could increase the sensitivity of CNEs to irradiation.In a summary,the novel multifunctional nanocomposite Fe3O4/Ag/C225 might be a potential radiosensitizer for treating malign tumors in the clinic.

  11. Intracavitary brachytherapy significantly enhances local control of early T-stage nasopharyngeal carcinoma: the existence of a dose-tumor-control relationship above conventional tumoricidal dose

    International Nuclear Information System (INIS)

    Purpose: To study the efficacy of intracavitary brachytherapy (ICT) in early T-stage nasopharyngeal carcinoma (NPC). Methods and Materials: All T1 and T2 (nasal infiltration) NPC treated with a curative intent from 1984 to 1996 were analyzed (n = 509). One hundred sixty-three patients were given ICT after radical external radiotherapy (ERT) (Group A). They were compared with 346 patients treated by ERT alone (Group B). The ERT delivered the tumoricidal dose (uncorrected BED-10 ≥75 Gy) to the primary tumor and did not differ between the two groups in technique or dosage. The ICT delivered a dose of 18-24 Gy in 3 fractions over 15 days to a point 1 cm perpendicular to the midpoint of the plane of the sources. ICT was used to treat local persistence diagnosed at 4-6 weeks after ERT (n = 101) or as an adjuvant for the complete responders to ERT (n = 62). Results: The two groups did not differ in patients' age or sex, rate of distant metastasis, rate of regional failure, overall survival, or the follow-up duration. However, Group A had significantly more T2 lesions and Group B had significantly more advanced N-stages. Local failure was significantly less (crude rates 6.75% vs. 13.0%; 5-year actuarial rates 5.40% vs. 10.3%) and the disease-specific mortality was significantly lower (crude rates 14.1 % vs. 21.7%; 5-year actuarial rates 11.9% vs. 16.4%) in Group A compared to Group B. Multivariate analysis showed that the ICT was the only significant prognostic factor predictive for fewer local failures (Cox regression p = 0.0328, risk ratio = 0.49, 95% confidence interval (95% CI) = 0.256-0.957). However, when ICT was excluded from the Cox regression model, the total physical dose or the total BED-10 uncorrected for tumor repopulation during the period of radiotherapy became significant in predicting ultimate local failure rate. The two groups were comparable in the incidence rates of each individual chronic radiation complication and the actuarial cumulative rate of

  12. A case-control study of nasopharyngeal carcinoma in the high background radiation areas of Yangjiang, China

    International Nuclear Information System (INIS)

    The main purposes of this study were to identify the major determinants of nasopharyngeal carcinoma (NPC) in the high-background radiation areas (HBRA) in Yangjiang, China and to evaluate their potential confounding effects on the NPC risk associated with exposure to high background radiation. A matched case-control study was conducted using those who died of NPC during the period 1987-1995. Two controls were randomly selected for each case from those who died from causes other than malignancies and external causes. Cases and their controls were matched with respect to sex and the years of birth and death (±5 years). Study subjects' next-of-kin were interviewed using a standardized questionnaire to collect information on socioeconomic status, dietary habits, tobacco smoking and alcohol consumption, disease history, pesticide use, medical X-ray exposure, the family history of NPC and so on. We succeeded in interviewing 97 cases and 192 controls. Univariate conditional logistic regression analysis showed that NPC risk was associated with the consumption of salted fish, homemade pickles, and fermented soy beans, education levels, the history of chronic rhinitis, and the family history of NPC. Multivariate conditional logistic regression analysis revealed that education levels (Odds ratio (OR) for middle school or higher levels vs. no school education=3.8, 95% CI=1.2 to 11.8), salted fish intake (OR=3.2, 95% CI=1.7 to 6.1), the history of chronic rhinitis (OR=3.6, 95% CI=1.3 to 10.1), and the family history of NPC (OR=14.2, 95% CI=2.7 to 73.4) were independent risk factors of NPC. Tobacco smoking (OR=1.2, 95% CI=0.7 to 2.1), and alcohol consumption (OR=0.9, 95% CI=0.5 to 1.9) were not significantly related to NPC risk. The ORs of NPC risk comparing HBRA and a nearby control area before and after adjustment for the major risk determinants identified in the present study were 0.86 (95% CI=0.50 to 1.50) and 0.87 (95% CI=0.45 to 1.67), respectively. Salted fish intake was

  13. Matrix metalloproteinase 12 is induced by heterogeneous nuclear ribonucleoprotein K and promotes migration and invasion in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Overexpression of heterogeneous nuclear ribonucleoprotein K (hnRNP K), a DNA/RNA binding protein, is associated with metastasis in nasopharyngeal carcinoma (NPC). However, the mechanisms underlying hnRNP K-mediated metastasis is unclear. The aim of the present study was to determine the role of matrix metalloproteinase (MMP) in hnRNP K-mediated metastasis in NPC. We studied hnRNP K-regulated MMPs by analyzing the expression profiles of MMP family genes in NPC tissues and hnRNP K-knockdown NPC cells using Affymetrix microarray analysis and quantitative RT-PCR. The association of hnRNP K and MMP12 expression in 82 clinically proven NPC cases was determined by immunohistochemical analysis. The hnRNP K-mediated MMP12 regulation was determined by zymography and Western blot, as well as by promoter, DNA pull-down and chromatin immunoprecipitation (ChIP) assays. The functional role of MMP12 in cell migration and invasion was demonstrated by MMP12-knockdown and the treatment of MMP12-specific inhibitor, PF-356231. MMP12 was overexpressed in NPC tissues, and this high level of expression was significantly correlated with high-level expression of hnRNP K (P = 0.026). The levels of mRNA, protein and enzyme activity of MMP12 were reduced in hnRNP K-knockdown NPC cells. HnRNP K interacting with the region spanning −42 to −33 bp of the transcription start site triggered transcriptional activation of the MMP12 promoter. Furthermore, inhibiting MMP12 by MMP12 knockdown and MMP12-specific inhibitor, PF-356231, significantly reduced the migration and invasion of NPC cells. Overexpression of MMP12 was significantly correlated with hnRNP K in NPC tissues. HnRNP K can induce MMP12 expression and enzyme activity through activating MMP12 promoter, which promotes cell migration and invasion in NPC cells. In vitro experiments suggest that NPC metastasis with high MMP12 expression may be treated with PF-356231. HnRNP K and MMP12 may be potential therapeutic markers for NPC, but

  14. Association of the p53 or GSTM1 polymorphism with the risk of nasopharyngeal carcinoma: A meta-analysis

    Science.gov (United States)

    WU, MUYUN; HUANG, SHUJING; LIU, DONG; PENG, MIAO; YANG, FAN; WANG, XICHENG

    2016-01-01

    p53 and glutathione S-transferase M1 (GSTM1) are the most popular suppressor genes. Several previous studies demonstrated positive associations of these gene polymorphisms with numerous cancer types, including hepatocellular cancer, while the association between p53/GSTM1 polymorphisms and the nasopharyngeal carcinoma (NPC) risk was inconsistent and underpowered. However, no studies investigating the combinational effect of these two genes on NPC risk were performed. To confirm the effects of p53 and GSTM1 polymorphisms on the risk of NPC, a meta-analysis of all the available previous studies associating p53 and GSTM1 with the risk of NPC was performed. A comprehensive search of PubMed, Web of Science and SD database until November 2014 was performed to identify the relevant studies. The data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. Finally, five studies with 1,419 cases and 1,707 controls were included for the p53 polymorphism and three studies with 837 cases and 1,299 controls were included for the GSTM1 polymorphism. Regarding p53, a significantly increased NPC risk was observed in the overall population (C vs. G, OR, 1.245; 95% CI, 1.045–1.483; P=0.014; additive models: CC vs. GG, OR, 1.579; 95% CI, 1.100–2.265; P=0.013 and CG vs. GG, OR, 1.230; 95% CI, 1.039–1.456; P=0.016; dominant model, OR, 1.321; 95% CI, 1.127–1.549; P=0.001; recessive model, OR, 1.429; 95% CI, 1.017–2.009; P=0.040). Concerning GSTM1, a significantly increased NPC risk was observed in the overall population (null versus non-null, OR, 1.282; 95% CI, 1.075–1.530; P=0.006). In the subgroup analyses stratified by the source of controls, a significant association of p53 with NPC risk was also demonstrated, while no association with GSTM1 was observed. Therefore, the p53 G72C polymorphism may have a susceptible

  15. SKF95365 induces apoptosis and cell-cycle arrest by disturbing oncogenic Ca2+ signaling in nasopharyngeal carcinoma cells

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    Zhang J

    2015-10-01

    Full Text Available Jinyan Zhang,1 Jiazhang Wei,2 Qian He,3 Yan Lin,1 Rong Liang,1 Jiaxiang Ye,1 Zhe Zhang,4 Yongqiang Li1 1Department of Medical Oncology, Affiliated Cancer Hospital of Guangxi Medical University, 2Department of Otolaryngology-Head and Neck Oncology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 3Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Japan; 4Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China Background: Aberrant modulation of store-operated calcium ions (Ca2+ entry promotes the progression of human malignancies. Previously, we reported that the blockage of store-operated Ca2+ entry inhibited epidermal growth factor (EGF-stimulated migration and distant metastasis in nasopharyngeal carcinoma (NPC cells. However, the effects of pharmacological blocker on other Ca2+ signaling-regulated malignant characteristics in NPC cells remained poorly understood. Methods: We examined the effects of SKF96365, an inhibitor of store-operated Ca2+ channel, on EGF-launched Ca2+ signaling in two NPC cell lines. We determined the effects of SKF96365 on cell proliferation, colony formation, apoptosis, and cell-cycle status in vitro. We further elucidated the antitumor activity of SKF96365 in xenograft-bearing mice. Results: It was found that SKF96365 disturbed the thapsigargin (TG-stimulated Ca2+ release from endoplasmic reticulum and the subsequent Ca2+ influx. SKF96365 alone stimulated Ca2+ responses merely due to endoplasmic reticulum-released Ca2+. SKF96365 promoted cell mortality, inhibited colony formation, and induced apoptosis and cell-cycle arrest, while blunting the EGF-evoked Ca2+ signaling. Furthermore, we confirmed that SKF96365 reduced NPC xenograft growth while activating caspase-7-related apoptotic pathway. Conclusion: SKF96365 exerts multiple antitumor

  16. Interleukins, laminin and epstein - barr virus latent membrane protein 1 (EBV LMP1 Promote metastatic phenotype in nasopharyngeal carcinoma

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    Khoo Alan SB

    2010-10-01

    Full Text Available Abstract Background Nasopharyngeal carcinoma (NPC is a type of neoplasm that is highly prevalent in East Asia and Africa with Epstein-Barr virus (EBV, genetic, and dietary factors implicated as possible aetiologic factors. Previous studies suggested the association of certain cytokines with the invasion and metastatic properties of NPC. The present study examined the roles of EBV latent membrane protein-1 (LMP1, interleukin-6 (IL-6, interleukin-10 (IL-10, transforming growth factor-beta 1 (TGF-β1 and laminin in the regulation of matrix-metalloproteinases (MMPs and vascular endothelial growth factor (VEGF in NPC. The effects of these factors on bmi-1, an oncogene, and ngx6, a tumour suppressor gene, were also investigated. Methods TW01 cells expressing LMP1 (TW01-LMP1 were established via transfection with the B95.8 EBV LMP1 gene. Both TW01 and TW01-LMP1 cells were treated with 100 pg/ml IL-6, 1000 pg/ml IL-10 and 100 pg/ml TGF-β1, separately and also in combination at their respective concentration for 48 hours. Treated cells were subjected to laminin adherence assay. The cells were also cultured with and without laminin and assayed for MMP-3, MMP-9 and VEGF production using enzyme-linked immunosorbent assay (ELISA. The cellular apoptotic property was analysed using caspase-3 apoptosis assay. The expression of bmi-1 and ngx6 gene was investigated using real time reverse transcriptase polymerase chain reaction. Results LMP1 was found to reduce the adherence of NPC cells towards laminin (p bmi-1 and suppressed the expression of ngx6. Conclusions We conclude that IL-6 reduced cell adherence towards laminin and increased MMP-9 production in NPC cells. Our data suggested that EBV LMP1 was able to confer resistance of apoptosis and increased MMP-9 production in NPC cells. When cultured on laminin, TW01 cells expressing the EBV LMP1 (TW0-LMP1 that were treated with IL-6 at 100 pg/ml displayed increased MMP-9 production, up-regulation of bmi-1

  17. A case-control study of nasopharyngeal carcinoma among inhabitants in high background radiation areas of Yangjiang, China

    International Nuclear Information System (INIS)

    Objective: The purpose of the study was to confirm and explore main risk factors of nasopharyngeal carcinoma (NPC) in cohort members of the investigated areas, and evaluate effects of confounding factors on cancer risk associated with exposure to high background radiation. Methods: The deceased cases of NPC during the period of 1987-1995 were selected as study subjects for each of whom two controls were randomly selected from potential control subjects who died from causes other than malignant tumors and external causes, and matched for sex and years of birth and death (within 5 years). Using structure questionnaire, the relevant information including socioeconomic status, dietary habits, smoking and alcohol consumption, history of illness, agricultural use of pesticide, medical X-ray exposure and familial history of NPC were collected. The odds ratio (OR) was used as a measure of association between NPC and the risk factors. Results: 102 cases and 202 controls were successfully investigated. Single factor conditional logistic regression analysis showed that the occurrence of NPC was closely positively associated with intake of salted fish, pickles, fermented soybeans, cured meats, history of chronic rhinitis and familial history of NPC. Further multiple conditional logistic regression analysis turned out that intake of salted fish, history of chronic rhinits and familial history of NPC were the independent risk factors of NPC. After controlling for history of chronic rhinits and familial history of NPC, the results based on multiple conditional logistic regression analysis from high background radiation, intake of salted fish and fermented soybeans, tobacco smoking and alcohol consumption showed that only intake of salted fish was a significant risk factor (OR = 2.8, 95% CI 1.52-5.18), tobacco smoking (OR = 1.2, 95% CI 0.65-2.22), alcohol consumption (OR = 0.83, 95% CI 0.38-1.78) and exposure to high background radiation (OR= 0.86, 95% CI 0.44-1.68) did not

  18. {sup 18}F-fluorodeoxyglucose positron emission tomography for predicting tumor response to radiochemotherapy in nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Su, Meng; Wei, Hangping; Lin, Ruifang; Zhang, Xuebang; Zou, Changlin [The First Affiliated Hospital of Wenzhou Medical University, Department of Radiation Oncology and Chemotherapy, Wenzhou, Zhejiang province (China); Zhao, Liang [The First Affiliated Hospital of Wenzhou Medical University, Department of Positron Emission Tomography, Wenzhou, Zhejiang province (China)

    2015-08-15

    The aim of this study was to evaluate the value of {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in predicting tumor response to radiochemotherapy in nasopharyngeal carcinoma (NPC). From July 2012 to March 2014, 46 NPC patients who had undergone PET scanning before receiving definitive intensity-modulated radiotherapy (IMRT) treatment in our hospital were enrolled. Factors potentially affecting tumor response to treatment were studied by multiple logistic regression analysis. After radiochemotherapy, 32 patients had a clinical complete response (CR), making the CR rate 69.6 %. Multiple logistic regression analysis demonstrated that the maximal standard uptake value (SUV{sub max}) of the primary tumor was the only factor related to tumor response (p = 0.001), and that the logistic model had a high positive predictive value (90.6 %). The area under the receiver operating characteristic (ROC) curve was 0.809, with a best cutoff threshold at 10.05. Patients with SUV{sub max} ≤ 10 had a higher CR rate than those with SUV{sub max} > 10 (p < 0.001). The SUV{sub max} of the primary tumor before treatment is an independent predictor of tumor response in NPC. (orig.) [German] Das Ziel der Arbeit bestand darin, den Wert der {sup 18}F-Fluordesoxyglukose-Positronenemissionstomographie ({sup 18}F-FDG-PET) zur Vorhersage des Tumoransprechens auf eine Radiochemotherapie beim Nasopharynxkarzinom (NPC) zu beurteilen. Von Juli 2012 bis Maerz 2014 wurden 46 NPC-Patienten, die sich vor definitiver intensitaetsmodulierter Strahlentherapie (IMRT) in unserem Krankenhaus einem PET-Scan unterzogen hatten, in die Studie aufgenommen. Faktoren, die moeglicherweise das Tumoransprechen auf die Behandlung beeinflussen, wurden mittels multipler logistischer Regressionsanalyse untersucht. Nach der Radiochemotherapie hatten 32 Patienten eine klinisch komplette Remission (CR), so dass eine CR-Rate von 69,6 % erreicht wurde. Die multiple logistische Regressionsanalyse zeigte

  19. A case-control study of nasopharyngeal carcinoma in the high background radiation areas of Yangjiang, China

    Energy Technology Data Exchange (ETDEWEB)

    Zou Jianming; Zha Yongru [Guangdong Inst. of Prevention and Treatment of Occupational Diseases, Guangzhou (China); Sun Quanfu; Akiba, Suminori; Yuan Yongling; Tao Zufan; Wei Luxin; Sugahara, Tsutomu

    2000-10-01

    The main purposes of this study were to identify the major determinants of nasopharyngeal carcinoma (NPC) in the high-background radiation areas (HBRA) in Yangjiang, China and to evaluate their potential confounding effects on the NPC risk associated with exposure to high background radiation. A matched case-control study was conducted using those who died of NPC during the period 1987-1995. Two controls were randomly selected for each case from those who died from causes other than malignancies and external causes. Cases and their controls were matched with respect to sex and the years of birth and death ({+-}5 years). Study subjects' next-of-kin were interviewed using a standardized questionnaire to collect information on socioeconomic status, dietary habits, tobacco smoking and alcohol consumption, disease history, pesticide use, medical X-ray exposure, the family history of NPC and so on. We succeeded in interviewing 97 cases and 192 controls. Univariate conditional logistic regression analysis showed that NPC risk was associated with the consumption of salted fish, homemade pickles, and fermented soy beans, education levels, the history of chronic rhinitis, and the family history of NPC. Multivariate conditional logistic regression analysis revealed that education levels (Odds ratio (OR) for middle school or higher levels vs. no school education=3.8, 95% CI=1.2 to 11.8), salted fish intake (OR=3.2, 95% CI=1.7 to 6.1), the history of chronic rhinitis (OR=3.6, 95% CI=1.3 to 10.1), and the family history of NPC (OR=14.2, 95% CI=2.7 to 73.4) were independent risk factors of NPC. Tobacco smoking (OR=1.2, 95% CI=0.7 to 2.1), and alcohol consumption (OR=0.9, 95% CI=0.5 to 1.9) were not significantly related to NPC risk. The ORs of NPC risk comparing HBRA and a nearby control area before and after adjustment for the major risk determinants identified in the present study were 0.86 (95% CI=0.50 to 1.50) and 0.87 (95% CI=0.45 to 1.67), respectively. Salted fish

  20. Long-Term Outcomes of Early-Stage Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiotherapy Alone

    Energy Technology Data Exchange (ETDEWEB)

    Su Shengfa [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Department of Radiation Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou (China); Department of Oncology, GuiYang Medical College Hospital, Guiyang, Guizhou (China); Han Fei; Zhao Chong; Chen Chunyan; Xiao Weiwei; Li Jiaxin [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Department of Radiation Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou (China); Lu Taixiang, E-mail: ssf2010@sina.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Department of Radiation Oncology, Cancer Center, Sun Yat-Sen University, Guangzhou (China)

    2012-01-01

    Purpose: Reports of intensity-modulated radiotherapy (IMRT) for early-stage nasopharyngeal carcinoma (NPC) have been limited. The present study evaluated the long-term survival outcomes and toxicity of early-stage NPC patients treated with IMRT alone. Methods and Materials: Between February 2001 and January 2008, 198 early-stage (T1-T2bN0-N1M0) NPC patients had undergone IMRT alone. The data from these patients were retrospectively analyzed. The patients were treated to 68 Gy at 2.27 Gy/fraction prescribed to the planning target volume of the primary nasopharygeal gross tumor volume. The Radiation Therapy Oncology Group scoring system was used to assess the toxicity. Results: At a median follow-up of 50.9 months (range, 12-104), the 5-year estimated disease-specific survival, local recurrence-free survival, and distant metastasis-free survival rate was 97.3%, 97.7%, and 97.8%, respectively. The 5-year local recurrence-free survival rate was 100% for those with Stage T1 and T2a and 94.2% for those with Stage T2b lesions (p = 0.252). The 5-year distant metastasis-free survival rate for Stage T1N0, T2N0, T1N1, and T2N1 patients was 100%, 98.8%, 100%, and 93.8%, respectively (p = .073). All local recurrence occurred in patients with T2b lesions. Five patients developed distant metastasis. Of these 5 patients, 4 had had Stage T2bN1 disease and 1 had had Stage T2bN0 disease with retropharyngeal lymph node involvement. The most common acute toxicities were mainly Grade 1 or 2. At 24 months after IMRT, no Grade 3 or 4 xerostomia had developed, and 62 (96.9%) of 64 evaluated patients were free of trismus; only 2 patients (3.1%) had Grade 1 trismus. Radiation encephalopathy and cranial nerve injury were not observed. Conclusions: IMRT alone for Stage T1N0, T2N0, T1N1, and T2N1 yielded satisfactory survival outcomes with acceptable toxicity, and no differences were found in survival outcomes among these four subgroups. Patients with Stage T2b lesions might have relatively

  1. Proteomic analysis on N, N′-dinitrosopiperazine-mediated metastasis of nasopharyngeal carcinoma 6-10B cells

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    Li Yuejin

    2012-11-01

    Full Text Available Abstract Background Nasopharyngeal carcinoma (NPC has a high metastatic feature. N,N′-Dinitrosopiperazine (DNP is involved in NPC metastasis, but its mechanism is not clear. The aim of this study is to reveal the pathogenesis of DNP-involved metastasis. 6-10B cells with low metastasis are from NPC cell line SUNE-1, were used to investigate the mechanism of DNP-mediated NPC metastasis. Results 6-10B cells were grown in DMEM containing 2H4-L-lysine and 13C 6 15 N4-L-arginine or conventional L-lysine and L-arginine, and identified the incorporation of amino acid by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Labeled 6-10B cells were treated with DNP at 0 -18 μM to establish the non-cytotoxic concentration (NCC range. NCC was 0 -10 μM. Following treatment with DNP at this range, the motility and invasion of cells were detected in vitro, and DNP-mediated metastasis was confirmed in the nude mice. DNP increased 6-10B cell metastasis in vitro and vivo. DNP-induced protein expression was investigated using a quantitative proteomic. The SILAC-based approach quantified 2698 proteins, 371 of which showed significant change after DNP treatment (172 up-regulated and 199 down-regulated proteins. DNP induced the change in abundance of mitochondrial proteins, mediated the status of oxidative stress and the imbalance of redox state, increased cytoskeletal protein, cathepsin, anterior gradient-2, and clusterin expression. DNP also increased the expression of secretory AKR1B10, cathepsin B and clusterin 6-10B cells. Gene Ontology and Ingenuity Pathway analysis showed that DNP may regulate protein synthesis, cellular movement, lipid metabolism, molecular transport, cellular growth and proliferation signaling pathways. Conclusion DNP may regulate cytoskeletal protein, cathepsin, anterior gradient-2, and clusterin expression, increase NPC cells motility and invasion, is involved NPC metastasis.

  2. Volumetric modulated arc therapy for nasopharyngeal carcinoma: A dosimetric comparison with TomoTherapy and step-and-shoot IMRT

    International Nuclear Information System (INIS)

    Purpose: Volumetric modulated arc therapy (VMAT), a novel technique, employs a linear accelerator to conduct dynamic modulation rotation radiotherapy. The goal of this study was to compare VMAT with helical tomotherapy (HT) and step-and-shoot intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC) patients with regard to the sparing effect on organs at risk (OARs), dosimetric quality, and efficiency of delivery. Materials and methods: Twenty patients with NPC treated by HT were re-planned by VMAT (two arcs) and IMRT (7–9 fields) for dosimetric comparison. The target area received three dose levels (70, 60, and 54 Gy) in 33 fractions using simultaneous integrated boosts technique. The Philips Pinnacle Planning System 9.0 was adopted to design VMAT, using SmartArc as the planning algorithm. For a fair comparison, the planning target volume (PTV) coverage of the 3 plans was normalized to the same level. Dosimetric comparisons between VMAT, HT, and IMRT plans were analyzed to evaluate (1) coverage, homogeneity, and conformity of PTV, (2) sparing of OARs, (3) delivery time, and (4) monitor units (MUs). Results: The VMAT, HT, and IMRT plans had similar PTV coverage with an average of 96%. There was no significant difference between VMAT and HT in homogeneity, while the homogeneity indices of VMAT (1.06) and HT (1.06) were better than IMRT plans (1.07, p < 0.05). HT plans provided a better conformity index (1.17) than VMAT (1.28, p = 0.01) and IMRT (1.36, p = 0.02). When compared with IMRT, VMAT and HT had a better sparing effect on brain stem and spinal cord (p < 0.05). The effect of parotid sparing was similar between VMAT (mean = 26.3 Gy) and HT (mean = 27.5 Gy), but better than IMRT (mean = 31.3 Gy, p < 0.01). The delivery time per fraction for VMAT (5.7 min) were much lower than for HT (9.5 min, p < 0.01) and IMRT (9.2 min, p < 0.01). Conclusions: Our results indicate that VMAT provides better sparing of normal tissue, homogeneity, and

  3. Sequencing of DC-SIGN promoter indicates an association between promoter variation and risk of nasopharyngeal carcinoma in cantonese

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    Liu Wen-Sheng

    2010-11-01

    Full Text Available Abstract Background The dendritic cell-specific intercellular adhesion molecule 3 grabbing non-integrin (DC-SIGN is an important pathogen recognition receptor of the innate immune system. DC-SIGN promoter variants play important role in the susceptibility to various infectious diseases. Nasopharyngeal carcinoma (NPC is a malignancy that is common in southern China and whether DC-SIGN promoter variants have effects on susceptibility to NPC is still unknown. The aim of this study is to ascertain the potential involvement of DC-SIGN promoter single nucleotide polymorphisms (SNPs in NPC susceptibility. Methods We conducted a case control study based on Cantonese population including 444 NPC patients and 464 controls matched on age and sex. The 1041 bp of DC-SIGN promoter region was directly sequenced for all samples. Sequence alignment and SNP search were inspected using DNAStar analysis programs and haplotype frequencies were estimated in Haploview V 4.0. The associations between the SNPs and the risk of NPC were analyzed using chi-square test and non-conditional logistic regression analysis with SPSS 13.0 software. Results A total of six variants were observed in the DC-SIGN promoter region and DC-SIGN -139 GG and -939 AA were significantly associated with NPC risk with adjusted Odds Ratios (ORs of 2.10 (95% confidence interval [CI] = 1.23-3.59; P = 0.006 and 2.52 (1.29-4.93; P = 0.007 respectively and subjects carrying the risk allele DC-SIGN -871 G had 1.47-fold (95% CI = 1.14-1.90 increased risks of developing NPC (P = 0.003. Haplotype analysis revealed that h1 'AAAG' was significantly associated with protection against NPC (OR = 0.69; P = 0.0002 and the association was still significant when using 1000 permutation test runs (P = 0.001. Conclusions Our study indicated that DC-SIGN promoter variants appear to be involved in the susceptibility to NPC and the detailed mechanism of this effect need further studies.

  4. Advances in hepatocellular carcinoma: Nonalcoholic steatohepatitis-related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Fauzia; Z; Khan; Ryan; B; Perumpail; Robert; J; Wong; Aijaz; Ahmed

    2015-01-01

    An increase in the prevalence of obesity and diabetes mellitus has been associated with the rise in non-alcoholic fatty liver disease(NAFLD). Two-thirds of the obese and diabetic populations are estimated to develop NAFLD. Currently, NAFLD is the most common etiology for chronic liver disease globally. The clinical spectrum of NAFLD ranges from simple steatosis, an accumulation of fat greater than 5% of liver weight, to nonalcoholic steatohepatitis(NASH), a more aggressive form with necroinflammation and fibrosis. Among the patients who develop NASH, up to 20% may advance to cirrhosis and are at risk for complications of end-stage liver disease. One of the major complications observed in patients with NASH-related cirrhosis is hepatocellular carcinoma(HCC), which has emerged as the sixth most common cancer and second leading etiology of cancer-related deaths worldwide. The incidence of HCC in the United States alone has tripled over the last three decades. In addition, emerging data are suggesting that a small proportion of patients with NAFLD may be at higher risk for HCC in the absence of cirrhosis - implicating obesity and diabetes mellitus as potential risk factors for HCC.

  5. A large cohort study reveals the association of elevated peripheral blood lymphocyte-to-monocyte ratio with favorable prognosis in nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Jing Li

    Full Text Available BACKGROUND: Nasopharyngeal carcinoma (NPC is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20-30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients. METHODS: A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS, disease-free survival (DFS, distant metastasis-free survival (DMFS and loco-regional recurrence-free survival (LRRFS, respectively. RESULTS: Univariate analysis revealed that higher LMR level (≥ 5.220 was significantly associated with superior OS, DFS and DMFS (P values <0.001. The higher lymphocyte count (≥ 2.145 × 10(9/L was significantly associated with better OS (P = 0.002 and DMFS (P = 0.031, respectively, while the lower monocyte count (<0.475 × 10(9/L was associated with better OS (P = 0.012, DFS (P = 0.011 and DMFS (P = 0.003, respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR = 0.558, 95% confidence interval or 95% CI = 0.417-0.748; P<0.001, DFS (HR = 0.669, 95% CI = 0.535-0.838; P<0.001 and DMFS (HR = 0.543, 95% CI = 0.403-0.732; P<0.001, respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053 and DMFS (P = 0.080. CONCLUSIONS: The

  6. 鼻咽癌患者放射治疗后医院感染危险因素分析%Risk factors for nosocomial infections in nasopharyngeal carcinoma patients during radiotherapy

    Institute of Scientific and Technical Information of China (English)

    刘斌; 刘丽霞; 臧爱民; 田会平

    2014-01-01

    measures . RESULTS The nosocomial infections occurred in 159 patients during the radiotherapy with the infection rate of 88 .3% ,the incidence of the oral mucosa infections was 57 .9% ,the skin infections 27 .0% ,the upper respiratory tract infections 15 .1% .There were 45 (28 .3% ) patients with nosocomial infections on the fist week of radiothera-py .The incidence of nosocomial infections was 92 .6% in the patients with advanced nasopharyngeal carcinoma , significantly higher than 68 .8% in the patients with early nasopharyngeal carcinoma ,and there was significant difference (P<0 .05) .As compared with the oral mucosal reaction ,the radiodermatitis ,the body mass index ,the hemoglobin content ,or the total white blood cell counts ,the difference between the patients without nosocomial infections and the patients with severe nosocomial infections was significant (P< 0 .05) .Totally 496 strains of pathogens have been isolated ,including 398 (80 .2% ) strains of gram-negative bacteria ,42 (8 .5% ) strains of gram-positive bacteria ,and 56 (11 .3% ) strains of fungi .CONCLUSION The damages of radiation to the oral mu-cosa and skin of radiation fields are mainly involved in the nosocomial infections in the patients with nasopharynge-al carcinoma during the radiotherapy ,including the suppression of bone marrow and the damage to immunity ,re-sulting in the decreased resistance of the patients .It is necessary for the hospital to develop corresponding preven-tion measures according to the risk factors .

  7. Survival Analysis of Inpatients with Nasopharyngeal Carcinoma%鼻咽癌住院病例生存分析

    Institute of Scientific and Technical Information of China (English)

    陈梅英; 许可葵; 史百高; 廖先珍; 肖水源

    2012-01-01

    目的 分析湖南省某三甲医院1992-2005年鼻咽癌住院病例生存情况,为医生制订最佳治疗方案和鼻咽癌防控措施提供科学依据. 方法 收集湖南省某三甲医院1992-2005年鼻咽癌住院病例生存资料,采用SPSS 15.0和Excel 2003软件进行统计学分析. 结果 随访湖南省某三甲医院1992-2005年鼻咽癌住院病例4600例,随访截止时间为2010年12月31日,其中生存1740例,因本病死亡2819例,因其他原因死亡12例,中途失访24例,完全失访5例,随访应答率99.89%,数据删失率38.65%.1年生存率为93.47%,3年生存率为76.50%,5年生存率为62.69%,10年生存率为44.26%,15年生存率为38.88%,中位生存期为88.56个月(7.38年),最长生存期328.94个月(27.41年).采用Log-rank检验进行单因素分析显示不同性别、不同年龄、不同职业、不同文化程度、不同医保情况、不同临床分期、不同首次治疗方法、不同放疗进展情况鼻咽癌病例的生存率差异均有统计学意义(P<0.05).用Cox比例风险回归模型进行多因素分析显示不同年龄、不同性别、不同职业、不同临床分期、不同首次治疗方法鼻咽癌病例的生存率差异均有统计学意义(P<0.05).鼻咽癌预后主要影响因素为年龄、性别、职业、临床分期、首次治疗方法. 结论 湖南省某三甲医院1992-2005年鼻咽癌住院病例1、3、5年生存率相对于该院1987-1991年鼻咽癌住院病例1、3、5年生存率均有不同程度的提高;且该院1992-2005年鼻咽癌住院病例生存率同国内外相关文献报道相比,已达到或超过国内同级医院水平.%Objective To analyze the survival situation of inpatients with nasopharyngeal carcinoma (NPC) hospitalized in a 3A— grade hospital in Hunan Province from 1992 to 2005, and to provide scientific reference for formulating the optimum therapy, prevention and control measures for nasopharyngeal carcinoma. Methods The survival data

  8. Direct puncture embolization for the treatment of advanced juvenile nasopharyngeal angiofibroma

    International Nuclear Information System (INIS)

    Objective: To discuss the clinical application of direct puncture tumor embolization, which is used as a preoperative supplementary embolization,in treating juvenile nasopharyngeal angiofibroma (JNA). Methods: Twenty-nine patients were enrolled in this study. The shape and location of JNA were documented through the carotid angiography. Then, an 18-gauge needle was used to puncture the tumor. After the needle's position was confirmed to be in the right site and it was certain that no contrast leaked into the brain, 20-25% N-butyl-2-cyanoacrylate was slowly injected under fluoroscopic guidance until the entire JNA was fully filled with it. Results: Angiography revealed that the JNA received its blood supply from both the internal carotid artery and the external carotid artery in all 29 patients. After direct puncture tumor embolization the tumor stain became lessened and the distal end of the supplying arteries was not obviously displayed. Surgical resection was carried out within one week after embolization and the blood loss during the surgery was significantly reduced to 150-500 ml (mean 350 ml). Conclusion: Percutaneous direct puncture tumor embolization is a safe treatment for juvenile nasopharyngeal angiofibroma, it can effectively occlude the tumor's vessels and markedly reduce the blood loss during the surgery. (authors)

  9. Pro. Piao Bingkui’s Proven Case of Nasopharyngeal Carcinoma%朴炳奎教授治疗鼻咽癌验案一则

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    王兵; 赵彪; 乔红丽; 侯炜

    2013-01-01

    [目的]总结朴炳奎教授中医药辨证治疗鼻咽癌的临床经验。[方法]通过对临床验案的治疗思路以及处方用药分析,阐述朴炳奎教授活法圆机,运用扶正培元、抗癌解毒中药调治鼻咽癌的经验。[结果]本案朴炳奎教授根据患者既往治疗,证情变化,运用中医药长期维持治疗,使患者临床症状明显改善,生活质量显著提高,取得满意的临床疗效。[结论]朴炳奎教授对于鼻咽癌根据不同个体的不同病程时期进行辨证论治,扶正培本,解毒抗癌,减轻放、化疗的毒副反应,提高机体的抗病能力,减少复发转移率,具有重要临床指导意义。%[Objective] To sum up the clinical experience of treating nasopharyngeal carcinoma with TCM syndrome differentiation by professor Piao Bingkui. [Method] By analyzing the idea of Piao's therapy and medication of the proven case, it elaborates Pro. Piao Bingkui's clinical experience on using Chinese herbs, supporting the health and strengthening the root, anti-cancer and detoxification, to treat nasopharyngeal carcinoma. [Results] Pro. Piao Bingkui adepted at long-term maintenance therapy of TCM, which relieved the patient's clinical symptoms, and improved the quality of life significantly, and achieved satisfactory clinical outcome, according to the patient's previous treatment, the condition changes. [Conclusion] Pro. Piao Bingkui treated nasopharyngeal carcinoma depending on the different courses of individual, who used the methods of supporting the health and strengthening the root, anti-cancer and detoxification, could reduce the radiotherapy and chemotherapy toxicity, improve the body's resistance to disease and reduce the recurrence rate. It has important clinical significance.

  10. Research progress of molecular marker in metastasis of nasopharyngeal carcinoma%鼻咽癌转移相关分子标志物的研究进展

    Institute of Scientific and Technical Information of China (English)

    詹德超; 余忠华

    2015-01-01

    Nasopharyngeal carcinoma is a malignant neoplasm which arises from the mucosal epithelium cells of the nasopharynx,it is also one of the common malignant tumors in southern China. Most nasopharyngeal carcinomas are poorly differentiated carcinomas. Nasopharyngeal carcinomas are high degree of malignancy,which prone to distant metastasis.The invasion and metastasis of neoplasm are associated with the perverted movement of cells,which is a dy-namic process of biologic behavior interactions among adhesion,degradation and angiogenesis in cancer cells. Howev-er,the molecular mechanisms underlying NPC invasion and metastasis have not fully elucidated. With the development of Modem molecular biology,more and more new molecular markers in NPC,such as biomarkers have been gotten to know the related molecules expression and molecular regulation, which play important roles in screening tumor mark-ers with more high sensitivity and specificity,achieving early diagnosis ,predicting treatment prognoses and providing new therapeutic strategies to make it more pertinent in anti-tumor therapy. This study is aimed to review the research progress of molecular marker in metastasis of nasopharyngeal carcinoma.%鼻咽癌是一种来源于鼻黏膜上皮细胞的恶性肿瘤,是我国南方常见的恶性肿瘤之一。鼻咽癌大多数为低分化癌,恶性程度较高,易发生远处转移。国内外研究表明,肿瘤的侵袭和转移与细胞的异常运动有关,是肿瘤细胞的粘附、降解、运动以及血管生成等多种生物学行为互相作用的动态过程。但是NPC浸润转移的分子机制至今尚未完全阐明。随着现代分子生物学的发展,越来越多鼻咽癌转移的相关分子标志物逐渐被发现。深入了解这些分子标志物的表达及调控,筛选出对鼻咽癌具有较高敏感性、特异性并可进行早期诊断及评估预后的标记物,寻找出药物新靶点进行针对性更强的抗肿瘤治疗具有

  11. THE EXPRESSION OF CONNEXIN GENES IN NASOPHARYNGEAL CARCINOMA CELLS AND THE EFFECT OF RETINOIC ACID ON THE REGULATION OF THOSE GENES

    Institute of Scientific and Technical Information of China (English)

    JIANG Ning; BIN Liang-hua; TANG Xiang-na; ZHOU Ming; ZENG Zhao-yang; Li Gui-yuan

    1999-01-01

    Objective: To detect which members in the connexin gene family are expressed in nasopharyngeal carcinoma (NPC) cell line HNE1, and the mechanism by which those genes are specifically switched on and off during retinoic acid (RA) induction. Methods: Establishing the cell growth curves of NPC cells. Observing the effect of RA on connexin genes by Northern hybridization. Results: Two genes Cx46 and Cx37, belonging to the connexin gene family, were expressed in HNE, The down-regulation of Cx46 and Cx37, up-regulation of RARa and growth inhibition was observed in HNE1, after exposure to RA. The gene expression and cell growth in HNE1 cells was restored after removal of RA. Conclusion: Two members of the connexin gene family: Cx37 and Cx46 were expressed in HNE1 cells, RA can inhibit the expression of those two genes mediated by RARa, and the effects of RA on HNE1 are reversible.

  12. Cells in G2/M phase increased in human nasopharyngeal carcinoma cell line by EBV-LMP1 through activation of NF-κB and AP-1

    Institute of Scientific and Technical Information of China (English)

    LIN DENG; JING YANG; XIAO RONG ZHAO; XI YUN DENG; LIANG ZENG; HUAN HUA GU; MIN TANG; YA CAO

    2003-01-01

    Although previous studies showed that the principal oncoprotein encoded by Epstein-Barr virus, latentmembrane protein 1(LMP1), could induce the nasopharyngeal carcinoma cells in G2/M phase increased, littleis known about the target molecules and mechanisms. The present study demonstrated that LMP1 couldinduce the accumulation of p53 protein and upregulate its transactivity in a dose dependent manner, whichresulted in the decrease of the kinase activity of cdc2/cyclin B complex and inducing arrest at G2/M phasethrough the activation of NF-κB and AP-1 signaling pathways, and the effect of NF-κB was more obviousthan that of AP-1. This study provided some significant evidence for further elucidating the molecularmechanisms that LMP1 had effects on the surveillance mechanism of cell cycle and promoting the survivalof transformed cells and tumorigenesis.

  13. Salvage surgery for nasopharyngeal cancer

    Institute of Scientific and Technical Information of China (English)

    Raymond K.Tsang; William I.Wei

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is a special type of head and neck cancer with a widely variable geographical variation in incidence.The central location of the tumor inside the head coupled with the radiosensitivity of the tumor to radiation made radiation therapy the first choice in primary treatment of NPC.Advances in radiotherapy and chemotherapy have markedly improved the local control of NPC.Unfortunately, a small but significant number of patients still suffered from loco-regional failures that would be amenable to re-treatment.Traditional form of retreatment was to employ a second course of radiation.The efficacy of re-irradiation to treat local of regional recurrent NPC has been suboptimal.Moreover, the local tissue had already received a high dose of radiation and the second radiation could result in radiation toxicities to the local tissue, leading to significant complications.Surgical salvage, on the other hand, could spare the patients from complications of retreatment.Due to the difficult access of the nasopharynx, various surgical approaches had been devised for nasopharyngectomy.The maxillary swing approach had the largest published experience with over 300 cases from various centers.In the recent decade, the endoscopic approach with or without robotic assistance had gained popularity for resecting small, centrally located recurrences.This minimally invasive approach further reduced the morbidity for treating locally recurrent NPC.Nodal recurrences had been a rare entity after the introduction of modern radiotherapy technique and concurrent chemotherapy.Treatment of nodal failure with second radiation has dismal results.Surgical removal of the lymph node harboring the recurrence should be in the form of a formal radical neck dissection.In cases of extensive nodal recurrence where microscopic disease may be present after a formal neck dissection, additional radiotherapy can be delivered with after-loading brachytherapy.Surgical treatment played a

  14. 全人源抗鼻咽癌噬菌体单链抗体的筛选与鉴定%Screening and characterization of human scFv antibodies against nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    李艳东; 谢平丽; 王甲甲; 李跃辉; 胡锦跃; 李官成

    2009-01-01

    目的 从全人源抗鼻咽癌噬菌体抗体库中筛选特异性单链抗体(ScFv),并对其特异性进行鉴定.方法 通过噬菌体表面展示技术把ScFv表达在噬菌体表面,以鼻咽癌细胞作为抗原,用抗原递减法,通过"吸附-洗脱-扩增"过程筛选并富集特异性抗体,及ELISA筛选,获得特异阳性克隆进行免疫组化鉴定并测序.结果 通过对抗体库进行三轮正负淘洗和富集后,随机挑选4212个克隆进行ELISA,发现3个克隆对CNE2呈强阳性反应,而与人正常细胞系HUVEC等呈弱阳性反应或不反应.对克隆HNSAO33进一步进行免疫细胞化学验证,结果与ELISA反应一致;免疫组织化学鉴定表明克隆HNSAO33与鼻咽癌组织和鼻咽组织阳性率的差别有统计学意义.结论 通过淘选富集、ELISA和免疫化学鉴定获得特异性较强的噬菌体克隆,为鼻咽癌发病机制的研究和临床诊断以及治疗奠定了基础.%Objective To screen the anti-nasopharyngeal carcinoma scFv from a human anti-nasopharyngeal carcinoma single-chain phage antibody library, and identify its characteristics. Methods The single-chain phage antibody library was subjected to three rounds of positive and negative cell panning and enrichment, and then it was selected by ELISA. The binding specificity of phage antibodies with naso-pharyngeal carcinoma cells was confirmed by immunohistochemistry. Results After panning, enrichment and testing by ELISA, 3 phage an-tibody clones reacting with CNE2 more strongly than HUVEC and NP69 were picked out from 4212 clones. One clone, HNSAO33, was fur-ther analyzed after DNA sequencing. The results of immunohistochemistry with cultured cells were similar to those of ELISA. HNSAO33 spe-cifically reacted to nasopharyngeal carcinoma cells in most human nasopharyngeal carcinoma tissue sections except a few human normal naso-pharyngeal tissue sections. The distinction of positive rates was of a great statistical significance. Conclusion ELISA

  15. Nutritional Status and Nutritional Intervention of Patients with Nasopharyngeal Carcinoma%鼻咽癌患者的营养状况及营养干预

    Institute of Scientific and Technical Information of China (English)

    韦燕

    2013-01-01

    鼻咽癌患者在放化疗治疗时营养不足和营养风险问题比较普遍,营养不良反过来影响患者体质与行为能力,限制患者对治疗的依从性和耐受性.对住院的鼻咽癌患者进行营养筛查,能早期识别和确定存在营养风险和营养不良的患者,从而给予及时有效的营养支持.营养干预的时间是个体化很强的问题,不同患者对治疗的耐受性不同也决定了干预时间的个体化.营养干预的方式、干预的时机及持续的时间仍需更多的研究来进一步明确.%Undernutrition and nutritional risk of nasopharyngeal carcinoma patients during radiotherapy and chemotherapy are common.Undernutrition affects the patient's physical and capacity,limits the compliance and tolerance of the treatment.Nutritional screening for hospitalized patients with nasopharyngeal carcinoma can early i-dentify and determine the existence of the nutritional risk and undernutrition, to give the effective nutrition support promptly.The timing of the nutrition intervention is highly individualized, different treatment tolerance of different patients determines the individualized intervention timing.Nutrition intervention methods, timing and the lasting time still need more research to further clarify.

  16. Variability of Gross Tumor Volume in Nasopharyngeal Carcinoma Using 11C-Choline and 18F-FDG PET/CT.

    Directory of Open Access Journals (Sweden)

    Jun Jiang

    Full Text Available This study was conducted to evaluate the variability of gross tumor volume (GTV using 11C-Choline and 18F-FDG PET/CT images for nasopharyngeal carcinomas boundary definition. Assessment consisted of inter-observer and inter-modality variation analysis. Four radiation oncologists were invited to manually contour GTV by using PET/CT fusion obtained from a cohort of 12 patients with nasopharyngeal carcinoma (NPC and who underwent both 11C-Choline and 18F-FDG scans. Student's paired-sample t-test was performed for analyzing inter-observer and inter-modality variability. Semi-automatic segmentation methods, including thresholding and region growing, were also validated against the manual contouring of the two types of PET images. We observed no significant variation in the results obtained by different oncologists in terms of the same type of PET/CT volumes. Choline fusion volumes were significantly larger than the FDG volumes (p < 0.0001, mean ± SD = 18.21 ± 8.19. While significantly consistent results were obtained between the oncologists and the standard references in Choline volumes compared with those in FDG volumes (p = 0.0025. Simple semi-automatic delineation methods indicated that 11C-Choline PET images could provide better results than FDG volumes (p = 0.076, CI = [-0.29, 0.025]. 11C-Choline PET/CT may be more advantageous in GTV delineation for the radiotherapy of NPC than 18F-FDG. Phantom simulations and clinical trials should be conducted to prove the possible improvement of the treatment outcome.

  17. VEGF-specific siRNAs modified with 2′-deoxy effectively suppress VEGF expression and inhibit growth of nasopharyngeal carcinoma xenograft in a mouse model

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Vascular endothelial growth factor (VEGF) is up-regulated in the vast majority of human tumors. The up-regulation of VEGF not only plays important roles in tumor angiogenesis, but also provides a target for tumor treatment with small interfering RNA (siRNA) that targets VEGF; however, it is unclear whether a quite high up-regulation of VEGF will affect the efficiency of RNA interference strategies targeting VEGF. A high level expression of VEGF was found in CNE cells from a nasopharyngeal carcinoma cell line. In this study, we investigate whether VEGF-specific siRNAs can effectively suppress VEGF expression in CNE cells, and study the methods for the use of VEGF-specific siRNAs as potential therapeutic agents. CNE cells with high VEGF expression induced by hypoxia were transfected with VEGF-specific siRNAs. The expression of VEGF was effectively suppressed by VEGF-specific siRNAs, measured by ELISA, Western blot analysis and RT-PCR. Furthermore, experiments in nude mice bearing nasopharyngeal carcinoma xenograft were initiated 5 d after injection of CNE cells. VEGF-specific siRNAs were modified with 2′-deoxy, then injected into the tumors, and a liposome-mediated siRNA transfection system and ultrasound exposure were used to help delivery of the siRNAs. Tumor growth was reduced significantly after 3 weeks’ treatment. These studies suggest that VEGF-specific siRNAs still can effectively suppress VEGF expression even in tumor cell lines with a relatively high level of VEGF expression, such as CNE, and VEGF-specific siRNAs modified with 2′-deoxy can be used as potential agents for tumor therapy.

  18. Adding maximum standard uptake value of primary lesion and lymph nodes in 18F-fluorodeoxyglucose PET helps predict distant metastasis in patients with nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Qi Shi

    Full Text Available To find out the most valuable parameter of 18F-Fluorodeoxyglucose positron emission tomography for predicting distant metastasis in nasopharyngeal carcinoma.From June 2007 through December 2010, 43 non-metastatic NPC patients who underwent 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT before radical Intensity-Modulated Radiation Therapy were enrolled and reviewed retrospectively. PET parameters including maximum standardized uptake value (SUV max, mean standardized uptake value (SUV mean, metabolic tumor volume (MTV, and total lesion glucose (TLG of both primary tumor and cervical lymph nodes were calculated. Total SUV max were recorded as the sum of SUV max of primary tumor and cervical lymph nodes. Total SUV mean, Total MTV and Total TLG were calculated in the same way as Total SUV max.The median follow-up was 32 months (range, 23-68 months. Distant metastasis was the main pattern of treatment failure. Univariate analysis showed higher SUV max, SUV mean, MTV, and TLG of primary tumor, Total SUV max, Total MTV, Total TLG, and stage T3-4 were factors predicting for significantly poorer distant metastasis-free survival (p = 0.042, p = 0.008, p = 0.023, p = 0.023, p = 0.024, p = 0.033, p = 0.016, p = 0.015. In multivariate analysis, Total SUV max was the independent predictive factor for distant metastasis (p = 0.046. Spearman Rank correlation analysis showed mediate to strong correlationship between Total SUV max and SUV max-T, and between Total SUV max and SUV max-N(Spearman coefficient: 0.568 and 0.834; p = 0.000 and p = 0.000.Preliminary results indicated that Total SUV max was an independently predictive factor for distant metastasis in patients of nasopharyngeal carcinoma treated with Intensity-Modulated Radiation Therapy.

  19. Nicotine promotes proliferation of human nasopharyngeal carcinoma cells by regulating α7AChR, ERK, HIF-1α and VEGF/PEDF signaling.

    Directory of Open Access Journals (Sweden)

    Dingbo Shi

    Full Text Available Nicotine, the major component in cigarette smoke, can promote tumor growth and angiogenesis, but the precise mechanisms involved remain largely unknown. Here, we investigated the mechanism of action of nicotine in human nasopharyngeal carcinoma (NPC cells. Nicotine significantly promoted cell proliferation in a dose and time-dependent manner in human NPC cells. The mechanism studies showed that the observed stimulation of proliferation was accompanied by the nicotine-mediated simultaneous modulation of α7AChR, HIF-1α, ERK and VEGF/PEDF signaling. Treatment of NPC cells with nicotine markedly upregulated the expression of α7AChR and HIF-1α proteins. Transfection with a α7AChR or HIF-1α-specific siRNA or a α7AChR-selective inhibitor significantly attenuated the nicotine-mediated promotion of NPC cell proliferation. Nicotine also promoted the phosphorylation of ERK1/2 but not JNK and p38 proteins, thereby induced the activation of ERK/MAPK signaling pathway. Pretreatment with an ERK-selective inhibitor effectively reduced the nicotine-induced proliferation of NPC cells. Moreover, nicotine upregulated the expression of VEGF but suppressed the expression of PEDF at mRNA and protein levels, leading to a significant increase of the ratio of VEGF/PEDF in NPC cells. Pretreatment with a α7AChR or ERK-selective inhibitor or transfection with a HIF-1α-specific siRNA in NPC cells significantly inhibited the nicotine-induced HIF-1α expression and VEGF/PEDF ratio. These results therefore indicate that nicotine promotes proliferation of human NPC cells in vitro through simultaneous modulation of α7AChR, HIF-1α, ERK and VEGF/PEDF signaling and suggest that the related molecules such as HIF-1α might be the potential therapeutic targets for tobacco-associated diseases such as nasopharyngeal carcinomas.

  20. Interleukins, laminin and epstein - barr virus latent membrane protein 1 (EBV LMP1) Promote metastatic phenotype in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Nasopharyngeal carcinoma (NPC) is a type of neoplasm that is highly prevalent in East Asia and Africa with Epstein-Barr virus (EBV), genetic, and dietary factors implicated as possible aetiologic factors. Previous studies suggested the association of certain cytokines with the invasion and metastatic properties of NPC. The present study examined the roles of EBV latent membrane protein-1 (LMP1), interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-β1) and laminin in the regulation of matrix-metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) in NPC. The effects of these factors on bmi-1, an oncogene, and ngx6, a tumour suppressor gene, were also investigated. TW01 cells expressing LMP1 (TW01-LMP1) were established via transfection with the B95.8 EBV LMP1 gene. Both TW01 and TW01-LMP1 cells were treated with 100 pg/ml IL-6, 1000 pg/ml IL-10 and 100 pg/ml TGF-β1, separately and also in combination at their respective concentration for 48 hours. Treated cells were subjected to laminin adherence assay. The cells were also cultured with and without laminin and assayed for MMP-3, MMP-9 and VEGF production using enzyme-linked immunosorbent assay (ELISA). The cellular apoptotic property was analysed using caspase-3 apoptosis assay. The expression of bmi-1 and ngx6 gene was investigated using real time reverse transcriptase polymerase chain reaction. LMP1 was found to reduce the adherence of NPC cells towards laminin (p < 0.05) as compared to control. Treatment with IL-6 at 100 pg/ml enhanced the production of MMP-9 in both TW01 and TW01-LMP1 cells (p < 0.05). When cultured on laminin, the levels of MMP-3 and VEGF were significantly increased (p < 0.05) in TW01-LMP1 cells. TW01-LMP1 cells had relatively greater resistance to apoptosis as compared to TW01 cells (p < 0.05). Laminin, IL-6 and LMP1 were found to up-regulate the expression of bmi-1 and suppressed the expression of ngx6. We conclude that IL-6 reduced cell

  1. Image-based Multilevel Subdivision of M1 Category in TNM Staging System for Metastatic Nasopharyngeal Carcinoma.

    Science.gov (United States)

    Shen, Lujun; Li, Wang; Wang, Siyang; Xie, Guofeng; Zeng, Qi; Chen, Chen; Shi, Feng; Zhang, Ying; Wu, Ming; Shu, Wanhong; Pan, Changchuan; Xia, Yunfei; Wu, Peihong

    2016-09-01

    Purpose To establish an image-based M1 category subdivision system for personalized prognosis prediction and treatment planning in patients with metastatic nasopharyngeal carcinoma (NPC). Materials and Methods A total of 1172 patients with metachronous metastasic NPC were retrospectively enrolled (the dataset is from Sun Yat-sen University Cancer Center for derivation, and the combined datasets are from Guangzhou Medical University Cancer Center and the Fifth Affiliated Hospital of Sun Yat-sen University for validation). The Ethics Committee of the three centers approved this study. A general subdivision system of the M1 category was established on the basis of the most influential metastatic features for overall survival (OS). The following multilevel subdivision system for precise subdivision of the M1 category was designed: M [number of locations]-Location [number of lesions], with B indicating bone, L indicating the lung, H indicating the liver, and N indicating a node. The correlation of the M1 subdivisions with OS was determined with Cox regression. The best treatment response was assessed with Response Evaluation Criteria in Solid Tumors 1.1 guidelines and modified Response Evaluation Criteria in Solid Tumors criteria. Results Multivariate analysis in the derivation cohort showed that the number of metastatic lesions (multiple or single), the number of metastatic locations (multiple or single), liver involvement, and bone involvement were independent prognostic factors for OS. In general, subdividing the cohort by the number of metastatic lesions and the number of metastatic locations resulted in three subcategories of differential OS: M1a, a single lesion in a single organ or location; M1b, multiple lesions in a single organ or location; and M1c, metastases in multiple locations (for M1b vs M1a, hazard ratio [HR] = 2.28, 95% confidence interval [CI]: 1.71, 3.05; for M1c vs M1a, HR = 3.65, 95% CI: 2.75, 4.85); these subdivisions were externally validated

  2. Recent advances in multidisciplinary management ofhepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Asmaa I Gomaa; Imam Waked

    2015-01-01

    The incidence of hepatocellular carcinoma (HCC)is increasing, and it is currently the second leadingcause of cancer-related death worldwide. Potentiallycurative treatment options for HCC include resection,transplantation, and percutaneous ablation, whereaspalliative treatments include trans-arterial chemoembolization(TACE), radioembolization, and systemictreatments. Due to the diversity of available treatmentoptions and patients' presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved moleculartargeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC.

  3. Advances in Management of Hepatocellular Carcinoma.

    Science.gov (United States)

    Intaraprasong, Pongphob; Siramolpiwat, Sith; Vilaichone, Ratha-Korn

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor and a high impact health problem worldwide. The prevalence of HCC is particularly high in many Asian and African countries. Some HCC patients have no symptoms prior to diagnosis and many of them therefore present at late stage and have a grave prognosis. The well-established causes of HCC are chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection or alcoholic cirrhosis and nonalcoholic steatohepatitis. The Barcelona Clinic Liver Cancer (BCLC) Staging System remains the most widely used for HCC management guidelines. To date, the treatments for HCC are still very challenging for physicians due to limited resources in many parts of the world, but many options of management have been proposed, including hepatic resection, liver transplantation, ablative therapy, chemoembolization, sora nib and best supportive care. This review article describes the current evidence-based management of HCC with focus on early to advance stages that impact on patient overall survival. PMID:27644603

  4. Homozygous Wildtype of XPD K751Q Polymorphism Is Associated with Increased Risk of Nasopharyngeal Carcinoma in Malaysian Population

    OpenAIRE

    Munn-Sann Lye; Shaneeta Visuvanathan; Pei-Pei Chong; Yoke-Yeow Yap; Chin-Chye Lim; Eng-Zhuan Ban

    2015-01-01

    The xeroderma pigmentosum group D (XPD) gene encodes a DNA helicase, an important component in transcription factor IIH (TFIIH) complex. XPD helicase plays a pivotal role in unwinding DNA at the damaged region during nucleotide excision repair (NER) mechanism. Dysfunctional XPD helicase protein from polymorphic diversity may contribute to increased risk of developing cancers. This study aims to determine the association between XPD K751Q polymorphism (rs13181) and risk of nasopharyngeal carci...

  5. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

    Motzer, Robert J; Escudier, Bernard; McDermott, David F;

    2015-01-01

    in patients with renal-cell carcinoma who had received previous treatment. METHODS: A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg......BACKGROUND: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus...... patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.)....

  6. Clinical value of radionuclide bone imaging in 343 primary nasopharyngeal carcinoma cases%鼻咽癌343例放射性核素骨显像的临床分析

    Institute of Scientific and Technical Information of China (English)

    邱素芳; 潘建基; 唐明灯; 林少俊; 杨凌; 林端瑜

    2008-01-01

    Objective To analyze the radionuclide bone imaging in 343 primary nasopharyngeal carcinoma cases and to know the positive ratio and its prognosis. Methods 343 cases with primary NPC were examined by radionuclide bone imaging in order to find if there was bone metastases and analyze in single and multi factors, and then to know its prognosis. Results The positive ratio of 343 NPC cases was 32.9 %, men 37.5%, women 17.7%. There was significant statistic value in sex, age and staging through Binary Logistic Regress analysis. Men, the more advanced staging, the older people, the earlier to metastases.The overall accumulate survival ratio was 1 year 92.1%, 2 year 83.9 %, 3 year 78.8 %. Conclusion Nasopharyngeal carcinoma is easy to metastases. Radionuclide bone imaging should be performed in the patients with NPC because it is important to evaluate the staging and therapy.%目的 通过分析鼻咽癌初治患者放射性核素骨显像资料,了解骨转移发生情况及其预后.方法 对343例鼻咽癌初治患者均行常规放射性核素骨显像检查,对其进行单因素及多因素分析,并在治疗后1、2、3年进行随访.结果 343例患者初诊时骨转移发生率为32.9%,其中男性37.5%,女性17.7%,多因素分析结果显示不同性别、年龄、病期间差异有统计学意义.总体累计生存率为:1年92.1%,2年83.9%,3年78.8%.结论 鼻咽癌放射性核素骨显像灵敏度较高,对鼻咽癌的诊断、分期、治疗及预后判断有重要作用,应作为鼻咽癌患者的常规检查.

  7. Detecção de Epstein-Barr vírus no carcinoma da nasofaringe: implicações numa área de baixo risco Epstein-Barr virus detection in nasopharyngeal carcinoma: implications in a low-risk area

    Directory of Open Access Journals (Sweden)

    Eduardo Breda

    2010-06-01

    Full Text Available Têm sido publicados vários estudos acerca da infecção por Epstein-Barr vírus (EBV e o desenvolvimento de carcinoma da nasofaringe (NPC. As prevalências dos tipos histológicos e a presença de infecção latente pelo EBV são diferentes em regiões endémicas e não endémicas. OBJETIVO: O objectivo deste estudo consistiu na detecção de EBV em tecido tumoral da nasofaringe e sangue periférico de doentes com NPC e em indivíduos saudáveis, provenientes duma área não-endémica, de baixo risco. MÉTODOS: Detecção de EBV em amostras de doentes com carcinoma da nasofaringe e indivíduos saudáveis. Neste estudo de série foram avaliadas as implicações clínicas da presença de EBV circulante no sangue periférico de doentes com carcinoma da nasofaringe. RESULTADOS: Este estudo indica que a frequência de casos EBV positivos detectados no sangue periférico é superior em tumores de estádio mais avançado. CONCLUSÕES: Estes resultados indicam que se observam diferenças na pesquisa do vírus Epstein-Barr no grupo de doentes com NPC e no grupo controlo, sem tumor. Este estudo pode ajudar na compreensão dos mecanismos biológicos do cancro da nasofaringe e da correlação destes tumores com a infecção por EBV numa área não-endémica, de baixo risco.Several studies have been published concerning Epstein-barr virus (EBV infection and nasopharyngeal cancer (NPC development. The incidences of histological types are different according to endemic or non-endemic regions. Latent EBV infection is found in almost all cases of NPC in endemic regions, but normally absent in type I carcinomas, more common in non-endemic regions. AIM: The purpose of this hospital-based study was to analyze the presence of EBV in nasopharyngeal tumor tissues and in peripheral blood of nasopharyngeal cancer patients and healthy individuals, in a low risk, non-endemic area. METHODS: EBV detection in samples of nasopharyngeal cancer patients and healthy

  8. Kinase inhibitors for advanced medullary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Martin Schlumberger

    2012-01-01

    Full Text Available The recent availability of molecular targeted therapies leads to a reconsideration of the treatment strategy for patients with distant metastases from medullary thyroid carcinoma. In patients with progressive disease, treatment with kinase inhibitors should be offered.

  9. Applications of Parenteral Nutrition in Patients with Nasopharyngeal Carcinoma Concurrent Radiotherapy and Chemotherapy%肠外营养在鼻咽癌同步放化疗患者中的应用

    Institute of Scientific and Technical Information of China (English)

    张慧; 郑晓宇

    2014-01-01

    鼻咽癌放化疗患者口腔反应较重,影响进食,当营养低于机体需要量时,越来越多的患者选择肠外营养途径满足机体需要。回顾我科2012年1月~2013年7月共收治119例鼻咽癌放化疗同步的患者,其中32例通过肠外营养补充营养素,采取有效护理干预帮住患者顺利完成治疗。%Radiotherapy and chemotherapy can lead to severe reactions in the oral cavity of the patients suf ering from nasopharyngeal carcinoma, which keep them from feeding. As nutrition taken in fails to satisfy the body requirements, more and more patients with nasopharyngeal carcinoma tend to do parenteral nutrition injection so as to meet such body requirements. After reviewing 110 cases of patients with nasopharyngeal carcinoma who receive synchronous radiotherapy and chemotherapy in our department from January, 2012 to July, 2013, we find that there are 32 cases replenishing nutrition by way of parenteral nutrition injection in which the ef ective nursing intervention is adopted to help such patients successful y complete their treatment.

  10. Expression of Telomerase Subunits in Nasopharyngeal Carcinoma%鼻咽癌组织端粒酶各组分基因表达的研究

    Institute of Scientific and Technical Information of China (English)

    王行炜; 肖健云; 赵素萍; 田勇泉; 王光平

    2001-01-01

    目的:探讨端粒酶各组分基因在鼻咽癌(nasopharyngeal carcinoma,NPC)组织及鼻咽慢性炎症粘膜(chronic inflammation of nasopharyngeal epithelium,CINE)组织中的表达情况。方法:利用RT-PCR方法检测鼻咽癌组织及鼻咽慢性炎症粘膜组织端粒酶各组分基因(hTR、TP1mRNA和hTERTmRNA)的表达。结果:43例NPC组织中,hTR、TP1mRNA和hTERTmRNA表达阳性率分别为90.7%、88.4%和88.4%;16例CINE组织中,hTR、TP1mRNA和hTERTmRNA表达阳性率为87.5%、87.5%和0%;仅hTERTmRNA在鼻咽癌组织中的表达显著高于鼻咽慢性炎症粘膜组织中的表达,而hTR或TP1mRNA在鼻咽癌组织中的表达和鼻咽慢性炎症粘膜组织中的表达无明显差异。表明hTR和TP1mRNA广泛存在于鼻咽癌和鼻咽慢性炎症粘膜组织中,而hTERTmRNA仅在鼻咽癌组织中表达。结论:hTERTmRNA可能在端粒酶活性调节中起重要作用;hTERTmRNA的表达水平,可作为鼻咽癌诊断指标之一。%Objective:This study was designed to ascertain telomerase subunits expression in nasopharyngeal carcinoma (NPC) as well as in chronic inflammation of nasopharyngeal epithelium (CINE). Methods:Telomerase subunits(hTR,TP1 mRNA, hTERT mRNA) expression was determined with reverse transcription-polymerase chain reaction (RT-PCR) in 43 cases of NPC and 16 cases of CINE. Results:The positive rates of hTR,TP1 mRNA and hTERT mRNA were 90.7% ,88% , and 88% in 43 NPCs, and 87.5% , 87.5% , and 0 in 16 CINEs respectively. hTERT mRNA exoressuib was significantly higher in NPC than in CINE,but no statistical difference for hTR or TP1 mRNA occurred in two groups of patients. Conclusion:These findings revealed that hTR and TP1 mRNA were widely expressed in both NPC and CINE, but hTERT mRNA was limited in NPC, which suggests that hTERT mRNA may play a critical role in activation of telomerase. The authers’findings also indicate that detection of hTERT mRNA may

  11. Long-term outcome and late toxicities of simultaneous integrated boost-intensity modulated radiotherapy in pediatric and adolescent nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chang-Juan Tao; Ai-Hua Lin; Jun Ma; Ying Sun; Xu Liu; Ling-Long Tang; Yan-Ping Mao; Lei Chen; Wen-Fei Li; Xiao-Li Yu; Li-Zhi Liu; Rong Zhang

    2013-01-01

    The application of simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) in pediatric and adolescent nasopharyngeal carcinoma (NPC) is underevaluated. This study aimed to evaluate long-term outcome and late toxicities in pediatric and adolescent NPC after SIB-IMRT combined with chemotherapy. Thirty-four patients (aged 8-20 years) with histologically proven, non-disseminated NPC treated with SIB-IMRT were enrol ed in this retrospective study. The disease stage distribution was as fol ows:stage I, 1 (2.9%);stage III, 14 (41.2%);and stage IV, 19 (55.9%). Al patients underwent SIB-IMRT and 30 patients also underwent cisplatin-based chemotherapy. The prescribed dose of IMRT was 64-68 Gy in 29-31 fractions to the nasopharyngeal gross target volume. Within the median fol ow-up of 52 months (range, 9-111 months), 1 patient (2.9%) experienced local recurrence and 4 (11.8%) developed distant metastasis (to the lung in 3 cases and to multiple organs in 1 case). Four patients (11.8%) died due to recurrence or metastasis. The 5-year locoregional relapse-free survival, distant metastasis-free survival, disease-free survival, and overal survival rates were 97.1%, 88.2%, 85.3%, and 88.2%, respectively. The most common acute toxicities were grades 3-4 hematologic toxicities and stomatitis. Of the 24 patients who survived for more than 2 years, 16 (66.7%) and 15 (62.5%) developed grades 1-2 xerostomia and ototoxicity, respectively. Two patients (8.3%) developed grade 3 ototoxicity; no grade 4 toxicities were observed. SIB-IMRT combined with chemotherapy achieves excellent long-term locoregional control in pediatric and adolescent NPC, with mild incidence of late toxicities. Distant metastasis is the predominant mode of failure.

  12. Long-term outcome and late toxicities of simultaneous integrated boost-intensity modulated radiotherapy in pediatric and adolescent nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Li-Zhi Liu

    2013-10-01

    Full Text Available The application of simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT in pediatric and adolescent nasopharyngeal carcinoma (NPC is underevaluated. This study aimed to evaluate long-term outcome and late toxicities in pediatric and adolescent NPC after SIB-IMRT combined with chemotherapy. Thirty-four patients (aged 8-20 years with histologically proven, non-disseminated NPC treated with SIB-IMRT were enrolled in this retrospective study. The disease stage distribution was as follows: stage I, 1 (2.9%; stage III, 14 (41.2%; and stage IV, 19 (55.9%. All patients underwent SIB-IMRT and 30 patients also underwent cisplatin-based chemotherapy. The prescribed dose of IMRT was 64-68 Gy in 29-31 fractions to the nasopharyngeal gross target volume. Within the median follow-up of 52 months (range, 9-111 months, 1 patient (2.9% experienced local recurrence and 4 (11.8% developed distant metastasis (to the lung in 3 cases and to multiple organs in 1 case. Four patients (11.8% died due to recurrence or metastasis. The 5-year locoregional relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 97.1%, 88.2%, 85.3%, and 88.2%, respectively. The most common acute toxicities were grades 3-4 hematologic toxicities and stomatitis. Of the 24 patients who survived for more than 2 years, 16 (66.7% and 15 (62.5% developed grades 1-2 xerostomia and ototoxicity, respectively. Two patients (8.3% developed grade 3 ototoxicity; no grade 4 toxicities were observed. SIB-IMRT combined with chemotherapy achieves excellent long-term locoregional control in pediatric and adolescent NPC, with mild incidence of late toxicities. Distant metastasis is the predominant mode of failure.

  13. EGCG Inhibits Proliferation, Invasiveness and Tumor Growth by Up-Regulation of Adhesion Molecules, Suppression of Gelatinases Activity, and Induction of Apoptosis in Nasopharyngeal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Chih-Yeu Fang

    2015-01-01

    Full Text Available (−-Epigallocatechin-3-gallate (EGCG, a major green tea polyphenol, has been shown to inhibit the proliferation of a variety of tumor cells. Epidemiological studies have shown that drinking green tea can reduce the incidence of nasopharyngeal carcinoma (NPC, yet the underlying mechanism is not well understood. In this study, the inhibitory effect of EGCG was tested on a set of Epstein Barr virus-negative and -positive NPC cell lines. Treatment with EGCG inhibited the proliferation of NPC cells but did not affect the growth of a non-malignant nasopharyngeal cell line, NP460hTert. Moreover, EGCG treated cells had reduced migration and invasive properties. The expression of the cell adhesion molecules E-cadherin and β-catenin was found to be up-regulated by EGCG treatment, while the down-regulation of matrix metalloproteinases (MMP-2 and MMP-9 were found to be mediated by suppression of extracellular signal-regulated kinase (ERK phosphorylation and AP-1 and Sp1 transactivation. Spheroid formation by NPC cells in suspension was significantly inhibited by EGCG. Oral administration of EGCG was capable of suppressing tumor growth in xenografted mice bearing NPC tumors. Treatment with EGCG was found to elevate the expression of p53 and p21, and eventually led to apoptosis of NPC cells via caspase 3 activation. The nuclear translocation of NF-κB and β-catenin was also suppressed by EGCG treatment. These results indicate that EGCG can inhibit the proliferation and invasiveness, and induce apoptosis, of NPC cells, making it a promising agent for chemoprevention or adjuvant therapy of NPC.

  14. A dosimetric comparison of two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal cancer.

    Science.gov (United States)

    Chitapanarux, Imjai; Chomprasert, Kittisak; Nobnaop, Wannapa; Wanwilairat, Somsak; Tharavichitkul, Ekasit; Jakrabhandu, Somvilai; Onchan, Wimrak; Traisathit, Patrinee; Van Gestel, Dirk

    2015-05-01

    The purpose of this investigation was to evaluate the potential dosimetric benefits of a two-phase adaptive intensity-modulated radiotherapy (IMRT) protocol for patients with locally advanced nasopharyngeal cancer (NPC). A total of 17 patients with locally advanced NPC treated with IMRT had a second computed tomography (CT) scan after 17 fractions in order to apply and continue the treatment with an adapted plan after 20 fractions. To simulate the situation without adaptation, a hybrid plan was generated by applying the optimization parameters of the original treatment plan to the anatomy of the second CT scan. The dose-volume histograms (DVHs) and dose statistics of the hybrid plan and the adapted plan were compared. The mean volume of the ipsilateral and contralateral parotid gland decreased by 6.1 cm(3) (30.5%) and 5.4 cm(3) (24.3%), respectively. Compared with the hybrid plan, the adapted plan provided a higher dose to the target volumes with better homogeneity, and a lower dose to the organs at risk (OARs). The Dmin of all planning target volumes (PTVs) increased. The Dmax of the spinal cord and brainstem were lower in 94% of the patients (1.6-5.9 Gy, P < 0.001 and 2.1-9.9 Gy, P < 0.001, respectively). The Dmean of the contralateral parotid decreased in 70% of the patients (range, 0.2-4.4 Gy). We could not find a relationship between dose variability and weight loss. Our two-phase adaptive IMRT protocol improves dosimetric results in terms of target volumes and OARs in patients with locally advanced NPC. PMID:25666189

  15. Intensity-modulated radiotherapy for stage IVA/IVB nasopharyngeal carcinoma. Clinical outcomes and patterns of failure in an endemic area in China

    Energy Technology Data Exchange (ETDEWEB)

    Zeng, Lei; Tian, Yun-Ming; Sun, Xue-Ming; Huang, Ying; Chen, Chun-Yan; Han, Fei; Liu, Shuai; Lan, Mei; Guan, Ying [Collaborative Innovation Center of Cancer Medicine, State Key Laboratory Oncology in South China, Guangzhou (China); Sun Yat-Sen University Cancer Center, Department of Radiation Oncology, Guangzhou (China); Deng, Xiao-Wu; Lu, Tai-Xiang [Sun Yat-Sen University Cancer Center, Department of Radiation Oncology, Guangzhou (China); Collaborative Innovation Center of Cancer Medicine, State Key Laboratory Oncology in South China, Guangzhou (China)

    2014-11-15

    The purpose of this study was to analyze the mode of relapse patterns and survival of 209 patients with stage IVA and IVB nasopharyngeal carcinoma (NPC). A total of 209 patients who underwent magnetic resonance imaging (MRI) and were subsequently histologically diagnosed with nondisseminated stage IV NPC received intensity-modulated radiotherapy (IMRT) as their primary treatment and were included in this retrospective study. Median follow-up time was 65 months (range, 3-108 months). The 5-year overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates for patients with stage IVA and stage IVB NPC were 72.7 vs. 60.0 % (p = 0.319), 62.9 vs. 51.3 % (p = 0.070), 82.9 vs. 93.1 % (p = 0.070), 82.9 vs. 82.9 % (p = 0.897), 76.4 vs. 58.5 % (p = 0.003), respectively. Age older than 44 years was found to be a statistically significant adverse independent prognostic factor for OS. Patients with advanced N status had worse OS, DFS, and DMFS rates. Patients with a primary gross tumor volume (GTV-P) ≥ 55.11 ml had worse OS, DFS, and LRRFS rates. The results of treating stage IVA NPC with IMRT were excellent. Distant metastasis remains the most difficult treatment challenge for patients with stage IVA and IVB NPC, and more effective systemic chemotherapy should be explored. (orig.) [German] Ziel dieser Studie war die Analyse der Rezidivmuster und des Ueberlebens von 209 Patienten mit nasopharyngealem Karzinom (NPC) im Stadium IVA und IVB. Insgesamt 209 Patienten, die mittels MRT und anschliessender histologischer Untersuchung mit nichtdisseminiertem NPC im Stadium IV diagnostiziert worden waren, erhielten eine intensitaetsmodulierte Strahlentherapie (IMRT) als Primaerbehandlung und wurden in diese retrospektive Studie aufgenommen. Die mediane Follow-up-Dauer betrug 65 Monate (Bereich 3-108 Monate). Das 5-Jahres-Gesamtueberleben (OS), das

  16. MRI-detected skull-base invasion. Prognostic value and therapeutic implication in intensity-modulated radiotherapy treatment for nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Yi-Kan; Jiang, Ning; Yue, Dan; Tang, Ling-Long; Zhang, Fan; Lin, Li; Liu, Xu; Chen, Lei; Ma, Jun [Sun Yat-sen University Cancer Center, Department of Radiation Oncology, Guangzhou (China); Liu, Li-Zhi [Sun Yat-sen University Cancer Center, Department of Radiology, Guangzhou (China)

    2014-10-15

    With advances in imaging and radiotherapy, the prognostic value of skull-base invasion in nasopharyngeal carcinoma (NPC) needs to be reassessed. We aimed to define a classification system and evaluate the prognostic value of the classification of magnetic resonance imaging (MRI)-detected skull-base invasion in NPC treated with intensity-modulated radiotherapy (IMRT). We retrospectively reviewed 749 patients who underwent MRI and were subsequently histologically diagnosed with nondisseminated NPC and treated with IMRT. MRI-detected skull-base invasion was not found to be an independent prognostic factor for overall survival (OS), distant metastasis-free survival (DMFS), local relapse-free survival (LRFS), or disease-free survival (DFS; p > 0.05 for all). Skull-base invasion was classified according to the incidence of each site (type I sites inside pharyngobasilar fascia and clivus vs. type II sites outside pharyngobasilar fascia). The 5-year OS, DMFS, LRFS, and DFS rates in the classification of skull-base invasion in NPC were 83 vs. 67 %, 85 vs.75 %, 95 vs. 88 %, and 76 vs. 62 %, respectively (p < 0.05 for all). Multivariate analysis indicated the classification of skull-base invasion was an independent prognostic factor. MRI-detected skull-base invasion is not an independent prognostic factor in patients with NPC treated with IMRT. However, classification according to the site of invasion has prognostic value. Therefore, patients with various subclassifications of stage T3 disease may receive treatment with different intensities; however, further studies are warranted to prove this. (orig.) [German] Aufgrund der Fortschritte der bildgebenden Verfahren und der Strahlentherapie muss der prognostische Wert der Invasion des nasopharyngealen Karzinoms (NPC) in die Schaedelbasis erneut bewertet werden. Unser Ziel ist die Definition eines Klassifikationssystems und die Untersuchung des prognostischen Werts der Klassifikation der MRT-ermittelten Invasion des mit

  17. RKIP在鼻咽癌侵袭转移中的作用及机制研究%The roles and mechanisms of RKIP in the invasion and metastasis of nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    王园园; 贺秋艳; 易红梅; 肖志强

    2015-01-01

    目的:研究Raf激酶抑制蛋白(Raf kinase inhibitory protein,RKIP)在鼻咽癌(nasopharyngeal carcinoma,NPC)侵袭转移中的作用及其机制.方法:采用免疫组织化学染色检测RKIP在转移潜能不同的NPC组织中的表达,分析其表达水平与NPC临床病理特征和患预后的关系;采用脂质体转染技术建立RKIP表达改变的稳定转染NPC细胞系,采用刮痕愈合实验和Transwell小室侵袭实验检测细胞的体外运动和侵袭能力,采用Western blot检测NF-κB信号分子磷酸化水平.结果:RKIP在NPC组织中的表达显著低于正常鼻咽粘膜组织,在有转移NPC组织中的表达明显低于无转移NPC组织,在颈淋巴结转移癌组织中的表达明显低于原发癌;RKIP表达水平与NPC的淋巴结转移、远处转移、临床分期以及NPC患的总生存期负相关;RKIP表达上调降低5-8F NPC细胞的体外运动和侵袭能力,而RKIP表达下调增强6-10B NPC细胞的体外运动和侵袭能力;RKIP表达水平与NPC细胞NF-κB信号通路的活性负相关,NF-κB抑制剂Bay11-7082能抑制RKIP下调的6-10B细胞的体外运动和侵袭.结论:RKIP可能是NPC的一个转移抑制蛋白,RKIP低表达的NPC患预后差,RKIP表达下调通过活化NF-κB通路促进NPC的侵袭和转移.%Objective: To investigate the roles and mechanisms of Raf kinase inhibitory protein (RKIP) in the invasion and metastasis of nasopharyngeal carcinoma (NPC).Methods: Immunohistochemistry was performed to detect the expression levels of RKIP in the NPC tissue specimens with different metastasis; Establishment of stable transfected NPC cell lines with RKIP expression changes using lipofectamine 2000; Scratch wound-wealing assay and traswell invasion assay were performed to determine the ability of cell migration and invasion; Western blot was used to detect the phosphorylated levels of NF-κB signaling molecules in NPC cells.Results: RKIP expression was signiifcantly reduced in the NPCs relative to normal

  18. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    OpenAIRE

    Ryuichi Kita; Toru Kimura; Hiroki Nishikawa; Yukio Osaki

    2012-01-01

    Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of ...

  19. Diffusion tensor imaging and 1H-MR spectroscopy study on radiation-induced injury of the brain after nasopharyngeal carcinoma radiotherapy

    International Nuclear Information System (INIS)

    Objective: To investigate the changes of brain tissue in bilateral temporal lobes at different stages after nasopharyngeal carcinoma radiotherapy by diffusion tensor imaging (DTI) and 1H-MR spectroscopy (1H-MRS). Methods: DTI and 1H-MRS were performed in 48 patients with nasopharyngeal carcinoma, in which conventional MRI revealed normal findings after radiotherapy. Twenty-four healthy controls were enrolled in this study and underwent the same MR scanning, After the image processing and spectral analysis, apparent diffusion coefficient (ADC), fractional anisotropy (FA) and 3 eigenvalue λ1, λ2, λ3 of DTI and the NAA/Cho, NAA/Cr, Cho/Cr of 1H-MRS were measured in bilateral temporal lobes. Forty-eight NPC patients were divided into 3 groups [less than 6 months (16 cases), 6 to 12 months (6 cases) and more than 12 months(26 cases) after radiotherapy] according to different stages of radiation- induced injury of brain, each group's DTI and 1H-MRS data were measured respectively and one-way ANOVA was applied to analyze each parameter. Results: The FA value of each test group (less than 6 months, 6 to 12 months and more than 12 months) and the control group were 0.445±0.017, 0.460± 0.016, 0.461±0.025, 0.473±0.023 respectively. The ADC values of each group were (8.51±0.43) × 10-4, (8.48±0.34) × 10-4, (8.40±0.33) × 10-4, (8.68±0.57) × 10-4 mm2/s respectively. And the maximum eigenvalue λ1 of each group were (1.251±0.065) × 10-3, (1.293±0.051) × 10-3, (1.317± 0.074) × 10-3, (1.350±0.091) × 10-3 mm2/s. The three indicators were significantly different among groups (F=10.873, 3.399, 9.750 respectively, P2, λ3 values showed no significant difference among the groups. The NAA/Cho of 1H-MRS of each groups were 0.910±0.112, 0.972±0.101, 1.060± 0.095, 1.261±0.105 respectively, and the NAA/Cr were 1.212±0.236, 1.208±0.183, 1.228± 0.236, 1.435±0.225 respectively. Both of them had significant differences among groups (F=52.840, 8.176 respectively, P1H

  20. Arsenic Trioxide Induced Differentiation and Apoptosis in Human Nasopharyngeal Carcinoma Xenografts in BALB/C Nude Mice

    Institute of Scientific and Technical Information of China (English)

    ZHENGYuwu; DUCaiwen; LIDerui; LINYingcheng; WUMingyao

    2004-01-01

    To study the effect of arsenic trioxide (As2O3) on human poorly differentiated nasopharyngeal cancer cell line, CSNE-1, in vivo and its possible mechanism of action. Methods: CSNE-1 cells were established as xenografts in BALB/C nude mice. The tumor-bearing mice were treated with As2O3 at the dose of 5 mg/kg every day. The tumor growth was observed by tumor-growth curve. Morphologic changes were studied under light microscopy and electron microscopy. TUNEL was used to detect apoptosis. The expression of PCNA, p53, Bcl-2 and Bax were determined by immunohistochemistry. Results: The cell growth and proliferate activity were significantly inhibited by As203 at the dose of 5 mg/kg every day. Morphologic changes such as the formation of keratinization of tumor cells, decreased ratio of nuclear/cytoplasm, increased organelle and plasmic fibril in cytoplasm were identified. Cytodesma, desmosomes and micro-process were seen under light microscopy and transmission electron microscopy, which revealed that the cancer cells underwent differentiation. In addition, remarkable cell apoptosis were observed by TUNEL assay. Over expression of p53 and Bax was detected in the As203 treatment group when compared with control group. Conclusion: As203 inhibited proliferation of human poorly differentiated nasopharyngeal cancer cell CSNE-1 by inducing differentiation and apoptosis, which may be related to the up-regulation of p53 and Bax expression.

  1. Nasopharyngeal Chondrolipoma

    Directory of Open Access Journals (Sweden)

    A. J. Kinshuck

    2010-01-01

    Full Text Available In this case report, we describe the presentation and treatment of a patient with nasopharyngeal chondrolipoma. Lipomas are common soft tissue tumours, although their incidence in the nasopharynx is very low. A rarer variant of lipoma, chondrolipomas are benign mesenchymal tumours. They are formed by the proliferation of mature adipocytes and contain different amounts of mature cartilaginous tissue; Weiss “Enzinger and Weiss's soft tissue tumours”, 4th ed: Mosby, St Louis; 2001 This represents the second reported case of a nasopharyngeal chondrolipoma. An endonasal approach to excision has not been previously described.

  2. Analysis of 153 cases of nasopharyngeal carcinoma diagnosed before starting prompt auxiliary examination%鼻咽癌确诊前首次提示辅助检查153例分析

    Institute of Scientific and Technical Information of China (English)

    上官翰京; 蔡成福; 刘存山; 骆献阳

    2015-01-01

    Objective:To provide the reference for the clinical diagnosis of nasopharyngeal carcinoma.Methods: 153 patients with nasopharyngeal carcinoma were selected from January 2013 to July 2014.We analyzed the first presentation auxiliary examination results of them.Results:VCA-IgA antibody test in 10 cases,magnetic resonance imaging(MRI) examination in 15 cases,CT scan in 23 cases,cervical lymph node biopsy in 6 cases,30 cases of nasal endoscopy,54 cases of nasopharyngeal mirror,5 cases of PET/CT. Conclusion:The first hint of auxiliary examination of nasopharyngeal carcinoma is diversity.It has very important significance to the diagnosis and treatment as soon as possible.%目的:为临床诊断鼻咽癌提供参考。方法:2013年1月-2014年7月收治鼻咽癌患者153例,对其首次提示辅助检查结果进行分析。结果:VCA-IgA抗体检查10例,磁共振(MRI)检查15例,CT扫描23例,颈淋巴结活检6例,鼻内镜30例,鼻咽镜54例,PET/CT 5例。结论:鼻咽癌的首次提示辅助检查呈多样性,对明确诊断及尽早治疗都有很重要的意义。

  3. 细胞自噬及其在鼻咽癌中的作用%Autophagy and its role in nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    王佳(综述); 周文胜(审校)

    2015-01-01

    Autophagy, an important homeostatic cellular recycling mechanism, is now emerging as a crucial player in response to metabolic and therapeutic stresses, which attempts to maintain/restore metabolic homeostasis through the catabolic lysis of excessive or unnecessary proteins and injured or aged organelles.Autophagy is particularly active during metabolic stress. In the cancer cell it fulfils a dual role, having tumor-promoting and tumor-suppressing properties. Functional autophagy prevents necrosis and inflammation, which can lead to genetic instability. On the other hand, autophagy might be important for tumor progression by providing energy through its recycling mechanism during unfavorable metabolic circumstances. Recently, several studies have shown that autophagy play an important role in treatment of nasopharyngeal carcinoma. hTis review will summarize the signaltransductionpathway of autophagy, its relationship with tumor and its role in the nasopharyngeal carcinoma treatment in order to give a comprehensive understanding of the function of autophagy.%自噬作为一个重要的自我平衡的细胞回收机制,现逐渐发现在新陈代谢和治疗应激中起了关键作用。它通过消除细胞内过多不必要的蛋白质及受损或衰老的细胞器成分来维持/恢复新陈代谢的稳定。在代谢应激的情况下,自噬被激活。在癌细胞中自噬有两个方面的作用:肿瘤促进作用和肿瘤抑制作用。有功能的自噬可防止会导致遗传不稳定性发生的细胞坏死和炎症反应。另一方面,自噬通过不利代谢环境的循环机制提供能量对肿瘤进程起了重要作用。最近,许多研究表明,自噬在鼻咽癌的治疗中起了重要作用。本文将对自噬所依赖的信号转导途经、自噬与肿瘤的关系、自噬在鼻咽癌治疗中的作用进行综述,以便对自噬功能有个全面的理解。

  4. Association of polymorphisms hOGG1 rs1052133 and hMUTYH rs3219472 with risk of nasopharyngeal carcinoma in a Chinese population