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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. Leucopenia and treatment efficacy in advanced nasopharyngeal carcinoma

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    Su, Zhen; Mao, Yan-Ping; OuYang, Pu-Yun; Tang, Jie; Lan, Xiao-Wen; Xie, Fang-Yun

    2015-01-01

    Background Leucopenia or neutropenia during chemotherapy predicts better survival in several cancers. We aimed to assess whether leucopenia could be a biological measure of treatment and a marker of efficacy in advanced nasopharyngeal carcinoma (ANPC). Methods We retrospectively analyzed 3826 patients with ANPC who received chemoradiotherapy. Leucopenia was categorised on the basis of worst grade during treatment according to the National Cancer Institute Common Toxicity Criteria version 4.0:...

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

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    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. 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.

  5. 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

  6. Survival benefit of adding chemotherapy to intensity modulated radiation in patients with locoregionally advanced nasopharyngeal carcinoma.

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    Xuemei Ji

    Full Text Available BACKGROUND: To evaluate the contribution of chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma (NPC treated by intensity modulated radiotherapy (IMRT and to identify the optimal combination treatment strategy. PATIENTS AND METHODS: Between 2006 and 2010, 276 patients with stage II-IVb NPC were treated by IMRT alone or IMRT plus chemotherapy. Cisplatin-based chemotherapy included neoadjuvant or concurrent, or neoadjuvant plus concurrent protocols. The IMRT alone and chemoradiotherapy groups were well-matched for prognostic factors, except N stage, with more advanced NPC in the chemoradiotherapy arm. RESULTS: With a mean follow-up of 33.8 months, the 3-year actuarial rates of overall survival (OS, metastasis-free survival (MFS, relapse-free survival (RFS, and disease-free survival (DFS were 90.3%, 84.2%, 80.3%, and 69.2% for all of the patients, respectively. Compared with the IMRT alone arm, patients treated by concurrent chemoradiotherapy had a significantly better DFS (HR = 2.64; 95% CI, 1.12-6.22; P = 0.03, patients with neoadjuvant-concurrent chemoradiotherapy had a significant improvement in RFS and DFS (HR = 4.03; 95% CI, 1.35-12.05; P = 0.01 and HR = 2.43; 95% CI, 1.09-5.44; P = 0.03, neoadjuvant chemoradiotherapy provided no significant benefit in OS, MFS, RFS, and DFS. Stage group and alcohol consumption were prognostic factors for OS and N stage was a significant predictor for DFS. CONCLUSIONS: Addition of concurrent or neoadjuvant-concurrent chemotherapy to IMRT is available to prolong RFS or DFS for locoregionally advanced NPC. Such work could be helpful to guide effective individualized therapy.

  7. 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.

  8. Impact of Plasma Epstein-Barr Virus-DNA and Tumor Volume on Prognosis of Locally Advanced Nasopharyngeal Carcinoma

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    Meng Chen

    2015-01-01

    Full Text Available This retrospective study aims to examine the association of plasma Epstein-Barr virus- (EBV- DNA levels with the tumor volume and prognosis in patients with locally advanced nasopharyngeal carcinoma (NPC. A total of 165 patients with newly diagnosed locally advanced NPC were identified from September 2011 to July 2012. EBV-DNA was detected using fluorescence quantitative polymerase chain reaction (PCR amplification. The tumor volume was calculated by the systematic summation method of computer software. The median copy number of plasma EBV-DNA before treatment was 3790 copies/mL. The median gross tumor volume of the primary nasopharyngeal tumor (GTVnx, the lymph node lesions (GTVnd, and the total GTV before treatment were 72.46, 23.26, and 106.25 cm3, respectively; the EBV-DNA levels were significantly correlated with the GTVnd and the total GTV (P<0.01. The 2-year overall survival (OS rates in patients with positive and negative pretreatment plasma EBV-DNA were 100% and 98.4% (P=1.000, and the disease-free survival (DFS rates were 94.4% and 80.8% (P=0.044, respectively. These results indicate that high pretreatment plasma EBV-DNA levels in patients with locally advanced NPC are associated with the degree of lymph node metastasis, tumor burden, and poor prognosis.

  9. 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).

  10. 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.

  11. Significant survival benefit of adjuvant chemotherapy after concurrent chemoradiotherapy in locally advanced high-risk nasopharyngeal carcinoma

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    Liang, Zhong-Guo; Chen, Xiao-Qian; Lin, Guo-Xiang; Yu, Bin-Bin; Chen, Kai-Hua; Zhong, Qiu-Lu; Nong, Si-Kai; Li, Ling; Qu, Song; Su, Fang; Zhao, Wei; Li, Ye; Zhu, Xiao-Dong

    2017-01-01

    The present study aimed to define high-risk patients who may benefit from additional adjuvant chemotherapy (AC) after concurrent chemotherapy in combination with intensity-modulated radiotherapy among patients with loco-regionally advanced nasopharyngeal carcinoma (NPC). A cohort of 511 NPC patients who received concomitant chemoradiotherapy (CCRT) with or without AC between January 2007 and December 2012 were retrospectively analysed. One hundred seventy-seven patients received CCRT alone, whereas 334 received CCRT + AC. The survival analysis showed that ages >45 years old, T3-T4 stages, N2-N3 disease and serum albumin levels ≤42 g/L were significant independent prognostic factors for overall survival (OS). Using these four risk factors, a prognostic model for OS was created as follows: (1) low-risk group: 0–1 risk factors; and (2) high-risk group: 2–4 risk factors. In the CCRT alone and CCRT + AC groups, significant differences in survival were found between the high- and low-risk groups. Patients in the high-risk group exhibited improved OS due to the addition of AC to CCRT, but no survival benefits were found in the low-risk group. In conclusion, high-risk patients may benefit from the addition of AC to CCRT regarding OS. PMID:28150694

  12. Nasopharyngeal carcinoma and Dermatomyositis: a case report

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    P. Sfriso

    2011-09-01

    Full Text Available Nasopharyngeal carcinoma has long been reported as the predominant type of cancer associated with dermatomyositis in many several Asian countries, including Hong Kong, Singapore, and Southern-Cina. Dermatomyositis is one of the idiopathic inflammatory myopathies showing characteristic cutaneous manifestations. Reviews from the western literature have demonstrated that certain cancers, such as ovarian and breast carcinoma in women and lung and prostate carcinoma in men, are highly associated with DM relative to the general population. We report the case of a Caucasian Italian patient with nasopharyngeal carcinoma and dermatomyositis. Considering the rarity of nasopharyngeal carcinoma among whites, both the detection and the report of each new case are noteworthy in defining the geographic and ethnic distribution of this tumor.

  13. Paraneoplastic Neurological Disorder in Nasopharyngeal Carcinoma

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    Ng, Sze Yin; Kongg, Min Han; Yunus, Mohd Razif Mohamad

    2017-01-01

    Paraneoplastic neurological disorder (PND) is a condition due to immune cross-reactivity between the tumour cells and the normal tissue, whereby the “onconeural” antibodies attack the normal host nervous system. It can present within weeks to months before or after the diagnosis of malignancies. Nasopharyngeal carcinoma is associated with paraneoplastic syndrome, for example, dermatomyositis, and rarely with a neurological disorder. We report on a case of nasopharyngeal carcinoma with probable PND. Otolaryngologists, oncologists and neurologists need to be aware of this condition in order to make an accurate diagnosis and to provide prompt treatment. PMID:28381934

  14. Nasopharyngeal carcinoma presented as cavernous sinus tumour.

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    Moona, Mohammad Shafi; Mehdi, Itrat

    2011-12-01

    A 32 year Libyan male presented with the complaints of headache and diplopia. He was diagnosed with a cavernous sinus meningioma on the basis of MRI findings but no initial biopsy was taken. Depending on the radiologic diagnosis the patient was treated with gamma knife surgery twice, abroad. During follow up he developed left ear deafness and left cervical lymph adenopathy. An ENT evaluation with biopsy from the nasopharynx and cervical lymph node was taken. The histopathologic diagnosis of the resected tumour showed a nasopharyngeal carcinoma with cervical lymph node metastasis (poorly differentiated lympho-epithelial carcinoma). The cavernous sinus tumour which was initially treated as a meningioma was in fact metastasis from the nasopharyngeal carcinoma, making this an interesting and rare occurrence.

  15. 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.

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

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    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

  17. 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

  18. 局部晚期鼻咽癌综合治疗研究进展%Combined Treatment of Loco-regionally Advanced Nasopharyngeal Carcinoma

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    高云生

    2012-01-01

    局部晚期鼻咽癌的治疗以放、化综合治疗为主,方案有诱导化疗、同期放化疗和辅助化疗及其不同的组合.同期放化疗(或加辅助化疗)是NCCN指南推荐的治疗方式.鼻咽癌的新辅助化疗虽然对提高总生存作用尚不肯定,但是其高缓解率及减少远处转移的潜能,可能使部分患者受益.含有紫杉类药物的新辅助化疗方案、靶向药物联合同期化疗亦成为临床研究的热点.%Radiotherapies combined with chemotherapy, such as neo-adjuvant chemotherapy, concomitant chemo-radiotherapy, and adjuvant chemotherapy, are recommended in the treatment of loco-regionally advanced nasopharyngeal carcinoma (NPC). Concurrent chemo-radiotherapy is the standard treatment for advanced NPC. Although whether neo-adjuvant chemotherapy could improve the overall survival still remains uncertain, this treatment can increase the response rate and potentially eradicate the subclinical metastasis in patients with advanced NPC. The addition of paclitaxel and cisplatin-based neo-adjuvant chemotherapy has shown potential in terms of therapeutic efficacy and safety. The clinical trials of the neo-adjuvant chemotherapy combined with subsequent chemo-radiotherapy are more widely studied than independent radiotherapy and chemotherapy. Targeted therapy in combination with radiotherapy and chemotherapy is also popular in current studies.

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

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    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.

  20. MicroRNAs in nasopharyngeal carcinoma

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    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.

  1. A Review: Proteomics in Nasopharyngeal Carcinoma

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    Ze-Tan Chen

    2015-07-01

    Full Text Available Although radiotherapy is generally effective in the treatment of major nasopharyngeal carcinoma (NPC, this treatment still makes approximately 20% of patients radioresistant. Therefore, the identification of blood or biopsy biomarkers that can predict the treatment response to radioresistance and that can diagnosis early stages of NPC would be highly useful to improve this situation. Proteomics is widely used in NPC for searching biomarkers and comparing differentially expressed proteins. In this review, an overview of proteomics with different samples related to NPC and common proteomics methods was made. In conclusion, identical proteins are sorted as follows: Keratin is ranked the highest followed by such proteins as annexin, heat shock protein, 14-3-3σ, nm-23 protein, cathepsin, heterogeneous nuclear ribonucleoproteins, enolase, triosephosphate isomerase, stathmin, prohibitin, and vimentin. This ranking indicates that these proteins may be NPC-related proteins and have potential value for further studies.

  2. Epstein-Barr virus and nasopharyngeal carcinoma

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    Lawrence S Young; Christopher W Dawson

    2014-01-01

    Since its discovery 50 years ago, Epstein-Barr virus (EBV) has been linked to the development of cancers originating from both lymphoid and epithelial cells. Approximately 95% of the world’s population sustains an asymptomatic, life-long infection with EBV. The virus persists in the memory B-cell pool of normal healthy individuals, and any disruption of this interaction results in virus-associated B-cel tumors. The association of EBV with epithelial cel tumors, specifical y nasopharyngeal carcinoma (NPC) and EBV-positive gastric carcinoma (EBV-GC), is less clear and is currently thought to be caused by the aberrant establishment of virus latency in epithelial cells that display premalignant genetic changes. Although the precise role of EBV in the carcinogenic process is currently poorly understood, the presence of the virus in al tumor cel s provides opportunities for developing novel therapeutic and diagnostic approaches. The study of EBV and its role in carcinomas continues to provide insight into the carcinogenic process that is relevant to a broader understanding of tumor pathogenesis and to the development of targeted cancer therapies.

  3. Current and emerging treatment options for nasopharyngeal carcinoma

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    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

  4. 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.

  5. Distinct serumal proteomic patterns between ascending and descending types of loco-regionally advanced nasopharyngeal carcinoma assessed by surface enhanced laser desorption ionization and artificial neural network analyses

    Institute of Scientific and Technical Information of China (English)

    GUO Xiang; MIN Hua-qing; ZENG Yi-xin; CAO Su-mei; YU Jie-kai; HONG Ming-huang; ZHANG Chang-qing; LI Ning-wei; XIANG Yan-qun; QIAN Chao-nan; HU Xun

    2005-01-01

    @@ Nasopharyngeal carcinoma (NPC) is rare in most countries,especially in Europe and North America (incidence rate below 1/100 000 people per year). However, it has a high incidence in several southern areas in China, especially in the Cantonese region, including Guangzhou city, where the incidence rate is approximately 30-80/100 000 people per year.1 In the high incidence areas, more than 95% NPCs are poorly differentiated (WHO types 2 and 3), which are sensitive to radiotherapy and chemotherapy. Besides its special epidemiological and pathological characteristics, NPC differs from other head and neck cancers in terms of its unique clinical development features. The advanced NPCs can be divided into three clinical types:2 (a) cranial type (A or ascending type) is characterized by direct extension of the tumor toward the base of skull with involvement of the cranial nerves Ⅰ, Ⅲ, Ⅳ, Ⅴ1 and Ⅵ and/or destruction of the bone, but without cervical lymphadenopathy. About 12.4% patients belonged to this type; (b) generalized cervical lymphadenopathy type (D or descending type) has the special feature of extensive metastasis in the cervical lymph nodes on one or both sides with a large mass of 8 cm×8 cm, yet without affecting the cranial nerves (42.2%); (c) mixed type (AD or ascending-descending type) shows the features of both the above 2 types, but cervical lymphadenopathy usually remains localized for a long time and the size of the mass rarely reaches 8 cm×8 cm (30.0%). A representative example of type A and type D patients is shown in Fig. 1. Different clinical subsets have different biological behaviors, different treatment outcomes, and deserve different therapeutic plans. Therefore, defining NPC clinical types is useful for the individualized therapeutic planning.

  6. 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.

  7. Meningeal carcinomatosis in undifferentiated nasopharyngeal carcinoma: a case report.

    Science.gov (United States)

    Cushman, Daniel M; Giese, German; Rouhani, Panta

    2014-07-01

    Meningeal carcinomatosis is the tumoral invasion of the leptomeninges. It is caused by the spread of malignant cells throughout the subarachnoid space, which produces signs and symptoms due to multifocal involvement. Cranial nerve symptoms are the most common focal findings. The diagnosis is usually made by imaging and/or cytology. Head and neck cancers are the cause of approximately 2% of all cases of meningeal carcinomatosis; in very rare cases, they are caused by a nasopharyngeal carcinoma. We report a case of meningeal carcinomatosis that was caused by a recurrence of undifferentiated nasopharyngeal carcinoma. The patient, a 60-year-old woman, experienced no focal neurologic symptoms and exhibited no radiologic evidence of meningeal involvement. We also review the literature on meningeal carcinomatosis secondary to nasopharyngeal carcinoma.

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

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A proposal concerning the histological typing of primary nasopharyngeal carcinoma is offered in order to coincide with pathologic terms used both by Chinese and foreign pathologists and reflect the achievements in the research field of NPC. This proposal was worked out mainly basing upon the authors' diagnostic experience gained in the past 30 years and the international criteria for tumor classification. Primary nasopharyngeal carcinoma could be classified into four major types, namely, keratinizing squamous cell carcinoma (KSCC), non- keratinizing carcinoma (NKC), adenocarcinoma (AC) and carcinoma in-situ (CIS). KSCC could be graded as being well, moderately and poorly differentiated according to the amount of keratinization and intercellular bridges presented in the biopsy slide. The NKC is the most frequent type seen in the high-incidence area of NPC, and could also be subdivided into differentiated and undifferentiated variants. Actually, three grades of KSCC and two variants of NKC are a reflection of different degrees of squamous differentiation. They are consistently associated with Epstein-Barr virus (EBV) infection. There are two major nasopharyngeal AC is rarely infected with EBV. There are two subtypes of CIS, namely, squamous- and columnar-cell type. The histological typing concerning the primary nasopharyngeal carcinoma offered above is really a practical proposal and also coincided with the international usage. This proposal can be mastered easily and the authors recommend its routine use in diagnostic pathology.

  9. 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

  10. 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

  11. Epstein-Barr virus-targeted therapy in nasopharyngeal carcinoma

    NARCIS (Netherlands)

    Stoker, S.D.; Novalić, Z.; Wildeman, M.A.; Huitema, A.D.R.; Verkuijlen, S.A.W.M.; Juwana, H.; Greijer, A.E.; Tan, I.B.; Middeldorp, J.M.; de Boer, J.P.

    2015-01-01

    Purpose Despite successful primary treatment of nasopharyngeal carcinoma (NPC), the incidence of distant metastasis remains 25-34 %. Treatment options are limited, and survival is poor. Intratumoural Epstein-Barr virus (EBV) was used as treatment target. In NPC, EBV is present in a latent state, exp

  12. 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

  13. 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 Denmark. RESULTS: The prevalence rate of EBV-associated gastric carcinomas was 8.5% in both populations. CONCLUSION: The findings of this study argue against a general susceptibility to EBV-associated carcinomas among the Inuit....

  14. 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.

  15. Late neurotoxicity after nasopharyngeal carcinoma treatment;Toxicite neurologique tardive apres traitement des carcinomes nasopharynges

    Energy Technology Data Exchange (ETDEWEB)

    Siala, W.; Mnejja, W.; Daoud, J. [Hopital Habib-Bourguiba, Service de Radiotherapie Carcinologique, Sfax (Tunisia); Khabir, A.; Boudawara, T. [Hopital Habib-Bourguiba, Service d' Anatomopathologie, Sfax (Tunisia); Ben Mahfoudh, K. [Hopital Habib-Bourguiba, Service de Radiologie, Sfax (Tunisia); Ghorbel, A. [Hopital Habib-Bourguiba, Service d' ORL, Sfax (Tunisia); Frikha, M. [Hopital Habib-Bourguiba, Service de Carcinologie Medicale, Sfax (Tunisia)

    2009-12-15

    Purpose A retrospective analysis of risk factors for late neurological toxicity after nasopharyngeal carcinoma radiotherapy. Patients and methods Between 1993 and 2004, 239 patients with non metastatic nasopharyngeal carcinoma were treated by radiotherapy associated or not to chemotherapy. Radiotherapy was delivered with two modalities: hyperfractionated for 82 patients and conventional fractionation for 157 patients. We evaluated the impact of tumour stage, age, gender, radiotherapy schedule and chemotherapy on neurological toxicity. Results After a mean follow-up of 107 months (35-176 months), 21 patients (8.8%) developed neurological complications, such as temporal necrosis in nine cases, brain stem necrosis in five cases, optics nerve atrophy in two cases and myelitis in one case. Five- and ten-year free of toxicity survival was 95 and 84% respectively. Young patients had greater risk of temporal necrosis, and hyperfractionated radiotherapy was associated with a significantly higher risk of neurological complications (14.6% vs 5.7%, p = 0.02). On multivariate analysis, hyperfractionation and age were insignificant. Conclusion Late neurological toxicity after radiotherapy for nasopharyngeal carcinoma was rare. Younger age and hyperfractionation were considered as risk factors of neurological toxicity in our study

  16. Favorable prognosis of female patients with nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xing Lu; Fei-Li Wang; Xiang Guo; Lin Wang; Hai-Bo Zhang; Wei-Xiong Xia; Si-Wei Li

    2013-01-01

    The female sex is traditionally considered a favorable prognostic factor for nasopharyngeal carcinoma (NPC).However,no particular study has reported this phenomenon.To explore the prognostic impact of gender on patients with NPC after definitive radiotherapy,we reviewed the clinical data of 2,063 consecutive patients treated between 1st January 2000 and 31st December 2003 in the Sun Yat-sen University Cancer Center.The median follow-up for the whole series was 81 months.The female and male patients with early stage disease comprised 49.4% and 28.1% of the patient population,respectively.Both the 5-year overall survival (OS) and disease-specific survival (DSS) rates of female patients were significantly higher than those of male patients (OS:79% vs.69%,P < 0.001; DSS:81% vs.70%,P < 0.001).For patients with Iocoregionally advanced NPC,the 5-year OS and DSS rates of female vs.male patients were 74% vs.63% (P < 0.001) and 76% vs.64%,respectively (P < 0.001).A multivariate analysis showed that gender,age,and TNM stage were independent prognostic factors for the 5-year OS and DSS of NPC patients.The favorable prognosis of female patients is not only attributed to the early diagnosis and treatment but might also be attributed to some intrinsic factors of female patients.

  17. The diagnosis of nasopharyngeal carcinoma by optical coherence tomography (OCT)

    Science.gov (United States)

    Li, J. H.; Du, Y.

    2016-06-01

    We have attempted to explore the intrinsic differences in the optical properties of the nasopharyngeal carcinoma (NPC) and normal tissue by optical coherence tomography (OCT). OCT imaging of normal tissue provided three layers of epithelium, lamina propria, and the brighter interface of basement membrane; while carcinomas disrupted the layered construction embedded in signal-poor images. The morphologies were consistent with histological findings. Sensitivity and specificity were 90% and 100%, respectively. This pilot study demonstrates that NPC could be diagnosed by visualization, which implies that OCT might be potentially used to differentiate normal from NPC tissue in the early stage as an invasive biopsy.

  18. Diagnosis of Post-Radiotherapy Local Failures in Nasopharyngeal Carcinoma: A Prospective Institutional Study

    OpenAIRE

    2014-01-01

    Background This prospective study was conducted to evaluate and compare the efficacies of nasopharyngoscopy and CT scan in the diagnosis of local failure of external beam radiotherapy (EBRT) for nasopharyngeal carcinoma. Methods Total 52 patients of histopathologically proven nasopharyngeal carcinoma treated with external beam radiotherapy (EBRT), were included in this study. For every patient computed tomography (CT), nasopharyngoscopy and nasopharyngeal biopsies were performed 3 months afte...

  19. 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.

  20. 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

  1. A case series of Nasopharyngeal Carcinoma among Indians, a low risk population, in Perak State, Malaysia.

    Science.gov (United States)

    Anusha, B; Philip, R; Norain, K; Harvinder, S; Gurdeep, S M

    2012-12-01

    Nasopharyngeal carcinoma (NPC) is rare among people of Indian ethnicity. A short retrospective case review of clinical records of Indian patients diagnosed with nasopharyngeal carcinoma in a period of 5 years was conducted. Their slides were further subjected to EBV encoded RNA (EBER) - In- situ Hybridization (ISH). The histologic subtype was nonkeratinizing carcinoma in all 4 patients. All were Epstein Barr Virus (EBV) positive. We believe that the crucial factor responsible for nasopharyngeal carcinoma is genetics; either a genetic susceptibility among high risk groups or genetic resistance/immunity in low risk groups. Further genetic studies are required to look for somatic or inherited chromosomal mutations among the various risk populations.

  2. 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.

  3. 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.

  4. Early discrimination of nasopharyngeal carcinoma based on tissue deoxyribose nucleic acid surface-enhanced Raman spectroscopy analysis

    Science.gov (United States)

    Qiu, Sufang; Li, Chao; Lin, Jinyong; Xu, Yuanji; Lu, Jun; Huang, Qingting; Zou, Changyan; Chen, Chao; Xiao, Nanyang; Lin, Duo; Chen, Rong; Pan, Jianji; Feng, Shangyuan

    2016-12-01

    Surface-enhanced Raman spectroscopy (SERS) was employed to detect deoxyribose nucleic acid (DNA) variations associated with the development of nasopharyngeal carcinoma (NPC). Significant SERS spectral differences between the DNA extracted from early NPC, advanced NPC, and normal nasopharyngeal tissue specimens were observed at 678, 729, 788, 1337, 1421, 1506, and 1573 cm-1, which reflects the genetic variations in NPC. Principal component analysis combined with discriminant function analysis for early NPC discrimination yielded a diagnostic accuracy of 86.8%, 92.3%, and 87.9% for early NPC, advanced NPC, and normal nasopharyngeal tissue DNA, respectively. In this exploratory study, we demonstrated the potential of SERS for early detection of NPC based on the DNA molecular study of biopsy tissues.

  5. Prognostic Value of Plasma Epstein-Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era.

    Science.gov (United States)

    Chen, Wen-Hui; Tang, Lin-Quan; Guo, Shan-Shan; Chen, Qiu-Yan; Zhang, Lu; Liu, Li-Ting; Qian, Chao-Nan; Guo, Xiang; Xie, Dan; Zeng, Mu-Sheng; Mai, Hai-Qiang

    2016-02-01

    This study aimed to evaluate the prognostic value of plasma Epstein-Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level EBV DNA ≥ 4000  copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68-84]) versus (93%, 95% CI [90-96], P EBV DNA levels (HR = 3.324, 95% CI, 1.80-6.138, P EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647-14.956, P EBV DNA levels (HR = 3.753, 95% CI, 1.701-8.284, P EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized clinical trials are needed to further evaluate whether plasma EBV DNA levels could be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients.

  6. Conformal radiotherapy for locally advanced juvenile nasopharyngeal angio-fibroma

    Directory of Open Access Journals (Sweden)

    Supriya Mallick

    2015-01-01

    Full Text Available Purpose: To assess the efficacy of radiation in the treatment of juvenile nasopharyngeal angiofibroma (JNA. Materials and Methods: Data were retrieved for JNA treated with radiotherapy from 1987-2012. The demographics, treatment and outcome data were recorded in predesigned proforma. Results: Data of 32 patients were retrieved. Median age was 17 years (range: 12-33 years. All patients received radiation because of refractory, residual or unresectable locally advanced disease. All patients were planned with a three-dimensional conformal technique (3DCRT. The median radiation dose was 30 Gray (range: 30-45 Gray. Median follow-up was 129 months (range: 1-276 months. At the last follow-up, 13 patients were found to have a radiological complete response. Two patients progressed 38 and 43 months after completion of treatment and opted for alternative treatment. One patient developed squamous cell carcinoma of the nasal ale 15 years after radiation. Conclusion: Conformal radiotherapy shows promise as an alternative treatment approach for locally advanced JNA and confers long-term disease control with minimal toxicity.

  7. Concurrent alterations of RAGE, RECK, and MMP9 protein expression are relevant to Epstein-Barr virus infection, metastasis, and survival in nasopharyngeal carcinoma

    OpenAIRE

    2014-01-01

    This study aimed to concurrently investigate the expressions of receptor for advanced glycation end products (RAGE), reversion inducing cysteine-rich protein with Kazal motifs (RECK) and matrix metalloproteinase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and their correlations with clinicopathological properties. Using immunohistochemistry, we found that RECK expression was downregulated in NPC tissues compared with chronic nasopharyngitis (CNT) tissues, while RAGE and MMP9 expressions were u...

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

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    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.

  9. Metabolic disorders and the risk of nasopharyngeal carcinoma: a case-control study in Italy.

    Science.gov (United States)

    Zucchetto, Antonella; Taborelli, Martina; Bosetti, Cristina; Montella, Maurizio; La Vecchia, Carlo; Franchin, Gianni; Libra, Massimo; Serraino, Diego; Polesel, Jerry

    2016-07-29

    The aim of this study is to evaluate the association between metabolic disorders and the risk of nasopharyngeal carcinoma, considering different histological subtypes. Between 1992 and 2008, we carried out a multicentre case-control study in Italy. One-hundred and ninety-seven White patients with histologically confirmed nasopharyngeal carcinoma were enrolled as cases. The control group included 592 cancer-free patients, frequency matched by study centre, area of residence, sex, age and period of interview. Odds ratios (OR) and corresponding 95% confidence intervals (CI), for nasopharyngeal carcinoma according to obesity and self-reported history of other metabolic disorders, were calculated through logistic regression models adjusted for matching variables and tobacco smoking and drinking habits. Obesity (OR=1.44; 95% CI: 0.88-2.36), diabetes mellitus (OR=0.91; 95% CI: 0.42-1.98), hypertension (OR=0.79; 95% CI: 0.48-1.32), hypercholesterolaemia (OR=1.41; 95% CI: 0.84-2.35) and metabolic syndrome (i.e. at least three among the four previously cited metabolic disorders; OR=1.11; 95% CI: 0.86-1.43) were not significantly associated with the overall risk of nasopharyngeal carcinoma. However, the associations observed for diabetes mellitus, hypercholesterolaemia and metabolic syndrome were stronger among differentiated nasopharyngeal carcinomas than among undifferentiated ones. In particular, 21.7% of differentiated nasopharyngeal carcinoma cases and 7.8% of controls reported a history of metabolic syndrome (OR=3.37; 95% CI: 1.05-10.81). The results of the study indicated no overall association between metabolic disorders and nasopharyngeal carcinoma. Nonetheless, although the small sample size calls for caution in interpretation, metabolic disorders could increase the risk of differentiated nasopharyngeal carcinoma. This finding further supports a different aetiology of the two histological subtypes.

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

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    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.

  11. FREQUENT STRUCTURE ALTERATIONS OF p53 GENE IN NASOPHARYNGEAL CARCINOMA

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    龙江斌; 区宝祥; 梁启万; 李辉梅

    1998-01-01

    By southern hybridization with 1.8 kb cDNA probe,a high freqnency (40.5%) of structural abnormality of p 53 gene was observed in primary nasopharyngeal carcinoma (NPC) biopsies. The regioas of exons 1 to 4 of the gene were examined by poiymerase chain reaction-single strand conformation polymorphism, no point nmtation was found. Because very low rate of point mutation had been reported in exons 5 to 8,we considered that structural ahnormality in the region of exons 1 to 8 of the gene might be uncommon in NPC. The speetrophotometer scaaning analysis of outoradiograms and rehybridization investigation of nitrocellulose filter with exon 11 probe indicated that most of structure aberrations we observed might be rearrangement occurring in exon ll.

  12. A Study of 358 Cases of Locally Advanced Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiation Therapy: Improving the Seventh Edition of the American Joint Committee on Cancer T-Staging System

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    Qin Zhou

    2017-01-01

    Full Text Available To evaluate the rationality and limitations of the seventh edition of the American Joint Committee on Cancer (the 7th AJCC edition T-staging system for locally advanced nasopharyngeal carcinoma (NPC. The prognosis of 358 patients with stage T3/T4 NPC treated with intensity-modulated radiotherapy (IMRT was analyzed with the Kaplan–Meier method or the log-rank test. The 7th AJCC staging system of NPC has some limitations in that the T category is neither the significant factor in OS/LRFS nor the independent prognostic factor in OS/LRFS/DMFS/DFS (P>0.05. After adjustment by anatomic structures, univariate analysis has shown that the adjusted-T category has statistical significance between T3 and T4 for OS (86.4% and 71.3%, P=0.002, LRFS (97% and 90.9%, P=0.048, DMFS (90.9% and 77.2%, P=0.001, and DFS (86.2% and 67.5%, P=0.000, and multivariate analysis has shown that the adjusted-T category is an independent prognostic factor for OS/DMFS/DFS (with the exception of LRFS. Then, GTV-P was taken into consideration. Multivariate analysis showed that these nT categories serve as suitable independent prognostic factors for OS/DMFS/DFS (P<0.001 and LRFS (HR = 3.131; 95% CI, 1.090–8.990; P=0.043. The 7th AJCC staging system has limitations and should be improved by including the modifications suggested, such as anatomic structures and tumor volume adjustment.

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

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    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.

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

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    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.

  15. 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

  16. CXCL12 genetic variants as prognostic markers in nasopharyngeal carcinoma

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    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

  17. Proceedings of the 7th Biannual International Symposium on Nasopharyngeal Carcinoma 2015

    OpenAIRE

    Chang, Ellen T.; Mckay, James D.; Gaborieau, Valerie; Kaderi, Mohamed Arifin Bin; Purnomosari, Dewajani; Voegele, Catherine; LeCalvez-Kelm, Florence; Byrnes, Graham; Brennan, Paul; Devi, Beena; Zhang, Y; Fan, Y.; Sun, K.; Du, Z.; Sun, H

    2016-01-01

    Table of contents A1 Hope and despair in the current treatment of nasopharyngeal cancer IB Tan I1 NPC international incidence and risk factors Ellen T Chang I2 Familial nasopharyngeal carcinoma and the use of biomarkers Chien-Jen Chen, Wan-Lun Hsu, Yin-Chu Chien I3 Genetic susceptibility risk factors for sporadic and familial NPC: recent findings Allan Hildesheim I5 Genetic and environmental risk factors for nasopharyngeal cancer in Southeast Asia James D McKay, Valerie Gaborieau, Mohamed Ari...

  18. Induction Chemotherapy Improved Long-term Outcomes of Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Analysis of 5-year Survival Outcomes in the Era of Intensity-modulated Radiotherapy

    Science.gov (United States)

    Peng, Hao; Chen, Lei; Zhang, Jian; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Yuan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2017-01-01

    Background: The aim of this study is to evaluate the long-term therapeutic gain of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). Methods: Data on 957 patients with stage T1-2N2-3 or T3-4N1-3 NPC treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance influence of various covariates. Patient survival between IC and non-IC groups were compared. Results: For the 318 pairs selected from the original 957 patients by PSM, the median follow-up duration was 57.13 months (range, 1.27-78.1 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and locoregional relapse-free survival (LRRFS) rates for IC group vs. non-IC group were 87.2% vs. 80.8% (P = 0.023), 88.1% vs. 83.2% (P = 0.071), 80.7% vs. 71.4% (P = 0.011) and 92.1% vs. 86.7% (P = 0.081), respectively. Multivariate analysis identify IC as an independent prognostic factor for OS (HR, 0.595; 95% CI, 0.397-0.891; P = 0.012) and DFS (HR, 0.627; 95% CI, 0.451-0.872; P = 0.006). After excluding the patients not receiving concurrent chemotherapy, IC was found to be an independent prognostic factor for OS (HR, 0.566; 95% CI, 0.368-0.872; P = 0.01), DMFS (HR, 0.580; 95% CI, 0.367-0.916; P = 0.02) and DFS (HR, 0.633; 95% CI, 0.444-0.903; P = 0.012). Conclusions: IC is an effective treatment modality for patients with stage T1-2N2-3 and T3-4N1-3 NPC, and the incorporation of IC with standard CCRT could achieve the best therapeutic gain. PMID:28261337

  19. Radiological, pathological and DNA remission in recurrent metastatic nasopharyngeal carcinoma

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    Chan Anthony TC

    2006-10-01

    Full Text Available Abstract Background Circulating plasma Epstein Barr Virus DNA (EBV-DNA is a sensitive and specific marker of nasopharyngeal carcinoma (NPC. The mainstay of treatment of metastatic NPC is systemic chemotherapy and resection for solitary metastasis. Despite high response rate to chemotherapy, complete remission is uncommonly seen. Case Presentation We report a case of recurrent metastatic NPC in a 43-year-old man, who achieved complete remission three times with chemotherapy and surgery. Serial plasma EBV-DNA levels were measured during the course of disease. The patient had three episodes of recurrences of NPC manifested as distant metastasis. Both time, rise in the plasma EBV-DNA level preceded detection of recurrences by imaging. Following systemic chemotherapy, he achieved complete remission each time, of which was confirmed by 18-flourodeoxyglucose positron emission tomography and hepatectomy pathology. The plasma EBV-DNA level dropped to zero copy/ml at the time of each remission. Conclusion This case highlights the high chemosensitivity of NPC by illustrating a rare occurrence of complete response of metastatic NPC to chemotherapy. This case also underscores the usefulness of EBV-DNA as a useful tool in monitoring NPC by its ability to detect early recurrence and excellent correlation with treatment response.

  20. 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.

  1. Incidence of nasopharyngeal carcinoma in Malaysia, 1968--1977.

    Science.gov (United States)

    Armstrong, R W; Kannan Kutty, M; Dharmalingam, S K; Ponnudurai, J R

    1979-10-01

    A record of all known cases of nasopharyngeal carcinoma in Malaysia is complete for 10 years from 1968 to 1977. Special efforts in case-finding were made in the State of Selangor where conditions are optimal. Age-adjusted incidence rates among Chinese males and females were 16.5 and 7.2 per 100,000, among Malay males and females 2.3 and 0.7 and among Indian males, 1.0. There were no significant changes in incidence rates over the 10-year period for sex and ethnic groups, or for Chinese subethnic groups. In Chinese subethnic groups, rates were highest among Cantonese, moderate among Khek and lowest among Hokkien and Teochiu. Standardized incidence ratios using Selangor as the standard population indicate considerable under-reporting in the less urban states of Malaysia, particularly among females. In Selangor, incidence rates were similar for urban and rural residents, but the frequency of cases was higher among Chinese working in industry and living in poor neighbourhoods.

  2. 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.

  3. Descriptive epidemiology of nasopharyngeal carcinoma in Peninsular Malaysia.

    Science.gov (United States)

    Prasad, U; Rampal, L

    1992-03-01

    Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Malaysia, a country in Southeast Asia with a multiracial population. While hospital-based data on NPC and data from a few states have been reported, a comprehensive study involving every known NPC patient in the whole of Peninsular Malaysia in one particular year had never been done. In the present study, the computed incidence rate was not only adjusted for age, sex, ethnicity, and place of residence, but also direct standardization methods of Rothman and Dever were used to reduce any distortion. The mean age of the 365 new cases of NPC registered in 1988 was 46.8 years (SD +/- 12.2 years). The ages of patients ranged from 10 to 80 years. The incidence in both sexes rose after the age of 20-29 years and reached a plateau between 40 and 49 years. No further rise was exhibited after age 60 years. The Chinese had the highest age-adjusted incidence rates, particularly for the age group 40-49 years, where the incidence rate was 40.1 per 100,000 for males and 14.9 for females. The average age-adjusted male/female ratio was 2.8:1. Age-adjusted incidence varied by place of residence. The pattern that emerged from the data indicated the possibility of interaction between genetic susceptibility and environmental cofactors in the etiology of NPC.

  4. 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.

  5. Hypothalmic hypopituitarism following cranial irradiation for nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lam, K.S.L.; Wang, C.; Yeung, R.T.T.; Ma, J.T.C.; Ho, J.H.C.; Tse, V.K.C.; Ling, N.

    1986-06-01

    Eight patients, one male and seven females, with no pre-existing hypothalamic-pituitary disease, who developed symptoms of hypopituitarism following cranial irradiation for nasopharyngeal carcinoma were studied 5 years or more after radiotherapy. All were GH deficient. Four of the patients with no GH response during insulin tolerance tests (ITT) showed increased GH in response to synthetic human growth hormone releasing factor (GRF-44). Four patients had impaired cortisol responses to ITT, and gradual but diminished cortisol responses to ovine corticotrophin releasing factor (CRF-41). There was no significant difference between mean peak increments in response to ITT and those in response to CRF-41. TSH responses to TRH were delayed in five and absent in two patients; four of these had low free T4 index. Prolactin was raised in all seven women and increased further in response to TRH. Two patients had impaired gonadotrophin responses to LHRH. None of the patients had clinical or biochemical evidence of diabetes insipidus. These data suggest that post-irradiation hypopituitarism in these patients results from radiation damage to the hypothalamus leading to varying degrees of deficiency of the hypothalamic releasing or inhibitory factors.

  6. Radiological, pathological and DNA remission in recurrent metastatic nasopharyngeal carcinoma

    Science.gov (United States)

    Chan, Stephen L; Hui, Edwin P; Leung, Sing F; Chan, Anthony TC; Ma, Brigette BY

    2006-01-01

    Background Circulating plasma Epstein Barr Virus DNA (EBV-DNA) is a sensitive and specific marker of nasopharyngeal carcinoma (NPC). The mainstay of treatment of metastatic NPC is systemic chemotherapy and resection for solitary metastasis. Despite high response rate to chemotherapy, complete remission is uncommonly seen. Case Presentation We report a case of recurrent metastatic NPC in a 43-year-old man, who achieved complete remission three times with chemotherapy and surgery. Serial plasma EBV-DNA levels were measured during the course of disease. The patient had three episodes of recurrences of NPC manifested as distant metastasis. Both time, rise in the plasma EBV-DNA level preceded detection of recurrences by imaging. Following systemic chemotherapy, he achieved complete remission each time, of which was confirmed by 18-flourodeoxyglucose positron emission tomography and hepatectomy pathology. The plasma EBV-DNA level dropped to zero copy/ml at the time of each remission. Conclusion This case highlights the high chemosensitivity of NPC by illustrating a rare occurrence of complete response of metastatic NPC to chemotherapy. This case also underscores the usefulness of EBV-DNA as a useful tool in monitoring NPC by its ability to detect early recurrence and excellent correlation with treatment response. PMID:17076893

  7. Human papillomavirus detection in moroccan patients with nasopharyngeal carcinoma

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    Belghmi Khalid

    2011-02-01

    Full Text Available Abstract Background Nasopharyngeal carcinoma (NPC is a malignant tumor which arises in surface epithelium of the posterior wall of the nasopharynx. There's is evidence that Epstein Barr virus (EBV is associated to NPC development. However, many epidemiologic studies point to a connection between viral infections by the human papillomavirus (HPV and NPC. Method Seventy Moroccan patients with NPC were screened for EBV and HPV. EBV detection was performed by PCR amplification of BZLF1 gene, encoding the ZEBRA (Z Epstein-Barr Virus Replication Activator protein, and HPV infection was screened by PCR amplification with subsequent typing by hybridization with specific oligonucleotides for HPV types 16, 18, 31, 33, 35, 45 and 59. Results The age distribution of our patients revealed a bimodal pattern. Sixty two cases (88.9% were classified as type 3 (undifferentiated carcinoma, 6 (8.6% as type 2 (non keratinizing NPC and only 2 (2.9% cases were classified as type 1 (keratinizing NPC. EBV was detected in all NPC tumors, whereas HPV DNA was revealed in 34% of cases (24/70. Molecular analysis showed that 20.8% (5/24 were infected with HPV31, and the remaining were infected with other oncogenic types (i.e., HPV59, 16, 18, 33, 35 and 45. In addition, statistical analysis showed that there's no association between sex or age and HPV infection (P > 0.1. Conclusion Our data indicated that EBV is commonly associated with NPC in Moroccan patients and show for the first time that NPC tumours from Moroccan patients harbour high risk HPV genotypes.

  8. 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

  9. 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.

  10. Andrographolide suppresses proliferation of nasopharyngeal carcinoma cells via attenuating NF-κB pathway.

    Science.gov (United States)

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

    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 inhibited the proliferation and invasion of NPC cells (P Andro-mediated anticancer activities in nasopharyngeal carcinoma.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

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

    Institute of Scientific and Technical Information of China (English)

    ZHENG; Xiao-kang

    2001-01-01

    [1]Carlos AP, Luther WB. Carcinoma of the nasopharynx. In: Principles and Practice of Radiation Oncology [M]. 3th ed. Philadelphial: JB Lippincott, 1997; 930.[2]Yang TS, Ng KT, Wang HM, et al. Prognostic factors of locoregionally recurrent nasopharyngeal carcinoma ? a retrospective review of 182 cases [J]. Am J Clin Oncol 1996; 19:337.[3]Lee AW, Law SC, Foo W, et al. Retrospective analysis of patients with nasopharyngeal carcinoma treated during 1976-1985: survival after local recurrence [J]. Int J Radiat Oncol Biol Phys 1993; 26:773.[4]Lee AW, Poon YF, Foo W, et al. Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns of failure [J]. Int J Radiat Oncol Biol Phys 1992; 23:261.[5]Sanguineti G, Geara FB, Garden AS. Carcinoma of nasopharynx treated by radiotherapy alone: determinants of local and regional control [J]. Int J Radiat Oncol Biol Phys 1997; 37:973.[6]Lee AW, Foo W, Law SC, et al. Reirradiation for recurrent nasopharyngeal carcinoma: factors affecting the therapeutic ratio and ways for improvement [J]. Int J Radioat Oncol Biol Phys 1997; 38:43.[7]Chua DT, Sham JS, Kwong DL, et al. Locally recurrent nasopharyngeal carcinoma: treatment result for patients with computed tomography assessment [J]. Int J Radioat Oncol Biol Phys 1998; 41:379.[8]Teo PM, Kwan WH, Chan AT, et al. How successful is high-dose (>or = 60 Gy) reirradiation using mainly external beams in salvaging local failures of nasopharyngeal carcinoma [J]? Int J Radioat Oncol Biol Phys 1998; 40:897.[9]Pryzant RM, Wendt CD, Delclos L, et al. Retreatment of nasopharyngeal carcinoma in 53 patients [J]. Int J Radiat Oncol Biol Phys 1992; 22:94l.[10]Bajada C, Selch M, De SA, et al. Application of stereotactic radiosurgery to the head and neck region [J]. Acta Neurochir Suppl Wien 1994; 62:114.[11]Mitsuhashi N, Sakurai H, Katano S, et al. Stereotactic radiotherapy for locally recurrent

  19. 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.

  20. Knowledge of Nasopharyngeal Carcinoma Among Hmong Populations in Central California

    Directory of Open Access Journals (Sweden)

    Teng Vang

    2007-01-01

    Full Text Available The prevalence of nasopharyngeal cancer (NPC is high and the incidence is increasing among the Hmong community. To date, there have been few studies on NPC and other cancers in the Hmong population. The purpose of this study was to measure theknowledge of a rural Hmong community in California in regards to nasopharyngeal cancer. A questionnaire that evaluated knowledge of nasopharyngeal cancer was developed and given to 145 Hmong participants. The participants’ knowledge varied with age and educational level but not with gender. Middle-aged generations had thehighest level of knowledge on nasopharyngeal cancer. In contrast, low knowledge of NPC was revealed in the older generations. Participants with no school were the least knowledgeable about nasopharyngeal cancer. Those participants with the highest formal education were most knowledgeable about the disease. Hmong males and females areboth knowledgeable of nasopharyngeal cancer. This study provides insights for public health practitioners regarding culturally-sensitive strategies to control the increase of NPC in Hmong populations.

  1. [Undifferentiated naso-pharyngeal carcinoma of the Schmincke-Regaud type. Apropos of 3 cases].

    Science.gov (United States)

    James, J M; Weill, B; Bernadou, A; Temim, L; Tricot, G; Diebold, J; Zittoun, R; Bilski-Pasquier, G

    1976-01-01

    The authors present 3 cases of undifferentiared naso-pharyngeal carcinoma of the Schmincke-Regaud type. They study the anatomopathological, appearances, the geographic distribution, the background, the clinical expression and course, the immunological, virological and genetic factors of this very curious type of cancer the diagnosis and treatment of which remain difficult.

  2. Nasopharyngeal Carcinoma in Children A report of three cases with review of literature

    Directory of Open Access Journals (Sweden)

    Rauf Ahmad, A. Ahad, M. Latif, Rafiq Ahmad, Sajad M. Qazi, *Reyaz A. Tasleem

    1999-04-01

    Full Text Available Nasopharyngeal carcinoma is rare in children and adolescents. Nevertheless, it is considered to beIhe only tumour of surface epithelium afflicting children and young adults. Three such cases seenom a period of eight years (1990-1997 are reported with a review of relevant literature.

  3. 鼻咽癌患者同步放化疗期间营养状况变化及其营养支持治疗的影响%Nutritional status assessment and effect of nutritional intervention during concurrent radiochemotherapy for locally advanced nasopharyngeal carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    崔巍; 韩磊

    2011-01-01

    OBJECTIVE: To discuss the change of nutrition indices during concurrent radiochemotherapy in locally advanced nasopha-ryngeal carcinoma patients and the influence of intervention, to improve nutrition level and guarantee effectiveness. METHODS: From January to October of 2010, clinical data of initial treatment in 48 locally advanced nasopharyngeal carcinoma patients were collected, and all patients accepted concurrent radiochemotherapy. Weight (W), Hemoglobin ( Hb) , total protein (TP), albumin (Alb) were observed weekly. Nutrition intervention were given in partial of patients with weight lost rapidly . Single variance analysis was used to assess the change of nutrition indices and the nutrition intervention. RESULTS: Forty-eight patients completed concurrent radiochemotherapy. The median concurrent radiochemotherapy was 3 cycles. It was decreasing with treatment in weight of 48 patients. The 4th week of radiochemotherapy was inflection point. Part of patients whose weigh lost more quickly was given nutrition intervention. The difference of weight lost between nutrition intervention group (A) and no nutrition intervention group (B) was significant(P 0. 05). CONCLUSIONS: The nutrition indices of patients with locally advanced nasopharyngeal carcinoma were decreasing during concurrent radiochemotherapy. Nutrition intervention in time can restrain loss of weight, improve quality of life. Nutrition intervention should be important in comprehensive treatment of nasopharyngeal carcinoma.%目的:探讨局部晚期鼻咽癌治疗期间营养指标变化,便于提前采取干预措施,增加营养,保证疗效.方法:2010-01-2010-10收集48例初治局部晚期鼻咽癌患者的临床资料,全部患者均接受同步放化疗,治疗期间观察体质量(W)、血红蛋白(Hb)、总蛋白(TP)、白蛋白(ALB)以及营养干预后相关指标的变化,将患者分为未营养干预组(A组)和营养支持组(B组),分析营养干预对营养指标变化的影响.结果:48

  4. 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.

  5. 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.

  6. Meta-analysis of the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese.

    Science.gov (United States)

    Jin, Bin; Dong, Pin; Li, Keyong; Shen, Bin; Xie, Jin

    2014-01-01

    Glutathione S-transferase T1 (GSTT1) null genotype has been proven to be associated with risks of many cancers. There were also many studies assessing on the association between GSTT1 null genotype and nasopharyngeal carcinoma risk in Chinese, but the findings from those studies were inconsistent. We performed a meta-analysis to provide a more precise assessment on the effect of GSTT1 null genotype on nasopharyngeal carcinoma risk. The PubMed and Wanfang databases were searched to identify eligible case-control studies on the association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese. The pooled odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were used to assess the association. Eight case-control studies with a total of 3,702 individuals were finally included in the meta-analysis. Meta-analysis of a total of eight studies showed that GSTT1 null genotype was significantly associated with increased risk of nasopharyngeal carcinoma in Chinese (OR = 2.27; 95% CI 1.41-3.67; P = 0.001). The finding from cumulative meta-analysis showed that there was a trend of more obvious association between GSTT1 null genotype and risk of nasopharyngeal carcinoma in Chinese as data accumulated by publication year. Therefore, the GSTT1 null genotype is significantly associated with increased risk of nasopharyngeal carcinoma in Chinese.

  7. Immunohistochemical Study to Evaluate the Prognostic Significance of Four Biomolecular Markers in Radiotherapy of Nasopharyngeal Carcinoma

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    Kim, Yeon Joo; Lee, Seung Hee; Wu, Hong Gyun; Go, Heoun Jeong; Jeon, Yoon Kyung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2010-11-15

    We performed an immunohistochemical study with pre-treatment biopsy specimens to evaluate the prognostic significance of four biomolecular markers which can be used as a predictive assay for radiotherapy (RT) treatment of nasopharyngeal carcinoma (NPC). From January 1998 through December 2006, 68 patients were histologically diagnosed as non-metastatic NPC and treated by RT. Only 38 patients had the paraffin block for the immunohistochemical study. Thirty-one patients had undifferentiated carcinoma and 7 patients had squamous cell carcinoma. Thirty two patients (84%) had advanced stage NPC (2002 AJCC Stage III{approx}IV). Immunohistochemical staining was performed for Met, COX-2, nm23-H1, and epidermal growth factor receptor (EGFR) expression using routine methods. The median follow-up time was 30 months (range, 11 to 83 months) for all patients, and 39 months (range, 19 to 83 months) for surviving patients. The 5-year overall survival (OS) rate of the patients with high Met extent ({>=}50%) was significantly lower than that of the patients with low Met extent (48% vs. 84%, p=0.02). In addition, Met extent was also a significant prognostic factor in multivariate analysis (p=0.01). No correlation was observed between Met extent and T stage, N stage, stage group, gender, age, and the response to chemotherapy or RT. Met extent showed moderate correlation with COX-2 expression (Pearson coefficient 0.496, p<0.01), but COX-2 expression did not affect OS. Neither nm23-H1 or EGFR expression was a prognostic factor for OS in this study. High Met extent ({>=}50%) might be an independent prognostic factor that predicts poor OS in NPC treated with RT.

  8. 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.

  9. 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.

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

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    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).

  11. 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.

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

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    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.

  13. CFTR is a potential marker for nasopharyngeal carcinoma prognosis and metastasis.

    Science.gov (United States)

    Tu, Ziwei; Chen, Qu; Zhang, Jie Ting; Jiang, Xiaohua; Xia, Yunfei; Chan, Hsiao Chang

    2016-11-22

    While there is an increasing interest in the correlation of cystic fibrosis transmembrane conductance regulator (CFTR) and cancer incidence, the role of CFTR in nasopharyngeal carcinoma (NPC) development remains unknown. In this study, we aimed to explore the prognostic value of CFTR in NPC patients. The expression of CFTR was determined in NPC cell lines and tissues. Statistical analysis was utilized to evaluate the correlation between CFTR expression levels and clinicopathological characteristics and prognosis in 225 cases of NPC patients. The results showed that CFTR was down-regulated in NPC tissues and cell lines. Low expression of CFTR was correlated with advanced stage (p = 0.026), distant metastasis (p CFTR as an independent prognostic factor (p = 0.003). Additionally, wound healing and transwell assays revealed that overexpression of CFTR inhibited NPC cell migration and invasion, whereas knockdown of CFTR promoted cell migration and invasion. Thus, the current study indicates that CFTR, as demonstrated to play an important role in tumor migration and invasion, may be used as a potential prognostic indicator in NPC.

  14. Central pontine myelinolysis (CPM and extrapontine myelinolysis (EPM following concurrent chemoradiotherapy for nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Chen-Hui Chong

    2016-06-01

    Full Text Available Central pontine myelinolysis (CPM is a disease that may present with coma, quadriplegia, or no symptoms at all. It is an iatrogenic demyelinating disease caused most frequently by overzealous correction of chronic hyponatremia and excessive swings in serum osmolality. Lesions can also occur outside the pons as extrapontine myelinolysis (EPM. Herein we have reported a case of CPM and EPM in a patient after chemoradiotherapy for recurrent nasopharyngeal carcinoma.

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

    OpenAIRE

    2016-01-01

    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 ...

  16. 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.

  17. Unidimensional Measurement May Evaluate Target Lymph Nodal Response After Induction Chemotherapy for Nasopharyngeal Carcinoma.

    Science.gov (United States)

    Chen, Chuanben; Zhang, Mingwei; Xu, Yuanji; Yue, Qiuyuan; Bai, Penggang; Zhou, Lin; Xiao, Youping; Zheng, Dechun; Lin, Kongqi; Qiu, Sufang; Chen, Yunbin; Pan, Jianji

    2016-03-01

    The aim of the study was to evaluate whether short axis and long axis on axial and coronal magnetic resonance imaging planes would reflect the tumor burden or alteration in size after induction chemotherapy in nasopharyngeal carcinoma. Patients with pathologically confirmed nasopharyngeal carcinoma (n = 37) with at least 1 positive cervical lymph node (axial short axis ≥15 mm) were consecutively enrolled in this prospective study. Lymph nodal measurements were performed along its short axis and long axis in both axial and coronal magnetic resonance imaging planes at diagnosis and after 2 cycles of induction chemotherapy. In addition, lymph nodal volumes were automatically calculated in 3D treatment-planning system, which were used as reference standard. Student's t test or nonparametric Mann-Whitney U test was used to compare the continuous quantitative variables. Meanwhile, the κ statistic and McNemar's test were used to evaluate the degree of agreement and discordance in response categorization among different measurements. Axial short axis was significantly associated with volumes at diagnosis (P unidimensional measurements to assess tumor response, coronal short-axis showed the best concordance (κ=0.792) to the volumes. Axial short axis may effectively reflect tumor burden or change in tumor size in the assessment of target lymph nodal response after induction chemotherapy for nasopharyngeal carcinoma. However, it should be noted that axial short axis may amplify the therapeutic response. In addition, the role of coronal short axis in the assessment of tumor response needs further evaluation.

  18. 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.

  19. Two legume defense proteins suppress the mobility of nasopharyngeal carcinoma cells.

    Science.gov (United States)

    Dan, Xiuli; Ng, Tzi Bun

    2016-12-01

    A 16-kDa trypsin inhibitor was isolated from an edible legume using various chromatographic procedures. The protein was unadsorbed on Affi-gel blue gel but adsorbed on DEAE-Sepharose and Mono Q following which media the protein was subsequently subjected to gel filtration on Superdex 75 and a final 21-fold purification was achieved. This trypsin inhibitor showed remarkable pH and thermal stability. Its inhibitory activity was impaired in the presence of 1 mM dithiothreitol. The anti-proliferative and anti-mobility activities of this trypsin inhibitor and a hemagglutinin isolated from the same legume were tested on nasopharyngeal carcinoma cells. These two defense proteins demonstrated discrepant anti-proliferative efficacies that the hemagglutinin could greatly suppress the proliferation of nasopharyngeal carcinoma cells, while the trypsin inhibitor revealed a minor effect. However, these two proteins could both attenuate the mobility of nasopharyngeal carcinoma cells. The present study revealed the potential of applying plant defense proteins in cancer treatment.

  20. 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

  1. Dosimetric comparison of RapidArc with fixed gantry dynamic IMRT for loco-regionally advanced nasopharyngeal carcinoma%局部进展期鼻咽癌快速旋转调强与固定野动态调强放疗的剂量学比较

    Institute of Scientific and Technical Information of China (English)

    吴昊; 韩树奎; 孙艳; 蒋璠

    2010-01-01

    目的 比较快速旋转调强与固定野动态调强放疗技术在局部进展期鼻咽癌治疗中的剂量学差异.方法 选取10例局部进展期鼻咽癌患者,采用两种治疗技术设计同步推量调强放疗计划.在满足95%计划靶体积达60 Gy情况下,比较两种计划的剂量体积直方图、靶区和危及器官剂量、机器跳数、治疗时间.结果 快速旋转调强与固定野动态调强放疗计划在局部进展期鼻咽癌治疗剂量学上无差异.快速旋转调强计划比固定野动态调强放疗技术的靶区平均剂量略升高,最大、最小剂量无差异,脑干、下颌骨及整个治疗区域正常组织受量降低,腮腺、视神经、晶体等危及器官剂量无差异.快速旋转调强计划比固定野动态调强放疗计划的总机器跳数平均减少了57%(589.5 MU:1381.0 MU),每次治疗时间平均减少了70%(2.33 min:7.82 min).结论 两种放疗技术的治疗计划剂量分布基本一致,均能满足临床治疗需要.快速旋转调强放疗每次治疗时间明显缩短,其总机器跳数的降低减少了正常组织受照剂量.%Objective To compare the dosimetric difference of RapidArc and fixed gantry angle dynamic IMRT (dIMRT) for loco-regionally advanced nasopharyngeal carcinoma.Methods Ten previously treated patients with loco-regionally advanced nasopharyngeal carcinoma were replanned with RapidArc and dIMRT, respectively.The prescription dose was GTV 70 Gy/33 f and PTV 60 Gy/33 f.All plans met the requirement:95% of PTV was covered by 60 Gy.Dose-volume histogram data, isodose distribution, monitor units,and treatment time were compared.Results Dose distribution has no significant difference between the two techniques.RapidArc reduced the dose of the brainstem, mandible, and other normal tissues compared with dIMRT.Mean monitor units were 589.5 and 1381.0 for RapidArc and dIMRT (reduced by 57% relatively).Mean treatment time was 2.33 min and 7.82 min for RapidArc and d

  2. Therapeutic implications of Epstein–Barr virus infection for the treatment of nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Hutajulu SH

    2014-09-01

    Full Text Available Susanna Hilda Hutajulu,1 Johan Kurnianda,1 I Bing Tan,2,3 Jaap M Middeldorp4 1Department of Internal Medicine, Faculty of Medicine Universitas Gadjah Mada/Dr Sardjito General Hospital, Yogyakarta, Indonesia; 2Department of Ear, Nose and Throat, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; 3Department of Ear, Nose and Throat, Faculty of Medicine Universitas Gadjah Mada/Dr Sardjito General Hospital, Yogyakarta, Indonesia; 4Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands Abstract: Nasopharyngeal carcinoma (NPC is highly endemic in certain regions including the People's Republic of China and Southeast Asia. Its etiology is unique and multifactorial, involving genetic background, epigenetic, and environment factors, including Epstein–Barr virus (EBV infection. The presence of EBV in all tumor cells, aberrant pattern of antibodies against EBV antigens in patient sera, and elevated viral DNA in patient circulation as well as nasopharyngeal site underline the role of EBV during NPC development. In NPC tumors, EBV expresses latency type II, where three EBV-encoded proteins, Epstein–Barr nuclear antigen 1, latent membrane protein 1 and 2 (LMP1, 2, are expressed along with BamH1-A rightward reading frame 1, Epstein–Barr virus-encoded small nuclear RNAs, and BamH1-A rightward transcripts. Among all encoded proteins, LMP1 plays a central role in the propagation of NPC. Standard treatment of NPC consists of radiotherapy with or without chemotherapy for early stage, concurrent chemoradiotherapy in locally advanced tumors, and palliative systemic chemotherapy in metastatic disease. However, this standard care has limitations, allowing recurrences and disease progression in a certain proportion of cases. Although the pathophysiological link and molecular process of EBV-induced oncogenesis are not fully understood, therapeutic approaches targeting the virus may increase the

  3. POPULATION CHARACTERS IN HIGH RISK PEDIGREES OF NASOPHARYNGEAL CARCINOMA (NPC)

    Institute of Scientific and Technical Information of China (English)

    HUANG Teng-bo; ZHANG Jin-ming; HUANG Hui-ming; LI Jing-lian; HUANG Guo-dong

    1999-01-01

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

  4. Prospective study on comparison between Docetaxol-Nedaplatin and Cisplatin-Fluorouracil regimens inducing radiotherapy for locally advanced nasopharyngeal carcinoma%多西他赛加奈达铂和顺铂加氟尿嘧啶方案诱导化疗局部晚期鼻咽癌的前瞻性研究

    Institute of Scientific and Technical Information of China (English)

    陈冬平; 余意; 齐斌

    2012-01-01

    Objective To compare the short term results and adverse effects of docetaxel-nedaplatin (DN) and cisplatin-fluorouracil (PF) regimens for induction chemotherapy in locally advanced nasopharyngeal carcinoma.Methods 86 locally advanced nasopharyngeal carcinoma patients were randomly allocated into either experimental or control group.There were 44 and 42 cases in thc experimental group (DN regime) and control group (PF regime),respectively.All patients received radical radiotherapy in 10 days after two courses of induction chemotherapy.Results (1) Adverse effects:DN group got less adverse effect in the bone marrow inhibit.gastrointestinal reactions,vasculitis,and mucosal reactions compared with PF group.The gastrointestinal reactions,vasculitis,and mucosal had statistical significance (P<0.05).PF group got significant less alopecia (P<0.05).(2) Clinical outcomes:short-term response rate after induction chemotherapy in DN group( 51.1% ) was significantly better than that of the PF group( 29.3% ) (P<0.05); one-year overall survival (OS)rates both were 100%; and one-year disease free survival (PFS) between the two groups( DN was 97.7%,PF was 92.9% )were not significantly different.Conclusion DN regimen has less adverse reactions,better short-terrn response rates and same survival rates.DN regimen could be a better option as reduction chemotherapy for locally advgnced nasopharyngeal carcinoma.%目的 比较多西他赛联合奈达铂(DN)方案和顺铂联合氟尿嘧啶(PF)方案诱导化疗治疗局部晚期鼻咽癌的近期疗效和不良反应.方法 86例局部中晚期鼻咽癌患者随机分为DN组(44例)和PF组(42例),两组患者均给予根治性放疗,诱导化疗PF组采用PF方案,DN组采用DN方案,诱导化疗第二疗程后十天内开始放疗.结果 不良反应:DN组在骨髓抑制反应、胃肠道反应、脉管炎、黏膜炎方面均小于PF组,其中胃肠道反应、脉管炎、黏膜炎方面差异有显著性沪< 0.05); DN

  5. Clinical significance of hypoxia in nasopharyngeal carcinoma with a focus on existing and novel hypoxia molecular imaging.

    Science.gov (United States)

    Yip, Connie; Cook, Gary J R; Wee, Joseph; Fong, Kam Weng; Tan, Terence; Goh, Vicky

    2016-04-01

    Locally advanced nasopharyngeal carcinoma (NPC) is still associated with significant locoregional failure and poor overall survival (OS) after chemoradiation. The maximal therapeutic effect of conventional chemotherapy combined with radiation may have been reached and there is a clinical need to identify additional adverse prognostic factors that could be targeted therapeutically. Hypoxia, a known prognostic factor in head and neck cancers is an attractive target in NPC with various treatment strategies available such as hypoxic cell sensitisers/cytotoxins and increasing intratumoral oxygen delivery, to overcome the poorer outcomes associated with this phenotype. Thus, we aim to review the clinical significance of hypoxia as well as the current and future of molecular hypoxia imaging in NPC.

  6. 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.

  7. 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.

  8. Unidimensional measurement may be superior to assess primary tumor response after neoadjuvant chemotherapy for nasopharyngeal carcinoma.

    Science.gov (United States)

    Chen, Chuanben; Lin, Xiurong; Xu, Yuanji; Bai, Penggang; Xiao, Youping; Pan, Yuhui; Li, Chao; Lin, Zhizhong; Zhang, Mingwei; Chen, Yunbin

    2017-02-01

    Application of current response evaluation criteria in solid tumors (RECIST 1.1) for assessment of irregularly shaped nasopharyngeal carcinoma (NPC) is a gray area with much ambiguity. Our aim was to compare unidimensional measurements (UDM) and bidimensional measurements (BDM) on magnetic resonance images in alternative planes for measurement of tumor response after neoadjuvant chemotherapy (NACT) in patients with locally advanced NPC. 59 patients with untreated non-metastatic NPC were prospectively enrolled. The size or change in size of the primary tumor and retropharyngeal nodes was assessed by UDM and BDM on axial and coronal planes before and after 2 cycles of NACT. Tumor volume was considered as the reference standard. Correlation between volume and diameter was analyzed using a general linear model. The degree of agreement and discordance of response classification based on different measures were evaluated with κ statistic and McNemar's test, respectively. Both axial UDM (RECIST 1.1) and axial BDM (WHO) showed a significant association with volumetric standard. However, the agreement of axial UDM with VM was better than that of axial BDM (κ value: 0.514 to 0.372). In addition, when increasing coronal planes to evaluate tumor response with UDM and BDM, an inferior agreement between coronal BDM and VM was still observed. Notably, coronal UDM showed the best consistency with volume (κ = 0.585). Hence, axial UDM showed better correlation with volumetric measurements than axial BDM. Since coronal UDM showed high correlation to VM, we suggest further research to assess its use for response assessment of NPC after NACT.

  9. 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.

  10. 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.

  11. Concurrent alterations of RAGE, RECK, and MMP9 protein expression are relevant to Epstein-Barr virus infection, metastasis, and survival in nasopharyngeal carcinoma.

    Science.gov (United States)

    Zhou, Dong-Ni; Deng, Yan-Fei; Li, Rong-Hua; Yin, Ping; Ye, Chun-Sheng

    2014-01-01

    This study aimed to concurrently investigate the expressions of receptor for advanced glycation end products (RAGE), reversion inducing cysteine-rich protein with Kazal motifs (RECK) and matrix metalloproteinase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and their correlations with clinicopathological properties. Using immunohistochemistry, we found that RECK expression was downregulated in NPC tissues compared with chronic nasopharyngitis (CNT) tissues, while RAGE and MMP9 expressions were upregulated. We further found that RECK expression level was inversely correlated with MMP9 expression level in NPC, whereas RAGE expression level was positively correlated with MMP9 expression level. Moreover, aberrant expressions of these proteins had a positive correlation with the titers of EBVCA-IgA, lymphatic metastasis, recurrence and survival. Together, these findings suggest that dysregulations of RECK and RAGE expressions may be collectively involved in tumor progression of NPC by regulating MMP9 expression and that they may be a good prognostic predictors for NPC.

  12. 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.

  13. Plasma Epstein-Barr virus DNA as a biomarker for nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    KC Allen Chan

    2014-01-01

    Nasopharyngeal carcinoma (NPC) is common in southern China and Southeast Asia. Epstein-Barr virus (EBV) infection is an important etiology for NPC, and EBV genome can be detected in almost all tumor tissues of NPC in this region. Plasma EBV DNA, when quantitatively analyzed using real-time polymerase chain reaction (PCR), has been developed as a biomarker for NPC. In this review, the different clinical applications of plasma EBV DNA in the management of NPC, including screening, monitoring, and prognostication, are discussed. In addition, the biological issues of circulating EBV DNA, including the molecular nature and clearance kinetics, are also explored.

  14. Gemcitabine Induced Radiation Recall Myositis in a Patient with Relapsed Nasopharyngeal Carcinoma

    Science.gov (United States)

    Patel, Sagar C.; Paulino, Arnold C.; Johnston, Danielle; Wiederhold, Lee; Castillo, Richard; Venkatramani, Rajkumar

    2016-01-01

    Radiation recall reaction is an acute inflammatory response evident in previously irradiated fields, induced by chemotherapy administration. Sixteen-year-old female with relapsed nasopharyngeal carcinoma was treated with gemcitabine and oxaliplatin. Disease remission was observed after four cycles. After the seventh cycle, patient developed acute pain and swelling involving the neck muscles. The affected muscles were within the previous irradiation field. Her symptoms improved with corticosteroid treatment. In contrast to other chemotherapy agents, gemcitabine can induce recall reaction involving deeper tissues. Gemcitabine therapy should be discontinued in the event of a radiation recall, as subsequent exposure will likely exacerbate symptoms. PMID:27637134

  15. 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.

  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. Clinical significance of plasma epstein-barr virus DNA quantitative monitoring in the treatment and follow-up for locally advanced nasopharyngeal carcinoma%血浆EB病毒DNA定量监测在局部晚期鼻咽癌治疗及随访中的临床意义

    Institute of Scientific and Technical Information of China (English)

    张倩; 孙秀锦; 宋丹

    2014-01-01

    Objective To explore the clinical significance of plasma epstein⁃barr virus DNA( EBV⁃DNA) quantitative moni⁃toring in the treatment and follow⁃up for locally advanced nasopharyngeal carcinoma. Methods Plasma EBV⁃DNA levels of 156 locally advanced nasopharyngeal cancer patients were detected during concurrent radiochemotherapy with 0, 2, 4, 6, 8 weeks, and plasma EBV⁃DNA levels of patients with who plasma EBV⁃DNA⁃positive before the treatment and followed up were detected after 6, 12, 18, 24 months, using quantitative PCR technique. The efficacy and recurrence and metastasis situation during two years after treatment were evaluated respectively. Results Plasma EBV⁃DNA⁃positive rate of 156 patients was 91�0% (142/156) before concurrent radio⁃chemotherapy, and positive rate of 9�6% ( 15/156) after 8 weeks of the treatment. One hundred and twenty⁃seven out of 142 plasma EBV⁃DNA⁃positive patients with pre⁃treatment, plasma EBV⁃DNA levels showed a trend of decline from the treatment of 2 weeks. On 6 weeks of the treatment, DNA replication were not detected in 127 patients. The other plasma EBV⁃DNA level of 15 cases maintained the positive level after 8 weeks of the treatment. One hundred and nineteen cases were complete response and 37 cases were partial re⁃sponse, of which the plasma EBV⁃DNA positive rate of 8 weeks after the treatment was 3�4% (4/119) and 29�7% (11/37), respec⁃tively. 135 out of 142 patients with pre⁃treatment plasma EBV⁃DNA⁃positive were followed up for two years, 1⁃, 2⁃year recurrence rate was 14�1% (19/135) and 23�0% (31/135), respectively. By receiver operating characteristic curve analysis, 1⁃, 2⁃year plasma EBV⁃DNA levels were higher judged on accuracy of 1⁃, 2⁃year recurrence rate (Az1=0�944,Az2=0�925;P<0�05). Conclusion Quantification of plasma EBV⁃DNA level can better reflect the efficacy of locally advanced nasopharyngeal carcinoma after comprehen⁃sive treatment

  18. 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.

  19. 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.

  20. 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.

  1. Salinomycin radiosensitizes human nasopharyngeal carcinoma cell line CNE-2 to radiation.

    Science.gov (United States)

    Zhang, Yongqin; Zuo, Yun; Guan, Zhifeng; Lu, Weidong; Xu, Zheng; Zhang, Hao; Yang, Yan; Yang, Meilin; Zhu, Hongcheng; Chen, Xiaochen

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is primarily treated by chemoradiation. However, how to promote radiation sensitivity in NPC remains a challenge. Salinomycin is potentially useful for the treatment of cancer. This study aimed to explore the radiosensitivity of salinomycin on human nasopharyngeal carcinoma cell line CNE-2. CNE-2 were treated with salinomycin or irradiation, alone or in combination. The cytotoxicity effects of salinomycin were measured using CCK-8 assay. Clonogenic survival assay was used to evaluate the effects of salinomycin on the radiosensitivity of CNE-2. The changes of cell cycle distribution and apoptosis were assayed using flow cytometry. The expression of Caspase3/Bax/Bal-2 was detected by Western blotting. DNA damage was detected via γ-H2AX foci counting. The results showed that salinomycin induced apoptosis and G2/M arrest, increased Bax and cleaved Caspase3, decreased Bcl-2 expression, and increased the formation of γ-H2AX nuclear foci. These data suggest that salinomycin may be a radiosensitizer for NPC radiotherapy.

  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. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. A dosimetric evaluation of flattening filter-free volumetric modulated arc therapy in nasopharyngeal carcinoma

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    Guishan Fu

    2014-01-01

    Full Text Available Purpose: To explore the dosimetric effects of flattening filter-free (FFF beams in volumetric modulated arc therapy (VMAT of nasopharyngeal carcinoma via a retrospective planning study. Materials and Methods: A linear accelerator (LINAC was prepared to operate in FFF mode and the beam data were collected and used to build a model in TPS. For 10 nasopharyngeal carcinoma (NPC cases, VMAT plans of FFF beams and normal flattened (FF beams were designed. Differences of plan quality and delivery efficiency between FFF-VMAT plans and filter filtered VMAT (FF-VMAT plans were analyzed using two-tailed paired t-tests. Results: Removal of the flattening filter increased the dose rate. Averaged beam on time (BOT of FFF-VMAT plans was decreased by 24.2%. Differences of target dose coverage between plans with flattened and unflattened beams were statistically insignificant. For dose to normal organs, up to 4.9% decrease in V35 of parotid grand and 4.5% decrease in averaged normal tissue (NT dose was observed. Conclusions: The TPS used in our study was able to handle FFF beams. The FFF beam prone to improve the normal tissue sparing while achieving similar target dose distribution. Decreasing of BOT in NPC cases was valuable in terms of patient′s comfort.

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

    Directory of Open Access Journals (Sweden)

    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.

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

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    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.

  8. Nodal metastases of nasopharyngeal carcinoma: patterns of disease on MRI and FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Ng Shu-Hang; Ko Sheung-Fat [Department of Diagnostic Radiology, Chang Gung Memorial Hospital Linkou Medical Center (Taiwan); Chang Joseph Tung-Chieh [Department of Radiation Oncology, Chang Gung Memorial Hospital Linkou Medical Center (Taiwan); Chan Sheng-Chieh; Chang Yu-Chen; Yen Tzu-Chen [Department of Nuclear Medicine, Chang Gung Memorial Hospital Linkou Medical Center, 5 Fu-Shin St, 333, Kueishan, Taoyuan (Taiwan); Wang Hung-Ming [Department of Medical Oncology, Chang Gung Memorial Hospital Linkou Medical Center (Taiwan); Liao Chun-Ta [Department of Otorhinolaryngology, Chang Gung Memorial Hospital Linkou Medical Center (Taiwan)

    2004-08-01

    The patterns of nodal spread of nasopharyngeal carcinoma (NPC) have an important influence on treatment planning, but have not yet been fully addressed. We prospectively used MRI and FDG PET to document the patterns of nodal spread in NPC. One hundred and one patients with newly diagnosed NPC were studied with MRI and FDG PET. On MRI, nodes were considered as metastatic according to criteria regarding size, the presence of nodal necrosis, and extracapsular spread. FDG PET images were interpreted visually, and nodes were considered metastatic if they showed prominent FDG uptake against the background. Nodal metastases were found in 89 of our 101 patients. Analysis of the distributions of nodal metastases in these 89 patients showed that retropharyngeal nodes were less frequently involved than cervical nodes (82.0% vs 95.5%). The vast majority of cervical nodal metastases were to the internal jugular chain, including nodes at levels II, III, and IV, with decreasing incidences of 95.5%, 60.7%, and 34.8%, respectively. Level V nodal involvement was found in 27% of patients. Supraclavicular fossa nodal metastases were not uncommon and occurred in 22.5% of patients. Skip metastases in the lower-level nodes or supraclavicular fossa nodes occurred in 7.9% of patients. Mediastinal and abdominal metastatic adenopathy was present in 4.5% and 3.4% of patients, respectively, and was associated with advanced nodal metastasis in the supraclavicular fossa. Level VI (2.2%), level VII (1.1%), submandibular (2.2%), and parotid (3.4%) nodal metastases were uncommon and were always associated with advanced ipsilateral nodal metastases of the neck. We conclude that the combined use of FDG PET and MRI can comprehensively depict the pattern of nodal metastasis in NPC patients. Nodal metastases principally affected level II nodes, from which lymphatic spread extended down in an orderly manner to involve level III, level IV, and the supraclavicular fossa nodes, or extended posteriorly to

  9. Epstein-barr virus latent membrane protein 1 polymorphism in nasopharyngeal carcinoma and other oral cavity tumors in Russia.

    Science.gov (United States)

    Senyuta, Natalia; Yakovleva, Larissa; Goncharova, Elena; Scherback, Liana; Diduk, Sergey; Smirnova, Ksenia; Maksimovich, Dmitry; Gurtsevitch, Vladimir

    2014-02-01

    The genetic structure of EBV LMP1 alleles isolated from tumor, blood, and throat washing samples of 22 nasopharyngeal carcinoma patients, 17 patients with other non-EBV-related tumors of the oral cavity, and 19 blood donors have been studied in representatives of Central Russia and the Republics of Northern Caucasus, regions which are non-endemic for nasopharyngeal carcinoma. The analysis of the LMP1 alleles collected revealed that they practically matched previously described LMP1 variants; however, some characteristic features were also detected. In particular, the G212S substitution in LMP1 isolates investigated was not observed at all. Tumor samples obtained from nasopharyngeal carcinoma and other tumors of the oral cavity did not differ significantly either in the frequency of "high oncogenic" LMP1 alleles with 10 aa and/or 23 aa deletions (LMP1(China1) and/or LMP1(Med+)), nor in the number of 11 aa repeats and the frequency of 5 aa motif insertions. No differences in the frequency of amino acid substitutions between LMP1 alleles obtained from tumor and throat washing samples of both patient groups were also detected. The data obtained may indicate that in both nasopharyngeal carcinoma patients and patients with other tumors of the oral cavity, the EBV strains with similar LMP1 variants are found to persist. This observation allows us to suggest that in non-endemic areas, EBV strains with any LMP1 alleles can initiate the nasopharyngeal carcinoma development but only in those individuals who have a genetic predisposition to the disease and are subjected to specific environmental, and/or dietary factors present in certain geographic areas.

  10. Factors influencing the incidence of sinusitis in nasopharyngeal carcinoma patients after intensity-modulated radiation therapy.

    Science.gov (United States)

    Su, Yan-xia; Liu, Lan-ping; Li, Lei; Li, Xu; Cao, Xiu-juan; Dong, Wei; Yang, Xin-hua; Xu, Jin; Yu, Shui; Hao, Jun-fang

    2014-12-01

    The aim of the study was to investigate the incidence of sinusitis in nasopharyngeal carcinoma (NPC) patients before and after intensity-modulated radiation therapy (IMRT) and to analyze factors associated with the incidence of sinusitis following IMRT. We retrospectively analyzed 283 NPC patients who received IMRT in our hospital from March 2009 to May 2011. The diagnostic criteria for sinusitis are based on computed tomography (CT) or magnetic resonance imaging (MRI) findings. CT or MRI scans were performed before and after IMRT to evaluate the incidence of sinusitis. Factors influencing the incidence of sinusitis were analyzed by log-rank univariate and logistic multivariate analyses. Among the 283 NPC patients, 128 (45.2 %) suffered from sinusitis before radiotherapy. The incidence rates of sinusitis in patients with T1, T2, T3, and T4 NPC before radiotherapy were 22.6, 37.5, 46.8, and 61.3 %, respectively (χ 2 = 14.548, p = 0.002). Among the 155 NPC patients without sinusitis before radiotherapy, the incidence rates of sinusitis at the end of radiotherapy and at 1, 3, 6, 9, 12, and 18 months after radiotherapy were 32.9, 43.2, 61.3, 68.4, 73.5, 69.7, and 61.3 %, respectively (χ 2 = 86.461, p sinusitis in NPC patients after IMRT (p = 0.003, 0.006, 0.002, and 0.020). Multivariate analysis showed that T stage, invasion of the nasal cavity, and nasal irrigation were influential factors for the incidence of sinusitis in NPC patients after IMRT (p = 0.002, 0.002, and 0.000). There was a higher incidence of sinusitis with higher T stage among NPC patients before radiotherapy, and the incidence of sinusitis in NPC patients after IMRT was high (45.2 %). The incidence of sinusitis increased rapidly within the first 3 months after IMRT, and the number of sinusitis cases peaked at 6-9 months after IMRT and showed a trend toward stabilization after 1 year. Advanced T stage, invasion of the nasal cavity, and nasal irrigation were positively associated with the incidence

  11. Identification of genes involved in Epstein-Barr virus-associated nasopharyngeal carcinoma

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    Wang, Junguo; Mei, Fang; Gao, Xia; Wang, Shoulin

    2016-01-01

    Nasopharyngeal carcinoma (NPC) is the most common cancer originating from the nasopharynx, and can be induced by infection with Epstein-Barr virus (EBV). To study the mechanisms of EBV-associated NPC, a microarray of the GSE12452 dataset was analyzed. GSE12452 was downloaded from Gene Expression Omnibus and consisted of 31 NPC samples and 10 normal healthy nasopharyngeal tissue samples. The differentially-expressed genes (DEGs) were screened using the linear models for microarray data package in R. Using Database for Annotation, Visualization and Integrated Discovery software, potential functions of the DEGs were predicted by Gene Ontology and pathway enrichment analyses. With the information from the Search Tool for the Retrieval of Interacting Genes/Proteins database, the protein-protein interaction (PPI) network was visualized by Cytoscape. Furthermore, modules of the PPI network were searched using ClusterONE in Cytoscape. A total of 951 DEGs were screened in the NPC samples compared with the normal healthy nasopharyngeal tissue samples. Function enrichment indicated that the upregulated genes were associated with the cell cycle, cytoskeleton organization and DNA metabolism. Meanwhile, the downregulated genes were mainly associated with cell differentiation, hormone metabolism, inflammatory response and immune response. PPI networks for the DEGs suggested that upregulated mitotic arrest deficient 2-like 1 (MAD2L1; degree=133), proliferating cell nuclear antigen (PCNA; degree=125) and cyclin B1 (CCNB1; degree=115), and downregulated member A1 of aldehyde dehydrogenase 1 (ALDH1A1; degree=15) may be of great importance as they exhibited higher degrees on interaction. Mucin 1 (MUC1) was a key node of module 4. Overall, the study indicated that MAD2L1, CCNB1, PCNA, ALDH1A1 and MUC1 may have a correlation with EBV-associated NPC. PMID:27698802

  12. 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.

  13. Significance of Cell-Free Epstein-Barr Virus DNA in Monitoring Prognosis of Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    SurmeiCao; HuaqingMin; JinsongGao; MinghuongHong; XibinXiao; ChangqingZhong; XiaodongLiu; AilonZhong; XiangGuo

    2004-01-01

    OBJECTIVE It has been reported that cell-free Epstein-Barr virus (EBVDNA) in plasma was useful in diagnosing and monitoring nasopharyngeal carcinoma (NPC). The current study was designed to evaluate the significance of EBV-DNA in monitoring the prognosis of nasopharyngeal carcinoma and comparing its significance with that of plasma VCA/IgA and EA/IgA levels. METHODS EBV-DNA, VCA/IgA, and EA/IgA levels in plasma were determined in NPC patients with different prognosis after radiotherapy, including 30 distant metastatic patients, 22 local recurrence patients and 24 individuals with remission who had been followed-up for more than 2 years after treatment. EBV-DNA was determined using a real-time quantitative PCR system, and levels of VCA/IgA and EA/IgA were measured using standard immunofluorescence. In a cohort study, the indexes were determined after different radiation periods for the 20 new cases of nasopharyngeal carcinoma. RESULTS The median plasma EBV-DNA concentration was 135,100 copies/ml (interquartile range: 5,525-1,003 750)in metastatic group, 20,500 copies/ml (interquartile range: 0-58,500) in the local recurrence group and 0 copies/ml (interquartile range: 0-0) in the continuous remission group (P<0.05). The levels of VCA/IgA and EA/IgA showed no significant differences among the different groups. The high level of EBV-DNA concentration in the metastatic group was more than that in the local recurrence group. A level of 1,000,000 copies/ml of EBV DNA was an indication of distant metastasis of the NPC patients with a sensitivity of 27.3%. However, the sensitivity was 0 in the local recurrence group. For the 20 new patients, EBV-DNA concentration gradually decreased during the radiation period. Before radiation there were 32,050 copies/ml (interquartile range: 3,880-317,750), 0 copies/ml (interquartile range: 0-14 375) after a 40 Gy radiation dose and 0 copies/ml (interquartile range: 0-2940)after the radiation was finished (P<0.05). However, the levels of

  14. 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.

  15. 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.

  16. 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

  17. 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.

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

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    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

  19. [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.

  20. 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.

  1. Identification of a Novel Methylated Gene in Nasopharyngeal Carcinoma: TTC40

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    Wajdi Ayadi

    2014-01-01

    Full Text Available To further explore the epigenetic changes in nasopharyngeal carcinoma (NPC, methylation-sensitive arbitrarily primed PCR was performed on NPC biopsies and nontumor nasopharyngeal samples. We have shown mainly two DNA fragments that appeared to be differentially methylated in NPCs versus nontumors. The first, defined as hypermethylated, corresponds to a CpG island at the 5′-end of the tetratricopeptide repeat domain 40 (TTC40 gene, whereas the second, defined as hypo-methylated, is located on repetitive sequences at chromosomes 16p11.1 and 13.1. Thereafter, the epigenetic alteration on the 5′-TTC40 gene was confirmed by methylation-specific PCR, showing a significant aberrant methylation in NPCs, compared to nontumors. In addition, the bisulfite sequencing analysis has shown a very high density of methylated cytosines in C15, C17, and X666 NPC xenografts. To assess whether TTC40 gene is silenced by aberrant methylation, we examined the gene expression by reverse transcription-PCR. Our analysis showed that the mRNA expression was significantly lower in tumors than in nontumors, which is associated with 5′-TTC40 gene hypermethylation. In conclusion, we found that the 5′-TTC40 gene is frequently methylated and is associated with the loss of mRNA expression in NPCs. Hypermethylation of 5′-TTC40 gene might play a role in NPC development; nevertheless, other studies are needed.

  2. Detection and Its Implication of Heat Stress Protein 27 and P21 in Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the expression of heat stress protein 27 (HSP27) and P21 in nasopharyngeal carcinoma (NPC) tissue, and to evaluate the significance of both HSP27 and P21 in the pathogenesis, development and prognosis of NPC. Indirect immunof1uorescence method combined with SABC was applied. Our results showed that (1) the positive rates of HSP27 and P21 expressed in NPC tissue in 36 cases were 88. 9 % and 94.4 %; (2) while in 10 hyperplastic nasopharyngitis tissues, the positive rate of HSP27 and P21 were both 5; (3) all the 5 normal tissues were negatively stained. It is obvious that a co-expressing tendency of HSP27 and P21 could be identified, and it was associated with the degree of malignancy and the clinical stage of NPC. It is concluded that the positive expression of HSP27 and P21 may have clinical significance in the evaluation of the occurring, development and prognosis of NPC, and in NPC treatment.

  3. 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

  4. Light-activated hypericin induces cellular destruction of nasopharyngeal carcinoma cells

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    Xu, C. S.; Leung, A. W. N.

    2010-01-01

    Hypericin from Hypericum perforatum plants shows an important promise in the photodynamic therapy on malignant tumor. The present study investigated that light-activated hypericin induced the cellular destruction of nasopharyngeal carcinoma cells. The result showed that hypericin resulted in a drug- and light-dose dependent cytotoxicity in the CNE-2 cells, meaning the photocytotoxicity of hypericin depends on both of the drug concentration (0 - 2.5 μM) and light-doses (1 - 8 J/cm2). We further investigated the apoptosis of the CNE-2 cells 8 hours after photosensitization of hypericin using fluorescence microscopy with Hoechst 33258 staining. Flow cytometry with annexin V-FITC and PI staining was used to analyze early and late apoptosis. These data demonstrated that light-activated hypericin could significantly lead to the cellular destruction of the CNE-2 cells and induce early apoptosis as a prominent mode of cell death.

  5. Notch inhibition suppresses nasopharyngeal carcinoma by depleting cancer stem-like side population cells.

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    Yu, Shudong; Zhang, Ruxin; Liu, Fenye; Wang, Hong; Wu, Jing; Wang, Yanqing

    2012-08-01

    The cancer stem cell (CSC) is responsible for the initiation, proliferation and radiation resistance. Side population (SP) cells are a rare subset of cells enriched with CSCs. The targeting of key signaling pathways that are active in CSCs is a therapeutic approach to treating cancer. Notch signaling is important for the self-renewal and maintenance of stem cells. Our previous studies demonstrated that downregulation of Notch signaling could enhance radiosensitivity of nasopharyngeal carcinoma (NPC) cells. In this study, we found that Notch signaling was highly activated in SP cells compared with that of non-SP (NSP) cells of NPC. Therefore, Notch inhibition could reduce the proportion of SP cells. As SP cells decreased, proliferation, anti-apoptosis and tumorigenesis were also decreased. This study shows that Notch inhibition may be a promising clinical approach in CSC-targeting therapy for NPC.

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

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    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.

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

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    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.

  8. Incidence of nasopharyngeal carcinoma in Malaysia, with special reference to the state of Selangor.

    Science.gov (United States)

    Armstrong, R W; Kutty, M K; Dharmalingam, S K

    1974-07-01

    A "registry" of all known cases of nasopharyngeal carcinoma in Malaysia, 1968-72, was established. Attention was focused on the State of Selangor where conditions are best for case finding. Age-adjusted incidence rates among Chinese males and females were 17·3 and 7·3 per 100,000; among Malay males and females, the rates were 2·5 and 0·3 and among Indian males, 1·1. The detailed ethnicity of 192 cases in Selangor was established. Estimated incidence rates for the Chinese sub-groups agreed with the pattern observed elsewhere: highest among the Cantonese, lowest among the Hokkien/Teochiu, with the Khek in between. There was no correlation between histological type and sub-ethnic group among the Chinese cases.

  9. Multidisciplinary Treatment Approach in a Patient with History of Nasopharyngeal Carcinoma

    Directory of Open Access Journals (Sweden)

    Atacan Yavuz

    2014-01-01

    Full Text Available Radiotherapy in NPC patients has side effects on the dentition, which affects quality of life dramatically. This case report presents multidisciplinary dental treatment approach in a 17-year-old male patient with a history of nasopharyngeal carcinoma (NPC, which was treated with chemotherapy and radiotherapy. The adolescent patient applied to dental hospital 4 years after the radiotherapy with aesthetic and functional problems on dentition affecting psychological, social, and physical aspects of his life. The dentition of the patient demonstrated the severe destruction as a devastating side effect of radiotherapy. With a successful multidisciplinary approach, our patient’s aesthetics, function, and self-confidence were obtained. Well-established procedures, which include preventative care and maintenance, can reduce the duration and expenses of the treatment and help in challenging the life-long complications of radiotherapy.

  10. 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.

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

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    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.

  12. 局部晚期鼻咽癌调强放疗联合同期化疗的比较%A Comparative Study of Intensity-Modulated Radiotherapy with Concurrent FP or TP Chemotherapy in Patients with Locally Advanced Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    尹宏; 何志刚; 向舫; 李煜; 罗英

    2016-01-01

    Objective:To investigate the differents in patients with locally advanced nasopharyngeal carcinoma who received intensity-modulated radiotherapy( IMRT) with two kind of chemotherapies.Methods:A retrospective analysis was performed on the clinical data of 120 patients with stageⅢorⅣa nasopharyngeal carcinoma who were admitted to our hospital from May 2010 to October 2012.60 received IMRT with 5-fluorouracil plus nedaplatin ( FP) chemotherapy,and 60 received IMRT with taxol plus nedaplatin (TP) chemotherapy.The Kaplan-Meier method wasused to calculate the survival rates,and the log-rank test was used to analyze the survival difference;the chisquare test was used to compare the acute toxicities in the two groups.Results:The follow-up rate was 100.00%.The 1、2-yearssurvival rate in the IMRT/FP group were 100.00%and 95.0%respectively, versus 100%and 91.7%in the IMRT/TP group.No significant difference was found between the two groups (P>0.05).The incidence rates of leukopenia ( grade≥3 ) , thrombocytopenia ( grade≥3 ) in the IMRT/FP group were 28.3% and 15.0%respectively, versus 65.0%and 23.3%in the IMRT/TP group ( P<0.05) .Conclusion:Compares with IMRT with concurrent FP chemotherapy, IMRT with concurrent TP chemotherapy does not lead to significantly better in survival rate, but have more acute toxicities.%目的:比较局部晚期鼻咽癌行调强放疗( IMRT)同期FP、TP方案化疗的差异。方法:将我院2010年5月至2012年10月收治的120例Ⅲ期、Ⅳa期局部晚期鼻咽癌患者分为2组,观察组行IMRT同期FP化疗,对照组行IMRT同期TP化疗。比较2组的疗效和不良反应。结果:随访率100%,观察组1年生存率为100畅00%,2年生存率为95畅0%;对照组1年生存率为100畅00%,2年生存率为91畅7%,2组比较无显著性差异( P>0畅05)。≥3级白细胞减少、血小板减少发生率观察组分别为28畅3%和15畅0%,对照组分别为65畅0%和23畅3%,2

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

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    Lam, K.S.; Ho, J.H.; Lee, A.W.; Tse, V.K.; Chan, P.K.; Wang, C.; Ma, J.T.; Yeung, R.T.

    1987-09-01

    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.

  14. Investigation of salivary function and oral microbiota of radiation caries-free people with nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Jingyang Zhang

    Full Text Available Radiation caries have been reported to be correlated with radiotherapy-induced destruction of salivary function and changes in oral microbiota. There have been no published reports detailing patients who have remained radiation caries-free following radiotherapy for nasopharyngeal carcinoma. The aim of this study was to investigate the relationship between salivary function, oral microbiota and the absence of radiation caries. Twelve radiation caries-free patients and nine patients exhibiting radiation caries following irradiated nasopharyngeal carcinoma were selected. V40, the dose at which the volume of the contralateral parotid gland receives more than 40 Gy, was recorded. Stimulated saliva flow rate, pH values and buffering capacity were examined to assess salivary function. Stimulated saliva was used for molecular profiling by Denaturing Gradient Gel Electrophoresis. Mutans streptococci and Lactobacilli in saliva were also cultivated. There were no significant differences in V40 between radiation caries-free individuals and those with radiation caries. Compared with normal values, the radiation caries-free group had significantly decreased simulated saliva flow rate, while there were no significant differences in the saliva pH value and buffering capacity. Similar results were observed in the radiation caries group. There was no statistical difference in microbial diversity, composition and log CFU counts in cultivation from the radiation caries-free group and the radiation caries group. Eleven genera were detected in these two groups, among which Streptococcus spp. and Neisseria spp. had the highest distribution. Our results suggest that changes in salivary function and in salivary microbiota do not explain the absence of radiation caries in radiation caries-free individuals.

  15. EFFECTS OF EB VIRUS ENCODED LMP1 ON DIFFERENTIATION OF NASOPHARYNGEAL CARCINOMA CELLS

    Institute of Scientific and Technical Information of China (English)

    林素暇; 宗永生; 林汉良; 钟碧玲; 李智; 梁英杰

    2003-01-01

    Objective: To investigate the effects of Epstein- Barr virus (EBV) encoded latent membrane protein 1 (LMP1) expression on tumor cell differentiation in early-stage nasopharyngeal carcinoma (NPC). Methods: Thirty-one biopsies of early-stage NPC were collected from the Cancer Center, Sun Yat-sen University. All 31 NPCs were of non-keratinizing carcinoma in histological type. The Epstein-Barr virus early RNAs (EBERs) were detected by use of DAKO PNA Probe (Y5200) and PNA ISH Detection Kit (K5201). The LMP1, (α-catenin, (β-catenin, (γ-catenin, high- molecular and low-molecular weight cytokeratins were detected by immunohistochemistry. Results: All 31 carcinoma biopsies studied showed a considerable number of EBERs-positive tumor cells, and 19 out of 31 cases (61.29%) expressed LMP1. The mean percentage of (γ-catenin expression in LMP1 positive group (53.25±34.12% ) was significantly lower than that (80.42±15.77%) in LMP1 negative group, (P<0.01). The (γ-catenin expression was positively correlated with the expression of low molecular weight cytokeratin (r=0.440, P<0.05). There were positive correlations for the expression of (α-catenin, (β-catenin and (γ-catenin in between. Conclusion: The LMP1 could down-regulate the expression of (γ-catenin and thus inhibit the tumor cell differentiation in early-stage NPC.

  16. A comparative study of intensity-modulated radiotherapy with concurrent PF or TP chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma%局部及区域晚期鼻咽癌调强放疗同期PF和TP化疗比较研究

    Institute of Scientific and Technical Information of China (English)

    许建华; 郭文杰; 卞秀华; 姜雪松; 郭业松; 黄生富; 何侠

    2013-01-01

    目的 比较调强放疗(IMRT)同期PF(奈达铂加氟尿嘧啶)、TP(紫杉醇加奈达铂)化疗治疗局部及区域晚期鼻咽癌的疗效及急性不良反应.方法 回顾分析本院2009-2010年间收治的152例Ⅲ、Ⅳa期患者资料,其中80例IMRT同期PF化疗,72例IMRT同期TP化疗,两组患者总化疗疗程至少为2个周期.Kaplan-Meier法计算生存率并Logrank法检验,x2检验两组急性不良反应.结果 随访率100%.IMRT同期PF和TP化疗组2年无复发生存率、无远处转移生存率、无进展生存率、疾病相关死亡率分别为95%和97%、82%和83%、81%和79%、13%和12%(x2=0.03、0.02、0.62、0.22,P=0.861、0.881、0.431、0.638);≥3级白细胞减少、≥3级中性粒细胞减少、≥3级血小板减少、≥≥2级肝功能损害、≥3级口腔黏膜炎发生率分别为33%和60%、23%和47%、14%和28%、8%和18%、12%和25%(x2=11.33、10.29、4.59、3.94、3.94,P=0.001、0.001、0.032、0.047、0.047).结论 IMRT同期TP方案较PF方案化疗在鼻咽癌中并未显示出生存优势,且不良反应更高.%Objective To investigate the survival data and acute toxicities in patients with locoregionally advanced nasopharyngeal carcinoma who receive intensity-modulated radiotherapy (IMRT)with concurrent chemotherapy using nedaplatin plus 5-fluorouracil (PF) or taxol plus nedaplatin (TP).Methods A retrospective analysis was performed on the clinical data of 152 patients with stage Ⅲ or Ⅳa nasopharyngeal carcinoma who were admitted to our hospital in 2009-2010.Of the 152 patients,80 received IMRT with concurrent PF chemotherapy,and 72 received IMRT with concurrent TP chemotherapy;there were at least 2 cycles of concurrent chemotherapy in both groups.The Kaplan-Meier method was used to calculate the survival rates,and the log-rank test was used to analyze the survival difference ; the chisquare test was used to compare the acute toxicities in the two groups.Results The

  17. 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

  18. 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)

  19. Induction chemotherapy with cisplatin, epirubicin, and paclitaxel (CEP), followed by concomitant radiotherapy and weekly paclitaxel for the management of locally advanced nasopharyngeal carcinoma. A hellenic cooperative oncology group phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Fountzilas, G.; Kalogera-Fountzila, A.; Karanikiotis, C.; Nicolaou, A.; Plataniotis, G.; Daniilidis, J. [AHEPA Hospital, Aristotle Univ. of Thessaloniki, Thessaloniki (Greece); Tolis, C.; Bai, M.; Tsekeris, P. [Univ. of Ioannina Medical School, Ioannina (Greece); Misailidou, D. [' ' Papageorgiou' ' Hospital, Thessaloniki (Greece); Samantas, E.; Athanassiou, E. [' ' Agii Anargiri' ' Cancer Hospital, Athens (Greece); Papamichael, D.; Catodritis, N. [Bank of Cyprus Oncology Center, Nicosia (Cyprus); Makatsoris, T. [' ' Rio' ' Hospital, Univ. of Patras Medical School, Rio, Patras (Greece); Papakostas, P. [' ' Ippokration' ' Hospital, Athens (Greece); Zamboglou, N. [Dept. of Radiotherapy, Klinikum Offenbach, Offenbach (Germany)

    2005-04-01

    Background: clinical research on the treatment of nasopharyngeal cancer (NPC) has been focused primarily on the reduction of incidence of the development of distant metastases as well as the improvement of locoregional control. Patients and methods: untreated patients with stage IIB-IVB nonmetastatic NPC were treated with three cycles of induction chemotherapy (IC) consisting of epirubicin 75 mg/m{sup 2} followed by paclitaxel 175 mg/m{sup 2} as 3-h infusion on day 1 and cisplatin 75 mg/m{sup 2} on day 2 every 3 weeks, followed by concomitant radiation therapy (70 Gy), and chemotherapy (CCRT) with weekly paclitaxel 60 mg/m{sup 2}. Results: from November 1999 until April 2003, 47 patients entered the study. Complete response rate post IC therapy was 15%, which was raised to 66% after the completion of CCRT. The most frequent side effect from IC was myelotoxicity (55%), whereas stomatitis and xerostomia were the most pronounced (grade 3, 4) toxicities during CCRT. The presence of Epstein-Barr virus (EBV) was detected either by in situ hybridization in tumor tissue sections or by polymerase chain reaction in the peripheral blood in 37 out of 46 patients tested (80%). All three histological types were associated with the presence of EBV. After a median follow-up of 23.5 months, median time to treatment failure was 17.9 months, whilst median survival has not been reached yet. Conclusion: IC followed by CCRT is feasible and produces durable complete responses in the majority of patients with NPC. The case detection rate of EBV in this study appears to be similar to that reported from endemically infected regions. (orig.)

  20. 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.

  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. 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.

  3. 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.

  4. Long-term survival following two recurrences and re-irradiation courses for a nasopharyngeal carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Haddad P

    2010-10-01

    Full Text Available "nBackground: Local recurrence in Nasopharyngeal Carcinoma (NPC presents is a major challenge. Patients experience substantial morbidity as well as poor survival if no further treatment is offered. Residual or recurrent nasopharyngeal carcinoma is usually managed by chemotherapy, stereotactic radiosurgery, external beam radiation therapy (EBRT, interstitial, and intracavitary brachytherapy or salvage surgery. This case presents the treatment of two consecutive localized recurrences of NPC."n "nCase presentation: The patient was a 59-year-old man who underwent a course of radical external-beam radiotherapy for a primary NPC in 1999, then another course of external radiation in 2004 for his first recurrence, and finally a course of brachytherapy for the second recurrence in 2005. The patient is well now in 2010, with no signs of disease five years after the third radiotherapy."n "nConclusion: Our experience of re-irradiation for this twice recurrent nasopharyngeal carcinoma has been promising with encouraging tumor control and acceptable treatment-related toxicity profile. This case indicates the efficacy of definitive re-irradiation for regional recurrence and the necessity for long-term observation for the salvageable early-stage local failure.

  5. 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.

  6. 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

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

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    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

  8. 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

  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. 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.

  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. 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.

  14. 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.

  15. LASSO NTCP predictors for the incidence of xerostomia in patients with head and neck squamous cell carcinoma and nasopharyngeal carcinoma.

    Science.gov (United States)

    Lee, Tsair-Fwu; Liou, Ming-Hsiang; Huang, Yu-Jie; Chao, Pei-Ju; Ting, Hui-Min; Lee, Hsiao-Yi; Fang, Fu-Min

    2014-08-28

    To predict the incidence of moderate-to-severe patient-reported xerostomia among head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). Multivariable normal tissue complication probability (NTCP) models were developed by using quality of life questionnaire datasets from 152 patients with HNSCC and 84 patients with NPC. The primary endpoint was defined as moderate-to-severe xerostomia after IMRT. The numbers of predictive factors for a multivariable logistic regression model were determined using the least absolute shrinkage and selection operator (LASSO) with bootstrapping technique. Four predictive models were achieved by LASSO with the smallest number of factors while preserving predictive value with higher AUC performance. For all models, the dosimetric factors for the mean dose given to the contralateral and ipsilateral parotid gland were selected as the most significant predictors. Followed by the different clinical and socio-economic factors being selected, namely age, financial status, T stage, and education for different models were chosen. The predicted incidence of xerostomia for HNSCC and NPC patients can be improved by using multivariable logistic regression models with LASSO technique. The predictive model developed in HNSCC cannot be generalized to NPC cohort treated with IMRT without validation and vice versa.

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

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    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

  17. 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)

  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. Long-term treatment results for nasopharyngeal carcinoma: The Sahlgrenska Univ. Hospital experience

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    Taheri-Kadkhoda, Zahra; Bjoerk-Eriksson, Thomas; Mercke, Claes [Dept. of Oncology, Sahlgrenska Univ. Hospital, Goeteborg (Sweden); Johansson, Karl-Axel [Dept. of Radiophysics, Sahlgrenska Univ. Hospital, Goeteborg (Sweden)

    2007-08-15

    Nasopharyngeal carcinoma (Nc) is a rare disease in Sweden. For evaluation of the treatment outcomes in our NPC patients, 52 new cases that were referred to our department between 1991 and 2002 were retrospectively analysed. Tumor stage, according to the 1997 AJCC staging system, was I in five, II in ten, III in 12 and IV in 25 patients. Majority of the patients (87%) had World Health Organization type II-III tumors. Neoadjuvant chemotherapy was delivered in 33 patients. Thirty-two patients received hyperfractionated accelerated radiation therapy with a median dose of 64.6Gy (1.7Gy/fr bid). Conventional external irradiation with a median dose of 66Gy (2Gy/fr) was delivered to 18 patients. An intracavitary brachy-boost of 4.5-12Gy was delivered to 40 patients. Two patients were excluded from the analysis due to treatment refusal. For the patients with tumor stages I-IVB, the 5-year disease-free and overall survival rates were 61% and 55%, respectively. The 5-year local, regional, and distant relapse-free survival rates were 70%, 92% and 77%, respectively. The most frequent late side effects were xerostomia (98%), otitis (70%) and hearing deterioration (64%). Our data suggest that optimization of the treatment outcomes in NPC patients requires implementation of new therapeutic strategies.

  20. Concomitant chemoradiotherapy with CDDP and 5FU for nasopharyngeal carcinoma. The initial evaluation and side effects

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    Takeuchi, Yousuke; Suzuki, Haruhiko; Shigehara, Takeo; Omura, Ken; Shimada, Fumiyuki; Hatano, Kazuo; Sekiya, Yuichi; Togawa, Takashi [Chiba Cancer Center Hospital (Japan)

    1998-03-01

    Concomitant chemoradiotherapy with CDDP and 5FU was given to 18 patients with nasopharyngeal carcinoma during January 1994-October 1996. One and 17 were in Stages III-IV respectively. None had distant metastasis. The median duration of follow-up of all patients was 23.5 months (6-45). Objective response (CR+PR) of the primary lesion and the regional nodes was 18/18 (100%), whereas CR was 2/18 (11%). CR+PR and CR at the primary lesion were 18/18 (100%) and 5/18 (28%) respectively. Two patients died of disease at T site. One patient was alive with disease. The remaining 15 (83%) patients were relapse free alive. There were 2 relapses, 1 at T+M, and 1 at T+N sites. Side effects, especially myelosuppression and mucositis, were severe. Leukopenia and mucositis in grade 3-4 were 78% and 89% respectively. In conclusion, this regimen has been effective in short term follow-up. However, because of severe side effects, further modifications are required. Long term follow-up are required to define final effectiveness of this regimen. (author)

  1. 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.

  2. 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.

  3. [Endoscopic surgery and reconstruction for extensive osteoradionecrosis of skull base after radiotherapy for nasopharyngeal carcinoma].

    Science.gov (United States)

    Chen, Z; Qiu, Q H; Zhan, J B; Zhu, Z C; Peng, Y; Liu, H

    2016-12-07

    Objective: To investigate the clinical efficacy of endoscopic surgery for extensive osteoradionecrosis (ORN) of skull base in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Methods: Seventeen patients diagnosed as ORN of skull base after radiotherapy for NPC and underwent endoscopic surgery were retrospectively studied with their clinic data. Results: Based on the CT and endoscopic examination, all patients had large skull base defects with bone defects averaged 7.02 cm(2) (range, 3.60 - 14.19 cm(2)). Excepting for curetting the sequestra, endoscopic surgery was also used to repair the wound or to protect the internal carotid artery with flap in 12 patients. No bone reconstructions were conducted in all patients with the bone defects of skull base. CT examinations were taken after endoscopic surgery when required. The postoperative follow-up ranged from 8 months to 6 years (average, 14 months). Aside from 1 patient with delayed cerebrospinal fluid (CSF), others had no related complications. Conclusions: The patients with extensive ORN can be treated with endoscopic surgery to curette the necrotic bone of skull base, and endoscopic reconstruction provides an alternative technique. It may not be necessary to reconstruct the bone defects at skull base, however, the exposed important structures of skull base, such as internal carotid artery, need to repair with soft tissue such as flap.

  4. Reexploring the Possible Roles of Some Genes Associated with Nasopharyngeal Carcinoma Using Microarray-based Detection

    Institute of Scientific and Technical Information of China (English)

    Wei-Yi FANG; Xin LI; Yan-Qing DING; Kai-Tai YAO; Teng-Fei LIU; Wei-Bing XIE; Xu-Yu YANG; Shuang WANG; Cai-Ping REN; Xin DENG; Qiu-Zhen LIU; Zhong-Xi HUANG

    2005-01-01

    In gene expression profiling, nasopharyngeal carcinoma (NPC) 5-8F cells differ from 6-10B cells in terms of their high tumorigenicity and metastatic ability. Differentially expressed genes from the two cell types were analyzed by combining with MILANO (the automatic custom annotation of microarray results which is based on all the available published work in PubMed). The results showed that five genes, including CTSD, P63, CSE1L, BPAG1 and EGR1, have been studied or mentioned in published work on NPC. Subsequently, we revaluated the roles of these genes in the pathogenesis of NPC by combining the data of gene chips from NPCs versus NPs and pooled cells from 5-8F, 6-10B and CNE2 versus NPs. The results suggested that the roles of BPAG1 and EGR1 are possibly different from those reported in previous NPC studies. These five genes are likely to be involved in the proliferation, apoptosis, invasion and metastasis of NPC. A reexploration of the genes will further define their roles in the pathogenesis of NPC.

  5. A Therapeutic Approach to Nasopharyngeal Carcinomas by DNAzymes Targeting EBV LMP-1 Gene

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    Lun-Quan Sun

    2010-09-01

    Full Text Available Epstein-Barr virus (EBV-encoded latent membrane protein 1 (LMP1 has been known to have oncogenic properties during latent infection in nasopharyngeal carcinoma (NPC. Genetic manipulation of LMP1 expression may provide a novel strategy for the treatment of NPC. DNAzymes are synthetic, single-stranded DNA catalysts that can be engineered to bind and cleave the target mRNA of a disease-causing gene. By targeting the LMP1 mRNA, we successfully obtained a phosphorothioate-modified ‘‘10–23’’ DNAzyme namely DZ1, through screening a series of DNAzymes. DZ1 could significantly down-regulate the expression of LMP1 in NPC cells, inhibit cell proliferation, metastasis, promote apoptosis and enhance radiosensitivity of NPC through interfering signal pathways which are abnormally activated by LMP1, including NF-κB, AP-1 and STAT3 signal pathways. Together, interfering LMP1 signaling pathway could be a promising strategy to target the malignant phenotypes of NPC.

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

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    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.

  7. Nasopharyngeal carcinomas: from biology to clinic; Les carcinomes du nasopharynx: de la biologie a la clinique

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    Rivera, S.; Maingon, P. [Centre Georges-Francois-Leclerc, Dept. de Radiotherapie, 21 - Dijon (France); Keryer, C.; Busson, P. [Institut Gustave-Roussy, CNRS/UMR 8126, 94 - Villejuif (France)

    2005-02-15

    Nasopharyngeal carcinomas (NPC) are very different from other head and neck cancers because of their specific multi-factorial etiology and their geographic distribution. Epstein-Barr Virus (EBV) is implicated in onco-genesis of NPC in association with genetic alterations such as inactivation of the p16/Ink4, p19/ARF, RASSFI or Blu genes. Tumoral tissues include a very abundant characteristic lymphoid infiltrate. Inflammatory cytokines are produced by both malignant and infiltrating cells. There is no efficient immune response against the tumor. On the opposite, infiltrating lymphocytes might play a role in tumor development. Serological methods and detection of circulating viral DNA are expected to become useful for early detection of relapse and on a longer term for primary screening. NPC are often diagnosed at a late stage because patients may remain asymptomatic for a long time. Computed tomography (CT scan) and magnetic resonance imaging (MRI) are complementary for the initial evaluation. Positron emission tomography (PET) is efficient for the evaluation of treatment efficiency and detection of relapses. Treatment is based on radiotherapy and chemotherapy. Their optimal use needs to be evaluated by phase III trials but positive results have been obtained by concomitant association of radiotherapy and chemotherapy. Targeted therapies are being studied with strategies based on disruption of viral latency, use of replicative adeno-viruses or anti-tumor vaccination. (author)

  8. Relationship between individual radiosensitivity and radiation encephalopathy of nasopharyngeal carcinoma after radiotherapy

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    Tang Yamei; Peng Ying; Xing Yigang [Dept. of Neurology, The Second Affiliated Hospital, Sun Yat-Sen Univ., Guangzhou (China); Zhang Yinyin [Dept. of Internal Medicine, The Second Affiliated Hospital, Sun Yat-Sen Univ., Guangzhou (China); Guo Ling [Dept. of Nasopharyngeal Carcinoma, Cancer Center of Sun Yat-Sen Univ., Guangzhou (China); Luo Qingliang [Beijing Inst. of Radiation Medicine, BJ (China)

    2008-10-15

    Purpose: to analyze the relationship between individual radiosensitivity and the morbidity and severity of radiation encephalopathy (RE) induced by radiotherapy of nasopharyngeal carcinoma (NPC) patients. Patients and methods: in this study, 26 patients with RE (experimental group) and 26 patients without RE (control group) after radiotherapy of NPC were included. The experimental group was divided into two subgroups, that is, group 1 with 1-2 grade and group 2 with 3-4 grade, according to the RTOG/EORTC Score. Individual radiosensitivity was determined by the total chromosomal aberration rate measured in in vitro irradiated lymphocytes by a metaphase detection technique. Chromosomal aberration rate was correlated to development of RE in order to investigate the relationship between radiosensitivity and RE. Results: the total chromosomal aberration rate was found to be a risk factor for the onset of RE. The total chromosomal aberration rate was positively correlated to the severity of RE. Patients with a high radiosensitivity had shorter latency than those with a low or intermediate radiosensitivity. Conclusion: in NPC patients, individual radiosensitivity as determined by the proportion of lethal chromosomal aberrations in in vitro irradiated lymphocytes might be associated with the development of RE and has the potential to predict the morbidity and severity of RE. (orig.)

  9. Nasopharyngeal adenoid cystic carcinoma: magnetic resonance imaging features in ten cases

    Institute of Scientific and Technical Information of China (English)

    Xue-Wen Liu; Pei-Hong Wu; Chuan-Miao Xie; Hui Li; Rong Zhang; Zhi-Jun Geng; Yun-Xian Mo; Jing Zhao; Mu-Yan Cai; Yan-Chun Lv

    2012-01-01

    Nasopharyngeal adenoid cystic carcinoma (NACC) is a rare malignancy with high local invasiveness.To date,there is no consensus on the imaging characteristics of NACC.To address this,we retrospectively reviewed 10 cases of NACC and summarized the magnetic resonance imaging (MRI) features.MR images of 10 patients with histologically validated NACC were reviewed by two experienced radiologists.The location,shape,margin,signal intensity,lesion texture,contrast enhancement patterns,local invasion,and cervical lymphadenopathy of all tumors were evaluated.Clinical and pathologic records were also reviewed.No patients were positive for antibodies against Epstein-Barr virus (EBV).The imaging patterns of primary tumors were classified into two types as determined by location,shape,and margin.Of all patients,7 had tumors with a type 1 imaging pattern and 3 had tumors with a type 2 imaging pattern.The 4 tubular NACCs were all homogeneous tumors,whereas 3 (60%) of 5 cribriform NACCs and the sole solid NACC were heterogeneous tumors with separations or central necrosis on MR images.Five patients had perineural infiltration and intracranial involvement,and only 2 had cervical lymphadenopathy.Based on these results,we conclude that NACC is a local,aggressive neoplasm that is often negative for EBV infection and associated with a low incidence of cervical lymphadenopathy.Furthermore,MRI features of NACC vary in locations and histological subtypes.

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

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    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.

  11. A rare case of nasopharyngeal carcinoma in a patient with multiple myeloma after treatment by lenalidomide.

    Science.gov (United States)

    Xu, Gaixiang; Wang, Bo; Yang, Min; Qian, Wenbin

    2015-01-01

    Multiple myeloma (MM) is a plasma-cell malignancy leading to a significant life-expectancy shortening. Lenalidomide is an oral immunomodulatory drug (IMiD) approved in the United States for patients with MM. Although the introduction of lenalidomide combined with dexamethasone (Len/Dex) has improved the outcome of patients with relapsed/refractory multiple myeloma (RRMM), it is a common knowledge that lenalidomide has been linked to the development of secondary primary malignancies in the MM patients, especially in those who use lenalidomide as a maintenance therapy. In the published literature, these are also many cases reported by clinicians in different secondary primary malignancies after the diagnosis of MM treated with lenalidomide. In this present article, we provided our patient who was identified nasopharyngeal carcinoma (NPC) 46 months after the diagnosis of MM and 21 months after lenalidomide treatment. To the best of our knowledge, this is the first case report related to the occurrence of NPC in a patient with MM after treatment by lenalidomide. Although it is not very sure that the incidence of NPC was associated with the use of lenalidomide, we clinicians should pay adequate attention to this phenomenon in the clinical processing. And much more cooperative studies of large numbers of MM patients are needed to evaluate a possible association between lenalidomide and NPC.

  12. Comprehensive profiling of EBV gene expression in nasopharyngeal carcinoma through paired-end transcriptome sequencing.

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    Hu, Lijuan; Lin, Zhirui; Wu, Yanheng; Dong, Juqin; Zhao, Bo; Cheng, Yanbing; Huang, Peiyu; Xu, Lihua; Xia, Tianliang; Xiong, Dan; Wang, Hongbo; Li, Manzhi; Guo, Ling; Kieff, Elliott; Zeng, Yixin; Zhong, Qian; Zeng, Musheng

    2016-03-01

    The latent expression pattern of Epstein-Barr Virus (EBV) genes in nasopharyngeal carcinoma (NPC) has been extensively investigated, and the expression of several lytic genes in NPC has been reported. However, comprehensive information through EBV transcriptome analysis in NPC is limited. We performed paired-end RNA-seq to systematically and comprehensively characterize the expression of EBV genes in NPC tissue and C666-1 NPC cell line, which consistently carries EBV. In addition to the transcripts restricted to type II latency infection, the type III latency EBNA3s genes and a substantial number of lytic genes, such as BZLF1, BRLF1, and BMRF1, were detected through RNA-seq and were further verified in C666-1 cells and NPC tissue through realtime PCR.We also performed clustering analysis to classify NPC patient groups in terms of EBV gene expression, which presented two subtypes of NPC samples. Results revealed interesting patterns of EBV gene expression in NPC patients. This clustering was correlated with many signaling pathways, such as those related to heterotrimeric G-protein signaling, inflammation mediated by chemokine and cytokine signaling, ribosomes, protein metabolism, influenza infection, and ECM-receptor interaction. Our combined findings suggested that the expression of EBV genes in NPC is restricted not only to type II latency genes but also to type III latency and lytic genes. This study provided further insights into the potential role of EBV in the development of NPC.

  13. Friend Leukemia Virus Integration 1 Expression Has Prognostic Significance in Nasopharyngeal Carcinoma

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    Xuexia Liang

    2014-08-01

    Full Text Available This study aimed to investigate the expression pattern and prognostic value of friend leukemia virus integration 1 (FLI-1 in nasopharyngeal carcinoma (NPC. Immunohistochemistry (IHC staining of FLI-1 was performed in specimens from 198 untreated NPC patients. Ninety-nine patients were randomly assigned to the training set to analyze the prognostic value of FLI-1 and other clinicopathological characteristics, while the others were assigned to the testing set for validation. Clinicopathological data were compared using the Pearson chi-square test. Univariate and multivariate analyses were performed using the Cox proportional hazards model to test independent prognostic factors and calculate the hazard ratio (HR and 95% confidence interval (CI. Cytoplasmic FLI-1 expression positively correlated with N stage, distant metastasis and death (P<0.05 and also predicted poorer overall survival (OS (P=0.014, distant metastasis-free survival (DMFS (P=0.010, progression-free survival (PFS (P=0.031. In multivariate analysis, FLI-1 expression and clinical stage were both independent prognostic factors of poor OS and DMFS. Prognoses of patients in the training set, the testing set, and the entire set were clearly divided into four risk subgroups by supplementing FLI-1 with clinical stage. These results indicate that FLI-1 expression is an independent prognostic factor for NPC patients and suggest that supplementing FLI-1 with clinical stage could be helpful for more accurate risk definition.

  14. 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.

  15. Fisetin inhibits migration, invasion and epithelial-mesenchymal transition of LMP1-positive nasopharyngeal carcinoma cells.

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    Li, Rong; Zhao, Yinhai; Chen, Jin; Shao, Songjun; Zhang, Xiujuan

    2014-02-01

    Fisetin (3,3',4',7-tetrahydroxyflavone) has been reported to possess certain anticancer properties. It may inhibit tumor cell proliferation, metastasis and induce apoptosis. However, the effects of fisetin in preventing the metastasis of nasopharyngeal carcinoma (NPC) cells remain to be determined. The epithelial-mesenchymal transition (EMT) is involved in several metastatic malignancies including NPC. It has been reported that the Epstein-Barr virus latent membrane protein-1 (LMP1) induced EMT and is associated with the metastasis of NPC. The aim of this study was to examine the effects of fisetin in preventing the migration and invasion of LMP1-expressing NPC cells (CNE1-LMP1 cells), as well as to investigate whether fisetin may inhibit the molecular changes associated with EMT induced by LMP1. The investigation demonstrated that fisetin suppressed the migration and invasion of CNE1-LMP1 cells under non-cytotoxic concentrations. Fisetin inhibited molecular changes associated with EMT induced by LMP1, upregulated the epithelial marker, E-cadherin protein, and downregulated the mesenchymal marker, vimentin protein, levels. Fisetin also significantly reduced the levels of Twist protein, an EMT regulator. The investigation suggested that fisetin inhibits the migration and invasion of LMP1-positive NPC cells, and the molecular mechanism involves fisetin reversing the EMT induced by LMP1 and downregulates the expression of Twist. This study indicated that fisetin serves as a potential candidate for the treatment of cancer metastasis.

  16. Radiation therapy for nasopharyngeal carcinoma: the predictive value of interim survival assessment.

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    Toya, Ryo; Murakami, Ryuji; Saito, Tetsuo; Murakami, Daizo; Matsuyama, Tomohiko; Baba, Yuji; Nishimura, Ryuichi; Hirai, Toshinori; Semba, Akiko; Yumoto, Eiji; Yamashita, Yasuyuki; Oya, Natsuo

    2016-09-01

    Pretreatment characteristics are suggested as predictive and/or prognostic factors for nasopharyngeal carcinoma (NPC); however, individual tumor radiosensitivities have previously not been considered. As boost planning is recommended for NPC, we performed interim assessments of magnetic resonance (MR) images for boost planning and retrospectively evaluated their predictive value for the survival of NPC patients. Radiation therapy via elective nodal irradiation (median dose: 39.6 Gy) with/without chemotherapy was used to treat 63 NPC patients. Boost irradiation (median total dose: 70 Gy) was performed based on the interim assessment. The largest lymph node (LN) was measured on MR images acquired at the time of interim assessment. The site of first failure was local in 8 (12.7%), regional in 7 (11.1%), and distant in 12 patients (19.0%). All 7 patients with regional failure harbored LNs ≥15 mm at interim assessment. We divided the 63 patients into two groups based on LN size [large (≥15 mm), n = 10 and small (interim assessment could predict survival in NPC patients.

  17. 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.

  18. Partial Least Square Discriminant Analysis Discovered a Dietary Pattern Inversely Associated with Nasopharyngeal Carcinoma Risk.

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    Lo, Yen-Li; Pan, Wen-Harn; Hsu, Wan-Lun; Chien, Yin-Chu; Chen, Jen-Yang; Hsu, Mow-Ming; Lou, Pei-Jen; Chen, I-How; Hildesheim, Allan; Chen, Chien-Jen

    2016-01-01

    Evidence on the association between dietary component, dietary pattern and nasopharyngeal carcinoma (NPC) is scarce. A major challenge is the high degree of correlation among dietary constituents. We aimed to identify dietary pattern associated with NPC and to illustrate the dose-response relationship between the identified dietary pattern scores and the risk of NPC. Taking advantage of a matched NPC case-control study, data from a total of 319 incident cases and 319 matched controls were analyzed. Dietary pattern was derived employing partial least square discriminant analysis (PLS-DA) performed on energy-adjusted food frequencies derived from a 66-item food-frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with multiple conditional logistic regression models, linking pattern scores and NPC risk. A high score of the PLS-DA derived pattern was characterized by high intakes of fruits, milk, fresh fish, vegetables, tea, and eggs ordered by loading values. We observed that one unit increase in the scores was associated with a significantly lower risk of NPC (ORadj = 0.73, 95% CI = 0.60-0.88) after controlling for potential confounders. Similar results were observed among Epstein-Barr virus seropositive subjects. An NPC protective diet is indicated with more phytonutrient-rich plant foods (fruits, vegetables), milk, other protein-rich foods (in particular fresh fish and eggs), and tea. This information may be used to design potential dietary regimen for NPC prevention.

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

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    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

  20. Epigenetic Silencing of Cellular Retinol-Binding Proteins in Nasopharyngeal Carcinoma

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    Joseph Kwong

    2005-01-01

    Full Text Available Aberrant retinoid signaling in human cancers is extending from the nucleus to the cytoplasm. Recently, we have demonstrated frequent epigenetic inactivation of a retinoic acid receptor (RAR, RARβ2, in nasopharyngeal carcinoma (NPC. To further explore targets contributing to aberrant retinoid signaling in NPC, the expression of cellular retinol-binding proteins (CRBPs, cellular retinoic acid-binding proteins (CRABPs, RARs, and retinoid X receptors (RXRs was examined. Apart from RARβ2, transcriptional silencing of two CRBPs, CRBPI and CRBPIV, was observed in NPC cell lines and xenografts. Hypermethylation of CRBPI and CRBPIV CpG islands was found to be closely correlated with the loss of expression. Treatment with the DNA methyltransferase inhibitor, 5-aza2'-deoxycytidine, resulted in reexpression of CRBPI and CRBPIV gene expression in NPC cell lines. Both CRBPI and CRBPIV hypermethylations were also observed in 43/48 (87.8% and 26/48 (54.2% primary NPC tumors, respectively. Here, we reported for the first time that CRBPIV was transcriptionally inactivated by promoter hypermethylation in human cancer. Simultaneous methylation of CRBPI, CRBPIV, and RARβ2 was commonly found in NPC primary tumors. Our findings implied that epigenetic disruption of the CRBPs, CRBPI and CRBPIV, is important in NPC tumorigenesis and may contribute to the loss of retinoic acid responsiveness in cancer.

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

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

    2016-02-25

    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, <0.001-0.001). The odds ratios (95% confidence interval) comparing the extreme quartiles of the three significant scores were 0.47 (0.32-0.68) (HEI-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.

  2. 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.

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

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    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.

  4. 2-Methoxyestradiol induces cell cycle arrest and apoptosis of nasopharyngeal carcinoma cells

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    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.

  5. Changes in c-Kit expression levels during the course of radiation therapy for nasopharyngeal carcinoma

    Science.gov (United States)

    Jiang, Feng; Hu, Wei; Zhang, Bicheng; Xu, Jing; Shui, Yongjie; Zhou, Xiaofeng; Ren, Xiaoqiu; Chen, Xiaozhong; Shen, Li; Wei, Qichun

    2016-01-01

    In the era of intensity-modulated radiotherapy, distant metastasis is currently the main cause of treatment failure for nasopharyngeal carcinoma (NPC). Additional therapeutic strategies are required to control the metastasis and improve survival. One strategy is targeted therapy, for example against c-Kit. In the current study, the frequency of c-Kit expression was determined immunohistochemically in 106 NPC patients. c-Kit expression changes during the course of radiation therapy were detected in 41 cases via weekly biopsy. Twelve cases (11.3%) had c-Kit expression scores of 3+ and 16 (15.1%) had scores of 2+. Thus, c-Kit overexpression (2+ or 3+) was observed in 28 (26.4%) patients. There were 35 (33.0%) and 43 (40.6%) patients with c-Kit expression scores of 1+ and 0, respectively. Furthermore, a trend of decreased c-Kit expression was observed after commencing radiotherapy according to the 41 NPC patients who were biopsied weekly. Therefore, c-Kit overexpression was identified to be common in NPC, and evaluating c-Kit as a therapeutic target for metastatic NPC via c-Kit overexpression subsequent to first line treatment may be of interest. To the best of our knowledge, the present study is the first to demonstrate a trend of decreased c-Kit expression during the course of radiotherapy. PMID:27699010

  6. 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.

  7. SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma

    Science.gov (United States)

    Luo, Yanzhang; Mok, Tin Seak; Lin, Xiuxian; Zhang, Wanling; Cui, Yizhi; Guo, Jiahui; Chen, Xing; Zhang, Tao; Wang, Tong

    2017-01-01

    Nasopharyngeal carcinoma (NPC) is a serious threat to public health, and the biomarker discovery is of urgent needs. The data-independent mode (DIA) based sequential window acquisition of all theoretical fragment-ion spectra (SWATH) mass spectrometry (MS) has been proved to be precise in protein quantitation and efficient for cancer biomarker researches. In this study, we performed the first SWATH-MS analysis comparing the NPC and normal tissues. Spike-in stable isotope labeling by amino acids in cell culture (super-SILAC) MS was used as a shotgun reference. We identified and quantified 1414 proteins across all SWATH-MS analyses. We found that SWATH-MS had a unique feature to preferentially detect proteins with smaller molecular weights than either super-SILAC MS or human proteome background. With SWATH-MS, 29 significant differentially express proteins (DEPs) were identified. Among them, carbonic anhydrase 2 (CA2) was selected for further validation per novelty, MS quality and other supporting rationale. With the tissue microarray analysis, we found that CA2 had an AUC of 0.94 in differentiating NPC from normal tissue samples. In conclusion, SWATH-MS has unique features in proteome analysis, and it leads to the identification of CA2 as a potentially new diagnostic biomarker for NPC. PMID:28117408

  8. 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.

  9. Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptor-mediated endocytosis by molecular targeted nanomedicine

    Directory of Open Access Journals (Sweden)

    Xie M

    2013-07-01

    Full Text Available M Xie, H Zhang, Y Xu, T Liu, S Chen, J Wang, T ZhangDepartment of Otorhinolaryngology Head and Neck Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, People's Republic of ChinaAbstract: Immunohistochemistry and an immunofluorescence technique was used to detect folate receptor expression in tissue samples and cell lines of head and neck squamous carcinoma, including 20 tissue samples of nasopharyngeal carcinoma, 16 tissue samples of laryngeal carcinoma, and HNE-1, HNE-2, CNE-1, CNE-2, SUNE-1, 5-8F, and Hep-2 cell lines. Iron staining, electron microscopy, and magnetic resonance imaging were used to observe endocytosis of folate-conjugated cisplatin-loaded magnetic nanoparticles (CDDP-FA-ASA-MNP in cultured cells and transplanted tumors. As shown by immunohistochemistry, 83.3% (30/36 of the head and neck squamous carcinomas expressed the folate receptor versus none in the control group (0/24. Only the HNE-1 and Hep-2 cell lines expressed the folate receptor, and the other five cell lines did not. Endocytosis of CDDP-FA-ASA-MNP was seen in HNE-1 and Hep-2 cells by iron staining and electron microscopy. A similar result was seen in transplanted tumors in nude mice. Magnetic resonance imaging showed low signal intensity of HNE-1 cells and HNE-1 transplanted tumors on T2-weighted images after uptake of CDDP-FA-ASA-MNP, and this was not seen in CNE-2 transplanted tumors. In conclusion, head and neck squamous carcinoma cell strongly expressed the folate receptor, while normal tissue did not. The folate receptor can mediate endocytosis of folate-conjugated anticancer nanomedicines, and lays the foundation for molecular targeted treatment of cancer.Keywords: nasopharyngeal carcinoma, laryngeal carcinoma, folate receptor, molecular targeting, cisplatin, nanomedicine

  10. 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

  11. Retropharyngeal abscess after radiation therapy and cis-platinum, 5-fluorouracil treatment for nasopharyngeal carcinoma with collagen disease. Report of two patients and a review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Hareyama, Masato; Nagakura, Hisayasu; Tamakawa, Mitsuharu [Sapporo Medical Univ. (Japan)] [and others

    1996-06-01

    Collagen disease are frequently associated with malignant tumors. Recently, radiotherapy combined with chemotherapy has been recommended for improving the efficacy of treatment for nasopharyngeal carcinoma. Two patients with nasopharyngeal carcinoma complicated by collagen diseases (dermatomyositis in one, and Sjoegren`s syndrome with mixed connective tissue disease in the other) were given radiotherapy combined with chemotherapy consisting of cis-platinum and 5-fluorouracil. Following this combination therapy, both patients developed retropharyngeal abscess and ulceration of the mucosal membrane on the posterior wall of the oropharynx; there was no tumor cell involvement. Because these injuries were more severe than would have been expected from radiotherapy alone, It is recommended that special attention be paid to combination therapy in patients with nasopharyngeal carcinoma complicated by collagen disease. (author)

  12. 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.

  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. 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.

  15. Short-Term Effect of Different Teaching Methods on Nasopharyngeal Carcinoma for General Practitioners in Jakarta, Indonesia

    Science.gov (United States)

    Wildeman, Maarten A.; Fles, Renske; Adham, Marlinda; Mayangsari, Ika D.; Luirink, Ilse; Sandberg, Mara; Vincent, Andrew D.; Fardizza, Faiziah; Musa, Zanil; Armiyanto; Middeldorp, Jaap M.; Gerritsen, Geerten; Suwanto, Ronny; Tan, I. Bing

    2012-01-01

    In Indonesia, Nasopharyngeal Carcinoma (NPC) is the most frequent cancer of the head and neck region. At first presentation in the hospital most patients already have advanced NPC. Our previous study showed that general practitioners (GPs) working in Yogyakarta, Indonesia lack the knowledge necessary for early detection of NPC. By providing training on early symptoms of NPC we hope that the diagnosis and referral will occur at an earlier stage. Here we assess the current NPC knowledge levels of GPs in Jakarta, evaluate improvement after training, compare the effectiveness of two training formats, and estimate the loss of recall over a two week period. Methods Two Indonesian GPs visited 31 Primary Health Care Centres (PHCCs) and provided a lecture on NPC. The alternative format consisted of a symposium at the Universitas Indonesia, Jakarta, presented by local head and neck surgeons, with all GPs in the region being invited. To evaluate the effect of both formats a questionnaire was conducted before and after. Results The lecture in the PHCCs was attended by 130 GPs. Sixty-six GPs attended the training in the university hospital and 40 GPs attended both. Pre training the NPC knowledge level was poor with an average of 1.6 symptoms being correctly identified out of a potential maximum of 12, this was increased to 4.9 post training (p<0.0001). GPs attending the PHCC course recorded a greater increase in correct symptoms than those attending the symposium (3.8 vs. 2.8; p = 0.01). After a two week period the knowledge levels had declined slightly from 5.5 correctly identified symptoms to 4.2 (p = 0.25). Conclusion These results confirm our findings regarding GPs insufficient knowledge of NPC. Lectures in the PHCC and a symposium have both been proven to be effective training tools in the education of GPs. PMID:22431981

  16. 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.

  17. Short-term effect of different teaching methods on nasopharyngeal carcinoma for general practitioners in Jakarta, Indonesia.

    Directory of Open Access Journals (Sweden)

    Maarten A Wildeman

    Full Text Available UNLABELLED: In Indonesia, Nasopharyngeal Carcinoma (NPC is the most frequent cancer of the head and neck region. At first presentation in the hospital most patients already have advanced NPC. Our previous study showed that general practitioners (GPs working in Yogyakarta, Indonesia lack the knowledge necessary for early detection of NPC. By providing training on early symptoms of NPC we hope that the diagnosis and referral will occur at an earlier stage. Here we assess the current NPC knowledge levels of GPs in Jakarta, evaluate improvement after training, compare the effectiveness of two training formats, and estimate the loss of recall over a two week period. METHODS: Two Indonesian GPs visited 31 Primary Health Care Centres (PHCCs and provided a lecture on NPC. The alternative format consisted of a symposium at the Universitas Indonesia, Jakarta, presented by local head and neck surgeons, with all GPs in the region being invited. To evaluate the effect of both formats a questionnaire was conducted before and after. RESULTS: The lecture in the PHCCs was attended by 130 GPs. Sixty-six GPs attended the training in the university hospital and 40 GPs attended both. Pre training the NPC knowledge level was poor with an average of 1.6 symptoms being correctly identified out of a potential maximum of 12, this was increased to 4.9 post training (p<0.0001. GPs attending the PHCC course recorded a greater increase in correct symptoms than those attending the symposium (3.8 vs. 2.8; p = 0.01. After a two week period the knowledge levels had declined slightly from 5.5 correctly identified symptoms to 4.2 (p = 0.25. CONCLUSION: These results confirm our findings regarding GPs insufficient knowledge of NPC. Lectures in the PHCC and a symposium have both been proven to be effective training tools in the education of GPs.

  18. 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.

  19. 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

  20. 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....

  1. Quantification of Epstein-Barr virus DNA load in nasopharyngeal brushing samples in the diagnosis of nasopharyngeal carcinoma in southern China.

    Science.gov (United States)

    Zheng, Xiao-Hui; Lu, Li-Xia; Li, Xi-Zhao; Jia, Wei-Hua

    2015-09-01

    Nasopharyngeal carcinoma (NPC) is highly incident in southern China, where 40% of world's new cases arise each year. Detection of Epstein-Barr virus (EBV) DNA load in nasopharyngeal (NP) brush/swab samples has gradually been established as a method for diagnosis of NPC. However, its applicable value in NPC diagnosis has never been investigated in southern China. It is important to explore whether such a test could be applicable to our local population. A total of 245 consecutive participants undergoing NP brushing examination were recruited to obtain the NP brushing samples in this study. Quantitative PCR assays were used to obtain the EBV DNA load. Mann-Whitney, ANOVA and receiver operating characteristic tests were used to analyze its diagnostic value. NP brushing samples from NPC patients showed extremely high levels of EBV DNA load (mean = 46360 copy/ng DNA) compared to its expression from non-NPC control (mean = 28 copy/ng DNA) and high-risk control (mean = 50 copy/ng DNA) groups. It produced 96% sensitivity and 97% specificity, at the COV = 225 copy/ng DNA. Furthermore, EBV DNA load could reflect disease progress. Our data showed a better performance of EBV DNA load in NP brushing samples compared with an initial biopsy, immunoglobulin A (IgA) antibody titers to viral capsid antigen in serum and EBV DNA load in plasma. Detection of EBV DNA load in NP brushing samples could be an effective supplement for NPC diagnosis. Being minimally invasive and low cost, NP brush sampling combined with EBV DNA detection demonstrates great potential for screening high-risk populations for NPC.

  2. The use of biologically related model (Eclipse for the intensity-modulated radiation therapy planning of nasopharyngeal carcinomas.

    Directory of Open Access Journals (Sweden)

    Monica W K Kan

    Full Text Available Intensity-modulated radiation therapy (IMRT is the most common treatment technique for nasopharyngeal carcinoma (NPC. Physical quantities such as dose/dose-volume parameters are used conventionally for IMRT optimization. The use of biological related models has been proposed and can be a new trend. This work was to assess the performance of the biologically based IMRT optimization model installed in a popular commercial treatment planning system (Eclipse as compared to its dose/dose volume optimization model when employed in the clinical environment for NPC cases.Ten patients of early stage NPC and ten of advanced stage NPC were selected for this study. IMRT plans optimized using biological related approach (BBTP were compared to their corresponding plans optimized using the dose/dose volume based approach (DVTP. Plan evaluation was performed using both biological indices and physical dose indices such as tumor control probability (TCP, normal tissue complication probability (NTCP, target coverage, conformity, dose homogeneity and doses to organs at risk. The comparison results of the more complex advanced stage cases were reported separately from those of the simpler early stage cases.The target coverage and conformity were comparable between the two approaches, with BBTP plans producing more hot spots. For the primary targets, BBTP plans produced comparable TCP for the early stage cases and higher TCP for the advanced stage cases. BBTP plans reduced the volume of parotid glands receiving doses of above 40 Gy compared to DVTP plans. The NTCP of parotid glands produced by BBTP were 8.0 ± 5.8 and 7.9 ± 8.7 for early and advanced stage cases, respectively, while those of DVTP were 21.3 ± 8.3 and 24.4 ± 12.8, respectively. There were no significant differences in the NTCP values between the two approaches for the serial organs.Our results showed that the BBTP approach could be a potential alternative approach to the DVTP approach for NPC.

  3. Amplification of Epstein-Barr Virus (EBV) DNA by Superinfection with a Strain of EBV Derived from Nasopharyngeal Carcinoma

    OpenAIRE

    1988-01-01

    Epstein-Barr virus (EBV) from a nasopharyngeal carcinoma (NPC) hybrid cell line (NPC-KT) lacking defective viral DNA molecules superinfected Raji cells and induced EBV early antigens (EA), as did virus from P3HR-1 cells, which contained defective molecules. The EBV polypeptides induced by NPC-KT appeared to be identical to those induced by P3HR-1 virus. The ability of NPC-KT virus to induce EA was enhanced more than 10-fold by treatment of superinfected cells with dimethyl sulfoxide; however,...

  4. Methylation associated inactivation of RASSF1A and its synergistic effect with activated K-Ras in nasopharyngeal carcinoma

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    Yu Jing

    2009-12-01

    Full Text Available Abstract Background Epigenetic silencing of tumor suppressor genes associated with promoter methylation is considered to be a hallmark of oncogenesis. RASSF1A is a candidate tumor suppressor gene which was found to be inactivated in many human cancers. Although we have had a prelimilary cognition about the function of RASSF1A, the exact mechanisms about how RASSF1A functions in human cancers were largely unknown. Moreover, the effect of mutated K-Ras gene on the function of RASSF1A is lacking. The aim of this study was to investigate the expression profile and methylation status of RASSF1A gene, and to explore its concrete mechanisms as a tumor suppressor gene in Nasopharyngeal Carcinoma. Methods We examined the expression profile and methylation status of RASSF1A in two NPC cell lines, 38 primary nasopharyngeal carcinoma and 14 normal nasopharyngeal epithelia using RT-PCR and methylated specific PCR(MSP respectively. 5-aza-dC was then added to confirm the correlation between hypermethylation status and inactivation of RASSF1A. The NPC cell line CNE-2 was transfected with exogenous pcDNA3.1(+/RASSF1A plasmid in the presence or absence of mutated K-Ras by liposome-mediated gene transfer method. Flow cytometry was used to examine the effect of RASSF1A on cell cycle modulation and apoptosis. Meanwhile, trypan blue dye exclusion assays was used to detect the effect of RASSF1A transfection alone and the co-transfection of RASSF1A and K-Ras on cell proliferation. Results Promoter methylation of RASSF1A could be detected in 71.05% (27/38 of NPC samples, but not in normal nasopharyngeal epithelia. RASSF1A expression in NPC primary tumors was lower than that in normal nasopharyngeal epithelial (p p p p Conclusion Expression of RASSF1A is down-regulated in NPC due to the hypermethylation of promoter. Exogenous expression of RASSF1A is able to induce growth inhibition effect and apoptosis in tumor cell lines, and this effect could be enhanced by activated

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

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    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.

  6. 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.

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

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    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.

  8. Exosomal HIF1α supports invasive potential of nasopharyngeal carcinoma-associated LMP1-positive exosomes.

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    Aga, M; Bentz, G L; Raffa, S; Torrisi, M R; Kondo, S; Wakisaka, N; Yoshizaki, T; Pagano, J S; Shackelford, J

    2014-09-11

    It has emerged recently that exosomes are potential carriers of pro-tumorigenic factors that participate in oncogenesis. However, whether oncogenic transcription factors are transduced by exosomes is unknown. Hypoxia-inducible factor-1α (HIF1α) transcriptionally regulates numerous key aspects of tumor development and progression by promoting a more aggressive tumor phenotype, characterized by increased proliferation and invasiveness coupled with neoangiogenesis. It has been shown that the principal oncoprotein of Epstein-Barr virus (EBV), latent membrane protein 1 (LMP1), drives oncogenic processes and tumor progression of the highly invasive EBV malignancy, nasopharyngeal carcinoma (NPC). We now demonstrate that endogenous HIF1α is detectable in exosomes and that LMP1 significantly increases levels of HIF1α in exosomes. HIF1 recovered from exosomes retains DNA-binding activity and is transcriptionally active in recipient cells after exosome uptake. We also show that treatment of EBV-negative cells with LMP1-exosomes increases migration and invasiveness of NP cell lines in functional assays, which correlates with the phenotype associated with epithelial-mesenchymal transition (EMT). In addition, we provide evidence that HIF1α itself participates in exosome-mediated pro-metastatic effects in recipient cells, as exosome-mediated delivery of active and inactive forms of HIF1α results in reciprocal changes in the expression of E- and N-cadherins associated with EMT. Further, immunohistochemical analysis of NPC tumor tissues revealed direct correlation between protein levels of LMP1 and of the endosome/exosome marker tetraspanin, CD63, which suggests an increase in exosome formation in this EBV-positive malignancy. We hypothesize that exosome-mediated transfer of functional pro-metastatic factors by LMP1-positive NPC cells to surrounding tumor cells promotes cancer progression.

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

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    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. 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.

  11. 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

  12. Radiation-induced cranial neuropathy in patients with nasopharyngeal carcinoma. A follow-up study

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    Rong, X.; Tang, Y.; Lu, K.; Peng, Y. [Sun Yat-sen Memorial Hospital, Guangzhou (China). Dept. of Neurology; Chen, M. [Sun Yat-sen Univ., Guangzhou (China). Dept. of Nasopharyngeal Carcinoma

    2012-03-15

    The purpose of the current study was to investigate the long-term characteristics of radiation-induced cranial nerve injury in nasopharyngeal carcinoma (NPC) patients. We studied cranial nerve palsy (CNP) in 328 NPC patients who received radiotherapy between 1994 and 2006. Follow-up was 93.6% complete as of December 2009. A total of 72 patients with CNP were recruited for analysis (56 men and 16 women). Patients with evidence of residual or recurrent tumor accompanied by CNP were excluded. The characteristics of CNP and the relationship with the radiation fields as well as re-radiotherapy were evaluated. After a mean follow-up of 11.2 years, 72 patients were found to have developed CNP. The latency of palsy ranged from 0.6-16.0 years. For the 67 patients with first course radiation, the glossopharyngeal and vagus nerves were the most vulnerable combination, occurring in 57 patients (85.1%). Patients with facial-cervical field radiation had a significantly longer latency comparing with that of patients with facial-cervical split fields (p = 0.021). In the first 5 years, 49.3% of patients developed CNP, while 40.3% presented CNP in the second 5-year period. In patients with first course radiation, 61 patients had more than one CNP. With regard to the 5 patients with re-radiation, most of them had multiple upper cranial nerve injuries. Radiation therapy of NPC patients may lead to cranial neuropathy. Patients with facial-cervical radiation fields had a longer latency for the manifestation of CNP compared with those patients who were treated with split fields. In patients with re-radiotherapy, the frequency of upper cranial nerve injury increased greatly.

  13. 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.)

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

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

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    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.

  20. 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.

  1. Role of Epstein-Barr virus DNA measurement in plasma in the clinical management of nasopharyngeal carcinoma in a low risk area.

    NARCIS (Netherlands)

    Kalpoe, J.; Dekker, P.B.; Krieken, J.H.J.M. van; Jong, R.J.; Kroes, A.C.

    2006-01-01

    OBJECTIVE: To evaluate the role of quantitative measurement of Epstein-Barr virus (EBV) DNA in the clinical management of nasopharyngeal carcinoma (NPC) in a low tumour risk area (western Europe). METHODS: 22 consecutive Dutch NPC patients (11 europid) were studied. EBV DNA load in pretreatment and

  2. 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.

  3. Prognostic impact of pretherapeutic gamma-glutamyltransferase on patients with nasopharyngeal carcinoma

    Science.gov (United States)

    Peng, Hai-Hua; Huang, Wen-Jin; Cai, Long-Mei; Zhou, Tong-Chong

    2017-01-01

    Background Gamma-glutamyltransferase (GGT) is a membrane-bound enzyme involved in the metabolism of glutathione. Studies suggested that GGT played an important role in the tumor development, progression, invasion and drug resistance and prognosis. The association between GGT and prognosis of patients with nasopharyngeal carcinoma (NPC) was unknown. This study was conducted to investigate the association of pretherapeutic serum level of GGT with clinical-pathological parameters and survival in patients with NPC. Methods Two hundred and twenty-two patients with NPC were recruited in this study and were stratified into two GGT risk groups (≤ 34.5 U/L, > 34.5 U/L). The association of pretherapeutic serum GGT levels with clinical–pathological parameters was examined. Univariate and multivariate survival analyses were performed. Findings The pretherapeutic serum level of GGT was not associated with gender, age, pathology, T stage, N stage, TNM stage, chemotherapy or radiotherapy in patients with NPC. Patients in the high-risk GGT group had a poorer survival than the low-risk GGT group (3-year overall survival, 74.2% vs. 50.2%, P = 0.001; 3-year progression-free survival, 76.4% vs. 47.1%, P < 0.001; 3-year loco-regional relapse-free survival, 76.4% vs. 51.3%, P < 0.001; 3-year distant metastasis-free survival, 89.5% vs. 66.4%, P < 0.001). Multivariate analysis suggested that patients in the high-risk GGT group had 2.117 (95% confidence interval [CI], 1.225 ∼ 3.659, P = 0.007) times the risk of death, 2.836 (95% CI, 1.765 ∼ 4.557, P < 0.001) times the risk of progression, 2.551 (95% CI, 1.573 ∼ 4.138, P < 0.001) times the risk of relapse, and 3.331 (95% CI, 1.676 ∼ 6.622, P < 0.001) times the risk of metastasis compared with those in the low-risk GGT group. Conclusion The pretherapeutic serum level of GGT might serve as a novel independent prognostic factor for overall-survival, progression-free survival, loco-regional relapse-free survival and distant

  4. Pretreatment hematologic markers as prognostic factors in patients with nasopharyngeal carcinoma

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    Su, Li; Zhang, Mingwei; Zhang, Weijian; Cai, Chuanshu; Hong, Jinsheng

    2017-01-01

    Abstract Background: Pretreatment hematologic parameters of the inflammatory response, including lymphocyte, neutrophil, and platelet counts, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio, have emerged as prognostic factors for patients with cancer. This systematic review and meta-analysis aimed to summarize the association between the hematologic markers and prognosis of nasopharyngeal carcinoma (NPC). Methods: A systematic search of PubMed, Google Scholar, MEDLINE, EMBASE, Web of Science, and the Cochrane Library was conducted up to April 2016. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were extracted and synthesized to examine prognostic outcomes including cancer-specific survival (CSS), overall survival (OS), progression-free survival (PFS), distant metastasis-free survival, and local relapse-free survival (LRFS). Results: Fourteen studies comprising 11,651 NPC patients were ultimately included, and all eligible studies were conducted in East Asia. The OS, CSS, PFS, distant metastasis-free survival, and LRFS risks differed among patients according to hematologic marker levels. All of the parameters were associated with prognostic outcomes in patients with NPC. NLR and lymphocyte counts were most commonly reported. A high NLR was significantly associated with poor NPC prognosis (pooled HR 1.42, 95% CI 1.21–1.67 for CSS; pooled HR 1.77, 95% CI 1.41–2.23 for OS; pooled HR 1.67, 95% CI 1.36–2.06 for PFS; pooled HR 1.64, 95% CI 1.15–2.34 for LRFS). High lymphocyte count indicated favorable NPC prognosis (pooled HR 0.72, 95% CI 0.64–0.81 for OS; pooled HR 0.71, 95% CI 0.56–0.91 for PFS). Conclusions: Meta-analysis indicated that NLR and lymphocyte counts could be prognostic predictors in NPC for East Asian population. Patients with a high NLR or low lymphocyte count had poor prognosis. However, due to the limitation of included population, the conclusion was limited to East Asian

  5. Synergistic Effect of Combination Topotecan and Chronomodulated Radiation Therapy on Xenografted Human Nasopharyngeal Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, YanLing; Chen, Xin; Ren, PeiRong; Su, Zhou; Cao, HongYing; Zhou, Jie; Zou, XiaoYan; Fu, ShaoZhi; Lin, Sheng; Fan, Juan; Yang, Bo; Sun, XiaoYang [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Zhou, Yan; Chen, Yue [Department of Medical Imaging, Luzhou Medical College, Luzhou (China); Yang, LingLin, E-mail: yanglinglin2003@tom.com [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China); Wu, JingBo, E-mail: wjb6147@163.com [Department of Oncology, Affiliated Hospital of Luzhou Medical College, Luzhou (China)

    2013-10-01

    Purpose: To investigate the in vivo chronomodulated radiosensitizing effect of topotecan (TPT) on human nasopharyngeal carcinoma (NPC) and its possible mechanisms. Methods and Materials: Xenografted BALB/c (nu/nu) NPC mice were synchronized with an alternation of 12 hours of light from 0 to 12 hours after light onset (HALO) and 12 hours of darkness to establish a unified biological rhythm. Chronomodulated radiosensitization of TPT was investigated by analysis of tumor regrowth delay (TGD), pimonidazole hydrochloride, histone H2AX phosphorylation, (γ-H2AX) topoisomerase I (Top I), cell cycle, and apoptosis after treatment with (1) TPT (10 mg/kg) alone; (2) radiation therapy alone (RT); and (3) TPT+RT at 3, 9, 15, and 21 HALO. The tumor-loaded mice without any treatment were used as controls. Results: The TPT+RT combination was more effective than TPT or RT as single agents. The TPT+RT combination at 15 HALO was best (TGD = 58.0 ± 3.6 days), and TPT+RT at 3 HALO was worst (TGD = 35.0 ± 1.5 days) among the 4 TPT+RT groups (P<.05). Immunohistochemistry analysis revealed a significantly increased histone H2AX phosphorylation expression and decreased pimonidazole hydrochloride expression in the TPT+RT group at the same time point. The results suggested that the level of tumor hypoxia and DNA damage varied in a time-dependent manner. The expression of Top I in the TPT+RT group was also significantly different from the control tumors at 15 HALO (P<.05). Cell apoptosis index was increased and the proportion of cells in S phase was decreased (P<.05) with the highest value in 15 HALO and the lowest in 3 HALO. Conclusions: This study suggested that TPT combined with chronoradiotherapy could enhance the radiosensitivity of xenografted NPC. The TPT+RT group at 15 HALO had the best therapeutic effect. The chronomodulated radiosensitization mechanisms of TPT might be related to circadian rhythm of tumor hypoxia, cell cycle redistribution, DNA damage, and expression of Top I.

  6. 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

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

    Science.gov (United States)

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

    2012-04-01

    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-to-female 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

  8. 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.

  9. Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal carcinoma cells in vitro

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    C.W. Du

    2006-05-01

    Full Text Available Nasopharyngeal carcinoma (NPC is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1. Arsenic trioxide (As2O3 has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5/mL were cultured with or without 3 µM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i the colony formation inhibition rate (75.41 ± 3.9% in HNE1-LMP1 cells vs 37.89 ± 4.9% in HNE1 cells, the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 ± 3.5 vs 65.87 ± 5.9%, the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 ± 3.7 and 27.91 ± 2.1%, and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 ± 3.9 vs 29.19 ± 6.27% were all significantly different between the two cell lines (P < 0.01. ii LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.

  10. Comparison of efficacy of induction chemotherapy plus intensi-ty-modulated radiotherapy and concurrent chemo-radiotherapy plus adjuvant chemotherapy for patients with loco-regionally ad-vanced nasopharyngeal carcinoma%调强放疗结合诱导化疗或同期加辅助化疗治疗局部晚期鼻咽癌的疗效比较

    Institute of Scientific and Technical Information of China (English)

    丘文泽; 黄培钰; 施君理; 夏海群; 赵充; 曹卡加

    2015-01-01

    Objective: To compare the efficacy of induction chemotherapy (IC) plus intensity-modulated radiotherapy (IMRT) with that of concurrent chemo-radiotherapy (CCRT) plus adjuvant chemotherapy (AC) for patients with loco-regionally advanced naso-pharyngeal carcinoma (NPC). Methods:Data of 240 patients with loco-regionally advanced NPC were reviewed. These patients were admitted to the Sun Yat-sen University Cancer Center between January 2004 and December 2008. Among the 240 patients, 117 under-went the IC+IMRT and 123 were treated with the CCRT+AC. The IC+IMRT group received a regimen including cisplatin and 5-fluoro-uracil (5-FU). The CCRT+AC group received cisplatin concurrently with radiotherapy and subsequently received adjuvant cisplatin and 5-FU. The survival rates of the patients were assessed by Kaplan-Meier analysis, and the survival curves were compared by Log-rank test. Multivariate analysis was conducted using Cox proportional hazard regression model. Results:The 5-year overall survival (OS), disease-free survival, distant metastasis-free survival, local relapse-free survival, and the nodal relapse-free survival were 78.0%versus 78.7%, 68.9%versus 67.5%, 79.0%versus 77.0%, 91.6%versus 91.0%, and 95.3%versus 93.7%in the IC+IMRT and CCRT+AC groups, respectively. The survival between the two groups exhibited no significant differences. Higher rates of Grades 3 to 4 nau-sea-vomiting (8.1%vs. 1.7%, P=0.023) and leukopenia (9.7%vs. 0.9%, P=0.006) were observed in the CCRT+AC group. Multivariate analysis revealed that N stage and age were significant prognostic factors for the OS of the patients with loco-regionally advanced NPC. Conclusion:The treatment outcomes of IC+IMRT and CCRT+AC were similar. Distant metastasis remained as the predominant mode of treatment failure.%目的:比较诱导化疗加调强放疗和同期放化疗加辅助化疗治疗局部晚期鼻咽癌的疗效。方法:收集2004年1月至2008年12月中山大学肿瘤医院收治的经病

  11. Dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor NVP-BEZ235 has a therapeutic potential and sensitizes cisplatin in nasopharyngeal carcinoma.

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    Fen Yang

    Full Text Available Phosphoinositide 3-kinase (PI3K/AKT/mammalian target of rapamycin inhibitor (mTOR pathway is often constitutively activated in human tumor cells and thus has been considered as a promising drug target. To ascertain a therapeutical approach of nasopharyngeal carcinoma (NPC, we hypothesized NVP-BEZ235, a novel and potent imidazo[4,5-c] quinolone derivative, that dually inhibits both PI3K and mTOR kinases activities, had antitumor activity in NPC. Expectedly, we found that NVP-BEZ235 selectively inhibited proliferation of NPC cells rather than normal nasopharyngeal cells using MTT assay. In NPC cell lines, with the extended exposure, NVP-BEZ235 selectively inhibited proliferation of NPC cells harboring PIK3CA mutation, compared to cells with wild-type PIK3CA. Furthermore, exposure of NPC cells to NVP-BEZ235 resulted in G1 growth arrest by Propidium iodide uptake assay, reduction of cyclin D1and CDK4, and increased levels of P27 and P21 by Western blotting, but negligible apoptosis. Moreover, we found that cisplatin (CDDP activated PI3K/AKT and mTORC1 pathways and NVP-BEZ235 alleviated the activation by CDDP through dually targeting PI3K and mTOR kinases. Also, NVP-BEZ235 combining with CDDP synergistically inhibited proliferation and induced apoptosis in NPC cells. In CNE2 and HONE1 nude mice xenograft models, orally NVP-BEZ235 efficiently attenuated tumor growth with no obvious toxicity. In combination with NVP-BEZ235 and CDDP, there was dramatic synergy in shrinking tumor volumes and inducing apoptosis through increasing Noxa, Bax and decreasing Mcl-1, Bcl-2. Based on the above results, NVP-BEZ235, which has entered phase I/II clinical trials in patients with advanced solid tumors, has a potential as a monotherapy or in combination with CDDP for NPC treatment.

  12. Identification of Differentially Expressed Genes in Metastatic and Non-Metastatic Nasopharyngeal Carcinoma Cells by Suppression Subtractive Hybridization

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    Xu-Yu Yang

    2005-01-01

    Full Text Available Background & Objective: Nasopharyngeal carcinoma (NPC is an epithelial neoplasm with high occurrence rates in southern China. The disease often metastasizes to regional lymphnodes at a very early stage. Local recurrences and metastasis occur frequently in patients with NPC and are a leading cause of death, despite improvements on treatment modalities. The molecular mechanism underlying the metastasis of nasopharyngeal carcinoma remains poorly understood, however, and requires additional elucidation. The aim of this study was to explore possible NPC gene candidates that may play key roles in NPC metastasis. Methods: Subtractive suppression hybridization (SSH was performed to isolate differentially expressed clones between the metastatic 5-8F and non-metastatic 6-10B nasopharyngeal carcinoma cell lines. Differentially expressed clones were screened and confirmed by reverse Northern blotting. The sequences of cDNA fragments were subsequently analyzed and compared to known sequences in Genbank. Results & Discussion: The SSH library contained thousands of positive clones. Random analysis of 300 clones by PCR demonstrated that 269 clones contained inserted fragments. Reverse Northern blot confirmed that 20 out of 192 clones examined were significantly up-regulated in the 5-8F cell line. Among these 20 clones, 16 were previously identified genes (flotilin-2, ezrin, pim-3, fli-1, mel, neugrin, znf216, ASB1, raly, UBE2A, keratin6A, TMED7, EIF3S9, FTL, two ribosomal proteins RPL21 and RPL16, two were predicted genes (c9orf74 and MDS006, and two sequences shared no homology with known genes listed in GenBank and may represent novel genes. The proposed functions of the genes identified in this study include cell signal transduction, cell survival, transcription regulation, cell mobility, protein synthesis, and DNA damage repair. Flotillin-2, fli-1, pim-3 and ezrin have previously been reported to be associated with tumor metastasis and progression. The

  13. Comparison of Epstein-Barr virus genotypes and clinicohistopathological features of nasopharyngeal carcinoma between Guilin, China and Fukuoka, Japan.

    Science.gov (United States)

    Zhou, Yingqiong; Nabeshima, Kazuki; Koga, Kaori; Aoki, Mikiko; Hayashi, Hiroyuki; Hamasaki, Makoto; Iwasaki, Hiroshi

    2008-06-01

    Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is endemic to Guilin, China, but not Fukuoka, Japan. To examine whether the NPC in these two cities are distinct in their association with EBV, we analyzed the histology and EBV genotypes in 163 NPC from Guilin, 52 NPC from Fukuoka and non-cancerous control nasopharyngeal tissues (n=22 each) by in situ hybridization and PCR. The proportion of EBV-positive NPC from Guilin (95%) was higher than that of Fukuoka (55%, pEBV-positivity was higher in NKC-U than KSCC in the two cities. EBV genotype A was highly prevalent in Guilin and Fukuoka. However, the BamHI f variant was predominant in Guilin (79%), whereas all the identified types were the F prototype in Fukuoka. The genetic structure and biological functions of the EBV strain associated with endemic NPC in Guilin were probably different from those of Fukuoka. The genetic differences between Guilin and Fukuoka may mirror the differences in histology and patient profiles.

  14. New advances in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sonia; Pascual; Iván; Herrera; Javier; Irurzun

    2016-01-01

    Hepatocellular carcinoma(HCC)is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths.Most HCC are associated withwell known underlying risk factors,in fact,HCC arise in cirrhotic patients in up to 90%of cases,mainly due to chronic viral hepatitis and alcohol abuse.The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients.HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified.The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient atrisk for developing HCC.The diagnosis of HCC can be based on non-invasive criteria(only in cirrhotic patient)or pathology.Accurately staging patients is essential to oncology practice.The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function.Treatment allocation is based on several factors:Liver function,size and number of tumours,macrovascular invasion or extrahepatic spread.The recommendations in terms of selection for different treatment strategies must be based on evidence-based data.Resection,liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates.Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment.Finally,in patients with advanced HCC with preserved liver function,sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients.

  15. 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.

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

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    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.

  17. 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.)

  18. Association of E-cadherin and β-catenin with metastasis in nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    李智; 任艺; 林素暇; 梁英杰; 梁惠珍

    2004-01-01

    Background This study was designed to detect methylation of E-cadherin gene promoter and gene mutation of β-catenin in exon 3 and their expression of protein and mRNA in primary tumor and lymph node metastatic tumor of nasopharyngeal carcinoma (NPC), and investigate the mechanism of invasion and metastasis of neoplastic cells in NPC.Methods Fourty-two fresh biopsy samples were taken from untreated NPC patients at the Affiliated Hospital of Sun Yat-sen Medical College, Sun Yat-sen University, Guangzhou, China during the period of 1999-2002. Among them 21 were taken from primary tumors and the other 21 from lymph node metastatic tumors. The gene promoter methylation of E-cadherin was detected by methylation-specific PCR (MSP). The mutation in exon 3 of β-catenin was detected by direct sequencing analysis. RT-PCR, Western blot and immunohistochemical staining were used to detect the mRNA and protein expression patterns in both primary and metastatic tumors of NPC. Results Down-regulated expression of E-cadherin in metastatic tumor was compared with that in primary tumor. Reduced expression of E-cadherin was found to be correlated with lymph node metastatic tumor of NPC (P=0.004); but there was no obvious correlation between primary and metastatic tumors in the expression of β-catenin (P=0.698). The mRNA expression level of E-cadherin in metastatic tumors decreased significantly compared with that in primary tumors. However, little change was observed in the mRNA level of β-catenin in different tumor tissues. Only 4 samples (19.1%) displayed gene promoter methylation of E-cadherin in primary tumor and 10 samples (47.6%) showed methylated form of E-cadherin. The gene promoter methylation of E-cadherin was more common in metastatic tumor than in primary tumor of NPC (P=0.024). Only 2 (4.76%) of the 42 samples showed mutations in exon 3 of β-catenin at 41 (T41A, ACCGCC) and codon 47 (S47T, AGTACT). The cytoplasmic and nuclear expression of β-catenin in tumor

  19. 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

  20. Matrix metalloproteinase 13‐containing exosomes promote nasopharyngeal carcinoma metastasis

    OpenAIRE

    2015-01-01

    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 kno...

  1. Pediatric nasopharyngeal carcinoma: Anatomo-clinic aspects, therapeutic results and progressive particularities;Le cancer du cavum de l'enfant et l'adulte jeune: aspects anatomocliniques, therapeutiques et particularites evolutives

    Energy Technology Data Exchange (ETDEWEB)

    Frikha, M.; Toumi, N. [Service de carcinologie medicale, CHU Habib-Bourguiba, Sfax (Tunisia); Ghorbel, L.; Ben Salah, H.; Daoud, J. [Service de carcinologie radiotherapie, CHU Habib-Bourguiba, Sfax, (Tunisia); Khabir, A.; Boudawara, T. [Service d' anatomopathologie, CHU Habib-Bourguiba, Sfax (Tunisia); Karray, H. [Service de virologie, CHU Habib-Bourguiba, Sfax (Tunisia); Gargouri, R. [Centre de biotechnologie, Sfax (Tunisia); Ghorbel, A. [Service d' ORL, CHU Habib-Bourguiba, Sfax (Tunisia)

    2010-06-15

    Purpose We retrospectively analyzed anatomo-clinic, therapeutic and progressive particularities of 74 young patients (= 20 years) with nasopharyngeal carcinoma treated between 1993 and 2005. Patients and methods Initial work-up included a fiberoptic naso-fiberscopy with biopsy, computed tomography and/or MRI of nasopharynx and neck, chest X-ray, abdominal ultrasonography and bone scan. Patients were treated with either primary chemotherapy (epirubicin and cisplatin) followed by radiotherapy or concomitant radio chemotherapy (five fluorouracil and cisplatin). Radiotherapy was delivered to a total dose of 70 to 75 Gy to nasopharynx and involved cervical lymph nodes and 50 Gy to the remainder cervical areas. Results The median age was 16 years. Sixty-three percent of patients had undifferentiated tumors. Sixty-six percent had locally advanced tumor. With a median follow-up of 107 months, one patient presented a local relapse, 24 patients developed distant metastases with a median delay of 7 months. The 5 years overall survival and disease-free survival were 66 and 65 %. Late complications were dominated by dry mouth and endocrine disorders. Comments Pediatric nasopharyngeal carcinoma is characterized by an early metastatic diffusion. Local control is excellent but with severe late toxicities. New techniques of radiotherapy and new molecules of chemotherapy could improve these results. (authors)

  2. 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.

  3. The Evolution of and Risk Factors for Neck Muscle Atrophy and Weakness in Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy: A Retrospective Study in an Endemic Area.

    Science.gov (United States)

    Zhang, Lu-Lu; Mao, Yan-Ping; Zhou, Guan-Qun; Tang, Ling-Long; Qi, Zhen-Yu; Lin, Li; Yao, Ji-Jin; Ma, Jun; Lin, Ai-Hua; Sun, Ying

    2015-08-01

    The aim of this study was to investigate the evolution of sternocleidomastoid muscle (SCM) atrophy in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT), and the relationship between SCM atrophy and neck weakness.Data were retrospectively analyzed from 223 biopsy-proven NPC patients with no distant metastasis who underwent IMRT with or without chemotherapy. The volume of SCM was measured on pretreatment magnetic resonance imaging (MRI), and MRIs were conducted 1, 2, and 3 years after the completion of IMRT. Change in SCM volume was calculated and classified using the late effects of normal tissues-subjective, objective, management, and analytic system. The grade of neck muscle weakness, classified by the Common Terminology Criteria for Adverse Events V 3.0, was measured 3 years after the completion of IMRT.The average SCM atrophy ratio was -10.97%, -18.65%, and -22.25% at 1, 2, and 3 years postirradiation, respectively. Multivariate analysis indicated N stage and the length of time after IMRT were independent prognostic variables. There were significant associations between the degree of SCM atrophy and neck weakness.Radical IMRT can cause significant SCM atrophy in NPC patients. A more advanced N stage was associated with more severe SCM atrophy, but no difference was observed between N2 and N3. SCM atrophy progresses over time during the 3 years following IMRT. Grade of SCM atrophy is significantly associated with neck weakness.

  4. Extra-cellular release and blood diffusion of BART viral micro-RNAs produced by EBV-infected nasopharyngeal carcinoma cells

    OpenAIRE

    Baconnais Sonia; Amiel Corinne; Schneider Véronique; Témam Stéphane; Lang Philippe; Guigay Joël; Vérillaud Benjamin; Klibi Jihène; Bombik Izabela; Gelin Aurore; Gourzones Claire; Jimenez Anne-Sophie; Busson Pierre

    2010-01-01

    Abstract Background Nasopharyngeal carcinoma (NPC) is a human epithelial malignancy consistently associated with the Epstein-Barr virus. The viral genome is contained in the nuclei of all malignant cells with abundant transcription of a family of viral microRNAs called BART miRNAs. MicroRNAs are well known intra-cellular regulatory elements of gene expression. In addition, they are often exported in the extra-cellular space and sometimes transferred in recipient cells distinct from the produc...

  5. Cisplatin, tegafur-uracil and leucovorin plus mitomycin C: an acceptably effective and toxic regimen for patients with recurrent or metastatic nasopharyngeal carcinoma

    Directory of Open Access Journals (Sweden)

    Chia-Hsun Hsieh

    2013-10-01

    Full Text Available Background: This prospective phase II clinical trial evaluated the efficacy and toxicity of cisplatin, oral tegafur-uracil, leucovorin, and mitomycin C in patients with recurrent or metastatic nasopharyngeal carcinoma. Methods: Patients with histologically proven non-keratinizing or undifferentiated nasopharyngeal carcinoma were prospectively enrolled from April 2002 to June 2005. Cisplatin 50 mg/m 2 on day 1, 22 and mitomycin C 6 mg/m 2 on day 1 were administered. Oral tegafur-uracil 300 mg/m 2 /day and oral leucovorin 60 mg/day were given on day 1-14 and day 22-35, respectively. Each cycle was repeated every 6 weeks. Primary and secondary endpoints are response rate and toxic profiles with survivals, respectively. Results: Twenty-two patients with the median age of 47 (35-69 years were enrolled in the study. Sixteen (72.7% patients had undifferentiated nasopharyngeal carcinoma. The regimen was well-tolerated by all patients with the exception of one patient (4.6% who experienced grade IV anorexia, and two patients (9.1% who had grade IV vomiting. There was no treatment-related death. The overall response rate was 59.1%, including 3 (13.6% complete remissions. The median duration of response was 15.9 months, the median time to tumor progression was 10.0 months, and the median overall survival was 16.0 months. Conclusion: This outpatient chemotherapy regimen is acceptably effective and toxic among patients with recurrent or metastatic nasopharyngeal carcinoma.

  6. 鼻咽癌放疗对耳损伤的临床观察%Effect of Radiotherapy on Ear Function in Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    薛英; 彭涛

    2012-01-01

    目的:探讨放疗对鼻咽癌患者耳部结构及功能的影响.方法:选择无耳病及听力正常的163例鼻咽癌患者,于放疗前及放疗后不同时间点检测其耳部的结构及听功能状态.结果:随放疗时间及放疗结束后的时间延长,外耳道炎、分泌性中耳炎及化脓性中耳炎的发生率增加,不同性质的耳聋的发生率及听力损失的程度亦逐渐增加.结论:放疗对鼻咽癌患者的耳部的结构及功能损伤明显,严重影响鼻咽癌患者生存质量.%Objective: To study the changes of ear function and construction after radiotherapy in naso-pharyngeal carcinoma. Methods: Hearing and physical examination were performed in 163 patients with nasopharyngeal carcinoma at different time after radiotherapy. Results: The incidence of the otitis externa,secretory otitis media, suppurative otitis media, different type hearing loss and extent of hearing loss was increased according to radiotherapeutic time and the time after radiation. Conclusion: Injury of structure and function of ear was apparently affected after radio-theray of nasopharyngeal carcinoma and life quality of patients with nasopharyngeal carcinoma was markedly lowered.

  7. The Evolution of and Risk Factors for Neck Muscle Atrophy and Weakness in Nasopharyngeal Carcinoma Treated With Intensity-Modulated Radiotherapy

    OpenAIRE

    Zhang, Lu-lu; Mao, Yan-Ping; Zhou, Guan-Qun; Tang, Ling-Long; Qi, Zhen-Yu; Lin, Li; Yao, Ji-Jin; Ma, Jun; Lin, Ai-Hua; Sun, Ying

    2015-01-01

    Abstract The aim of this study was to investigate the evolution of sternocleidomastoid muscle (SCM) atrophy in nasopharyngeal carcinoma (NPC) patients following intensity-modulated radiotherapy (IMRT), and the relationship between SCM atrophy and neck weakness. Data were retrospectively analyzed from 223 biopsy-proven NPC patients with no distant metastasis who underwent IMRT with or without chemotherapy. The volume of SCM was measured on pretreatment magnetic resonance imaging (MRI), and MRI...

  8. {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.)

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. The Impact of Clinical Stage on Radiation Doses to Organs at Risk Following Intensity-modulated Radiotherapy in Nasopharyngeal Carcinoma: A Prospective Analysis.

    Science.gov (United States)

    Xu, Lin; Yao, Ji-Jin; Zhou, Guan-Qun; Zhang, Wang-Jian; Liu, Guo-Long; Liu, Li-Zhi; Ma, Jun; Sun, Ying

    2016-01-01

    Background: The development of intensity-modulated radiotherapy (IMRT) has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study was to investigate the impact of clinical stage on radiation doses to organs at risk (OARs) in NPC. Material and Methods: One hundred and forty-eight patients with newly diagnosed and untreated NPC were prospectively enrolled. Based on the anatomic definition and pathogenesis of radiation induced injury, a total of 28 OARs surrounding the nasopharynx were contoured on axial computed tomography (CT) planning images in each patient. Dose-volume histograms, as well as the mean and maximal doses for each structure, were calculated. Results: Radiation doses to 15 OARs (including the brain stem, temporal lobe and eye) were positively correlated with T stage, the radiation doses to 13 OARs (including the brachial plexus, parotid and thyroid) increased significantly with N stage, and the radiation doses to the spinal cord and mandible had no association with T or N stage. Based on the characteristic of excess rates, 9 OARs (e.g. spinal cord, eye, trachea, and et al.) met tolerance doses easily in all stages, 9 OARs (e.g. brain stem, temporal lobe, brachial plexus, and et al.) easily in early stages but with difficulty in advanced stages, and 10 OARs (e.g. cochlea, parotid, thyroid, and et al.) with difficulty in all stages. Conclusions: The radiation doses to most of OARs are associated with T or N stage, and there are three kinds of patterns for them: 1) meet tolerance doses easily in all stages; 2) meet tolerance doses easily in early stages but with difficulty in advanced stages; and 3) meet tolerance doses with difficulty in all stages.

  14. The effect of the target-organ geometric complexity on the choice of delivery between RapidArc and sliding-window IMRT for nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kan, Monica W.K., E-mail: kanwkm@ha.org.hk [Department of Oncology, Princess Margaret Hospital, Hong Kong (Hong Kong); Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong (Hong Kong); Leung, Lucullus H.T. [Department of Oncology, Princess Margaret Hospital, Hong Kong (Hong Kong); Yu, Peter K.N. [Department of Physics and Materials Science, City University of Hong Kong, Kowloon Tong, Hong Kong (Hong Kong)

    2013-10-01

    We attempted to assess the effect of target-organ geometric complexity on the plan quality of sliding-window intensity-modulated radiotherapy (IMRT), double-arc (RA2), and triple-arc (RA3) RapidArc volumetric-modulated arc radiotherapy for nasopharyngeal carcinoma (NPC). Plans for 9-field sliding-window IMRT, RA2, and RA3 were optimized for 36 patients with NPC ranging from T1 to T4 tumors. Initially the patients were divided into 2 groups, with group A representing the most simple early stage (T1 and T2) cases, whereas group B represented the more complex advanced cases (T3 and T4). Evaluation was performed based on target conformity, target dose homogeneity, organ-sparing capability, and delivery efficiency. Based on the plan quality results, a subgroup of advanced cases, group B2, representing the most demanding task was distinguished and reported separately from the rest of the group B cases, B1. Detailed analysis was performed on the anatomic features for each group of cases, so that planners can easily identify the differences between B1 and B2. For the group A cases, RA3 plans were superior to the IMRT plans in terms of organ sparing, whereas target conformity and dose homogeneity were similar. For the group B1 cases, the RA3 plans produced almost equivalent plan quality as the IMRT plans. For the group B2 cases, for most of which large target volumes were adjacent to (5 mm or less) and wrapping around the brain stem, RA2 and RA3 were inferior to the IMRT regarding both target dose homogeneity and conformity. RA2 plans were slightly inferior to IMRT and RA3 plans for most cases. The plan comparison results depend on the target to brain stem distances and the target sizes. The plan quality results together with the anatomic information may allow the evaluation of the 3 treatment options before actual planning.

  15. Which T category of nasopharyngeal carcinoma may benefit most from volumetric modulated arc therapy compared with step and shoot intensity modulated radiation therapy.

    Directory of Open Access Journals (Sweden)

    Ying Sun

    Full Text Available BACKGROUND: To compare volumetric modulated arc therapy (VMAT with conventional step and shoot intensity modulated radiation therapy (s-IMRT in nasopharyngeal carcinoma (NPC patients, and identify which T category patient gains the maximum benefit from VMAT. METHODS: Fifty-two patients that randomly selected from 205 patients received VMAT at a single center were retrospectively replanned with s-IMRT. For a fair comparison, the planning target volume (PTV coverage of the 2 plans was normalized to the same level. A standard planning constraint set was used; the constraints for the organs at risk (OARs were individually adapted. The calculated doses to the PTV and OARs were compared for s-IMRT and VMAT plans generated using the Monaco treatment planning system. RESULTS: VMAT and s-IMRT plans had similar PTV coverage and OAR sparing within all T categories. However, in stratified analysis, VMAT plans lead to better or similar sparing of the OARs in early T category patients; and lead to poorer sparing of the OARs in advanced T category patients (P<0.05. VMAT shows significant advantages for low dose burden (P<0.05 compared with s-IMRT. The delivery time per fraction for VMAT (424±64 s was shorter than s-IMRT (778 ± 126 s, p<0.01. CONCLUSIONS: VMAT provides similar dose coverage of the PTVs and similar/better normal tissue sparing in early T category NPC, and poorer OARs sparing in advanced T category NPC. And VMAT shows significant advantages for low dose burden and delivery time.

  16. A comparison of anatomical and dosimetric variations in the first 15 fractions, and between fractions 16 and 25, of intensity-modulated radiotherapy for nasopharyngeal carcinoma.

    Science.gov (United States)

    Yang, Haihua; Tu, Yu; Wang, Wei; Hu, Wei; Ding, Weijun; Yu, Changhui; Zhou, Chao

    2013-11-04

    The purpose of this study was to compare anatomical and dosimetric variations in first 15 fractions, and between fractions 16 and 25, during intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). Twenty-three NPC patients who received IMRT in 33 fractions were enrolled. Each patient had two repeat computed tomography (CT) scans before the 16th and 25th fraction. Hybrid IMRT plans were generated to evaluate the dosimetric changes. There was a significant decrease of the transverse diameter of nasopharyngeal and neck as well as gross tumor volume (GTV) in the primary nasopharyngeal carcinoma (GTVnx) and involved lymph nodes (GTVnd) during the first 15 fractions, and between fraction 16 and 25 (p fractions treatment compared to that between fraction 16 and 25 (p fractions (p fraction 16 and 25. While the maximum dose to the spinal cord was significantly increased both in the first 15 fractions, and between fraction 16 and 25 (p fractions compared to that between fraction 16 and 25 (p fractions, and between fractions 16 and 25, of IMRT.

  17. 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 ...

  18. 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.

  19. 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.

  20. 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.

  1. 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.

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

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    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/.

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

    Science.gov (United States)

    Wu, Danxin; Zhang, Yu; Huang, Jie; Fan, Zirong; Shi, Fengrong; Wang, Senming

    2014-01-10

    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.

  4. Protein expression of nucleophosmin, annexin A3 and nm23-H1 correlates with human nasopharyngeal carcinoma radioresistance in vivo.

    Science.gov (United States)

    Qu, Song; Li, Xiao-Yu; Liang, Zhong-Guo; Li, Ling; Huang, Shi-Ting; Li, Jia-Quan; Li, Dan-Rong; Zhu, Xiao-Dong

    2016-07-01

    Radioresistance is a significant obstacle in the treatment of endemic nasopharyngeal carcinoma (NPC). The present study aimed to identify proteins associated with radioresistance in NPC in vitro and in vivo. Proteomics analyses were conducted to screen for differentially-expressed proteins (DEPs) in parental CNE-2 cells and CNE-2R cells. Using proteomics approaches, 16 DEPs were identified. Of these DEPs, nucleophosmin (NPM1), annexin A3 and nm23-H1, were verified using western blot analyses. The tumorigenicity was investigated using mouse xenograft tumorigenicity assays, and tumor growth curves were generated. The protein expression of NPM1, annexin A3 and nm23-H1 was examined by immunohistochemically staining tumor tissues. NPM1 and annexin A3 protein levels were downregulated in the CNE-2R cells, whereas nm23-H1 expression was upregulated. In vivo tests showed that compared with the CNE-2 tumors, CNE-2R tumor growth was significantly retarded (PA3 expression was significantly lower in non-irradiated (NIR)-CNE-2R tumors compared with NIR-CNE-2 tumors (PA3 and nm23-H1 expression correlated with the cellular and tumor radioresponse. These proteins are involved in the regulation of intracellular functions, including stress responses, cell proliferation and DNA repair. However, further clinical evaluations are required.

  5. Association between interferon gamma 13-CA-repeats polymorphism and metastasis of nasopharyngeal carcinoma in a population of Northern China.

    Science.gov (United States)

    Hao, Kaifei; Yan, Zhaohui; Shuang, Yu; Sun, Jinsong; Tao, Shudong; Fu, Wenyuan; Liu, Lei

    2015-01-01

    Interferon Gamma gamma (IFN-γ) 13-CA-repeats polymorphism is associated with a variety of diseases; here we report its association with nasopharyngeal carcinoma (NPC) metastasis in a retrospective analysis of a cohort of 220 NPC patients in the northern China. The results showed that the distributions of CA13-/CA13-genotypes were significantly higher in the patients with lymph node metastasis (P<0.05) and distant metastasis (P<0.001); there was a significant difference between NPC patients with stage I+II and those with stage III+IV regarding CA13+/CA13-(P<0.001) and CA13-/CA13- genotypes (P<0.001); further analysis showed a more pronounced difference between NPC patients with stage I+II+III and those with stage IV for CA13-/CA13-genotype (P<0.001), whereas no difference was found for CA13+/CA13- genotype (P=0.790). Thus, we identify that IFN-γ 13-CA-repeat polymorphism is significantly associated with the metastasis of NPC, which may provide insights into its prognosis and individualized treatment.

  6. 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.

  7. Prognostic scoring system for locoregional control among the patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy

    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 prognostic value of T category for locoregional control in patients with nasopharyngeal carcinoma (NPC) has decreased with the extensive use of intensity-modulated radiotherapy (IMRT). We aimed to develop a prognostic scoring system (PSS) that incorporated tumor extension and clinical characteristics for locoregional control in NPC patients treated with IMRT. The magnetic resonance imaging scans and medical records of 717 patients with nonmetastatic NPC treated with IMRT at Sun Yat-sen University Cancer Center between January 2003 and January 2008 were reviewed. Age, pathologic classification, primary tumor extension, primary gross tumor volume (GTV-p), T and N categories, and baseline lactate dehydrogenase (LDH) level were analyzed. Hierarchical cluster analysis as well as univariate and multivariate analyses were used to develop the PSS. Independent prognostic factors for locoregional relapse included N2-3 stage, GTV-p≥26.8 mL, and involvement of one or more structures within cluster 3. We calculated a risk score derived from the regression coefficient of each factor and classified patients into four groups:low risk (score 0), intermediate risk (score>0 and≤1), high risk (score>1 and≤2), and extremely high risk (score>2). The 5-year locoregional control rates for these groups were 97.4%, 93.6%, 85.2%, and 78.6%, respectively (P<0.001). We have developed a PSS that can help identify NPC patients who are at high risk for locoregional relapse and can guide individualized treatments for NPC patients.

  8. 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

  9. Red Meat and Processed Meat Consumption and Nasopharyngeal Carcinoma Risk: A Dose-response Meta-analysis of Observational Studies.

    Science.gov (United States)

    Li, Fuqin; Duan, Fujiao; Zhao, Xia; Song, Chunhua; Cui, Shuli; Dai, Liping

    2016-01-01

    The purpose of this study is to clarify and quantify the potential dose-response association between the intake of total red and total processed meat and risk of nasopharyngeal carcinoma (NPC). Relevant studies were identified by searching PubMed, EMBASE, and Chinese databases (CNKI and Wanfang). The summary relative risk (RR) with 95% confidence interval (95%CI) was calculated. A total of 15 independent studies with 12,735 subjects were identified. Compared with the low-rank intake, the summary RR of NPC was 1.35 (95%CI, 1.21-1.51) for total red meat and 1.46 (95%CI, 1.34-1.64) for total processed meat. For the moderate-rank intake, the summary RR of NPC was 1.54 (95%CI, 1.36-1.79) for total red meat and 1.59 (95%CI, 1.3-1.90) for total processed meat. The summary RR for high-rank intake was 1.71 (95%CI, 1.14-2.55) for total red meat and 2.11 (95%CI, 1.31-3.42) for total processed meat. The combined estimates showed obvious evidence of statistically significant association between total red and total processed meat consumption dose and risk of NPC (Ptrendprocessed meat is associated with a significantly increased risk of NPC.

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

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    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.

  11. 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.

  12. 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.

  13. Serum CXCL9 levels are associated with tumor progression and treatment outcome in patients with nasopharyngeal carcinoma.

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    Li-Jen Hsin

    Full Text Available OBJECTIVES: The aim of this cohort study was to examine the role of the chemokine (C-X-C motif ligand 9 (CXCL9 on nasopharyngeal carcinoma (NPC. MATERIALS & METHODS: Sera from 205 NPC patients and 231 healthy individuals, and 86 NPC tumor samples were enrolled. CXCL9 expression in tissue samples was analyzed by quantitative real-time PCR and immunohistochemistry. CXCL9 serum concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: CXCL9 expression was significantly higher in tumors than in normal epithelium. CXCL9 serum concentrations were also significantly higher in NPC patients compared to those in healthy individuals (516.8±617.6 vs. 170.7±375.0 pg/mL, P290 pg/mL, median before treatment had worse prognoses for overall survival and disease-free survival (P = 0.045 and P = 0.008, respectively. Multivariate logistic regression analyses also indicated that higher CXCL9 serum levels were an independent prognostic factor for disease-free survival (P = 0.015. CONCLUSION: Our study demonstrated that CXCL9 is associated with tumor burden and aggressiveness of NPC tumors and the serum level of this ligand may be useful as a prognostic indicator.

  14. 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.

  15. Application of circulating plasma/serum EBV DNA in the clinical management of nasopharyngeal carcinoma.

    Science.gov (United States)

    Yip, Timothy T C; Ngan, Roger K C; Fong, Alvin H W; Law, Stephen C K

    2014-06-01

    Elevated levels of circulating cell-free Epstein-Barr virus (EBV) DNA have been detected in plasma and serum samples from nasopharyngeal cancer (NPC) patients by quantitative real time PCR (qPCR) test. This qPCR test for circulating EBV DNA was found to be useful in the clinical management of NPC patients. For instance, EBV DNA qPCR test has good sensitivity and specificity in the detection of NPC at disease onset. Increase of the viral DNA load was found in NPC patients at late stages of disease. High EBV DNA load at disease onset or detectable viral load post-treatment was associated with poor survival or frequent relapse in NPC patients. Residual EBV DNA load after primary treatment could be a useful indicator to justify adjuvant chemotherapy. The qPCR test might also be applied to define a poor prognostic group in patients at early stage (I/II) for implementing concurrent chemo-radiotherapy (chemo-RT) to improve patients' outcome. The test is also useful to monitor distant metastases or response to radiotherapy, chemo-RT or surgery. Supplementary tests, however, are needed to pick up EBV negative WHO type I NPC and test improvement is needed to increase sensitivity in detecting stage I disease and local recurrence.

  16. 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.

  17. Low Prognostic Nutritional Index (PNI Predicts Unfavorable Distant Metastasis-Free Survival in Nasopharyngeal Carcinoma: A Propensity Score-Matched Analysis.

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    Lin Yang

    Full Text Available Poor nutritional status is associated with progression and advanced disease in patients with cancer. The prognostic nutritional index (PNI may represent a simple method of assessing host immunonutritional status. This study was designed to investigate the prognostic value of the PNI for distant metastasis-free survival (DMFS in patients with nasopharyngeal carcinoma (NPC.A training cohort of 1,168 patients with non-metastatic NPC from two institutions was retrospectively analyzed. The optimal PNI cutoff value for DMFS was identified using the online tool "Cutoff Finder". DMFS was analyzed using stratified and adjusted analysis. Propensity score-matched analysis was performed to balance baseline characteristics between the high and low PNI groups. Subsequently, the prognostic value of the PNI for DMFS was validated in an external validation cohort of 756 patients with NPC. The area under the receiver operating characteristics curve (AUC was calculated to compare the discriminatory ability of different prognostic scores.The optimal PNI cutoff value was determined to be 51. Low PNI was significantly associated with poorer DMFS than high PNI in univariate analysis (P<0.001 as well as multivariate analysis (P<0.001 before propensity score matching. In subgroup analyses, PNI could also stratify different risks of distant metastases. Propensity score-matched analyses confirmed the prognostic value of PNI, excluding other interpretations and selection bias. In the external validation cohort, patients with high PNI also had significantly lower risk of distant metastases than those with low PNI (Hazards Ratios, 0.487; P<0.001. The PNI consistently showed a higher AUC value at 1-year (0.780, 3-year (0.793 and 5-year (0.812 in comparison with other prognostic scores.PNI, an inexpensive and easily assessable inflammatory index, could aid clinicians in developing individualized treatment and follow-up strategies for patients with non-metastatic NPC.

  18. 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

  19. 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.

  20. Gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p inhibit growth of EBV-positive nasopharyngeal carcinoma

    OpenAIRE

    Cai, Longmei; Li, Jinbang; Zhang,Xiaona; Lu, Yaoyong; WANG, Jianguo; Lyu, Xiaoming; Chen, Yuxiang; Liu, Jinkun; Cai, Hongbing; Wang, Ying; Li, Xin

    2015-01-01

    Epstein-Barr virus (EBV) infection is a major etiological factor for nasopharyngeal carcinoma (NPC). Several EBV-encoded BART miRNAs have been associated with viral latency, immune escape, cell survival, cell proliferation and apoptosis. Here, we report that EBV-miR-BART7-3p, an EBV-encoded BART miRNA highly expressed in NPC, was correlated with cell-cycle progression in vitro and increased tumor formation in vivo. This viral miRNA stimulated the PTEN/PI3K/Akt pathway and induced c-Myc and c-...

  1. Prognostic value of anti-Epstein-Barr virus antibodies in nasopharyngeal carcinoma (NPC)

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    Liu, Mu-Tai; Yeh, Chi-Yuan [Chang-Hua Christian Hospital, Chang-Hua (Taiwan, Province of China)

    1998-03-01

    Eighty patients with histological diagnoses of nasopharyngeal cancer (NPC) were referred to Chang-Hua Christian Hospital for curative radiotherapy from 1985 to 1995. A mean dose of 7,020 cGy in 39 fractions was delivered to the primary tumor using a telecobalt-60 unit or 6-10 MV X-ray linear accelerator. Pre- and postradiotherapy serum levels of anti-Epstein-Barr virus (EBV)/VCA IgG and IgA were determined for all patients using the indirect immunoperoxidase assay. Multivariate analysis was done to determine which factors affected the patients` treatment outcome and survival. Five patients were excluded from this study due to incomplete radiotherapy, leaving 75 patients eligible for analysis. Overall local control was 77.3%, with a mean disease-free interval of 19.7 months. Factors affecting local control included radiation dose and pretreatment anti-EBV/VCA IgG titer. The overall 5-year actuarial survival for the 75 patients was 75%, with a median survival of 129.5 months. The 5-year actuarial survival rates for stage I+II, III, and IV patients were 90%, 40%, and 45%, respectively. Prognostic factors for survival included tumor histological type and pretreatment anti-EBV/VCA IgA titer, while prognostic factors for local control included total radiation dose received and pretreatment anti-EBV/VCA IgG titer. We found that there was a significant difference in the geometric mean titer of anti-EBV/VCA IgA antibodies before and after radiotherapy. Prognostic factors affecting NPC patients` actuarial survival included tumor histology and pretreatment IgA titer, while prognostic factors for local control of NPC included total radiation dose received and pretreatment IgG titer. (K.H.)

  2. 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.

  3. Avaliação dos fatores clínicos e do tratamento em pacientes com carcinoma indiferenciado da nasofaringe Assessment of clinical and therapeutic factors in patients with nasopharyngeal undifferentiated carcinoma

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    Helma Maria Chedid

    2008-08-01

    Full Text Available O carcinoma de nasofaringe é neoplasia rara, com incidência maior em países do Sudeste Asiático. OBJETIVO: Avaliar dados demográficos, clínicos, terapêuticos e prognósticos do carcinoma indiferenciado de nasofaringe em um serviço de referência. CASUÍSTICA E MÉTODO: Estudo retrospectivo de 46 pacientes, de janeiro de 1978 a agosto de 2000. Nenhum paciente foi previamente tratado e não apresentava tumor sincrônico e metástase à distância. RESULTADOS: A idade variou de 14 a 78 anos (média, 46, sendo 35 (76% pacientes masculinos. Todos eram de etnia caucasiana ou afro-brasileira. O tempo de história variou de 1 a 48 meses (média, 7, sendo 47% tabagistas e 33% etilistas. O sintoma mais relatado foi a presença de nódulo no pescoço (34 pacientes. Quanto ao estadiamento clínico, 22 foram estadiados como T1/T2 e 24 como T3/T4, enquanto 24 foram classificados como N2 e 16, N3. O tratamento instituído com finalidade curativa foi a radioterapia, associada à quimioterapia concomitante nos estádios III e IV. Dos 27 pacientes com seguimento após o tratamento inicial, 52% apresentavam-se vivos e livres de doença há três anos. CONCLUSÃO: Os pacientes eram de estádio clínico avançado, com sobrevida livre de doença em três anos de 52%.The nasopharyngeal carcinoma (NPC is a rare cancer with a high incidence in Southern Asia. AIM: to study the demographic, clinical, therapeutic, and prognostic factors of nasopharyngeal undifferentiated carcinoma in a reference service. MATERIALS AND METHODS: A retrospective study was made of 46 patients from January 1998 to August 2000. The patients had no previous treatment and did not present any evidence of synchronous tumors or distance metastases. RESULTS: The age ranged from 14 to 78 years (mean = 46 years; 35 (76% patients were male. All patients were Caucasian or African-Brazilian. The onset of initial symptoms ranged from 1 to 48 months (mean = 7 months; 47% of the subjects smoked

  4. 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.

  5. Blockage of SSRP1/Ets-1/Pim-3 signalling enhances chemosensitivity of nasopharyngeal carcinoma to docetaxel in vitro.

    Science.gov (United States)

    Ai, Jingang; Li, Wei; Zeng, Ruifang; Xie, Zuozhong; Liu, Honghui; Hou, Minghua; Tan, Guolin

    2016-10-01

    Nasopharyngeal carcinoma (NPC) is a rare cancer in most parts of the world, but is prevalent in South China area. Besides, therapeutic outcome is still unsatisfactory for patients with refractory and relapsed NPC, even though receiving a second line of docetaxel-based chemotherapy. These reasons require a better understanding of mechanisms underlying the carcinogenesis, malignancy and chemoresistance. In the basis of our previous finding of SSRP1 over-expression in NPC cell lines, this study continuously discovered up-regulated Ets-1, phosphor-Ets-1 and Pim-3 in NPC tissues with immunohistochemistry assay and revealed a close correlation of these up-regulated proteins with NPC proliferation and invasion. Using gene-silencing technology followed by western blot and immunocytochemistry detections, SSRP1 was found to facilitate the translocation of phosphor-Ets-1 from cytoplasm to cell nucleus, but have marginal effect on Ets-1 expression and phosphorylation. Pim-3 was positively regulated by Ets-1. In NPC HNE-1 cells, all SSRP1, Ets-1 and Pim-3 knockdown diminished the cell proliferation, enhanced the apoptosis, as well as inhibited the autophagy, invasion and clonogenicity in the presence or absence of docetaxel at IC25. Exposure of HNE-1 cells to docetaxel (IC25) alone had modest effect on cell proliferation and autophagy, and was not as effective as docetaxel treatment after knockdown of SSRP1, Ets-1 or Pim-3 on induction of the apoptosis and on inhibition of the invasion and clonogenicity. Our data indicate that SSRP1/Ets-1/Pim-3 signalling is tightly associated with the proliferation, apoptosis, autophagy, invasion and clonogenicity of NPC cells, and blockage of this signalling facilitates chemosensitivity of the cells to docetaxel.

  6. Prostate Tumor Overexpressed 1 (PTOV1 Is a Novel Prognostic Marker for Nasopharyngeal Carcinoma Progression and Poor Survival Outcomes.

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    Qi Yang

    Full Text Available Prostate tumor overexpressed 1 (PTOV1 has been reported to contribute to increased cancer proliferation. However, the clinical significance of PTOV1 in the development and progression of nasopharyngeal carcinoma (NPC is unclear. Our study aimed to investigate the expression pattern of PTOV1 in NPC and its correlation with clinicopathological features of patients.Western blotting and real-time PCR were conducted to examine PTOV1 expression levels in NPC cell lines and biopsy tissues compared with normal controls. Immunohistochemistry (IHC was performed to analyze PTOV1 protein expression in paraffin-embedded tissues from 123 patients. Statistical analyses were applied to evaluate the clinical significance of PTOV1 expression.PTOV1 mRNA and protein levels were upregulated in NPC cell lines and clinical samples. IHC analyses showed that PTOV1 was highly expressed in 68 (55.3% of 123 NPC specimens. Statistical analysis revealed that PTOV1 expression was significantly correlated with clinical stage (P < 0.001, T classification (P = 0.042 and N classification (P = 0.001. Patients with a higher PTOV1 expression had shorter overall survival compared with those with a lower PTOV1 expression level, especially in lower N stage patients. Multivariate analyses suggested that PTOV1 expression was an independent prognostic marker for survival in NPC patients.Our data demonstrated that PTOV1 overexpression is associated with poor survival outcomes of NPC patients, especially in N0-1 patients. Hence, PTOV1 may help to detect early lymph node metastasis of NPC patients and serve as an independent prognostic biomarker for human NPC.

  7. 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.

  8. Immunophenotyping at the Time of Diagnosis Distinguishes Two Groups of Nasopharyngeal Carcinoma Patients: Implications for Adoptive Immunotherapy

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    Jiang Li, Qiu-yan Chen, Haoyuan Mo, Yi-lan Zhang, Zhou-feng Huang, Yi-xin Zeng

    2011-01-01

    Full Text Available Background: Adoptive immunotherapy with EBV-specific CTLs (EBV-CTL has been used to treat EBV-associated nasopharyngeal carcinoma (NPC but only a fraction of the patients shows noticeable clinical response.Patients and Methods: Sixty-seven newly diagnosed NPC patients from 2005 to 2007 and 21 healthy donors were collected. Immunological parameters and immune function of PBMCs and EBV-CTL were analyzed by flow cytometer analysis (FACS and 51Cr releasing experiment; Molecular characteristics on NPC tumor cells were investigated by immunochemical staining and statistic analysis.Results: NPC patients can be classified into two groups based on the percentage of CD3+ T cells in peripheral blood before accepted any treatment, (>52.6%, mean-2SE from healthy controls, NPC Group 1; <52.6%, NPC Group 2. The patients in Group 2 showed a significant decrease of CD3+CD8+ T-cells, CD3+CD4+ T-cells and CD3+CD45RO+ memory T cells, and increase of CD3-CD16+ NK cells compared to Group 1 patients and healthy controls (P<0.001. EBV-specific T cell responses, were weaker in this group of patients and their tumor cells expressed lower levels of the EBV encoded latent membrane protein (LMP-1 and HLA class II protein compared with the patients of NPC Group 1 (P<0.05 .Conclusion: These findings demonstrate that NPC patients could be distinguished on the basis of their immune status which will affect the efficacy of EBV-CTL immunotherapy.

  9. 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.

  10. Quercetin-induced inhibition and synergistic activity with cisplatin – a chemotherapeutic strategy for nasopharyngeal carcinoma cells

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    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.

  11. A global view of the oncogenic landscape in nasopharyngeal carcinoma: an integrated analysis at the genetic and expression levels.

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    Chunfang Hu

    Full Text Available Previous studies have reported that the tumour cells of nasopharyngeal carcinoma (NPC exhibit recurrent chromosome abnormalities. These genetic changes are broadly assumed to lead to changes in gene expression which are important for the pathogenesis of this tumour. However, this assumption has yet to be formally tested at a global level. Therefore a genome wide analysis of chromosome copy number and gene expression was performed in tumour cells micro-dissected from the same NPC biopsies. Cellular tumour suppressor and tumour-promoting genes (TSG, TPG and Epstein-Barr Virus (EBV-encoded oncogenes were examined. The EBV-encoded genome maintenance protein EBNA1, along with the putative oncogenes LMP1, LMP2 and BARF1 were expressed in the majority of NPCs that were analysed. Significant downregulation of expression in an average of 76 cellular TSGs per tumour was found, whilst a per-tumour average of 88 significantly upregulated, TPGs occurred. The expression of around 60% of putative TPGs and TSGs was both up-and down-regulated in different types of cancer, suggesting that the simplistic classification of genes as TSGs or TPGs may not be entirely appropriate and that the concept of context-dependent onco-suppressors may be more extensive than previously recognised. No significant enrichment of TPGs within regions of frequent genomic gain was seen but TSGs were significantly enriched within regions of frequent genomic loss. It is suggested that loss of the FHIT gene may be a driver of NPC tumourigenesis. Notwithstanding the association of TSGs with regions of genomic loss, on a gene by gene basis and excepting homozygous deletions and high-level amplification, there is very little correlation between chromosomal copy number aberrations and expression levels of TSGs and TPGs in NPC.

  12. HLA class II alleles and the presence of circulating Epstein-Barr virus DNA in greek patients with nasopharyngeal carcinoma

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    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.)

  13. A study of radiation-induced cerebral vascular injury in nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis.

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    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.

  14. 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.

  15. Correlation of a hypoxia based tumor control model with observed local control rates in nasopharyngeal carcinoma treated with chemoradiotherapy

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    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.

  16. miR-200b Suppresses Cell Growth, Migration and Invasion by Targeting Notch1 in Nasopharyngeal Carcinoma

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    Xu Yang

    2013-11-01

    Full Text Available Background/Aims: MicroRNAs (miRNAs are a class of small noncoding RNA molecules that play important roles in carcinogenesis and tumor progression. We investigated the roles and mechanisms of miR-200b in human nasopharyngeal carcinoma (NPC. Methods: We used quantitative real-time polymerase chain reaction (qRT-PCR analyses to measure levels of miR-200b and Notch1 in NPC specimens and cell lines. Human NPC cell lines stably expressing miR-200b or control were used to analyze the tumour-suppressive effect of miR-200b. Luciferase reporter assays were used to determine the association between miR-200b and the Notch1 3' untranslated region. Results: We found that miR-200b is significantly downregulated in NPC tissues and cell lines. Gain-of-function and loss-of-function studies demonstrated that miR-200b suppresses NPC cell growth, migration and invasion in vitro. Importantly, overexpression of miR-200b effectively repressed tumor growth in nude mouse models. Integrated analysis identified Notch1 as a direct and functional target of miR-200b. Overexpression of Notch1 reversed the inhibitory effect of miR-200b on NPC cell growth and invasion. Conclusion: These results indicate that miR-200b exerts tumor-suppressive effects in NPC carcinogenesis through the suppression of Notch1 expression and suggest a therapeutic application of miR-200b in NPC.

  17. 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

  18. 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

  19. High-Sensitivity C-Reactive Protein Complements Plasma Epstein-Barr Virus Deoxyribonucleic Acid Prognostication in Nasopharyngeal Carcinoma: A Large-Scale Retrospective and Prospective Cohort Study

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    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.

  20. Epstein-Barr virus infection and persistence in nasopharyngeal epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Chi Man Tsang; Wen Deng; Yim Ling Yip; Mu-Sheng Zeng; Kwok Wai Lo; Sai Wah Tsao

    2014-01-01

    Epstein-Barr virus (EBV) infection is closely associated with undifferentiated nasopharyngeal carcinoma (NPC), strongly implicating a role for EBV in NPC pathogenesis; conversely, EBV infection is rarely detected in normal nasopharyngeal epithelial tissues. In general, EBV does not show a strong tropism for infecting human epithelial cels, and EBV infection in oropharyngeal epithelial cels is believed to be lytic in nature. To establish life-long infection in humans, EBV has evolved efficient strategies to infect B cels and hijack their celular machinery for latent infection. Lytic EBV infection in oropharyngeal epithelial cels, though an infrequent event, is believed to be a major source of infectious EBV particles for salivary transmission. The biological events associated with nasopharyngeal epithelial cells are only beginning to be understood with the advancement of EBV infection methods and the availability of nasopharyngeal epithelial cel models for EBV infection studies. EBV infection in human epithelial cels is a highly inefficient process compared to that in B cels, which express the complement receptor type 2 (CR2) to mediate EBV infection. Although receptor(s) on the epithelial cell surface for EBV infection remain(s) to be identified, EBV infection in epithelial cels could be achieved via the interaction of glycoproteins on the viral envelope with surface integrins on epithelial cels, which might trigger membrane fusion to internalize EBV in cels. Normal nasopharyngeal epithelial cells are not permissive for latent EBV infection, and EBV infection in normal nasopharyngeal epithelial cells usually results in growth arrest. However, genetic alterations in premalignant nasopharyngeal epithelial cells, including p16 deletion and cyclin D1 overexpression, could override the growth inhibitory effect of EBV infection to support stable and latent EBV infection in nasopharyngeal epithelial cells. The EBV episome in NPC is clonal in nature, suggesting that NPC

  1. Sequence analysis of the Epstein-Barr virus (EBV BRLF1 gene in nasopharyngeal and gastric carcinomas

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    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.

  2. 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

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    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.)

  3. Conserved mutation of Epstein-Barr virus-encoded BamHI-A Rightward Frame-1 (BARF1 gene in Indonesian nasopharyngeal carcinoma

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    Hutajulu Susanna H

    2010-09-01

    Full Text Available Abstract Background BamHI-A rightward frame-1 (BARF1 is a carcinoma-specific Epstein-Barr virus (EBV encoded oncogene. Here we describe the BARF1 sequence diversity in nasopharyngeal carcinoma (NPC, other EBV-related diseases and Indonesian healthy EBV carriers in relation to EBV genotype, viral load and serology markers. Nasopharyngeal brushings from 56 NPC cases, blood or tissue from 15 other EBV-related disorders, spontaneous B cell lines (LCL from 5 Indonesian healthy individuals and several prototype EBV isolates were analysed by PCR-direct sequencing. Results Most NPC isolates revealed specific BARF1 nucleotide changes compared to prototype B95-8 virus. At the protein level these mutations resulted in 3 main substitutions (V29A, W72G, H130R, which are not considered to cause gross tertiary structure alterations in the hexameric BARF1 protein. At least one amino acid conversion was detected in 80.3% of NPC samples compared to 33.3% of non-NPC samples (p Conclusion The sequence variation of BARF1 observed in Indonesian NPC patients and controls may reflect a natural selection of EBV strains unlikely to be predisposing to carcinogenesis. The conserved nature of BARF1 may reflect an important role in EBV (epithelial persistence.

  4. Therapeutic targeting of regulatory T cells enhances tumor-specific CD8+ T cell responses in Epstein–Barr virus associated nasopharyngeal carcinoma

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    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.

  5. Chemoradiotherapy Versus Radiotherapy Alone in Stage II Nasopharyngeal Carcinoma: A Systemic Review and Meta-analysis of 2138 Patients

    Science.gov (United States)

    Xu, Cheng; Zhang, Li-He; Chen, Yu-Pei; Liu, Xu; Zhou, Guan-Qun; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2017-01-01

    Background: To explore the value of chemoradiotherapy (CRT) in stage II nasopharyngeal carcinoma (NPC) compared to radiotherapy (RT) alone which includes two-dimensional radiotherapy (2D-RT) and intensity-modulated radiotherapy (IMRT). Methods:All topic-related comparative articles were identified by a comprehensive search of public databases (MEDLINE, EMBASE, Cochrane Library and CBMdisc). The primary outcomes were overall survival (OS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS). Secondary outcomes were grade 3-4 acute toxicity events. We performed subgroup analysis of CRT versus 2D-RT/IMRT alone to investigate the optimal modality. Sensitivity analysis focused on CRT versus IMRT alone was used to assess stability of the study results. Results:Eleven comparative studies (2138 patients) were eligible. CRT had significantly higher OS (HR = 0.67, 95% CI = 0.45-0.98, P = 0.04) and LRRFS (HR = 0.61, 95% CI = 0.46-0.80, P = 0.0003) than RT alone, but no significant difference was observed in DMFS (HR = 0.83, 95% CI = 0.52-1.31, P = 0.41). Meanwhile, CRT was associated with higher frequencies of grade 3-4 leukopenia, mucositis and nausea (P = 0.005, 0.03, < 0.0001, respectively). Subgroup analysis showed that IMRT alone could achieve equivalent OS, LRRFS and DMFS compared to CRT (P = 0.14, 0.06, 0.89, respectively). Significant value was only observed in LRRFS for CRT compared to 2D-RT alone (P = 0.01). Sensitivity analysis for the comparison of CRT and IMRT alone demonstrated generally stable outcomes, in support of the final conclusions. Conclusions:In the treatment of patients with stage II NPC, CRT was better than 2D-RT alone with significant benefit in LRRFS. IMRT alone was superior to CRT with equivalent survival outcomes and fewer grade 3-4 acute toxicities. PMID:28243333

  6. Genomic sequencing and comparative analysis of Epstein-Barr virus genome isolated from primary nasopharyngeal carcinoma biopsy.

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    Hin Kwok

    Full Text Available Whether certain Epstein-Barr virus (EBV strains are associated with pathogenesis of nasopharyngeal carcinoma (NPC is still an unresolved question. In the present study, EBV genome contained in a primary NPC tumor biopsy was amplified by Polymerase Chain Reaction (PCR, and sequenced using next-generation (Illumina and conventional dideoxy-DNA sequencing. The EBV genome, designated HKNPC1 (Genbank accession number JQ009376 is a type 1 EBV of approximately 171.5 kb. The virus appears to be a uniform strain in line with accepted monoclonal nature of EBV in NPC but is heterogeneous at 172 nucleotide positions. Phylogenetic analysis with the four published EBV strains, B95-8, AG876, GD1, and GD2, indicated HKNPC1 was more closely related to the Chinese NPC patient-derived strains, GD1 and GD2. HKNPC1 contains 1,589 single nucleotide variations (SNVs and 132 insertions or deletions (indels in comparison to the reference EBV sequence (accession number NC007605. When compared to AG876, a strain derived from Ghanaian Burkitt's lymphoma, we found 322 SNVs, of which 76 were non-synonymous SNVs and were shared amongst the Chinese GD1, GD2 and HKNPC1 isolates. We observed 88 non-synonymous SNVs shared only by HKNPC1 and GD2, the only other NPC tumor-derived strain reported thus far. Non-synonymous SNVs were mainly found in the latent, tegument and glycoprotein genes. The same point mutations were found in glycoprotein (BLLF1 and BALF4 genes of GD1, GD2 and HKNPC1 strains and might affect cell type specific binding. Variations in LMP1 and EBNA3B epitopes and mutations in Cp (11404 C>T and Qp (50134 G>C found in GD1, GD2 and HKNPC1 could potentially affect CD8(+ T cell recognition and latent gene expression pattern in NPC, respectively. In conclusion, we showed that whole genome sequencing of EBV in NPC may facilitate discovery of previously unknown variations of pathogenic significance.

  7. The synergistic effect of chemical carcinogens enhances Epstein-Barr virus reactivation and tumor progression of nasopharyngeal carcinoma cells.

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    Chih-Yeu Fang

    Full Text Available Seroepidemiological studies imply a correlation between Epstein-Barr virus (EBV reactivation and the development of nasopharyngeal carcinoma (NPC. N-nitroso compounds, phorbols, and butyrates are chemicals found in food and herb samples collected from NPC high-risk areas. These chemicals have been reported to be risk factors contributing to the development of NPC, however, the underlying mechanism is not fully understood. We have demonstrated previously that low dose N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 0.1 µg/ml had a synergistic effect with 12-O-tetradecanoylphorbol-13-acetate (TPA and sodium butyrate (SB in enhancing EBV reactivation and genome instability in NPC cells harboring EBV. Considering that residents in NPC high-risk areas may contact regularly with these chemical carcinogens, it is vital to elucidate the relation between chemicals and EBV and their contributions to the carcinogenesis of NPC. In this study, we constructed a cell culture model to show that genome instability, alterations of cancer hallmark gene expression, and tumorigenicity were increased after recurrent EBV reactivation in NPC cells following combined treatment of TPA/SB and MNNG. NPC cells latently infected with EBV, NA, and the corresponding EBV-negative cell, NPC-TW01, were periodically treated with MNNG, TPA/SB, or TPA/SB combined with MNNG. With chemically-induced recurrent reactivation of EBV, the degree of genome instability was significantly enhanced in NA cells treated with a combination of TPA/SB and MNNG than those treated individually. The Matrigel invasiveness, as well as the tumorigenicity in mouse, was also enhanced in NA cells after recurrent EBV reactivation. Expression profile analysis by microarray indicates that many carcinogenesis-related genes were altered after recurrent EBV reactivation, and several aberrations observed in cell lines correspond to alterations in NPC lesions. These results indicate that cooperation between chemical

  8. {sup 18}F-fluorodeoxyglucose positron emission tomography for predicting tumor response to radiochemotherapy in nasopharyngeal carcinoma

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    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

  9. Prognostic value and staging classification of retropharyngeal lymph node metastasis in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.

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    Ling-Long Tang

    Full Text Available BACKGROUND: The development of intensity-modulated radiotherapy (IMRT has revolutionized the management of nasopharyngeal carcinoma (NPC. The purpose of this study was to evaluate the prognostic value and classification of TNM stage system for retropharyngeal lymph node (RLN metastasis in NPC in the IMRT era. MATERIAL AND METHODS: We retrospectively reviewed data from 749 patients with biopsy-proven, non-metastatic NPC. All patients received IMRT as the primary treatment. Chemotherapy was administered to 86.2% (424/492 of the patients with stage III or IV disease. RESULTS: The incidence of RLN metastasis was 64.2% (481/749. Significant differences were observed in the 5-year disease-free survival (DFS; 70.6% vs. 85.4%, P<0.001 and distant metastasis-free survival (DMFS; 79.2% vs. 90.1%, P<0.001 rates of patients with and without RLN metastasis. In multivariate analysis, RLN metastasis was an independent prognostic factor for disease failure and distant failure (P = 0.005 and P = 0.026, respectively, but not for locoregional recurrence. Necrotic RLN metastases have a negative effect on disease failure, distant failure and locoregional recurrence in NPC with RLN metastasis (P = 0.003, P = 0.018 and P = 0.005, respectively. Survival curves demonstrated a significant difference in DFS between patients with N0 disease and N1 disease with only RLN metastasis (P = 0.020, and marginally statistically significant differences in DMFS and DFS between N1 disease with only RLN metastasis and other N1 disease (P = 0.058 and P = 0.091, respectively. In N1 disease, no significant differences in DFS were observed between unilateral and bilateral RLN metastasis (P = 0.994. CONCLUSIONS: In the IMRT era, RLN metastasis remains an independent prognostic factor for DFS and DMFS in NPC. It is still reasonable for RLN metastasis to be classified in the N1 disease, regardless of laterality. However, there is a need to investigate the feasibility of classifying RLN

  10. 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.

  11. 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

  12. 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 .

  13. 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

  14. 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

  15. Human Ribosomal Proteins RPeL27, RPeL43, and RPeL41 Are Upregulated in Nasopharyngeal Carcinoma Cell Lines

    Science.gov (United States)

    Ng, Kher-Lee

    2016-01-01

    Apart from their canonical role in ribosome biogenesis, there is increasing evidence of ribosomal protein genes' involvement in various cancers. A previous study by us revealed significant differential expression of three ribosomal protein genes (RPeL27, RPeL41, and RPeL43) between cell lines derived from tumor and normal nasopharyngeal epithelium. However, the results therein were based on a semiquantitative assay, thus preliminary in nature. Herein, we provide findings of a deeper analysis of these three genes in the context to nasopharyngeal carcinoma (NPC) tumorigenesis. Their expression patterns were analyzed in a more quantitative manner at transcript level. Their protein expression levels were also investigated. We showed results that are contrary to previous report. Rather than downregulation, these genes were significantly overexpressed in NPC cell lines compared to normal control at both transcript and protein levels. Nevertheless, their association with NPC has been established. Immunoprecipitation pulldown assays indicate the plausible interaction of either RPeL27 or RPeL43 with POTEE/TUBA1A and ACTB/ACTBL2 complexes. In addition, RPeL43 is shown to bind with MRAS and EIF2S1 proteins in a NPC cell line (HK1). Our findings support RPeL27, RPeL41, and RPeL43 as potential markers of NPC and provide insights into the interaction targets of RPeL27 and RPeL43 proteins. PMID:28018022

  16. Frequent Hypermethylation of RASSF1A, TSLC1, High Viral Load of Epstein-Barr Virus DNA in Nasopharyngeal Carcinoma, Matched Tumor-Adjacent Tissues

    Directory of Open Access Journals (Sweden)

    Liang Zhou

    2005-09-01

    Full Text Available We examined the promoter hypermethylation of tumorsuppressor genes RASSF1A, TSLC1, quantitated EBV DNA load in nasopharyngeal carcinoma (NPC tissues (T tissues, matched tumor-adjacent tissues outside 0.5 cm (P tissues, outside 1.0 cm (Z tissues to evaluate the role of promoter hypermethylation of RASSF1A, TSLC1 as well as viral load in the pathogenesis of NPC. Methylation-specific polymerase chain reaction (PCR for RASSF1A, TSLC1, quantitative real-time PCR analysis of EBV DNA were performed on matched T, P, Z tissues (n = 28 as well as chronic nasopharyngitis tissues (n = 8. Hypermethylated RASSF1A was frequently detected in the T (82%, P tissues (75%, but less frequently in Z tissues (46%. The average quantities of EBV DNA (copies/μg DNA in matched T, P, Z tissues were 673,000, 90,000, 7000. The differences of promoter hypermethylation of RASSF1A, EBV viral load among T, P, Z tissues were statistically significant, with more frequent methylation, higher viral load detected when tissues examined were nearer to the NPC tissues. Our results suggest that aberrant hypermethylation of RASSF1A, high EBV load might be important events in NPC pathogenesis, they may be useful molecular diagnostic markers for this cancer.

  17. 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

  18. Expression of p53 and p21WAF1 Protein in Advanced Nasopharyngeal Carcinoma before and after Intratumoral Injection of RAd-p53 and Their Relationships with Short-term Prognosis%p53和p21wAF1在鼻咽癌rAd-p53瘤内注射前后的表达及其与近期预后的关系

    Institute of Scientific and Technical Information of China (English)

    兰桂萍; 司勇锋; 翁敬锦; 韦海明; 覃扬达; 何宁

    2012-01-01

    目的 探讨重组人p53腺病毒(rAd-p53)瘤内注射前后鼻咽癌(NPC)组织中p53蛋白和p21WAF1蛋白的表达情况,及其与鼻咽癌近期疗效的关系.方法 应用免疫组织化学法检测12例鼻咽慢性炎组织和63例确诊中晚期鼻咽癌组织的p53和p21WAF1蛋白表达情况.63例中晚期鼻咽癌随机分为2组:p53治疗组(32例):rAd-p53瘤内注射+同步放化疗;常规治疗组(31例):同步放化疗.分析两组治疗前及放疗至20 Gy时p53和p21 WAF1蛋白表达情况及其与预后的关系.结果 NPC组织中p53和p21 WAF1蛋白阳性表达率分别为49.21%和46.03%,和鼻咽黏膜慢性炎相比差异有统计学意义(P<0.05).NPC组织中p53和p21WAF1蛋白表达有相关性(rs=0.556,P=0.000).放疗前及放疗至20 Gy时,鼻咽癌p53治疗组和p21WAF1蛋白阳性表达率差异有统计学意义(P<0.05);两组p53蛋白和p21 WAF1蛋白阳性表达与1年无瘤生存率有关(P<0.05).结论 rAd-p53瘤内注射后p53和p21WAF1蛋白的阳性表达可能在抑制鼻咽癌复发或转移进程中起着重要作用,并预示较好的预后.%Objective To investigate the expression of p53 and p21WAF1 in the NPC cells before and after intratumoral injection of recombinant adenovirus p53(rAd-p53) and their relationships with short-term prognosis. Methods The expression of p53 and p21WAF1 protein were examined by immunochemistry in 12 cases of chronic nasopharynxitis and 63 cases with advanced stage nasopharyngeal carcinoma. Sixty-three cases of NPC were randomly divided into two groups:the p53 therapy group(32 cases) for rAd-p53 intratumoral injection plus radiotherapy and chemotherapy;and the common therapy group(31 cases) for radiotherapy and chemotherapy. The expression levels of p53 and p21WAF1 in biopsy samples from all the cases before and at the 20 Gy of radiotherapy were analyzed; And their relationship with prognosis was also analyzed. Results The expression of p53 and p21WAF1 in 63 cases of NPC was 49. 21

  19. Endoscope-guided interstitial intensity-modulated brachytherapy and intracavitary brachytherapy as boost radiation for primary early T stage nasopharyngeal carcinoma.

    Directory of Open Access Journals (Sweden)

    Xiang-Bo Wan

    Full Text Available BACKGROUND: Intracavitary brachytherapy (ICBT is usually applied as boost radiotherapy for superficial residual of nasopharyngeal carcinoma (NPC after primary extern-beam radiptherapy (ERT. Here, we evaluated the outcome of endoscope-guided interstitial intensity-modulated brachytherapy (IMBT boost radiation for deep-seated residual NPC. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred and thirteen patients with residual NPC who were salvaged with brachytherapy boost radiation during 2005-2009 were analyzed retrospectively. Among these patients, 171 patients had superficial residual NPC (≤1 cm below the nasopharyngeal epithelium were treated with ICBT boost radiation, and interstitial IMBT boost radiation was delivered to 42 patients with deep-seated residual NPC (>1 cm below the nasopharyngeal epithelium. We found that IMBT boost subgroup had a higher ratio of T2b (81.0% VS 34.5%, P<0.001 and stage II (90.5% VS 61.4%, P = 0.001 than that of ICBT boost subgroup. The dosage of external-beam radiotherapy in the nasopharyngeal (63.0±3.8 VS 62.6±4.3 Gray (Gy, P = 0.67 and regional lymph nodes (55.8±5.0 VS 57.5±5.7 Gy, P = 0.11 was comparable in both groups. For brachytherapy, IMBT subgroup had a lower boost radiation dosage than ICBT subgroup (11.0±2.9 VS 14.8±3.2 Gy, P<0.01. Though the IMBT group had deeper residual tumors and received lower boost radiation dosages, both subgroups had the similar 5-year actuarial overall survival rate (IMBT VS ICBT group: 96.8% VS 93.6%, P = 0.87, progression-free survival rate (92.4% VS 86.5%, P = 0.41 and distant metastasis-free survival rate (94.9% VS 92.7%, P = 0.64. Moreover, IMBT boost radiation subgroup had a similar local (97.4% VS 94.4%, P = 0.57 and regional (95.0% VS 97.2%, P = 0.34 control to ICBT subgroup. The acute and late toxicities rates were comparable between the both subgroups. CONCLUSIONS/SIGNIFICANCE: IMBT boost radiation may be a promising therapeutic

  20. 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.

  1. 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.

  2. 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

  3. Tetrandrine Induces Apoptosis of Human Nasopharyngeal Carcinoma NPC-TW 076 Cells through Reactive Oxygen Species Accompanied by an Endoplasmic Reticulum Stress Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Ya-Jing Lin

    2016-10-01

    Full Text Available Nasopharyngeal carcinoma (NPC is an epithelial malignancy of the head and neck and the incidence is higher in Southeast Asia. Tetrandrine (TET is a bisbenzylisoquinoline alkaloid, a natural product, and exhibits biological activities including action against many human cancer cell lines. However, the molecular mechanism of TET-induced cell apoptosis in human NPC cells is still unclear. In the present study, we investigated TET-induced apoptotic cell death and associated possible signal pathways on human nasopharyngeal carcinoma NPC-TW 076 cells in vitro. Phase contrast microscopy was used to examine cell morphology and DAPI staining was used to examine chromatin condensation. Flow cytometry assay was used to measure total viable cells, cell cycle and sub-G1 phase distribution, reactive oxygen species (ROS, Ca2+, and mitochondria membrane potential (ΔΨm in NPC-TW 076 cells. Results indicate that TET induced cell death through the cell morphological changes, caused G0/G1 phase arrest, increased ROS and Ca2+ production, and finally caused apoptotic cell death in NPC-TW 076 cells. There was no influence on the level of ΔΨm after TET treatment. Western blotting indicated that TET increased endoplasmic reticulum (ER stress associated protein expression such as GADD153, GRP78, ATF-6α and ATF-6 βwhich indicated that TET induced cell death through ER stress. ER stress is a potential target in cancer treatment, so the ability of TET to induce ER stress response and to activate programming cell death in NPC-TW 076 cells make this molecule become a promising anticancer agent.

  4. In vitro and in vivo efficacy of afatinib as a single agent or in combination with gemcitabine for the treatment of nasopharyngeal carcinoma

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    Xue C

    2016-03-01

    Full Text Available Cong Xue,1 Ying Tian,2 Jing Zhang,3 Yuanyuan Zhao,1 Jianhua Zhan,2 Wenfeng Fang,1 Li Zhang1 1Department of Medical Oncology, 2Department of Research, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, 3Department of Medical Oncology, The First Affiliated Hospital of Guangzhou Traditional Chinese Medicine University, Guangzhou, Guangdong, People’s Republic of China Purpose: Epidermal growth factor receptor (EGFR is usually overexpressed in nasopharyngeal carcinoma (NPC. We tested the antitumor effects of irreversible ErbB family inhibitor afatinib on human NPC using in vitro and in vivo models.Materials and methods: The effect of afatinib on NPC cells was evaluated using the Cell Counting Kit 8 (CCK8 assay, flow cytometry, and Western blot analyses. The effect of afatinib, as either a single agent or in combination with gemcitabine (GEM, on tumor growth was determined using NPC tumor xenografts in mice.Results: Afatinib inhibited cell growth in all three NPC cell lines tested in a dose-dependent manner. Afatinib promoted cell cycle arrest at the S and G2/M phases, and it significantly inhibited epidermal growth factor (EGF-induced activation of EGFR and its downstream signaling factors. Co-treatment with afatinib and GEM more effectively inhibited tumor growth than either drug alone but was associated with increased toxicity.Conclusion: Afatinib induced cell cycle arrest and inhibited the proliferation of NPC cell lines. Afatinib in combination with GEM demonstrated significant antitumor effect in an NPC xenograft model. The administration of afatinib with GEM in NPC needs to be modified in order to be effective and tolerable. Keywords: nasopharyngeal carcinoma, EGFR, afatinib, gemcitabine, preclinical

  5. 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.

  6. 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.

  7. 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.

  8. SU-E-T-808: Volumetric Modulated Arc Radiotherapy Vs. Intensity-Modulated Radiotherapy for Early-Stage Nasopharyngeal Carcinoma: A Dosimetric Study

    Energy Technology Data Exchange (ETDEWEB)

    Lu, J-Y; Huang, B-T; Zhang, W-Z [Cancer Hospital of Shantou University Medical College, Shantou, Guangdong (China)

    2015-06-15

    Purpose: To compare volumetric modulated arc radiotherapy (VMAT) technique with fixed-gantry intensity-modulated radiotherapy (IMRT) technique for early-stage nasopharyngeal carcinoma. Methods: CT datasets of ten patients with early-stage nasopharyngeal carcinoma were included. Dual-arc VMAT and nine-field IMRT plans were generated for each case, and were then compared in terms of planning-target-volume (PTV) coverage, conformity index (CI) and homogeneity index (HI), as well as organ-at-risk (OAR) sparing, planning time, monitor units (MUs) and delivery time. Results: Compared with the IMRT plans, the VMAT plans provided comparable HI and CI of PTVnx (PTV of primary tumor of nasopharynx), superior CI and inferior HI of PTVnd (PTV of lymph nodes), as well as superior CI and comparable HI of PTV60 (high-risk PTV). The VMAT plans provided better sparing of the spinal cord, oral cavity and normal tissue, but inferior sparing of the brainstem planning OAR volume (PRV), larynx and parotids, as well as comparable sparing of the spinal cord PRV, brainstem, lenses, optic nerves, optic chiasm. Moreover, the average planning time (181.6 ± 36.0 min) for the VMAT plans was 171% more than that of the IMRT plans (68.1 ± 7.6 min). The MUs of the VMAT plans (609 ± 43) were 70% lower than those of the IMRT plans (2071 ± 262), while the average delivery time (2.2 ± 0.1 min) was 66% less than that of the IMRT plans (6.6 ± 0.4 min). Conclusion: Compared with the IMRT technique, the VMAT technique can achieve similar or slightly superior target dose distribution, with no significant advantages on OAR sparing, and it can achieve significant reductions of MUs and delivery time.

  9. Tetrandrine Induces Apoptosis of Human Nasopharyngeal Carcinoma NPC-TW 076 Cells through Reactive Oxygen Species Accompanied by an Endoplasmic Reticulum Stress Signaling Pathway.

    Science.gov (United States)

    Lin, Ya-Jing; Peng, Shu-Fen; Lin, Meng-Liang; Kuo, Chao-Lin; Lu, Kung-Wen; Liao, Ching-Lung; Ma, Yi-Shih; Chueh, Fu-Shin; Liu, Kuo-Ching; Yu, Fu-Shun; Chung, Jing-Gung

    2016-10-12

    Nasopharyngeal carcinoma (NPC) is an epithelial malignancy of the head and neck and the incidence is higher in Southeast Asia. Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid, a natural product, and exhibits biological activities including action against many human cancer cell lines. However, the molecular mechanism of TET-induced cell apoptosis in human NPC cells is still unclear. In the present study, we investigated TET-induced apoptotic cell death and associated possible signal pathways on human nasopharyngeal carcinoma NPC-TW 076 cells in vitro. Phase contrast microscopy was used to examine cell morphology and DAPI staining was used to examine chromatin condensation. Flow cytometry assay was used to measure total viable cells, cell cycle and sub-G₁ phase distribution, reactive oxygen species (ROS), Ca(2+), and mitochondria membrane potential (ΔΨm) in NPC-TW 076 cells. Results indicate that TET induced cell death through the cell morphological changes, caused G₀/G₁ phase arrest, increased ROS and Ca(2+) production, and finally caused apoptotic cell death in NPC-TW 076 cells. There was no influence on the level of ΔΨm after TET treatment. Western blotting indicated that TET increased endoplasmic reticulum (ER) stress associated protein expression such as GADD153, GRP78, ATF-6α and ATF-6 βwhich indicated that TET induced cell death through ER stress. ER stress is a potential target in cancer treatment, so the ability of TET to induce ER stress response and to activate programming cell death in NPC-TW 076 cells make this molecule become a promising anticancer agent.

  10. An analysis of brachytherapy with computed tomography-guided permanent implantation of Iodine-125 seeds for recurrent nonkeratin nasopharyngeal carcinoma

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    Shen X

    2015-05-01

    Full Text Available Xinying Shen,1,2 Yong Li,2 Yanfang Zhang,2 Jian Kong,2 Yanhao Li1 1Department of Interventional Radiology, Nanfang Hospital, Southern Medical University, Guangzhou, 2Department of Interventional Radiology, Shenzhen People’s Hospital, The Second Clinical Medical College of Jinan University, Shenzhen, People’s Republic of China Background: 125I seed implantation is a new method in treatment of nasopharyngeal carcinoma (NPC, and it is worthwhile to evaluate its feasibility. In this study, we performed brachytherapy with computed tomography (CT-guided permanent implantation of 125I seeds in the treatment of patients with the recurrence of NPC.Methods: A total 30 patients (20 male and ten female at the median age of 55 (range 25–80 years were diagnosed with recurrent nonkeratin NPC, with a total 38 lesions and a short disease-free interval (median ~11 months after primary radiotherapy alone or combined with chemotherapy. Patients received CT scan, starting from 2 months after the treatment. Follow-up was conducted for ~2–38 months to observe the local control rate and overall survival rate. We also analyzed the possible correlation between survival periods and the status of recurrent tumors.Results: The local control rates at 6, 12, 24, 30, and 36 months after the procedure of 125I seed implantation were 86.8%, 73.7%, 26.3%, 15.8%, and 5.3%, respectively. The overall 1-, 2-, and 3-year survival rates were 80.0% (24/30, 30.0% (9/30, and 6.7% (2/30, respectively, with a median survival period of 18 months (17.6±8.6 months. Interestingly, the survival periods of the patients who had primary radiotherapy with or without chemotherapy were 15.8±7.9 and 24.3±7.9 months, respectively. Kaplan–Meier survival analysis demonstrated that χ2 (log rank was 7.555, with very significant difference (P<0.01. The survival periods of patients in tumor stages I, II, III, and IV were 25.4±8.7, 19.8±9.4, 16.1±4.5, and 12.8±7.8 months, respectively, with

  11. 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.

  12. 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...

  13. 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.

  14. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma

    DEFF Research Database (Denmark)

    Motzer, Robert J; Escudier, Bernard; McDermott, David F;

    2015-01-01

    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...... 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...... 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.)....

  15. 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

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    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

  16. The application of detection of plasma Epstein-Barr virus DNA in nasopharyngeal carcinoma%血浆EB病毒DNA检测在鼻咽癌中的应用进展

    Institute of Scientific and Technical Information of China (English)

    黄爽; 管西寅; 应红梅

    2012-01-01

    EB病毒(Epstein-Barr virus,EBV)与鼻咽癌的发生、发展密切相关,采用PCR方法对鼻咽癌患者不同阶段的血浆EB病毒DNA (EBV DNA)进行定量检测可有效评估患者对治疗的反应,预测复发、转移的风险,治疗前的EBV DNA基线浓度与肿瘤负荷密切相关,而治疗后的EBV DNA含量与肿瘤复发转移关系更密切.EBV DNA定量检测有望成为一种新的肿瘤预后指标.本文就鼻咽癌患者不同时期的EBV DNA水平在诊断、分期、疗效评估和预后预测中的应用进行综述.%Epstein-Barr virus (EBV) is closely related to the occurrence and development of nasopharyngeal carcinoma. The quantitative detection of Epstein-Barr virus DNA (EBV DNA) in plasma from the patients with nasopharyngeal carcinoma using the polymerase chain reaction (PCR)-based strategies can effectively evaluate the response to treatments and predict the risk of recurrence and metastasis. The pre-treatment EBV DNA base line is in accordance with the tumor load, and the post-treatment EBV DNA levels can predict the recurrence and metastasis of the nasopharyngeal carcinoma. It would be a new tumor-maker. This article briefly reviewed the application of plasma EBV DNA from different phases of nasopharyngeal carcinoma patients in the diagnosis, evaluation, monitoring and prognosis-prediction.

  17. 鼻咽癌门诊化疗的观察护理--附89例报告%Observation and Nursing of Outpatient Chemotherapy of Nasopharyngeal Carcinoma (Attached Report of 89 Cases)

    Institute of Scientific and Technical Information of China (English)

    温冬梅; 黄丽源; 陈洁丽; 何曙云

    2002-01-01

    Objective To observe the characteristic of nursing patients with nasopharyngeal carcinoma who receivechemotherapy in outpatient. Method Collecting datum of 89 cases who received DDP + 5 - FU chemotheropy from January1998 to September, 1998 collecting the various reaction, and stressing nursing and prevention. Result The patients sufferedfrom such reactions as gastro - intestinal reaction, arrest of bone barrow. Stomatitis, diarrhea, constipation, shiver fever andphlebitis. Conclusion The reactions should be treated in time.

  18. Human Leukocyte Antigens and Epstein-Barr Virus-Associated Nasopharyngeal Carcinoma: Old Associations Offer New Clues into the Role of Immunity in Infection-Associated Cancers

    Directory of Open Access Journals (Sweden)

    Wen-Hui eSu

    2013-12-01

    Full Text Available Nasopharyngeal carcinoma (NPC is an Epstein-Barr virus (EBV associated tumor. In addition to EBV, host genetic factors are believed to be important determinants of NPC risk. Of all genes studies to date, human leukocyte antigen (HLA genes have shown the most consistent evidence for association with NPC, both from candidate-gene studies and genome-wide association studies (GWAS. In this report we summarize results from recent studies that evaluated the association between HLA and NPC, and discuss whether findings reflect direct causal associations for HLA genes and/or indirect associations that mark causal associations with other genes in the gene-dense major histocompatibility (MHC region where HLA resides. We also compare GWAS results across cancer sites for which strong hits in the MHC region were observed to generate new hypotheses regarding the role of HLA genes in the development of EBV-associated cancers such as NPC. Of note, we report that MHC associations for EBV-associated cancers (NPC, EBV+ Hodgkin lymphoma are driven by HLA class I genes. In contrast, MHC associations for other viral-associated cancers (cervical cancer, hepatocellular carcinoma or other hematopoetic cancers (EBV- Hodgkin lymphoma, leukemia, non-Hodgkin lymphomas are driven by HLA class II genes, and those for other solid tumors with less clear links to infections (lung, testicular, prostate cancers are driven by non-HLA genes in the MHC region. Future studies should aim to better understand these patterns.

  19. 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

  20. 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.

  1. 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.

  2. Recurrent Overexpression of c-IAP2 in EBV-Associated Nasopharyngeal Carcinomas: Critical Role in Resistance to Toll-like Receptor 3-Mediated Apoptosis

    Directory of Open Access Journals (Sweden)

    Luc Friboulet

    2008-11-01

    Full Text Available The oncogenic process leading to nasopharyngeal carcinoma (NPC requires the combination of genetic and epigenetic alterations, latent infection by the Epstein-Barr virus and local inflammation. A transcriptome analysis of NPC xenografts identified the gene encoding the cellular inhibitor of apoptosis protein 2 (c-IAP2 among the top five most intensely expressed. Consistently, the very high levels of the c-IAP2 protein were detected in 11 of 13 NPC biopsies. RMT 5265, a structural analog of second mitochondria-derived activator of caspase (SMAC, induced the rapid degradation of c-IAP2 in nasopharyngeal epithelial cells, whether malignant or not, but blocked clonal cell growth in NPC cells only. In short-term experiments, RMT 5265 induced apoptosis in a fraction of NPC cells, and this apoptosis was dramatically enhanced when RMT 5265 was combined with Toll-like receptor 3 (TLR3 stimulation. By contrast, the cooperative effect with tumor necrosis factor α was only marginal. The apoptosis induced by the combination of RMT 5265 and TLR3 stimulation was mediated by caspase-8 and associated with a decrease in the cellular content of the long isoform of FLICE-like inhibitory protein. Similar caspase-8 activation was obtained when siRNA knockdown of c-IAP2 was combined with TLR3 stimulation. In conclusion, c-IAP2 has a specific protective function in NPC cells challenged by TLR3 agonists. This protective function is probably important to make NPC cells tolerant to their own production of small viral RNAs, which are potential agonists of TLR3. Our data will help to design a rational use of IAP inhibitors in NPC patients.

  3. 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.

  4. The Epstein-Barr Virus-encoded miR-BART22 targets MAP3K5 to promote host cell proliferative and invasive abilities in nasopharyngeal carcinoma

    Science.gov (United States)

    Chen, Ruichao; Zhang, Minfeng; Li, Qiulian; Xiong, Hanzhen; Liu, Shaoyan; Fang, Weiyi; Zhang, Qianbing; Liu, Zhen; Xu, Xuehu; Jiang, Qingping

    2017-01-01

    miR-BART22, a new discovered Epstein-Barr virus (EBV) miRNA, is abundant in Nasopharyngeal carcinoma (NPC). It has been reported that miR-BART22 promoted the tumor development by down-modulating EBV LMP2 expression to evade the host immune response. But its cell target genes have still been obscure. We have reported an inverse correlation between the BART-22 and MAP3K5 protein expression in NPC tissues and NPC cell lines. Meanwhile, MAP3K5 protein expression level was significantly decreased in primary NPC tissues compared with nasopharyngitis when MAP3K5 mRNA expression was consistent in two group tissues. According to our data and target prediction by miRnada, we assume MAP3K5 is an important target gene of NPC. MAP3K5, also named apoptosis signal-regulating kinase1 (ASK1), is an important early answer gene in P38MAPK pathway and an apoptosis-related gene. In present study, MAP3K5 was verified the target gene of miR-BART22 by luciferase assay. miRBART-22 decreased MAP3K5 protein level. Moreover, it also decreased MAP3K5 downstream gene MAP2K4 expression in P38MAPK pathway, and even their activated phosphorylation forms. Additionally, we found stable transfection of miR-BAT22 could improve tumor cells' proliferative and invasive abilities in NPC cell line 5-8F. The data highlight the role of the EBV miR-BART22 in regulating genes involving in apoptosis and some important pathways to promote cancer development. And it also raises the possibility that inhibitors of miR-BART22 can be as a therapeutic strategy for NPC and other EBV-infected tumors treatment. PMID:28243335

  5. A Dosimetric Study of Using Fixed-Jaw Volumetric Modulated Arc Therapy for the Treatment of Nasopharyngeal Carcinoma with Cervical Lymph Node Metastasis.

    Directory of Open Access Journals (Sweden)

    Wu-Zhe Zhang

    Full Text Available To study the dosimetric difference between fixed-jaw volumetric modulated radiotherapy (FJ-VMAT and large-field volumetric modulated radiotherapy (LF-VMAT for nasopharyngeal carcinoma (NPC with cervical lymph node metastasis.Computed tomography (CT datasets of 10 NPC patients undergoing chemoradiotherapy were used to generate LF-VMAT and FJ-VMAT plans in the Eclipse version 10.0 treatment planning system. These two kinds of plans were then compared with respect to planning-target-volume (PTV coverage, conformity index (CI, homogeneity index (HI, organ-at-risk sparing, monitor units (MUs and treatment time (TT.The FJ-VMAT plans provided lower D2% of PGTVnd (PTV of lymph nodes, PTV1 (high-risk PTV and PTV2 (low-risk PTV than did the LF-VMAT plans, whereas no significant differences were observed in PGTVnx (PTV of primary nasopharyngeal tumor. The FJ-VMAT plans provided lower doses delivered to the planning organ at risk (OAR volumes (PRVs of both brainstem and spinal cord, both parotid glands and normal tissue than did the LF-VMAT plans, whereas no significant differences were observed with respect to the oral cavity and larynx. The MUs of the FJ-VMAT plans (683 ± 87 were increased by 22% ± 12% compared with the LF-VMAT plans (559 ± 62. In terms of the TT, no significant difference was found between the two kinds of plans.FJ-VMAT was similar or slightly superior to LF-VMAT in terms of PTV coverage and was significantly superior in terms of OAR sparing, at the expense of increased MUs.

  6. 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.

  7. Prognostic value of fluorodeoxyglucose positron emission tomography-computed tomography before and after radiotherapy in locally advanced nasopharyngeal carcinoma%局部晚期鼻咽癌放疗前后氟脱氧葡萄糖PET-CT摄取值与预后关系的研究

    Institute of Scientific and Technical Information of China (English)

    谢鹏; 岳金波; 孙新东; 冯瑞; 孔莉; 付政; 郑劲松; 赵献光; 于金明

    2009-01-01

    etabolic response to radiotherapy may predict the prognosis of paitents with locally advanced NPC. The prognosis is poor for patients with high FDG uptake before and after radiotherapy or SUV max-N SUV max-P .%中SUV max 较高者及淋巴结转移灶SUV max 值高于原发灶SUV max 者预后较差.

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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。

  13. 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。

  14. Case-control study and nursing strategy on correlation factors of nasopharyngeal carcinoma in Guangzhou%广州地区鼻咽癌患者非职业相关因素的调查

    Institute of Scientific and Technical Information of China (English)

    唐国文

    2014-01-01

    目的 探讨广州地区鼻咽癌患者非职业相关因素及护理对策.方法 以我院确诊的60例鼻咽癌患者为观察组,行1:1匹配病例对照研究,应用单因素及多因素条件Logistic回归对广州地区鼻咽癌非职业相关因素进行分析,计算各因素与鼻咽癌的OR值及其95%可信区间.结果 研究提示常吃烧烤食品(P=0.044)、常吃腌制食品(P=0.027)、酗酒(P=0.040)、抽烟(P=0.035)、常用语言为粤语(P=0.033)、一、二级血亲存在鼻咽癌患者(P=0.003)、慢性鼻炎病史(P=0.016)、精神刺激史(P=0.033)、EB病毒感染(P=0.007)为危险因素;常吃蔬菜(P=0.002)、经常运动(P=0.012)为保护因素.结论 广州地区鼻咽癌的发病与饮食因素、生活方式、遗传因素、既往病史及EB病毒感染密切相关,针对鼻咽癌的发生发展情况,采取合适的护理对策,提倡合理的膳食、良好的生活方式以及加强患者的心理安抚,可以有效降低鼻咽癌的发病率和(或)减轻患者心理负担.%Objective To investigate the correlation factors of nasopharyngeal carcinoma in Guangzhou.Methods A hospital-based 1:1 matched case-control study about nasopharyngeal carcinoma was conducted,calculated the factors associated with the extent of nasopharyngeal carcinoma and 95% confidence interval.Results The analysis showed that barbecue food,pickled food,alcoholism,smoking,Cantonese,nasopharyngeal carcinoma history in immediate family,chronic rhinitis,psychic attack and EBV infection were risk factors of nasopharyngeal carcinoma (P=0.044,0.027,0.040,0.035,0.033,0.003,0.016,0.033,0.007); while eating vegetable and taking exercise frequently were protective factors (P=0.002,0.012).Conclusions Dietary factor,life-style,genetic factor,disease history and EBV infection are closely related to nasopharyngeal carcinoma in Guangzhou.It maybe helpful to decreasing the incidence of nasopharyngeal carcinoma and/or reducing the psychological burden of patients to

  15. Advances in the pathology of penile carcinomas.

    Science.gov (United States)

    Chaux, Alcides; Cubilla, Antonio L

    2012-06-01

    The incidence of penile cancer varies from country to country, with the highest figures reported for countries in Africa, South America, and Asia and lowest in the United States and Europe. Causes of this variation are not clear, but they are thought to be related to human papillomavirus infection, smoking, lack of circumcision, chronic inflammation, and poor genital hygiene. Most penile tumors are squamous cell carcinomas, and a variegated spectrum of distinct morphologies is currently recognized. Each one of these subtypes has distinctive pathologic and clinical features. About half of penile carcinomas are usual squamous cell carcinomas, and the rest corresponds to verrucous, warty, basaloid, warty-basaloid, papillary, pseudohyperplastic, pseudoglandular, adenosquamous, sarcomatoid, and cuniculatum carcinomas. Previous studies have found a consistent association of tumor cell morphology and human papillomavirus presence in penile carcinomas. Those tumors composed of small- to intermediate-sized, basaloid ("blue") cells are often human papillomavirus positive, whereas human papillomavirus prevalence is lower in tumors showing large, keratinizing, maturing eosinophilic ("pink") cells. Human papillomavirus-related tumors affect younger patients, whereas human papillomavirus-unrelated tumors are seen in older patients with phimosis, lichen sclerosus, or squamous hyperplasia. This morphologic distinctiveness is also observed in penile intraepithelial neoplasia. The specific aim of this review is to provide a detailed discussion on the macroscopic and microscopic features of all major subtypes of penile cancer. We also discuss the role of pathologic features in the prognosis of penile cancer, the characteristics of penile precursor lesions, and the use of immunohistochemistry for the diagnosis of invasive and precursor lesions.

  16. Vismodegib induces significant clinical response in locally advanced trichoblastic carcinoma.

    Science.gov (United States)

    Lepesant, P; Crinquette, M; Alkeraye, S; Mirabel, X; Dziwniel, V; Cribier, B; Mortier, L

    2015-10-01

    Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.

  17. 鼻咽癌放疗后困难气道1例报道%A case of radiation-induced difficult airway in a patient with nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Deke Li; Staying Wang; Kun Chen

    2012-01-01

    In this report, we describe radiation-induced difficult airway management in a patient with nasopharyngeal carcinoma. The patient was presented to receive laparoscopic cholecystectomy for gallbladder stone. He had been diagnosed to have nasopharyngeal cancer about 2 years ago. In operation, after sleeping, the patient was manual controlled ventilation. However, we subsequently found that his neck campaign was limited and mask ventilation was obstructed. We immediately performed oropharyngeal airway, then mask ventilation improved. Fully surface anesthesia with tetracaine atomizing to the root of tongue, larynx wall and piriform recess, the patient was endotracheal intubated with fiberoptic bronchoscope. After intubation, the patient inhaled 2.5% sevoflurane, then esmeron (50 mg) and remifentanyl (0.1 μg/kg every minute) were administrated by intravenous. After the treatment, the patient's life indexes were normal and steady. In conclusion, patients with nasopharyngeal carcinoma (NPC) after radiation therapy should be based on comprehensive evaluation of upper airway and obstructive condition before operation, then perform safe and effective tracheal intubation methods under spontaneous breathing.

  18. Matrine-induced apoptosis of human nasopharyngeal carcinoma cells via in vitro vascular endothelial growth factor-A/extracellular signal-regulated kinase1/2 pathway inactivation.

    Science.gov (United States)

    Xie, M; He, G; Wang, R; Shi, S; Chen, J; Ye, Y; Xie, L; Yi, X; Tang, A

    2014-07-01

    Matrine, a main active extract from Sophora flavescens Ait, has been demonstrated to exert anticancer effects on various cancer cell lines, such as malignant melanoma, breast cancer, and lung cancer. However, it is currently unclear whether matrine could also elicit an inhibitory effect on growth of nasopharyngeal carcinoma (NPC), let alone the possible molecular mechanisms. Therefore, in a previous study, we investigated matrine-induced proliferation inhibition and apoptosis in NPC cells. It was shown that proliferation of human NPC cells (CNE1 and CNE2) was significantly diminished by matrine in a dose- and time-dependent manner, and apoptosis was induced in both 2 NPC cells, particularly in CNE2 cells. Moreover, the increased apoptosis rate in matrine-treated CNE2 cells confirmed the proapoptotic activity of matrine. We further found that matrine treatment dose- and time-dependently reduced the levels of vascular endothelial growth factor-A (VEGF-A), and inactivated extracellular signal-regulated kinase1/2 (ERK1/2), followed by increased expression of downstream target caspase-3. Overall, we conclude that matrine could induce apoptosis of human NPC cells via VEGF-A/ERK1/2 pathway, which supports the potential use of matrine in clinically treating NPC.

  19. Gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p inhibit growth of EBV-positive nasopharyngeal carcinoma

    Science.gov (United States)

    Wang, Jianguo; Lyu, Xiaoming; Chen, Yuxiang; Liu, Jinkun; Cai, Hongbing; Wang, Ying; Li, Xin

    2015-01-01

    Epstein-Barr virus (EBV) infection is a major etiological factor for nasopharyngeal carcinoma (NPC). Several EBV-encoded BART miRNAs have been associated with viral latency, immune escape, cell survival, cell proliferation and apoptosis. Here, we report that EBV-miR-BART7-3p, an EBV-encoded BART miRNA highly expressed in NPC, was correlated with cell-cycle progression in vitro and increased tumor formation in vivo. This viral miRNA stimulated the PTEN/PI3K/Akt pathway and induced c-Myc and c-Jun. Knockdown of PTEN mimicked EBV-miR-BART7-3p-induced tumorigenic phenotype. Based on these results, we conducted a therapeutic experiment by using gold nano-particles (AuNPs) carrying anti-EBV-miR-BART7-3p. Silencing of EBV-miR-BART7-3p reduced tumor growth in animal model. We conclude that EBV-miR-BART7-3p favors carcinogenesis, representing a potential target for miRNA-based therapy. PMID:25691053

  20. Correlation of chromosomal polysomy with overexpression of c-myc and c-erbB-2 in primary nasopharyngeal carcinoma: Tissue microarray study

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Many genes may be involved in nasopharyngeal carcinoma (NPC) development and progression. Several known oncogenes, including c-myc and c-erb-B2, have been shown to have structural alteration and aberrant expression in NPC. Here, we constructed a tissue microarray to determine the status of c-myc and c-erbB-2 oncogenes at the DNA and protein levels using interphase fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) and to define the diagnostic, prognostic importance of the genetic changes. Results showed that amplification of c-myc and c-erbB-2 was not found in NPC. Polysomy 8 and 17 were observed in 43%-50% and 20%-27% of NPC tumors, respectively. Overexpressions of c-myc and c-erbB-2 oncoproteins were detected in 53.6% and 54.5% cases of NPC with polysomy 8 and 17, respectively. There was no significant correlation between c-myc and c-erbB-2 staining and the clinical stage. But overexpression of c-erbB-2 was associated with polysomy 17 in NPC. These findings suggest that chromosomal polysomy, not gene amplification, may be partially responsible for the upregulated expression of c-erbB-2 oncogene in NPC.

  1. Effect of Kangfuxin Solution on Chemo/Radiotherapy-Induced Mucositis in Nasopharyngeal Carcinoma Patients: A Multicenter, Prospective Randomized Phase III Clinical Study

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    Yangkun Luo

    2016-01-01

    Full Text Available Objective. To evaluate the efficacy and safety of Kangfuxin Solution, a pure Chinese herbal medicine, on mucositis induced by chemoradiotherapy in nasopharyngeal carcinoma patients. Methods. A randomized, parallel-group, multicenter clinical study was performed. A total of 240 patients were randomized to receive either Kangfuxin Solution (test group or compound borax gargle (control group during chemoradiotherapy. Oral mucositis, upper gastrointestinal mucositis, and oral pain were evaluated by Common Terminology Criteria for Adverse Events (CTCAE v3.0 and the Verbal Rating Scale (VRS. Results. Of 240 patients enrolled, 215 were eligible for efficacy analysis. Compared with the control group, the incidence and severity of oral mucositis in the test group were significantly reduced (P=0.01. The time to different grade of oral mucositis occurrence (grade 1, 2, or 3 was longer in test group (P<0.01, and the accumulated radiation dose was also higher in test group comparing to the control group (P<0.05. The test group showed lower incidence of oral pain and gastrointestinal mucositis than the control group (P<0.01. No significant adverse events were observed. Conclusion. Kangfuxin Solution demonstrated its superiority to compound borax gargle on mucositis induced by chemoradiotherapy. Its safety is acceptable for clinical application.

  2. The experimental study on the radioimmunotherapy of the nasopharyngeal carcinoma overexpressing HER2/neu in nude mice model with intratumoral injection of {sup 188}Re-herceptin

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    Li Guiping [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China) and Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China)]. E-mail: ligp@fimmu.com; Wang Yongxian [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, the Chinese Academy of Sciences, Shanghai, 201800 (China)]. E-mail: yongxianw@163.com; Huang Kai [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Zhang Hui [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Peng Wuhe [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Zhang Chunfu [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China)

    2005-01-01

    The therapeutic efficacy of radioimmunotherapy (RIT) of {sup 188}Re-labeled herceptin, which is a humanized anti-p185-HER2/neu monoclonal antibody (mAb), was studied. The nude mice bearing nasopharyngeal carcinoma (NPC) expressing HER2/neu protooncogene were injected with {sup 188}Re-herceptin intratumorally and intravenously. The biodistribution was observed on day 2 (n=3). The tumor growth inhibition rate (IR) was determined by measurement of tumor volume. In the intratumorally treated mice, tumor uptake of {sup 188}Re-herceptin was significantly greater than in the intravenously treated mice [11.53% injected dose (ID)/g vs. 2.79% ID/g at 48 h], and lower normal organ uptake was also seen. The intratumoral administration of {sup 188}Re-herceptin caused greater inhibition of tumor growth at the fourth week as compared to the intravenous administration. It is concluded that intratumoral administration of {sup 188}Re-herceptin makes high level of radioactivity retained in tumor with significantly lower radioactivity retained in normal tissues, and provides a more effective regional therapy for NPC overexpressing HER2/neu.

  3. Epstein-Barr Virus, Human Papillomavirus, and Flow Cytometric Cell Cycle Kinetics in Nasopharyngeal Carcinoma and Inverted Papilloma among Egyptian Patients

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    S. K. Kassim

    1998-01-01

    Full Text Available It is widely accepted that the Epstein-Barr virus is etiologically associated with the development of nasopharyngeal carcinoma. The human papillomavirus is also associated with inverted papilloma. We used the polymerase chain reaction technique to detect both viruses in both types of tumors. Flow cytometry was also used to study the DNA pattern and proliferative behavior of the tumors in relation to the viruses. EBV was detected in 13/20 (65% of NPC specimens, and in none of IP (n = 10 or control specimens (n = 10. This indicates the contribution of EBV as an etiologic factor in NPC. Five cases of NPC (25% were positive for HPV 16, two of them were EBV positive. Four HPV 16 positive cases were found among cases with inverted papilloma, but none among the control cases. Flow cytometry revealed that all NPC, IP, and control samples were diploid except one aneuploid NPC sample. Proliferative capacity (PC of primary tumors was predictive of tumor recurrence in NPC. Using 13.6% as a cut-off point for PC, we were able to discriminate between high risk and low risk groups with 100% sensitivity and 86% specificity. PC can be used as a baseline prognostic parameter in NPC, making it possible to modify courses of treatment in an attempt to inhibit tumor recurrence.

  4. Delayed-type hypersensitivity (DTH) immune response related with EBV-DNA in nasopharyngeal carcinoma treated with autologous dendritic cell vaccination after radiotherapy.

    Science.gov (United States)

    Li, Feng; Song, Dan; Lu, Yue; Zhu, Huanfeng; Chen, Zhenzhang; He, Xia

    2013-04-01

    The aim of this work was to investigate the outcome of an autologous dendritic cell (DC) vaccination in patients with stage II/III nasopharyngeal carcinomas (NPC). From 38 patients with stage II/III Epstein-Barr virus (EBV)-associated NPCs after a radiotherapy, 16 human leukocyte antigen-A2 (HLA-A2)-positive patients were enrolled and medicated with autologous DCs, which were pulsed with HLA-A2-restricted EBV-encoded latent membrane protein 2A (LMP2A) peptides. The lymphocyte subsets, serum cytokines, and EBV-DNA levels as well as the delayed-type hypersensitivity (DTH) responses were determined after vaccination combined with a radiotherapy/chemotherapy. The serum levels of interleukin-2 and interferon-γ (PEBV LMP2A peptides in a DTH test. The serum EBV-DNA level decreased significantly from 1519 ± 384 to 1214 ± 211 copies/mL in the 9 DTH-positive patients (P=0.0310). No unanticipated or serious toxicity was observed and the vaccine was well tolerated. In conclusion, in NPC patients vaccinated after radiotherapy with autologous DCs, which were pulsed with EBV LMP2A peptides, Th1-specific immune responses were elicited particularly in DTH test positive individuals. The clinical results obtained are encouraging and the EBV-specific HLA-A2-restricted DC vaccination is a promising treatment for EBV-related NPCs.

  5. Dose-volume relationships for moderate or severe neck muscle atrophy after intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma

    Science.gov (United States)

    Zhang, Lu-Lu; Wang, Xiao-Ju; Zhou, Guan-Qun; Tang, Ling-Long; Lin, Ai-Hua; Ma, Jun; Sun, Ying

    2015-01-01

    This study aimed to identify the dosimetric parameters and radiation dose tolerances associated with moderate or severe sternocleidomastoid muscle (SCM) atrophy after intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). We retrospectively analysed 138 patients treated with IMRT between 2011 and 2012 for whom IMRT treatment plans and pretreatment and 3-year post-IMRT MRI scans were available. The association between mean dose (Dmean), maximum dose (Dmax), VX (% SCM volume that received more than X Gy), DX (dose to X% of the SCM volume) at X values of 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80 and SCM atrophy at 3 years after IMRT were analyzed. All dosimetric parameters, except V40, V50 and V80, were significantly associated with moderate or severe SCM atrophy. Multivariate analysis showed that V65 was an independent predictor of moderate or severe SCM atrophy (P < 0.001). Receiver operating characteristic (ROC) curve indicated a V65 of 21.47% (area under ROC curves, 0.732; P < 0.001) was the tolerated dose for moderate or severe SCM atrophy. We suggest a limit of 21.47% for V65 to optimize NPC treatment planning, whilst minimizing the risk of moderate or severe SCM atrophy. PMID:26678599

  6. Lasiodin inhibits proliferation of human nasopharyngeal carcinoma cells by simultaneous modulation of the Apaf-1/caspase, AKT/MAPK and COX-2/NF-κB signaling pathways.

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    Lianzhu Lin

    Full Text Available Rabdosia serra has been widely used for the treatment of the various human diseases. However, the antiproliferative effects and underlying mechanisms of the compounds in this herb remain largely unknown. In this study, an antiproliferative compound against human nasopharyngeal carcinoma (NPC cells from Rabdosia serra was purified and identified as lasiodin (a diterpenoid. The treatment with lasiodin inhibited cell viability and migration. Lasiodin also mediated the cell morphology change and induced apoptosis in NPC cells. The treatment with lasiodin induced the Apaf-1 expression, triggered the cytochrome-C release, and stimulated the PARP, caspase-3 and caspase-9 cleavages, thereby activating the apoptotic pathways. The treatment with lasiodin also significantly inhibited the phosphorylations of the AKT, ERK1/2, p38 and JNK proteins. The pretreatment with the AKT or MAPK-selective inhibitors considerably blocked the lasiodin-mediated inhibition of cell proliferation. Moreover, the treatment with lasiodin inhibited the COX-2 expression, abrogated NF-κB binding to the COX-2 promoter, and promoted the NF-κB translocation from cell nuclei to cytosol. The pretreatment with a COX-2-selective inhibitor abrogated the lasiodin-induced inhibition of cell proliferation. These results indicated that lasiodin simultaneously activated the Apaf-1/caspase-dependent apoptotic pathways and suppressed the AKT/MAPK and COX-2/NF-κB signaling pathways. This study also suggested that lasiodin could be a promising natural compound for the prevention and treatment of NPC.

  7. Combined Transfection with EBV-Specific Epitopes and HLA-A2 genes is More Effective than Separate Transfection in Promoting CTL Lysis against Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Weijun Ding; Choylen Fong

    2004-01-01

    To augment specific cytotoxic T lymphocyte (CTL) lysis is a promising strategy for cancer therapy. In this study,we examined the boosting effect of CTLs upon autologous lymphoblastoid B cell lines (LCLs) transfected with diverse plasmids, to explore the possible CTL-based immunotherapy of nasopharyngeal carcinoma (NPC).FCM analysis displayed rather high ratio (>30%) of successfully transfected LCLs by utilizing the DMRIE-C kit. CTL assays demonstrated that substantially higher ratio of CTL specific lysis was observed upon the LCLs transfected with both expression vectors encoding EBV-specific epitopes and their presentation molecule HLA-A2, in contrast with those transfected separately. By transfecting the vector encoding HLA-A2 alone, only the LCLs of HLA-A2+ donors elicited markedly higher CTL lysis. CTL assays also showed that there existed no marked differences upon transfection by either different vectors (pcDNA3, pNGVL3 or pNGVL3-hFlex), or different EBV-derived peptides (LMP2Pep1 or LMP2Pep2), or with or without the doubled DNA sequence encoding peptides. This study indicated a promising immunotherapy strategy on NPC through boosting and eliciting the EBV-specific CTL activation by transferring vectors encoding both EBV-specific epitopes and their presentation molecule HLA-A2 into autologous LCL, the presentation cells of MHC/peptide tetrameric complex.

  8. Combined Transfection with EBV-Specific Epitopes and HLA-A2 genes is More Effective than Separate Transfection in Promoting CTL Lysis against Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    WeijunDing; ChoylenFong

    2004-01-01

    To augment specific cytotoxic T lymphocyte (CTL) lysis is a promising strategy for cancer therapy. In this study,we examined the boosting effect of CTLs upon autologous lymphoblastoid B cell lines (LCLs) transfected with diverse plasmids, to explore the possible CTL-based immunotherapy of nasopharyngeal carcinoma (NPC).FCM analysis displayed rather high ratio (>30%) of successfully transfected LCLs by utilizing the DMRIE-C kit. CTL assays demonstrated that substantially higher ratio of CTL specific lysis was observed upon the LCLs transfected with both expression vectors encoding EBV-specific epitopes and their presentation molecule HLA-A2, In contrast with those transfected separately. By transfecting the vector encoding HLA-A2 alone, only the LCLs of HLA-A2+ donors elicited markedly higher CTL lysis. CTL assays also showed that there existed no marked differences upon transfection by either different vectors (pcDNA3, pNGVL3 or pNGVL3-hFIex), or different EBV-derived peptides (LMP2Pep1 or LMP2Pep2), or with or without the doubled DNA sequence encoding peptides. This study indicated a promising immunotherapy strategy on NPC through boosting and eliciting the EBV-specific CTL activation by transferring vectors encoding both EBV-specific epitopes and their presentation molecule HLA-A2 into autologous LCL, the presentation cells of MHC/peptide tetrameric complex.

  9. Clinical Outcomes of Volume-Modulated Arc Therapy in 205 Patients with Nasopharyngeal Carcinoma: An Analysis of Survival and Treatment Toxicities.

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    Rui Guo

    Full Text Available To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT for nasopharyngeal carcinoma (NPC.205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria.The median follow-up period was 37.3 months (range, 6.3-45.1 months. The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05. The most common acute and late side effects were grade 2-3 mucositis (78% and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT, respectively.VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

  10. Reversal effect of GnT-V on the radioresistance of human nasopharyngeal carcinoma cells by alteration β1, 6-GlcNAc branched N-glycans.

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    Wu, Jun-Bo; Shen, Li; Qiu, Li; Duan, Qi-Wen; Luo, Zhi-Guo; Dong, Xiao-Xia

    2015-01-01

    Radiotherapy is the primary treatment for human nasopharyngeal carcinoma (NPC), yet radioresistance remains a major obstacle to successful treatment in many cases. N-acetylglucosaminyltransferase V (GnT-V), which synthesizes β1, 6-GlcNAc branched N-glycans, is closely related to the radiosensitivity of NPC cells. However, a better understanding of the functional role of GnT-V in NPC radioresistance and the related mechanisms is urgently needed. In the present study, a radioresistant NPC cell line, CNE-2R, was established by repeated γ-irradiation. We found that GnT-V levels, as well as β1, 6-GlcNAc branched N-glycans were significantly increased in the CNE-2R cells as compared with that in the parental cells. Meanwhile, knockdown of GnT-V in the CNE-2R cells enhanced cell radiosensitivity and inhibited the formation of β1, 6-branched N-glycans. In addition, the regulated expression of GnT-V in the CNE-2R cells converted the heterogeneous N-glycosylated forms of CD147. Furthermore, swainsonine, an inhibitor of N-glycan biosynthesis, was also able to reverse the radioresistance of the CNE-2R cells. Taken together, the present study revealed a novel mechanism of GnT-V as a regulator of radioresistance in NPC cells, which may be useful for fully understanding the biological role of N-glycans in NPC radioresistance.

  11. Regulation of Survivin and CDK4 by Epstein-Barr virus encoded latent membrane protein 1 in nasopharyngeal carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Mi Dan AI; Li Li LI; Xiao Rong ZHAO; Yong WU; Jian Ping GONG; Ya CAO

    2005-01-01

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

  12. Extra-cellular release and blood diffusion of BART viral micro-RNAs produced by EBV-infected nasopharyngeal carcinoma cells

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    Baconnais Sonia

    2010-10-01

    Full Text Available Abstract Background Nasopharyngeal carcinoma (NPC is a human epithelial malignancy consistently associated with the Epstein-Barr virus. The viral genome is contained in the nuclei of all malignant cells with abundant transcription of a family of viral microRNAs called BART miRNAs. MicroRNAs are well known intra-cellular regulatory elements of gene expression. In addition, they are often exported in the extra-cellular space and sometimes transferred in recipient cells distinct from the producer cells. Extra-cellular transport of the microRNAs is facilitated by various processes including association with protective proteins and packaging in secreted nanovesicles called exosomes. Presence of microRNAS produced by malignant cells has been reported in the blood and saliva of tumor-bearing patients, especially patients diagnosed with glioblastoma or ovarian carcinoma. In this context, it was decided to investigate extra-cellular release of BART miRNAs by NPC cells and their possible detection in the blood of NPC patients. To address this question, we investigated by quantitative RT-PCR the status of 5 microRNAs from the BART family in exosomes released by NPC cells in vitro as well as in plasma samples from NPC xenografted nude mice and NPC patients. Results We report that the BART miRNAs are released in the extra-cellular space by NPC cells being associated, at least to a large extent, with secreted exosomes. They are detected with a good selectivity in plasma samples from NPC xenografted nude mice as well as NPC patients. Conclusions Viral BART miRNAs are secreted by NPC cells in vitro and in vivo. They have enough stability to diffuse from the tumor site to the peripheral blood. This study provides a basis to explore their potential as a source of novel tumor biomarkers and their possible role in communications between malignant and non-malignant cells.

  13. Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas

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    Glaser, R.; Zhang, Haizhang (Ohio State Univ. Medical Center, Columbus (USA)); Yao, Kaitai; Zhu, Hecheng; Wang, Fuxi; Li, Guiyuan; Wen, Dongseng; Li, Yingping (Hunan Medical Univ., Changsha (China))

    1989-12-01

    Two epithelia tumor cell lines were established from biopsy specimens of nasopharyngeal carcinomas (NPC). The specimens were taken from poorly differentiated squamous cell carcinomas of the nasopharynx. The tissues were prepared for cell culture and eventually two continuous epithelia cell lines were obtained and designated HONE-1 and HNE-1. Light and electron microscopic examination of these two cell lines demonstrated cells with an epithelial morphology including the presence of desmosomes. It was found that early-passage uncloned HNE-1 cells (passage 23) could be superinfected with B95-8 and NPC-EBV isolates as demonstrated by the induction of Epstein-Barr virus (EBV)-specific early antigen(s) in a small percentage of the cells; HONE-1 cells could also be superinfected with EBV. Southern blot analysis detected EBV DNA in samples from uncloned HNE-1 cells at passages 12, 17, 21, 27, and 35. However, by passage 45, EBV DNA could no longer be detected in HNE-1 cells by Southern blot analysis. The EBV genome was detected in parental HONE-1 cells at subculture 9 and in clone 40 cells up to passage 40 thus far. The data suggest that EBV genome-positive HNE-1 and HONE-1 cells were lost as the cells were cultivated in vitro and that cloning the cells at an early passage level may be critical in maintaining EBV genome-positive epithelial NPC cells. These EBV genome-positive epithelia NPC cell lines will be useful for studying the association of EBV and NPC.

  14. Suppressing tumor growth of nasopharyngeal carcinoma by hTERTC27 polypeptide delivered through adeno-associated virus plus adenovirus vector cocktail

    Institute of Scientific and Technical Information of China (English)

    Xiong Liu; Xiang-Ping Li; Ying Peng; Samuel S.Ng; Hong Yao; Zi-Feng Wang; Xiao-Mei Wang; Hsiang-Fu Kung; Marie C.M.Lin

    2012-01-01

    Nasopharyngeal carcinoma(NPC) is a metastatic carcinoma that is highly prevalent in Southeast Asia.Our laboratory has previously demonstrated that the C-terminal 27-kDa polypeptide of human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human glioblastoma and melanoma cells.In this study,we investigated the antitumor effect of hTERTC27 in human C666-1 NPC cells xenografted in a nude mouse model.A cocktail of vectors comprising recombinant adeno-associated virus (rAAV) and recombinant adenovirus (rAdv) that each carry hTERTC27 (rAAV-hTERTC27 and rAdv-hTERTC27; the cocktail was abbreviated to rAAV/rAdv-hTERTC27) was more effective than either rAAV-hTERTC27 or rAdv-hTERTC27 alone in inhibiting the growth of C666-1 NPC xenografts.Furthermore,we established three tumors on each mouse and injected rAAV/rAdv-hTERTC27 into one tumor per mouse.Although hTERTC27 expression could only be detected in the injected tumors,reduced tumor growth was observed in the injected tumor as well as the uninjected tumors,demonstrating that the vector cocktail could provoke an antitumor effect on distant,metastasized tumors.Further studies showed the observed antitumor effects included inducing necrosis and apoptosis and reducing microvessel density.Together,our data suggest that the rAAV/rAdv-hTERTC27 cocktail can potently inhibit NPC tumor growth in both local and metastasized tumors and should be further developed as a novel gene therapy strategy for NPC.

  15. Parkin基因甲基化对鼻咽癌早期诊断及预后判断的价值研究%Parkin gene promoter methylation in nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    江波; 倪海峰; 周珍; 李勇; 黄光武

    2016-01-01

    目的:研究Parkin基因甲基化在鼻咽癌早期诊断及预后判断中的价值。方法运用甲基化特异性PCR检测54例鼻咽癌组织、16例慢性鼻咽炎症组织和16例正常鼻咽上皮组织中Parkin基因启动子区甲基化情况,并分析其与鼻咽癌临床生物学因素的关系。结果慢性鼻咽炎症组织和正常鼻咽上皮组织中均未检测到Parkin基因甲基化,而在鼻咽癌组织中甲基化率为62.96%(34/54),3种鼻咽组织Parkin基因甲基化情况比较有统计学差异(P<0.05)。进一步统计学分析发现鼻咽癌组织Parkin基因甲基化与其临床生物学因素均无关(均P>0.05)。结论 Parkin基因甲基化具有肿瘤特异性,与鼻咽癌发生、发展密切相关,有望成为早期分子生物学辅助诊断的标志物,但不能作为判断鼻咽癌预后的预测指标。%Objective To investigate Parkin gene promoter methylation in nasopharyngeal carcinoma (NPC). Methods The methylation- specific PCR (MSP) was used to detect methylation level of Parkin gene in 54 tissue specimens of NPC, 16 specimens of chronic nasopharyngitis and 16 specimens of normal nasopharyngeal epithelia tissues, and its relationship with the clinical and biological features of NPC was analyzed. Results Parkin gene promoter methylation was detected in 62.96%(34/54) of NPC specimens, not in any specimens of chronic nasopharyngitis and normal nasopharyngeal epithelia tissues(P0.05). Conclusion Parkin gene promoter methylation has high specificity in distinguishing NPC from normal nasopharyngeal tissues and inflammatory nasopharyngeal disease, suggesting that it may be used for early molecular diagnosis of NPC.

  16. 鼻咽癌放疗患者口腔感染的影响因素研究%Factors influencing oral infection in patients with radiotherapy for nasopharyn-geal carcinoma

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    吴春苏; 陈清华

    2016-01-01

    目的:研究鼻咽癌放疗患者口腔感染的影响因素。方法回顾性分析291例鼻咽癌患者的临床资料,对其进行为期1年的随访,利用单因素和多因素分析方法进行数据统计,分析鼻咽癌放疗患者口腔感染的影响因素。结果患者住院30天后发生口腔感染,感染有113例约占38.83%,数据显示47例为真菌感染,感染菌种以白假丝酵母菌培养阳性为主有32例占68.08%,热带假丝酵母菌其次;41例为细菌培养阳性感染;25例为混合感染。咪康唑、酮康唑耐药率最高,其他病原菌耐药率都很低。单因素分析显示,癌症病期、口腔自洁、口腔pH值、口腔环境、性别、营养状况、年龄、文化程度以及是否化疗作为患者发生口腔感染的相关因素(P﹤0.05);多元Logistic分析显示,口腔环境差,癌症晚期,口腔自洁差,是否愿意化疗及年龄是本研究的危险因素。结论口腔感染受多方面综合因素影响,加强真菌感染的危险因素控制,如抗菌药物的合理应用,加强无菌操作和营养支持,控制危险因素的发生,结合病情制定有效方案。%Objective To investigate the factors influencing oral infection in patients who were treated with radiother-apy for nasopharyngeal carcinoma. Method The clinical profiles of 291 cases of nasopharyngeal cancer patients who were followed for 1 year were retrospectively analyzed, univariate and multivariate analysis were applied to investigate the factors that influence oral infection in nasopharyngeal cancer patients receiving radiotherapy. Result Oral infection developed in 113 patients (38.83%) after 30 days of hospitalization, in which 47 cases were fungal infection, with positive candida albicans culture in 32 cases (68.08%), and some were candida tropicalis;another 41 cases were with positive in-fection of germiculture; and other 25 cases were mixed infection. Most pathogenic bacterium were

  17. Integrated mRNA and microRNA transcriptome sequencing characterizes sequence variants and mRNA–microRNA regulatory network in nasopharyngeal carcinoma model systems

    Directory of Open Access Journals (Sweden)

    Carol Ying-Ying Szeto

    2014-01-01

    Full Text Available Nasopharyngeal carcinoma (NPC is a prevalent malignancy in Southeast Asia among the Chinese population. Aberrant regulation of transcripts has been implicated in many types of cancers including NPC. Herein, we characterized mRNA and miRNA transcriptomes by RNA sequencing (RNASeq of NPC model systems. Matched total mRNA and small RNA of undifferentiated Epstein–Barr virus (EBV-positive NPC xenograft X666 and its derived cell line C666, well-differentiated NPC cell line HK1, and the immortalized nasopharyngeal epithelial cell line NP460 were sequenced by Solexa technology. We found 2812 genes and 149 miRNAs (human and EBV to be differentially expressed in NP460, HK1, C666 and X666 with RNASeq; 533 miRNA–mRNA target pairs were inversely regulated in the three NPC cell lines compared to NP460. Integrated mRNA/miRNA expression profiling and pathway analysis show extracellular matrix organization, Beta-1 integrin cell surface interactions, and the PI3K/AKT, EGFR, ErbB, and Wnt pathways were potentially deregulated in NPC. Real-time quantitative PCR was performed on selected mRNA/miRNAs in order to validate their expression. Transcript sequence variants such as short insertions and deletions (INDEL, single nucleotide variant (SNV, and isomiRs were characterized in the NPC model systems. A novel TP53 transcript variant was identified in NP460, HK1, and C666. Detection of three previously reported novel EBV-encoded BART miRNAs and their isomiRs were also observed. Meta-analysis of a model system to a clinical system aids the choice of different cell lines in NPC studies. This comprehensive characterization of mRNA and miRNA transcriptomes in NPC cell lines and the xenograft provides insights on miRNA regulation of mRNA and valuable resources on transcript variation and regulation in NPC, which are potentially useful for mechanistic and preclinical studies.

  18. 局部复发性鼻咽癌的临床病理学特征%Pathological characteristics of loco-regional recurrent nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    雍娟娟; 吴秋良; 宗永生; 侯景辉; 梁建中; 匡亚玲; 奚少彦; 卢佳斌

    2014-01-01

    Purpose To investigate the pathological characteristics of loco-regional recurrent nasopharyngeal carcinoma ( rNPC ) . Methods Nasopharyngeal biopsy specimens of 46 rNPCs and 63 primary NPCs were collected. HE staining, immunohistochemistry and EBV small RNAs ( EBERs) in-situ hybridization were performed. Results The over-expression rates of both p63 and CK5/6 in rNPC were significantly higher than those of primary NPCs (P=0. 005, P=0. 026), while no statistical significance of Ki-67 over-ex-pression existed between the two groups ( P=0. 387 ) . More necrotic tissues, inflammatory exudates, giant bizarre carcinoma cells, desmoplastic stroma, giant bizarre tumor cells and higher degree of squamous differentiation were found in rNPCs. The carcinoma cells of 5 rNPCs were negative for both EBERs in-situ hybridization and LMP-1 immunohistochemical staining. Conclusion The loco-re-gional rNPC has two peaks of latency interval:2~5 and 9~11 years. The loco-regional rNPC cells have higher degree of squamous differentiation with higher expression of p63 and CK5/6, as well as more invasive ability. In addition, both EBERs in-situ hybridization and LMP-1 immunostaining are negative in 10. 87% (5/46) of loco-regional rNPC.%目的:探讨局部复发性鼻咽癌的临床病理学特征。方法收集46例局部复发性鼻咽癌和63例原发性鼻咽癌活检组织,行HE染色、免疫组化、EBERs原位杂交检测。结果局部复发性鼻咽癌中p63和CK5/6的强阳性表达率均高于原发性鼻咽癌(P=0.005和P=0.026);Ki-67的强阳性表达率差异无显著性(P=0.387);组织坏死、炎性渗出和间质促纤维增生明显;畸形瘤巨细胞多见,癌细胞鳞状分化程度更高。5例复发性鼻咽癌细胞EBERs原位杂交和LMP-1免疫组化标记均为阴性。结论(1)局部复发性鼻咽癌有2个复发间歇高峰,即2~5年和9~11年。(2)局部复发性鼻咽癌细胞p63和CK5/6强阳性表达率、鳞状分化程度更高

  19. P53、MDM2在鼻咽癌组织中的表达及其与鼻咽癌生物学行为、预后关系的分析研究%Expression of p53 and MDM2 in Nasopharyngeal Carcinoma and their Correlation with the Biological Behavior and Prognosis of Nasopharyngeal Carcinoma

    Institute of Scientific and Technical Information of China (English)

    张鹏; 吴松珂; 徐鹏; 冯梅; 范子煊; 李厨荣; 付彬玉; 王卫东; 郎锦义

    2012-01-01

    目的:探讨P53、MDM2在鼻咽癌组织中的表达及与鼻咽癌生物学行为和生存率之间的关系.方法:回顾分析我院2005年~2009年行根治性放化疗治疗的96例鼻咽癌患者,所有患者治疗前行鼻咽部活检病理证实,均采用6MV-X线调强放疗联合以顺铂为主的方案同步化疗,随访3年以上.通过免疫组化SP法检测96例鼻咽癌标本中P53、MDM2蛋白的表达水平,并分析其与临床参数、预后之间关系.结果:P53、MDM2在96例鼻咽癌中阳性表达率分别为65.6%(63/96)、79.17%(76/96).P53的阳性表达率与不同T分期有关(P=0.000);MDM2在不同N分期的鼻咽癌组织中的表达的差异性具有统计学意义(P=0.001);P53的阳性表达在不同临床分期中的差异性具有统计学意义(P=0.037).P53与MDM2的表达呈负相关(r=-3.24,P<0.05).3年无瘤生存率(DFS)及总生存率(OS)分别为73.9%、84.4%.结论:P53、MDMZ的表达与鼻咽癌的生物学行为有关;P53与MDM2的表达呈负相关;P53表达是影响总生存率的预后因素,可以作为评价预后的指标.%Objective; To determine the expression of p53 and MDM2 in nasopharyngeal carcinoma and to investigate the relationship between them and biological behavior , survival rate of nasopharyngeal carcinoma. Methods: Clinical data of 96 nasopharyngeal carcinoma patients accepted radical radiotherapy and chemotherapy in our hospital from 2005 - 2009 were retrospective analyzed. All patients were diagnosed by biopsy of the nasopharynx before treatment. Patients accepted the 6-MV X-ray intensity-modulated radiotherapy combined with cisplatin-based chemotherapy regimen and were followed up for more than 3 years. The expression levels of P53, MDM2 protein in 96 cases of nasopharyngeal specimens were detected by immunohistochemical SP method and their relationship with the clinical parameters, prognosis were analyzed. Results; The positive expression rate of P53 and MDM2 was 65. 6% (63/96) , 79. 17% (76

  20. A Glucosamine-Specific Lectin from Green Dragon No. 8 Beans (Phaseolus vulgaris Induced Apoptosis on Nasopharyngeal Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Yau Sang Chan

    2015-01-01

    Full Text Available A lectin exhibiting antiproliferative activity on tumor cell lines but devoid of antifungal activity has been purified from Phaseolus vulgaris cv. Green Dragon no. 8 seeds. The lectin was a 60 kDa dimeric protein with two 30 kDa subunits. It was a glucosamine-specific lectin as implied from the inhibitory effect of glucosamine on hemagglutinating activity of the lectin. The steps for isolation of the lectin involved Affi-gel blue gel (affinity gel, Mono Q (anion exchanger, and Superdex 75 column (size exclusion. The lectin was purified 20.8-fold from the crude extract of the beans. The purified lectin showed antiproliferative activity on breast cancer MCF7 cell line and nasopharyngeal cancer HONE1 and CNE2 cell lines, but a low activity on normal skin fibroblast HSF98 cell line. The lectin was shown to induce apoptosis on HONE1 cells, as indicated by increased phosphatidylserine externalization and mitochondrial depolarization. It also blocked HONE1 cell division and kept the cells at the G2/M phase of the cell cycle.

  1. A Glucosamine-Specific Lectin from Green Dragon No. 8 Beans (Phaseolus vulgaris) Induced Apoptosis on Nasopharyngeal Carcinoma Cells.

    Science.gov (United States)

    Chan, Yau Sang; Xia, Lixin; Ng, Tzi Bun

    2015-01-01

    A lectin exhibiting antiproliferative activity on tumor cell lines but devoid of antifungal activity has been purified from Phaseolus vulgaris cv. Green Dragon no. 8 seeds. The lectin was a 60 kDa dimeric protein with two 30 kDa subunits. It was a glucosamine-specific lectin as implied from the inhibitory effect of glucosamine on hemagglutinating activity of the lectin. The steps for isolation of the lectin involved Affi-gel blue gel (affinity gel), Mono Q (anion exchanger), and Superdex 75 column (size exclusion). The lectin was purified 20.8-fold from the crude extract of the beans. The purified lectin showed antiproliferative activity on breast cancer MCF7 cell line and nasopharyngeal cancer HONE1 and CNE2 cell lines, but a low activity on normal skin fibroblast HSF98 cell line. The lectin was shown to induce apoptosis on HONE1 cells, as indicated by increased phosphatidylserine externalization and mitochondrial depolarization. It also blocked HONE1 cell division and kept the cells at the G2/M phase of the cell cycle.

  2. Long-term outcomes of a phase II randomized controlled trial comparing intensity-modulated radiotherapy with or without weekly cisplatin for the treatment of locally recurrent nasopharyngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying Guan; Shuai Liu; HanYu Wang; Ying Guo; WeiWei Xiao; ChunYan Chen; Chong Zhao; TaiXiang Lu; Fei Han

    2016-01-01

    Background: Salvage treatment for locally recurrent nasopharyngeal carcinoma (NPC) is complicated and relatively limited. Radiotherapy, combined with effective concomitant chemotherapy, may improve clinical treatment out‑comes. We conducted a phase II randomized controlled trial to evaluate the efcacy of intensity‑modulated radio‑therapy with concomitant weekly cisplatin on locally recurrent NPC. Methods: Between April 2002 and January 2008, 69 patients diagnosed with non‑metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group (n = 34) or radiotherapy alone group(n= 35). All patients received intensity‑modulated radiotherapy. The radiotherapy dose for both groups was 60 Gy in 27 fractions for 37 days (range 23–53 days). The concomitant chemotherapy schedule was cisplatin 30 mg/m2 by intravenous infusion weekly during radiotherapy. Results: The median follow‑up period of all patients was 35 months (range 2–112 months). Between concomitant chemoradiotherapy and radiotherapy groups, there was only significant difference in the 3‑year and 5‑year overall survival (OS) rates (68.7% vs. 42.2%, P = 0.016 and 41.8% vs. 27.5%, P = 0.049, respectively). Subgroup analysis showedthat concomitant chemoradiotherapy significantly improved the 5‑year OS rate especially for patients in stage rT3–4 (33.0% vs. 13.2%, P = 0.009), stages III–IV (34.3% vs. 13.2%, P = 0.006), recurrence interval >30 months (49.0% vs. 20.6%,P= 0.017), and tumor volume >26 cm3 (37.6% vs. 0%, P = 0.006). Conclusion: Compared with radiotherapy alone, concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC, especially those with advanced T category (rT3–4) and stage (III–IV) diseases, recurrence intervals >30 months, and tumor volume >26 cm3.

  3. Development of a ten-signature classifier using a support vector machine integrated approach to subdivide the M1 stage into M1a and M1b stages of nasopharyngeal carcinoma with synchronous metastases to better predict patients' survival.

    Science.gov (United States)

    Jiang, Rou; You, Rui; Pei, Xiao-Qing; Zou, Xiong; Zhang, Meng-Xia; Wang, Tong-Min; Sun, Rui; Luo, Dong-Hua; Huang, Pei-Yu; Chen, Qiu-Yan; Hua, Yi-Jun; Tang, Lin-Quan; Guo, Ling; Mo, Hao-Yuan; Qian, Chao-Nan; Mai, Hai-Qiang; Hong, Ming-Huang; Cai, Hong-Min; Chen, Ming-Yuan

    2016-01-19

    The aim of this study was to develop a prognostic classifier and subdivided the M1 stage for nasopharyngeal carcinoma patients with synchronous metastases (mNPC). A retrospective cohort of 347 mNPC patients was recruited between January 2000 and December 2010. Thirty hematological markers and 11 clinical characteristics were collected, and the association of these factors with overall survival (OS) was evaluated. Advanced machine learning schemes of a support vector machine (SVM) were used to select a subset of highly informative factors and to construct a prognostic model (mNPC-SVM). The mNPC-SVM classifier identified ten informative variables, including three clinical indexes and seven hematological markers. The median survival time for low-risk patients (M1a) as identified by the mNPC-SVM classifier was 38.0 months, and survival time was dramatically reduced to 13.8 months for high-risk patients (M1b) (P < 0.001). Multivariate adjustment using prognostic factors revealed that the mNPC-SVM classifier remained a powerful predictor of OS (M1a vs. M1b, hazard ratio, 3.45; 95% CI, 2.59 to 4.60, P < 0.001). Moreover, combination treatment of systemic chemotherapy and loco-regional radiotherapy was associated with significantly better survival outcomes than chemotherapy alone (the 5-year OS, 47.0% vs. 10.0%, P < 0.001) in the M1a subgroup but not in the M1b subgroup (12.0% vs. 3.0%, P = 0.101). These findings were validated by a separate cohort. In conclusion, the newly developed mNPC-SVM classifier led to more precise risk definitions that offer a promising subdivision of the M1 stage and individualized selection for future therapeutic regimens in mNPC patients.

  4. CSPG4 Gene Expression in Nasopharyngeal Carcinoma and Control Tissues%CSPG4基因在鼻咽癌中的表达分析

    Institute of Scientific and Technical Information of China (English)

    宋亚莉; 李小玲; 黄丽丽; 李俏; 孙梦熙; 张文玲; 石磊; 范松青; 龚朝建

    2012-01-01

    目的:研究硫酸软骨素多糖蛋白4(CSPG4)基因在鼻咽癌及对照组织中的表达.方法:采用实时荧光定量PCR测定CSPG4基因在4例正常鼻咽上皮和18例鼻咽癌组织(其中Ⅱ期6例,Ⅲ期5例,Ⅳ期7例)中的表达情况;通过构建包含92例对照和1 87例鼻咽癌的组织芯片,应用免疫组织化学检测CSPG4蛋白的表达和分布.结果:正常鼻咽上皮中CSPG4基因mRNA表达水平较低,在鼻咽癌中CSPG4表达上调且与临床分期呈正相关,差异具有统计学意义(P=0.017)免疫组织化学结果表明鼻咽癌中CSPG4蛋白表达水平高于对照组,91.98%的鼻咽癌组织中CSPG4为强阳性表达,而对照组的强阳性率为76.09%(P=0.001)结论:CSPG4在鼻咽癌中随着临床进展表达逐渐上调,可能参与了鼻咽癌的发生发展,具体机制及临床应用前景值得进一步深入研究.%Objective: To study the expression of chondroitin sulfate proteoglycan 4 (CSPG4) gene in nasopharyngeal carcinoma (NPC) and control tissues. Methods: The CSPG4 mRNA expression of gene in 4 cases with normal nasopharyngeal epithelial tissue and 18 cases with NPC, including 6 stage- Ⅱ, 5 stage-Ⅲ, and 7 stage-Ⅳ cases, was determined by real-time quantitative PCR. A tissue microarray containing 92 cases of control and 187 cases of NPC tissues was constructed, and the CSPG4 protein expression level was assayed by immunohistochemistry. Results: CSPG4 mRNA was barely expressed in the normal tissues of nasopharyngeal epithelium, but significantly upregulated in the NPC biopsies (P=0.017) and positively correlated with the NPC clinical stage. The CSPG4 protein expression was also higher in NPC than in the controls. CSPG4 was significantly expressed in 91.98% of NPC cases, whereas the percentage of high CSPG4 expression cases was 76.09% in the control group (P=0.001). Conclusion: The CSPG4 gene is upregulated in NPC biopsies and is directly associated with NPC clinical staging, implying the probable

  5. Evolution of systemic therapy of advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Thomas Yau; Pierre Chan; Richard Epstein; Ronnie T Poon

    2008-01-01

    Hepatocellular carcinoma (HCC) commonly occurs in hepatitis B endemic areas, especially in Asian countries. HCC is highly refractory to cytotoxic chemotherapy. This resistance is partly related to its tumor biology, pharmacokinetic properties, and both intrinsic and acquired drug resistance. There is no convincing evidence thus far that systemic chemotherapy improves overall survival in advanced HCC patients.Other systemic approaches, such as hormonal therapy and immunotherapy, have also disappointing results. Recently, encouraging results have been shown in using sorafenib in the treatment of advanced HCC patients. In this review, we concisely summarize the evolution of developments in the systemic therapy of advanced HCC.

  6. 鼻咽癌放化疗结合患者生活质量的质性研究%Qualitative research on living quality of nasopharyngeal carcinoma patients under-going chemoradiotherapy

    Institute of Scientific and Technical Information of China (English)

    李小冬; 于晓燕; 鲍婷婷; 邾萍; 徐德静

    2016-01-01

    Objective Deeply investigate the personal experience and demand about living quality of patients with nasopharyngeal carcinoma who have received chemoradiotherapy, and explore related factors that affect the living quality of the patients, so as to offer theoretical foundation for overall clinical nursing process for patients with nasopha-ryngeal carcinoma. Methods Based on the grounded theory, face-to-face and semi-structural depth interview was car-ried out on 10 patients with nasopharyngeal carcinoma. The data was analyzed by the phenomenon analysis method Co-laizzi. Results Both the physical condition and mode of life of the patients receiving radiotherapy and chemotherapy had been changed, and chemoradiotherapy had restrained their body freedom, character, their social and interpersonal rela-tions, and the patients' living quality was affected at different levels. Conclusions The results above provide the basis for holistic nursing care and further improve the living quality of patients with nasopharyngeal carcinoma.%目的:深入了解鼻咽癌放化疗结合患者有关生活质量的个人体验及需求,探索影响患者生活质量的相关因素,为鼻咽癌患者临床整体护理的实施提供理论依据。方法采用扎根理论研究方法,对10例鼻咽癌放化结合患者进行面对面半结构式深度访谈,访谈资料用现象学分析方法Colaizzi法分析。结果放疗及化疗使患者身体状况和生活方式发生改变,限制了患者的躯体、角色、社会及人际关系,不同程度的影响着患者的生活质量。结论以上结果为护理人员对鼻咽癌患者实施整体护理提供了依据,护士应对患者进行全身心的护理,以提高患者的生活质量。

  7. Single arc volumetric-modulated arc therapy is sufficient for nasopharyngeal carcinoma: a dosimetric comparison with dual arc VMAT and dynamic MLC and step-and-shoot intensity-modulated radiotherapy

    OpenAIRE

    NING, ZHONG-HUA; Mu, Jin-Ming; Jin, Jian-Xue; Li, Xiao-Dong; LI, QI-LIN; GU, WEN-DONG; Huang, Jin; Han, Yang; PEI, HONG-LEI

    2013-01-01

    Background The performance of single arc VMAT (VMAT1) for nasopharyngeal carcinoma (NPC) on the Axesse linac has not been well described in previous studies. The purpose of this study is to assess the feasibility of VMAT1 for NPC by comparing the dosimetry, delivery efficiency, and accuracy with dual arc VMAT (VMAT2), dynamic MLC intensity-modulated radiotherapy (dIMRT), and step-and-shoot intensity-modulated radiotherapy (ssIMRT). Methods Twenty consecutive patients with non-metastatic NPC w...

  8. Prospective hormone study of hypothalamic-pituitary function in patients with nasopharyngeal carcinoma after high dose irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ming-Shen; Lin, Fang-Jen; Huang, Miau-Ju; Wang, Pei-Wan; Tang, Simon; Leung, Wei-Man; Leung, Wan (Chang-Gung Memorial Hospital, Taipei (Taiwan))

    1989-09-01

    With the aim of evaluating the effect of high dose irradiation (6,500 cGy/36 fractions or higher) to pituitary fossa, a prospective study was carried out in patients with nasopharyngeal cancer by a serial determination of several hormones in the serum, before and after the course of radiation therapy (RT). The radiation treatment field was at least 1 cm above the skull base with bilateral parallel opposing fields. Hormone assays were performed three times on each patient: (1)prior to, (2)one month after, (3)15-18 months after radiation therapy. The study included determination of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), cortisol, growth hormone (GH) and prolactin concentrations and LH-releasing hormone, thyrotrophin-releasing hormone stimulation and insulin tolerance tests were also carried out. Complete profiles were obtained in 24 patients (16 males and 8 females), aged 16-67 years. The results showed a significant decrease in the level of serum peak value of LH in males 18 months after therapy, and also in GH both one month and 18 months after therapy. A significant increase in the peak value of serum TSH was observed after therapy. Decreased serum FSH, cortisol and prolactin levels were noted, but these did not reach statistical significance. The decrease in GH level appeared earlier and was more sensitive than that found for the other hormones, and could prove to be a useful parameter for clinical evaluation. None of the patients showed any clinically recognizable symptoms or signs of hormone deficiency in the 18-33 months following completion of the radiation therapy. (author).

  9. Systemic treatment of advanced colorectal carcinoma.

    NARCIS (Netherlands)

    Laarhoven, H.W.M. van; Punt, C.J.A.

    2004-01-01

    For advanced colorectal cancer (ACC), 5-fluorouracil (5-FU) based chemotherapy has been the standard for some decades. Attempts have been made to improve its results by biochemical modulation and schedule modulation of 5-FU which, in combination with leucovorin (LV), has been regarded as standard ch

  10. Preclinical evaluation of PI3K inhibitor BYL719 as a single agent and its synergism in combination with cisplatin or MEK inhibitor in nasopharyngeal carcinoma (NPC)

    Science.gov (United States)

    Wong, Chi Hang; Ma, Brigette Buig Yue; Cheong, Hio Teng; Hui, Connie Wun Chun; Hui, Edwin Pun; Chan, Anthony Tak Cheung

    2015-01-01

    Nasopharyngeal carcinoma (NPC) is endemic to Southeast Asia and over 40% of NPC tissues harbor PIK3CA amplifications. This study aims to study the preclinical activity of a novel PI3K inhibitor, BYL719, in 6 NPC cell lines: C666-1, CNE-2, HK1, HK1-EBV, HONE-1 and HONE-1-LMP1. Over 70% of growth inhibition was attained when NPC cell lines were exposed to increasing concentrations of BYL719, with IC50 values at the low micro-molar range. Two BYL719-sensitive cell lines that harbor PIK3CA mutations, CNE-2 and HONE-1, were selected for further analysis on the effect of BYL719 on cell cycle progression, apoptosis and PI3K signaling. BYL719 significantly reduced the phosphorylation of Akt, and the Akt-mTOR axis downstream effector S6 in these 2 cell lines, but a feedback activation of MAPK was observed at 72 hours post-treatment. BYL719 induced G0/G1 cell cycle arrest and apoptosis in both cell lines. In 3D cell culture models, the growth of NPC spheroids was significantly inhibited in a dose-depending manner. When BYL719 was combined with a MEK inhibitor (AZD6244) in a 3D cell culture system, strong synergism on NPC cell growth was observed with attenuation of MAPK activation. A synergistic inhibitory effect on growth was observed when BYL719 was combined with higher dose levels of cisplatin. These data suggest that BYL719 has preclinical activity in NPC cell lines especially in those which harbor PIK3CA mutation. Combination with a MEK inhibitor maybe a useful strategy that warrants further investigation. PMID:26101713

  11. Association of ABCC2 and CDDP-Resistance in Two Sublines Resistant to CDDP Derived from a Human Nasopharyngeal Carcinoma Cell Line

    Directory of Open Access Journals (Sweden)

    Si Ming Xie

    2010-01-01

    Full Text Available Cisplatin (CDDP is one of the most active drugs to treat nasopharyngeal carcinoma (NPC patients. To further understand the mechanisms of CDDP-resistance in NPC, two CDDP-resistant sublines (CNE2-CDDP and CNE2-CDDP-5Fu derived from parental NPC cell line CNE2 were established. It was found that at the IC50 level, the resistance of CNE2-CDDP and CNE2-CDDP-5Fu against CDDP was 2.63-fold and 5.35-fold stronger than that of parental CNE2, respectively. Of the four ABC transporters (ABCB1, ABCC1, ABCC2 and ABCG2 related to MDR, only ABCC2 was found to be elevated both in CDDP-resistant sublines, with ABCC2 located in nucleus of CNE2-CDDP-5Fu but not in CNE2-CDDP and parental CNE2. Further research showed that compared to untreated CNE2, the intracellular levels of CDDP were decreased by 2.03-fold in CNE2-CDDP and 2.78-fold in CNE2-CDDP-5Fu. After treatment with PSC833, a modulator of MDR associated transporters including ABCC2, the intracellular level of CDDP was increased in CDDP-resistant sublines, and the resistance to CDDP was partially reversed from 2.63-fold to 1.62-fold in CNE2-CDDP and from 5.35-fold to 4.62-fold in CNE2-CDDP-5Fu. These data indicate that ABCC2 may play an important role in NPC resistant to CDDP.

  12. Plasma microRNA profiling in nasopharyngeal carcinoma patients revealsmiR-548q andmiR-483-5p as potential biomarkers

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    Xiao-Hui Zheng; Cui Cui; Hong-Lian Ruan; Wen-Qiong Xue; Shao-Dan Zhang; Ye-Zhu Hu; Xin-Xi Zhou; Wei-Hua Jia

    2014-01-01

    MicroRNAs (miRNAs), which play a role in tumorigenesis, may also serve as diagnostic or prognostic biomarkers. However, studies on human miRNA profiles in plasma from nasopharyngeal carcinoma (NPC) patients are in their infancy. Here, we used microarrays to perform systematic profiling of human miRNAs in plasma from NPC patients. We subsequently used real-time quantitative polymerase chain reaction (Q-PCR) to validate miRNAs with aberrant expression that could serve as potential biomarkers. By comparing the plasma miRNA profiles of 31 NPC patients and 19 controls, 39 of 887 human miRNAs were found to be aberrantly expressed. Considering the fold change andP value,miR-548q andmiR-483-5p were validated in 132 samples from 82 NPC patients and 50 controls. Moreover, high expression of miR-548q andmiR-483-5p was further found in 3 NPC celllines and clinical biopsy tissues from 54 NPC patients and 22 controls. Our results revealed thatmiR-548q andmiR-483-5p are potential biomarkers of NPC. Combining the receiver operating characteristic (ROC) analyses of these 2 miRNAs, an area under the ROC curve (AUC) of 0.737 with 67.1% sensitivity and 68.0% specificity were obtained, showing the preliminary diagnostic value of plasma miRNAs. Moreover, most NPC patients with a poor outcome exhibited high expression (> median) ofmiR-548q (70.6%) andmiR-483-5p (64.7%) in tissue samples, indicating their prognostic value. The high expression levels ofmiR-548q andmiR-483-5p in plasma, celllines, and clinical tissues of NPC patients indicate that their roles in NPC should be explored in the future.

  13. High cell density and latent membrane protein 1 expression induce cleavage of the mixed lineage leukemia gene at 11q23 in nasopharyngeal carcinoma cell line

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    Sim Sai-Peng

    2010-09-01

    Full Text Available Abstract Background Nasopharyngeal carcinoma (NPC is commonly found in Southern China and South East Asia. Epstein-Barr virus (EBV infection is well associated with NPC and has been implicated in its pathogenesis. Moreover, various chromosome rearrangements were reported in NPC. However, the underlying mechanism of chromosome rearrangement remains unclear. Furthermore, the relationship between EBV and chromosome rearrangement with respect to the pathogenesis of NPC has not been established. We hypothesize that during virus- or stress-induced apoptosis, chromosomes are initially cleaved at the base of the chromatin loop domain structure. Upon DNA repair, cell may survive with rearranged chromosomes. Methods In this study, cells were seeded at various densities to induce apoptosis. Genomic DNA extracted was processed for Southern hybridization. In order to investigate the role of EBV, especially the latent membrane protein 1 (LMP1, LMP1 gene was overexpressed in NPC cells and chromosome breaks were analyzed by inverse polymerase chain (IPCR reaction. Results Southern analysis revealed that high cell density resulted in cleavage of the mixed lineage leukemia (MLL gene within the breakpoint cluster region (bcr. This high cell density-induced cleavage was significantly reduced by caspase inhibitor, Z-DEVD-FMK. Similarly, IPCR analysis showed that LMP1 expression enhanced cleavage of the MLL bcr. Breakpoint analysis revealed that these breaks occurred within the matrix attachment region/scaffold attachment region (MAR/SAR. Conclusions Since MLL locates at 11q23, a common deletion site in NPC, our results suggest a possibility of stress- or virus-induced apoptosis in the initiation of chromosome rearrangements at 11q23. The breakpoint analysis results also support the role of chromatin structure in defining the site of chromosome rearrangement.

  14. Embryonic stem cells markers SOX2, OCT4 and Nanog expression and their correlations with epithelial-mesenchymal transition in nasopharyngeal carcinoma.

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    Weiren Luo

    Full Text Available Expression of embryonic stem cells (ESCs markers (SOX2, OCT4, Nanog and Nestin is crucial for progression of various human malignancies. The purpose of this study was to investigate the expression and prognostic impact of these molecules in nasopharyngeal carcinoma (NPC patients by immunohistochemistry and immunofluorescence. In the present study, we found that the expression levels of SOX2, OCT4 and Nanog were highly expressed in NPC compared with the non-tumorous tissues. Furthermore, these proteins correlated significantly with several clinicalpathological factors and epithelial-mesenchymal transition (EMT-associated indicators (E-cadherin/N-cadherin and Snail. In multivariate analyses, high expression of OCT4 (P = 0.013 and Nanog (P = 0.040, but not that of SOX2, was associated with worse survival and had strongly independent prognostic effects. Of note, OCT4 and Nanog were more frequently located at the invasive front of tumors, and correlated significantly with various aggressive behaviors including T classification, N classification, M classification and clinical stage. Furthermore, patients with co-expression of OCT4 and Nanog in the invasive front had significantly worse survival (P = 0.005. Interestingly, at the invasive front, these molecules correlated significantly with Nestin expression in endothelial cells (P<0.001. These findings provide evidence that ESCs biomarkers OCT4 and Nanog serves as independent prognostic factors for NPC. Additionally, cancer cells in the invasive front of NPC acquiring ESCs-like features should be maintained by vascular niches.

  15. The correlation between the comprehensive nutrition index and quality of life of patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy.

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    Ma, Liqin; Wu, Tingting; Pan, Jianji; Kong, Xiangquan; Guo, Qiaojuan; Yang, Ling; Zhang, Yu; Lin, Shaojun; Chen, Chuanben; Huang, Chaobin

    2014-01-01

    The purpose of this study was to compare the changing tendency of nutrition with 54 nasopharyngeal carcinoma patients during intensity-modulated radiation therapy (IMRT), and to investigate the correlation between comprehensive nutritional status and quality of life (QoL), which was assessed by the European Organization for Research and Treatment of Cancer Core Quality-of-Life Questionnaire. The nutritional index, including body mass index, ideal body weight percentage, usual body weight percentage, albumin, hemoglobin, and total lymphocyte count (TLC), was evaluated at 2 time points: within 48 h after admission (T1) and at the end of treatment with IMRT (T2). A statistically significant downgrade of every index was observed during IMRT. A comprehensive nutritional model was established by principal components analysis at T2. QoL scores of functional (P = 0.002) and the global QoL scales (P = 0.001) existed a positive correlation with comprehensive nutritional status. QoL scores of symptom scales (P = 0.002) and 6 single items (P = 0.005) had a negative correlation with it. The scores of global QoL scales in comprehensive nutrition of normal (20.4%), moderate (55.6%), and severe malnutrition (24.1%) were 69.70 ± 17.98, 48.33 ± 19.25, and 37.18 ± 24.67, respectively. Patients with different nutritional status had different QoL (B = 10.405, SE = 2.828, t = 3.680, P = 0.001). Multiaspect nutritional supports should be enhanced to improve patients' comprehensive nutritional status during treatment.

  16. Radiation-induced changes in normal-appearing gray matter in patients with nasopharyngeal carcinoma: a magnetic resonance imaging voxel-based morphometry study

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    Lv, Xiao-Fei; Zheng, Xiao-Li; Zhang, Wei-Dong; Liu, Li-Zhi; Zhang, You-Ming [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 Imaging and Interventional Radiology, Guangzhou (China); Chen, Ming-Yuan [Sun Yat-sen University Cancer Center, Department of Nasopharyngeal Carcinoma, Guangzhou (China); Li, Li [Sun Yat-sen University Cancer Center, Department of Medical Imaging and Interventional Radiology, Guangzhou (China)

    2014-05-15

    Evidence is accumulating that temporal lobe radiation necrosis in patients with nasopharyngeal carcinoma (NPC) after radiotherapy (RT) could involve gray matter (GM). The purpose of the study was to assess the radiation-induced GM volume differences between NPC patients who had and had not received RT and the effect of time after RT on GM volume differences in those patients who had received RT. We used magnetic resonance imaging voxel-based morphometry (VBM) to assess differences in GM volume between 30 NPC patients with normal-appearing whole-brain GM after RT and 15 control patients with newly diagnosed but not yet medically treated NPC. Correlation analyses were used to investigate the relationship between GM volume changes and time after RT. Patients who had received RT had GM volume decreases in the bilateral superior temporal gyrus, left middle temporal gyrus, right fusiform gyrus, right precentral gyrus, and right inferior parietal lobule (p < 0.001, uncorrected, cluster size >100 voxels). Moreover, the correlation analysis indicated that regional GM volume loss in the left superior temporal gyrus, left middle temporal gyrus, and right fusiform gyrus were negatively related to the mean dose to the ipsilateral temporal lobe, respectively. These results indicate that GM volume deficits in bilateral temporal lobes in patients who had received RT might be radiation-induced. Our findings might provide new insight into the pathogenesis of radiation-induced structural damage in normal-appearing brain tissue. Yet this is an exploratory study, whose findings should therefore be taken with caution. (orig.)

  17. Molecular characterization and clinical implications of spindle cells in nasopharyngeal carcinoma: a novel molecule-morphology model of tumor progression proposed.

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    Weiren Luo

    Full Text Available Up to now, the precise molecular and morphological changes underlying the invasive and metastatic properties of nasopharyngeal carcinoma (NPC remain largely unresolved. We speculate that neoplastic spindle cells, which are prominently found in the invasive tumor front and the surrounding stroma, might be responsible for the aggressive patterns. Expression profiling of various biomarkers relevant to cancer stem cells (CSCs and epithelial-mesenchymal transition (EMT was performed by tissue microarray-based immunohistochemistry in NPC samples. The expression of EBER and LMP1 was detected by in situ hybridization and immunohistochemistry, respectively. We found that overexpression of CSCs-related markers (ALDH1, Nanog and ABCG2 and up-regulation of EMT markers (Fibronectin, MMP-2, Periostin, SPARC, Snail and Slug, together with E- to N-cadherin switching, occurred preferentially in tumors containing a large proportion of spindle-shaped malignant cells. Furthermore, CSCs-like properties were highly present in spindle cells compared with non-spindle cells of tumors, and correlated strongly with EMT features. In addition, EBV-related factors EBER and LMP1 were highly expressed and correlated strongly with CSCs and EMT characteristics in neoplastic spindle cells. Importantly, high proportion of spindle cells (≥20% correlated significantly with various aggressive aspects including lymph node metastasis (P = 0.031 and local recurrence (P = 0.014. Patients with high proportion of spindle cells had poor survival (P = 0.004, though it was not an independent value. In conclusion, we demonstrate that spindle cells could be valuable morphological indicators of tumor progression and unfavorable prognosis of NPC. An integrated molecule-morphology model of NPC firstly constructed may shed significant light on the metastatic cascade and clinical relevance of patients.

  18. Distribution, characterization, and induction of CD8+ regulatory T cells and IL-17-producing CD8+ T cells in nasopharyngeal carcinoma

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    Li Jiang

    2011-11-01

    Full Text Available Abstract Background CD8+ effector cells often have an antitumor function in patients with cancer. However, CD8+Foxp3+ regulatory T cells (Tcregs and interleukin (IL-17-producing CD8+ T cells (Tc17 cells also derive from the CD8+ T cell lineage. Their role in the antitumor response remains largely unknown. In the present study, we aimed to investigate the distribution, characterization, and generation of CD8+ Tcregs and Tc17 cells in NPC patients. Methods Peripheral blood and tumor biopsy tissues from 21 newly diagnosed patients with nasopharyngeal carcinoma (NPC were collected, along with peripheral blood from 21 healthy donors. The biological characteristics of Tcregs and Tc17 cells from blood and tumor tissues were examined by intracellular staining, tetramer staining and fluorescence-activated cell sorting (FACS analysis. The suppressive function of Tcregs was investigated using a proliferation assay that involved co-culture of sorted CD8+CD25+ T cells with naïve CD4+ T cells in vitro. Results We observed an increased prevalence of Tcregs and Tc17 cells among tumor-infiltrating lymphocytes (TILs and different distribution among peripheral blood mononuclear cells (PBMCs in NPC patients. Cytokine profiles showed that the Tcregs expressed a high level of IL-10 and low level of transforming growth factor β, whereas Tc17 cells expressed a high level of tumor necrosis factor α. Interestingly, both subsets expressed a high level of interferon γ in TILs, and the Tcregs suppressed naïve CD4+ T cell proliferation by a cell contact-dependent mechanism in vitro. Moreover, we demonstrated the existence of Epstein-Barr virus latent membrane protein (LMP 1 and LMP2 antigen-specific Tcregs in NPC. Conclusions Our data provide new insights into the composition and function of CD8+ T-cell subsets in NPC, which may have an important influence on NPC immunotherapy.

  19. A risk score model for the metastasis of level Ib lymph node based on the clinicopathological features of nasopharyngeal carcinoma in a large sample.

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    Yi, Wei; Li, Xian; Liu, Zhigang; Jiang, Changbin; Niu, Daoli; Xia, Yunfei

    2014-09-01

    The aim of the present study was to develop a metastatic risk score model of neck level Ib lymph nodes in primary nasopharyngeal carcinoma (NPC) to guide the level Ib radiotherapy. There were a total of 1,557 patients enrolled in the study, and of these patients, 1,145 were included in the training set. Univariate χ(2) analysis and multivariate logistic regression analyses were used to screen the independent risk factors to construct the risk score model. A total of 85 patients in the validating set underwent a pathology biopsy of level Ib lymph nodes to test the model. The remaining 327 patients from the prognostic-research set were used to evaluate the prognostic impact of level Ib irradiation in high- and low-risk groups. The independent risk factors in the model were carotid sheath involvement, the maximal diameter of the neck lymph nodes (≥20 mm) and the involvement of the level II/III/IV lymph nodes. The involvement of level IV was assigned score 2 and the other risk factors were assigned score 1. According to the total scores, the patients were divided into the low- (total score, 0-1; level Ib metastasis rate, 0.5%) and high-risk groups (total score, 2-4; level Ib metastasis rate, 8.5%). In the validating set, the metastatic rate of level Ib in 43 low-risk patients was 0%, and the rate was 31.0% (13/42) in 42 high-risk patients. In the prognostic-research set, the prognosis of 137 low-risk patients was not affected by level Ib irradiation. However, level Ib unirradiation was an independent prognostic factor for the locoregional recurrence in 190 high-risk patients. According to the data, the novel score model could help assess the metastatic risk of level Ib in primary NPC, and the radiotherapy on level Ib may impact the locoregional recurrence in high-risk patients.

  20. Epstein-Barr virus glycoprotein gH/gL antibodies complement IgA-viral capsid antigen for diagnosis of nasopharyngeal carcinoma.

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    Li, Rui-Chen; Du, Yong; Zeng, Qiu-Yao; Tang, Lin-Quan; Zhang, Hua; Li, Yan; Liu, Wan-Li; Zhong, Qian; Zeng, Mu-Sheng; Huang, Xiao-Ming

    2016-03-29

    To determine whether measuring antibodies against Epstein-Barr virus (EBV) glycoprotein gH/gL in serum could improve diagnostic accuracy in nasopharyngeal carcinoma (NPC) cases, gH/gL expressed in a recombinant baculovirus system was used in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in two independent cohorts. Binary logistic regression analyses were performed using results from a training cohort (n = 406) to establish diagnostic mathematical models, which were validated in a second independent cohort (n = 279). Levels of serum gH/gL antibodies were higher in NPC patients than in healthy controls (p gH/gL ELISA had a sensitivity of 83.7%, specificity of 82.3% and area under the curve (AUC) of 0.893 (95% CI, 0.862-0.924) for NPC diagnosis. Furthermore, gH/gL maintained diagnostic capacity in IgA-VCA negative NPC patients (sensitivity = 78.1%, specificity = 82.3%, AUC = 0.879 [95% CI, 0.820 - 0.937]). Combining gH/gL and viral capsid antigen (VCA) detection improved diagnostic capacity as compared to individual tests alone in both the training cohort (sensitivity = 88.5%, specificity = 97%, AUC = 0.98 [95% CI, 0.97 - 0.991]), and validation cohort (sensitivity = 91.2%, specificity = 96.5%, AUC = 0.97 [95% CI, 0.951-0.988]). These findings suggest that EBV gH/gL detection complements VCA detection in the diagnosis of NPC and aids in the identification of patients with VCA-negative NPC.

  1. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

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    Twu, Chih-Wen [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, Wen-Yi [Section of Basic Medicine, Department of Nursing, Hung Kuang University, Taichung, Taiwan (China); Chen, Chien-Chih [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Liang, Kai-Li; Jiang, Rong-San [Department of Otorhinolaryngology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wu, Ching-Te [Department of Radiation Oncology, Taichung Veterans General Hospital–Chiayi Branch, Chiayi, Taiwan (China); Shih, Yi-Ting [Department of Radiation Oncology, St. Martin De Porres Hospital, Chiayi, Taiwan (China); Lin, Po-Ju; Liu, Yi-Chun [Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Lin, Jin-Ching, E-mail: jclin@vghtc.gov.tw [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine, China Medical University, Taichung, Taiwan (China)

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  2. Repressing malic enzyme 1 redirects glucose metabolism,unbalances the redox state, and attenuates migratory and invasive abilities in nasopharyngeal carcinoma cell lines

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    Fang-Jing Zheng; Hao-Bin Ye; Man-Si Wu; Yi-Fan Lian; Chao-Nan Qian; Yi-Xin Zeng

    2012-01-01

    A large amount of nicotinamide adenine dinucleotide phosphate (NADPH) is required for fatty acid synthesis and maintenance of the redox state in cancer cells.Malic enzyme 1 (ME1)-dependent NADPH production is one of the three pathways that contribute to the formation of the cytosolic NADPH pool.ME1 is generally considered to be overexpressed in cancer cells to meet the high demand for increased de novo fatty acid synthesis.In the present study,we found that glucose induced higher ME1 activity and that repressing ME1 had a profound impact on glucose metabolism of nasopharyngeal carcinoma (NPC) cells.High incorporation of glucose and an enhancement of the pentose phosphate pathway were observed in ME1-repressed cells.However,there were no obvious changes in the other two pathways for glucose metabolism:glycolysis and oxidative phosphorylation.Interestingly,NADPH was decreased under lowglucose condition in ME1-repressed cells relative to wild-type cells,whereas no significant difference was observed under high-glucose condition.ME1-repressed cells had significantly decreased tolerance to lowglucose condition.Moreover,NADPH produced by ME1 was not only important for fatty acid synthesis but also essential for maintenance of the intracellular redox state and the protection of cells from oxidative stress.Furthermore,diminished migration and invasion were observed in ME1-repressed cells due to a reduced level of Snail protein.Collectively,these results suggest an essential role for ME1 in the production of cytosolic NADPH and maintenance of migratory and invasive abilities of NPC cells.

  3. Effect of Dosimetric Factors on Occurrence and Volume of Temporal Lobe Necrosis Following Intensity Modulated Radiation Therapy for Nasopharyngeal Carcinoma: A Case-Control Study

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    Zhou, Xin; Ou, Xiaomin; Xu, Tingting; Wang, Xiaosheng; Shen, Chunying [Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai (China); Ding, Jianhui [Department of Diagnostic Radiology, Fudan University Shanghai Cancer Center, Shanghai (China); Hu, Chaosu, E-mail: hucsu62@yahoo.com [Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai (China)

    2014-10-01

    Purpose: To determine dosimetric risk factors for the occurrence of temporal lobe necrosis (TLN) among nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT) and to investigate the impact of dose-volume histogram (DVH) parameters on the volume of TLN lesions (V-N). Methods and Materials: Forty-three NPC patients who had developed TLN following IMRT and 43 control subjects free of TLN were retrospectively assessed. DVH parameters included maximum dose (Dmax), minimum dose (Dmin), mean dose (Dmean), absolute volumes receiving specific dose (Vds) from 20 to 76 Gy (V20-V76), and doses covering certain volumes (Dvs) from 0.25 to 6.0 cm{sup 3} (D0.25-D6.0). V-Ns were quantified with axial magnetic resonance images. Results: DVH parameters were ubiquitously higher in temporal lobes with necrosis than in healthy temporal lobes. Increased Vds and Dvs were significantly associated with higher risk of TLN occurrence (P<.05). In particular, Vds at a dose of ≥70 Gy were found with the highest odds ratios. A common increasing trend was detected between V-N and DVH parameters through trend tests (P for trend of <.05). Linear regression analysis showed that V45 had the strongest predictive power for V-N (adjusted R{sup 2} = 0.305, P<.0001). V45 of <15.1 cm{sup 3} was relatively safe as the dose constraint for preventing large TLN lesions with V-N of >5 cm{sup 3}. Conclusions: Dosimetric parameters are significantly associated with TLN occurrence and the extent of temporal lobe injury. To better manage TLN, it would be important to avoid both focal high dose and moderate dose delivered to a large area in TLs.

  4. MICA Gene Deletion in 3411 DNA Samples from Five Distinct Populations in Mainland China and Lack of Association with Nasopharyngeal Carcinoma (NPC) in a Southern Chinese Han population.

    Science.gov (United States)

    Wang, WenYi; Tian, Wei; Zhu, FaMing; Li, LiXin; Cai, JinHong; Wang, Fan; Liu, KangLong; Jin, HeKun; Wang, JunLong

    2016-11-01

    Deletion of major histocompatibility complex class I chain-related genes A (MICA*Del) was investigated in 3,411 DNA samples from two southern Chinese Han populations (Hunan Han, HNH; Guangdong Han, GDH), two northern Chinese populations (Inner Mongolia Han, IMH; Inner Mongolia Mongol, IMM) and one southeastern Chinese Han population (Fujian Han, FJH) using an in-house polymerase chain reaction-sequence specific priming (PCR-SSP) assay, which enables direct discrimination between heterozygote and homozygote for MICA*Del. MICA*Del showed a frequency ranging from 0.8% in FJH to 5.7% in IMM (Pcorrected populations. In contrast to the association reported recently in a Taiwan Chinese population and a Malaysian Chinese cohort, MICA*Del distribution did not differ between 1,120 patients with nasopharyngeal carcinoma (NPC) and 1,483 normal controls in the HNH population (1.03% in NPC cases vs 1.18% in the controls, OR (95% CI) = 0.87 (0.51-1.47), p = 0.69). Further gender-stratified analysis also failed to disclose any male-specific association reported in a Taiwan Chinese population. Multi-locus typing of the 94 samples carrying MICA*Del revealed two new haplotypes, HLA-A*11:01-B*13:01-MICA*Del-MICB*009N-DRB1*04:06 and HLA-B*35:01-MICA*Del-MICB*009N-DRB1*15:01, in addition to HLA-B*48-MICA*Del. Unexpectedly, two samples with MICA*Del in the HNH population were each consistently found to have two distinct MICA alleles, indicating the existence of two MICA gene copies on certain HLA haplotypes. Based on the results from a sizeable case-control study, our data suggest that there is no association between MICA*Del and NPC in the southern Chinese Han population.

  5. 实时荧光定量RT-PCR检测鼻咽癌Survivin mRNA基因表达%Detection of Survivin mRNA in nasopharyngeal carcinoma by real-time fluorescence quantitative RT-PCR

    Institute of Scientific and Technical Information of China (English)

    Shengmiao Fu; Junhong Cai; Zhihua Tu; Yutian Wang; Liqun Deng; Zhu Liang; Zhenqun Lin; Xuanju Gong

    2008-01-01

    Objective:To establish the method of real time fluorescence quantitative RT-PCR for detecting the expression of Survivin mRNA in nasopharyngeal carcinoma (NPC) tissues.Methods:The total RNA was extracted from NPC cell line CNE-2 and tissues with Trizol and then been transcribed reversely to cDNA,a method of real time fluorescence quantitative RT-PCR for detecting the expression of Survivin mRNA in NPC tissues had been established,in which chronic nasopharyngitis patients' nasopharynx tissues treated as control group.Results:The expression of Survivin mRNA all could be detected either in CNE-2 cells,NPC tissues or in chronic nasopharyngitis patients' nasopharynx tissues,and there was higher the expression level of Survivin mRNA in NPC tissues than which in chronic nasopharyngitis patients' nasopharynx tissues,the difference was significant (P<0.01).The expression of Survivin mRNA could be detected both in stage Ⅰ+Ⅱ and stage Ⅲ+Ⅳ NPC,and there was no significant difference in relative quantifications of gene expression between these two groups (P>0.05).There was no relationship between Survivin mRNA expression and age and sex of NPC patients (P>0.05).Conclusion:Real time fluorescence quantitative RT-PCR is a rapid,effective and high sensitive method for detecting the expression of Survivin mRNA in NPC tissues.The overexpression of Survivin mRNA may play some roles in pathogenesis of NPC.

  6. Study of consolidation chemotherapy in advanced epithelial ovarian carcinoma

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    Cheng Ning-hai; Huang Hui-fang; Pan Lin-ya; Shen Keng; Wu Ming; Yang Jia-xin

    2007-01-01

    Objective: A prospective randomized study was designed to evaluate the role of consolidation chemotherapy in advanced epithelial ovarian carcinoma.Methods: 50 patients with advanced epithelial ovarian carcinoma treated in our hospital during the period from March 2000 to October 2005 were enrolled in this study.All patients had achieved clinical complete remission by means of standard treatments, and were randomly divided into consolidation chemotherapy group and control group.Relapse rate, and disease-free survival(DFS) time were analyzed in both groups.Results: 24 patients were assigned in consolidation chemotherapy group, and 26 patients in control group.Tumor relapse interval in consolidation group was (26.5±7.4) months, vs.(16.8±7.0) months in control group respectively, P=0.001.Time to relapse(TTR) in consolidation group was (19.2±6.8) months, vs.(10.0±6.9)months in control group, P=0.002.Analysis of DFS time and overall survival time, Log Rank test:P=0.042 and P= 0.062, respectively.Conclusions: Consolidation chemotherapy could be the relevant factor that postpones tumor relapse interval and prolongs DFS time in advanced epithelial ovarian carcinoma patients who had achived chlinical complete remission.But so far the statistic result of our clinical study is beyond the conclusion that consolidation chemotherapy can decrease relapse rate or increase survival rate.Muhicenter randomized clinical trial should be performed to confirm the role of consolidation chemotherapy in advanced epithelial ovarian carcinoma.

  7. Combined modality therapy for locally advanced penile squamous cell carcinoma.

    Science.gov (United States)

    Pedrick, T J; Wheeler, W; Riemenschneider, H

    1993-12-01

    We report here a patient who presented with locally advanced Jackson Stage IV penile squamous cell carcinoma who was managed with preoperative 5-fluorouracil, mitomycin C chemotherapy, and concurrent radiation therapy. He experienced an excellent partial response which allowed more limited surgery than would otherwise be indicated. He is still