Epstein-Barr virus infection and nasopharyngeal carcinoma.

PubMed

Tsao, Sai Wah; Tsang, Chi Man; Lo, Kwok Wai

2017-10-19

Epstein-Barr virus (EBV) is associated with multiple types of human cancer, including lymphoid and epithelial cancers. The closest association with EBV infection is seen in undifferentiated nasopharyngeal carcinoma (NPC), which is endemic in the southern Chinese population. A strong association between NPC risk and the HLA locus at chromosome 6p has been identified, indicating a link between the presentation of EBV antigens to host immune cells and NPC risk. EBV infection in NPC is clonal in origin, strongly suggesting that NPC develops from the clonal expansion of a single EBV-infected cell. In epithelial cells, the default program of EBV infection is lytic replication. However, latent infection is the predominant mode of EBV infection in NPC. The establishment of latent EBV infection in pre-invasive nasopharyngeal epithelium is believed to be an early stage of NPC pathogenesis. Recent genomic study of NPC has identified multiple somatic mutations in the upstream negative regulators of NF-κB signalling. Dysregulated NF-κB signalling may contribute to the establishment of latent EBV infection in NPC. Stable EBV infection and the expression of latent EBV genes are postulated to drive the transformation of pre-invasive nasopharyngeal epithelial cells to cancer cells through multiple pathways.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Author(s).

Chromosome 3p12.3-p14.2 and 3q26.2-q26.32 are genomic markers for prognosis of advanced nasopharyngeal carcinoma.

PubMed

Sheu, Jim Jinn-Chyuan; Lee, Chia-Huei; Ko, Jenq-Yuh; Tsao, George S W; Wu, Chung-Chun; Fang, Chih-Yeu; Tsai, Fuu-Jen; Hua, Chun-Hung; Chen, Chi-Long; Chen, Jen-Yang

2009-10-01

Nasopharyngeal carcinoma is an epithelial malignancy with a remarkable racial and geographic distribution. Previous cytogenetic studies have shown nasopharyngeal carcinoma to be characterized by gross genomic aberrations. However, identification of susceptible gene loci in advanced nasopharyngeal carcinoma has been poorly discussed. A genome-wide survey of gene copy number changes was initiated with two nasopharyngeal carcinoma cell lines by array-based comparative genomic hybridization analysis. These alterations were confirmed by a parallel analysis with the data from the gene expression microarray and were validated by quantitative PCR. Clinical association of the defined target genes was analyzed by fluorescence in situ hybridization on 48 metastatic tumors. A high percentage of genes were consistently altered in dosage and expression levels with gain on 3q26.2-q26.32 and losses on 3p12.3-p14.2 and 9p21.3-p23. Six candidate genes, GPR160 (3q26.2-q27), SKIL (3q26), ADAMTS9 (3p14.2-p14.3), LRIG1 (3p14), MPDZ (9p22-p24), and ADFP (9p22.1) were validated by quantitative PCR. Fluorescence in situ hybridization studies revealed amplification of GPR160 (in 25% of cases) and SKIL (33%); and deletion of ADAMTS9 (30%), LRIG1 (35%), MPDZ (15%), and ADFP (15%). Clinical association analyses indicated a poor survival rate with genetic alterations at the defined 3p deletion (P = 0.0012) and the 3q amplification regions (P = 0.0114). The combined microarray technologies suggested novel candidate oncogenes, amplification of GPR160 and SKIL at 3q26.2-q26.32, and deletion of tumor suppressor genes ADAMTS9 and LRIG1 at 3p12.3-p14.2. Altered expression of these genes may be responsible for malignant progression and could be used as potential markers for nasopharyngeal carcinoma.

Multiparametric Detection of Antibodies against Different EBV Antigens to Predict Risk for Nasopharyngeal Carcinoma in a High-Risk Population of China.

PubMed

Chen, Hao; Chen, Shulin; Lu, Jie; Wang, Xueping; Li, Jianpei; Li, Linfang; Fu, Jihuan; Scheper, Thomas; Meyer, Wolfgang; Peng, Yu-Hui; Liu, Wanli

2017-09-01

In this study, we aimed to use the combined detection of multiple antibodies against Epstein-Barr virus (EBV) antigens to develop a model for screening and diagnosis of nasopharyngeal carcinoma (NPC). Samples of 300 nasopharyngeal carcinoma patients and 494 controls, including 294 healthy subjects (HC), 99 non-nasopharyngeal carcinoma cancer patients (NNPC), and 101 patients with benign nasopharyngeal lesions (BNL), were incubated with the EUROLINE Anti-EBV Profile 2, and band intensities were used to establish a risk prediction model. The nasopharyngeal carcinoma risk probability analysis based on the panel of VCAgp125 IgA, EBNA-1 IgA, EA-D IgA, EBNA-1 IgG, EAD IgG, and VCAp19 IgG displayed the best performance. When using 26.1% as the cutoff point in ROC analysis, the AUC value and sensitivity/specificity were 0.951 and 90.7%/86.2%, respectively, in nasopharyngeal carcinoma and all controls. In nasopharyngeal carcinoma and controls without the non-nasopharyngeal carcinoma and BNL groups, the AUC value and sensitivity/specificity were 0.957 and 90.7%/88.1%, respectively. The diagnostic specificity and sensitivity of the EUROLINE Anti-EBV Profile 2 assay for both nasopharyngeal carcinoma and early-stage nasopharyngeal carcinoma were higher than that of mono-antibody detection by immune-enzymatic assay and real-time PCR (EBV DNA). In the VCA-IgA-negative group, 82.6% of nasopharyngeal carcinoma patients showed high probability for nasopharyngeal carcinoma, and the negative predictive value was 97.1%. In the VCA-IgA-positive group, 73.3% of healthy subjects showed low probability. The positive predictive value reached 98.2% in this group. The nasopharyngeal carcinoma risk probability value determined by the EUROLINE Anti-EBV Profile 2 might be a suitable tool for nasopharyngeal carcinoma screening. Cancer Prev Res; 10(9); 542-50. ©2017 AACR . ©2017 American Association for Cancer Research.

Identification of nasopharyngeal carcinoma from photoluminescence spectra of 3C-SiC nanocrystals

NASA Astrophysics Data System (ADS)

Wang, Li-Fen; Guo, Jun-Hong; Huang, Zhi-Chun; Gu, Jian-Sen; Feng, Li-Ren; Liu, Li-Zhe

2017-09-01

The identification of intracellular pH (pHi) during carcinogenesis progression plays a crucial role in the studies of biochemistry, cytology, and clinical medicine. In this work, 3C-SiC nanocrystals (NCs), which can effectively monitor the pH environment by using the linear relation between photoluminescence intensity and surface OH- and H+ concentration, are adapted as fluorescent probes for monitoring carcinogenesis progression of nasopharyngeal carcinoma. Our results demonstrated that 3C-SiC NCs are compatible with living cells and have low cytotoxicity. The pHi measurements in different carcinogenesis environments indicate the validity and sensitivity of this technology in identifying nasopharyngeal carcinoma in application.

RNA Related to That of a Murine Leukemia Virus in Burkitt's Tumors and Nasopharyngeal Carcinomas

PubMed Central

Kufe, D.; Hehlmann, R.; Spiegelman, S.

1973-01-01

RNA homologous to that of the Rauscher leukemia virus has been detected in Burkitt's lymphomas and nasopharyngeal carcinomas. Earlier excellent experimental evidence has linked these two human tumors with the Epstein-Barr virus, a DNA-containing agent. PMID:4346039

Incidence of nasopharyngeal carcinoma in Chinese immigrants, compared with Chinese in China and South East Asia: review.

PubMed

Yu, W M; Hussain, S S M

2009-10-01

To evaluate the literature and to compare published data on age-standardised incidence rates of nasopharyngeal carcinoma in Chinese people living in and outside China. Systematic review of incidence rate studies and statistical incidence data concerning nasopharyngeal carcinoma in Chinese populations from 1960 to 2008. Sixteen papers were identified from the PubMed, Embase and Scopus electronic databases and from a hand search of the reference lists of the retrieved papers. Further searches for raw data on age-specific and age-standardised incidence rates of nasopharyngeal carcinoma were conducted. Textbooks on relevant subjects were referred to for background information. A total of 19 papers met the inclusion criteria. Seven studies included raw data on age-specific and age-standardised incidence rates of nasopharyngeal carcinoma in Chinese people. Twelve other studies reported on changes in the incidence of nasopharyngeal carcinoma in Chinese populations in selected countries or regions. Studies on age-specific and age-standardised rates obtained data from individual registries. Studies on incidence rates obtained data from hospital records, cancer notifications (from all sections of the medical profession), pathology records and death certificates. The results showed a decline in age-standardised incidence rates of nasopharyngeal carcinoma in Chinese immigrant populations, compared with Chinese people in China. There was also a trend towards decreasing incidence the further the population had immigrated. Thus, the incidence of nasopharyngeal carcinoma in Singaporean Chinese was higher than that in Hawaiian Chinese, and that in Hawaiian Chinese was higher than that in Californian Chinese. This review found a decreasing trend in the incidence of nasopharyngeal carcinoma in Chinese migrants living in countries with a low risk of the disease.

Habitual Consumption of Soy Products and Risk of Nasopharyngeal Carcinoma in Chinese Adults: A Case-Control Study

PubMed Central

Liu, Yuan-ting; Fan, Yu-ying; Xu, Chun-hua; Lin, Xiao-ling; Lu, Yun-kai; Zhang, Xing-lan; Zhang, Cai-xia; Chen, Yu-ming

2013-01-01

Background and Objectives Many studies have shown a negative association between the consumption of soy products and the risk of some cancers, but little is known about the effect of soy consumption on nasopharyngeal carcinoma. We assessed the association between the consumption of soy products on nasopharyngeal carcinoma risk in Chinese individuals. Methods This case-control study included 600 (448 males and 152 females) incident cases of nasopharyngeal carcinoma, and an equal number of controls, matched according to gender, age (± 3 y) and household type to the nasopharyngeal carcinoma cases. All subjects were recruited from hospitals in Guangzhou, China. A face-to-face interview was conducted with each study individual to collect general information and habitual dietary intake using a 78-item quantitative food-frequency questionnaire. Odds ratios and their 95% confidence intervals were estimated using conditional logistic regression analyses. Results The median intakes of soy foods (in protein) were 0.5/0.5, 1.4/1.7, 2.7/3.3 and 6.1/7.7 (male/female) g/d in the quartiles 1 to 4. Both univariate and multivariate analyses showed no significant association between the consumption of soy proteins or soy isoflavones and the risk of nasopharyngeal carcinoma. The adjusted odds ratios (95% confidence intervals) between extreme quartiles were 0.97 (0.66-1.45) for soy proteins and 0.97 (0.66-1.42) for total isoflavones. Null associations were also observed between intake of the individual isoflavones daidzein, genistein and glycitein and NPC risk, with adjusted odds ratios for the extreme quartiles ranging between 0.73 and 1.23. Conclusion Habitual consumption of soy products had no significant effect on the risk of nasopharyngeal carcinoma in Chinese adults with a relatively low intake. PMID:24155974

Radiotherapy-induced hypopituitarism in nasopharyngeal carcinoma: the tip of an iceberg.

PubMed

Ipekci, S H; Cakir, M; Kiyici, A; Koc, O; Artac, M

2015-07-01

Radiation-induced hypopituitarism is an important late complication of cranial radiotherapy in children and adults. The purpose of this cross-sectional study was to evaluate the effects of radiotherapy on pituitary function in adult nasopharyngeal carcinoma patients. Pituitary function was evaluated in 30 patients after cranial radiotherapy for nasopharyngeal carcinoma. Somatotroph and corticotroph axes were assessed by insulin tolerance test while gonadotroph and thyroid axes were evaluated by basal pituitary and end organ hormone levels at 10-133 months after radiotherapy. At least one hormonal disorder was observed in 28 (93%) patients after radiotherapy. 26 (87%) patients had one or more anterior pituitary hormone deficiencies. The rates of pituitary hormone deficiencies were 77% for growth hormone, followed by adrenocorticotropic hormone (73%), thyroid-stimulating hormone (27%) and gonadotropins (7%). Hyperprolactinemia was present in 13 (43%) patients. Radiation-induced hypopituitarism is more common than expected in patients with nasopharyngeal carcinoma. © Georg Thieme Verlag KG Stuttgart · New York.

Rare metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes: A case report and literature review.

PubMed

Cai, Changjing; Shen, Hong; Liu, Wenqiang; Ma, Junli; Zhang, Yan; Yin, Ling; Li, Jindong; Shen, Liangfang; Zeng, Shan

2017-11-01

Thyroid metastasis from nasopharyngeal carcinoma is rare. Metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes hasn't been reported before. We want to share our experience about the treatment choice. A 27-year-old man was diagnosed with nasopharyngeal nonkeratinizing carcinoma in August 2004. In March 2013 he underwent a thyroid carcinoma radical operation, and histological examination revealed metastasis to the thyroid gland from nasopharyngeal carcinoma. An 18F-FDG-PET/CT scan and biopsy showed metastatic abdominal lymph nodes of nasopharyngeal carcinoma in April 2015. A 27-year-old man was diagnosed with metastasis of nasopharyngeal carcinoma to the thyroid gland with subsequent metastatic abdominal lymph nodes. The patient was treated with concurrent chemotherapy and radiotherapy for nasopharyngeal carcinoma and metastasis to the thyroid gland. The metastases to the abdominal lymph nodes received chemotherapy. After 6 cycles of chemotherapy with gemcitabine, cisplatin, and 5-fluorouracil for metastasis to the abdominal lymph nodes, the patient is currently asymptomatic with stable disease and improved quality of life. The treatment choice for metastasis of nasopharyngeal carcinoma depends on the clinical disease extent, and surgery and/or chemo-radiation therapy must be drafted to the individual patient in order to improve the prognosis and quality of life.

Comprehensive genomic profiling of different subtypes of nasopharyngeal carcinoma reveals similarities and differences to guide targeted therapy.

PubMed

Ali, Siraj M; Yao, Ming; Yao, Jicheng; Wang, Jing; Cheng, Yuwei; Schrock, Alexa B; Chirn, Gung-Wei; Chen, Hui; Mu, Shuo; Gay, Laurie; Elvin, Julia A; Suh, James; Miller, Vincent A; Stephens, Philip J; Ross, Jeffrey S; Wang, Kai

2017-09-15

To date, no targeted therapy has been approved for nasopharyngeal carcinoma (NPC), and this underscores the need for an in-depth understanding of clinically relevant genomic alterations (CRGAs). Comprehensive genomic profiling was performed for 190 NPC patients, including 20 patients with nasopharyngeal adenocarcinoma (NPAC), 62 patients with nasopharyngeal squamous cell carcinoma (NPSCC), and 108 patients with nasopharyngeal undifferentiated carcinoma (NPUC). The associations of genes and pathways with subtypes, Epstein-Barr virus (EBV) infections, and the tumor mutation burden (TMB) were statistically evaluated. Although the overall rates of genomic alterations were similar, the 3 NPC subtypes exhibited different mutational landscapes. Notably, mutations in a proven-treatable target gene, isocitrate dehydrogenase 2 (IDH2), were significantly associated with NPUC but not with NPAC or NPSCC. The top 5 ranked CRGAs included CDKN2A (29%), IDH2 (16%), SMARCB1 (7%), PIK3CA (6%), and NF1 (5%) in NPUC; CDKN2A (27%), PIK3CA (23%), FBXW7 (11%), PTEN (11%), and EGFR (8%) in NPSCC; and CDKN2A (20%), KRAS (15%), CCND1 (10%), MAP3K1 (10%), and NOTCH1 (10%) in NPAC. The incidence of EBV infections significantly correlated with the subtypes and with TP53, CDKN2A, and CDKN2B. The TMB status correlated with the subtypes and with LRP1B, FBXW7, and PIK3CA mutations as well as DNA repair, phosphoinositide 3-kinase/mammalian target of rapamycin, and mitogen-activated protein kinase pathways. These results indicate that different NPC subtypes harbor different CRGAs. Both EBV infections and the TMB are associated with the NPC subtypes as well as the alterations of individual genes and pathways. The high frequency of IDH2 mutations in NPUC may facilitate potential targeted therapy and will ultimately point to new therapeutic strategies. Cancer 2017;123:3628-37. © 2017 American Cancer Society. © 2017 American Cancer Society.

[Long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma].

PubMed

Zhang, Xiangmin; Yu, Lijiang; Wu, Wei; Wu, Xiuhong; Xiao, Fufu; Zeng, Guoxing; Lan, Xiaolin

2013-02-01

To evaluate the long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma. Sixty-five cases of nasopharyngeal carcinoma patients were randomly divided into study group of 32 patients and control group of 33 patents. The submandibular gland was transferred to submental region on 32 cases with nasopharyngeal carcinoma before receiving conventional radiotherapy and a block was used to cover the submental region. Before radiotherapy, two groups of submandibular gland function was detected by imaging of the submandibular gland. At 60 months after radiotherapy, submandibular gland function was detected by 99mTc radionuclide scanning, the questionnaire about the degree of xerostomia was investigated respectively. Five-year survival rate was counted. After following up for 60 months, submandibular gland uptake and secretion function in the study group was significantly higher than that in the control group, there was significant difference between the two groups (P < 0.01) respectively. The incidence of moderate or severe xerostomia in the study group was significantly lower than that in the control group (15.4% vs 76.9%, P < 0.01). Five-year survival rate of the study group and control group was 81.3% and 78.8% respectively, there was no significant difference between the two groups (P > 0.05). The long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma was well. It could improve the quality of life in nasopharyngeal carcinoma patients after radiotherapy, and did not affect the long-term efficacy of nasopharyngeal carcinoma.

Use Dose Bricks Concept to Implement Nasopharyngeal Carcinoma Treatment Planning

PubMed Central

Wu, Jia-Ming; Yu, Tsan-Jung; Yeh, Shyh-An; Chao, Pei-Ju; Huang, Chih-Jou

2014-01-01

Purpose. A “dose bricks” concept has been used to implement nasopharyngeal carcinoma treatment plan; this method specializes particularly in the case with bell shape nasopharyngeal carcinoma case. Materials and Methods. Five noncoplanar fields were used to accomplish the dose bricks technique treatment plan. These five fields include (a) right superior anterior oblique (RSAO), (b) left superior anterior oblique (LSAO), (c) right anterior oblique (RAO), (d) left anterior oblique (LAO), and (e) superior inferior vertex (SIV). Nondivergence collimator central axis planes were used to create different abutting field edge while normal organs were blocked by multileaf collimators in this technique. Results. The resulting 92% isodose curves encompassed the CTV, while maximum dose was about 115%. Approximately 50% volume of parotid glands obtained 10–15% of total dose and 50% volume of brain obtained less than 20% of total dose. Spinal cord receives only 5% from the scatter dose. Conclusions. Compared with IMRT, the expenditure of planning time and costing, “dose bricks” may after all be accepted as an optional implementation in nasopharyngeal carcinoma conformal treatment plan; furthermore, this method also fits the need of other nonhead and neck lesions if organ sparing and noncoplanar technique can be executed. PMID:24967395

Identification of patients with nasopharyngeal carcinoma by serum protein profiling using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.

PubMed

Zhu, Xiao-Dong; Su, Fang; Liang, Zhong-Guo; Li, Ling; Qu, Song; Liang, Xia; Wang, Qi; Liang, Shi-Xiong; Chen, Long

2014-08-01

As diagnosis of nasopharyngeal carcinoma at an early disease stage is important, we attempted to distinguish between patients with nasopharyngeal carcinoma and noncancer controls by using serum protein profiles. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and CM10 protein chip were used to detect the serum proteomic patterns of 65 patients with nasopharyngeal carcinoma before radiotherapy and 93 noncancer controls. Proteomic spectra of serum samples from 50 nasopharyngeal carcinoma patients and 60 noncancer controls were used as a training set. The validity of the classification tree was then challenged with a blind test set which included another 15 patients with nasopharyngeal carcinoma and 33 noncancer controls. Biomarker Wizard 3.01 and Biomarker Pattern 5.01 were used in combination to analyze the data and to develop diagnostic models. 21 protein peaks were significantly different between nasopharyngeal carcinoma and controls. 4 mass peaks (M4182, M5343, M5913 and M8702 mass/charge ratio) were chosen automatically to construct a classification tree. The classification tree correctly determined 93.8 % (45/48) of the test samples with 93.3 % (14/15) of the nasopharyngeal carcinoma samples and 93.9 % (31/33) of the noncancer samples. Using a combination of serum protein profiles and Epstein-Barr viral capsid antigen immunoglobulin A antibody tests, the diagnostic sensitivity and specificity were increased to 100 and 97 %, respectively. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry could correctly distinguish nasopharyngeal carcinoma from noncancer individuals and showed great potential for the development of a screening test for the detection of nasopharyngeal carcinoma.

Elevated expression of CD93 promotes angiogenesis and tumor growth in nasopharyngeal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bao, Lili; Tang, Mingming; Zhang, Qicheng

2016-08-05

CD93, also known as the complement component C1q receptor (C1qRp), has been reported to promote the progression of some cancer types. However, the expression and physiological significance of CD93 in nasopharyngeal carcinoma (NPC) remain largely elusive. In this study, we first examined the expression of CD93 in NPC and experimentally manipulated its expression. We observed that vascular CD93 expression is elevated in NPC and is correlated with T classification, N classification, distant metastasis, clinical stage and poor prognosis (all P < 0.05). In addition, overexpression of CD93 promoted angiogenesis in vitro. What’s more, we found that CD93 was highly expressed in NPC tissuesmore » and cells, and the regulation of CD93 on cell proliferation was determined by cell counting kit (CCK)-8 assay and cell cycle analyses. Our findings provide unique insight into the pathogenesis of NPC and underscore the need to explore novel therapeutic targets such as CD93 to improve NPC treatment. -- Highlights: •This is the first research about the relationship between CD93 and nasopharyngeal carcinoma. •We explored the prognostic significance of vascular CD93 expression in nasopharyngeal carcinoma. •We researched on angiogenesis and cell proliferation of nasopharyngeal carcinoma and how CD93 affected them.« less

Metastasis-suppressing NID2, an epigenetically-silenced gene, in the pathogenesis of nasopharyngeal carcinoma and esophageal squamous cell carcinoma.

PubMed

Chai, Annie Wai Yeeng; Cheung, Arthur Kwok Leung; Dai, Wei; Ko, Josephine Mun Yee; Ip, Joseph Chok Yan; Chan, Kwok Wah; Kwong, Dora Lai-Wan; Ng, Wai Tong; Lee, Anne Wing Mui; Ngan, Roger Kai Cheong; Yau, Chun Chung; Tung, Stewart Yuk; Lee, Victor Ho Fun; Lam, Alfred King-Yin; Pillai, Suja; Law, Simon; Lung, Maria Li

2016-11-29

Nidogen-2 (NID2) is a key component of the basement membrane that stabilizes the extracellular matrix (ECM) network. The aim of the study is to analyze the functional roles of NID2 in the pathogenesis of nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC). We performed genome-wide methylation profiling of NPC and ESCC and validated our findings using the methylation-sensitive high-resolution melting (MS-HRM) assay. Results showed that promoter methylation of NID2 was significantly higher in NPC and ESCC samples than in their adjacent non-cancer counterparts. Consistently, down-regulation of NID2 was observed in the clinical samples and cell lines of both NPC and ESCC. Re-expression of NID2 suppresses clonogenic survival and migration abilities of transduced NPC and ESCC cells. We showed that NID2 significantly inhibits liver metastasis. Mechanistic studies of signaling pathways also confirm that NID2 suppresses the EGFR/Akt and integrin/FAK/PLCγ metastasis-related pathways. This study provides novel insights into the crucial tumor metastasis suppression roles of NID2 in cancers.

Metastasis-suppressing NID2, an epigenetically-silenced gene, in the pathogenesis of nasopharyngeal carcinoma and esophageal squamous cell carcinoma

PubMed Central

Chai, Annie Wai Yeeng; Cheung, Arthur Kwok Leung; Dai, Wei; Ko, Josephine Mun Yee; Ip, Joseph Chok Yan; Chan, Kwok Wah; Kwong, Dora Lai-Wan; Ng, Wai Tong; Lee, Anne Wing Mui; Ngan, Roger Kai Cheong; Yau, Chun Chung; Tung, Stewart Yuk; Lee, Victor Ho Fun; Lam, Alfred King-Yin; Pillai, Suja; Law, Simon; Lung, Maria Li

2016-01-01

Nidogen-2 (NID2) is a key component of the basement membrane that stabilizes the extracellular matrix (ECM) network. The aim of the study is to analyze the functional roles of NID2 in the pathogenesis of nasopharyngeal carcinoma (NPC) and esophageal squamous cell carcinoma (ESCC). We performed genome-wide methylation profiling of NPC and ESCC and validated our findings using the methylation-sensitive high-resolution melting (MS-HRM) assay. Results showed that promoter methylation of NID2 was significantly higher in NPC and ESCC samples than in their adjacent non-cancer counterparts. Consistently, down-regulation of NID2 was observed in the clinical samples and cell lines of both NPC and ESCC. Re-expression of NID2 suppresses clonogenic survival and migration abilities of transduced NPC and ESCC cells. We showed that NID2 significantly inhibits liver metastasis. Mechanistic studies of signaling pathways also confirm that NID2 suppresses the EGFR/Akt and integrin/FAK/PLCγ metastasis-related pathways. This study provides novel insights into the crucial tumor metastasis suppression roles of NID2 in cancers. PMID:27793011

Dosimetric verification for primary focal hypermetabolism of nasopharyngeal carcinoma patients treated with dynamic intensity-modulated radiation therapy.

PubMed

Xin, Yong; Wang, Jia-Yang; Li, Liang; Tang, Tian-You; Liu, Gui-Hong; Wang, Jian-She; Xu, Yu-Mei; Chen, Yong; Zhang, Long-Zhen

2012-01-01

To make sure the feasibility with (18F)FDG PET/CT to guided dynamic intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma patients, by dosimetric verification before treatment. Chose 11 patients in III~IVA nasopharyngeal carcinoma treated with functional image-guided IMRT and absolute and relative dosimetric verification by Varian 23EX LA, ionization chamber, 2DICA of I'mRT Matrixx and IBA detachable phantom. Drawing outline and making treatment plan were by different imaging techniques (CT and (18F)FDG PET/CT). The dose distributions of the various regional were realized by SMART. The absolute mean errors of interest area were 2.39%±0.66 using 0.6 cc ice chamber. Results using DTA method, the average relative dose measurements within our protocol (3%, 3 mm) were 87.64% at 300 MU/min in all filed. Dosimetric verification before IMRT is obligatory and necessary. Ionization chamber and 2DICA of I'mRT Matrixx was the effective dosimetric verification tool for primary focal hyper metabolism in functional image-guided dynamic IMRT for nasopharyngeal carcinoma. Our preliminary evidence indicates that functional image-guided dynamic IMRT is feasible.

Oral sex is a risk factor for human papillomavirus-associated nasopharyngeal carcinoma in husbands of women with cervical cancer.

PubMed

Huang, Lee-Wen; Seow, Kok-Min

2010-01-01

Sexually transmitted human papillomavirus (HPV) is etiologically related to cervical carcinoma and a distinct subset of cancers of the nasopharyngeal tract. We report 2 patients with HPV-associated cervical cancer and synchronous diagnoses of HPV-related head and neck cancer of their husbands. These patients had active oral sex for more than 20 years. The first patient was a 64-year-old woman who had an abnormal Papanicolaou smear and was found to have squamous cell carcinoma of the cervix on cervical punched biopsy. Her husband was diagnosed with laryngeal squamous cell carcinoma 1 year previously, and was treated with total laryngectomy and adjuvant radiation. HPV-16 DNA was detected in both their tumor specimens using polymerase chain reaction. The other patient was a 50-year-old female with cervical carcinoma treated surgically and with concurrent chemo-radiotherapy. HPV-31 DNA was detected in her tumor specimen. Three years later, her husband presented with nasopharyngeal carcinoma, although not a tobacco or alcohol user. HPV-18 DNA was detected in his tumor specimen.These findings strongly suggest that HPV may play a major role in the carcinogenesis of urogenital and nasopharyngeal tumors and the transmission potential of orogenital sex. Copyright 2010 S. Karger AG, Basel.

Efficient Immortalization of Primary Nasopharyngeal Epithelial Cells for EBV Infection Study

PubMed Central

Yip, Yim Ling; Pang, Pei Shin; Deng, Wen; Tsang, Chi Man; Zeng, Musheng; Hau, Pok Man; Man, Cornelia; Jin, Yuesheng; Yuen, Anthony Po Wing; Tsao, Sai Wah

2013-01-01

Nasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic

ARHGAP42 promotes cell migration and invasion involving PI3K/Akt signaling pathway in nasopharyngeal carcinoma.

PubMed

Hu, Qian; Lin, Xiao; Ding, Linxiaoxiao; Zeng, Yinduo; Pang, Danmei; Ouyang, Nengtai; Xiang, Yanqun; Yao, Herui

2018-06-24

Rho GTPase-activating protein 42 was identified as an inhibitor of RhoA to maintain normal blood pressure homeostasis. However, the effect of ARHGAP42 in promoting cell malignancy in nasopharyngeal carcinoma is demonstrated in this study. Microarray and real-time quantitative PCR were used for a mRNA profiling of ARHGAP42 in nasopharyngeal primary and metastatic carcinoma tissues. Western blot and immunohistochemical staining were used for detecting the expression of ARHGAP42 protein in nasopharyngeal carcinoma tissues and cell lines. The overexpression and silence experiments of ARHGAP42 were performed in NPC cell lines using siRNA and expressive plasmid for evaluating cancer cell migration and invasion in vitro. Real-time quantitative PCR, western blot, and transwell test were employed for with the function of ARHGAP42 and its antisense lncRNA uc010rul. We confirmed the elevated expression of ARHGAP42 in metastatic NPC tissues of mRNA and protein for the first time. Immunohistochemical analysis indicated that NPC patients with highly ARHGAP42 expression were significantly associated with shorter metastasis-free survival. Knockdown of ARHGAP42 resulted in significant inhibition of nasopharyngeal cancer cell migration and invasion in vitro, and the overexpression of ARHGAP42 showed the opposite effects. In addition, the silence of uc010rul resulted in ARHGAP42 expression decrease and significant inhibition of nasopharyngeal cancer cell migration and invasion. High expression of ARHGAP42 is associated with poor metastasis-free survival of nasopharyngeal carcinoma patients. ARHGAP42 promotes migration and invasion of nasopharyngeal carcinoma cells in vitro; the antisense lncRNA may be involved in this effect. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Nivolumab in Treating Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer

ClinicalTrials.gov

2018-05-23

Nasopharyngeal Nonkeratinizing Carcinoma; Recurrent Nasopharynx Carcinoma; Stage III Nasopharyngeal Carcinoma AJCC v7; Stage IV Nasopharyngeal Carcinoma AJCC v7; Stage IVA Nasopharyngeal Carcinoma AJCC v7; Stage IVB Nasopharyngeal Carcinoma AJCC v7; Stage IVC Nasopharyngeal Carcinoma AJCC v7

Sensitivity and specificity of narrow-band imaging nasoendoscopy compared to histopathology results in patients with suspected nasopharyngeal carcinoma

NASA Astrophysics Data System (ADS)

Adham, M.; Musa, Z.; Lisnawati; Suryati, I.

2017-08-01

Nasopharyngeal carcinoma (NPC) is a disease which is prevalent in developing countries like Indonesia. There were 164 new cases of nasopharyngeal carcinoma in the ear, nose, and throat (ENT) oncology outpatient clinic of the Cipto Mangunkusumo hospital in 2014, and 142 cases in 2015. Unfortunately, almost all of these cases presented at an advanced stage. The success of nasopharyngeal carcinoma treatment is largely determined by the stage when patients are diagnosed; it is critical to diagnose NPC as early as possible. Narrow-band imaging (NBI) is an endoscopic instrument with a light system that can improve the visualization of blood vessels of mucosal epithelial malignant tumors. NBI is expected to help clinicians to assess whether a lesion is malignant or not; to do so, it is important to know the value of sensitivity and specificity. This study is a cross-sectional form of a diagnostic test which was performed in the outpatient clinic of the ENT Head and Neck Surgery Department for the Cipto Mangunkusumo Hospital, from January to June 2016, and involved 56 subjects. Patients with a nasopharyngeal mass discovered by physical examination or imaging, and a suspected nasopharyngeal carcinoma were included as a subject. An NBI examination and biopsy was performed locally. Based on this research, NBI could be used as a screening tool for nasopharyngeal carcinoma with high sensitivity (100%), but with a low specificity result (6.7%).

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

PubMed Central

Turnbull, David

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. PMID:21272440

Automated Ki-67 Quantification of Immunohistochemical Staining Image of Human Nasopharyngeal Carcinoma Xenografts.

PubMed

Shi, Peng; Zhong, Jing; Hong, Jinsheng; Huang, Rongfang; Wang, Kaijun; Chen, Yunbin

2016-08-26

Nasopharyngeal carcinoma is one of the malignant neoplasm with high incidence in China and south-east Asia. Ki-67 protein is strictly associated with cell proliferation and malignant degree. Cells with higher Ki-67 expression are always sensitive to chemotherapy and radiotherapy, the assessment of which is beneficial to NPC treatment. It is still challenging to automatically analyze immunohistochemical Ki-67 staining nasopharyngeal carcinoma images due to the uneven color distributions in different cell types. In order to solve the problem, an automated image processing pipeline based on clustering of local correlation features is proposed in this paper. Unlike traditional morphology-based methods, our algorithm segments cells by classifying image pixels on the basis of local pixel correlations from particularly selected color spaces, then characterizes cells with a set of grading criteria for the reference of pathological analysis. Experimental results showed high accuracy and robustness in nucleus segmentation despite image data variance. Quantitative indicators obtained in this essay provide a reliable evidence for the analysis of Ki-67 staining nasopharyngeal carcinoma microscopic images, which would be helpful in relevant histopathological researches.

[Inhibitive effect of matrine modification X on the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice].

PubMed

Shi, Shujing; Tang, Anzhou; Yin, Shaolin; Wang, Lisheng; Xie, Mao; Yi, Xiang

2014-11-01

To evaluate the inhibitive effect of matrine modification X on the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice. Tumor model was established by subcutaneous inoculation of nasopharyngeal carcinoma cell CNE2 into nude mice, which was used to evaluate the antitumor effect of matrine modification X in vivo. The expression levels of Bax, Bcl-2, Caspase3 were detected by real-time PCR and western blot. The growth of xenografts in nude mice was significantly suppressed after application of matrine modification X in a dose-dependent manner. The inhibition rates were 32.55% and 44.89% when treated at medium and high dose respectively. Real-time fluorescence quantitative-PCR and Western Blot results showed that the expression of Bax and Caspase3 increased, while the expression of Bcl-2 decreased in a dose-dependent manner. The change of high dose group was obvious, and the difference was statistically significant (P < 0.05). Matrine modification X could significantly inhibit the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice, probably by inducing the apoptosis of nasopharyngeal carcinoma cells, and the possible mechanism is related to regulating the expression level of Bax/Bcl-2 and Casepase3.

Photodynamic effects of pyropheophorbide-a methyl ester in nasopharyngeal carcinoma cells.

PubMed

Xu, Chuan Shan; Leung, Albert Wing Nang

2006-08-01

Nasopharyngeal carcinoma (NPC) is one of the most common cancers, and exploring novel therapeutic modalities will improve the clinical outcomes. It has been confirmed that photodynamic therapy can efficiently deactivate malignant cells. The aim of the present study was to explore the photodynamic effects of pyropheophorbide-a methyl ester (MPPa) in CNE2 nasopharyngeal carcinoma cells. CNE2 cells were subjected to photodynamic therapy with MPPa, in which the drug concentration was 0.25 to 4 microM and light energy 1 to 8 J/cm(2). Photodynamic toxicity was investigated 24 h after treatment. Apoptosis was determined using flow cytometry with annexin V-FITC and propidum iodine staining and with nuclear staining with Hoechst 33258. The mitochondrial membrane potential (DeltaPsim) was evaluated by Rhodamine 123 assay. There was no dark cytotoxicity of MPPa in the CNE2 cells at doses of 0.25-4 microM, and MPPa resulted in dose- and light-dependent phototoxicity. The apoptotic rate 8 h after PDT with MPPa (2 microM) increased to 16.43% under a light energy of 2 J/cm(2). Mitochondrial membrane potential (DeltaPsim) collapsed when the CNE2 cells were exposed to 2 microM MPPa for 20 h and then 2 J/cm(2) irradiation. Photodynamic therapy with MPPa significantly enhanced apoptosis and the collapse of DeltaPsim. This can be developed for treating nasopharyngeal carcinoma.

Medical History, Medication Use, and Risk of Nasopharyngeal Carcinoma.

PubMed

Xiao, Xiling; Zhang, Zhe; Chang, Ellen T; Liu, Zhiwei; Liu, Qing; Cai, Yonglin; Chen, Guomin; Huang, Qi-Hong; Xie, Shang-Hang; Cao, Su-Mei; Shao, Jian-Yong; Jia, Wei-Hua; Zheng, Yuming; Liao, Jian; Chen, Yufeng; Lin, Longde; Ernberg, Ingemar; Huang, Guangwu; Zeng, Yi; Zeng, Yi-Xin; Adami, Hans-Olov; Ye, Weimin

2018-04-26

Because persistent inflammation may render the nasopharyngeal mucosa susceptible to carcinogenesis, chronic ear/nose/throat (ENT) disease and its treatment might influence the risk of nasopharyngeal carcinoma (NPC). Existing evidence is, however, inconclusive and often based on methodologically suboptimal epidemiologic studies. In a population-based case-control study in southern China, we enrolled 2532 NPC cases and 2597 controls aged 20-74 years from 2010 to 2014. Odds ratios were estimated for associations between NPC risk and history of ENT and related medications. Any history of chronic ENT disease was associated with a 34% increased risk of NPC. Similarly, use of nasal drops or aspirin was associated with approximately doubled risk of NPC. However, in secondary analyses restricted to chronic ENT diseases and related medication use at least 5 years prior to diagnosis/interview, most results were statistically non-significant, except a history of uncured ENT diseases, untreated nasal polyps, and earlier age at first diagnosis of ENT disease and first or most recent aspirin use. Overall, these findings suggest that ENT disease and related drug use are most likely early indications rather than causes of NPC, although the possibility of a modestly increased NPC risk associated with these diseases and related drugs cannot be excluded.

Epstein-Barr virus and nasopharyngeal carcinoma

PubMed Central

Young, Lawrence S.; Dawson, Christopher W.

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-cell tumors. The association of EBV with epithelial cell tumors, specifically 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 all tumor cells 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. PMID:25418193

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

PubMed Central

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

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 cells. These cancer stem-like cells (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. PMID:25223912

Prognostic aspects in the treatment of juvenile nasopharyngeal carcinoma: a systematic review.

PubMed

Gioacchini, Federico Maria; Tulli, Michele; Kaleci, Shaniko; Magliulo, Giuseppe; Re, Massimo

2017-03-01

To systematically review and discuss the published data about treatments and outcomes for children and adolescents affected by nasopharyngeal carcinoma. In April 2015, an appropriate string was run on PubMed to retrieve all relevant articles. A cross-check was performed by two of the authors on abstracts and full-text articles found using the selected inclusion and exclusion criteria. A meta-analysis concerning the rate of reported disease-free survival and overall survival was performed. Fifteen studies were identified comprising a total of 865 subjects affected by nasopharyngeal carcinoma. According to the American Joint Committee for Cancer Staging system, the majority of tumors were classified as Stage IV (57.3 %). All included patients underwent radiotherapy, while 687 (79.4 %) received also some regimen of chemotherapy. On the basis of our statistical analysis, the mean (95 % CI) rate of disease-free survival was 66 % (95 % CI 56-76). The mean (95 % CI) rate of the overall survival resulted 68 % (95 % CI 58-78). On the basis of our analysis, it may be affirmed that the prognosis of juvenile nasopharyngeal carcinoma is still unsatisfactory. New reports on homogeneous populations are needed to better define the most influencing prognostic factors and to evaluate the introduction of possible alternative therapeutic protocols.

Inhibition of Notch-1 pathway is involved in rottlerin-induced tumor suppressive function in nasopharyngeal carcinoma cells

PubMed Central

Hou, Yingying; Feng, Shaoyan; Wang, Lixia; Zhao, Zhe; Su, Jingna; Yin, Xuyuan; Zheng, Nana; Zhou, Xiuxia; Xia, Jun; Wang, Zhiwei

2017-01-01

Recent studies have revealed that rottlerin is a natural chemical drug to exert its anti-cancer activity. However, the molecular mechanisms of rottlerin-induced tumor suppressive function have not been fully elucidated. Notch signaling pathway has been characterized to play a crucial role in tumorigenesis. Therefore, regulation of Notch pathway could be beneficial for the treatment of human cancer. The aims of our current study were to explore whether rottlerin could suppress Notch-1 expression, which leads to inhibition of cell proliferation, migration and invasion in nasopharyngeal carcinoma cells. We performed several approaches, such as CTG, Flow cytometry, scratch healing assay, transwell and Western blotting. Our results showed that rottlerin treatment inhibited cell growth, migration and invasion, and triggered apoptosis, and arrested cell cycle to G1 phase. Moreover, the expression of Notch-1 was obvious decreased in nasopharyngeal carcinoma cells after rottlerin treatment. Importantly, overexpression of Notch-1 promoted cell growth and invasion, whereas down-regulation of Notch-1 inhibited cell growth and invasion in nasopharyngeal carcinoma cells. Notably, we found the over-expression of Notch-1 could abrogate the anti-cancer function induced by rottlerin. Strikingly, our study implied that Notch-1 could be a useful target of rottlerin for the prevention and treatment of human nasopharyngeal carcinoma. PMID:28977931

Radiotherapy induces cell cycle arrest and cell apoptosis in nasopharyngeal carcinoma via the ATM and Smad pathways.

PubMed

Li, Ming-Yi; Liu, Jin-Quan; Chen, Dong-Ping; Li, Zhou-Yu; Qi, Bin; He, Lu; Yu, Yi; Yin, Wen-Jin; Wang, Meng-Yao; Lin, Ling

2017-09-02

Nasopharyngeal carcinoma (NPC) is a common malignant neoplasm of the head and neck which is harmful to human's health. Radiotherapy is commonly used in the treatment of NPC and it induces immediate cell cycle arrest and cell apoptosis. However, the mechanism remains unknown. Evidences suggested the activation of Ataxia telangiectasia mutated (ATM) pathway and Smad pathway are 2 of the important crucial mediators in the function of radiotherapy. In this study, we performed in vitro assays with human nasopharyngeal carcinoma CNE-2 cells and in vivo assays with nude mice to investigate the role of the ATM and Smad pathways in the treatment of nasopharyngeal carcinoma with radiotherapy. The results suggested that radiation induced activation of ATM pathway by inducing expression of p-ATM, p-CHK1, p-CHK2, p15 and inhibiting expression of p-Smad3. In addition, Caspase3 expression was increased while CDC25A was decreased, leading to cell cycle arrest and cell apoptosis. On the other hand, activation of Smad3 can inhibited the ATM pathway and attenuated the efficacy of radiation. In summary, we suggest that both ATM and Smad pathways contribute to the cell cycle arrest and cell apoptosis during nasopharyngeal carcinoma cells treated with radiation.

Comprehensive Pathway-Based Association Study of DNA Repair Gene Variants and the Risk of Nasopharyngeal Carcinoma

PubMed Central

Qin, Hai-De; Shugart, Yin Yao; Bei, Jin-Xin; Pan, Qing-Hua; Chen, Lina; Feng, Qi-Sheng; Chen, Li-Zhen; Huang, Wei; Liu, Jian Jun; Jorgensen, Timothy J.; Zeng, Yi-Xin; Jia, Wei-Hua

2011-01-01

DNA repair plays a central role in protecting against environmental carcinogenesis, and genetic variants of DNA repair genes have been reported to be associated with several human malignancies. To assess whether DNA gene variants were associated with nasopharyngeal carcinoma (NPC) risk, a candidate gene association study was conducted among the Cantonese population within the Guangdong Province, China --the ethnic group with the highest risk for NPC. A two-stage study design was utilized. In the discovery stage, 676 tagging SNPs covering 88 DNA repair genes were genotyped in a matched case-control study (cases/controls = 755/755). Eleven SNPs with Ptrend <0.01 were identified. Seven of these SNPs were located within three genes, RAD51L1, BRCA2 and TP53BP1. In the validation stage, these 11 SNPs were genotyped in a separate Cantonese population (cases/controls = 1,568/1,297). Two of the SNPs (rs927220 and rs11158728) – both in RAD51L1 – remained strongly associated with NPC. The SNP rs927220 had a significant Pcombined of 5.55 × 10−5, with OR = 1.20 (95%CI = 1.10 to 1.30), Bonferroni corrected P = 0.0381. The other SNP (rs11158728), which is in strong LD with rs927220 (r2 = 0.7), had a significant Pcombined of 2.0 × 10−4, Bonferroni corrected P = 0.1372. Gene-environment interaction analysis suggested that the exposures of salted-fish consumption and cigarette smoking had potential interactions with DNA repair gene variations, but need to be further investigated. Our findings support the notion that DNA repair genes, in particular RAD51L1, play a role in NPC etiology and development. PMID:21368091

Individualized treatment in stage IVC nasopharyngeal carcinoma.

PubMed

Chan, Oscar S H; Ngan, Roger K C

2014-09-01

The stage IVC nasopharyngeal carcinoma is a catch-all entity covering minute solitary metastasis to bulky disseminated disease. Prognosis varies greatly within this stage group. A subset of patients with oligometastases may benefit from aggressive local ablative therapy. Meanwhile, in multiple metastatic diseases, customizing conventional cytotoxics basing on individual tumor characteristics and previous chemotherapy responses can be a new direction to improve therapeutic results. Prognostic models built on clinical features and genomic profiles can be utilized to stratify different risk groups and tailor therapy schemes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma.

PubMed

Chow, Yock Ping; Tan, Lu Ping; Chai, San Jiun; Abdul Aziz, Norazlin; Choo, Siew Woh; Lim, Paul Vey Hong; Pathmanathan, Rajadurai; Mohd Kornain, Noor Kaslina; Lum, Chee Lun; Pua, Kin Choo; Yap, Yoke Yeow; Tan, Tee Yong; Teo, Soo Hwang; Khoo, Alan Soo-Beng; Patel, Vyomesh

2017-03-03

In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies.

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma

PubMed Central

Chow, Yock Ping; Tan, Lu Ping; Chai, San Jiun; Abdul Aziz, Norazlin; Choo, Siew Woh; Lim, Paul Vey Hong; Pathmanathan, Rajadurai; Mohd Kornain, Noor Kaslina; Lum, Chee Lun; Pua, Kin Choo; Yap, Yoke Yeow; Tan, Tee Yong; Teo, Soo Hwang; Khoo, Alan Soo-Beng; Patel, Vyomesh

2017-01-01

In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies. PMID:28256603

Chemoradiation in nasopharyngeal carcinoma: a 6-year experience in Tehran cancer institute.

PubMed

Kalaghchi, Bita; Kazemian, Ali; Hashem, Farnaz Amouzegar; Aghili, Mehdi; Farhan, Farshid; Haddad, Peiman

2011-01-01

To determine the addition of value of neoadjuvant, concurrent and adjuvant chemotherapy to radiation in the treatment of nasopharyngeal carcinoma with regard to the overall survival (OS) and disease free survival (DFS) within a six year period in Tehran cancer institute. Files of all patients with nasopharyngeal carcinoma treated by radiotherapy with or without concurrent chemotherapy in a curative setting in Tehran cancer institute during the period of 1999-2005 were retrospectively reviewed.. A total of 103 patients with nasopharyngeal carcinoma had been treated during the study period with radiotherapy or chemoradiotherapy in our institute. There were 29 (28.2%) females and 74 (71.8%) males. The median age at the time of radiotherapy was 47 years old (range 9-75 years). The patients were followed 2 to 76 months with a median follow-up of 14 months. Time of first recurrence after treatment was 3-44 months with a median of 10 months.. Survival in 2 groups of patients treated with radiotherapy alone or chemoradiation did not have a significant difference (P>0.1). Two-year survival in patients treated with or without adjuvant chemotherapy and had local recurrence after treatment did not have significant difference (P>0.1). Two-year survival in patients with or without local recurrence after treatment did not have significant difference (P>0.1). A beneficial affect or a survival benefit of adjuvant/neoadjuvant chemotherapy and concurrent chemoradiation was not observed in Iranian patients.

[In vitro study of joint intervention of E-cad and Bmi-1 mediated by transcription activator-like effector nuclease in nasopharyngeal carcinoma].

PubMed

Luo, Tingting; Yan, Aifen; Liu, Lian; Jiang, Hong; Feng, Cuilan; Liu, Guannan; Liu, Fang; Tang, Dongsheng; Zhou, Tianhong

2018-03-28

To explore the effect of intervention of E-cadherin (E-cad) and B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) mediated by transcription activator-like effector nuclease (TALEN) on the biological behaviors of nasopharyngeal carcinoma cells.
 Methods: Multi-locus gene targeting vectors pUC-DS1-CMV-E-cad-2A-Neo-DS2 and pUC-DS1-Bmi-1 shRNA-Zeo-DS2 were constructed, and the E-cad and Bmi-1 targeting vectors were transferred with TALEN plasmids to CNE-2 cells individually or simultaneously. The integration of target genes were detected by PCR, the expressions of E-cad and Bmi-1 were detected by Western blot. The changes of cell proliferation were detected by cell counting kit-8 (CCK-8) assay. The cell cycle and apoptosis were detected by flow cytometry. The cell migration and invasion were detected by Transwell assay.
 Results: The E-cad and Bmi-1 shRNA expression elements were successfully integrated into the genome of CNE-2 cells, the protein expression level of E-cad was up-regulated, and the protein expression level of Bmi-1 was down-regulated. The intervention of E-cad and Bmi-1 didn't affect the proliferation, cell cycle and apoptosis of CNE-2 cells, but it significantly inhibited the migration and invasion ability of CNE-2 cells. Furthermore, the intervention of E-cad and Bmi-1 together significantly inhibited the migration ability of nasopharyngeal carcinoma cells compared with the intervention of E-cad or Bmi-1 alone (all P<0.01).
 Conclusion: The joint intervention of E-cad and Bmi-1 mediated by TALEN can effectively inhibit the migration and invasion of nasopharyngeal carcinoma cells in vitro, which may lay the preliminary experimental basis for gene therapy of human cancer.

Various 30 and 69 bp deletion variants of the Epstein-Barr virus LMP1 may arise by homologous recombination in nasopharyngeal carcinoma of Tunisian patients.

PubMed

Hadhri-Guiga, Boutheina; Khabir, Abdel-Majid; Mokdad-Gargouri, Raja; Ghorbel, Abdel-Monem; Drira, Mohamed; Daoud, Jamel; Frikha, Mounir; Jlidi, Rachid; Gargouri, Ali

2006-01-01

Nasopharyngeal carcinoma (NPC) occurs with a striking geographic distribution, it is endemic in certain areas of Southeast Asia and North Africa. NPC is tightly linked to Epstein-Barr virus (EBV), however, only a small subset of EBV genes are expressed, among them the latent membrane protein 1 (LMP1). LMP1 is considered as the main EBV oncoprotein and its 30 bp deleted-variant has been reported to be more prevalent in biopsies of NPC. We have assessed the 30 bp deletion and the XhoI polymorphisms of the BNLF1 gene in 30 peripheral bloods of NPC patients and 62 nasopharyngeal biopsies, 42 being confirmed as undifferentiated nasopharyngeal carcinoma and 20 are normal nasopharyngeal epithelium cells. Our results show that 100% of individuals retained the XhoI restriction site. A rare NPC variant, having a 69 bp deletion in the C-terminus region of the BNLF1 gene, covering the 30 bp deletion, was found in two NPC biopsies. The deleted 30 and 69 bp deleted-variants are significantly (p = 0.006) more frequent in NPC (71.42%) than in control biopsies (52%). In peripheral blood of NPC patients, the deleted-variants (47%) are also lower than in tumor tissues (p = 0.0004), suggesting that the deletion could be associated with a risk of tumor genesis. Direct repeats, located at the extremities of the 30 and 69 bp deletions, should be involved in this process. We propose that other deletions could be found since another similar direct repeat is present at the vicinity of the former ones.

Acute oral mucositis in nasopharyngeal carcinoma patients treated with radiotherapy: association with genetic polymorphism in DNA DSB repair genes.

PubMed

Ren, Jing-Hua; Dai, Xiao-Fang; Yan, Guo-Li; Jin, Min; Liu, Cui-Wei; Yang, Kun-Yu; Wu, Gang; Ma, C-M Charlie

2014-03-01

The aim of this study was to investigate the association between polymorphic variants of DNA repair genes with the susceptibility of acute oral mucositis (OM) in nasopharyngeal carcinoma (NPC) patients treated with radiotherapy. The study population consisted of 120 NPC patients treated with intensity-modulated radiation therapy (IMRT). Among them 70 patients also received concurrent chemotherapy. Genotypes in DNA repair genes Ku70 c.-1310C>G (rs2267437), Ku70 c.1781G> T (rs132788), Ku80 c.2099-2408G> A (rs3835), Ku80 c.*841G> A (rs2440) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) c.2888 + 713C> T (rs2213178) were determined by polymerase chain reaction combined with the restriction fragment length polymorphism (PCR-RFLP) technique. Mucositis was scored using the Common Terminology Criteria (CTC) for Adverse Events v.3.0 scale. The population was divided into the CTC0-2 group (CTC toxicity grade 0, 1 and 2) and the CTC3 + group (CTC toxicity grade 3 and above). Odd ratios (OR) and 95% confidence intervals (CI) were calculated using the multivariate logistic regression analysis. A significant difference in Ku70 c.1781G> T genotype distribution was observed between the CTC0-2 and CTC3 + groups for the 120 patients analyzed. The GG carriers were at higher risks for severe OM (CTC3+) compared with the TT homozygotes (OR = 3.000, 95% CI = 1.287-6.994, p = 0.011). No association was found between Ku70 (c.-1310C> G), Ku80 (c.2099-2408G> A, c.*841G> A), DNA-PKcs (c.2888 + 713 C > T) and the development of severe oral mucositis. Stratification analyses for the 50 patients treated with radiation alone further confirmed the association between the variant genotype of GG and severe OM (OR = 5.128, 95% CI = 1.183-22.238, p = 0.029). Concurrent radiochemotherapy increased the risk of severe OM for both the TT homozygotes and GG genotypes. Our study suggests that the Ku70 c.1781G> T polymorphism may be a susceptibility factor for radiation-induced oral mucositis

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Liang; Department of Otolaryngology, Guangzhou General Hospital of PLA Guangzhou Command, Guangzhou 510010; Tang, Yanping

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 proteinmore » 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.« less

Apoptosis and expression of cytokines triggered by pyropheophorbide-a methyl ester-mediated photodynamic therapy in nasopharyngeal carcinoma cells.

PubMed

Li, K M; Sun, X; Koon, H K; Leung, W N; Fung, M C; Wong, R N S; Lung, Maria L; Chang, C K; Mak, N K

2006-12-01

The photodynamic properties of pyropheophorbide-a methyl ester (MPPa), a semi-synthetic photosensitizer derived from chlorophyll a, were evaluated in a human nasopharyngeal carcinoma HONE-1 cell line. MPPa was non-toxic to the HONE-1. At the concentrations of 0.5-2μM, MPPa-mediated a drug dose-dependent photocytotoxicity in the HONE-1 cells. Confocal microscopy revealed a subcellular localization of MPPa in mitochondria and the Golgi apparatus. MPPa PDT-induced apoptosis was associated with the collapse of mitochondrial membrane potential, release of cytochrome c, the up-regulation of endoplasmic reticulum (ER) stress proteins (calnexin, Grp 94 and Grp78), and the activation of caspases-3 and -9. The photocytotoxicity was reduced by the corresponding specific caspase inhibitors. MPPa PDT-treated HONE-1 cells also up-regulated the gene expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) and beta-chemokines (MIP-1β, MPIF-1, and MPIF-2). These results suggest that the MPPa may be developed as a chlorophyll-based photosensitizer for the treatment of nasopharyngeal carcinoma.

Prognostic value of 18F-FDG-PET/CT in patients with nasopharyngeal carcinoma: a systematic review and meta-analysis.

PubMed

Lin, Jie; Xie, Guozhu; Liao, Guixiang; Wang, Baiyao; Yan, Miaohong; Li, Hui; Yuan, Yawei

2017-05-16

The prognostic role of 18F-fluorodeoxyglucose positron emission tomography CT (18F-FDG PET/CT) parameters is still controversial in nasopharyngeal carcinoma patients. We sought to perform a systematic review and meta-analysis to explore the prognostic value of maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on event-free survival (EFS) and overall survival (OS) in nasopharyngeal carcinoma patients. Fifteen studies comprising 1,938 patients were included in this study. The combined hazard ratios (HRs) for EFS were 2.63 (95%CI 1.71-4.05) for SUVmax, 2.55 (95%CI 1.49-4.35) for MTV, and 3.32 (95%CI 1.23-8.95) for TLG. The pooled HRs for OS were 2.07 (95%CI 1.54-2.79) for SUVmax, 3.86 (95%CI 1.85-8.06) for MTV, and 2.60 (95%CI 1.55-4.34) for TLG. The prognostic role of SUVmax, MTV and TLG remained similar in the sub-group analyses. A systematic literature search was performed to identify studies which associated 18F-FDG PET/CT to clinical survival outcomes of nasopharyngeal carcinoma patients. The summarized HRs for EFS and OS were estimated by using fixed- or random-effect models according to heterogeneity between trials. The present meta-analysis confirms that high values of SUVmax, MTV and TLG predicted a higher risk of adverse events or death in patients with nasopharyngeal carcinoma, despite clinically heterogeneous nasopharyngeal carcinoma patients and the various methods adopted between these studies.

Olfactory Training in Improving Sense of Smell After Radiation Therapy in Patients With Paranasal Sinus or Nasopharyngeal Cancer

ClinicalTrials.gov

2017-07-11

Stage 0 Nasopharyngeal Carcinoma; Stage 0 Paranasal Sinus Cancer; Stage I Nasopharyngeal Carcinoma; Stage I Paranasal Sinus Cancer; Stage II Nasopharyngeal Carcinoma; Stage II Paranasal Sinus Cancer; Stage IIA Nasopharyngeal Carcinoma; Stage IIB Nasopharyngeal Carcinoma; Stage III Nasopharyngeal Carcinoma; Stage III Paranasal Sinus Cancer; Stage IV Nasopharyngeal Carcinoma; Stage IV Paranasal Sinus Cancer; Stage IVA Nasopharyngeal Carcinoma; Stage IVA Paranasal Sinus Cancer; Stage IVB Nasopharyngeal Carcinoma; Stage IVB Paranasal Sinus Cancer; Stage IVC Nasopharyngeal Carcinoma; Stage IVC Paranasal Sinus Cancer

KAI1 overexpression promotes apoptosis and inhibits proliferation, cell cycle, migration, and invasion in nasopharyngeal carcinoma cells.

PubMed

Guo, Zheng; Wang, Yili; Yang, Jing; Zhong, Jinghua; Liu, Xia; Xu, Mingjun

The purpose of this study is to characterize the effect of KAI1 overexpression on the biological behavior of nasopharyngeal carcinoma (NPC) cells. Nasopharyngeal carcinoma is a highly malignant tumor with a high rate of incidence in China. Currently, there are no ideal therapeutic options for patients with NPC, but a targeted therapy would have great potential for treating it. Therefore, there is an urgent need for novel therapeutic targets to provide new options for treating NPC. The KAI1 gene was originally identified as a metastasis suppressor gene for advanced human cancer. In NPC cell lines and tissues, the expression of KAI1 decreased as the metastatic potential of cells increased, but its potential as a therapeutic target has not been elucidated. Non-transformed nasopharyngeal epithelium cell NP69 and NPC cell line C666-1 were cultured and KAI1 expression in these cells was detected by qRT-PCR and Western blot. After the transfection of KAI1-pCDNA3.1 to NP69 and C666-1, the KAI1 expression in these cells was detected by qRT-PCR and Western blot, the proliferation was performed by MTS, the cell cycle and apoptosis were performed by flow cytometry, the migration and invasion were examined by transwell. Our results showed that KAI1 was significantly upregulated in C666-1 cells compared to that in NP69 cells. In addition, KAI1 overexpression significantly inhibited the proliferation, cell cycle, migration, and invasion, and promoted apoptosis of C666-1 cells, but had no significant effect on NP69 cells. Our findings suggest that KAI1 overexpression promotes apoptosis and inhibits proliferation, cell cycle, migration, and invasion in NPC cells. We hypothesize that KAI1 overexpression could be a potential therapeutic target for NPC. Copyright © 2016 Elsevier Inc. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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.

Nasopharyngeal Carcinoma in Children: Comparison of Conventional and Intensity-Modulated Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laskar, Siddhartha; Bahl, Gaurav; Muckaden, MaryAnn

2008-11-01

Purpose: To evaluate the efficacy of intensity-modulated radiotherapy (IMRT) in reducing the acute toxicities associated with conventional RT (CRT) in children with nasopharyngeal carcinoma. Patients and Methods: A total of 36 children with nonmetastatic nasopharyngeal carcinoma, treated at the Tata Memorial Hospital between June 2003 and December 2006, were included in this study. Of the 36 patients, 28 were boys and 8 were girls, with a median age of 14 years; 4 (11%) had Stage II and 10 (28%) Stage III disease at presentation. All patients had undifferentiated carcinoma and were treated with a combination of chemotherapy and RT. Ofmore » the 36 patients, 19 underwent IMRT and 17 underwent CRT. Results: After a median follow-up of 27 months, the 2-year locoregional control, disease-free, and overall survival rate was 76.5%, 60.6%, and 71.3%, respectively. A significant reduction in acute Grade 3 toxicities of the skin (p = 0.006), mucous membrane (p = 0.033), and pharynx (p = 0.035) was noted with the use of IMRT. The median time to the development of Grade 2 toxicity was delayed with IMRT (skin, 35 vs. 25 days, p = 0.016; mucous-membrane, 39 vs. 27 days, p = 0.002; and larynx, 50 vs. 28 days, p = 0.009). The duration of RT significantly influenced disease-free survival on multivariate analysis (RT duration >52 days, hazard ratio = 5.49, 95% confidence interval, 1.14-26.45, p = 0.034). The average mean dose to the first and second planning target volume was 71.8 Gy and 62.5 Gy with IMRT compared with 66.3 Gy (p = 0.001) and 64.4 Gy (p = 0.046) with CRT, respectively. Conclusion: The results of our study have shown that IMRT significantly reduces and delays the onset of acute toxicity, resulting in improved tolerance and treatment compliance for children with nasopharyngeal carcinoma. Also, IMRT provided superior target coverage and normal tissue sparing compared with CRT.« less

Salvage surgery in the treatment of local recurrences of nasopharyngeal carcinomas.

PubMed

Salom, María Cecilia; López, Fernando; Pacheco, Esteban; Muñoz, Gabriela; García-Cabo, Patricia; Fernández, Laura; Suárez, Vanessa; Llorente, José Luis

2018-04-03

Chemoradiotherapy is the treatment of choice for nasopharyngeal carcinoma. Local recurrences are one of the leading causes of death in these patients, and surgical salvage the treatment of choice. Our goal was to evaluate and compare the results of salvage surgery in the treatment of local recurrence of nasopharyngeal carcinomas comparing endoscopic to open approaches. Twenty patients with local recurrence of nasopharyngeal carcinomas underwent surgery: 12 patients underwent open surgery and 8 endoscopic endonasal transpterygoid nasopharyngectomy. One patient was classified as rT1; 3 as rT2;2 as rT3; and 6 as rT4 in the group of open approaches; in the endoscopic series, 2 patients were rT1, 5 rT2 and one rT3. In 3 patients (25%) operated by an open approach (one rT4, one rT3 and one rT2) a complete gross resection was not achieved. Gross total resection was achieved in patients operated by endoscopic surgery. The complication rate in the group operated by an open approach was 92% (5 minor complications, 5 moderate complications, and one serious complication) and in the group that underwent endoscopic surgery all patients had some complication (7 had minor complications and one patient developed a severe complication). Survival at 3 and 5 years was 53% and 42% with the open approach and 100% and 50% with the endoscopic approach, respectively. Endoscopic approaches decrease the morbidity associated with open approaches and allow for favourable oncological control. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

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

PubMed Central

2010-01-01

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 < 0.001) and 40.0% of healthy LCLs (p = 0.074). NPC isolates also showed more frequent codon mutation than non-NPC samples. EBV strain typing revealed most isolates as EBV type 1. The viral load of either NPC or non-NPC samples was high, but only in non- NPC group it related to a particular BARF1 variant. Serology on NPC sera using IgA/EBNA-1 ELISA, IgA/VCA-p18 ELISA and immunoblot score showed no relation with BARF1 sequence diversity (p = 0.802, 0.382 and 0.058, respectively). NPC patients had variable antibody reactivity against purified hexameric NPC-derived BARF1 irrespective of the endogenous BARF1 sequence. 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. PMID:20849661

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

PubMed

Hutajulu, Susanna H; Hoebe, Eveline K; Verkuijlen, Sandra Awm; Fachiroh, Jajah; Hariwijanto, Bambang; Haryana, Sofia M; Stevens, Servi Jc; Greijer, Astrid E; Middeldorp, Jaap M

2010-09-19

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. 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 < 0.001) and 40.0% of healthy LCLs (p = 0.074). NPC isolates also showed more frequent codon mutation than non-NPC samples. EBV strain typing revealed most isolates as EBV type 1. The viral load of either NPC or non-NPC samples was high, but only in non- NPC group it related to a particular BARF1 variant. Serology on NPC sera using IgA/EBNA-1 ELISA, IgA/VCA-p18 ELISA and immunoblot score showed no relation with BARF1 sequence diversity (p = 0.802, 0.382 and 0.058, respectively). NPC patients had variable antibody reactivity against purified hexameric NPC-derived BARF1 irrespective of the endogenous BARF1 sequence. 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.

Cytotoxic T Cell Adoptive Immunotherapy as a Treatment for Nasopharyngeal Carcinoma

PubMed Central

Crooks, Pauline; Morrison, Leanne; Stevens, Natasha; Davis, Joanne E.; Corban, Monika; Hall, David; Panizza, Benedict; Coman, William B.; Coman, Scott; Moss, Denis J.

2014-01-01

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). We assess the safety and tolerability of adoptive transfer of autologous cytotoxic T lymphocytes (CTLs) specific for the EBV latent membrane protein (LMP) in a patient with recurrent NPC. After infusion, the majority of pulmonary lesions were no longer evident, although the primary tumor did not regress. PMID:24351754

Cytotoxic T cell adoptive immunotherapy as a treatment for nasopharyngeal carcinoma.

PubMed

Lutzky, Viviana P; Crooks, Pauline; Morrison, Leanne; Stevens, Natasha; Davis, Joanne E; Corban, Monika; Hall, David; Panizza, Benedict; Coman, William B; Coman, Scott; Moss, Denis J

2014-02-01

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC). We assess the safety and tolerability of adoptive transfer of autologous cytotoxic T lymphocytes (CTLs) specific for the EBV latent membrane protein (LMP) in a patient with recurrent NPC. After infusion, the majority of pulmonary lesions were no longer evident, although the primary tumor did not regress.

Differential diagnosis of primary nasopharyngeal lymphoma and nasopharyngeal carcinoma focusing on CT, MRI, and PET/CT.

PubMed

Cho, Kyu-Sup; Kang, Dae-Woon; Kim, Hak-Jin; Lee, Jong-Kil; Roh, Hwan-Jung

2012-04-01

No study has done a comparative analysis of radiologic imaging findings between primary nasopharyngeal lymphoma (PNL) and nasopharyngeal carcinoma (NPC). The purpose of this study was to analyze computed tomography (CT) and magnetic resonance (MR) images and to evaluate the maximum standardized uptake value (SUV max) of positron emission tomography (PET)/CT between PNL and NPC, knowing the imaging features that distinguish PNL from NPC. Cross-sectional study. University tertiary care facility. The authors analyzed the features on CT, MR imaging, and PET/CT of 16 patients diagnosed with PNL and 32 patients diagnosed with NPC histopathologically. Patients with PNL had a larger tumor volume and showed symmetry of tumor shape than did patients with NPC. Patients with PNL also had higher tumor homogeneity than NPC patients on CT, T2-weighted, and postcontrast MR images. All PNL patients showed a high degree of enhancement without invasion to the adjacent deep structure. The involvement of the Waldeyer ring was significantly higher in PNL patients. Cervical and retropharyngeal lymphadenopathy and PET/CT SUV max showed no significant difference between PNL and NPC. If the images present a bulky, symmetric nasopharyngeal mass with marked homogeneity, a high degree of enhancement, and a higher Waldeyer ring involvement combined with no invasion into the deep structure, PNL should be considered over NPC.

The effect of EBV on WIF1, NLK, and APC gene methylation and expression in gastric carcinoma and nasopharyngeal cancer.

PubMed

Zhao, Zhenzhen; Liu, Wen; Liu, Jincheng; Wang, Jiayi; Luo, Bing

2017-10-01

Epstein-Barr virus (EBV) is an important DNA tumor virus that is associated with approximately 10% of gastric carcinomas and 99% of nasopharyngeal cancers (NPC). DNA methylation and microRNAs (miRNAs) are the most studied epigenetic mechanisms that can prompt disease susceptibility. This study aimed to detect the effect of EBV on Wnt inhibitory factor 1 (WIF1), Nemo-like kinase (NLK), and adenomatous polyposis coli (APC) gene methylation, and expression in gastric carcinoma and NPC. The WIF1, NLK, and APC gene mRNA expression levels were measured by real-time quantitative RT-PCR in four EBV-positive cell lines and four EBV-negative cell lines. Bisulfite genomic sequencing or methylation-specific PCR was used to detect the methylation status of the WIF1, NLK, and APC promoters. All cell lines were treated with 5-azacytidine (5-aza-dC), miR-BART19-3p mimics or an inhibitor, and analyzed by flow cytometry and MTT cell proliferation assays. The WIF1, NLK, and APC promoters were hypermethylated in all eight cell lines. 5-Aza-dC displayed a growth inhibitory effect on cells . After transfection with miR-BART19-3p mimics, the expression of WIF1, and APC decreased, and the cellular proliferation rate increased. After transfection with the miR-BART19-3p inhibitor, the expression levels were higher, and the cell growth was inhibited. In the NPC and GC cell lines, the promoters of WIF1, NLK, and APC are highly methylated, and the expression of these three genes is regulated by miR-BART19-3p. The activity of the Wnt pathway in EBV-associated tumors may be enhanced by miR-BART19-3p. © 2017 Wiley Periodicals, Inc.

Inhibition of EGF expression and NF-κB activity by treatment with quercetin leads to suppression of angiogenesis in nasopharyngeal carcinoma.

PubMed

Huang, Dong-Yan; Dai, Zhi-Rao; Li, Wei-Min; Wang, Rong-Guan; Yang, Shi-Ming

2018-05-01

The present study was performed to investigate the effect of quercetin on nasopharyngeal carcinoma (NPC) angiogenesis. The real-time RT-PCR and enzyme-linked immunosorbent assays (ELISA) were performed to analyze the expression levels of vascular endothelial growth factor (VEGF) in nasopharyngeal carcinoma cell lines prior to and after the quercetin treatment. Effect of quercetin on the rate of cell proliferation was measured by MTT assay. It was observed that quercetin treatment at a concentration of 10 mg/mL reduced the rate of NPC039 cell viability to 36% compared to control after 24 h. The expression of VEGF and activity of NF-κB was also markedly reduced. The ability of tube formation in HUVECs was inhibited significantly on exposure to quercetin compared to the untreated cells. Therefore, quercetin plays an important role in the inhibition of NPC039 nasopharyngeal carcinoma and can be of therapeutic importance.

Nasopharyngeal carcinoma: clinical and radiographic findings in children

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bass, I.S.; Haller, J.O.; Berdon, W.E.

1985-09-01

Nasopharyngeal carcinoma (NPC) in childhood occurs so infrequently that it is not suspected in affected children until the disease has been present for a long time and local spreading has occurred. The survival rates are therefore quite poor. Six children with NPC are described. A massive local lymph node spread simulating lymphoma was present in half of the patients; in the other half the disease was more subtle, presenting with epistaxis and CNS involvement. If an evaluation of the nasopharynx were part of the initial physical examination in children, the diagnosis of NPC would be made earlier and survival ratesmore » would improve.« less

[Rare earth elements contents and distribution characteristics in nasopharyngeal carcinoma tissue].

PubMed

Zhang, Xiangmin; Lan, Xiaolin; Zhang, Lingzhen; Xiao, Fufu; Zhong, Zhaoming; Ye, Guilin; Li, Zong; Li, Shaojin

2016-03-01

To investigate the rare earth elements(REEs) contents and distribution characteristics in nasopharyngeal carcinoma( NPC) tissue in Gannan region. Thirty patients of NPC in Gannan region were included in this study. The REEs contents were measured by tandem mass spectrometer inductively coupled plasma(ICP-MS/MS) in 30 patients, and the REEs contents and distribution were analyzed. The average standard deviation value of REEs in lung cancer and normal lung tissues was the minimum mostly. Light REEs content was higher than the medium REEs, and medium REEs content was higher than the heavy REEs content. REEs contents changes in nasopharyngeal carcinoma were variable obviously, the absolute value of Nd, Ce, Pr, Gd and other light rare earth elements were variable widely. The degree of changes on Yb, Tb, Ho and other heavy rare earth elements were variable widely, and there was presence of Eu, Ce negative anomaly(δEu=0. 385 5, δCe= 0. 523 4). The distribution characteristic of REEs contents in NPC patients is consistent with the parity distribution. With increasing atomic sequence, the content is decline wavy. Their distribution patterns were a lack of heavy REEs and enrichment of light REEs, and there was Eu , Ce negative anomaly.

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

NASA Astrophysics Data System (ADS)

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.

Gallic Acid Inhibited Matrix Invasion and AP-1/ETS-1-Mediated MMP-1 Transcription in Human Nasopharyngeal Carcinoma Cells

PubMed Central

S. Pang, Jong-Hwei; Yen, Jia-Hau; Wu, Hsiao-Ting; Huang, Sheng-Teng

2017-01-01

Gallic acid is a trihydroxybenzoic acid found in natural herbal plants. Gallic acid has been reported to inhibit the migration and invasive capability of various cancers. Little is known about the underlying mechanisms of invasion responsible for cancer metastasis via gallic acid. The present study was intended to investigate the anti-invasive effect of gallic acid on human nasopharyngeal carcinoma cells (NPC-BM1) and its related mechanism. Gallic acid inhibited the invasion of NPC-BM1 cells dose- and time-dependently without significant cytotoxic effect. Affymetrix oligonucleotide microarray analysis revealed matrix metalloproteinase-1 (MMP-1) as the most down-regulated gene in NPC-BM1 cells by gallic acid. The cytosolic and secreted MMP-1 levels were both found to be inhibited by gallic acid as demonstrated by western blot analysis and ELISA respectively. The mRNA expression and transcription of MMP-1 gene was also down-regulated as determined by RT/real-time PCR and promoter activity assay. The expression of two major transcription binding factors in the MMP-1 promoter, AP-1 and ETS-1, were demonstrated to be reduced by gallic acid in NPC-BM1 cells. The effect of gallic acid was associated with the inhibition of p38 MAPK signaling pathway. In addition, gallic acid enhanced the gene expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) which further suppressed the MMP-1 activity. These findings may be useful to develop a novel chemotherapeutic agent to inhibit the metastasis of nasopharyngeal cancer. PMID:28672814

Gallic Acid Inhibited Matrix Invasion and AP-1/ETS-1-Mediated MMP-1 Transcription in Human Nasopharyngeal Carcinoma Cells.

PubMed

Pang, Jong-Hwei S; Yen, Jia-Hau; Wu, Hsiao-Ting; Huang, Sheng-Teng

2017-06-24

Gallic acid is a trihydroxybenzoic acid found in natural herbal plants. Gallic acid has been reported to inhibit the migration and invasive capability of various cancers. Little is known about the underlying mechanisms of invasion responsible for cancer metastasis via gallic acid. The present study was intended to investigate the anti-invasive effect of gallic acid on human nasopharyngeal carcinoma cells (NPC-BM1) and its related mechanism. Gallic acid inhibited the invasion of NPC-BM1 cells dose- and time-dependently without significant cytotoxic effect. Affymetrix oligonucleotide microarray analysis revealed matrix metalloproteinase-1 (MMP-1) as the most down-regulated gene in NPC-BM1 cells by gallic acid. The cytosolic and secreted MMP-1 levels were both found to be inhibited by gallic acid as demonstrated by western blot analysis and ELISA respectively. The mRNA expression and transcription of MMP-1 gene was also down-regulated as determined by RT/real-time PCR and promoter activity assay. The expression of two major transcription binding factors in the MMP-1 promoter, AP-1 and ETS-1, were demonstrated to be reduced by gallic acid in NPC-BM1 cells. The effect of gallic acid was associated with the inhibition of p38 MAPK signaling pathway. In addition, gallic acid enhanced the gene expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) which further suppressed the MMP-1 activity. These findings may be useful to develop a novel chemotherapeutic agent to inhibit the metastasis of nasopharyngeal cancer.

[Effect of intensity modulated radiation therapy on oral mucosa and immune function in patients with nasopharyngeal carcinoma].

PubMed

Liang, Shaoqiang; Zhang, Ning; Chen, Lusi; Zhang, Yang; Zheng, Zhenhe; Luo, Weijun; Xu, Tao; Lü, Zhiqian; Li, Shao'en

2018-05-28

control group (all P<0.01).
 Conclusion: In the process of treatment in patients with nasopharyngeal carcinoma, the use of IMRT on the basis of chemotherapy is more effective than the conventional two-dimensional radiotherapy, which can reduce the proportion of grade 4 (severe) acute oral mucosa reaction. It may be related to the protective effect of IMRT on immune function in the patients.

Nasopharyngeal carcinoma with headaches as the main symptom: A potential diagnostic pitfall.

PubMed

Wu, Zhou-Xue; Xiang, Li; Rong, Jin-Feng; He, Huai-Lin; Li, Dan

2016-01-01

The aim of this study was to investigate medical-related reasons for misdiagnosis of nasopharyngeal carcinoma. (NPC) patients presenting with headaches alone or accompanied by other symptoms. Two-hundred and nineteen NPC cases describing headaches as one of the initial symptoms during primary treatment were selected for this prospective study. Medical records were carefully collected and all data were summarized for final analyses. Distributions of NPC stage in the patients were: Stage II, 1.4%; stage III, 46.6%; stage IVA, 36.1%; stage IVB, 7.7%; and stage IVC, 8.2%. The ratio of men to women was 2.42:1 (155/64 cases). The total misdiagnosis rate was 43.4%. Patients that only complained of headaches had the highest misdiagnosis rate of 86.4% (19/22 cases). The lowest misdiagnosis rate of 10.9% (5/46 cases) was observed in patients with both headaches and epistaxis. The misdiagnosis rate in rural hospitals was more than two times that in provincial hospitals. Neurosurgery departments had a 100% misdiagnosis rate. Frequently, headaches are the only prominent symptom of NPC. Due to the various clinical manifestations, NPC patients encounter a high misdiagnosis rate, which leads to unsatisfactory treatment outcomes. Improved awareness of the various nonspecific symptoms of NPC by nonspecialist physicians will be a pivotal step in decreasing the misdiagnosis rate. Mini Abstract: The misdiagnosis rate of nasopharyngeal carcinoma (NPC) patients with headaches was 43.4%. Improved awareness of the various nonspecific symptoms of NPC is a pivotal step in decreasing the misdiagnosis rate.

[Dynamic observation on the short-term change of xerostomia after intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma].

PubMed

Li, Yanjie; Zhao, Changqing

2015-01-01

To dynamically analyze the change of xerostomia in patients with nasopharyngeal carcinoma after radiotherapy by DW MRI. Twenty-three nasopharyngeal carcinoma patients confirmed by pathology were enrolled. Male/Female: 19/4. The age was from 37 to 69 years. The patients were divided into two groups: G1, Dmean<26 Gy, G2, Dmean ≥ 26 Gy. All patients underwent salivary glands examination by DW MRI before IMRT, at the end of IMRT, 6 months and 12 months after IMRT, at the same time the ADC value of salivary glands were calculated. According to the RTOG/EORTC salivary gland injury grading standard and referring the subjective index, the degree of xerostomia was assessed. SPSS 13.0 and SAS 8.2 software were used to analyze the data. At the end of IMRT, the change tendency of ADC in parotid and submandibular glands value was different in patients with different degree of xerostomia (F = 11.52, P < 0.01). At the end of IMRT, a significant difference for degree of xerostomia could be found in patients within different irradiation dose groups (Z = -3.622, P < 0.01). Clinical stage, treatment mode and age had no significant effect on the degree of xerostomia for patients at the end of IMRT (Z value was -0.791, -0.949, 2.488, all P > 0.05). A significant difference of xerostomia degree in patients was found at the various follow-up time after IMRT (χ(2) = 19.59, P < 0.01). There is good correlation between the function of salivary gland and subjective rating of xerostomia in patients with nasopharyngeal carcinoma after radiotherapy. The degrees of salivary gland function and dry mouth in patients with nasopharyngeal carcinoma damage evaluate with illuminated dose increases. The function of salivary gland gradually restored and the degree of dry mouth gradually reduce with the extension of time after radiotherapy.

Bevacizumab, Cisplatin, Radiation Therapy, and Fluorouracil in Treating Patients With Stage IIB, Stage III, Stage IVA, or Stage IVB Nasopharyngeal Cancer

ClinicalTrials.gov

2018-01-04

Stage II Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage III Nasopharyngeal Undifferentiated Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7

XRCC3 polymorphisms are associated with the risk of developing radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with intensity modulation radiated therapy.

PubMed

Zou, Yan; Song, Tao; Yu, Wei; Zhao, Ruping; Wang, Yong; Xie, Ruifei; Chen, Tian; Wu, Bo; Wu, Shixiu

2014-03-01

The incidence of radiation-induced late xerostomia varies greatly in nasopharyngeal carcinoma patients treated with radiotherapy. The single-nucleotide polymorphisms in genes involved in DNA repair and fibroblast proliferation may be correlated with such variability. The purpose of this paper was to evaluate the association between the risk of developing radiation-induced late xerostomia and four genetic polymorphisms: TGFβ1 C-509T, TGFβ1 T869C, XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. The severity of late xerostomia was assessed using a patient self-reported validated xerostomia questionnaire. Polymerase chain reaction-ligation detection reaction methods were performed to determine individual genetic polymorphism. The development of radiation-induced xerostomia associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for equivalent uniform dose. A total of 43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox proportional hazard analyses showed a higher risk of late xerostomia for patients with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for higher risk of late xerostomia. To our knowledge, this is the first study that demonstrated an association between genetic polymorphisms and the risk of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. Our findings suggest that the polymorphisms in XRCC3 are significantly associated with the risk of developing radiation-induced late xerostomia.

Monoacylglycerol lipase promotes metastases in nasopharyngeal carcinoma.

PubMed

Hu, Wen-Rong; Lian, Yi-Fan; Peng, Li-Xia; Lei, Jin-Ju; Deng, Cheng-Cheng; Xu, Miao; Feng, Qi-Sheng; Chen, Li-Zhen; Bei, Jin-Xin; Zeng, Yi-Xin

2014-01-01

Monoacylglycerol lipase (MAGL) is a serine hydrolase that hydrolyzes monoacylglycerides into free fatty acids and glycerol. It has recently been found to be involved in cancer progression through the free fatty acid or endocannabinoid network after studies on its function in the endocannabinoid system. Here, we determined a role for MAGL in nasopharyngeal carcinoma (NPC), which is known for its high metastatic potential. Among the different NPC cells we tested, MAGL was highly expressed in high metastatic NPC cells, whereas low metastatic potential NPC cells exhibited lower expression of MAGL. Overexpression of MAGL in low metastatic NPC cells enhanced their motile behavior and metastatic capacity in vivo. Conversely, knockdown of MAGL reduced the motility of highly metastatic cells, reducing their metastatic capacity in vivo. Growth rate was not influenced by MAGL in either high or low metastatic cells. MAGL expression was associated with the epithelial-mesenchymal transition (EMT) proteins, such as E-cadherin, vimentin and Snail. It was also related to the sidepopulation (SP) of NPC cells. Our findings establish that MAGL promotes metastases in NPC through EMT, and it may serve as a target for the prevention of NPC metastases.

Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma

PubMed Central

Ni, Haifeng; Jiang, Bo; Zhou, Zhen; Yuan, Xiaoyang; Cao, Xiaolin; Huang, Guangwu; Li, Yong

2017-01-01

The aim of this study was to investigate the inactivation of the MutS homolog human 3 (MSH3) gene by promoter methylation in nasopharyngeal carcinoma (NPC). Methylation-specific PCR, semi-quantitative reverse transcription PCR and immunohistochemical analysis were used to detect methylation and the mRNA and protein expression levels of MSH3 in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues. The association between promoter methylation and mRNA expression, and the mRNA and protein expression of the gene and clinical factors was analyzed. The promoter methylation of MSH3 was detected in 50% (27/54) of the primary tumors, but not in the 16 NNE tissues. The mRNA and protein expression levels were significantly decreased in the 54 cases of human NPC as compared to the 16 NNE tissues (P<0.05). The MSH3-methylated cases exhibited significantly lower mRNA and protein expression levels than the unmethylated cases (P<0.05). The MSH3 mRNA and protein expression levels were significantly associated with the variable T stage (P<0.05); however, they did not correlate with the age and sex of the patients, or with the N stage, TNM classification or histopathological subtype (P>0.05). On the whole, MSH3 was frequently inactivated by promoter methylation and its mRNA and protein expression correlated with the primary tumor stage in NPC. PMID:28656302

Vorinostat and Azacitidine in Treating Patients With Locally Recurrent or Metastatic Nasopharyngeal Cancer or Nasal Natural Killer T-Cell Lymphoma

ClinicalTrials.gov

2018-04-20

Adult Nasal Type Extranodal NK/T-Cell Lymphoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Nasopharyngeal Undifferentiated Carcinoma; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Undifferentiated Carcinoma AJCC v7

Branchial cleft cyst: An unusual site for the cervical metastasis of nasopharyngeal carcinoma.

PubMed

Liao, Yu-Chang; Adel, Mohamad; Lee, Li-Yu; Chang, Kai-Ping

2018-04-01

Cancers found in the resected branchial cleft cyst are rare clinically but usually impose substantive diagnostic and treatment challenges for clinicians. A 31-year-old man presented with a lateral neck mass that was suspected to be an inflammatory branchial cleft cyst. After excision, the pathologic specimen revealed a benign cystic appearance with a focus of undifferentiated carcinoma. Serologic tests for Epstein-Barr virus were negative. A positron emission tomography scan and upper aerodigestive tract endoscopies were negative for any other suspicious lesion. The patient underwent random biopsies of the nasopharynx, tongue base, and hypopharynx and bil tonsillectomy. Pathologic examination of the nasopharyngeal biopsies showed the presence of undifferentiated carcinoma. The cancerous part of the branchial cleft cyst and this nasopharyngeal specimen were positive for the latent membrane protein-1 and EBV-encoded RNAs of Epstein-Barr virus (EBV) and confirmed our diagnosis. This is the first report of a NPC metastasizing to a branchial cleft cyst. Molecular diagnostic techniques facilitate the definite diagnosis that enabled us to refine treatment plans and offered the patient a favorable outcome. Copyright © 2017 Elsevier B.V. All rights reserved.

The time frame of Epstein-Barr virus latent membrane protein-1 gene to disappear in nasopharyngeal swabs after initiation of primary radiotherapy is an independently significant prognostic factor predicting local control for patients with nasopharyngeal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, S.-Y.; Chang, K.-P.; Graduate Institute of Clinical Medical Sciences, Chang Gung University, Linkou, Taiwan

Purpose: The presence of Epstein-Barr virus latent membrane protein-1 (LMP-1) gene in nasopharyngeal swabs indicates the presence of nasopharyngeal carcinoma (NPC) mucosal tumor cells. This study was undertaken to investigate whether the time taken for LMP-1 to disappear after initiation of primary radiotherapy (RT) was inversely associated with NPC local control. Methods and Materials: During July 1999 and October 2002, there were 127 nondisseminated NPC patients receiving serial examinations of nasopharyngeal swabbing with detection of LMP-1 during the RT course. The time for LMP-1 regression was defined as the number of days after initiation of RT for LMP-1 results tomore » turn negative. The primary outcome was local control, which was represented by freedom from local recurrence. Results: The time for LMP-1 regression showed a statistically significant influence on NPC local control both univariately (p < 0.0001) and multivariately (p = 0.004). In multivariate analysis, the administration of chemotherapy conferred a significantly more favorable local control (p = 0.03). Advanced T status ({>=} T2b), overall treatment time of external photon radiotherapy longer than 55 days, and older age showed trends toward being poor prognosticators. The time for LMP-1 regression was very heterogeneous. According to the quartiles of the time for LMP-1 regression, we defined the pattern of LMP-1 regression as late regression if it required 40 days or more. Kaplan-Meier plots indicated that the patients with late regression had a significantly worse local control than those with intermediate or early regression (p 0.0129). Conclusion: Among the potential prognostic factors examined in this study, the time for LMP-1 regression was the most independently significant factor that was inversely associated with NPC local control.« less

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

PubMed

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

2016-10-15

Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma on the mucosal lining of the nasopharynx. The etiology of NPC remains elusive despite many reported studies. Most studies employ a single platform approach, neglecting the cumulative influence of both the genome and transcriptome toward NPC development. We aim to employ an integrated pathway approach to identify dysregulated pathways linked to NPC. Our approach combines imputation NPC GWAS data from a Malaysian cohort as well as published expression data GSE12452 from both NPC and non-NPC nasopharynx tissues. Pathway association for GWAS data was performed using MAGENTA while for expression data, GSA-SNP was used with gene p values derived from differential expression values from GEO2R. Our study identified NPC association in the gene ontology (GO) axonemal dynein complex pathway (pGWAS-GSEA  = 1.98 × 10(-2) ; pExpr-GSEA  = 1.27 × 10(-24) ; pBonf-Combined  = 4.15 × 10(-21) ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (pAmpliSeq-GSEA  = 6.56 × 10(-4) ). Loss of function in the axonemal dynein complex causes impaired cilia function, leading to poor mucociliary clearance and subsequently upper or lower respiratory tract infection, the former of which includes the nasopharynx. Our approach illustrates the potential use of integrated pathway analysis in detecting gene sets involved in the development of NPC in the Malaysian cohort. © 2016 UICC.

Expression of mismatch repair gene PMS2 in nasopharyngeal carcinoma and regulation by glycogen synthase kinase-3β in vivo and in vitro.

PubMed

Fang, Jugao; Lei, Wenbin; Huang, Xiaoming; Li, Pingdong; Chen, Xiaohong; Zhu, Xiaolin; Wen, Weiping; Li, Huabin

2012-02-01

To evaluate the expression of mismatch repair gene PMS2 in human nasopharyngeal carcinoma (NPC) tissues and evaluate the effect of glycogen synthase kinase (GSK)-3β on PMS2 production in vivo and in vitro. The expression of PMS2 and inactivated phosphorylated GSK-3β(s9) was examined by immunohistochemical staining in 25 NPC tissues and the relation was determined by correlation analysis. The effect of GSK-3β transfection in CNE-2 cells on PMS2 production as well as cell apoptosis and chemosensitization were evaluated using small interference RNA (siRNA), immunoblotting and flow cytometric analysis in vitro. The expression of inactivated phosphorylated GSK-3β(s9) was found to negative correlated with PMS2 in vivo. And transfected GSK-3β was found to be able to enhance PMS2 production, and increase cell apoptosis in CNE-2 cells in combination with cisplatin administration in vitro. Inactivation of GSK-3β might be important for NPC tumorgenesis through negatively regulating PMS2 production, and enhanced PMS2 production by GSK-3β is beneficial for understanding the NPC tumorgenesis and developing potential strategy for future therapy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Nasopharyngeal carcinoma with central nervous system metastases: Two case reports and a review of the literature.

PubMed

Shen, Chunying; Ying, Hongmei; Lu, Xueguan; Hu, Chaosu

2017-12-01

Central nervous system (CNS) metastases are rarely seen in patients with nasopharyngeal carcinoma (NPC). Two NPC patients developed CNS metastases were collected in Fudan University Shanghai Cancer Center. The medical records were reviewed to document patients' characteristics, treatment, and outcomes. In addition, we also provide an overview of the literature concerning this scenario. Both patients were staged T4N1M0 with pathologically confirmed CNS metastases from nasopharyngeal carcinoma. After the completion of initial chemoradiotherapy, metastases to CNS including brain and/or spine occurred during follow-up. Surgical resection combined with palliative chemoradiation was offered to alleviate the symptoms. Although multiple treatment modalities were given, both patients succumbed to disease progression. The mechanism for CNS metastases is postulated through hematogenous route or cerebral spinal fluid spread. Good symptoms amelioration can be achieved with aggressive treatments such as surgery followed by palliative chemoradiation, but prognoses are ominous due to systematic disease dissemination.

Inactivation of MSH3 by promoter methylation correlates with primary tumor stage in nasopharyngeal carcinoma.

PubMed

Ni, Haifeng; Jiang, Bo; Zhou, Zhen; Yuan, Xiaoyang; Cao, Xiaolin; Huang, Guangwu; Li, Yong

2017-09-01

The aim of this study was to investigate the inactivation of the MutS homolog human 3 (MSH3) gene by promoter methylation in nasopharyngeal carcinoma (NPC). Methylation‑specific PCR, semi‑quantitative reverse transcription PCR and immunohistochemical analysis were used to detect methylation and the mRNA and protein expression levels of MSH3 in 54 cases of NPC tissues and 16 cases of normal nasopharyngeal epithelial (NNE) tissues. The association between promoter methylation and mRNA expression, and the mRNA and protein expression of the gene and clinical factors was analyzed. The promoter methylation of MSH3 was detected in 50% (27/54) of the primary tumors, but not in the 16 NNE tissues. The mRNA and protein expression levels were significantly decreased in the 54 cases of human NPC as compared to the 16 NNE tissues (P<0.05). The MSH3‑methylated cases exhibited significantly lower mRNA and protein expression levels than the unmethylated cases (P<0.05). The MSH3 mRNA and protein expression levels were significantly associated with the variable T stage (P<0.05); however, they did not correlate with the age and sex of the patients, or with the N stage, TNM classification or histopathological subtype (P>0.05). On the whole, MSH3 was frequently inactivated by promoter methylation and its mRNA and protein expression correlated with the primary tumor stage in NPC.

Identification of Genes with Allelic Imbalance on 6p Associated with Nasopharyngeal Carcinoma in Southern Chinese

PubMed Central

Wong, Alissa Michelle Go; Fan, Yan-Hui; Li, Miao-Xin; Bei, Jin-Xin; Jia, Wei-Hua; Zeng, Yi-Xin; Chan, Danny; Cheung, Kenneth M. C.; Sham, Pak; Chua, Daniel; Guan, Xin-Yuan; Song, You-Qiang

2011-01-01

Nasopharyngeal carcinoma (NPC) is a malignancy of epithelial origin. The etiology of NPC is complex and includes multiple genetic and environmental factors. We employed case-control analysis to study the association of chromosome 6p regions with NPC. In total, 360 subjects and 360 healthy controls were included, and 233 single nucleotide polymorphisms (SNPs) on 6p were examined. Significant single-marker associations were found for SNPs rs2267633 (p = 4.49×10−5), rs2076483 (most significant, p = 3.36×10−5), and rs29230 (p = 1.43×10−4). The highly associated genes were the gamma-amino butyric acid B receptor 1 (GABBR1), human leukocyte antigen (HLA-A), and HLA complex group 9 (HCG9). Haplotypic associations were found for haplotypes AAA (located within GABBR1, p-value  = 6.46×10−5) and TT (located within HLA-A, p = 0.0014). Further investigation of the homozygous genotype frequencies between cases and controls suggested that micro-deletion regions occur in GABBR1 and neural precursor cell expressed developmentally down-regulated 9 (NEDD9). Quantitative real-time polymerase chain reaction (qPCR) using 11 pairs of NPC biopsy samples confirmed the significant decline in GABBR1 and NEDD9 mRNA expression in the cancer tissues compared to the adjacent non-tumor tissue (p<0.05). Our study demonstrates that multiple chromosome 6p susceptibility loci contribute to the risk of NPC, possibly though GABBR1 and NEDD9 loss of function. PMID:21283797

Nasopharyngeal carcinoma heterogeneity of DNA content identified on cytologic preparations.

PubMed

Maohuai, C; Chang, A R; Lo, D

2001-06-01

To evaluate tumor heterogeneity of DNA content in nasopharyngeal carcinoma (NPC) performed on cytologic specimens. Image cytometric analysis of DNA ploidy status of 40 NPCs was performed on nasopharyngeal brushing smears stained with the Feulgen method after hematoxylin eosin staining. If the DNA distribution pattern from the same tumor exhibited diploid, aneuploid or/and tetraploid peaks or some combination of these patterns, the presence of tumor heterogeneity of DNA content was identified. Thirty-four cases (85%) had a nondiploid DNA pattern among the 40 NPCs. Twenty-eight cases exhibited tumor heterogeneity of DNA content (70%). Of the 28 tumors, 13 (46%) had a combination of diploid and tetraploid patterns, 10 (37%) had a combination of diploid and aneuploid patterns, 3 cases (11%) had a combination of tetraploid and aneuploid patterns, and 2 cases had two aneuploid stem lines. The relationship between DNA ploidy pattern and tumor histologic and cytologic morphology was also examined. There is a high incidence of DNA content heterogeneity in NPC. The relevance of tumor heterogeneity to the biologic behavior of NPC awaits further study. DNA quantification with image cytometry on destained cytologic preparations is feasible and reliable.

New Insights from Elucidating the Role of LMP1 in Nasopharyngeal Carcinoma

PubMed Central

Shair, Kathy H. Y.; Reddy, Akhil

2018-01-01

Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV) oncogenic protein that has no intrinsic enzymatic activity or sequence homology to cellular or viral proteins. The oncogenic potential of LMP1 has been ascribed to pleiotropic signaling properties initiated through protein-protein interactions in cytosolic membrane compartments, but the effects of LMP1 extend to nuclear and extracellular processes. Although LMP1 is one of the latent genes required for EBV-immortalization of B cells, the biology of LMP1 in the pathogenesis of the epithelial cancer nasopharyngeal carcinoma (NPC) is more complex. NPC is prevalent in specific regions of the world with high incidence in southeast China. The epidemiology and time interval from seroconversion to NPC onset in adults would suggest the involvement of multiple risk factors that complement the establishment of a latent and persistent EBV infection. The contribution of LMP1 to EBV pathogenesis in polarized epithelia has only recently begun to be elucidated. Furthermore, the LMP1 gene has emerged as one of the most divergent sequences in the EBV genome. This review will discuss the significance of recent advances in NPC research from elucidating LMP1 function in epithelial cells and lessons that could be learned from mining LMP1 sequence diversity. PMID:29561768

Nasopharyngeal carcinoma incidence in North Tunisia: negative trends in adults but not adolescents, 1994-2006.

PubMed

Wided, Ben Ayoub Hizem; Hamouda, Boussen; Hamadi, Hsairi; Mansour, Ben Abdallah

2015-01-01

Nasopharyngeal carcinoma (NPC) is the second most common neoplasm of head and neck in Tunisia. The distribution is bimodal with a first period occurrence between 15 and 20 years old and a second peak at around 50 years of age. Undifferentiated carcinoma of nasopharynx type III (UCNT) is the predominant histological type (93.4%). Data of cancer registry of North Tunisia confirmed that it is an intermediate risk area for NPC with overall ASRs of 3.6 and 1.6/100,000 respectively in males and females. This study aimed to present the evolution of incidence rate of nasopharyngeal carcinoma over a period of 12 years (1994-2006). Data of cancer registry of North Tunisia (NTCR), covering half of the Tunisian population, were used to determine evolution of NPC incidence, calculated by 5 year periods. The estimated annual percentage change (EAPC) was used as an estimate of the trend. To best summarize the behavior or the data trend across years, we used a join-point regression program. Between 1994 and 2006, we observed negative annual average change of standardized incidence in men and women (-3.3% and -2.7%) also for the standardized incidences which showed a rather important decline (26.4% in males and 22.3% in females). The truncated age standardized incidence rate of NPC in adults aged of 30 years old and more (N=1209) decreased by -0.4% per year from 1994 to 2006 over time in north Tunisia dropping from 6.09 to 4.14 person-years. However, the rate was relatively stable during this period among youths aged 0-29 years (N=233) in both sexes. NPC demonstrated a favorable evolution from 1994-2006 probably due to a improvement in socioeconomic conditions.

Synthesis and photodynamic activities of modified corrole derivatives on nasopharyngeal carcinoma cells

NASA Astrophysics Data System (ADS)

Chang, Chi K.; Kong, Pak-Wing; Liu, Hai-Yang; Yeung, Lam-Lung; Koon, Ho-Kee; Mak, Nai-Ki

2006-02-01

Ten trans-A2B and A3-type corrole photosensitizers carrying functional groups were synthesized and screened for PDT activities. Photocytotoxicity was measured by the MTT cell reduction assay on a cultured human nasopharyngeal carcinoma (NPC) cell line (HONE-1). Experimental results indicated that corroles containing a single hydroxyphenyl substituent (3, 4 and 5) exhibit the highest activity among the corrole derivatives investigated. Confocal microscopy revealed that the site of cellular localization of the photosensitizers is predominantly at mitochondria. Also, nuclear staining detected apoptotic cell death.

Omics-Based Identification of Biomarkers for Nasopharyngeal Carcinoma

PubMed Central

2015-01-01

Nasopharyngeal carcinoma (NPC) is a head and neck cancer that is highly found in distinct geographic areas, such as Southeast Asia. The management of NPC remains burdensome as the prognosis is poor due to the late presentation of the disease and the complex nature of NPC pathogenesis. Therefore, it is necessary to find effective molecular markers for early detection and therapeutic measure of NPC. In this paper, the discovery of molecular biomarker for NPC through the emerging omics technologies including genomics, miRNA-omics, transcriptomics, proteomics, and metabolomics will be extensively reviewed. These markers have been shown to play roles in various cellular pathways in NPC progression. The knowledge on their function will help us understand in more detail the complexity in tumor biology, leading to the better strategies for early detection, outcome prediction, detection of disease recurrence, and therapeutic approach. PMID:25999660

Clinical presentation of nasopharyngeal carcinoma in Sarawak Malaysia.

PubMed

Tiong, T S; Selva, K S

2005-12-01

Nasopharyngeal carcinoma (NPC) is a common cancer in Malaysia. The clinical presentation in Sarawak has not been well documented. A retrospective review of 213 selected NPC cases was undertaken on the clinical records in Sarawak General Hospital, Sarawak, from June 1999 to June 2003. There were 116 patients in Kuching and 97 in Serian. There were twice as many males as females. The youngest patient was 16 and the oldest 88 years old with a mean age of 51 years. The four most common symptoms in order of frequencies were cervical lymphadenopathy, epistaxis, hearing loss and diplopia. 80.8% of the patients presented with cervical lymphadenopathy and about 85% of the patients presented in the advanced stages. Very small percentages of the patients were found to have single presenting symptoms of epistaxis (2.4%) and hearing loss (0.5%).

Unusual coexistence of extramedullary plasmacytoma and nasopharyngeal carcinoma in nasopharynx.

PubMed

Du, Ri-Chang; Li, Hai-Nan; Huang, Wei; Tian, Xiao-Ying; Li, Zhi

2015-09-17

Nasopharyngeal carcinoma (NPC) is an EBV-associated malignant tumor of nasopharynx. As extremely rare condition, the second primary cancer of nasopharynx can occur in NPC patients synchronously or subsequently. Extramedullary plasmacytoma (EMP) is a rare tumor and commonly originates in the head and neck region. However, there is no report to describe a collision tumor of NPC and EMP occurring in the same nasopharyngeal mass. We report here an unusual case of synchronous coexistence of NPC and EMP occurring in the nasopharynx of an old male patient. A 63-year-old male patient presented with a 3-month history of right-sided nasal obstruction and recently intermittent epistaxis without enlargement of cervical lymph nodes. The solitary mass of nasopharynx was found by radiological and nasopharyngeal examination. Histologically, the mass contained two separated portions and displayed typically histological features of NPC and EMP, respectively. In EMP portion, the tumor was composed of monomorphic plasmacytoid-appearing cells with immuno-positive to CD79a, CD138, CD38, MUM-1 and CD56, but lack immunoreactivity to pan-CK (AE1/AE3), CD20, CD21 and EBERs. In NPC portion, the tumor cells formed irregular-shaped islands with diffusely immuno-positive to pan-CK (AE1/AE3), EMA and EBERs, but lack expressions of lymphoplasmacytic markers. A diagnosis of simultaneous occurrence of EMP and NPC in nasopharynx was made. There was no evidence of tumor recurrence or metastasis 18-month follow-up after radiotherapy. To our knowledge, it may be the first case of coexistence of EMP and NPC synchronously. In addition, the histological differential diagnosis and relevant potential mechanism of this unusual collision tumor were also discussed.

[Clinical efficacy of alternating chemo-radiotherapy for locally advanced nasopharyngeal carcinoma].

PubMed

You, Xi; Yang, Yucheng

2014-03-01

The purpose of this study is to investigate the effective of alternating Chemo-radiotherapy for locally Advanced Nasopharyngeal Carcinoma. Retrospective analysis 106 cases of patients with locally advanced nasopharyngeal carcinoma between November 2005 and March 2007. All patients received cisplatin-based chemotherapy but 15 patients received radiotherapy(RT) alone. Inducing chemotherapy (IC) + RT + adju-vant chemotherapy (AC) regimen in 36 patients, IC+RT regimen was delivered in 25 patients and AC + RT regimen in 30 patients. 61 patients received 1 to 2 cycles of inducing chemotherapy and 66 patients received 3 to 6 cycles of adjuvant chemotherapy after radiotherapy. Chemotherapy started on the first day after the end of the induction chemotherapy, adjuvant chemotherapy begun after radiotherapy for a week. All patients were treated by radiotherapy using 60 Co r-ray, the nasophyarynx primary site was given a total does of 68 -74 Gy. The lymph nodes of the neck was given 60 to 70 Gy. The prophylactic irradiation does of the neck was 48-50 Gy. RESCULT: The median follow up time was 51 months. A total of 58 patients died, the overall survival rate was 45% in whole groups. The 5-year overall survival rates were 33%, 63%, 60% and 50% in RT, IC + RT + AC, IC + RT and RT+AC group, respectively. The 5-year disease-free survival rates were 13%, 56%, 48% and 40% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year relapse-free survival rates were 13%, 53%, 48% and 50% in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The 5-year metastasis-free survival rates were 6%, 50%, 44% and 47% in RT, IC + RT + AC, IC+ RT and RT + AC group, respectively. There was significant difference in all groups (P < 0.05). The median time to relapses were 22 months, 29 months, 28 months and 25 months in RT, IC + RT + AC, IC + RT and RT + AC group, respectively. The median time to first distant metastasis were 10 months, 19 months, 15 months and 12 months in RT, IC

Nasopharyngeal carcinoma in Malaysian Chinese: occupational exposures to particles, formaldehyde and heat.

PubMed

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

2000-12-01

During 1990-1992, 282 Chinese residents of Selangor and the Federal Territory, Malaysia with histologically confirmed nasopharyngeal carcinoma (NPC) were interviewed about occupational history, diet, alcohol consumption, and tobacco use, as were an equal number of Malaysian Chinese population controls, pair-matched to cases by age and sex. Exposures to 20 kinds of workplace substances, solar and industrial heat, and cigarette smoke, were analysed by univariate and multivariate methods. Nasopharyngeal carcinoma was associated with occupational exposures to construction, metal and wood dusts; motor fuel and oil; paints and varnishes; certain other chemicals; industrial heat; solar heat from outdoor occupations; certain smokes; cigarette smoking; and childhood exposure to parental smoking. After adjustment for risk from diet and cigarette smoke, only wood dust (OR = 2.36; 95% CI : 1.33- 4.19), and industrial heat (OR = 2.21; 95% CI : 1.12-4.33) remained clearly associated. Wood dust remained statistically significant after further adjustment for social class. No significant crude or adjusted association was found between NPC and formaldehyde (adjusted OR = 0.71; 95% CI : 0.34-1.43). This study supports previous findings that some occupational inhalants are risk factors for NPC. The statistical effect of wood dust remained substantial after adjustment for diet, cigarette smoke, and social class. Intense industrial heat emerged as a previously unreported risk factor, statistically significant even after adjustment for diet and cigarette smoke. No association was found between NPC and formaldehyde.

Diffusion tensor imaging and 1H-MRS study on radiation-induced brain injury after nasopharyngeal carcinoma radiotherapy.

PubMed

Wang, H-Z; Qiu, S-J; Lv, X-F; Wang, Y-Y; Liang, Y; Xiong, W-F; Ouyang, Z-B

2012-04-01

To investigate the metabolic characteristics of the temporal lobes following radiation therapy for nasopharyngeal carcinoma using diffusion tensor imaging (DTI) and proton magnetic resonance spectroscopy ((1)H-MRS). DTI and (1)H-MRS were performed in 48 patients after radiotherapy for nasopharyngeal carcinoma and in 24 healthy, age-matched controls. All patients and controls had normal findings on conventional MRI. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), three eigenvalues λ1, λ2, λ3, N-acetylaspartic acid (NAA)/choline (Cho), NAA/creatinine (Cr), and Cho/Cr were measured in both temporal lobes. Patients were divided into three groups according to time after completion of radiotherapy: group 1, less than 6 months; group 2, 6-12 months; group 3, more than 12 months. Mean values for each parameter were compared using one-way analysis of variance (ANOVA). Mean FA in group 1 was significantly lower compared to group 3 and the control group (p < 0.05). Group-wise comparisons of apparent diffusion coefficient (ADC) values among all the groups were not significantly different. Eigenvalue λ1 was significantly lower in groups 1 and 3 compared to the control group (p < 0.05). NAA/Cho and NAA/Cr were significantly lower in each group compared to the control group (p < 0.01 for both). The decrease in NAA/Cho was greatest in group 1. There were no significant between-group differences regarding Cho/Cr. A combination of DTI and (1)H-MRS can be used to detect radiation-induced brain injury, in patients treated for nasopharyngeal carcinoma. Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Study on nasopharyngeal cancer tissue using surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ge, Xiaosong; Lin, Xueliang; Xu, Zhihong; Wei, Guoqiang; Huang, Wei; Lin, Duo

2016-10-01

Surface-enhanced Raman spectroscopy (SERS) can provide detailed molecular structure and composition information, and has demonstrated great potential in biomedical filed. This spectroscopy technology has become one of the most important optical techniques in the early diagnosis of cancer. Nasopharyngeal cancer (NPC) is a malignant neoplasm arising in the nasopharyngeal epithelial lining, which has relatively high incidence and death rate in Southeast Asia and southern China. This paper reviews the current progress of SERS in the field of cancer diagnostics, including gastric cancer, colorectal cancer, cervical cancer and nasopharyngeal cancer. In addition to above researches, we recently develop a novel NPC detection method based on tissue section using SERS, and obtain primary results. The proposed method has promising potential for the detection of nasopharyngeal carcinoma.

Modeling nasopharyngeal carcinoma in three dimensions

PubMed Central

Siva Sankar, Prabu; Che Mat, Mohd Firdaus; Muniandy, Kalaivani; Xiang, Benedict Lian Shi; Ling, Phang Su; Hoe, Susan Ling Ling; Khoo, Alan Soo-Beng; Mohana-Kumaran, Nethia

2017-01-01

Nasopharyngeal carcinoma (NPC) is a type of cancer endemic in Asia, including Malaysia, Southern China, Hong Kong and Taiwan. Treatment resistance, particularly in recurring cases, remains a challenge. Thus, studies to develop novel therapeutic agents are important. Potential therapeutic compounds may be effectively examined using two-dimensional (2D) cell culture models, three-dimensional (3D) spheroid models or in vivo animal models. The majority of drug assessments for cancers, including for NPC, are currently performed with 2D cell culture models. This model offers economical and high-throughput screening advantages. However, 2D cell culture models cannot recapitulate the architecture and the microenvironment of a tumor. In vivo models may recapitulate certain architectural and microenvironmental conditions of a tumor, however, these are not feasible for the screening of large numbers of compounds. By contrast, 3D spheroid models may be able to recapitulate a physiological microenvironment not observed in 2D cell culture models, in addition to avoiding the impediments of in vivo animal models. Thus, the 3D spheroid model offers a more representative model for the study of NPC growth, invasion and drug response, which may be cost-effective without forgoing quality. PMID:28454359

Widespread expression of prostate apoptosis response-4 in nasopharyngeal carcinoma.

PubMed

Lee, Jeng-Woei; Hsiao, Wei-Ting; Lee, Kuei-Fang; Sheu, Lai-Fa; Hsu, Hsue-Yin; Hsu, Lee-Ping; Su, Borcherng; Lee, Moon-Sing; Hsu, Yih-Chih; Chang, Chung-Hsing

2010-07-01

Prostate apoptosis response-4 (Par-4) augments apoptosis in various tumors, either during apoptotic insult or by ectopic overexpression. However, investigation of Par-4 expression in nasopharyngeal carcinoma (NPC) is lacking. Specimens from patients with NPC, hypopharyngeal carcinoma (HPC), or oral cavity cancer were examined for Par-4 expression using immunohistochemistry. NPC cell proliferation and apoptosis were analyzed using immunohistochemical staining for Ki67, B-cell lymphoma 2 (Bcl-2), and in situ terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick end-labeling (TUNEL) assay, respectively. Par-4 was ubiquitously expressed in NPC biopsies (96.2%, 25/26) and was significantly higher than in HPC (47.6%, 50/105, p < .0001) and oral cavity cancers (38.7%, 12/31, p < .0001). Remarkably, apoptosis of NPC cells was absent and Par-4 expression was associated with obvious expression of Bcl-2 and Ki67 in all patients tested with NPC. Immunohistochemistry results showed widespread expression of Par-4 in NPC and revealed sustainable proliferation of NPC cells regardless of Par-4 expression. .(c) 2009 Wiley Periodicals, Inc.

Study of single nucleotide polymorphisms of tumour necrosis factors and HSP genes in nasopharyngeal carcinoma in North East India.

PubMed

Lakhanpal, Meena; Singh, Laishram Chandreshwor; Rahman, Tashnin; Sharma, Jagnnath; Singh, M Madhumangal; Kataki, Amal Chandra; Verma, Saurabh; Pandrangi, Santhi Latha; Singh, Y Mohan; Wajid, Saima; Kapur, Sujala; Saxena, Sunita

2016-01-01

Nasopharyngeal carcinoma (NPC) is an epithelial tumour with a distinctive racial and geographical distribution. High incidence of NPC has been reported from China, Southeast Asia, and northeast (NE) region of India. The immune mechanism plays incredibly role in pathogenesis of NPC. Tumour necrosis factors (TNFs) and heat shock protein 70 (HSP 70) constitute significant components of innate as well as adaptive host immunity. Multi-analytical approaches including logistic regression (LR), classification and regression tree (CART) and multifactor dimensionality reduction (MDR) were applied in 120 NPC cases and 100 controls to explore high order interactions among TNF-α (-308 G>A), TNF β (+252 A>G), HSP 70-1 (+190 G>C), HSP 70-hom (+2437 T>C) genes and environmental risk factors. TNF β was identified as the primary etiological factor by all three analytical approaches. Individual analysis of results showed protective effect of TNF β GG genotype (adjusted odds ratio (OR2) = 0.27, 95 % CI = 0.125-0.611, P = 0.001), HSP 70 (+2437) CC genotype (OR2 = 0.17, 95 % CI = 0.0430.69, P = 0.013), while AG genotype of TNF β was found significantly associated with risk of NPC (OR2 = 1.97, 95 % CI = 1.019-3.83, P = 0.04). Analysis of environmental factors demonstrated association of alcohol consumption, living in mud houses and use of firewood for cooking as major risk factors for NPC. Individual haplotype association analysis showed significant risk associated with GTGA haplotype (OR = 68.61, 95 % CI = 2.47-190.37, P = 0.013) while a protective effect with CCAA and GCGA haplotypes (OR = 0.19, 95 % CI = 0.05-0.75, P = 0.019; OR = 0.01 95 % CI = 0.05-0.30, P = 0.007). The multi-analytical approaches applied in this study helped in identification of distinct gene-gene and gene-environment interactions significant in risk assessment of NPC.

Nasopharyngeal Case-Control Study

Cancer.gov

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

Epstein-Barr virus infection and nasopharyngeal carcinoma: the other side of the coin.

PubMed

Perri, Francesco; Della Vittoria Scarpati, Giuseppina; Giuliano, Mario; D'Aniello, Carmine; Gnoni, Antonio; Cavaliere, Carla; Licchetta, Antonella; Pisconti, Salvatore

2015-11-01

Oncogenic viruses may have a significant impact on the therapeutic management of several malignancies besides their well-known role in tumor pathogenesis. Epstein-Barr virus (EBV) induces neoplastic transformation of epithelial cells of the nasopharynx by various molecular mechanisms mostly involving activation of oncogenes and inactivation of tumor-suppressor genes. EBV infection can also induce the expression of several immunogenic peptides on the plasma membrane of the infected cells. Importantly, these virus-related antigens may be used as targets for antitumor immunotherapy-based treatment strategies. Two different immunotherapy strategies, namely adoptive and active immunotherapy, have been developed and strongly improved in the recent years. Furthermore, EBV infection may influence the use of targeted therapies for nasopharyngeal carcinoma (NPC) considering that the presence of EBV can induce important modifications in cell signaling. As an example, latent membrane protein type 1 is a viral transmembrane protein mainly involved in the cancerogenesis process, which can also mediate overexpression of the epidermal growth factor receptor (EGFR) in NPC cells, rendering them more sensitive to anti-EGFR therapy. Finally, EBV may induce epigenetic changes in the infected cells, such as DNA hypermethylation and histone deacetylation, that can sustain tumor growth and can thus be considered potential targets for novel therapies. In conclusion, EBV infection can modify important biological features of NPC cells, rendering them more vulnerable to both immunotherapy and targeted therapy.

The candidate tumor suppressor gene BLU, located at the commonly deleted region 3p21.3, is an E2F-regulated, stress-responsive gene and inactivated by both epigenetic and genetic mechanisms in nasopharyngeal carcinoma.

PubMed

Qiu, Guo-Hua; Tan, Luke K S; Loh, Kwok Seng; Lim, Chai Yen; Srivastava, Gopesh; Tsai, Sen-Tien; Tsao, Sai Wah; Tao, Qian

2004-06-10

Loss of heterozygosity at 3p21 is common in various cancers including nasopharyngeal carcinoma (NPC). BLU is one of the candidate tumor suppressor genes (TSGs) in this region. Ectopic expression of BLU results in the inhibition of colony formation of cancer cells, suggesting that BLU is a tumor suppressor. We have identified a functional BLU promoter and found that it can be activated by environmental stresses such as heat shock, and is regulated by E2F. The promoter and first exon are located within a CpG island. BLU is highly expressed in testis and normal upper respiratory tract tissues including nasopharynx. However, in all seven NPC cell lines examined, BLU expression was downregulated and inversely correlated with promoter hypermethylation. Biallelic epigenetic inactivation of BLU was also observed in three cell lines. Hypermethylation was further detected in 19/29 (66%) of primary NPC tumors, but not in normal nasopharyngeal tissues. Treatment of NPC cell lines with 5-aza-2'-deoxycytidine activated BLU expression along with promoter demethylation. Although hypermethylation of RASSF1A, another TSG located immediately downstream of BLU, was detected in 20/27 (74%) of NPC tumors, no correlation between the hypermethylation of these two TSGs was observed (P=0.6334). In addition to methylation, homozygous deletion of BLU was found in 7/29 (24%) of tumors. Therefore, BLU is a stress-responsive gene, being disrupted in 83% (24/29) of NPC tumors by either epigenetic or genetic mechanisms. Our data are consistent with the interpretation that BLU is a TSG for NPC.

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

PubMed Central

2014-01-01

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

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

PubMed

Zhang, Xiangmin; Liu, Folin; Lan, Xiaolin; Yu, Lijiang; Wu, Wei; Wu, Xiuhong; Xiao, Fufu; Li, Shaojin

2014-02-21

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

Closure of laryngotracheal cavity and tracheostomy for intractable aspiration secondary to radiation encephalopathy or radiation damage of cranial nerve after radiotherapy of nasopharyngeal carcinoma.

PubMed

Qu, Shenhong; Su, Zhengzhong; He, Xiaoguang; Li, Min; Li, Tianying

2006-09-01

Closure of the laryngotracheal cavity and tracheostomy is especially suitable for intractable aspiration secondary to radiation encephalopathy or damage of cranial nerve after radiation for nasopharyngeal carcinoma (NPC). To investigate the clinical value, technique, indications and contraindications of closure of the laryngotracheal cavity and tracheostomy for intractable aspiration secondary to radiation encephalopathy (REP) or radiation damage of cranial nerve after radiotherapy of NPC. Thirty patients, suffering from intractable aspiration secondary to radiotherapy for nasopharyngeal carcinoma, were treated with closure of the laryngotracheal cavity and tracheostomy and were observed for at least 1 year. Intractable aspiration and dyspnea were completely eradicated in all patients. The quality of their life was greatly improved.

Localized nasopharyngeal amyloidosis mimicking malignancy: A case report.

PubMed

Kim, Jong Seung; Kwon, Sam Hyun

2017-07-01

Nasopharyngeal amyloidosis is a benign, slowly progressive disease that is characterized by extracellular eosinophilic deposition. We report a rare case of localized nasopharyngeal amyloidosis. The initial chief complaint of this patient was frequent epistaxis and right aural fullness. The initial diagnosis was nasopharyngeal tumor. There is no universally effective medical treatment for nasopharyngeal amyloidosis but surgery can be an option. We performed careful observation with regular follow-up by nasopharyngoscopy and radiologic study. The patient reported no further complaints at 1-year follow-up and the lesion from nasopharyngeal amyloidosis was still present. Although it is rare, nasopharyngeal amyloidosis should be considered in the differential diagnosis of epistaxis, nasal obstruction, and otitis media with effusion, which are the main symptoms of nasopharyngeal carcinoma. In the absence of systemic disease, localized nasopharyngeal amyloidosis may be treated conservatively.

Progression of understanding for the role of Epstein-Barr virus and management of nasopharyngeal carcinoma.

PubMed

Nakanishi, Yosuke; Wakisaka, Naohiro; Kondo, Satoru; Endo, Kazuhira; Sugimoto, Hisashi; Hatano, Miyako; Ueno, Takayoshi; Ishikawa, Kazuya; Yoshizaki, Tomokazu

2017-09-01

Nasopharyngeal carcinoma (NPC) is very common in southern China and Southeast Asia. In regions where NPC is endemic, undifferentiated subtypes constitute most cases and are invariably associated with Epstein-Barr virus (EBV) infection, whereas the differentiated subtype is more common in other parts of the world. Undifferentiated NPC is a unique malignancy with regard to its epidemiology, etiology, and clinical presentation. Clinically, NPC is highly invasive and metastatic, but sensitive to both chemotherapy and radiotherapy (RT). Overall prognosis has dramatically improved over the past three decades because of advances in management, including the improvement of RT technology, the broader application of chemotherapy, and more accurate disease staging. Despite the excellent local control with modern RT, distant failure remains a challenging problem. Advances in molecular technology have helped to elucidate the molecular pathogenesis of NPC. This article reviews the contribution of EBV gene products to NPC pathogenesis and the current management of NPC.

Excavation of attractor modules for nasopharyngeal carcinoma via integrating systemic module inference with attract method.

PubMed

Jiang, T; Jiang, C-Y; Shu, J-H; Xu, Y-J

2017-07-10

The molecular mechanism of nasopharyngeal carcinoma (NPC) is poorly understood and effective therapeutic approaches are needed. This research aimed to excavate the attractor modules involved in the progression of NPC and provide further understanding of the underlying mechanism of NPC. Based on the gene expression data of NPC, two specific protein-protein interaction networks for NPC and control conditions were re-weighted using Pearson correlation coefficient. Then, a systematic tracking of candidate modules was conducted on the re-weighted networks via cliques algorithm, and a total of 19 and 38 modules were separately identified from NPC and control networks, respectively. Among them, 8 pairs of modules with similar gene composition were selected, and 2 attractor modules were identified via the attract method. Functional analysis indicated that these two attractor modules participate in one common bioprocess of cell division. Based on the strategy of integrating systemic module inference with the attract method, we successfully identified 2 attractor modules. These attractor modules might play important roles in the molecular pathogenesis of NPC via affecting the bioprocess of cell division in a conjunct way. Further research is needed to explore the correlations between cell division and NPC.

Neoadjuvant chemotherapy with continuous infusion of cisplatin and 5-fluorouracil, with or without leucovorin, for locally advanced nasopharyngeal carcinoma.

PubMed

Fonseca, E; Cruz, J J; Rodríguez, C A; Gómez-Bernal, A; Martín, G; Sánchez, P; Nieto, A; Soria, P; Vega, M J; Muñoz, A; Pardal, J L

1996-01-01

Cisplatin-based induction chemotherapy has been extensively tested in nasopharyngeal carcinoma for the improvement of local and systemic control and survival of this disease. In this study, we report the results of the treatment with induction chemotherapy in 40 patients with locally advanced carcinoma of the nasopharynx (LANPC) with four courses of cisplatin (P) 25 mg/m2 per day and 5-fluorouracil (F) 1000 mg/m2 per day both in a 4-days continuous infusion, with or without leucovorin (L) 250 mg/m2 per day in 2-hour infusion at the beginning of daily administration of PF, followed by sequential radiotherapy. All except one were in stage IV. The overall response after induction chemotherapy was 93%, with 55% CR and 38% PR. Definitive overall response after radiotherapy was 98%, with 80% CR and 18% PR. At a maximum follow up of 11 years, the overall survival rate is 55%. Induction chemotherapy with continuous infusion of PF with or without leucovorin followed by radiotherapy is a highly active regimen for the treatment of locally advanced nasopharyngeal carcinoma with response and survival rates comparable to other combinations of sequential or simultaneous chemotherapy and radiotherapy.

A model to predict the risk of lethal nasopharyngeal necrosis after re-irradiation with intensity-modulated radiotherapy in nasopharyngeal carcinoma patients.

PubMed

Yu, Ya-Hui; Xia, Wei-Xiong; Shi, Jun-Li; Ma, Wen-Juan; Li, Yong; Ye, Yan-Fang; Liang, Hu; Ke, Liang-Ru; Lv, Xing; Yang, Jing; Xiang, Yan-Qun; Guo, Xiang

2016-06-29

For patients with nasopharyngeal carcinoma (NPC) who undergo re-irradiation with intensity-modulated radiotherapy (IMRT), lethal nasopharyngeal necrosis (LNN) is a severe late adverse event. The purpose of this study was to identify risk factors for LNN and develop a model to predict LNN after radical re-irradiation with IMRT in patients with recurrent NPC. Patients who underwent radical re-irradiation with IMRT for locally recurrent NPC between March 2001 and December 2011 and who had no evidence of distant metastasis were included in this study. Clinical characteristics, including recurrent carcinoma conditions and dosimetric features, were evaluated as candidate risk factors for LNN. Logistic regression analysis was used to identify independent risk factors and construct the predictive scoring model. Among 228 patients enrolled in this study, 204 were at risk of developing LNN based on risk analysis. Of the 204 patients treated, 31 (15.2%) developed LNN. Logistic regression analysis showed that female sex (P = 0.008), necrosis before re-irradiation (P = 0.008), accumulated total prescription dose to the gross tumor volume (GTV) ≥145.5 Gy (P = 0.043), and recurrent tumor volume ≥25.38 cm(3) (P = 0.009) were independent risk factors for LNN. A model to predict LNN was then constructed that included these four independent risk factors. A model that includes sex, necrosis before re-irradiation, accumulated total prescription dose to GTV, and recurrent tumor volume can effectively predict the risk of developing LNN in NPC patients who undergo radical re-irradiation with IMRT.

Experimental Study of Nasopharyngeal Carcinoma Radionuclide Imaging and Therapy Using Transferred Human Sodium/Iodide Symporter Gene

PubMed Central

Zhong, Xing; Shi, Changzheng; Gong, Jian; Guo, Bin; Li, Mingzhu; Xu, Hao

2015-01-01

Purpose The aim of this study was to design a method of radionuclide for imaging and therapy of nasopharyngeal carcinoma (NPC) using the transferred human sodium/iodide symporter (hNIS) gene. Methods A stable NPC cell line expressing hNIS was established (CNE-2-hNIS). After 131I treatment, we detected proliferation and apoptosis of NPC cells, both in vitro and vivo. In vivo, the radioactivity of different organs of nude mice was counted and 99mTc imaging using SPECT was performed. The apparent diffusion coefficient (ADC) value changes of tumor xenografts were observed by diffusion-weighted magnetic resonance imaging (DW-MRI) within 6–24 days of 131I treatment. The correlation of ADC changes with apoptosis and proliferation was investigated. Post-treatment expression levels of P53, Bax, Bcl-2, Caspase-3, and Survivin proteins were detected by western blotting. Results 131I uptake was higher in CNE-2-hNIS than in CNE-2 cells. The proliferation and apoptosis rate decreased and increased respectively both in vitro and vivo in the experimental group after 131I treatment. The experimental group tumors accumulated 99mTc in vivo, leading to a good visualization by SPECT. DW-MRI showed that ADC values increased in the experimental group 6 days after treatment, while ADC values were positively and negatively correlated with the apoptotic and Ki-67 proliferation indices, respectively. After treatment, CNE-2-hNIS cells up-regulated the expression of P53 and Survivin proteins and activated Caspase-3, and down-regulated the expression of Bcl-2 proteins. Conclusions The radionuclide imaging and therapy technique for NPC hNIS-transfected cell lines can provide a new therapy strategy for monitoring and treatment of NPC. PMID:25615643

Apigenin enhances the antitumor effects of cetuximab in nasopharyngeal carcinoma by inhibiting EGFR signaling.

PubMed

Hu, Wen-Jian; Liu, Jing; Zhong, Lun-Kun; Wang, Jian

2018-06-01

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancers with poor prognosis. Despite that platinum-based chemotherapy concurrent with radiotherapy have made great achievements for the treatment of NPC, the therapeutic reaction and toxicity varies dramatically among individuals. Apigenin (API), a naturally occurring plant flavone, is considered to have anti-cancer effect. Cetuximab (CET), a well known epidermal growth factor receptor (EGFR) inhibitor, is widely used in various cancers, especially head and neck cancers. The aim of our study was to measure the combination of API and CET for the treatment of NPC in vitro and in vivo. Results demonstrated that combining API and CET could better suppress the viability of the human nasopharyngeal carcinoma cell lines (HONE1 and CNE2) and inhibit the growth of NPC than API or CET used alone. Besides, the combination of API with CET produced greater pro-apoptosis effect. Moreover, the increased G2/M phase arrest caused by CET could be remarkably enhanced by adding API in HONE1 and CNE2 cells. Although, both API and CET could decrease the expressions of p-EGFR, p-Akt, p-STAT3 and Cyclin D1. Combining them produced greater inhibition effect. These results suggested that the combination of API and CET may be a promising therapeutic approach for the treatment of NPC. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

[Expression of c-kit in North African nasopharyngeal carcinomas: correlation with age and LMP1].

PubMed

Charfi, S; Khabir, A; Ayadi, L; Mseddi, M; Makni, H; Gorbel, A; Daoud, J; Frikha, M; Jlidi, R; Busson, P; Boudawara, T S

2007-09-01

To determine the level and prognostic significance of c-kit expression in the two age groups of North African nasopharyngeal carcinomas. A retrospective study of 99 NPC specimens from Tunisian patients was investigated by immunohistochemistry. Immunohistochemical data were correlated with Epstein-Barr virus LMP1 expression and pathological, clinical and survival parameters. c-kit was detected in 79% of the cases for patients under 30 years of age (juvenile form) but in only 56% of specimens in patients over 30 years (P=0.039) and was significantly over-expressed for patients with lymph node involvement (P=0.015). LMP1 score was 5.78 (+/-1.84) for c-kit negative tumors compared to 8,23 (+/-2.39) for c-kit positive tumors (P=0.002). Multivariate analysis including age, lymph nodes involvement and LMP1 expression as co-variables, showed that only age (P=0.027) and LMP1 expression (P=0.005) were significantly correlated to the c-kit expression. c-kit is highly expressed in the juvenile form of North African nasopharyngeal carcinomas. There is a significant association between LMP1 and c-kit expression. The contrasted levels of C-kit expression in the two age groups strengthen the hypothesis that these clinical forms result from distinct oncogenic mechanisms.

Ternary copper(II) complex: NCI60 screening, toxicity studies, and evaluation of efficacy in xenograft models of nasopharyngeal carcinoma.

PubMed

Ahmad, Munirah; Suhaimi, Shazlan-Noor; Chu, Tai-Lin; Abdul Aziz, Norazlin; Mohd Kornain, Noor-Kaslina; Samiulla, D S; Lo, Kwok-Wai; Ng, Chew-Hee; Khoo, Alan Soo-Beng

2018-01-01

Copper(II) ternary complex, [Cu(phen)(C-dmg)(H2O)]NO3 was evaluated against a panel of cell lines, tested for in vivo efficacy in nasopharyngeal carcinoma xenograft models as well as for toxicity in NOD scid gamma mice. The Cu(II) complex displayed broad spectrum cytotoxicity against multiple cancer types, including lung, colon, central nervous system, melanoma, ovarian, and prostate cancer cell lines in the NCI-60 panel. The Cu(II) complex did not cause significant induction of cytochrome P450 (CYP) 3A and 1A enzymes but moderately inhibited CYP isoforms 1A2, 2C9, 2C19, 2D6, 2B6, 2C8 and 3A4. The complex significantly inhibited tumor growth in nasopharyngeal carcinoma xenograft bearing mice models at doses which were well tolerated without causing significant or permanent toxic side effects. However, higher doses which resulted in better inhibition of tumor growth also resulted in toxicity.

Epstein-Barr virus latent membrane protein-1 (LMP-1) 30-bp deletion and Xho I-loss is associated with type III nasopharyngeal carcinoma in Malaysia

PubMed Central

See, Hui Shien; Yap, Yoke Yeow; Yip, Wai Kien; Seow, Heng Fong

2008-01-01

Background Nasopharyngeal carcinoma (NPC) is a human epithelial tumour with high prevalence amongst Chinese in Southern China and South East Asia and is associated with the Epstein-Barr virus (EBV). The viral genome harbours an oncogene, namely, the latent membrane protein 1 (LMP1) gene and known variants such as the 30-bp deletion and loss of XhoI restriction site have been found. Less is known about the relationship between these variants and the population characteristics and histological type. Methods In this study, the EBV LMP1 gene variants from 42 NPC and 10 non-malignant archived formalin fixed, paraffin-embedded tissues, as well as plasma from another 35 patients with nasopharyngeal carcinoma were determined by using Polymerase Chain Reaction (PCR). Statistical analysis was performed by using SPSS programme. Results LMP1 30-bp deletion was detected in 19/34 (55.9%) of NPC tissues, 7/29 (24.1%) of plasma but absent in non-malignant tissues (8/8). Coexistence of variants with and without 30bp deletion was found only in 5/29 (17.2%) plasma samples but not in NPC tissues. The loss of XhoI restriction site in LMP1 gene was found in 34/39 (87.2%) of the NPC tissues and 11/30 (36.7%) of plasma samples. None of the non-malignant nasopharyngeal tissues (8/8) harbour XhoI-loss variants. LMP1 30-bp deletion was detected in 16/18 Chinese versus 3/15 Malays and 13/16 type III (undifferentiated carcinoma) versus 1/6 type I (keratinizing squamous cell carcinoma). XhoI-loss was found in 19/19 Chinese versus 14/19 Malays and 18/18 type III (undifferentiated) versus 2/5 type I (keratinizing squamous cell carcinoma). Statistical analysis showed that these variants were associated with ethnic race (30-bp deletion, p < 0.05; XhoI-loss, p = 0.046) and histological type of NPC (30-bp deletion, p = 0.011; XhoI-loss, p = 0.006). Nineteen out of 32 NPC tissues (19/32; 59.4%) and 6/24 (25%) of plasma samples showed the coexistence of both the 30-bp deletion and the loss of Xho

Risk factors for recurrent pneumonia in post-irradiated patients with nasopharyngeal carcinoma.

PubMed

Wang, Jing-Jie; Jiang, Rong-San; Yen, Ting-Ting; Liang, Kai-Li

2017-09-01

Nasopharyngeal carcinoma (NPC) is a common cancer in eastern Asia. Chemoradiotherapy is the main treatment modality for NPC. Dysphagia and aspiration is not uncommon in post-irradiated NPC patients. The purpose of this study was to investigate the risk factors for recurrent pneumonia and the prognosis. A retrospective chart review was conducted from January 2004 to December 2014. NPC patients who had been hospitalized for pneumonia in the study hospital were enrolled. The diagnosis of pneumonia was based on radiological evidence of chest inflammation and clinical symptoms. Patients' characteristics including demographic data, the hospital course, and the outcome of pneumonia were collected and analyzed. A total of 113 NPC patients were enrolled in this study. Among them, 96 NPC patients had pneumonia after radiotherapy: 43 had pneumonia twice, and 18 had multiple episodes of pneumonia. Forty-nine patients had tube feeding. The 30-day mortality rate was 51%. The mortality rate was significantly associated with metastatic nasopharyngeal carcinoma (r = 0.328, p < 0.001). Older age, smoking, body weight loss, and lower cranial nerve (vagus or hypoglossal nerve palsy) were significant predictors of multiple episodes of pneumonia (r 2  = 0.687, p = 0.033, 0.034, 0.036, and 0.027, respectively). We concluded that old age, smoking, body weight loss, and lower cranial nerve palsies are predisposing factors for multiple episodes of pneumonia in post-irradiated NPC patients. Metastatic cancer status usually leads to a lethal outcome. Early interventions to manage dysphagia in high-risk patients are necessary. Copyright © 2017. Published by Elsevier Taiwan LLC.

Monte Carlo evaluation of Acuros XB dose calculation Algorithm for intensity modulated radiation therapy of nasopharyngeal carcinoma

NASA Astrophysics Data System (ADS)

Yeh, Peter C. Y.; Lee, C. C.; Chao, T. C.; Tung, C. J.

2017-11-01

Intensity-modulated radiation therapy is an effective treatment modality for the nasopharyngeal carcinoma. One important aspect of this cancer treatment is the need to have an accurate dose algorithm dealing with the complex air/bone/tissue interface in the head-neck region to achieve the cure without radiation-induced toxicities. The Acuros XB algorithm explicitly solves the linear Boltzmann transport equation in voxelized volumes to account for the tissue heterogeneities such as lungs, bone, air, and soft tissues in the treatment field receiving radiotherapy. With the single beam setup in phantoms, this algorithm has already been demonstrated to achieve the comparable accuracy with Monte Carlo simulations. In the present study, five nasopharyngeal carcinoma patients treated with the intensity-modulated radiation therapy were examined for their dose distributions calculated using the Acuros XB in the planning target volume and the organ-at-risk. Corresponding results of Monte Carlo simulations were computed from the electronic portal image data and the BEAMnrc/DOSXYZnrc code. Analysis of dose distributions in terms of the clinical indices indicated that the Acuros XB was in comparable accuracy with Monte Carlo simulations and better than the anisotropic analytical algorithm for dose calculations in real patients.

Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1

PubMed Central

Zhou, Teng-Jian; Zhang, Shi-Li; He, Cheng-Yong; Zhuang, Qun-Ying; Han, Pei-Yu; Jiang, Sheng-Wei; Yao, Huan; Huang, Yi-Jun; Ling, Wen-Hua; Lin, Yu-Chun; Lin, Zhong-Ning

2017-01-01

Cancer stem cells (CSCs) are a small subset of malignant cells, possessing stemness, with strong tumorigenic capability, conferring resistance to therapy and leading to the relapse of nasopharyngeal carcinoma (NPC). Our previous study suggested that cyclooxygenase-2 (COX-2) would be a novel target for the CSCs-like side population (SP) cells in NPC. In the present study, we further found that COX-2 maintained the stemness of NPC by enhancing the activity of mitochondrial dynamin-related protein 1 (Drp1), a mitochondrial fission mediator, by studying both sorted SP cells from NPC cell lines and gene expression analyses in NPC tissues. Using both overexpression and knockdown of COX-2, we demonstrated that the localization of COX-2 at mitochondria promotes the stemness of NPC by recruiting the mitochondrial translocation of p53, increasing the activity of Drp1 and inducing mitochondrial fisson. Inhibition of the expression or the activity of Drp1 by siRNA or Mdivi-1 downregulates the stemness of NPC. The present study also found that inhibition of mitochondrial COX-2 with resveratrol (RSV), a natural phytochemical, increased the sensitivity of NPC to 5-fluorouracil (5-FU), a classical chemotherapy drug for NPC. The underlying mechanism is that RSV suppresses mitochondrial COX-2, thereby reducing NPC stemness by inhibiting Drp1 activity as demonstrated in both the in vitro and the in vivo studies. Taken together, the results of this study suggest that mitochondrial COX-2 is a potential theranostic target for the CSCs in NPC. Inhibition of mitochondrial COX-2 could be an attractive therapeutic option for the effective clinical treatment of therapy-resistant NPC. PMID:28435473

The current status of clinical trials focusing on nasopharyngeal carcinoma: A comprehensive analysis of ClinicalTrials.gov database.

PubMed

Peng, Hao; Chen, Lei; Chen, Yu-Pei; Li, Wen-Fei; Tang, Ling-Long; Lin, Ai-Hua; Sun, Ying; Ma, Jun

2018-01-01

Clinical Trials have emerged as the main force in driving the development of medicine. However, little is known about the current status of clinical trials regarding nasopharyngeal carcinoma (NPC). This study aimed at providing a comprehensive landscape of NPC-related trials on the basis of ClinicalTrials.gov database. We used the keyword "nasopharyngeal carcinoma" to search the ClinicalTrials.gov database and assessed the characteristics of these trials. Up to December 30, 2016, 462 eligible trials in total were identified, of which 222 (48.0%) recruited only NPC (NPC trials) and the other 240 (52.0%) recruited both NPC and other cancers (multiple cancer trials). Moreover, 47 (10.2%) were Epstein-Barr virus (EBV)-related trials and 267 (57.8%) focused on metastatic/recurrent disease. Compared with NPC trials, the multiple cancer trials had a higher percentage of phase 1 (26.7% vs. 6.7%, P < 0.001) studies and more patients with metastatic/recurrent disease (72.5% vs. 41.9%, P < 0.001). Notably, non-EBV trials had more phase 2 or 3 (78.4% vs. 48.8%, P < 0.001) and interventional studies (89.5% vs. 70.7%, P = 0.002) than EBV trials. Obviously, more phase 2/3 or 3 trials were conducted in patients with non-metastatic/recurrent disease (29.4% vs. 4.9%, P < 0.001); however, metastatic/recurrent trials were more likely to be anticancer (94.6% vs. 63.6%, P < 0.001). The role of plasma EBV DNA in clinical trials is underestimated, and high-level randomized clinical trials should be performed for patients with metastatic/recurrent disease.

Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia.

PubMed

Maklad, Ahmed Marzouk; Bayoumi, Yasser; Senosy Hassan, Mohamed Abdalazez; Elawadi, AbuSaleh A; AlHussain, Hussain; Elyamany, Ashraf; Aldhahri, Saleh F; Al-Qahtani, Khalid Hussain; AlQahtani, Mubarak; Tunio, Mutahir A

2016-01-01

We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66-70 Gy, 63 Gy to clinical target volume, and 50.4-56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. The median follow-up time was 52.2 months (range: 11-87 months). Epstein-Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range: 16-50 months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein-Barr virus were independent predictors for disease-free survival. Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein-Barr virus status before IMRT were important independent prognostic factors.

Patterns of failure and survival in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy in Saudi Arabia

PubMed Central

Maklad, Ahmed Marzouk; Bayoumi, Yasser; Senosy Hassan, Mohamed Abdalazez; Elawadi, AbuSaleh A; AlHussain, Hussain; Elyamany, Ashraf; Aldhahri, Saleh F; Al-Qahtani, Khalid Hussain; AlQahtani, Mubarak; Tunio, Mutahir A

2016-01-01

Background We aimed to investigate the patterns of failure (locoregional and distant metastasis), associated factors, and treatment outcomes in nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy (IMRT) combined with chemotherapy. Patients and methods From April 2006 to December 2011, 68 nasopharyngeal carcinoma patients were treated with IMRT and chemotherapy at our hospital. Median radiation doses delivered to gross tumor volume and positive neck nodes were 66–70 Gy, 63 Gy to clinical target volume, and 50.4–56 Gy to clinically negative neck. The clinical toxicities, patterns of failures, locoregional control, distant metastasis control, disease-free survival, and overall survival were observed. Results The median follow-up time was 52.2 months (range: 11–87 months). Epstein–Barr virus infection was positive in 63.2% of patients. Overall disease failure developed in 21 patients, of whom 85.8% belonged to stage III/IV disease. Among these, there were seven locoregional recurrences, three regional recurrences with distant metastases, and eleven distant metastases. The median interval from the date of diagnosis to failure was 26.5 months (range: 16–50 months). Six of ten (60%) locoregional recurrences were treated with reirradiation ± concurrent chemotherapy. The 5-year locoregional control, distant metastasis control, disease-free survival, and overall survival rates of whole cohort were 81.1%, 74.3%, 60.1%, and 73.4%, respectively. Cox regression analyses revealed that neoadjuvant chemotherapy, age, and Epstein–Barr virus were independent predictors for disease-free survival. Conclusion Neoadjuvant chemotherapy followed by IMRT with or without chemotherapy improves the long-term survival of Saudi patients with nasopharyngeal carcinoma. Distant metastasis was the main pattern of treatment failure. Neoadjuvant chemotherapy, age, and Epstein–Barr virus status before IMRT were important independent prognostic factors

Milk consumption in relation to incidence of nasopharyngeal carcinoma in 48 countries/regions.

PubMed

Mai, Zhi-Ming; Lo, Ching-Man; Xu, Jun; Chan, King-Pan; Wong, Chit-Ming; Lung, Maria Li; Lam, Tai-Hing

2015-12-21

Decreasing trends of nasopharyngeal carcinoma (NPC) incidence have been consistently reported in endemic populations but the etiology of NPC remains unclear. The objective of our study was to assess the international and local (Hong Kong) correlations of milk and dairy products per capita consumption with NPC incidence. We conducted an ecological study in 48 countries/regions. Age standardized incidence rates of NPC were obtained from the Cancer Incidence in Five Continents. Dairy product consumption and Human Development Index were obtained from the Food and Agriculture Organization of the United Nations and the United Nations Development Programme. Spearman correlation, multivariate analysis and time-lagged analysis were performed. The negative correlations between milk consumption and decreased age standardized incidence rates of NPC were observed in the 48 countries/regions adjusting for Human Development Index in endemic countries/regions. In Hong Kong, multivariate analysis, after adjusting for other potential confounders, including salted fish, cigarette, vegetable consumption and socioeconomic status, showed consistently negative and significant correlations between milk consumption and NPC incidence (The strongest coefficient (β) was observed at 10-year lag in males [β = -0.439; P < 0.01] and in females [β = -0.258; P < 0.01]). Our study showed the correlations on milk consumption per capita and against lower risk of NPC in 48 countries/regions and in Hong Kong. These hypothesis-generating results could support further studies on individual exposures and the disease.

One patient - three head and neck primaries: nasopharyngeal, tongue and thyroid cancers

PubMed Central

2013-01-01

Background We report a rare case of three head and neck malignancies in one patient. Squamous cell carcinoma of tongue and papillary thyroid carcinoma occurred as metachronous cancers in a patient with primary nasopharyngeal carcinoma. These three pathologically distinct malignancies of head and neck region in one patient is a rare phenomenon and is not reported so far. Case presentation A 60 year old Saudi female patient presented in March 2011 with locally advanced nasopharyngeal carcinoma. After completion of concurrent chemoradiation in June 2011, she developed two new primaries i-e thyroid cancer and tongue cancer in May 2012 along with recurrent nasopharyngeal carcinoma. We discuss histopathologic features, diagnostic tools and treatment modalities for this rarely existing case. Conclusion High index of suspicion and thorough work up is essential in follow up of patients with head and neck primary cancers. The effect of field cancerization and environmental factors need to be explored in greater depths in such selected cases. However, which patients are at increased risk of triplet primaries, is still unknown. PMID:24164964

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

PubMed

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

2013-01-01

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

Treatment results of nasopharyngeal carcinoma: a 15-year single institutional experience.

PubMed

Khademi, Bijan; Mahmoodi, Jalal; Omidvari, Shapour; Mohammadianpanah, Mohammad

2006-06-01

Nasopharyngeal Carcinoma (NPC) is a common malignant neoplasm of the head and neck that occurs most commonly in people in the South Eastern Asia but its condition in Iran is not much clear. In this retrospective study, we evaluated the treatment characteristics determining the outcome in patients with NPC. In this retrospective study, we reviewed the records of one hundred and seven patients with biopsy proven diagnosis of NPC who were referred to the radiation oncology department, Nemazee Hospital, Shiraz University of Medical Sciences, Iran, during the time period from January 1985 to December 2000. Eightyfive patients (79.4%) received 60-70Gy radiation (1.8- 2Gy/fraction, one fraction per day, and 5 fractions per week). Sixty-two patients (57.5%) received radiotherapy combined with adjuvant chemotherapy which consisted of cisplatin and 5-fluorouracil. Eighty-six patients (80.4%) had WHO II-III histopathologic diagnosis. According to the AJCC 1997 staging system, 4 (3.6%), 3 (2.7%), 33 (30.8%) and 67 (62%) patients were in stages I, II, III and IV, respectively. With a median follow-up of 12 months, the 2-year overall and disease-free survival rates were 35% and 21%, respectively. According to the multivariate analysis for overall survival, patients under 40 years had a better prognosis (p=0.041). Node stage and stage of disease were significant prognostic factors (p=0.0001). On multivariate analysis for disease-free survival, age and node stage were significant prognostic factors. The patients who received more than 60Gy radiation had a better prognosis (p=0.02), however; sequential adjuvant chemotherapy had no impact on survival and response (p=0.6). Our experience confirmed earlier reports showing poor outcomes for locoregionally advanced nasopharyngeal carcinomas. This study failed to demonstrate improvement in the outcome regarding overall and disease-free survival by adding sequential adjuvant chemotherapy after radiotherapy for patients with advanced NPC.

Step-by-step full mouth rehabilitation of a nasopharyngeal carcinoma patient with tooth and implant-supported prostheses: A clinical report

PubMed Central

Alikhasi, Marzieh; Kazemi, Mahmood; Nokar, Saeed; Khojasteh, Arash; Sheikhzadeh, Sedigheh

2011-01-01

This clinical report presents a 46-year-old man diagnosed with nasopharyngeal carcinoma with the chief complaint of masticatory and speech deficiency because of radiation therapy. After a period of controlling post radiation caries, the patient was rehabilitated with tooth and implant supported metal ceramic restorations following surgical and endodontic intervention. PMID:22090777

[Nasopharyngeal adenoid cystic carcinoma, a rare but highly challenging disease with unmet therapeutic needs: A case-report and review of the literature].

PubMed

Afani, L; Errihani, H; Benchafai, I; Lalami, Y

2016-07-01

Nasopharyngeal adenoid cystic carcinoma is a rare tumour. Compared with others nasopharyngeal tumours, it is characterised by slow evolution but it is locally aggressive and has a high tendency to recurrences. Due to the rarity of cases, no consensus exists about treatment approaches. We report the case of 45-year-old-man with a locally advanced adenoid cystic carcinoma. The patient received concurrent chemoradiation and had a good objective response. After one year, he developed a paucisymptomatic lung metastasis. The follow-up showed local recurrence after 3 years. One cycle of chemotherapy was given but poorly supported. Carbon ion radiotherapy was proposed. The aim of this work is to review the literature concerning this rare malignancy and discusses treatment approaches in initial situations and during recurrences. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Pulmonary lymphoepithelioma-like carcinoma with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene.

PubMed

Ose, Naoko; Kawai, Teruka; Ishida, Daisuke; Kobori, Yuko; Takeuchi, Yukiyasu; Senba, Hidetoshi

2016-11-01

A pulmonary lymphoepithelioma-like carcinoma (PLELC) is similar to a lymphoepithelioma, a subtype of nasopharyngeal carcinoma and commonly associated with Epstein-Barr virus infection which is a rare tumour and classified in the group of "other and unclassified carcinoma" in the latest 2015 World Health Organization (WHO) classification. Some reports of lymphoepithelioma-like carcinoma (LELC) have noted an epidermal growth factor receptor (EGFR) mutation, whereas none have noted a mutation of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene. This is the first reported case of PLELC with ALK rearrangement. A 76-year-old woman underwent a right lower lobectomy and complicated partial resection of the upper lobe with lymph node dissection under complete thoracoscopic approach. A histopathological diagnosis of PLELC was made and the stage was classified as T1aN1(#12l) M0, pl0, G2, Ly1, V1. The results of both ALK immunohistochemistry and EML4-ALK fusion gene on fluorescence in situ hybridization (FISH) examinations were positive; however, EGFR mutational analysis results showed wild-type mutation.

Multidisciplinary Treatment Approach in a Patient with History of Nasopharyngeal Carcinoma

PubMed Central

Yavuz, Atacan; Ağralı, Ömer Birkan; Çalışkan, Zeynep Lale; Türkaydın, Dilek; Sertgöz, Atilla; Doğan, Başak

2014-01-01

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. PMID:24523971

MiR-593 mediates curcumin-induced radiosensitization of nasopharyngeal carcinoma cells via MDR1.

PubMed

Fan, Haoning; Shao, Meng; Huang, Shaohui; Liu, Ying; Liu, Jie; Wang, Zhiyuan; Diao, Jianxin; Liu, Yuanliang; Tong, L I; Fan, Qin

2016-06-01

Curcumin (Cur) exhibits radiosensitization effects to a variety of malignant tumors. The present study investigates the radiosensitizing effect of Cur on nasopharyngeal carcinoma (NPC) cells and whether its mechanism is associated with microRNA-593 (miR-593) and multidrug resistance gene 1 (MDR1). A clonogenic assay was performed to measure the radiosensitizing effect. The expression of miR-593 and MDR1 was analyzed by quantitative polymerase chain reaction (qPCR) or western blot assay. A transplanted tumor model was established to identify the radiosensitizing effect in vivo . A luciferase-based reporter was constructed to evaluate the effect of direct binding of miR-593 to the putative target site on the 3' UTR of MDR1. The clonogenic assay showed that Cur enhanced the radiosensitivity of cells. Cur (100 mg/kg) combined with 4 Gy irradiation inhibited the growth of a transplanted tumor model in vivo , resulting in the higher inhibition ratio compared with the radiotherapy-alone group. These results demonstrated that Cur had a radiosensitizing effect on NPC cells in vivo and in vitro ; Cur-mediated upregulation of miR-593 resulted in reduced MDR1 expression, which may promote radiosensitivity of NPC cells.

SU-E-T-302: Dosimetric Comparison Between Volumetric Modulated Arc Radiotherapy and Intensity-Modulated Radiotherapy for Locally Recurrent Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, J-Y; Huang, B-T; Zhang, J-Y

2015-06-15

Purpose: To compare volumetric modulated arc radiotherapy (VMAT) technique with fixed-gantry intensity-modulated radiotherapy (IMRT) technique for locally recurrent nasopharyngeal carcinoma. Methods: CT datasets of eleven nasopharyngeal-carcinoma patients were included. Dual-arc VMAT and seven-field IMRT plans were created for each case, and were then compared in terms of conformity index (CI), homogeneity index (HI) of the planning target volume (PTV), organ-at-risk (OAR) sparing, monitor unit (MU) and delivery time. Results: The D98% (near-minimal dose) of PTV in the VMAT plans was slightly lower than that of the IMRT plans (P < 0.05), while the CI was higher than that of themore » IMRT plans (P < 0.05). No significant difference was found in the HI between the two plans (P > 0.05). Compared with the IMRT plans, the VMAT plans demonstrated lower Dmean (mean dose) of the bilateral temporal lobes and the whole surrounding normal tissue (P < 0.05), but slightly higher Dmean of brainstem (P < 0.05). In terms of the other OARs, no significant differences were found (P > 0.05). The MUs of the VMAT plans (672 ± 112) was significantly lower than that of the IMRT plans (917 ± 206), by 25 ± 13% (P < 0.05). The average delivery time of the VMAT plans (2.3 ± 0.1 min) was less than that of the IMRT plans (5.1 ± 0.4 min), by 54 ± 3%. Conclusion: For locally recurrent nasopharyngeal carcinoma, the VMAT technique could achieve equivalent or superior dose distribution of the target and better protect the bilateral temporal lobes, compared with the IMRT technique. Moreover, it could reduce the MU and delivery time effectively.« less

Nasopharyngeal Carcinoma with Cystic Cervical Metastasis Masquerading as Branchial Cleft Cyst: A Potential Pitfall in Diagnosis and Management.

PubMed

Sai-Guan, Lum; Min-Han, Kong; Kah-Wai, Ngan; Mohamad-Yunus, Mohd-Razif

2017-03-01

Most metastatic lymph nodes from head and neck malignancy are solid. Cystic nodes are found in 33% - 61% of carcinomas arise from Waldeyer's ring, of which only 1.8% - 8% originate are from the nasopharynx. Some cystic cervical metastases were initially presumed to be branchial cleft cyst. This case report aims to highlight the unusual presentation of cystic cervical metastasis secondary to nasopharyngeal carcinoma in a young adult. The histopathology, radiological features and management strategy were discussed. A 36-year-old man presented with a solitary cystic cervical swelling, initially diagnosed as branchial cleft cyst. Fine needle aspiration yielded 18 ml of straw-coloured fluid. During cytological examination no atypical cells were observed. Computed tomography of the neck showed a heterogeneous mass with multiseptation medial to the sternocleidomastoid muscle. Histopathological examination of the mass, post excision, revealed a metastatic lymph node. A suspicious mucosal lesion at the nasopharynx was detected after repeated thorough head and neck examinations and the biopsy result confirmed undifferentiated nasopharyngeal carcinoma. Cystic cervical metastasis may occur in young patients under 40 years. The primary tumour may not be obvious during initial presentation because it mimicks benign branchial cleft cyst clinically. Retrospective review of the computed tomography images revealed features that were not characteristic of simple branchial cleft cyst. The inadequacy of assessment and interpretation had lead to the error in diagnosis and subsequent management. Metastatic head and neck lesion must be considered in a young adult with a cystic neck mass.

Conventional and array-based comparative genomic hybridization analysis of nasopharyngeal carcinomas from the Mediterranean area.

PubMed

Rodriguez, S; Khabir, A; Keryer, C; Perrot, C; Drira, M; Ghorbel, A; Jlidi, R; Bernheim, A; Valent, A; Busson, P

2005-03-01

Nasopharyngeal carcinoma (NPC) occurs with a high incidence in Southeast Asia and to a lesser extent in the Mediterranean area, especially in Tunisia, Algeria, and Morocco. Cellular gene alterations combined with latent Epstein-Barr virus infection are thought to be essential for NPC oncogenesis. To date, chromosome analysis with comparative genomic hybridization (CGH) has been reported exclusively for NPCs from Southeast Asia. Although NPCs from the Mediterranean area have several distinct clinical and epidemiological features, CGH investigations have been lacking. Chromosome analysis was therefore undertaken on a series of NPC xenografts and biopsies derived from patients of Mediterranean origin. Four xenografts were investigated with a combination of conventional CGH, array-based CGH, and comparative expressed sequence hybridization. In addition, 23 fresh NPC biopsies were analyzed with conventional CGH. Data obtained from xenografts and fresh biopsies were consistent, except that amplification of genes at 18p was observed only in xenografts derived from metastatic tissues. Frequent gains associated with gene overexpression were detected at 1q25 approximately qter (64%) and 12p13 (50%). Losses were noticed mainly at 11q14 approximately q23 (50%), 13q12 approximately q31 (50%), 14q24 approximately q31 (43%), and 3p13 approximately p23 (43%). Comparison with previous reports suggests that Mediterranean NPCs have higher frequencies of gains at 1q and losses at 13q than their Asian counterparts.

Clinical Study of Nasopharyngeal Carcinoma Treated by Helical Tomotherapy in China: 5-Year Outcomes

PubMed Central

Du, Lei; Zhang, Xin-Xin; Ma, Lin; Feng, Lin-Chun; Li, Fang; Zhou, Gui-Xia; Qu, Bao-Lin; Xu, Shou-Ping; Xie, Chuan-Bin; Yang, Jack

2014-01-01

Background. To evaluate the outcomes of nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT). Methods. Between September 2007 and August 2012, 190 newly diagnosed NPC patients were treated with HT. Thirty-one patients were treated with radiation therapy as single modality, 129 with additional cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody therapy, and 30 with concurrent anti-EGFR monoclonal antibody therapy. Results. Acute radiation related side effects were mainly grade 1 or 2. Grade 3 and greater toxicities were rarely noted. The median followup was 32 (3–38) months. The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 96.1%, 98.2%, 92.0%, and 86.3%, respectively, at 3 years. Cox multivariate regression analysis showed that age and T stage were independent predictors for 3-year OS. Conclusions. Helical tomotherapy for NPC patients achieved excellent 3-year locoregional control, distant metastasis-free survival, and overall survival, with relatively minor acute and late toxicities. Age and T stage were the main prognosis factors. PMID:25114932

CD44+ Cancer Stem-Like Cells in EBV-Associated Nasopharyngeal Carcinoma

PubMed Central

Lun, Samantha Wei-Man; Cheung, Siu Tim; Cheung, Phyllis Fung Yi; To, Ka-Fai; Woo, John Kong-Sang; Choy, Kwong-Wai; Chow, Chit; Cheung, Chartia Ching-Mei; Chung, Grace Tin-Yun; Cheng, Alice Suk-Hang; Ko, Chun-Wai; Tsao, Sai-Wah; Busson, Pierre; Ng, Margaret Heung-Ling; Lo, Kwok-Wai

2012-01-01

Nasopharyngeal carcinoma (NPC) is a unique EBV-associated epithelial malignancy, showing highly invasive and metastatic phenotype. Despite increasing evidence demonstrating the critical role of cancer stem-like cells (CSCs) in the maintenance and progression of tumors in a variety of malignancies, the existence and properties of CSC in EBV-associated NPC are largely unknown. Our study aims to elucidate the presence and role of CSCs in the pathogenesis of this malignant disease. Sphere-forming cells were isolated from an EBV-positive NPC cell line C666-1 and its tumor-initiating properties were confirmed by in vitro and in vivo assays. In these spheroids, up-regulation of multiple stem cell markers were found. By flow cytometry, we demonstrated that both CD44 and SOX2 were overexpressed in a majority of sphere-forming C666-1 cells. The CD44+SOX2+ cells was detected in a minor population in EBV-positive xenografts and primary tumors and considered as potential CSC in NPC. Notably, the isolated CD44+ NPC cells were resistant to chemotherapeutic agents and with higher spheroid formation efficiency, showing CSC properties. On the other hand, microarray analysis has revealed a number of differentially expressed genes involved in transcription regulation (e.g. FOXN4, GLI1), immune response (CCR7, IL8) and transmembrane transport (e.g. ABCC3, ABCC11) in the spheroids. Among these genes, increased expression of CCR7 in CD44+ CSCs was confirmed in NPC xenografts and primary tumors. Importantly, blocking of CCR7 abolished the sphere-forming ability of C666-1 in vitro. Expression of CCR7 was associated with recurrent disease and distant metastasis. The current study defined the specific properties of a CSC subpopulation in EBV-associated NPC. Our findings provided new insights into developing effective therapies targeting on CSCs, thereby potentiating treatment efficacy for NPC patients. PMID:23285037

Effective inhibition of nasopharyngeal carcinoma in vitro and in vivo by targeting glycolysis with oxamate.

PubMed

Li, Xiaobing; Lu, Wenhua; Hu, Yumin; Wen, Shijun; Qian, Chaonan; Wu, Wenjing; Huang, Peng

2013-11-01

Elevated aerobic glycolysis in cancer cells (Warburg effect) has been observed in many tumor types including nasopharyngeal carcinoma (NPC), which can often be detected clinically using FDG-PET. However, the role of glycolysis in supporting the growth of NPC cells and its therapeutic implications still remain to be investigated. In the present study, we showed that the LDH inhibitor oxamate significantly suppressed NPC cell proliferation in vitro and tumor growth in vivo, yet exhibited minimum toxicity to normal nasopharyngeal epithelial cells in vitro and was well tolerated in mice. Moreover, oxamate exhibited cytotoxic effect in NPC cells under hypoxia. Mechanistic study showed that oxamate significantly inhibited LDH activity, leading to a substantial decrease in glucose uptake and lactate production. Combination of oxamate with a mitochondrial respiratory complex I inhibitor resulted in a significant depletion of cellular ATP and a synergistic killing of cancer cells. Our results suggest that inhibition of glycolysis by oxamate is an effective therapeutic strategy for treatment of NPC and that combination of this compound with mitochondrial-targeted agents may improve the therapeutic activity.

Involvement of Difference in Decrease of Hemoglobin Level in Poor Prognosis of Stage I and II Nasopharyngeal Carcinoma: Implication in Outcome of Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao Jin; State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University, Guangzhou; Department of Radiation Oncology, Anhui provincial hospital, Hefei

2012-03-15

Purpose: To investigate the effect of hemoglobin (Hb) concentration and the difference in its decrease during treatment on outcome of radiotherapy (RT) alone for patients with Stage I and II nasopharyngeal carcinoma. Methods and Materials: A total of 572 patients with Stage I-II nasopharyngeal carcinoma with RT alone between January 2001 and December 2004 were retrospectively analyzed. Patient characteristics, tumor variables, and Hb level, including pre-RT Hb, mid-RT Hb, and dynamic change of Hb between pre- and post- RT and its difference in decrease ( White-Up-Pointing-Small-Triangle Hb) were subjected to univariate and multivariable analysis to identify factors that predict disease-specificmore » survival (DSS), local regional recurrence-free survival (LRFS), and metastases-free survival (MFS). Results: The 5-year DSS was poorer in the Hb continuous decrease group than in the Hb noncontinuous decrease group (84% vs. 89%; p = 0.008). There was poorer 5-year DSS in patients with White-Up-Pointing-Small-Triangle Hb of >11.5 g/L than in those with White-Up-Pointing-Small-Triangle Hb of {<=}11.5 g/L (82% vs. 89%; p = 0.001), and poorer LRFS (79% vs. 83%; p = 0.035). Univariate and multivariate analysis showed that Hb decrease difference with greater than 11.5 g/L was an independent prognostic factor for DSS and LRFS. Conclusions: The difference in decrease of Hb level during the course of radiation treatment appeared as a poor prognostic factor in Stage I and II nasopharyngeal carcinoma patients.« less

Selenium-binding protein 1 in head and neck cancer is low-expression and associates with the prognosis of nasopharyngeal carcinoma

PubMed Central

Chen, Fasheng; Chen, Chen; Qu, Yangang; Xiang, Hua; Ai, Qingxiu; Yang, Fei; Tan, Xueping; Zhou, Yi; Jiang, Guang; Zhang, Zixiong

2016-01-01

Abstract Background: Selenium-binding protein 1 (SELENBP1) expression is reduced markedly in many types of cancers and low SELENBP1 expression levels are associated with poor patient prognosis. Methods: SELENBP1 gene expression in head and neck squamous cell carcinoma (HNSCC) was analyzed with GEO dataset and characteristics of SELENBP1 expression in paraffin embedded tissue were summarized. Expression of SELENBP1 in nasopharyngeal carcinoma (NPC), laryngeal cancer, oral cancer, tonsil cancer, hypopharyngeal cancer and normal tissues were detected using immunohistochemistry, at last, 99 NPC patients were followed up more than 5 years and were analyzed the prognostic significance of SELENBP1. Results: Analysis of GEO dataset concluded that SELENBP1 gene expression in HNSCC was lower than that in normal tissue (P < 0.01), but there was no significant difference of SELENBP1 gene expression in different T-stage and N-stage (P > 0.05). Analysis of pathological section concluded that SELENBP1 in the majority of HNSCC is low expression and in cancer nests is lower expression than surrounding normal tissue, even associated with the malignant degree of tumor. Further study indicated the low SELENBP1 expression group of patients with NPC accompanied by poor overall survival and has significantly different comparing with the high expression group. Conclusion: SELENBP1 expression was down-regulated in HNSCC, but has no associated with T-stage and N-stage of tumor. Low expression of SELENBP1 in patients with NPC has poor over survival, so SELENBP1 could be a novel biomarker for predicting prognosis. PMID:27583873

[Expression of C-fos in nasopharyngeal carcinoma and the relationship with chemosensitivity and prognosis].

PubMed

Liu, Y T; Zhao, F P; Miao, H B; Fu, S Z; Zhou, S; Zhang, X G; Qin, G

2018-05-01

Objective: To investigate the expression of C-fos in patients with nasopharyngeal carcinoma(NPC), and analyze the relationship between the expression of C-fos and the clinical characteristics, chemosensitivity and prognosis. Method: Clinical and follow-up data of 75 NPC patients was analyzed retrospectively. The expression of C-fos was detected by immunohistochemical assay, and chemosensitivity was detected by ATP bioluminescent anticancer drug sensitivity detection technology. The relationship between them was studied. Result: The expression of C-fos in NPC was statistically higher than that in the control nasopharyngeal mucosa( P <0.001). It was found that C-fos had no statistical relationship with the gender, age, pathologic type, clinical stage of tumor classification, lymph node status, metastasis status and overall stage of NPC patients( P >0.05). NPC had different chemosensitivity with 8 anticancer drugs( P <0.001).There was a significant difference in chemosensitivity of paclitaxel between the high expression of C-fos group and the low expression of C-fos group( P =0.036). The rate of tumor progression was significantly higher in NPC patients with high expression of C-fos than in the low expression group( P =0.014).There was no significant difference in overall survival between the two groups( P =0.076). Conclusion: C-fos is highly expressed in NPC tissues, and the high expression of C-fos in NPC tissues may be related to tumor progression and resistance to paclitaxel. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Comparison of SPECT/CT, MRI and CT in diagnosis of skull base bone invasion in nasopharyngeal carcinoma.

PubMed

Zhang, Shu-xu; Han, Peng-hui; Zhang, Guo-qian; Wang, Rui-hao; Ge, Yong-bin; Ren, Zhi-gang; Li, Jian-sheng; Fu, Wen-hai

2014-01-01

Early detection of skull base invasion in nasopharyngeal carcinoma (NPC) is crucial for correct staging, assessing treatment response and contouring the tumor target in radiotherapy planning, as well as improving the patient's prognosis. To compare the diagnostic efficacy of single photon emission computed tomography/computed tomography (SPECT/CT) imaging, magnetic resonance imaging (MRI) and computed tomography (CT) for the detection of skull base invasion in NPC. Sixty untreated patients with histologically proven NPC underwent SPECT/CT imaging, contrast-enhanced MRI and CT. Of the 60 patients, 30 had skull base invasion confirmed by the final results of contrast-enhanced MRI, CT and six-month follow-up imaging (MRI and CT). The diagnostic efficacy of the three imaging modalities in detecting skull base invasion was evaluated. The rates of positive findings of skull base invasion for SPECT/CT, MRI and CT were 53.3%, 48.3% and 33.3%, respectively. The sensitivity, specificity and accuracy were 93.3%, 86.7% and 90.0% for SPECT/CT fusion imaging, 96.7%, 100.0% and 98.3% for contrast-enhanced MRI, and 66.7%, 100.0% and 83.3% for contrast-enhanced CT. MRI showed the best performance for the diagnosis of skull base invasion in nasopharyngeal carcinoma, followed closely by SPECT/CT. SPECT/CT had poorer specificity than that of both MRI and CT, while CT had the lowest sensitivity.

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

PubMed

Zhang, Jingyang; Liu, Hongling; Liang, Xue; Zhang, Min; Wang, Renke; Peng, Guang; Li, Jiyao

2015-01-01

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.

Bile acids at neutral and acidic pH induce apoptosis and gene cleavages in nasopharyngeal epithelial cells: implications in chromosome rearrangement.

PubMed

Tan, Sang-Nee; Sim, Sai-Peng

2018-04-12

Chronic rhinosinusitis (CRS) increases the risk of developing nasopharyngeal carcinoma (NPC) while nasopharyngeal reflux is known to be one of the major aetiological factors of CRS. Bile acid (BA), the component of gastric duodenal contents, has been recognised as a carcinogen. BA-induced apoptosis was suggested to be involved in human malignancies. Cells have the potential and tendency to survive apoptosis. However, cells that evade apoptosis upon erroneous DNA repair may carry chromosome rearrangements. Apoptotic nuclease, caspase-activated deoxyribonuclease (CAD) has been implicated in mediating translocation in leukaemia. We hypothesised that BA-induced apoptosis may cause chromosome breaks mediated by CAD leading to chromosome rearrangement in NPC. This study targeted the AF9 gene located at 9p22 because 9p22 is one of the most common deletion sites in NPC. We tested the ability of BA at neutral and acidic pH in inducing phosphatidylserine (PS) externalisation, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) disruption, and caspase 3/7 activity in normal nasopharyngeal epithelial (NP69) and NPC (TWO4) cells. Inverse-PCR (IPCR) was employed to detect AF9 gene cleavages. To investigate the role of CAD in mediating these cleavages, caspase inhibition was performed. IPCR bands representing AF9 cleaved fragments were sequenced. BA-treated cells showed higher levels of PS externalisation, ROS production, MMP loss and caspase 3/7 activity than untreated control cells. The effect of BA in the induction of these intracellular events was enhanced by acid. BA at neutral and acidic pH also induced significant cleavage of the AF9 gene. These BA-induced gene cleavages were inhibited by Z-DEVD-FMK, a caspase-3 inhibitor. Intriguingly, a few chromosome breaks were identified within the AF9 region that was previously reported to participate in reciprocal translocation between the mixed lineage leukaemia (MLL) and AF9 genes in an acute

Salivary gland and nasopharyngeal cancers in individuals with acquired immunodeficiency syndrome in United States.

PubMed

Shebl, Fatma M; Bhatia, Kishor; Engels, Eric A

2010-05-15

Individuals with acquired immunodeficiency syndrome (AIDS) manifest an increased risk of cancer, particularly cancers caused by oncogenic viruses. Because some salivary gland and nasopharyngeal cancers are associated with Epstein Barr virus, the impact of AIDS on these cancers needs further evaluation. We used linked U.S. AIDS and cancer registry data (N = 519,934 people with AIDS) to derive standardized incidence ratios (SIRs) comparing risk of salivary gland and nasopharyngeal cancers to the general population. For salivary gland cancers (N = 43 cases), individuals with AIDS had strongly elevated risks for lymphoepithelial carcinoma (SIR 39, 95% CI 16-81) and squamous cell carcinoma (SIR 4.9, 95% CI 2.5-8.6). Among nasopharyngeal cancers (N = 39 cases), risks were elevated for both keratinizing and nonkeratinizing carcinomas (SIR 2.4, 95% CI 1.5-3.7 and SIR 2.4, 95% CI 1.2-4.4, respectively). The elevated risks of salivary gland and nasopharyngeal cancers among people with AIDS suggest that immunosuppression and oncogenic viral infections are etiologically important.

Salivary Gland and Nasopharyngeal Cancers in Individuals with Acquired Immunodeficiency Syndrome in United States

PubMed Central

Shebl, Fatma M.; Bhatia, Kishor; Engels, Eric A.

2009-01-01

Individuals with acquired immunodeficiency syndrome (AIDS) manifest an increased risk of cancer, particularly cancers caused by oncogenic viruses. Because some salivary gland and nasopharyngeal cancers are associated with Epstein Barr virus, the impact of AIDS on these cancers needs further evaluation. We used linked U.S. AIDS and cancer registry data (N=519,934 people with AIDS) to derive standardized incidence ratios (SIRs) comparing risk of salivary gland and nasopharyngeal cancers to the general population. For salivary gland cancers (N=43 cases), individuals with AIDS had strongly elevated risks for lymphoepithelial carcinoma (SIR 39, 95% CI 16-81) and squamous cell carcinoma (SIR 4.9, 95% CI 2.5-8.6). Among nasopharyngeal cancers (N=39 cases), risks were elevated for both keratinizing and non-keratinizing carcinomas (SIR 2.4, 95% CI 1.5-3.7, and SIR 2.4, 95% CI 1.2-4.4, respectively). The elevated risks of salivary gland and nasopharyngeal cancers among people with AIDS suggest that immunosuppression and oncogenic viral infections are etiologically important. PMID:19810095

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

PubMed Central

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

2015-01-01

We investigated the incidence of moderate to severe patient-reported xerostomia among nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT) and identified patient- and therapy-related factors associated with acute and chronic xerostomia toxicity. The least absolute shrinkage and selection operator (LASSO) normal tissue complication probability (NTCP) models were developed using quality-of-life questionnaire datasets from 67 patients with NPC. For acute toxicity, the dosimetric factors of the mean doses to the ipsilateral submandibular gland (Dis) and the contralateral submandibular gland (Dcs) were selected as the first two significant predictors. For chronic toxicity, four predictive factors were selected: age, mean dose to the oral cavity (Doc), education, and T stage. The substantial sparing data can be used to avoid xerostomia toxicity. We suggest that the tolerance values corresponded to a 20% incidence of complications (TD20) for Dis = 39.0 Gy, Dcs = 38.4 Gy, and Doc = 32.5 Gy, respectively, when mean doses to the parotid glands met the QUANTEC 25 Gy sparing guidelines. To avoid patient-reported xerostomia toxicity, the mean doses to the parotid gland, submandibular gland, and oral cavity have to meet the sparing tolerance, although there is also a need to take inherent patient characteristics into consideration. PMID:26289304

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

PubMed

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

2015-08-20

We investigated the incidence of moderate to severe patient-reported xerostomia among nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT) and identified patient- and therapy-related factors associated with acute and chronic xerostomia toxicity. The least absolute shrinkage and selection operator (LASSO) normal tissue complication probability (NTCP) models were developed using quality-of-life questionnaire datasets from 67 patients with NPC. For acute toxicity, the dosimetric factors of the mean doses to the ipsilateral submandibular gland (Dis) and the contralateral submandibular gland (Dcs) were selected as the first two significant predictors. For chronic toxicity, four predictive factors were selected: age, mean dose to the oral cavity (Doc), education, and T stage. The substantial sparing data can be used to avoid xerostomia toxicity. We suggest that the tolerance values corresponded to a 20% incidence of complications (TD20) for Dis = 39.0 Gy, Dcs = 38.4 Gy, and Doc = 32.5 Gy, respectively, when mean doses to the parotid glands met the QUANTEC 25 Gy sparing guidelines. To avoid patient-reported xerostomia toxicity, the mean doses to the parotid gland, submandibular gland, and oral cavity have to meet the sparing tolerance, although there is also a need to take inherent patient characteristics into consideration.

Neurosurgical interventions for patients with nasopharyngeal carcinoma: a single institution experience

PubMed Central

2013-01-01

Background Nasopharyngeal carcinoma (NPC) is a frequent head and neck cancer in southern China and Southeast Asia. The majority of NPC patients are managed by radiation oncologists, medical oncologists and head and neck surgeons. Actually, neurosurgical interventions are warranted under specific circumstances. In this article, we described our experience as neurosurgeons in the management of NPC patients. Methods Medical records of NPC patients who received neurosurgical procedure at Sun Yat-sen University Cancer Center were reviewed. Results Twenty-seven patients were identified. Among 27 cases, neurosurgical procedures were performed in 18 (66.7%) with radiation-induced temporal necrosis, 2 (7.4%) with radiation-induced sarcoma, 4 (14.8%) with synchronous NPC with primary brain tumors, 2 (7.4%) with recurrent NPC involving skull base, and 1 (3.7%) with metachronous skull eosinophilic granuloma, respectively. The diagnosis is challenging in specific cases and initial misdiagnoses were found in 6 (22.2%) patients. Conclusions For NPC patients with intracranial or skull lesions, the initial diagnosis can be occasionally difficult because of the presence or a history of NPC and related treatment. Unawareness of these entities can result in misdiagnosis and subsequent improper treatment. Neurosurgical interventions are necessary for the diagnosis and treatment for these patients. PMID:24034781

Real-time In vivo Diagnosis of Nasopharyngeal Carcinoma Using Rapid Fiber-Optic Raman Spectroscopy.

PubMed

Lin, Kan; Zheng, Wei; Lim, Chwee Ming; Huang, Zhiwei

2017-01-01

We report the utility of a simultaneous fingerprint (FP) (i.e., 800-1800 cm -1 ) and high-wavenumber (HW) (i.e., 2800-3600 cm -1 ) fiber-optic Raman spectroscopy developed for real-time in vivo diagnosis of nasopharyngeal carcinoma (NPC) at endoscopy. A total of 3731 high-quality in vivo FP/HW Raman spectra (normal=1765; cancer=1966) were acquired in real-time from 204 tissue sites (normal=95; cancer=109) of 95 subjects (normal=57; cancer=38) undergoing endoscopic examination. FP/HW Raman spectra differ significantly between normal and cancerous nasopharyngeal tissues that could be attributed to changes of proteins, lipids, nucleic acids, and the bound water content in NPC. Principal components analysis (PCA) and linear discriminant analysis (LDA) together with leave-one subject-out, cross-validation (LOO-CV) were implemented to develop robust Raman diagnostic models. The simultaneous FP/HW Raman spectroscopy technique together with PCA-LDA and LOO-CV modeling provides a diagnostic accuracy of 93.1% (sensitivity of 93.6%; specificity of 92.6%) for nasopharyngeal cancer identification, which is superior to using either FP (accuracy of 89.2%; sensitivity of 89.9%; specificity of 88.4%) or HW (accuracy of 89.7%; sensitivity of 89.0%; specificity of 90.5%) Raman technique alone. Further receiver operating characteristic (ROC) analysis reconfirms the best performance of the simultaneous FP/HW Raman technique for in vivo diagnosis of NPC. This work demonstrates for the first time that simultaneous FP/HW fiber-optic Raman spectroscopy technique has great promise for enhancing real-time in vivo cancer diagnosis in the nasopharynx during endoscopic examination.

Evaluation of Sixth Edition of AJCC Staging System for Nasopharyngeal Carcinoma and Proposed Improvement

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu Mengzhong; Tang Linglong; Zong Jingfeng

2008-03-15

Purpose: To evaluate the 6th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma and to search for ways to improve the system. Methods and Materials: We performed a retrospective review of data from 749 biopsy-proven nonmetastatic nasopharyngeal carcinoma patients. All patients had undergone contrast-enhanced computed tomography and had received radiotherapy as their primary treatment. Results: The T stage, N stage, and stage group were significant, independent predictors for disease-specific death. No significant differences were found between Stage T2a and T1 in local failure-free survival or between Stage N3a and N2 in distantmore » failure-free survival. Survival curves of the different T/N subsets showed a better segregation when T2a and N3a were downstaged to T1 and N2, respectively. The hazard ratio of disease-specific deaths for patients with T2N0 disease was similar to that of patients with T1N0 disease; the same result was found for the T3N0 and T4N0 subsets. Downstaging the T2N0 subset to Stage I, T3N0 to Stage II, and T4N0 to Stage III resulted in a more balanced patient distribution, better hazard consistency among subgroups, and improved hazard discrimination between overall stages. Conclusion: Using the 6th edition of the American Joint Committee on Cancer staging system produced an acceptable distribution of patient numbers and segregation of survival curves among the different stage groups. The prognostic accuracy of the staging system could be improved by recategorization of the T, N, and group stage criteria.« less

Intravoxel water diffusion heterogeneity MR imaging of nasopharyngeal carcinoma using stretched exponential diffusion model.

PubMed

Lai, Vincent; Lee, Victor Ho Fun; Lam, Ka On; Sze, Henry Chun Kin; Chan, Queenie; Khong, Pek Lan

2015-06-01

To determine the utility of stretched exponential diffusion model in characterisation of the water diffusion heterogeneity in different tumour stages of nasopharyngeal carcinoma (NPC). Fifty patients with newly diagnosed NPC were prospectively recruited. Diffusion-weighted MR imaging was performed using five b values (0-2,500 s/mm(2)). Respective stretched exponential parameters (DDC, distributed diffusion coefficient; and alpha (α), water heterogeneity) were calculated. Patients were stratified into low and high tumour stage groups based on the American Joint Committee on Cancer (AJCC) staging for determination of the predictive powers of DDC and α using t test and ROC curve analyses. The mean ± standard deviation values were DDC = 0.692 ± 0.199 (×10(-3) mm(2)/s) for low stage group vs 0.794 ± 0.253 (×10(-3) mm(2)/s) for high stage group; α = 0.792 ± 0.145 for low stage group vs 0.698 ± 0.155 for high stage group. α was significantly lower in the high stage group while DDC was negatively correlated. DDC and α were both reliable independent predictors (p < 0.001), with α being more powerful. Optimal cut-off values were (sensitivity, specificity, positive likelihood ratio, negative likelihood ratio) DDC = 0.692 × 10(-3) mm(2)/s (94.4 %, 64.3 %, 2.64, 0.09), α = 0.720 (72.2 %, 100 %, -, 0.28). The heterogeneity index α is robust and can potentially help in staging and grading prediction in NPC. • Stretched exponential diffusion models can help in tissue characterisation in nasopharyngeal carcinoma • α and distributed diffusion coefficient (DDC) are negatively correlated • α is a robust heterogeneity index marker • α can potentially help in staging and grading prediction.

XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells

PubMed Central

Ji, Jiao; Yu, Yan; Li, Zhi-Ling; Chen, Ming-Yuan; Deng, Rong; Huang, Xiang; Wang, Guang-Feng; Zhang, Meng-Xia; Yang, Qi; Ravichandran, Senthilkumar; Feng, Gong-Kan; Xu, Xue-Lian; Yang, Chen-Lu; Qiu, Miao-Zhen; Jiao, Lin; Yang, Dajun; Zhu, Xiao-Feng

2018-01-01

Rationale: Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. The presence of cancer stem cells (CSCs) in NPC contributes to tumor maintenance and therapeutic resistance, while the ability of CSCs to escape from the apoptosis pathway may render them the resistant property to the therapies. Inhibitor of apoptosis proteins family proteins (IAPs), which are overexpressed in nasopharyngeal carcinoma stem cells, may play an important role in maintaining nasopharyngeal cancer stem cell properties. Here, we develop a novel CSC-targeting strategy to treat NPC through inhibiting IAPs. Methods: Human NPC S-18 and S-26 cell lines were used as the model system in vitro and in vivo. Fluorescence activated cell sorting (FACS) assay was used to detect nasopharyngeal SP cells and CD44+ cells. The characteristics of CSCs were defined by sphere suspension culture, colony formation assay and cell migration. The role of XIAP on the regulation of Sox2 protein stability and ERK1-mediated phosphorylation of Sox2 signaling pathway were analyzed using immunoblotting, immunoprecipitation, immunofluorescence, phosphorylation mass spectrometry, siRNA silencing and plasmid overexpression. The correlation between XIAP and Sox2 in NPC biopsies and their role in prognosis was performed by immunohistochemistry. APG-1387 or chemotherapies-induced cell death and apoptosis in S-18 and S-26 were determined by WST, immunoblotting and flow cytometry assay. Results: IAPs, especially X chromosome-linked IAP (XIAP), were elevated in CSCs of NPC, and these proteins were critically involved in the maintenance of CSCs properties by enhancing the stability of Sox2. Mechanistically, ERK1 kinase promoted autophagic degradation of Sox2 via phosphorylation of Sox2 at Ser251 and further SUMOylation of Sox2 at Lys245 in non-CSCs. However, XIAP blocked autophagic degradation of Sox2 by inhibiting ERK1 activation in CSCs. Additionally, XIAP was positively correlated with Sox2

Evaluating hepatocellular carcinoma cell lines for tumour samples using within-sample relative expression orderings of genes.

PubMed

Ao, Lu; Guo, You; Song, Xuekun; Guan, Qingzhou; Zheng, Weicheng; Zhang, Jiahui; Huang, Haiyan; Zou, Yi; Guo, Zheng; Wang, Xianlong

2017-11-01

Concerns are raised about the representativeness of cell lines for tumours due to the culture environment and misidentification. Liver is a major metastatic destination of many cancers, which might further confuse the origin of hepatocellular carcinoma cell lines. Therefore, it is of crucial importance to understand how well they can represent hepatocellular carcinoma. The HCC-specific gene pairs with highly stable relative expression orderings in more than 99% of hepatocellular carcinoma but with reversed relative expression orderings in at least 99% of one of the six types of cancer, colorectal carcinoma, breast carcinoma, non-small-cell lung cancer, gastric carcinoma, pancreatic carcinoma and ovarian carcinoma, were identified. With the simple majority rule, the HCC-specific relative expression orderings from comparisons with colorectal carcinoma and breast carcinoma could exactly discriminate primary hepatocellular carcinoma samples from both primary colorectal carcinoma and breast carcinoma samples. Especially, they correctly classified more than 90% of liver metastatic samples from colorectal carcinoma and breast carcinoma to their original tumours. Finally, using these HCC-specific relative expression orderings from comparisons with six cancer types, we identified eight of 24 hepatocellular carcinoma cell lines in the Cancer Cell Line Encyclopedia (Huh-7, Huh-1, HepG2, Hep3B, JHH-5, JHH-7, C3A and Alexander cells) that are highly representative of hepatocellular carcinoma. Evaluated with a REOs-based prognostic signature for hepatocellular carcinoma, all these eight cell lines showed the same metastatic properties of the high-risk metastatic hepatocellular carcinoma tissues. Caution should be taken for using hepatocellular carcinoma cell lines. Our results should be helpful to select proper hepatocellular carcinoma cell lines for biological experiments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[A new applicator with regulatable air bag designed for intracavitary brachytherapy of nasopharyngeal carcinoma].

PubMed

Zhang, Ning; Wei, Guang-Yu; Tan, Yi-Chang; Huang, Ze-Li; Li, Shao-En; Lu, Zhi-Qian

2004-10-01

Nasopharynx applicator used in intracavitary brachytherapy plays an important role in the radiotherapy of nasopharyngeal carcinoma (NPC), its quality affects the efficiency of treatment. This study was to design a new applicator for clinical use. An inexpensive, reusable, and flexible latex nasopharynx applicator was designed. An air bag was placed at 15 mm from the foreside of the applicator, clung to the tube. The edge of air bag is tangent to the axis of tube. When the bag was full of air, the tube would hunch reversely,close to nasopharyngeal vault. After introduced into nasopharynx through middle nasal meatus, the applicator could be fixed in suitable position by its rotation, and air bag regulation, and confirmed its position by simulation. A total of 221 patients with NPC were treated with external beam radiation therapy in our hospital, and boosted HDR brachytherapy using this new applicator. The response rate was 92.6% in the primary tumor group (200/216), and 100% in the recurrent tumor group (5/5). Mucosal necrosis in the posterior or anterior wall of nasopharynx occurred in 5 patients, 8 patients experienced nasal congestion and nasal synechia. This new nasopharynx applicator is easy to operate, painless, and well dosage-distributed. Mucosal necrosis is likely due to higher fractional dose.

Investigation of Salivary Function and Oral Microbiota of Radiation Caries-Free People with Nasopharyngeal Carcinoma

PubMed Central

Zhang, Jingyang; Liu, Hongling; Liang, Xue; Zhang, Min; Wang, Renke; Peng, Guang; Li, Jiyao

2015-01-01

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. PMID:25860481

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

PubMed

Zhuang, Mingzhu; Zhao, Mouming; Qiu, Huijuan; Shi, Dingbo; Wang, Jingshu; Tian, Yun; Lin, Lianzhu; Deng, Wuguo

2014-01-01

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.

The Principal Genetic Determinants for Nasopharyngeal Carcinoma in China Involve the HLA Class I Antigen Recognition Groove

PubMed Central

Tang, Minzhong; Lautenberger, James A.; Gao, Xiaojiang; Sezgin, Efe; Hendrickson, Sher L.; Troyer, Jennifer L.; David, Victor A.; Guan, Li; Mcintosh, Carl E.; Guo, Xiuchan; Zheng, Yuming; Liao, Jian; Deng, Hong; Malasky, Michael; Kessing, Bailey; Winkler, Cheryl A.; Carrington, Mary; dé The, Guy; Zeng, Yi; O'Brien, Stephen J.

2012-01-01

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy facilitated by Epstein-Barr Virus infection. Here we resolve the major genetic influences for NPC incidence using a genome-wide association study (GWAS), independent cohort replication, and high-resolution molecular HLA class I gene typing including 4,055 study participants from the Guangxi Zhuang Autonomous Region and Guangdong province of southern China. We detect and replicate strong association signals involving SNPs, HLA alleles, and amino acid (aa) variants across the major histocompatibility complex-HLA-A, HLA –B, and HLA -C class I genes (PHLA-A-aa-site-62 = 7.4×10−29; P HLA-B-aa-site-116 = 6.5×10−19; P HLA-C-aa-site-156 = 6.8×10−8 respectively). Over 250 NPC-HLA associated variants within HLA were analyzed in concert to resolve separate and largely independent HLA-A, -B, and -C gene influences. Multivariate logistical regression analysis collapsed significant associations in adjacent genes spanning 500 kb (OR2H1, GABBR1, HLA-F, and HCG9) as proxies for peptide binding motifs carried by HLA- A*11:01. A similar analysis resolved an independent association signal driven by HLA-B*13:01, B*38:02, and B*55:02 alleles together. NPC resistance alleles carrying the strongly associated amino acid variants implicate specific class I peptide recognition motifs in HLA-A and -B peptide binding groove as conferring strong genetic influence on the development of NPC in China. PMID:23209447

Cannabis, tobacco and domestic fumes intake are associated with nasopharyngeal carcinoma in North Africa.

PubMed

Feng, B-J; Khyatti, M; Ben-Ayoub, W; Dahmoul, S; Ayad, M; Maachi, F; Bedadra, W; Abdoun, M; Mesli, S; Bakkali, H; Jalbout, M; Hamdi-Cherif, M; Boualga, K; Bouaouina, N; Chouchane, L; Benider, A; Ben-Ayed, F; Goldgar, D E; Corbex, M

2009-10-06

The lifestyle risk factors for nasopharyngeal carcinoma (NPC) in North Africa are not known. From 2002 to 2005, we interviewed 636 patients and 615 controls from Algeria, Morocco and Tunisia, frequency-matched by centre, age, sex, and childhood household type (urban/rural). Conditional logistic regression was used to evaluate the association of lifestyles with NPC risk, controlling for socioeconomic status and dietary risk factors. Cigarette smoking and snuff (tobacco powder with additives) intake were significantly associated with differentiated NPC but not with undifferentiated carcinoma (UCNT), which is the major histological type of NPC in these populations. As demonstrated by a stratified permutation test and by conditional logistic regression, marijuana smoking significantly elevated NPC risk independently of cigarette smoking, suggesting dissimilar carcinogenic mechanisms between cannabis and tobacco. Domestic cooking fumes intake by using kanoun (compact charcoal oven) during childhood increased NPC risk, whereas exposure during adulthood had less effect. Neither alcohol nor shisha (water pipe) was associated with risk. Tobacco, cannabis and domestic cooking fumes intake are risk factors for NPC in western North Africa.

Cannabis, tobacco and domestic fumes intake are associated with nasopharyngeal carcinoma in North Africa

PubMed Central

Feng, B-J; Khyatti, M; Ben-Ayoub, W; Dahmoul, S; Ayad, M; Maachi, F; Bedadra, W; Abdoun, M; Mesli, S; Bakkali, H; Jalbout, M; Hamdi-Cherif, M; Boualga, K; Bouaouina, N; Chouchane, L; Benider, A; Ben-Ayed, F; Goldgar, D E; Corbex, M

2009-01-01

Background: The lifestyle risk factors for nasopharyngeal carcinoma (NPC) in North Africa are not known. Methods: From 2002 to 2005, we interviewed 636 patients and 615 controls from Algeria, Morocco and Tunisia, frequency-matched by centre, age, sex, and childhood household type (urban/rural). Conditional logistic regression was used to evaluate the association of lifestyles with NPC risk, controlling for socioeconomic status and dietary risk factors. Results: Cigarette smoking and snuff (tobacco powder with additives) intake were significantly associated with differentiated NPC but not with undifferentiated carcinoma (UCNT), which is the major histological type of NPC in these populations. As demonstrated by a stratified permutation test and by conditional logistic regression, marijuana smoking significantly elevated NPC risk independently of cigarette smoking, suggesting dissimilar carcinogenic mechanisms between cannabis and tobacco. Domestic cooking fumes intake by using kanoun (compact charcoal oven) during childhood increased NPC risk, whereas exposure during adulthood had less effect. Neither alcohol nor shisha (water pipe) was associated with risk. Conclusion: Tobacco, cannabis and domestic cooking fumes intake are risk factors for NPC in western North Africa. PMID:19724280

Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence.

PubMed

Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

2015-01-01

There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma.

Tetrandrine Induces Apoptosis in Human Nasopharyngeal Carcinoma NPC-TW 039 Cells by Endoplasmic Reticulum Stress and Ca2+/Calpain Pathways.

PubMed

Liu, Kuo-Ching; Lin, Ya-Jing; Hsiao, Yung-Ting; Lin, Meng-Liang; Yang, Jiun-Long; Huang, Yi-Ping; Chu, Yung-Lin; Chung, Jing-Gung

2017-11-01

Tetrandrine is an alkaloid extracted from a traditional China medicine plant, and is considered part of food therapy as well. In addition, it has been widely reported to induce apoptotic cell death in many human cancer cells. However, the mechanism of Tetrandrine on human nasopharyngeal carcinoma cells (NPC) is still questioned. In our study, we examined whether Tetrandrine can induce apoptosis of NPC-TW 039 cells. We found that cell morphology was changed after treatment with different concentrations of Tetrandrine. Further, we indicated that the NPC-TW 039 cells viability decreased in a Tetrandrine dose-dependent manner. We also found that tetrandrine induced cell cycle arrest in G 0 /G 1 phase. Tetrandrine induced DNA condensation by DAPI staining as well. In addition, we found that Tetrandrine induced Ca 2+ release in the cytosol. At the same time, endoplasmic reticulum (ER) stress occurred. Then we used western blotting to examine the protein expression which is associated with mitochondria-mediated apoptotic pathways and caspase-dependent pathways. To further examine whether Ca 2+ was released or not with Tetrandrine induced-apoptosis, we used the chelator of Ca 2+ and showed that cell viability increased. At the same time, caspase-3 expression was decreased. Furthermore, confocal microscopy examination revealed that Tetrandrine induced expression of ER stress-related proteins GADD153 and GRP78. Our results indicate that Tetrandrine induces apoptosis through calcium-mediated ER stress and caspase pathway in NPC-TW 039 cells. In conclusion, Tetrandrine may could be used for treatment of human nasopharyngeal carcinoma in future. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Nasopharyngeal carcinoma as a paradigm of cancer genetics

PubMed Central

Simons, Malcolm J.

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 modern 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

Nasopharyngeal carcinoma as a paradigm of cancer genetics.

PubMed

Simons, Malcolm J

2011-02-01

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 modern 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

Epstein-Barr Virus (EBV)-associated Gastric Carcinoma

PubMed Central

Iizasa, Hisashi; Nanbo, Asuka; Nishikawa, Jun; Jinushi, Masahisa; Yoshiyama, Hironori

2012-01-01

The ubiquitous Epstein-Barr virus (EBV) is associated with several human tumors, which include lymphoid and epithelial malignancies. It is known that EBV persistently infects the memory B cell pool of healthy individuals by activating growth and survival signaling pathways that can contribute to B cell lymphomagenesis. Although the monoclonal proliferation of EBV-infected cells can be observed in epithelial tumors, such as nasopharyngeal carcinoma and EBV-associated gastric carcinoma, the precise role of EBV in the carcinogenic progress is not fully understood. This review features characteristics and current understanding of EBV-associated gastric carcinoma. EBV-associated gastric carcinoma comprises almost 10% of all gastric carcinoma cases and expresses restricted EBV latent genes (Latency I). Firstly, definition, epidemiology, and clinical features are discussed. Then, the route of infection and carcinogenic role of viral genes are presented. Of particular interest, the association with frequent genomic CpG methylation and role of miRNA for carcinogenesis are topically discussed. Finally, the possibility of therapies targeting EBV-associated gastric carcinoma is proposed. PMID:23342366

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

PubMed Central

Hutajulu, Susanna Hilda; Kurnianda, Johan; Tan, I Bing; Middeldorp, Jaap M

2014-01-01

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 cure rate and add clinical benefit. The promising results of early phase clinical trials on EBV-specific immunotherapy, epigenetic therapy, and treatment with viral lytic induction offer new options for treating NPC. PMID:25228810

LMP1-mediated glycolysis induces myeloid-derived suppressor cell expansion in nasopharyngeal carcinoma

PubMed Central

Cai, Ting-Ting; Ye, Shu-Biao; Liu, Yi-Na; He, Jia; Chen, Qiu-Yan; Mai, Hai-Qiang; Zhang, Chuan-Xia; Cui, Jun; Zhang, Xiao-Shi; Zeng, Yi-Xin

2017-01-01

Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections. The full process has been reconstituted in vitro. LMP1 promotes the expression of multiple glycolytic genes, including GLUT1. This metabolic reprogramming results in increased expression of the Nod-like receptor family protein 3 (NLRP3) inflammasome, COX-2 and P-p65 and, consequently, increased production of IL-1β, IL-6 and GM-CSF. Finally, these changes in the environment of malignant cells result in enhanced NPC-derived MDSC induction. One key step is the physical interaction of LMP1 with GLUT1 to stabilize the GLUT1 protein by blocking its K48-ubiquitination and p62-dependent autolysosomal degradation. This work indicates that LMP1-mediated glycolysis regulates IL-1β, IL-6 and GM-CSF production through the NLRP3 inflammasome, COX-2 and P-p65 signaling pathways to enhance tumor-associated MDSC expansion, which leads to tumor immunosuppression in NPC. PMID:28732079

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

PubMed

Fang, Chih-Yeu; Huang, Sheng-Yen; Wu, Chung-Chun; Hsu, Hui-Yu; Chou, Sheng-Ping; Tsai, Ching-Hwa; Chang, Yao; Takada, Kenzo; Chen, Jen-Yang

2012-01-01

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 carcinogens can

The Synergistic Effect of Chemical Carcinogens Enhances Epstein-Barr Virus Reactivation and Tumor Progression of Nasopharyngeal Carcinoma Cells

PubMed Central

Fang, Chih-Yeu; Huang, Sheng-Yen; Wu, Chung-Chun; Hsu, Hui-Yu; Chou, Sheng-Ping; Tsai, Ching-Hwa; Chang, Yao; Takada, Kenzo; Chen, Jen-Yang

2012-01-01

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 carcinogens can

Emodin suppresses the nasopharyngeal carcinoma cells by targeting the chloride channels.

PubMed

Ma, Lianshun; Yang, Yaping; Yin, Zizhang; Liu, Mei; Wang, Liwei; Chen, Lixin; Zhu, Linyan; Yang, Haifeng

2017-06-01

Emodin is a natural anthraquinone derivative isolated from the Rheum palmatum. Recent studies demonstrated that emodin has anti-cancer activity in different kinds of human cancer cell lines. However, the underlying mechanism has not been very well studied. Our previous studies showed chloride channels is an important target of anti-cancer drugs. Therefore, the purpose of this research was aimed to explore the role of chloride channels involving in the anti-cancer activity of emodin. The proliferation, cell cycle arrest and apoptosis of poorly differentiated human nasopharyngeal carcinoma cells (CNE-2Z) and normal nasopharyngeal epithelial cells (NP69-SV40T) were detected by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide(MTT)and flow cytometry. The results indicated that emodin inhibited the CNE-2Z cell growth more significantly than NP69-SV40T cells and induced cell cycle arrest and apoptosis in CNE-2Z cells but not in NP69-SV40T cells. Chloride channel blocker 5-nitro-2-(3-phenylprop ylamino)-benzoate (NPPB) or tamoxifen both can prevent the apoptosis of CNE-2Z cells induced by emodin. Optical microscope and atomic force microscope (AFM) demonstrated that emodin can induce apoptotic volume decrease (AVD) and ultrastructure changes in CNE-2Z cell and inhibited by chloride channel blocker. These data could be a further evidence of chloride channel for preventing CNE-2Z cells from apoptosis induced by emodin. Whole cell patch clamp study also demonstrated that emodin can activate chloride channel in CNE-2Z cells but not in NP69-SV40T cells. Furthermore, the activated chloride currents can also be inhibited by chloride channel blockers indicating that chloride channel may be the potential target molecular of emodin exerting its anti-tumor efficiency in CNE-2Z cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Sers Imaging of Nasopharyngeal Carcinoma Markers Using an Antibody-Conjugated Gold Nanoparticles Probe

NASA Astrophysics Data System (ADS)

Li, J.-H.; Du, Y.; Feng, G.-K.; Du, Y.-B.; Zhou, Y.-Q.; Zeng, M.-S.

2017-11-01

Surface-enhanced Raman scattering (SERS) nanotags as an ultrasensitive nanoprobe is becoming popular for the detection of biomarkers. Herein, antibody-conjugated gold nanoparticles (AuNPs) were used to target LMP2A in an LMP2A-infected CNE2 cell line. SERS maps showed that the LMP2A was distributed around the cell, which was consistent with the results of immunofl uorescence staining in the previous report. This location could be due to the specific binding of the bioconjugated nanotags to the receptors on the cell surface. However, the CNE2 cell line without LMP2A-infected showed no detectable signal at 1044 cm-1. The results demonstrated the potential feasibility of AuNPs nanotags as highly sensitive probes conjugated at the subcellular level for detection and localization of cancer markers in nasopharyngeal carcinoma (NPC).

Long non-coding RNA ZNF674-1 acts as a cancer suppressor in nasopharyngeal carcinoma.

PubMed

Nie, Guo-Hui; Li, Zhao; Duan, Hong-Fang; Luo, Liang; Hu, Hong-Yi; Chen, Xiao-Fan; Zhang, Wei

2018-06-01

Nasopharyngeal carcinoma (NPC) is the most frequently occurring carcinoma of the head and neck. The complexity of NPC makes it difficult for it to be diagnosed and treated at an early stage. Certain long non-coding RNAs (lncRNAs) are closely associated with the carcinogenesis of NPC. In the present study, the expression of lncRNA ZNF674-1 in NPC tissues and an NPC cell line was analyzed and was revealed to be downregulated compared with normal tissues and cells. When the expression of lncRNA ZNF674-1 was reduced in NPC cells, the proliferation, migration and invasion of these cells was promoted, whereas the apoptosis of these cells was decreased. On the contrary, when overexpressed, the expression of lncRNA ZNF674-1 inhibited the proliferation, invasion and migration of cells, but promoted cell apoptosis. The results of the present study reveal that the lncRNA ZNF67-1 may restrain the carcinogenesis of NPC, and may also serve as a potential biomarker for the early diagnosis and treatment of NPC.

Long-term observation after radiotherapy for nasopharyngeal carcinoma (NPC).

PubMed

Chen, W Z; Zhou, D L; Luo, K S

1989-02-01

One thousand one hundred twenty-seven cases of nasopharyngeal carcinoma were treated with routine radiotherapy from October 1969 to March 1976, of which 436 cases have survived for more than 5 years, 323 cases have survived for over 10 years. The follow-up rate was 98.4%. The present paper analyzes the factors involved in these 436 cases. All patients were treated with tele60Co unit, and in the neck some cases were treated with orthovoltage therapy. The total dose to the primary lesion was 60-75 Gy in 6-8 weeks and in a few cases over 80 Gy were needed, and 50 Gy were applied bilateral cervical lymphatic chain. In this series of cases the 10-year overall survival rate was 28.7%, with Stage I being 66.7%, Stage II 46.5%, Stage III 28.0%, and Stage IV 18.6%, respectively. Statistically, 68 cases died of cardiovascular and other diseases and should be eliminated for net survival calculations. Therefore, we could obtain an actual 10-year survival rate of 30.5%. However, it should be noted that most of these cases were advanced, with Stage III, IV accounting for 82.3%, thus at Stage I, II the 10-year survival rate was 48%, while at Stage III, IV rate was down to 24.5%, which was statistically significant (p less than 0.01). Local and cervical recurrence as well as distant spread of diseases, for these cases started from the fifth to the tenth year after radiotherapy, the mortality caused by the above-mentioned three sites together was 76.9%. According to these findings, we propose that follow-up after radiotherapy in NPC exceeds 10-years. Of the 323 NPC cases, 10 were nasopharyngeal local recurrence which were re-irradiated, accounting for 3.1%. This paper shows that the 3-year survival rate in the local recurrence which were re-irradiated was 34.5%, the 5-year survival rate was 14.8%, and the 10-year survival rate was 11.5%. The failure after re-irradiation was caused by local recurrence and metastasis with a mortality of 83.6%. These results emphasize that the success

(68)Ga-DOTA (0)-Tyr (3)-octreotide positron emission tomography in nasopharyngeal carcinoma.

PubMed

Schartinger, Volker H; Dudás, József; Url, Christoph; Reinold, Susanne; Virgolini, Irene J; Kroiss, Alexander; Riechelmann, Herbert; Uprimny, Christian

2015-01-01

PET/CT with (68)Ga-labelled [DOTA(0),Tyr(3)]-octreotide ((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 (68)Ga-DOTA-TOC uptake indicating expression of SSTR. Five patients with untreated, histologically proven EBV-positive NPC were referred for (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. (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.

Diet, living conditions and nasopharyngeal carcinoma in Tunisia--a case-control study.

PubMed

Jeannel, D; Hubert, A; de Vathaire, F; Ellouz, R; Camoun, M; Ben Salem, M; Sancho-Garnier, H; de-Thé, G

1990-09-15

We conducted a case-control study of nasopharyngeal carcinoma (NPC) in Tunisia, on diet, dietary patterns and life style, the characteristics of which had been defined by an anthropological study. Eighty incident cases, diagnosed in Tunisia between November 1986 and November 1987, were each matched for sex, age and place of residence to 2 controls. The subjects were asked for dietary data referring to the year preceding the diagnosis of NPC and, with help of their families, during childhood and after weaning. After adjustment for an empirical living conditions score, the following food items were found to be associated with an increased risk for NPC: preserved spiced meat (quaddid), basic stewing preparation (mixture of red and black pepper, garlic, oil, caraway and coriander), and harissa (red pepper, olive oil, garlic, caraway, salt) taken with bread as a snack during childhood and youth. Moreover, subjects who had been directly weaned from mother's milk on to an adult diet were found to be at higher risk for NPC.

Gene profiling, biomarkers and pathways characterizing HCV-related hepatocellular carcinoma

PubMed Central

De Giorgi, Valeria; Monaco, Alessandro; Worchech, Andrea; Tornesello, MariaLina; Izzo, Francesco; Buonaguro, Luigi; Marincola, Francesco M; Wang, Ena; Buonaguro, Franco M

2009-01-01

Background Hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC) worldwide. The molecular mechanisms of HCV-induced hepatocarcinogenesis are not yet fully elucidated. Besides indirect effects as tissue inflammation and regeneration, a more direct oncogenic activity of HCV can be postulated leading to an altered expression of cellular genes by early HCV viral proteins. In the present study, a comparison of gene expression patterns has been performed by microarray analysis on liver biopsies from HCV-positive HCC patients and HCV-negative controls. Methods Gene expression profiling of liver tissues has been performed using a high-density microarray containing 36'000 oligos, representing 90% of the human genes. Samples were obtained from 14 patients affected by HCV-related HCC and 7 HCV-negative non-liver-cancer patients, enrolled at INT in Naples. Transcriptional profiles identified in liver biopsies from HCC nodules and paired non-adjacent non-HCC liver tissue of the same HCV-positive patients were compared to those from HCV-negative controls by the Cluster program. The pathway analysis was performed using the BRB-Array- Tools based on the "Ingenuity System Database". Significance threshold of t-test was set at 0.001. Results Significant differences were found between the expression patterns of several genes falling into different metabolic and inflammation/immunity pathways in HCV-related HCC tissues as well as the non-HCC counterpart compared to normal liver tissues. Only few genes were found differentially expressed between HCV-related HCC tissues and paired non-HCC counterpart. Conclusion In this study, informative data on the global gene expression pattern of HCV-related HCC and non-HCC counterpart, as well as on their difference with the one observed in normal liver tissues have been obtained. These results may lead to the identification of specific biomarkers relevant to develop tools for detection, diagnosis, and classification

RERG suppresses cell proliferation, migration and angiogenesis through ERK/NF-κB signaling pathway in nasopharyngeal carcinoma.

PubMed

Zhao, Weilin; Ma, Ning; Wang, Shumin; Mo, Yingxi; Zhang, Zhe; Huang, Guangwu; Midorikawa, Kaoru; Hiraku, Yusuke; Oikawa, Shinji; Murata, Mariko; Takeuchi, Kazuhiko

2017-06-28

Nasopharyngeal carcinoma (NPC) is a malignancy of the head and neck that is prevalent in Southeast Asia and southern China. Recent studies in epigenetics suggest that DNA methylation plays a pivotal role in the onset and progression of cancer. Combining the methyl-DNA binding domain capture technique and cDNA microarray analysis, we identified a unique hypermethylated gene, RERG (Ras-like estrogen-regulated growth inhibitor), that was down-regulated in NPC tissues. RERG is a tumor suppressor gene that was first reported in breast cancer. However, the functions of RERG are largely unknown in other tumor types. RERG expression was assessed in human subjects (NPC primary tissues and non-cancer tissues) and cell lines (NPC cell lines and an immortalized epithelial cell line NP460). Further, we investigated the methylation rate of RERG in both human subject and cell lines. 5-Aza-2'-deoxycytidine (Aza) or combined with trichostatin A (TSA) were treated to three NPC cell lines (HK1, C666-1 and HK1_EBV). In addition, the role of RERG in NPC cells and its underlying mechanisms were explored by overexpression of RERG in NPC cell lines. RERG was significantly down-regulated in NPC cancer nests compared to normal nasopharyngeal epithelium cells. Furthermore, the RERG promoter was frequently methylated in NPC tissues and cell lines. The RERG methylation rate yielded an area under the curve (AUC) of receiver operating characteristic (ROC) curve was 0.897 (95%CI: 0.818-0.976). The down-regulation of RERG was restored in NPC cells treated with Aza and TSA. In addition, ectopic expression of RERG in NPC cell lines resulted in a significant suppression of cell proliferation, clonogenicity, migration and invasion. RERG-overexpressing cells showed significantly slower growth and less angiogenesis in tumor xenografts in nude mice. RERG suppressed the ERK/NF-κB signaling pathway and inhibited tumor growth and angiogenesis with down-regulation of MMPs and IL8 in tumors of nude mouse

Stereotactic radiotherapy for locally recurrent nasopharyngeal carcinoma.

PubMed

Leung, To-Wai; Wong, Victy Y W; Tung, Stewart Y

2009-11-01

To study the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) who were treated with stereotactic radiotherapy (SRT). Thirty patients with non-metastatic, locally recurrent NPC who were treated with curative intent between 1998 and 2002 were retrospectively analyzed. The International Union Against Cancer T-stage distribution at recurrence (rT) was as follows: rT1-14, rT2-7, rT3-3, and rT4-6. All patients were treated with SRT with a daily fractional dose of 2.5-4.5 Gy (median, 3 Gy) in 8-22 fractions (median, 18 fractions). Total equivalent dose (TED) was calculated by the linear-quadratic formula without a time factor correction. The 5-year actuarial overall survival rate, disease-specific survival rate, and local failure-free survival (LFFS) rate for the whole group were 40%, 41.4%, and 56.8%, respectively. The 3-year LFFS rates of rT1-2 and rT3-4 diseases were 65% and 66.7%, respectively. Seven of nine patients who received a TED <55 Gy recurred locally compared with 4 of 21 patients who received > or =55 Gy. Their corresponding 5-year LFFS rates were 22.2% and 75.8% (p = 0.005). The TED was the only factor significant in affecting the local control on univariate analyses. SRT is an effective treatment for locally recurrent NPC. TED > or =55 Gy should be given to secure a higher local control rate. The late complication rates were acceptable for patients with rT1-2 disease. For patients with rT3-4 disease, more works need to be done to further decrease the late complications.

The antiviral agent cidofovir [(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine] has pronounced activity against nasopharyngeal carcinoma grown in nude mice.

PubMed

Neyts, J; Sadler, R; De Clercq, E; Raab-Traub, N; Pagano, J S

1998-02-01

The effect of the antiviral agent (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl) cytosine (cidofovir) on the EBV-associated tumor nasopharyngeal carcinoma (NPC) was evaluated in NPC xenografts in athymic mice. Intratumoral injection arrested tumor growth within 1 week, and by 4 weeks, tumors regressed to 8-75% (39 +/- 33%) of the original size, whereas control tumors injected with PBS grew to 282 +/- 25% of the original size. Ganciclovir slowed but did not arrest or cause regression of tumor growth. A striking antitumor effect was also produced by systemic administration; at 4 weeks, tumors were 79 +/- 49% of the original size, compared with 635 +/- 91% for the controls. Widespread apoptosis was detected after treatment for 2-6 days in C15 as well as two other NPC xenografts, C17 and C18; the latter NPCs have mutations in the p53 gene. These data indicate that cidofovir induces rapid cell death through apoptosis in EBV-transformed epithelial cells.

Comparison of CYFRA 21-1 and tissue polypeptide specific antigen (TPS) for detecting nasopharyngeal carcinoma.

PubMed

Tai, Chih-Jaan; Liu, Feng-Yuan; Liang, Ji-An; Yang, Shih-Neng; Tsai, Ming-Hsui; Kao, Cbia-Hung

2002-01-01

CYFRA 21-1 is a tumor marker that is useful for detecting squamous cell carcinoma (SCC) of the lung. Tissue polypeptide specific antigen (TPS) is a tumor marker that indicates tumor proliferative rate rather than tumor burden. Our aim in this study was to compare the clinical value of CYFRA 21-1 and TPS in the detection of nasopharyngeal carcinoma (NPC). Serum levels of CYFRA 21-1 and TPS were measured in 60 patients with untreated NPC (including 36 differentiated SCC and 24 undifferentiated carcinomas) for comparison with each other. The cut-off values of CYFRA 21-1 and TPS, determined at the 95th percentile of the 43 healthy controls, were 2.50 ng/ml and 115.2 U/l, respectively. The results revealed that the mean serum values of CYFRA 21-1 (6.20 +/- 5.21 ng/ml) and TPS (153.9 +/- 17.3 U/l) in all 60 NPC patients were significantly higher than that in the 43 healthy controls (CYFRA 21-1 = 1.32 + 0.50 ng/ml, TPS = 85.0 +/- 16.0 U/l) (p value < 0.05). In addition, the detecting sensitivities of CYFRA 21-1 (60.0%) and TPS (58.3%) for all 60 NPC were not significantly different (p value > 0.05). In conclusion, our results suggest that both CYFRA 21-1 and TPS are potential tumor markers for the detection of NPC.

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

PubMed

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

2016-05-01

The aims of the study were to: (1) examine levels of trismus, xerostomia and nutritional status; (2) compare levels of trismus, xerostomia and nutritional status in patients with nasopharyngeal carcinoma (NPC) receiving different types of radiation modalities; and (3) identify factors related to NPC survivors' risk status for malnutrition and existing malnutrition. A cross-sectional study with consecutive sampling was conducted. NPC survivors were recruited from otolaryngology/oncology outpatient clinics in a medical centre in Northern Taiwan. Study measures included (1) Mandibular Function Impairment Questionnaire, (2) Xerostomia Questionnaire, (3) Mini Nutrition Assessment, (4) Hospital Anxiety and Depression Scale - Depression subscale, and (5) Symptom Severity Scale. A total of 110 subjects were recruited. Those receiving intensity-modulated radiation therapy had less trismus and xerostomia than patients receiving two-dimensional radiation therapy. Patients with female gender, advanced stage, completion of treatments within 1 year, higher levels of depression, more severe trismus and higher symptom severity tended to have malnutrition or were at risk of malnutrition. Trismus and xerostomia are long-term problems in some NPC survivors and may contribute to malnutrition. To better manage a patient's trismus and xerostomia and to enhance nutritional status, clinicians should develop a patient-specific care programme based on careful assessment and targeted measures to improve oral function and insure adequate nutritional intake. © 2014 John Wiley & Sons Ltd.

Synergistic effect of p53 on TSA-induced stanniocalcin 1 expression in human nasopharyngeal carcinoma cells, CNE2.

PubMed

Ching, L Y; Yeung, Bonnie H Y; Wong, Chris K C

2012-06-01

Human stanniocalcin 1 (STC1) has recently been identified as a putative protein factor involved in cellular apoptosis. The use of histone deacetylase inhibitor (i.e. trichostatin A (TSA)) and doxorubicin (Dox) is one of the common treatment methods to induce apoptosis in human cancer cells. A study on TSA and Dox-mediated apoptosis may shed light on the regulation and function of STC1 in cancer treatment. In this study, TSA and Dox cotreatment in human nasopharyngeal carcinoma cells (CNE2) elicited synergistic effects on STC1 gene expression and cellular apoptosis. An activation of p53 (TP53) transcriptional activity in Dox- or Dox+TSA-treated cells was revealed by the increased expression levels of p53 mRNA/protein as well as p53-driven luciferase activities. To elucidate the possible involvement of p53 in STC1 gene transcription, a vector expressing wild-type or dominant negative (DN) p53 was transiently transfected into the cells. Both STC1 promoter luciferase constructs and chromatin immunoprecipitation assays did not support the direct role of p53 in STC1 gene transactivation. However, the synergistic effects of p53 on the induction of NF-κB phosphorylation and the recruitment of acetylated histone H3 in STC1 promoter were observed in TSA-cotreated cells. The overexpression of exogenous STC1 sensitized apoptosis in Dox-treated cells. Taken together, this study provides data to show the cross talk of NF-κB, p53, and histone protein in the regulation of STC1 expression and function.

Rubus idaeus Inhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway.

PubMed

Hsin, Chung-Han; Huang, Cheng-Chen; Chen, Pei-Ni; Hsieh, Yih-Shou; Yang, Shun-Fa; Ho, Yu-Ting; Lin, Chiao-Wen

2017-01-01

Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

Caffeic Acid Phenethyl Ester Induces N-myc Downstream Regulated Gene 1 to Inhibit Cell Proliferation and Invasion of Human Nasopharyngeal Cancer Cells

PubMed Central

Chiang, Kun-Chun; Yang, Shih-Wei; Chang, Kai-Ping; Feng, Tsui-Hsia; Chang, Kang-Shuo; Tsui, Ke-Hung; Shin, Yi-Syuan; Chen, Chiu-Chun; Chao, Mei

2018-01-01

Caffeic acid phenethyl ester (CAPE), a bioactive component extracted from propolis, is widely studied due to its anti-cancer effect. Nasopharyngeal carcinoma (NPC) is distinct from other head and neck carcinomas and has a high risk of distant metastases. N-myc downstream regulated gene 1 (NDRG1) is demonstrated as a tumor suppressor gene in several cancers. Our result showed that CAPE treatment could repress NPC cell growth, through induction of S phase cell cycle arrest, and invasion. CAPE treatment stimulated NDRG1 expression in NPC cells. NDRG1 knockdown increased NPC cell proliferation and invasion and rendered NPC cells less responsive to CAPE growth-inhibiting effect, indicating CAPE repressed NPC cell growth partly through NDRG1indcution. CAPE treatment increased phosphorylation of ERK, JNK, and p38 in a dose- and time-dependent manner. Pre-treatments by inhibitors of ERK (PD0325901), JNK (SP600125), or p38 (SB201290), respectively, all could partly inhibit the CAPE effect on NDRG1 induction in NPC cells. Further, STAT3 activity was also repressed by CAPE in NPC cells. In summary, CAPE attenuates NPC cell proliferation and invasion by upregulating NDRG1 expression via MAPK pathway and by inhibiting phosphorylation of STAT3. Considering the poor prognosis of NPC patients with metastasis, CAPE could be a promising agent against NPC. PMID:29738439

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

PubMed Central

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

2014-01-01

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. PMID:25163814

Radiation-induced temporo-mandibular joint disorder in post-radiotherapy nasopharyngeal carcinoma patients: assessment and treatment.

PubMed

Wu, Vincent W C; Lam, Ying-Na

2016-06-01

Nasopharyngeal carcinoma (NPC) is endemic in southern China, and its incidence in Hong Kong is relatively high. Radiotherapy is the mainstay treatment for NPC due to its relatively high radiosensitivity and deep-seated anatomical position, which is not readily accessible by surgery. Although the technique of radiotherapy in NPC has been advancing and offers promising treatment outcome, complications around the irradiation areas are inevitable and the quality of life of the post-radiotherapy patients is often compromised. Trismus, which is defined as the restricted mouth opening or jaw movement due to the disorder of temporo-mandibular joint (TMJ), is one of the possible late complications for radiotherapy of NPC and is found in 5-17% of the post-radiotherapy (post-RT) patients. Trismus at early stage may only affect the speech, but in severe cases nutritional intake and oral hygiene condition may deteriorate seriously. This article reviewed the possible causes of radiation-induced TMJ damage, the various assessments including imaging modalities and possible treatments. The conclusion is that the availability of simple, yet effective examinations for trismus is essential for delaying the progression and restoring TMJ functions. Although there is no absolutely effective treatment for trismus, many supportive, restorative and palliative management are possible under different clinical situations.

Transpalatal insertion of radioactive gold grain for the treatment of persistent and recurrent nasopharyngeal carcinoma.

PubMed

Choy, D; Sham, J S; Wei, W I; Ho, C M; Wu, P M

1993-02-15

To evaluate the efficacy of radioactive gold grain implant via the split palate approach in the control of locally recurrent or persistent nasopharyngeal carcinoma. Forty-three patients, 10 for persistent NPC, 28 for first relapse in the nasopharynx, and five for second relapse in the nasopharynx, were treated. The diameter of the tumors at the time of gold grain implant ranged from 0.5 to 5 cm, the number of gold grains inserted varied from 4 to 14, the median number was seven. There was no significant difference in the control of the primary tumor for persistent disease (80% at 5 years), first relapse (61% at 5 years) and second relapse (80% at 3 years), p = 0.8845. The difference in survival between the three subgroups of patients, however, was highly significant (p = 0.0040). Thirty patients had CT evaluation before gold grain implant and the tumor was found confined to the nasopharynx in 21, in the remaining nine patients erosion of the sphenoid sinus or other parts of the base of skull was noted. The difference in the control between those patients with tumors confined to the nasopharynx and those patients with extranasopharyngeal extension of tumor almost reached statistical significance (81% and 44% respectively at 5 years, p = 0.0554). For the six patients who developed local recurrence after gold grain implant and were evaluable for the pattern of failure, the recurrent tumors were considered originating from another region of the nasopharynx in four, and in-field failure in the other two cases. Radioactive gold grain implant as salvage treatment provides satisfactory control of persistent and recurrent nasopharyngeal carcinoma. The local control was better when the tumor was localized to the nasopharynx, thus underlines the importance of close follow-up for early recognition of relapse and persistent tumor. However, such patients still suffered from high incidence of regional and distant failure, the pathophysiology and management of which require

Assessment of quality of life of nasopharyngeal carcinoma patients with EORTC QLQ-C30 and H and N-35 modules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cengiz, Mustafa; Ozyar, Enis; Esassolak, Mustafa

2005-12-01

Purpose: The current study reports on long-term quality of life (QoL) status after conventional radiotherapy in 187 nasopharyngeal carcinoma patients from 14 centers in Turkey. Patients and Methods: Patients with the diagnosis of nasopharyngeal carcinoma, who were treated in 14 centers in Turkey with minimum 6 months of follow-up and were in complete remission, were asked to complete Turkish versions of EORTC QLQ-C30 questionnaire and the HN-35 module. Each center participated with the required clinical data that included age at diagnosis, gender, symptoms on admission, follow-up period, treatment modalities, radiotherapy dose, and AJCC 1997 tumor stage. Each patient's 33 QoLmore » scores, which included function, global health status, and symptoms, were calculated as instructed in EORTC QLQ-C30 scoring manual. All of the scales and single-item measures range from 0 to 100. A high score represents a higher response level. Kruskal-Wallis and Mann-Whitney U nonparametric tests were used for comparisons. Results: One hundred eighty-seven patients with median age of 46 years (range, 16-79 years) participated and completed the questionnaires. Median follow-up time was 3.4 years (range, 6 months-24 years). All patients have received external-beam radiotherapy. Beside external-beam radiotherapy, 59 patients underwent brachytherapy boost, 70 patients received concomitant chemotherapy, and 95 patients received adjuvant/neoadjuvant chemotherapy. Most of the patients in the analysis (75%) were in advanced stage (Stage III, n = 85 [45.4%]; Stage IV, n = 55 [29%]). Mean global health status was calculated as 73. Parameters that increased global health status were male gender, early-stage disease, and less than 4-year follow-up (p < 0.05). Functional parameters were better in males and in early-stage disease. Factors that yielded better symptom scores were short interval after treatment (10 scores), male gender (7 scores), and lower radiation dose (6 scores). Neoadjuvant or

The influence of human papillomavirus on nasopharyngeal carcinoma in Japan.

PubMed

Kano, Makoto; Kondo, Satoru; Wakisaka, Naohiro; Moriyama-Kita, Makiko; Nakanishi, Yosuke; Endo, Kazuhira; Murono, Shigeyuki; Nakamura, Hiroyuki; Yoshizaki, Tomokazu

2017-06-01

Although Japan is a non-endemic area with nasopharyngeal carcinoma (NPC), the proportion of WHO type I NPC in Japan are different from that in non-endemic areas such as North America and Europe. Recently, it is said that not only Epstein-Barr virus (EBV) but also human papillomavirus (HPV) has an influence on NPC in non-endemic areas. The aim of this study is to clarify the influence of HPV on NPC in Japan. Paraffin-embedded tumor specimens were available for 59 patients with NPC diagnosed between 1996 and 2015. We detected the virus status by p16 immunohistochemistry, HPV PCR, and in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA. Kaplan-Meier curves were used to compare the overall survival by viral status. Among the 59 patients, 49 (83%) were EBV-positive/HPV-negative, 2 (3%) were EBV-positive/HPV-positive, and 8 (16%) were EBV-negative/HPV-negative. All HPV-positive NPCs were co-infected with EBV. There were no significant differences between the overall survival in the three groups (p=0.111). In Japan, HPV was detected in a few patients with NPC, and we suggest that HPV has no influence on NPC carcinogenesis in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Genetic factors leading to chronic Epstein-Barr virus infection and nasopharyngeal carcinoma in South East China: Study design, methods and feasibility

PubMed Central

2006-01-01

Nasopharyngeal carcinoma (NPC) is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals. Phase I, powered to detect single gene associations, enrolled 984 subjects to determine feasibility, to develop infrastructure and logistics and to determine error rates in sample handling. A microsatellite screen of Phase I study participants, genotyped for 319 alleles from 34 microsatellites spanning an 18-megabase region of chromosome 4 (4p15.1-q12), previously implicated by a linkage analysis of familial NPC, found 14 alleles marginally associated with developing NPC or chronic immunoglobulin A production (p = 0.001-0.03). These associations lost significance after applying a correction for multiple tests. Although the present results await confirmation, the Phase II study population has tripled patient enrolment and has included environmental covariates, offering the potential to validate this and other genomic regions that influence the onset of NPC. PMID:16848974

Facility Volume and Survival in Nasopharyngeal Carcinoma.

PubMed

Yoshida, Emi J; Luu, Michael; David, John M; Kim, Sungjin; Mita, Alain; Scher, Kevin; Shiao, Stephen L; Tighiouart, Mourad; Lee, Nancy Y; Ho, Allen S; Zumsteg, Zachary S

2018-02-01

Definitive treatment of nasopharyngeal carcinoma (NPC) is challenging owing to its rarity, complicated regional anatomy, and the intensity of therapy. In contrast to other head and neck cancers, the effect of facility volume has not been well described for NPC. The National Cancer Database was queried for patients with stage II-IVB NPC diagnosed from 2004 to 2014 and treated with definitive radiation. Patients with incomplete staging, unknown receipt or timing of treatment, unknown follow-up duration, incomplete socioeconomic information, or treatment outside the reporting facility were excluded. High-volume facilities (HVFs) were defined as the top 5% of facilities according to the annual facility volume. The present analysis included 3941 NPC patients treated at 804 facilities with a median follow-up duration of 59.4 months, including 1025 patients (26.0%) treated at HVFs. Treatment at HVFs was associated with significantly improved overall survival (OS) on multivariable analysis (hazard ratio 0.79, 95% confidence interval 0.69-0.90; P=.001). In propensity score-matched cohorts, 5-year OS was 69.1% versus 63.3% at HVFs versus lower volume facilities (LVFs), respectively (P=.003). Similar results were seen when facility volume was analyzed as a continuous variable. The effect of facility volume on survival varied by academic status (P=.002 for interaction). At academic centers, the propensity score-matched cohorts had 5-year OS of 71.4% compared with 62.4% (P<.001) at HVFs and LVFs, respectively. In contrast, the 5-year OS was 63.5% versus 67.9% (P=.68) in propensity score-matched patients at nonacademic HVFs and LVFs. Treatment at HVFs was associated with improved OS for patients with NPC, with the effect exclusively seen at academic centers. Copyright © 2017 Elsevier Inc. All rights reserved.

Contrasted frequencies of p53 accumulation in the two age groups of North African nasopharyngeal carcinomas.

PubMed

Khabir, A; Sellami, A; Sakka, M; Ghorbel, A M; Daoud, J; Frikha, M; Drira, M M; Busson, P; Jlidi, R

2000-10-01

EBV-associated nasopharyngeal carcinomas (NPCs) from Southeast Asia and North Africa have many common clinical and biological characteristics. However, they differ with regard to their age distribution. In Asia, NPC mainly affects patients in the 4th or 5th decade of their life, whereas in North Africa an additional peak of incidence is found between the ages of 10 and 20. The p53 gene is rarely mutated in NPC. However, several groups have reported a consistent accumulation of p53 in Asian NPCs. To determine whether p53 was also accumulated in North African NPCs, we investigated its expression, by immunohistochemistry, in a series of 90 Tunisian biopsies. Bc12 and CD95, two proteins involved in the regulation of cell survival and apoptosis, were investigated in the same study. We found accumulation of p53 in 81% of the cases for patients over 30 years of age, but in only 38% of specimens for younger patients (P = 0.00013). There was a trend toward a higher frequency of Bc12 detection in patients over 30, but it was not statistically significant. CD95 expression was detected in all biopsies, generally at a high level, even at advanced stages of the disease. The changing frequency of p53 accumulation, below and over 30, suggests that NPC cells often achieve malignant transformation through different pathways in both age groups.

Gene expression signatures differentiate ovarian/peritoneal serous carcinoma from breast carcinoma in effusions

PubMed Central

Davidson, Ben; Stavnes, Helene Tuft; Holth, Arild; Chen, Xu; Yang, Yanqin; Shih, Ie-Ming; Wang, Tian-Li

2011-01-01

Abstract Ovarian/primary peritoneal carcinoma and breast carcinoma are the gynaecological cancers that most frequently involve the serosal cavities. With the objective of improving on the limited diagnostic panel currently available for the differential diagnosis of these two malignancies, as well as to define tumour-specific biological targets, we compared their global gene expression patterns. Gene expression profiles of 10 serous ovarian/peritoneal and eight ductal breast carcinoma effusions were analysed using the HumanRef-8 BeadChip from Illumina. Differentially expressed candidate genes were validated using quantitative real-time PCR and immunohistochemistry. Unsupervised hierarchical clustering using all 54,675 genes in the array separated ovarian from breast carcinoma samples. We identified 288 unique probes that were significantly differentially expressed in the two cancers by greater than 3.5-fold, of which 81 and 207 were overexpressed in breast and ovarian/peritoneal carcinoma, respectively. SAM analysis identified 1078 differentially expressed probes with false discovery rate less than 0.05. Genes overexpressed in breast carcinoma included TFF1, TFF3, FOXA1, CA12, GATA3, SDC1, PITX1, TH, EHFD1, EFEMP1, TOB1 and KLF2. Genes overexpressed in ovarian/peritoneal carcinoma included SPON1, RBP1, MFGE8, TM4SF12, MMP7, KLK5/6/7, FOLR1/3, PAX8, APOL2 and NRCAM. The differential expression of 14 genes was validated by quantitative real-time PCR, and differences in 5 gene products were confirmed by immunohistochemistry. Expression profiling distinguishes ovarian/peritoneal carcinoma from breast carcinoma and identifies genes that are differentially expressed in these two tumour types. The molecular signatures unique to these cancers may facilitate their differential diagnosis and may provide a molecular basis for therapeutic target discovery. PMID:20132413

Statin treatment may lower the risk of postradiation epilepsy in patients with nasopharyngeal carcinoma.

PubMed

Rong, Xiaoming; Yin, Jing; Wang, Hongxuan; Zhang, Xiaoni; Peng, Ying

2017-12-01

This study aimed to clarify the effect of statins on preventing the risk of postradiation epilepsy. We performed a retrospective analysis of neurological nasopharyngeal carcinoma patients with a history of radiotherapy. Patients with a history of epilepsy before radiation and those who received prophylactically antiepileptic treatment were excluded. The demographic and clinical data of these patients were collected through chart review. We used Kaplan-Meier analysis (log-rank test) to examine the effect of statins on epilepsy-free survival. Cox regression analysis was utilized to identify independent predictive variables. Our study included 532 patients (405 males and 127 females) with a mean follow-up of 28.1 months. During follow-up, 471 (88.5%) patients developed radiation-induced brain necrosis (RN). Within a mean latency of 24.1 months, 88 (16.5%) patients experienced epilepsy, of whom 27 (27 of 88, 30.7%) patients suffered from epilepsy before the diagnosis of RN. Thirty-six (36 of 88, 40.9%) cases of epilepsy occurred after RN onset, and in 22 cases (22 of 88, 25.0%) epilepsy was the first presentation of RN. Three patients suffered from epilepsy but did not have RN. Eighty-eight patients in our cohort were treated with statins because of hyperlipidemia or prevention of cardiocerebrovascular diseases, of whom six (6.8%) developed epilepsy, whereas in those without statin, the epileptic rate was 18.5%. Log-rank test found that there was a significant difference in epilepsy-free survival between patients who used statins and those who did not (p = 0.016). After adjusting for confounding variables, multivariate Cox regression analysis revealed that statin use could still significantly reduce the risk of epilepsy after radiation (hazard ratio = 0.36, 95% confidence interval = 0.15-0.82, p = 0.015). However, for the patients who already suffered from RN, statin treatment did not lower the risk of post-RN epilepsy. Early statin use may reduce the risk of

What Is the Best Treatment of Locally Advanced Nasopharyngeal Carcinoma? An Individual Patient Data Network Meta-Analysis

PubMed Central

Ribassin-Majed, Laureen; Marguet, Sophie; Lee, Anne W.M.; Ng, Wai Tong; Ma, Jun; Chan, Anthony T.C.; Huang, Pei-Yu; Zhu, Guopei; Chua, Daniel T.T.; Chen, Yong; Mai, Hai-Qiang; Kwong, Dora L.W.; Cheah, Shie-Lee; Moon, James; Tung, Yuk; Chi, Kwan-Hwa; Fountzilas, George; Bourhis, Jean; Pignon, Jean Pierre

2017-01-01

Purpose The role of adjuvant chemotherapy (AC) or induction chemotherapy (IC) in the treatment of locally advanced nasopharyngeal carcinoma is controversial. The individual patient data from the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma database were used to compare all available treatments. Methods All randomized trials of radiotherapy (RT) with or without chemotherapy in nonmetastatic nasopharyngeal carcinoma were considered. Overall, 20 trials and 5,144 patients were included. Treatments were grouped into seven categories: RT alone (RT), IC followed by RT (IC-RT), RT followed by AC (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concomitant chemoradiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). P-score was used to rank the treatments. Fixed- and random-effects frequentist network meta-analysis models were applied. Results The three treatments with the highest probability of benefit on overall survival (OS) were CRT-AC, followed by CRT and IC-CRT, with respective hazard ratios (HRs [95% CIs]) compared with RT alone of 0.65 (0.56 to 0.75), 0.77 (0.64 to 0.92), and 0.81 (0.63 to 1.04). HRs (95% CIs) of CRT-AC compared with CRT for OS, progression-free survival (PFS), locoregional control, and distant control (DC) were, respectively, 0.85 (0.68 to 1.05), 0.81 (0.66 to 0.98), 0.70 (0.48 to 1.02), and 0.87 (0.61 to 1.25). IC-CRT ranked second for PFS and the best for DC. CRT never ranked first. HRs of CRT compared with IC-CRT for OS, PFS, locoregional control, and DC were, respectively, 0.95 (0.72 to 1.25), 1.13 (0.88 to 1.46), 1.05 (0.70 to 1.59), and 1.55 (0.94 to 2.56). Regimens with more chemotherapy were associated with increased risk of acute toxicity. Conclusion The addition of AC to CRT achieved the highest survival benefit and consistent improvement for all end points. The addition of IC to CRT achieved the highest effect on DC. PMID:27918720

Metastatic renal cell carcinoma in the nasopharynx.

PubMed

Atar, Yavuz; Topaloglu, Ilhan; Ozcan, Deniz

2013-01-01

Metastatic renal cell carcinoma of the nasopharynx, nasal cavity, and paranasal sinuses can be misdiagnosed as primary malignant or benign diseases. A 33-year-old male attended our outpatient clinic complaining of difficulty breathing through the nose, bloody nasal discharge, postnasal drop, snoring, and discharge of phlegm. Endoscopic nasopharyngeal examination showed a vascularized nasopharyngeal mass. Under general anesthesia, multiple punch biopsies were taken from the nasopharynx. Pathologically, the tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. After the initial pathological examination, the pathologist requested more information about the patient's clinical status. A careful history revealed that the patient had undergone left a nephrectomy for a kidney mass diagnosed as renal cell carcinoma 3 years earlier. Subsequently, nasopharyngeal metastatic renal cell carcinoma was diagnosed by immunohistochemical staining with CD10 and vimentin. Radiotherapy was recommended for treatment.

Genomic profiling of 766 cancer-related genes in archived esophageal normal and carcinoma tissues.

PubMed

Chen, Jing; Guo, Liping; Peiffer, Daniel A; Zhou, Lixin; Chan, Owen Tsan Mo; Bibikova, Marina; Wickham-Garcia, Eliza; Lu, Shih-Hsin; Zhan, Qimin; Wang-Rodriguez, Jessica; Jiang, Wei; Fan, Jian-Bing

2008-05-15

We employed the BeadArraytrade mark technology to perform a genetic analysis in 33 formalin-fixed, paraffin-embedded (FFPE) human esophageal carcinomas, mostly squamous-cell-carcinoma (ESCC), and their adjacent normal tissues. A total of 1,432 single nucleotide polymorphisms (SNPs) derived from 766 cancer-related genes were genotyped with partially degraded genomic DNAs isolated from these samples. This directly targeted genomic profiling identified not only previously reported somatic gene amplifications (e.g., CCND1) and deletions (e.g., CDKN2A and CDKN2B) but also novel genomic aberrations. Among these novel targets, the most frequently deleted genomic regions were chromosome 3p (including tumor suppressor genes FANCD2 and CTNNB1) and chromosome 5 (including tumor suppressor gene APC). The most frequently amplified genomic region was chromosome 3q (containing DVL3, MLF1, ABCC5, BCL6, AGTR1 and known oncogenes TNK2, TNFSF10, FGF12). The chromosome 3p deletion and 3q amplification occurred coincidently in nearly all of the affected cases, suggesting a molecular mechanism for the generation of somatic chromosomal aberrations. We also detected significant differences in germline allele frequency between the esophageal cohort of our study and normal control samples from the International HapMap Project for 10 genes (CSF1, KIAA1804, IL2, PMS2, IRF7, FLT3, NTRK2, MAP3K9, ERBB2 and PRKAR1A), suggesting that they might play roles in esophageal cancer susceptibility and/or development. Taken together, our results demonstrated the utility of the BeadArray technology for high-throughput genetic analysis in FFPE tumor tissues and provided a detailed genetic profiling of cancer-related genes in human esophageal cancer. (c) 2008 Wiley-Liss, Inc.

Changes of saliva microbiota in nasopharyngeal carcinoma patients under chemoradiation therapy.

PubMed

Xu, Yuan; Teng, Fei; Huang, Shi; Lin, Zhengmei; Yuan, Xiao; Zeng, Xiaowei; Yang, Fang

2014-02-01

A growing body of evidence has implicated human oral microbiota in the aetiology of oral and systemic diseases. Nasopharyngeal carcinoma (NPC), an epithelial-originated malignancy, has a complex aetiology not yet fully understood. Chemoradiation therapy of NPC can affect oral microbiota and is usually accompanied by plaque accumulation. Thus, the study aimed to understand the diversity, divergence and development of the oral microbiota in NPC patients and their associated treatment, which might provide useful insights into disease aetiology and treatment side effects. A longitudinal study was designed that included three Chinese adults with NPC. Saliva samples were collected at three time points: prior to the chemoradiation treatment (carcinoma baseline, or CB), 7 months post-treatment (carcinoma-after-therapy phase 1 or CA1) and 12 months post-treatment (carcinoma-after-therapy phase 2 or CA2). Pyrosequencing of the bacterial 16S ribosomal DNA (rDNA) V1-V3 hypervariable region was employed to characterise the microbiota. Saliva samples of three healthy subjects from our former study were employed as healthy controls. Principal coordinates analysis (PCoA), Metastats and random forest prediction models were used to reveal the key microbial members associated with NPC and its treatment programme. (1) In total, 412 bacterial species from at least 107 genera and 13 phyla were found in the saliva samples of the NPC patients. (2) PCoA revealed that not only were the microbiota from NPC patients distinct from those of healthy controls (p<0.001) but also that separation was found on the saliva microbiota between pre- and post-therapy (p<0.001) in the NPC samples. (3) At the genus level and the operational taxonomic unit (OTU) level, Streptococcus was found with lower abundance in NPC samples. (4) Chemoradiation therapy did not incur similar changes in microbiota structure among the three NPC patients; the microbiota in one of them stayed largely steady, while those in the

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

NASA Astrophysics Data System (ADS)

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

2016-01-01

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

Identification and validation nucleolin as a target of curcumol in nasopharyngeal carcinoma cells.

PubMed

Wang, Juan; Wu, Jiacai; Li, Xumei; Liu, Haowei; Qin, Jianli; Bai, Zhun; Chi, Bixia; Chen, Xu

2018-06-30

Identification of the specific protein target(s) of a drug is a critical step in unraveling its mechanisms of action (MOA) in many natural products. Curcumol, isolated from well known Chinese medicinal plant Curcuma zedoary, has been shown to possess multiple biological activities. It can inhibit nasopharyngeal carcinoma (NPC) proliferation and induce apoptosis, but its target protein(s) in NPC cells remains unclear. In this study, we employed a mass spectrometry-based chemical proteomics approach reveal the possible protein targets of curcumol in NPC cells. Cellular thermal shift assay (CETSA), molecular docking and cell-based assay was used to validate the binding interactions. Chemical proteomics capturing uncovered that NCL is a target of curcumol in NPC cells, Molecular docking showed that curcumol bound to NCL with an -7.8 kcal/mol binding free energy. Cell function analysis found that curcumol's treatment leads to a degradation of NCL in NPC cells, and it showed slight effects on NP69 cells. In conclusion, our results providing evidences that NCL is a target protein of curcumol. We revealed that the anti-cancer effects of curcumol in NPC cells are mediated, at least in part, by NCL inhibition. Many natural products showed high bioactivity, while their mechanisms of action (MOA) are very poor or completely missed. Understanding the MOA of natural drugs can thoroughly exploit their therapeutic potential and minimize their adverse side effects. Identification of the specific protein target(s) of a drug is a critical step in unraveling its MOA. Compound-centric chemical proteomics is a classic chemical proteomics approach which integrates chemical synthesis with cell biology and mass spectrometry (MS) to identify protein targets of natural products determine the drug mechanism of action, describe its toxicity, and figure out the possible cause of off-target. It is an affinity-based chemical proteomics method to identify small molecule-protein interactions

Symptom clusters in patients with nasopharyngeal carcinoma during radiotherapy.

PubMed

Xiao, Wenli; Chan, Carmen W H; Fan, Yuying; Leung, Doris Y P; Xia, Weixiong; He, Yan; Tang, Linquan

2017-06-01

Despite the improvement in radiotherapy (RT) technology, patients with nasopharyngeal carcinoma (NPC) still suffer from numerous distressing symptoms simultaneously during RT. The purpose of the study was to investigate the symptom clusters experienced by NPC patients during RT. First-treated Chinese NPC patients (n = 130) undergoing late-period RT (from week 4 till the end) were recruited for this cross-sectional study. They completed a sociodemographic and clinical data questionnaire, the Chinese version of the M. D. Anderson Symptom Inventory - Head and Neck Module (MDASI-HN-C) and the Chinese version of the Functional Assessment of Cancer Therapy - Head and Neck Scale (FACT-H&N-C). Principal axis factor analysis with oblimin rotation, independent t-test, one-way analysis of variance (ANOVA) and Pearson product-moment correlation were used to analyze the data. Four symptom clusters were identified, and labelled general, gastrointestinal, nutrition impact and social interaction impact. Of these 4 types, the nutrition impact symptom cluster was the most severe. Statistically positive correlations were found between severity of all 4 symptom clusters and symptom interference, as well as weight loss. Statistically negative correlations were detected between the cluster severity and the QOL total score and 3 out of 5 subscale scores. The four clusters identified reveal the symptom patterns experienced by NPC patients during RT. Future intervention studies on managing these symptom clusters are warranted, especially for the nutrition impact symptom cluster. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

Liu, Tao; Xu, Wen; Yan, Wei-Li; Ye, Ming; Bai, Yong-Rui; Huang, Gang

2007-12-01

To perform a systematic review to compare FDG-PET, CT, and MRI imaging for diagnosis of local residual or recurrent nasopharyngeal carcinoma. MEDLINE, EMBASE, the CBMdisc databases and some other databases were searched for relevant original articles published from January 1990 to June 2007. Inclusion criteria were as follows: Articles were reported in English or Chinese; FDG-PET, CT, or MRI was used to detect local residual or recurrent nasopharyngeal carcinoma; histopathologic analysis and/or close clinical and imaging follow-up for at least 6 months were the reference standard. Two reviewers independently extracted data. A software called "Meta-DiSc" was used to obtain pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR), summary receiver operating characteristic (SROC) curves, and the Q* index. Twenty-one articles fulfilled all inclusion criteria. The pooled sensitivity estimates for PET (95%) were significantly higher than CT (76%) (P<0.001) and MRI (78%) (P<0.001). The pooled specificity estimates for PET (90%) were significantly higher than CT (59%) (P<0.001) and MRI (76%) (P<0.001). The pooled DOR estimates for PET (96.51) were significantly higher than CT (7.01) (P<0.001) and MRI (8.68) (P<0.001). SROC curve for FDG-PET showed better diagnostic accuracy than CT and MRI. The Q* index for PET (0.92) was significantly higher than CT (0.72) (P<0.001) and MRI (0.76) (P<0.01). For PET, the sensitivity and diagnostic OR for using qualitative analysis were significantly higher than using both qualitative and quantitative analyses (P<0.01). For CT, the sensitivity, specificity, diagnostic OR, and the Q* index for dual-section helical and multi-section helical were all significantly higher than nonhelical and single-section helical (P<0.01). And the sensitivity for 'section thickness <5 mm' was significantly lower than ' =5 mm' (P<0.01), while the specificity was significantly higher (P<0.01). For MRI, there were no significant differences found

Effect of MLC leaf position, collimator rotation angle, and gantry rotation angle errors on intensity-modulated radiotherapy plans for nasopharyngeal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bai, Sen; Li, Guangjun; Wang, Maojie

The purpose of this study was to investigate the effect of multileaf collimator (MLC) leaf position, collimator rotation angle, and accelerator gantry rotation angle errors on intensity-modulated radiotherapy plans for nasopharyngeal carcinoma. To compare dosimetric differences between the simulating plans and the clinical plans with evaluation parameters, 6 patients with nasopharyngeal carcinoma were selected for simulation of systematic and random MLC leaf position errors, collimator rotation angle errors, and accelerator gantry rotation angle errors. There was a high sensitivity to dose distribution for systematic MLC leaf position errors in response to field size. When the systematic MLC position errors weremore » 0.5, 1, and 2 mm, respectively, the maximum values of the mean dose deviation, observed in parotid glands, were 4.63%, 8.69%, and 18.32%, respectively. The dosimetric effect was comparatively small for systematic MLC shift errors. For random MLC errors up to 2 mm and collimator and gantry rotation angle errors up to 0.5°, the dosimetric effect was negligible. We suggest that quality control be regularly conducted for MLC leaves, so as to ensure that systematic MLC leaf position errors are within 0.5 mm. Because the dosimetric effect of 0.5° collimator and gantry rotation angle errors is negligible, it can be concluded that setting a proper threshold for allowed errors of collimator and gantry rotation angle may increase treatment efficacy and reduce treatment time.« less

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

PubMed

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.

Sequence variations of Epstein-Barr virus-encoded BARF1 gene in nasopharyngeal carcinomas and healthy donors from southern and northern China.

PubMed

Liu, Jincheng; Ji, Xinqiang; Shen, Zhichao; Wang PhD, Yun; Luo PhD, Bing

2018-05-24

The BamHI A rightward frame 1 (BARF1) gene of the Epstein-Barr virus (EBV) is involved in carcinogenesis and immunomodulation of EBV-associated malignancies. The geographical distributions and the disease associations of BARF1 variants remain unclear. In the current study, the BARF1 variants in nasopharyngeal carcinoma (NPC) cases and healthy donors from southern and northern China, the NPC endemic and non-endemic areas, as well as in 153 sequenced EBV genomes from diseased and normal people from around the world, were determined and compared among areas and populations. Only 1 consistent coding change, V29A, and several consistent silent mutations were identified. Two BARF1 types (B95-8 and V29A) and 2 B95-8 subtypes (B95-8 t165545c and B95-8 P ) were classified. For Chinese isolates, the B95-8 type was dominant in both southern and northern China, but the isolates from southern China showed a higher frequency of the B95-8 t165545c subtype than the isolates from northern China (76.0%, 38/50 NPC cases and 50.7%, 37/73 healthy donors vs 26.4%, 24/91 NPC cases and 7.6%, 6/79 healthy donors, P < .0001). Furthermore, the B95-8 t165545c subtype was more frequent in NPC cases than healthy donors in both southern China (P = .005) and northern China (P = .001). For EBV genomes, the B95-8 P subtype was dominant in northern China, Europe, America, and Australia, while V29A was dominant in Africa. The B95-8 t165545c subtype was only identified in Asia and demonstrated high frequency (81.2%, 26/32) in genomes from NPC cases in southern China. These results further reveal conservation and possibly geographically spread variations of BARF1 and may also indicate the preference of EBV strains with the B95-8 t165545c subtype in NPC cases, without biological or pathogenic implications. © 2018 Wiley Periodicals, Inc.

Elective neck irradiation for nasopharyngeal carcinoma.

PubMed

Wang, C J; Chen, H C; Huang, E Y; Lee, S P

2000-07-01

This study was conducted to evaluate the effectiveness of elective neck irradiation (ENI) for nasopharyngeal carcinoma (NPC), and to analyze factors associated with ENI failure. A radiation port covering the side of a neck without gross nodal metastasis was qualified for evaluation of the effectiveness of ENI. From 1988 through 1992, a total of 261 patients with N0 (130 cases), N1 (91 cases), and N3 (40 cases) NPCs were studied. All patients were irradiated with 60Co teletherapy or 10 MV x-ray to a total dose of 46.8 Gy/26 fractions, followed by a boost treatment to the primary site to a total dose of 64.8 to 75.6 Gy/36-42 fractions. All ENI ports received irradiation to a dose of 46.8 to 60.8 Gy. The duration of follow-up was 6 to 10 years, with a median of 8.1 years. Factors associated with to the risk of ENI failure were analyzed. (1) The overall 5-year actuarial local control rate and actuarial survival rate were 74% and 63%, respectively. (2) Among the 261 cases in which ENI treatment was used, the treatment failed in 12 cases, accounting for a crude ENI failure rate of 5%. The overall 5- and 10-year cumulative risk of ENI failure was 5% and 7%, respectively. (3) Time from the start of treatment to ENI failure ranged from 9 to 66 months, with a median of 17 months. (4) Of the 12 patients for whom EMI failed, 11 (92%) had recurrence in the upper neck, and one in the lower neck. (5) Existence of prior failure at the primary site was the only factor significantly correlated with the risk of ENI failure (p < 0.001). The 5-year cumulative risk of ENI failure for patients with local failure vs. those without was 16% vs. 1% (p < 0.0001). Moderate-dose ENI was highly effective in the control of subclinical disease in the neck for NPC. ENI failure was closely associated with prior failure at the primary site, implying that local primary tumor failure may lead to an increased potential for metastasis to the neck.

Association between nasopharyngeal carcinoma and risk of optic neuropathy: A population-based cohort study.

PubMed

Fan, Chao-Yueh; Jen, Yee-Min; Su, Yuan-Chih; Chao, Hsing-Lung; Lin, Chun-Shu; Huang, Wen-Yen; Lin, Miao-Jung; Kao, Chia-Hung

2018-04-16

The purpose of this study was to assess the predictive factors of optic neuropathy among patients with nasopharyngeal carcinoma (NPC). The analysis included 16 297 patients with NPC and 65 187 controls. Each patient with NPC was randomly frequency-matched with 4 individuals without NPC by age, sex, and index year. Cox proportional hazard models were applied to measure the hazard ratios (HRs) and 95% confidence intervals (CIs) of optic neuropathy development associated with NPC. The risk of optic neuropathy was significantly higher in the NPC cohort (adjusted HR [aHR] 3.42; 95% CI 2.85-4.09; P < .001). Independent risk factors for optic neuropathy among patients with NPC included stroke (aHR 1.7; 95% CI 1.07-2.7; P = .03) and receipt of chemotherapy (aHR 1.55; 95% CI 1.17-2.06; P = .002). The risk of optic neuropathy was significantly higher in patients with NPC than in the general population. © 2018 Wiley Periodicals, Inc.

OPCML is a broad tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation.

PubMed

Cui, Yan; Ying, Ying; van Hasselt, Andrew; Ng, Ka Man; Yu, Jun; Zhang, Qian; Jin, Jie; Liu, Dingxie; Rhim, Johng S; Rha, Sun Young; Loyo, Myriam; Chan, Anthony T C; Srivastava, Gopesh; Tsao, George S W; Sellar, Grant C; Sung, Joseph J Y; Sidransky, David; Tao, Qian

2008-08-20

Identification of tumor suppressor genes (TSGs) silenced by CpG methylation uncovers the molecular mechanism of tumorigenesis and potential tumor biomarkers. Loss of heterozygosity at 11q25 is common in multiple tumors including nasopharyngeal carcinoma (NPC). OPCML, located at 11q25, is one of the downregulated genes we identified through digital expression subtraction. Semi-quantitative RT-PCR showed frequent OPCML silencing in NPC and other common tumors, with no homozygous deletion detected by multiplex differential DNA-PCR. Instead, promoter methylation of OPCML was frequently detected in multiple carcinoma cell lines (nasopharyngeal, esophageal, lung, gastric, colon, liver, breast, cervix, prostate), lymphoma cell lines (non-Hodgkin and Hodgkin lymphoma, nasal NK/T-cell lymphoma) and primary tumors, but not in any non-tumor cell line and seldom weakly methylated in normal epithelial tissues. Pharmacological and genetic demethylation restored OPCML expression, indicating a direct epigenetic silencing. We further found that OPCML is stress-responsive, but this response is epigenetically impaired when its promoter becomes methylated. Ecotopic expression of OPCML led to significant inhibition of both anchorage-dependent and -independent growth of carcinoma cells with endogenous silencing. Thus, through functional epigenetics, we identified OPCML as a broad tumor suppressor, which is frequently inactivated by methylation in multiple malignancies.

Ficlatuzumab With or Without Cetuximab in Treating Patients With Cetuximab-Resistant, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-02-02

Head and Neck Basaloid Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage IV Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Head and Neck Cancer; Oropharyngeal Cancer; HNSCC

EBV‐encoded miRNAs target ATM‐mediated response in nasopharyngeal carcinoma

PubMed Central

Lung, Raymond W‐M; Hau, Pok‐Man; Yu, Ken H‐O; Yip, Kevin Y; Tong, Joanna H‐M; Chak, Wing‐Po; Chan, Anthony W‐H; Lam, Ka‐Hei; Lo, Angela Kwok‐Fung; Tin, Edith K‐Y; Chau, Shuk‐Ling; Pang, Jesse C‐S; Kwan, Johnny S‐H; Busson, Pierre; Young, Lawrence S; Yap, Lee‐Fah; Tsao, Sai‐Wah

2018-01-01

Abstract Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignancy that is prevalent in southern China and Southeast Asia. It is consistently associated with latent Epstein–Barr virus (EBV) infection. In NPC, miR‐BARTs, the EBV‐encoded miRNAs derived from BamH1‐A rightward transcripts, are abundantly expressed and contribute to cancer development by targeting various cellular and viral genes. In this study, we establish a comprehensive transcriptional profile of EBV‐encoded miRNAs in a panel of NPC patient‐derived xenografts and an EBV‐positive NPC cell line by small RNA sequencing. Among the 40 miR‐BARTs, predominant expression of 22 miRNAs was consistently detected in these tumors. Among the abundantly expressed EBV‐miRNAs, BART5‐5p, BART7‐3p, BART9‐3p, and BART14‐3p could negatively regulate the expression of a key DNA double‐strand break (DSB) repair gene, ataxia telangiectasia mutated (ATM), by binding to multiple sites on its 3'‐UTR. Notably, the expression of these four miR‐BARTs represented more than 10% of all EBV‐encoded miRNAs in tumor cells, while downregulation of ATM expression was commonly detected in all of our tested sequenced samples. In addition, downregulation of ATM was also observed in primary NPC tissues in both qRT‐PCR (16 NP and 45 NPC cases) and immunohistochemical staining (35 NP and 46 NPC cases) analysis. Modulation of ATM expression by BART5‐5p, BART7‐3p, BART9‐3p, and BART14‐3p was demonstrated in the transient transfection assays. These findings suggest that EBV uses miRNA machinery as a key mechanism to control the ATM signaling pathway in NPC cells. By suppressing these endogenous miR‐BARTs in EBV‐positive NPC cells, we further demonstrated the novel function of miR‐BARTs in inhibiting Zta‐induced lytic reactivation. These findings imply that the four viral miRNAs work co‐operatively to modulate ATM activity in response to DNA damage and to maintain viral latency

EBV-encoded miRNAs target ATM-mediated response in nasopharyngeal carcinoma.

PubMed

Lung, Raymond W-M; Hau, Pok-Man; Yu, Ken H-O; Yip, Kevin Y; Tong, Joanna H-M; Chak, Wing-Po; Chan, Anthony W-H; Lam, Ka-Hei; Lo, Angela Kwok-Fung; Tin, Edith K-Y; Chau, Shuk-Ling; Pang, Jesse C-S; Kwan, Johnny S-H; Busson, Pierre; Young, Lawrence S; Yap, Lee-Fah; Tsao, Sai-Wah; To, Ka-Fai; Lo, Kwok-Wai

2018-04-01

Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignancy that is prevalent in southern China and Southeast Asia. It is consistently associated with latent Epstein-Barr virus (EBV) infection. In NPC, miR-BARTs, the EBV-encoded miRNAs derived from BamH1-A rightward transcripts, are abundantly expressed and contribute to cancer development by targeting various cellular and viral genes. In this study, we establish a comprehensive transcriptional profile of EBV-encoded miRNAs in a panel of NPC patient-derived xenografts and an EBV-positive NPC cell line by small RNA sequencing. Among the 40 miR-BARTs, predominant expression of 22 miRNAs was consistently detected in these tumors. Among the abundantly expressed EBV-miRNAs, BART5-5p, BART7-3p, BART9-3p, and BART14-3p could negatively regulate the expression of a key DNA double-strand break (DSB) repair gene, ataxia telangiectasia mutated (ATM), by binding to multiple sites on its 3'-UTR. Notably, the expression of these four miR-BARTs represented more than 10% of all EBV-encoded miRNAs in tumor cells, while downregulation of ATM expression was commonly detected in all of our tested sequenced samples. In addition, downregulation of ATM was also observed in primary NPC tissues in both qRT-PCR (16 NP and 45 NPC cases) and immunohistochemical staining (35 NP and 46 NPC cases) analysis. Modulation of ATM expression by BART5-5p, BART7-3p, BART9-3p, and BART14-3p was demonstrated in the transient transfection assays. These findings suggest that EBV uses miRNA machinery as a key mechanism to control the ATM signaling pathway in NPC cells. By suppressing these endogenous miR-BARTs in EBV-positive NPC cells, we further demonstrated the novel function of miR-BARTs in inhibiting Zta-induced lytic reactivation. These findings imply that the four viral miRNAs work co-operatively to modulate ATM activity in response to DNA damage and to maintain viral latency, contributing to the tumorigenesis of NPC. © 2017 The Authors

Detection of Epstein-Barr virus genome and latent infection gene expression in normal epithelia, epithelial dysplasia, and squamous cell carcinoma of the oral cavity.

PubMed

Kikuchi, Kentaro; Noguchi, Yoshihiro; de Rivera, Michelle Wendoline Garcia-Niño; Hoshino, Miyako; Sakashita, Hideaki; Yamada, Tsutomu; Inoue, Harumi; Miyazaki, Yuji; Nozaki, Tadashige; González-López, Blanca Silvia; Ide, Fumio; Kusama, Kaoru

2016-03-01

A relationship between Epstein-Barr virus (EBV) infection and cancer of lymphoid and epithelial tissues such as Burkitt's lymphoma, Hodgkin's disease, nasopharyngeal carcinoma (NPC), gastric carcinoma, and oral cancer has been reported. EBV is transmitted orally and infects B cells and epithelial cells. However, it has remained uncertain whether EBV plays a role in carcinogenesis of oral mucosal tissue. In the present study, we detected the EBV genome and latent EBV gene expression in normal mucosal epithelia, epithelial dysplasia, and oral squamous cell carcinoma (OSCC) to clarify whether EBV is involved in carcinogenesis of the oral cavity. We examined 333 formalin-fixed, paraffin-embedded tissue samples (morphologically normal oral mucosa 30 samples, gingivitis 32, tonsillitis 17, oral epithelial dysplasia 83, OSCC 150, and NPC 21). EBV latent infection genes (EBNA-2, LMP-1) were detected not only in OSCC (50.2 %, 10.7 %) but also in severe epithelial dysplasia (66.7 %, 44.4 %), mild to moderate epithelial dysplasia (43.1 %, 18.5 %), gingivitis (78.1 %, 21.9 %), and normal mucosa (83.3 %, 23.3 %). Furthermore, the intensity of EBV latent infection gene expression (EBER, LMP-1) was significantly higher in severe epithelial dysplasia (94.4 %, 72.2 %) than in OSCC (34.7 %, 38.7 %). These results suggest that EBV latent infection genes and their increased expression in severe epithelial dysplasia might play an important role in the dysplasia-carcinoma sequence in the oral cavity.

Choline and betaine intakes are associated with reduced risk of nasopharyngeal carcinoma in adults: a case-control study.

PubMed

Zeng, F-f; Xu, C-h; Liu, Y-t; Fan, Y-y; Lin, X-l; Lu, Y-k; Zhang, C-x; Chen, Y-m

2014-02-04

Intakes of choline and betaine have been inversely related to the risk of various neoplasms, but scant data exist on nasopharyngeal carcinoma (NPC). We examined the association between consumption of choline and betaine and risk of NPC. We conducted a case-control study with 600 incident NPC patients and 600 controls 1 : 1 matched by age, sex and household type in Guangdong, China. Dietary intake was assessed by a food frequency questionnaire through face-to-face interview. Intakes of total choline, betaine and choline+betaine were inversely related to NPC after adjustment for various lifestyle and dietary factors (all P-trend <0.001). Adjusted odds ratios (95% CI) for quartile 4 (vs quartile 1) were 0.42 (0.29, 0.61) for total choline, 0.50 (0.35, 0.72) for betaine and 0.44 (0.30, 0.64) for betaine+total choline. Regarding various sources of choline, lower NPC risk was associated with greater intakes of choline from phosphatidylcholine, free choline, glycerophosphocholine and phosphocholine, but not sphingomyelin. These findings are consistent with a beneficial effect of choline and betaine intakes on carcinogenesis.

Choline and betaine intakes are associated with reduced risk of nasopharyngeal carcinoma in adults: a case–control study

PubMed Central

Zeng, F-f; Xu, C-h; Liu, Y-t; Fan, Y-y; Lin, X-l; Lu, Y-k; Zhang, C-x; Chen, Y-m

2014-01-01

Background: Intakes of choline and betaine have been inversely related to the risk of various neoplasms, but scant data exist on nasopharyngeal carcinoma (NPC). We examined the association between consumption of choline and betaine and risk of NPC. Methods: We conducted a case–control study with 600 incident NPC patients and 600 controls 1 : 1 matched by age, sex and household type in Guangdong, China. Dietary intake was assessed by a food frequency questionnaire through face-to-face interview. Results: Intakes of total choline, betaine and choline+betaine were inversely related to NPC after adjustment for various lifestyle and dietary factors (all P-trend <0.001). Adjusted odds ratios (95% CI) for quartile 4 (vs quartile 1) were 0.42 (0.29, 0.61) for total choline, 0.50 (0.35, 0.72) for betaine and 0.44 (0.30, 0.64) for betaine+total choline. Regarding various sources of choline, lower NPC risk was associated with greater intakes of choline from phosphatidylcholine, free choline, glycerophosphocholine and phosphocholine, but not sphingomyelin. Conclusion: These findings are consistent with a beneficial effect of choline and betaine intakes on carcinogenesis. PMID:24169354

Locoregional control after intensity-modulated radiotherapy for nasopharyngeal carcinoma with an anatomy-based target definition.

PubMed

Kawashima, Mitsuhiko; Ariji, Takaki; Kameoka, Satoru; Ueda, Takashi; Kohno, Ryosuke; Nishio, Teiji; Arahira, Satoko; Motegi, Atsushi; Zenda, Sadamoto; Akimoto, Tetsuo; Tahara, Makoto; Hayashi, Ryuichi

2013-12-01

The objective of the study was to evaluate locoregional control after intensity-modulated radiotherapy for nasopharyngeal cancer using a target definition along with anatomical boundaries. Forty patients with biopsy-proven squamous cell or non-keratinizing carcinoma of the nasopharynx who underwent intensity-modulated radiotherapy between April 2006 and November 2009 were reviewed. There were 10 females and 30 males with a median age of 48 years (range, 17-74 years). More than half of the patients had T3/4 (n = 21) and/or N2/3 (n = 24) disease. Intensity-modulated radiotherapy was administered as 70 Gy/33 fractions with or without concomitant chemotherapy. The clinical target volume was contoured along with muscular fascia or periosteum, and the prescribed radiotherapy dose was determined for each anatomical compartment and lymph node level in the head and neck. One local recurrence was observed at Meckel's cave on the periphery of the high-risk clinical target volume receiving a total dose of <63 Gy. Otherwise, six locoregional failures were observed within irradiated volume receiving 70 Gy. Local and nodal control rates at 3 years were 91 and 89%, respectively. Adverse events were acceptable, and 25 (81%) of 31 patients who were alive without recurrence at 2 years had xerostomia of ≤Grade 1. The overall survival rate at 3 years was 87%. Target definition along with anatomically defined boundaries was feasible without compromise of the therapeutic ratio. It is worth testing this method further to minimize the unnecessary irradiated volume and to standardize the target definition in intensity-modulated radiotherapy for nasopharyngeal cancer.

Efficacy and safety of concurrent chemoradiation with weekly cisplatin ± low-dose celecoxib in locally advanced undifferentiated nasopharyngeal carcinoma: a phase II-III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Razmjou-Ghalaei, Sasan; Shafizad, Amin; Ashouri-Taziani, Yaghoub; Khademi, Bijan; Ahmadloo, Niloofar; Ansari, Mansour; Omidvari, Shapour; Mosalaei, Ahmad; Mosleh-Shirazi, Mohammad Amin

2011-01-01

This is the first study that aimed to determine the efficacy and safety of concurrent chemoradiation with weekly cisplatin ± celecoxib 100 mg twice daily in locally advanced undifferentiated nasopharyngeal carcinoma. Eligible patients had newly diagnosed locally advanced (T3-T4, and/or N2-N3, M0) undifferentiated nasopharyngeal carcinoma, no prior therapy, Karnofsky performance status ≥ 70, and normal organ function. The patients were assigned to receive 7 weeks concurrent chemoradiation (70 Gy) with weekly cisplatin 30 mg/m 2 with either celecoxib 100 mg twice daily, (study group, n = 26) or placebo (control group, n = 27) followed by adjuvant combined chemotherapy with cisplatin 70 mg/m 2 on day 1 plus 5-fluorouracil 750 mg/m 2 /d with 8-h infusion on days 1-3, 3-weekly for 3 cycles. Overall clinical response rate was 100% in both groups. Complete and partial clinical response rates were 64% and 36% in the study group and 44% and 56% in the control group, respectively (P > 0.25). The addition of celecoxib to concurrent chemoradiation was associated with improved 2-year locoregional control rate from 84% to 100% (P = 0.039). The addition of celecoxib 100 mg twice daily to concurrent chemoradiation improved 2-year locoregional control rate.

Gaining Insights on Nasopharyngeal Carcinoma Treatment Outcome Using Clinical Data Mining Techniques.

PubMed

Ghaibeh, A Ammar; Kasem, Asem; Ng, Xun Jin; Nair, Hema Latha Krishna; Hirose, Jun; Thiruchelvam, Vinesh

2018-01-01

The analysis of Electronic Health Records (EHRs) is attracting a lot of research attention in the medical informatics domain. Hospitals and medical institutes started to use data mining techniques to gain new insights from the massive amounts of data that can be made available through EHRs. Researchers in the medical field have often used descriptive statistics and classical statistical methods to prove assumed medical hypotheses. However, discovering new insights from large amounts of data solely based on experts' observations is difficult. Using data mining techniques and visualizations, practitioners can find hidden knowledge, identify interesting patterns, or formulate new hypotheses to be further investigated. This paper describes a work in progress on using data mining methods to analyze clinical data of Nasopharyngeal Carcinoma (NPC) cancer patients. NPC is the fifth most common cancer among Malaysians, and the data analyzed in this study was collected from three states in Malaysia (Kuala Lumpur, Sabah and Sarawak), and is considered to be the largest up-to-date dataset of its kind. This research is addressing the issue of cancer recurrence after the completion of radiotherapy and chemotherapy treatment. We describe the procedure, problems, and insights gained during the process.

Characterization of nasopharyngeal isolates of type b Haemophilus influenzae from Delhi

PubMed Central

Saikia, Kandarpa K.; Das, Bimal K.; Bewal, Ramesh K.; Kapil, Arti; Arora, N.K.; Sood, Seema

2012-01-01

Background & objectives: Haemophilus influenzae is an important cause of mortality and morbidity among young children in developing countries. Increasing incidence of antibiotic resistance especially production of extended spectrum beta lactamase (ESBL) has made treatment and management of H. influenzae infection more difficult. Nasopharyngeal H. influenzae isolates are excellent surrogate for determination of antibiotic resistance prevalent among invasive H. influenzae isolates. In this study, we characterized nasopharyngeal H. influenzae isolates obtained from healthy school going children in Delhi. Methods: Nasopharyngeal H. influenzae isolates were collected from healthy school going children and subjected to serotyping, fimbrial typing and antibiogram profiling. ESBL production was recorded using phenotypic as well as molecular methods. Multi locus sequence typing (MLST) of 13 representative nasopharyngeal H. influenzae isolates was performed as per guidelines. Results: A significant proportion (26 of 80, 32.5%) of nasopharyngeal isolates of H. influenzae were identified as serotype b. Fimbrial gene (hifA) was detected in 23 (28.75%) isolates. Resistance against commonly prescribed antibiotics (Amp, Tet, Chloro, Septran, Cephalexin) were observed to be high among the nasopharyngeal commensal H. influenzae. Extended spectrum beta lactamase (ESBL) production was observed in a five (6.25%) isolates by both double disk diffusion and molecular typing. MLST identified several novel alleles as well as novel sequence types. Interpretation & conclusions: Our findings showed high resistance against common antibiotics and detection of ESBL in nasopharyngeal H. influenzae isolates collected from normal healthy school going children in Delhi. Detection of H. influenzae type b capsular gene and the presence of fimbrial gene (hif A) suggest virulence potential of these isolates. Discovery of novel alleles and presence of new sequence types (STs) among nasopharyngeal H

Induction of nasal and nasopharyngeal tumours in Sprague-Dawley rats fed with Chinese salted fish.

PubMed

Zheng, X; Luo, Y; Christensson, B; Drettner, B

1994-01-01

Epidemiological studies have implied that Chinese salted fish is a human nasopharyngeal carcinogen. In the present study, 162 Sprague-Dawley rats were randomly assigned to one of four experimental groups. Rats in groups 1 (n = 41) and 3 (n = 40) were exposed to salted fish from birth through the breast feeding period by giving the maternal rats a diet containing 10% and 5% salted fish, respectively, later feeding the rats with pellets containing 10% and 5% of salted fish respectively. In group 2, the rats (n = 41) were given pellets containing 10% of salted fish from 6 weeks of age. Rats in group 4 (n = 40), serving as controls, were only given ordinary pellets. Three rats had nasopharyngeal tumours, 2 from group 1 had a poorly differentiated carcinoma and a squamous cell carcinoma. One rat from group 2 had a squamous cell carcinoma. Four rats had nasal tumours, one fibrosarcoma and one adenocarcinoma were found in rats from group 1. One rhabdomyosarcoma was found in group 2, and one soft tissue sarcoma was found in a rat in group 3. No nasal or nasopharyngeal tumours appeared in the control group. The difference in the occurrence of malignant nasal and nasopharyngeal tumours among the four experimental groups was statistically significant (one tailed p for trend = 0.041). The frequency of tumours appearing in other organs such as the breast, kidney, lung, liver and brain was not significantly different between the salted fish treated groups and the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Epigenetic dysregulation of key developmental genes in radiation-induced rat mammary carcinomas.

PubMed

Daino, Kazuhiro; Nishimura, Mayumi; Imaoka, Tatsuhiko; Takabatake, Masaru; Morioka, Takamitsu; Nishimura, Yukiko; Shimada, Yoshiya; Kakinuma, Shizuko

2018-02-13

With the increase in the number of long-term cancer survivors worldwide, there is a growing concern about the risk of secondary cancers induced by radiotherapy. Epigenetic modifications of genes associated with carcinogenesis are attractive targets for the prevention of cancer owing to their reversible nature. To identify genes with possible changes in functionally relevant DNA methylation patterns in mammary carcinomas induced by radiation exposure, we performed microarray-based global DNA methylation and expression profiling in γ-ray-induced rat mammary carcinomas and normal mammary glands. The gene expression profiling identified dysregulation of developmentally related genes, including the downstream targets of polycomb repressive complex 2 (PRC2) and overexpression of enhancer of zeste homolog 2, a component of PRC2, in the carcinomas. By integrating expression and DNA methylation profiles, we identified ten hypermethylated and three hypomethylated genes that possibly act as tumor-suppressor genes and oncogenes dysregulated by aberrant DNA methylation; half of these genes encode developmental transcription factors. Bisulfite sequencing and quantitative PCR confirmed the dysregulation of the polycomb-regulated developmentally related transcription-factor genes Dmrt2, Hoxa7, Foxb1, Sox17, Lhx8, Gata3 and Runx1. Silencing of Hoxa7 was further verified by immunohistochemistry. These results suggest that, in radiation-induced mammary gland carcinomas, PRC2-mediated aberrant DNA methylation leads to dysregulation of developmentally related transcription-factor genes. Our findings provide clues to molecular mechanisms linking epigenetic regulation and radiation-induced breast carcinogenesis and underscore the potential of such epigenetic mechanisms as targets for cancer prevention. © 2018 UICC.

Active immunotherapy with anti-idiotypic antibody for patients with nasopharyngeal carcinoma (NPC).

PubMed

Li, Guancheng; Xie, Lu; Zhou, Guohua; Zhu, Jiangao; Hu, Jinyue; Sun, Qubing

2002-12-01

Two anti-idiotypic monoclonal antibodies (Ab2), designated 2H4 and 5D3, against two antitumor antibodies Ab1 (FC2 and HNL5) that recognize nasopharyngeal carcinoma (NPC) associated antigen were generated. They could substitute NPC antigen to induce humoral and cellular immune response against NPC cells in syngeneic mice. Nineteen patients with NPC at stage IV were chosen for active immunotherapy. They were treated with aluminum hydroxide-precipitated Ab2 2H4 or 5D3 accompanying radiotherapy. None of the immunization of anti-idiotypic monoclonal antibody (mAb) was associated with toxicity or allergies reactions. Nine patients with radiotherapy alone served as control. Both anti-anti-idiotypic antibodies (Ab3) and anti-NPC antibodies (Ab1') were increased and human anti-mouse Ig antibodies (HAMA) occurred in nineteen patients of the experimental group; whereas the levels of Ab1' did not rise in the control group. Serum IL-2, IFN-gamma, and TNF-alpha levels were increased in most patients in the experimental group, while in the control group, there were no differences of Ab1' and cytokine level between pretherapy and posttherapy. In addition, IL-2 mRNA expression in peripheral blood mononuclear cells (PBMC) of NPC patients was closely related to serum IL-2 (r = +0.8829) by in situ hybridization. Therefore, mouse anti-idiotypic antibodies 2H4 and 5D3 are safe for active immunotherapy and might enhance humoral and/or cellular immunity of NPC patients receiving radiotherapy.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fogg, Mark; Murphy, John R.; Lorch, Jochen

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, asmore » 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu Sufang; Department of Radiation Oncology, National University Cancer Institute, National University Health System, National University of Singapore; Lin Shaojun

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 percentmore » 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.« less

Effects of Home Nursing Intervention on the Quality of Life of Patients with Nasopharyngeal Carcinoma after Radiotherapy and Chemotherapy.

PubMed

Shi, Ru-Chun; Meng, Ai-Feng; Zhou, Weng-Lin; Yu, Xiao-Yan; Huang, Xin-En; Ji, Ai-Jun; Chen, Lei

2015-01-01

The effects of home nursing intervention on the quality of life in patients with nasopharyngeal carcinoma (NPC) after radiotherapy and chemotherapy are unclear. According to the characteristics of nursing home patients with nasopharyngeal carcinoma, we should continuously improve the nursing plan and improve the quality of life of patients at home. We selected 180 patients at home with NPC after radiotherapy and chemotherapy. The patients were randomly divided into experimental and control groups (90 patients each). The experimental group featured intervention with an NPC home nursing plan, while the control group was given routine discharge and outpatient review. Nursing intervention for patients was mainly achieved by regular telephone follow-up and home visits. We use the quality of life scale (QOL-C30), anxiety scale (SAS) and depression scale (SDS) to evaluate these patients before intervention, and during follow-up at 1 month and 3 months after the intervention. Overall health and quality of life were significantly different between the groups (p<0.05), Emotional function score was significantly higher after intervention (p<0.05), as were cognitive function and social function scores after 3 months of intervention (p<0.05). Scores of fatigue, nausea and vomiting, pain, appetite and constipation were also significantly different between the two groups (p<0.05). Rates of anxiety and depression after 3 months of intervention were 11.1%, 22.2% and 34.4%, 53.3%, the differences being significant (p<0.05). NPC home nursing plan could effectively improve overall quality of life, cognitive function, social function (after 3 months) of patients, but improvement regarding body function is not suggested. Fatigue, nausea and vomiting, pain, appetite, constipation were clearly improved. We should further pursue a personalized, comprehensive measurements for nursing interventions and try to improve the quality of life of NPC patients at home.

High sensitivity of gold nanoparticles co-doped with Gd2O3 mesoporous silica nanocomposite to nasopharyngeal carcinoma cells

NASA Astrophysics Data System (ADS)

Wang, Hui; Zhang, Songjin; Tian, Xiumei; Liu, Chufeng; Zhang, Lei; Hu, Wenyong; Shao, Yuanzhi; Li, Li

2016-10-01

Nanoprobes for combined optical and magnetic resonance imaging have tremendous potential in early cancer diagnosis. Gold nanoparticles (AuNPs) co-doped with Gd2O3 mesoporous silica nanocomposite (Au/Gd@MCM-41) can produce pronounced contrast enhancement for T1 weighted image in magnetic resonance imaging (MRI). Here, we show the remarkably high sensitivity of Au/Gd@MCM-41 to the human poorly differentiated nasopharyngeal carcinoma (NPC) cell line (CNE-2) using fluorescence lifetime imaging (FLIM). The upconversion luminescences from CNE-2 and the normal nasopharyngeal (NP) cells (NP69) after uptake of Au/Gd@MCM-41 show the characteristic of two-photon-induced-radiative recombination of the AuNPs. The presence of the Gd3+ ion induces a much shorter luminescence lifetime in CNE-2 cells. The interaction between AuNPs and Gd3+ ion clearly enhances the optical sensitivity of Au/Gd@MCM-41 to CNE-2. Furthermore, the difference in the autofluorescence between CNE-2 and NP69 cells can be efficiently demonstrated by the emission lifetimes of Au/Gd@MCM-41 through the Forster energy transfers from the endogenous fluorophores to AuNPs. The results suggest that Au/Gd@MCM-41 may impart high optical resolution for the FLIM imaging that differentiates normal and high-grade precancers.

Outcomes of xerostomia-related quality of life for nasopharyngeal carcinoma treated by IMRT: based on the EORTC QLQ-C30 and H&N35 questionnaires.

PubMed

Bian, Xiuhua; Song, Tao; Wu, Shixiu

2015-01-01

The aim of this study was to review the published literature addressing the question of whether intensity-modulated radiotherapy (IMRT) resulted in an improvement of quality of life (QoL), especially xerostomia-related QoL of all nasopharyngeal carcinoma patients as time progressed. A literature search of PubMed, Embase and Google Scholar was performed, only reports containing original data of the QoL scores after treated by IMRT were included. Two independent reviewers extracted information of study design, study population, interventions, outcome measures and conclusions for each article. The inclusion criteria were met by 14 articles covering outcomes based on the questionnaires treated by IMRT. Data from same questionnaires (European Organization of Research and Treatment of Cancer QLQ-C30 and H&N35 questionnaires) were exacted and we analyzed four items (global health status, dry mouth and sticky saliva, swallowing, social eating and social contact), which have a close relationship with xerostomia-related QoL. Results indicated that a maximal deterioration of most QoL scales including global health status developed during treatment or at the end of the treatment course and then followed by a gradual recovery to 1 year, 1-2 years after IMRT, compared with their baseline level, some specific head and neck items, most in the EORTC QLQ H&N35, remained worse for the surviving patients. In conclusion, the published data reasonably support the benefits of IMRT in improving QoL, but xerostomia-related items still had a significantly negative effect in 2 years to impact a survivor's QoL.

Radiomic machine-learning classifiers for prognostic biomarkers of advanced nasopharyngeal carcinoma.

PubMed

Zhang, Bin; He, Xin; Ouyang, Fusheng; Gu, Dongsheng; Dong, Yuhao; Zhang, Lu; Mo, Xiaokai; Huang, Wenhui; Tian, Jie; Zhang, Shuixing

2017-09-10

We aimed to identify optimal machine-learning methods for radiomics-based prediction of local failure and distant failure in advanced nasopharyngeal carcinoma (NPC). We enrolled 110 patients with advanced NPC. A total of 970 radiomic features were extracted from MRI images for each patient. Six feature selection methods and nine classification methods were evaluated in terms of their performance. We applied the 10-fold cross-validation as the criterion for feature selection and classification. We repeated each combination for 50 times to obtain the mean area under the curve (AUC) and test error. We observed that the combination methods Random Forest (RF) + RF (AUC, 0.8464 ± 0.0069; test error, 0.3135 ± 0.0088) had the highest prognostic performance, followed by RF + Adaptive Boosting (AdaBoost) (AUC, 0.8204 ± 0.0095; test error, 0.3384 ± 0.0097), and Sure Independence Screening (SIS) + Linear Support Vector Machines (LSVM) (AUC, 0.7883 ± 0.0096; test error, 0.3985 ± 0.0100). Our radiomics study identified optimal machine-learning methods for the radiomics-based prediction of local failure and distant failure in advanced NPC, which could enhance the applications of radiomics in precision oncology and clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2014-01-01

Recent studies have shown association of mtDNA background with cancer development. We analyzed mitochondrial DNA (mtDNA) control region variation of 201 patients with nasopharyngeal carcinoma (NPC) and of 201 normal controls from Chaoshan Han Chinese to discern mtDNA haplogroup effect on the disease onset. Binary logistic regression analysis with adjustment for gender and age revealed that the haplogroup R9 (P = 0.011, OR = 1.91, 95% CI = 1.16–3.16), particularly its sub-haplogroup F1 (P = 0.015, OR = 2.43, 95% CI = 1.18–5.00), were associated significantly with increased NPC risk. These haplogroups were further confirmed to confer high NPC risk in males and/or individuals ≥40 years of age, but not in females or in subjects <40 years old. Our results indicated that mtDNA background confers genetic susceptibility to NPC in Chaoshan Han Chinese, and R9, particularly its sub-haplogroup F1, is a risk factor for NPC. PMID:24498198

Noninvasive detection of nasopharyngeal carcinoma based on saliva proteins using surface-enhanced Raman spectroscopy

NASA Astrophysics Data System (ADS)

Lin, Xueliang; Lin, Duo; Ge, Xiaosong; Qiu, Sufang; Feng, Shangyuan; Chen, Rong

2017-10-01

The present study evaluated the capability of saliva analysis combining membrane protein purification with surface-enhanced Raman spectroscopy (SERS) for noninvasive detection of nasopharyngeal carcinoma (NPC). A rapid and convenient protein purification method based on cellulose acetate membrane was developed. A total of 659 high-quality SERS spectra were acquired from purified proteins extracted from the saliva samples of 170 patients with pathologically confirmed NPC and 71 healthy volunteers. Spectral analysis of those saliva protein SERS spectra revealed specific changes in some biochemical compositions, which were possibly associated with NPC transformation. Furthermore, principal component analysis combined with linear discriminant analysis (PCA-LDA) was utilized to analyze and classify the saliva protein SERS spectra from NPC and healthy subjects. Diagnostic sensitivity of 70.7%, specificity of 70.3%, and diagnostic accuracy of 70.5% could be achieved by PCA-LDA for NPC identification. These results show that this assay based on saliva protein SERS analysis holds promising potential for developing a rapid, noninvasive, and convenient clinical tool for NPC screening.

Grave's disease induced by radiotherapy for nasopharyngeal carcinoma: A case report and review of the literature.

PubMed

Ma, Jin-An; Li, Xuezhen; Zou, Wen; Zhou, Yan

2013-07-01

Radiotherapy is an effective treatment for nasopharyngeal carcinoma (NPC). A number of thyroid dysfunctions are induced by damage resulting from the relatively high doses of radiation administered to the thyroid and pituitary gland during radiotherapy. Hypothyroidism constitutes the most frequent type of thyroid dysfunction induced by NPC radiotherapy, while hyperthyroidism, particularly Grave's disease, is extremely rare. The present study describes the case of a 40-year-old male who presented with Grave's disease 2 years after receiving radiotherapy for the treatment of NPC. The patient exhibited swelling of the eyes, an increased appetite, decreased levels of thyroid-stimulating hormone, increased levels of triiodothyronine (T3) and thyroxine (T4) demonstrated by the examination of thyroid function and enlargement of the bilateral intraocular rectus revealed by CT scan. The patient's symptoms were ameliorated following treatment with propylthiouracil and propranolol for 1 month, and the levels of T3 and T4 were restored to normal. The pathophysiological mechanism of radiotherapy-induced hyperthyroidism has yet to be elucidated. Hyperthyroidism is often neglected as several of its clinical manifestations are similar to other complications observed during and following cancer treatment. Therefore, it is necessary to monitor thyroid function following head and neck radiotherapy.

Spatial and temporal patterns of nasopharyngeal carcinoma mortality in China, 1973-2005.

PubMed

Xia, Changfa; Yu, Xue Qin; Zheng, Rongshou; Zhang, Siwei; Zeng, Hongmei; Wang, Jinfeng; Liao, Yilan; Zou, Xiaonong; Zuo, Tingting; Yang, Zhixun; Chen, Wanqing

2017-08-10

We fitted generalized linear models using data from three national retrospective surveys on cause of death in China to explore the spatial and temporal patterns of nasopharyngeal carcinoma (NPC) mortality over the period 1973 to 2005. The results suggest that there was a significant decrease in NPC mortality in China over time (p < 0.0001), the mortality rate ratio (RR) for the two later time periods were 0.59 (95% CI: 0.55-0.64) for 1990-1992 and 0.42 (95% CI: 0.39-0.45) for 2004-2005 compared to that of 1973-1975. Residents living in the South China areas have an elevated risk of mortality from NPC compared to those living in North China across all three time periods, with the RR being 4.96 (95% CI: 4.31-5.70) in 1973-1975, 12.83 (95% CI: 10.73-15.34) in 1990-1992 and 15.20 (95% CI: 12.34-18.72) in 2004-2005. Although NPC mortality in most areas of China has reduced to very low levels, the widening geographical disparities in NPC mortality are still noteworthy. It may be necessary to target public health policies to address the widening geographical disparities in NPC mortality. Copyright © 2017 Elsevier B.V. All rights reserved.

Birth order and risk of nasopharyngeal carcinoma in multiplex families from Taiwan.

PubMed

Liu, Zhiwei; Coghill, Anna E; Pfeiffer, Ruth M; Hsu, Wan-Lun; Lou, Pei-Jen; Wang, Cheng-Ping; Yu, Kelly J; Niwa, Shelley; Brotzman, Michelle; Ye, Weimin; Chen, Chien-Jen; Hildesheim, Allan

2016-12-01

A small proportion of individuals infected with Epstein-Barr virus (EBV) develop nasopharyngeal carcinoma (NPC). Timing of initial exposure could alter immunological responses to primary EBV infection and explain variation in cancer risk later in life. We measured early life family structure as a proxy for the timing of primary EBV infection to examine whether earlier age at infection alters NPC risk. We utilized data from 480 NPC cases and 1,291 unaffected siblings from Taiwanese NPC multiplex families (≥ 2 family members with NPC, N = 2,921). Information on birth order within the family was derived from questionnaires. We utilized logistic regression models to examine the association between birth order and NPC, accounting for correlations between relatives. Within these high-risk families, older siblings had an elevated risk of NPC. Compared with being a first-born child, the risk (95% CIs) of NPC associated with a birth order of two, three, four and five or more was 1.00 (0.71, 1.40), 0.88 (0.62, 1.24), 0.74 (0.53, 1.05) and 0.60 (0.43, 0.82), respectively (P for trend = 0.002). We observed no associations between NPC risk and the number of younger siblings or cumulative infant-years exposure. These associations were not modified by underlying genetic predisposition or family size. We observed that early life family structure was important for NPC risk in NPC multiplex families, with older siblings having a greater risk of disease. Future studies focusing on more direct measures of the immune response to EBV in early childhood could elucidate the underlying mechanisms. © 2016 UICC.

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

PubMed Central

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

2016-01-01

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

Identification of a functional variant in SPLUNC1 associated with nasopharyngeal carcinoma susceptibility among Malaysian Chinese.

PubMed

Yew, Poh-Yin; Mushiroda, Taisei; Kiyotani, Kazuma; Govindasamy, Gopala Krishnan; Yap, Lee-Fah; Teo, Soo-Hwang; Lim, Paul Vey-Hong; Govindaraju, Selvaratnam; Ratnavelu, Kananathan; Sam, Choon-Kook; Yap, Yoke-Yeow; Khoo, Alan Soo-Beng; Pua, Kin-Choo; Nakamura, Yusuke; Ng, Ching-Ching

2012-10-01

Nasopharyngeal carcinoma (NPC) is a multifactorial and polygenic disease with high incidence in Asian countries. Epstein-Barr virus infection, environmental and genetic factors are believed to be involved in the tumorigenesis of NPC. The association of single nucleotide polymorphisms (SNPs) in LPLUNC1 and SPLUNC1 genes with NPC was investigated by performing a two-stage case control association study in a Malaysian Chinese population. The initial screening consisted of 81 NPC patients and 147 healthy controls while the replication study consisted of 366 NPC patients and 340 healthy controls. The combined analysis showed that a SNP (rs2752903) of SPLUNC1 was significantly associated with the risk of NPC (combined P = 0.00032, odds ratio = 1.62, 95% confidence interval = 1.25-2.11). In the subsequent dense fine mapping of SPLUNC1 locus, 36 SNPs in strong linkage disequilibrium with rs2752903 (r(2) ≥ 0.85) were associated with NPC susceptibility. Screening of these variants by electrophoretic mobility shift and luciferase reporter assays showed that rs1407019 located in intron 3 (r(2)  = 0.994 with rs2752903) caused allelic difference in the binding of specificity protein 1 (Sp1) transcription factor and affected luciferase activity. This SNP may consequently alter the expression of SPLUNC1 in the epithelial cells. In summary, our study suggested that rs1407019 in intronic enhancer of SPLUNC1 is associated with NPC susceptibility in which its A allele confers an increased risk of NPC in the Malaysian Chinese population. Copyright © 2011 Wiley Periodicals, Inc.

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

PubMed

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.

Primary Treatment Results of Nasopharyngeal Carcinoma (NPC) in Yogyakarta, Indonesia

PubMed Central

Wildeman, Maarten A.; Fles, Renske; Herdini, Camelia; Indrasari, Rai S.; Vincent, Andrew D.; Tjokronagoro, Maesadji; Stoker, Sharon; Kurnianda, Johan; Karakullukcu, Baris; Taroeno-Hariadi, Kartika W.; Hamming-Vrieze, Olga; Middeldorp, Jaap M.; Hariwiyanto, Bambang; Haryana, Sofia M.; Tan, I. Bing

2013-01-01

Introduction Nasopharyngeal Carcinoma (NPC) is a major health problem in southern and eastern Asia. In Indonesia NPC is the most frequent cancer in the head and neck area. NPC is very sensitive to radiotherapy resulting in 3-year disease-free and overall survival of approximately 70% and 80%, respectively. Here we present routine treatment results in a prospective study on NPC in a top referral; university hospital in Indonesia. Methods All NPC patients presenting from September 2008 till January 2011 at the ear, nose and throat (ENT) department of the Dr. Sardjito General Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia, were possible candidates. Patients were included if the biopsy was a histological proven NPC without distant metastasis and were assessed during counselling sessions prior to treatment, as being able to complete the entire treatment. Results In total 78 patients were included for treatment analysis. The median time between diagnosis and start of radiotherapy is 120 days. Forty-eight (62%) patients eventually finished all fractions of radiotherapy. The median duration of the radiotherapy is 62 days for 66 Gy. Median overall survival is 21 months (95% CI 18–35) from day of diagnosis. Conclusion The results presented here reveal that currently the treatment of NPC at an Indonesian hospital is not sufficient and cannot be compared to the treatment results in literature. Main reasons for these poor treatment results are (1) a long waiting time prior to the start of radiotherapy, (2) the extended overall duration of radiotherapy and (3) the advanced stage of disease at presentation. PMID:23675501

Physiological β-catenin signaling controls self-renewal networks and generation of stem-like cells from nasopharyngeal carcinoma.

PubMed

Cheng, Yue; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Phoon, Yee Peng; Chiu, Pui Man; Lo, Paulisally Hau Yi; Waterman, Marian L; Lung, Maria Li

2013-09-27

A few reports suggested that low levels of Wnt signaling might drive cell reprogramming, but these studies could not establish a clear relationship between Wnt signaling and self-renewal networks. There are ongoing debates as to whether and how the Wnt/β-catenin signaling is involved in the control of pluripotency gene networks. Additionally, whether physiological β-catenin signaling generates stem-like cells through interactions with other pathways is as yet unclear. The nasopharyngeal carcinoma HONE1 cells have low expression of β-catenin and wild-type expression of p53, which provided a possibility to study regulatory mechanism of stemness networks induced by physiological levels of Wnt signaling in these cells. Introduction of increased β-catenin signaling, haploid expression of β-catenin under control by its natural regulators in transferred chromosome 3, resulted in activation of Wnt/β-catenin networks and dedifferentiation in HONE1 hybrid cell lines, but not in esophageal carcinoma SLMT1 hybrid cells that had high levels of endogenous β-catenin expression. HONE1 hybrid cells displayed stem cell-like properties, including enhancement of CD24(+) and CD44(+) populations and generation of spheres that were not observed in parental HONE1 cells. Signaling cascades were detected in HONE1 hybrid cells, including activation of p53- and RB1-mediated tumor suppressor pathways, up-regulation of Nanog-, Oct4-, Sox2-, and Klf4-mediated pluripotency networks, and altered E-cadherin expression in both in vitro and in vivo assays. qPCR array analyses further revealed interactions of physiological Wnt/β-catenin signaling with other pathways such as epithelial-mesenchymal transition, TGF-β, Activin, BMPR, FGFR2, and LIFR- and IL6ST-mediated cell self-renewal networks. Using β-catenin shRNA inhibitory assays, a dominant role for β-catenin in these cellular network activities was observed. The expression of cell surface markers such as CD9, CD24, CD44, CD90, and CD133

Combined chemo-radiotherapy in locally advanced nasopharyngeal carcinomas.

PubMed

Perri, Francesco; Della Vittoria Scarpati, Giuseppina; Buonerba, Carlo; Di Lorenzo, Giuseppe; Longo, Francesco; Muto, Paolo; Schiavone, Concetta; Sandomenico, Fabio; Caponigro, Francesco

2013-05-10

To provide efficacy and safety data about the combined use of radiotherapy and chemo-radiotherapy in nasopharyngeal carcinoma (NPC). We reviewed data of 40 patients with locally advanced NPC treated with induction chemotherapy followed by concomitant chemo-radiotherapy (CCRT) (22/40 patients) or CCRT alone (18/40) from March 2006 to March 2012. Patients underwent fiberoscopy with biopsy of the primitive tumor, and computed tomography scan of head, neck, chest and abdomen with and without contrast. Cisplatin was used both as induction and as concomitant chemotherapy, while 3D conformal radiation therapy was delivered to the nasopharynx and relevant anatomic regions (total dose, 70 Gy). The treatment was performed using 6 MV photons of the linear accelerator administered in 2 Gy daily fraction for five days weekly. This retrospective analysis was approved by the review boards of the participating institutions. Patients gave their consent to treatment and to anonymous analysis of clinical data. Thirty-three patients were males and 7 were females. Median follow-up time was 58 mo (range, 1-92 mo). In the sub-group of twenty patients with a follow-up time longer than 36 mo, the 3-year survival and disease free survival rates were 85% and 75%, respectively. Overall response rate both in patients treated with induction chemotherapy followed by CCRT and in those treated with CCRT alone was 100%. Grade 3 neutropenia was the most frequent acute side-effect and it occurred in 20 patients. Grade 2 mucositis was seen in 29 patients, while grade 2 xerostomia was seen in 30 patients. Overall toxicity was manageable and it did not cause any significant treatment delay. In the whole sample population, long term toxicity included grade 2 xerostomia in 22 patients, grade 1 dysgeusia in 17 patients and grade 1 subcutaneous fibrosis in 30 patients. Both CCRT and induction chemotherapy followed by CCRT showed excellent activity in locally advanced NPC. The role of adjuvant chemotherapy

Modulation of the tumor microenvironment by Epstein-Barr virus latent membrane protein 1 in nasopharyngeal carcinoma.

PubMed

Yoshizaki, Tomokazu; Kondo, Satoru; Endo, Kazuhira; Nakanishi, Yosuke; Aga, Mitsuharu; Kobayashi, Eiji; Hirai, Nobuyuki; Sugimoto, Hisashi; Hatano, Miyako; Ueno, Takayoshi; Ishikawa, Kazuya; Wakisaka, Naohiro

2018-02-01

Latent membrane protein 1 (LMP1) is a primary oncogene encoded by the Epstein-Barr virus, and various portions of LMP1 are detected in nasopharyngeal carcinoma (NPC) tumor cells. LMP1 has been extensively studied since the discovery of its transforming property in 1985. LMP1 promotes cancer cell growth during NPC development and facilitates the interaction of cancer cells with surrounding stromal cells for invasion, angiogenesis, and immune modulation. LMP1 is detected in 100% of pre-invasive NPC tumors and in approximately 50% of advanced NPC tumors. Moreover, a small population of LMP1-expressing cells in advanced NPC tumor tissue is proposed to orchestrate NPC tumor tissue maintenance and development through cancer stem cells and progenitor cells. Recent studies suggest that LMP1 activity shifts according to tumor development stage, but it still has a pivotal role during all stages of NPC development. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Analysis of nasopharyngeal carcinoma risk factors with Bayesian networks.

PubMed

Aussem, Alex; de Morais, Sérgio Rodrigues; Corbex, Marilys

2012-01-01

We propose a new graphical framework for extracting the relevant dietary, social and environmental risk factors that are associated with an increased risk of nasopharyngeal carcinoma (NPC) on a case-control epidemiologic study that consists of 1289 subjects and 150 risk factors. This framework builds on the use of Bayesian networks (BNs) for representing statistical dependencies between the random variables. We discuss a novel constraint-based procedure, called Hybrid Parents and Children (HPC), that builds recursively a local graph that includes all the relevant features statistically associated to the NPC, without having to find the whole BN first. The local graph is afterwards directed by the domain expert according to his knowledge. It provides a statistical profile of the recruited population, and meanwhile helps identify the risk factors associated to NPC. Extensive experiments on synthetic data sampled from known BNs show that the HPC outperforms state-of-the-art algorithms that appeared in the recent literature. From a biological perspective, the present study confirms that chemical products, pesticides and domestic fume intake from incomplete combustion of coal and wood are significantly associated with NPC risk. These results suggest that industrial workers are often exposed to noxious chemicals and poisonous substances that are used in the course of manufacturing. This study also supports previous findings that the consumption of a number of preserved food items, like house made proteins and sheep fat, are a major risk factor for NPC. BNs are valuable data mining tools for the analysis of epidemiologic data. They can explicitly combine both expert knowledge from the field and information inferred from the data. These techniques therefore merit consideration as valuable alternatives to traditional multivariate regression techniques in epidemiologic studies. Copyright © 2011 Elsevier B.V. All rights reserved.

Nonendemic HPV-Positive Nasopharyngeal Carcinoma: Association With Poor Prognosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stenmark, Matthew H., E-mail: stenmark@med.umich.edu; McHugh, Jonathan B.; Schipper, Matthew

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 viralmore » 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.« less

Genome-wide analyses of long noncoding RNA expression profiles correlated with radioresistance in nasopharyngeal carcinoma via next-generation deep sequencing.

PubMed

Li, Guo; Liu, Yong; Liu, Chao; Su, Zhongwu; Ren, Shuling; Wang, Yunyun; Deng, Tengbo; Huang, Donghai; Tian, Yongquan; Qiu, Yuanzheng

2016-09-06

Radioresistance is one of the major factors limiting the therapeutic efficacy and prognosis of patients with nasopharyngeal carcinoma (NPC). Accumulating evidence has suggested that aberrant expression of long noncoding RNAs (lncRNAs) contributes to cancer progression. Therefore, here we identified lncRNAs associated with radioresistance in NPC. The differential expression profiles of lncRNAs associated with NPC radioresistance were constructed by next-generation deep sequencing by comparing radioresistant NPC cells with their parental cells. LncRNA-related mRNAs were predicted and analyzed using bioinformatics algorithms compared with the mRNA profiles related to radioresistance obtained in our previous study. Several lncRNAs and associated mRNAs were validated in established NPC radioresistant cell models and NPC tissues. By comparison between radioresistant CNE-2-Rs and parental CNE-2 cells by next-generation deep sequencing, a total of 781 known lncRNAs and 2054 novel lncRNAs were annotated. The top five upregulated and downregulated known/novel lncRNAs were detected using quantitative real-time reverse transcription-polymerase chain reaction, and 7/10 known lncRNAs and 3/10 novel lncRNAs were demonstrated to have significant differential expression trends that were the same as those predicted by deep sequencing. From the prediction process, 13 pairs of lncRNAs and their associated genes were acquired, and the prediction trends of three pairs were validated in both radioresistant CNE-2-Rs and 6-10B-Rs cell lines, including lncRNA n373932 and SLITRK5, n409627 and PRSS12, and n386034 and RIMKLB. LncRNA n373932 and its related SLITRK5 showed dramatic expression changes in post-irradiation radioresistant cells and a negative expression correlation in NPC tissues (R = -0.595, p < 0.05). Our study provides an overview of the expression profiles of radioresistant lncRNAs and potentially related mRNAs, which will facilitate future investigations into the

Identifying FGA peptides as nasopharyngeal carcinoma-associated biomarkers by magnetic beads.

PubMed

Tao, Ya-Lan; Li, Yan; Gao, Jin; Liu, Zhi-Gang; Tu, Zi-Wei; Li, Guo; Xu, Bing-Qing; Niu, Dao-Li; Jiang, Chang-Bin; Yi, Wei; Li, Zhi-Qiang; Li, Jing; Wang, Yi-Ming; Cheng, Zhi-Bin; Liu, Qiao-Dan; Bai, Li; Zhang, Chun; Zhang, Jing-Yu; Zeng, Mu-Sheng; Xia, Yun-Fei

2012-07-01

Early diagnosis and treatment is known to improve prognosis for nasopharyngeal carcinoma (NPC). The study determined the specific peptide profiles by comparing the serum differences between NPC patients and healthy controls, and provided the basis for the diagnostic model and identification of specific biomarkers of NPC. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) can be used to detect the molecular mass of peptides. Mass spectra of peptides were generated after extracting and purification of 40 NPC samples in the training set, 21 in the single center validation set and 99 in the multicenter validation set using weak cationic-exchanger magnetic beads. The spectra were analyzed statistically using FlexAnalysis™ and ClinProt™ bioinformatics software. The four most significant peaks were selected out to train a genetic algorithm model to diagnose NPC. The diagnostic sensitivity and specificity were 100% and 100% in the training set, 90.5% and 88.9% in the single center validation set, 91.9% and 83.3% in the multicenter validation set, and the false positive rate (FPR) and false negative rate (FNR) were obviously lower in the NPC group (FPR, 16.7%; FNR, 8.1%) than in the other cancer group (FPR, 39%; FNR, 61%), respectively. So, the diagnostic model including four peptides can be suitable for NPC but not for other cancers. FGA peptide fragments identified may serve as tumor-associated biomarkers for NPC. Copyright © 2012 Wiley Periodicals, Inc.

Grave’s disease induced by radiotherapy for nasopharyngeal carcinoma: A case report and review of the literature

PubMed Central

MA, JIN-AN; LI, XUEZHEN; ZOU, WEN; ZHOU, YAN

2013-01-01

Radiotherapy is an effective treatment for nasopharyngeal carcinoma (NPC). A number of thyroid dysfunctions are induced by damage resulting from the relatively high doses of radiation administered to the thyroid and pituitary gland during radiotherapy. Hypothyroidism constitutes the most frequent type of thyroid dysfunction induced by NPC radiotherapy, while hyperthyroidism, particularly Grave’s disease, is extremely rare. The present study describes the case of a 40-year-old male who presented with Grave’s disease 2 years after receiving radiotherapy for the treatment of NPC. The patient exhibited swelling of the eyes, an increased appetite, decreased levels of thyroid-stimulating hormone, increased levels of triiodothyronine (T3) and thyroxine (T4) demonstrated by the examination of thyroid function and enlargement of the bilateral intraocular rectus revealed by CT scan. The patient’s symptoms were ameliorated following treatment with propylthiouracil and propranolol for 1 month, and the levels of T3 and T4 were restored to normal. The pathophysiological mechanism of radiotherapy-induced hyperthyroidism has yet to be elucidated. Hyperthyroidism is often neglected as several of its clinical manifestations are similar to other complications observed during and following cancer treatment. Therefore, it is necessary to monitor thyroid function following head and neck radiotherapy. PMID:23946792

Enhanced aerobic glycolysis of nasopharyngeal carcinoma cells by Epstein-Barr virus latent membrane protein 1.

PubMed

Sung, Wei-Wen; Chen, Peir-Rong; Liao, Ming-Hui; Lee, Jeng-Woei

2017-10-01

Latent membrane protein 1 (LMP1) is a principal viral oncoprotein in Epstein-Barr virus (EBV)-associated malignancies, including nasopharyngeal carcinoma (NPC), which acts through regulating tumorigenesis and metabolic reprogramming of cancers. In the presence of oxygen, we demonstrated that glucose consumption, lactate production and lactate dehydrogenase (LDH) activity were significantly increased upon LMP1 expression in NPC cells and in a LMP1 variant derived from NPC patients-transformed BALB/c-3T3 cells. The amounts of the α subunit of hypoxia-inducible factor-1 (HIF-1α), a key regulator of aerobic glycolysis, and its targets, pyruvate dehydrogenase kinase 1 (PDK1) and the pyruvate kinase M2 (PKM2) isoform, were also consistently elevated by LMP1. Moreover, in parallel with reductions in the oxygen consumption rate and mitochondrial membrane potential in cells, an augmented extracellular lactate concentration was observed due to LMP1 induction. In conclusion, our results proved facilitation of the Warburg effect by LMP1 through alteration of mitochondrial function in NPC cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical Utility of Epstein-Barr Virus DNA Testing in the Treatment of Nasopharyngeal Carcinoma Patients.

PubMed

Kim, Kelly Y; Le, Quynh-Thu; Yom, Sue S; Ng, Raymond H W; Chan, K C Allen; Bratman, Scott V; Welch, John J; Divi, Rao L; Petryshyn, Raymond A; Conley, Barbara A

2017-08-01

Epstein-Barr virus (EBV) DNA analysis has been shown to be useful for early detection, prognostication, and monitoring of treatment response of nasopharyngeal carcinoma (NPC), and the recent literature provides growing evidence of the clinical utility of EBV DNA testing, particularly to inform treatment decisions for NPC patients. Despite the fact that NPC is a rare disease, the NRG Oncology cooperative group has successfully activated a phase 2/3 randomized clinical trial for NPC with international partners and in that process has discovered that the development of a harmonized EBV DNA test is absolutely critical for integration into clinical trials and for future deployment in clinical and central laboratories. In November 2015, the National Cancer Institute (NCI) convened a workshop of international experts in the treatment of NPC and EBV testing to provide a forum for discussing the state of EBV DNA testing and its clinical utility, and to stimulate consideration of future studies and clinical practice guidelines for EBV DNA. This review provides a summary of that discussion. Published by Elsevier Inc.

Frequent NFIB-associated Gene Rearrangement in Adenoid Cystic Carcinoma of the Vulva.

PubMed

Xing, Deyin; Bakhsh, Salwa; Melnyk, Nataliya; Isacson, Christina; Ho, Julie; Huntsman, David G; Gilks, C Blake; Ronnett, Brigitte M; Horlings, Hugo M

2017-05-01

Adenoid cystic carcinoma is a rare malignant tumor that usually arises in the major and minor salivary glands and other locations containing secretory glands, including the lower female genital tract. Lower female genital tract carcinomas with adenoid cystic differentiation can be subclassified into 2 distinct groups based on the presence or absence of high-risk HPV. Cervical mixed carcinomas with some adenoid cystic differentiation are high-risk HPV-related but pure adenoid cystic carcinomas of vulvar and cervical origin appear to be unrelated to high-risk HPV. Mechanisms by which normal cells give rise to an HPV-unrelated adenoid cystic carcinoma remain largely unknown. Studies demonstrate that chromosomal translocation involving the genes encoding the transcription factors MYB and NFIB functions as a driving force of adenoid cystic carcinomas development regardless of anatomic site. The current study used fluorescence in situ hybridization with 3 different probes including MYB break-apart probe, NFIB break-apart probe, and MYB-NFIB fusion probe to assess for the presence of gene rearrangements in adenoid cystic carcinomas of the vulva. Six (66.7%) of 9 vulvar adenoid cystic carcinomas demonstrated NFIB rearrangement. Of these 6 cases with a disturbed NFIB, only 2 cases (33.3%) were positive for a MYB rearrangement that was also confirmed by a positive MYB-NFIB fusion pattern. NFIB-associated gene rearrangement is a frequent genetic event in vulvar adenoid cystic carcinomas. Chromosome translocations involving NFIB but with an intact MYB indicate the presence of novel oncogenic mechanisms for the development of adenoid cystic carcinomas of the vulva.

Low BRMS1 expression promotes nasopharyngeal carcinoma metastasis in vitro and in vivo and is associated with poor patient survival

PubMed Central

2012-01-01

Background Breast cancer metastasis suppressor 1 (BRMS1) is a metastasis suppressor gene. This study aimed to investigate the impact of BRMS1 on metastasis in nasopharyngeal carcinoma (NPC) and to evaluate the prognostic significance of BRMS1 in NPC patients. Methods BRMS1 expression was examined in NPC cell lines using quantitative reverse transcription-polymerase chain reaction and Western blotting. NPC cells stably expressing BRMS1 were used to perform wound healing and invasion assays in vitro and a murine xenograft assay in vivo. Immunohistochemical staining was performed in 274 paraffin-embedded NPC specimens divided into a training set (n = 120) and a testing set (n = 154). Results BRMS1 expression was down-regulated in NPC cell lines. Overexpression of BRMS1 significantly reversed the metastatic phenotype of NPC cells in vitro and in vivo. Importantly, low BRMS1 expression was associated with poor distant metastasis-free survival (DMFS, P < 0.001) and poor overall survival (OS, P < 0.001) in the training set; these results were validated in the testing set and overall patient population. Cox regression analysis demonstrated that low BRMS1 expression was an independent prognostic factor for DMFS and OS in NPC. Conclusions Low expression of the metastasis suppressor BRMS1 may be an independent prognostic factor for poor prognosis in NPC patients. PMID:22931099

[North African and Southeast Asian nasopharyngeal carcinomas: between the resemblance and the dissemblance].

PubMed

Ayadi, W; Khabir, A; Hadhri-Guiga, B; Fki, L; Toumi, N; Siala, W; Charfi, S; Fendri, A; Makni, H; Boudawara, T; Ghorbel, A; Gargouri, A; Jlidi, R; Gargouri, R; Busson, P; Drira, M; Daoud, J; Frikha, M; Hammami, A; Karray-Hakim, H

2010-04-01

Nasopharyngeal carcinoma (NPC) is an unusual head and neck cancer because of its unequal geographical distribution and its consistent association with the Epstein-Barr virus (EBV). This malignant tumor poses a serious public health problem in many countries, especially in Southeast Asia and North Africa where the recorded incidence are highest. During the past decade, a growing number of studies were undertaken to define the molecular basis of NPC. However, the analysis of several clinical and biological parameters of North African and Southeast Asian NPCs has shown notable differences, suggesting that they could result from a distinct combination of etiological factors. One intriguing characteristic of North African NPC, concerns its bimodal age distribution with a secondary peak of incidence in the range of 15-25 years, not observed in Asian NPC. In this juvenile form of NPC, immuno-histochemistry assay has shown that the two key proteins controlling the apoptotic-survival balance p53 and Bcl-2 are less frequently expressed whereas the transmembrane tyrosine-kinase receptor c-kit and the main EBV oncoprotein LMP1 were more abundant. In addition, the EBV serological alterations are less informative for the diagnosis of the juvenile compared to the adult form. In addition, most North African NPCs contain EBV strains with genetic polymorphisms distinct from those described in the Southeast Asia series (predominance of F, D, H1-H2, XhoI+ and f, C, H, XhoI- respectively). In contrast, studies relating on tumor chromosomal alterations or aberrant promoter methylation result in data very similar to those obtained from the Southeast Asia series, supporting the concept of a common molecular basis for all NPC regardless of patient geographic origin.

Central nervous system leukemia in a patient with concurrent nasopharyngeal carcinoma and acute myeloid leukaemia: A case report.

PubMed

Liu, Jun-Qing; Mai, Wen-Yuan; Wang, Si-Ben; Lou, Yin-Jun; Yan, Sen-Xiang; Jin, Jie; Xu, Wei-Lai

2017-12-01

Concurrent case of nasopharyngeal carcinoma (NPC) and acute myeloid leukemia (AML) has not been reported. Here, we report a case of NPC, who was concurrently suffered from AML one mother after the NPC diagnosis. The patient was a 45-year-old male who presented with a mass on his right side neck. The patient was diagnosed with Epstein-Barr virus negative type-2 non-keratinizing carcinoma with clivus involvement and unilateral metastasis to the cervical lymph node. He was treated with one cycle of cisplatin and 69.76 Gy of concurrent external-beam radiation. Three months after completion of chemo-radiotherapy, the patient was diagnosed as acute myeloid leukemia, which achieved complete remission after one course induction chemotherapy. Two months later, however, the patient was diagnosed as central nervous system leukemia. He ultimately died of relapsed leukemia. The overall survival of the patient was 10 months. The co-occurrence of NPC and AML is rare and prognosis is poor. Radiotherapy in NPC can disrupt the blood-brain barrier, which may contribute to the pathogenesis of central nervous system leukemia. Early alert and prevention of central nervous system leukemia following radiotherapy in NPC patient is recommended. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate.

PubMed

Guo, Charles C; Dancer, Jane Y; Wang, Yan; Aparicio, Ana; Navone, Nora M; Troncoso, Patricia; Czerniak, Bogdan A

2011-01-01

Recent studies have shown that most prostate cancers carry the TMPRSS2-ERG gene fusion. Here we evaluated the TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate (n = 12) in comparison with small cell carcinoma of the urinary bladder (n = 12) and lung (n = 11). Fluorescence in situ hybridization demonstrated rearrangement of the ERG gene in 8 cases of prostatic small cell carcinoma (67%), and the rearrangement was associated with deletion of the 5' ERG gene in 7 cases, but rearrangement of the ERG gene was not present in any small cell carcinoma of the urinary bladder or lung. Next we evaluated the TMPRSS2-ERG gene fusion in nude mouse xenografts that were derived from 2 prostatic small cell carcinomas carrying the TMPRSS2-ERG gene fusion. Two transcripts encoded by the TMPRSS2-ERG gene fusion were detected by reverse transcriptase polymerase chain reaction, and DNA sequencing demonstrated that the 2 transcripts were composed of fusions of exon 1 of the TMPRSS2 gene to exon 4 or 5 of the ERG gene. Our study demonstrates the specific presence of TMPRSS2-ERG gene fusion in prostatic small cell carcinoma, which may be helpful in distinguishing small cell carcinoma of prostatic origin from nonprostatic origins. The high prevalence of the TMPRSS2-ERG gene fusion in prostatic small cell carcinoma as well as adenocarcinoma implies that small cell carcinoma may share a common pathogenic pathway with adenocarcinoma in the prostate. Copyright © 2011 Elsevier Inc. All rights reserved.

Increased Risk of Ischemic Stroke in Young Nasopharyngeal Carcinoma Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Ching-Chih; Department of Otolaryngology, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan; Tumor Center, Buddhist Dalin Tzu Chi General Hospital, Chiayi, Taiwan

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

Differential protein-coding gene and long noncoding RNA expression in smoking-related lung squamous cell carcinoma.

PubMed

Li, Shicheng; Sun, Xiao; Miao, Shuncheng; Liu, Jia; Jiao, Wenjie

2017-11-01

Cigarette smoking is one of the greatest preventable risk factors for developing cancer, and most cases of lung squamous cell carcinoma (lung SCC) are associated with smoking. The pathogenesis mechanism of tumor progress is unclear. This study aimed to identify biomarkers in smoking-related lung cancer, including protein-coding gene, long noncoding RNA, and transcription factors. We selected and obtained messenger RNA microarray datasets and clinical data from the Gene Expression Omnibus database to identify gene expression altered by cigarette smoking. Integrated bioinformatic analysis was used to clarify biological functions of the identified genes, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, the construction of a protein-protein interaction network, transcription factor, and statistical analyses. Subsequent quantitative real-time PCR was utilized to verify these bioinformatic analyses. Five hundred and ninety-eight differentially expressed genes and 21 long noncoding RNA were identified in smoking-related lung SCC. GO and KEGG pathway analysis showed that identified genes were enriched in the cancer-related functions and pathways. The protein-protein interaction network revealed seven hub genes identified in lung SCC. Several transcription factors and their binding sites were predicted. The results of real-time quantitative PCR revealed that AURKA and BIRC5 were significantly upregulated and LINC00094 was downregulated in the tumor tissues of smoking patients. Further statistical analysis indicated that dysregulation of AURKA, BIRC5, and LINC00094 indicated poor prognosis in lung SCC. Protein-coding genes AURKA, BIRC5, and LINC00094 could be biomarkers or therapeutic targets for smoking-related lung SCC. © 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Chemoradiotherapy enhanced the efficacy of radiotherapy in nasopharyngeal carcinoma patients: a network meta-analysis

PubMed Central

He, Jian; Wu, Ping; Tang, Yaoyun; Liu, Sulai; Xie, Chubo; Luo, Shi; Zeng, Junfeng; Xu, Jing; Zhao, Suping

2017-01-01

Object A Bayesian network meta-analysis (NMA) was conducted to estimate the overall survival (OS) and complete response (CR) performance in nasopharyngeal carcinoma (NPC) patients who have been given the treatment of radiotherapy, concurrent chemoradiotherapy (C), adjuvant chemotherapy (A), neoadjuvant chemotherapy (N), concurrent chemoradiotherapy with adjuvant chemotherapy (C+A), concurrent chemoradiotherapy with neoadjuvant chemotherapy (C+N) and neoadjuvant chemotherapy with adjuvant chemotherapy (N+A). Methods Literature search was conducted in electronic databases. Hazard ratios (HRs) accompanied their 95% confidence intervals (95%CIs) or 95% credible intervals (95%CrIs) were applied to measure the relative survival benefit between two comparators. Meanwhile odd ratios (ORs) with their 95% CIs or CrIs were given to present CR data from individual studies. RESULTS Totally 52 qualified studies with 10,081 patients were included in this NMA. In conventional meta-analysis (MA), patients with N+C exhibited an average increase of 9% in the 3-year OS in relation to those with C+A. As for the NMA results, five therapies were associated with a significantly reduced HR when compared with the control group when concerning 5-year OS. C, C+A and N+A also presented a decreased HR compared with A. There was continuity among 1-year, 3-year and 5-year OS status. Cluster analysis suggested that the three chemoradiotherapy appeared to be divided into the most compete group which is located in the upper right corner of the cluster plot. Conclusion In view of survival rate and complete response, the NMA results revealed that C, C+A and C+N showed excellent efficacy. As a result, these 3 therapies were supposed to be considered as the first-line treatment according to this NMA. PMID:28418901

The effects of Chinese calligraphy handwriting and relaxation training in Chinese Nasopharyngeal Carcinoma patients: a randomized controlled trial.

PubMed

Yang, Xue-Ling; Li, Huan-Huan; Hong, Ming-Huang; Kao, Henry S R

2010-05-01

Chinese calligraphy handwriting is the practice of traditional Chinese brush writing, researches found calligraphy had therapeutic effects on certain diseases, some authors argued that calligraphy might have relaxation effect. This study was to compare the effects of calligraphy handwriting with those of progressive muscle relaxation and imagery training in Chinese Nasopharyngeal Carcinoma patients. This study was a randomized controlled trial. Two hundred and eighty-seven Nasopharyngeal Carcinoma patients were approached, ninety (31%) patients were recruited and randomized to one of the three treatment groups: progressive muscle relaxation and guided imagery training group, Calligraphy handwriting group, or a Control group. Seventy-nine (87.8%) completed all of the outcome measures. The primary treatment outcome was the changes of physiological arousal parameters measured by pre- and post-treatment differences of heart rate, blood pressure and respiration rate. The secondary outcomes included: modified Chinese version of Symptom Distress Scale, Profile of Mood State-Short Form, and Karnofsky Performance Status measured at baseline, during treatment (after the 2-week intervention), post-treatment (after the 4-week intervention) and after a 2-week follow-up. Effectiveness was tested by repeated measure ANOVA analyses. Cancer centre of a major university hospital in Guangdong, China. Results showed that both of calligraphy and relaxation training demonstrated slow-down effects on physiological arousal parameters. Moreover, calligraphy practice gradually lowered participants' systolic blood pressure (simple main effect of time at pre-treatment measure, p=.007) and respiration rate (p=.000) at pre- and post-treatment measures as the intervention proceeded, though with a smaller effect size as compared to relaxation. Both of calligraphy and relaxation training had certain symptom relief and mood improvement effects in NPC patients. Relaxation was effective in relieving

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

PubMed Central

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

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-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

Higher incidence of nasopharyngeal carcinoma in some regions in the world confers for interplay between genetic factors and external stimuli.

PubMed

Roy Chattopadhyay, Nabanita; Das, Piyanki; Chatterjee, Koustav; Choudhuri, Tathagata

2017-01-01

Nasopharyngeal carcinoma (NPC) is a rare variety of head and neck cancers. The risk factors include three major causes: genetic factors, viral infection, and environmental and dietary factors. The types of NPC show strong ethnic and geographic variations. The keratinizing and non-keratinizing types are prevalent in the lower incidence regions like North America and Europe; whereas the undifferentiated type is mostly found in the regions with higher incidences like China, North Africa, Arctic, and Nagaland of North-East India. These suggest a possible major role of the internal genetic factors for generation and promotion of this disease. Viral infections might accelerate the process of carcinogenesis by helping in cellular proliferation and loss of apoptosis. Diet and other environmental factors promote these neoplastic processes and further progression of the disease occurs.

Purified Hexameric Epstein-Barr Virus-Encoded BARF1 Protein for Measuring Anti-BARF1 Antibody Responses in Nasopharyngeal Carcinoma Patients▿

PubMed Central

Hoebe, E. K.; Hutajulu, S. H.; van Beek, J.; Stevens, S. J.; Paramita, D. K.; Greijer, A. E.; Middeldorp, J. M.

2011-01-01

WHO type III nasopharyngeal carcinoma (NPC) is highly prevalent in Indonesia and 100% associated with Epstein-Barr virus (EBV). NPC tumor cells express viral proteins, including BARF1, which is secreted and is considered to have oncogenic and immune-modulating properties. Recently, we found conserved mutations in the BARF1 gene in NPC isolates. This study describes the expression and purification of NPC-derived BARF1 and analyzes humoral immune responses against prototype BARF1 (B95-8) and purified native hexameric BARF1 in sera of Indonesian NPC patients (n = 155) compared to healthy EBV-positive (n = 56) and EBV-negative (n = 16) individuals. BARF1 (B95-8) expressed in Escherichia coli and baculovirus, as well as BARF1-derived peptides, did not react with IgG or IgA antibodies in NPC. Purified native hexameric BARF1 protein isolated from culture medium was used in enzyme-linked immunosorbent assay (ELISA) and revealed relatively weak IgG and IgA responses in human sera, although it had strong antibody responses to other EBV proteins. Higher IgG reactivity was found in NPC patients (P = 0.015) than in regional Indonesian controls or EBV-negative individuals (P < 0.001). IgA responses to native BARF1 were marginal. NPC sera with the highest IgG responses to hexameric BARF1 in ELISA showed detectable reactivity with denatured BARF1 by immunoblotting. In conclusion, BARF1 has low immunogenicity for humoral responses and requires native conformation for antibody binding. The presence of antibodies against native BARF1 in the blood of NPC patients provides evidence that the protein is expressed and secreted as a hexameric protein in NPC patients. PMID:21123521

Gonadotropin-releasing hormone inhibits the proliferation and motility of nasopharyngeal carcinoma cells

PubMed Central

TENG, LOONG HUNG; AHMAD, MUNIRAH; NG, WAYNE TIONG WENG; SABARATNAM, SUBATHRA; RASAN, MARIA ITHAYA; PARHAR, ISHWAR; KHOO, ALAN SOO BENG

2015-01-01

Gonadotropin-releasing hormone (GnRH), or its analogues have been demonstrated to exhibit anti-proliferative effects on tumour cells in ovarian, endometrial and breast cancer through GnRH-receptors (GnRH-R). However, the role of GnRH in nasopharyngeal carcinoma (NPC) remains to be elucidated. In order to investigate the effects of GnRH in NPC, the present study examined the expression of the GnRH-R transcript in NPC and investigated the phenotypic changes in HK1 cells, a recurrent NPC-derived cell line, upon receiving GnRH treatment. Firstly, the GnRH-R transcript was demonstrated in the NPC cell lines and four snap frozen biopsies using reverse transcription-quantitative polymerase chain reaction. In addition, immunohistochemistry revealed the expression of GnRH-R in two of the eight (25%) NPC specimens. Treatment with GnRH induced a rapid increase in intracellular ionised calcium concentration in the NPC cells. GnRH and its agonists, triptorelin and leuprolide, exerted anti-proliferative effects on the NPC cells, as determined using an MTS assay. GnRH did not induce any cell cycle arrest in the HK1 cells under the conditions assessed in the present study. Time-lapse imaging demonstrated a reduction in cell motility in the GnRH-treated cells. In conclusion, GnRH, or its analogues may have antitumour effects on NPC cells. The consequences of alterations in the levels of GnRH on the progression of NPC require further examination. PMID:26151677

A clinical study of 407 cases of nasopharyngeal carcinoma in Hong Kong

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teo, P.; Tsao, S.Y.; Shiu, W.

Four hundred and seven cases of nasopharyngeal carcinoma were analyzed retrospectively; 403/407 were evaluable for recurrence and survival. Parapharyngeal boost significantly decreased local recurrences in parapharyngeal diseases without base of skull involvement (T2p), but not with base of skull involvement (T3p). Enhanced local control of T2p with boost was significant without neoadjuvant chemotherapy. Tumors localized within the nasopharynx (T1) and tumors with nasal involvement (T2n) suffering from local persistences after external radiation therapy were treated with an intracavitary afterloading method. They had survival and recurrence rates comparable to complete responders to external radiation therapy. Patients with bulky cervical nodes (maximalmore » diameter greater than or equal to 4 cm, N1-N3), treated with neoadjuvant chemotherapy with cis-diamminedichloroplatinum II and 5-fluorouracil, had a regional failure rate, distant metastasis rate, actuarial survival rate, and disease-free survival rate comparable to those with smaller nodes treated with external radiation therapy alone. A simple modification of the Ho's classification by regrouping the T-stages into 'early T-stages' and 'advanced T-stages' and by combining the N1 and the N2 has greatly increased the power of the system in predicting local recurrence and distant metastasis, respectively. There was an overall improvement of the actuarial survival rate and disease-free survival rate over the historical control, and its significance is discussed.« less

Optimizing the induction chemotherapy regimen for patients with locoregionally advanced nasopharyngeal Carcinoma: A big-data intelligence platform-based analysis.

PubMed

Peng, Hao; Tang, Ling-Long; Chen, Bin-Bin; Chen, Lei; Li, Wen-Fei; Mao, Yan-Ping; Liu, Xu; Zhang, Yuan; Liu, Li-Zhi; Tian, Li; Guo, Ying; Sun, Ying; Ma, Jun

2018-04-01

This study aimed at identifying the optimal induction chemotherapy regimen for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy. We identified eligible patients with newly-diagnosed stage III-IVA NPC (excluding T3N0) between September 2009 and May 2015. Survival outcomes and grade 3-4 toxicities were compared between different IC regimen groups. In total, 3738 patients were eligible for this study, with 1572 (42.1%), 1085 (29.0%) and 1081 (28.9%) receiving TPF, PF and TP, respectively. In the whole population, multivariate analysis found that TPF seems to be better than PF and TP. Howerver, subgroup analysis revealed TPF and TP had same effectiveness in patients receiving a cumulative cisplatin dose (CCD) ≥200mg/m 2 in concurrent chemotherapy, while TPF shows relatively better survival benefit in patients receiving CCD<200mg/m 2 . Grade 3-4 toxicities were similar between TPF and TP groups, but were relatively higher than that in PF group. Our study concluded that induction TP regimen may be enough for patients receiving a CCD≥200mg/m 2 , while TPF may be superior to TP and PF for patients receiving a CCD<200mg/m 2 , although grade 3-4 toxic events were more common but tolerable. Further studies are needed to validate our findings. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed

Stoker, Sharon D; Wildeman, Maarten A; Fles, Renske; Indrasari, Sagung R; Herdini, Camelia; Wildeman, Pieter L; van Diessen, Judi N A; Tjokronagoro, Maesadji; Tan, I Bing

2014-01-01

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. 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. 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. 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.

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

PubMed

Dai, Wei; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Cheng, Yue; Zheng, Hong; Ngan, Roger Kai Cheong; Ng, Wai Tong; Lee, Anne Wing Mui; Yau, Chun Chung; Lee, Victor Ho Fu; Lung, Maria Li

2015-07-01

Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10(-9) ), but was less obvious in other types of solid tumors except for prostate and Epstein-Barr virus (EBV)-positive gastric cancer (FDR<10(-3) ). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Similar BCL-X but different BCL-2 levels in the two age groups of north African nasopharyngeal carcinomas.

PubMed

Khabir, Abdelmajid; Ghorbel, Abdelmoneem; Daoud, Jamel; Frikha, Mounir; Drira, Mohamed Mokhtar; Laplanche, Agnès; Busson, Pierre; Jlidi, Rachid

2003-01-01

Nasopharyngeal carcinomas (NPCs) are consistently associated with the Epstein-Barr virus (EBV). As Bcl-2 and Bcl-X are co-expressed in EBV-transformed B-lymphocytes, we attempted to determine their status in malignant NPC cells. A retrospective series of 100 NPC specimens from untreated Tunisian patients was investigated by immuno-histochemistry. Twenty seven of the patients were below 30 years old and therefore classified in the "juvenile" form of north African NPCs. Bcl-2 and Bcl-X expression was assessed semi-quantitatively using a score based on the percentage of positive cells and staining intensity. Intense Bcl-X expression was detected in malignant cells of 100% biopsy samples with similar scores for patients below 30 years or those aged 30 or over. Bcl-2 was detected in 89% biopsies but its expression differed considerably between the samples. The average Bcl-2 score was much lower for patients under 30 years (4.4+/-1.5 compared to 6.5+/-2 for older patients; P<10(-6)). Multivariate analysis demonstrated that no other clinical parameter, except the primary tumor size, was correlated to the Bcl-2 score. Bcl-X and Bcl-2 are co-expressed in 89% of NPCs whereas their expression is mutually exclusive in other head and neck carcinomas (particularly squamous cell carcinomas, SCC). The constantly high expression of Bcl-X is consistent with it being induced by the EBV protein Epstein-Barr nuclear antigen 1 (EBNA1), as recently reported in a murine model. The contrasted levels of Bcl-2 expression in the two age groups strengthen the hypothesis that these clinical forms result from distinct oncogenic mechanisms.

Predictive factors of tumor control and survival after radiosurgery for local failures of nasopharyngeal carcinoma.

PubMed

Chua, Daniel T T; Sham, Jonathan S T; Hung, Kwan-Ngai; Leung, Lucullus H T; Au, Gordon K H

2006-12-01

Stereotactic radiosurgery has been employed as a salvage treatment of local failures of nasopharyngeal carcinoma (NPC). To identify patients that would benefit from radiosurgery, we reviewed our data with emphasis on factors that predicted treatment outcome. A total of 48 patients with local failures of NPC were treated by stereotactic radiosurgery between March 1996 and February 2005. Radiosurgery was administered using a modified linear accelerator with single or multiple isocenters to deliver a median dose of 12.5 Gy to the target periphery. Median follow-up was 54 months. Five-year local failure-free probability after radiosurgery was 47.2% and 5-year overall survival rate was 46.9%. Neuroendocrine complications occurred in 27% of patients but there were no treatment-related deaths. Time interval from primary radiotherapy, retreatment T stage, prior local failures and tumor volume were significant predictive factors of local control and/or survival whereas age was of marginal significance in predicting survival. A radiosurgery prognostic scoring system was designed based on these predictive factors. Five-year local failure-free probabilities in patients with good, intermediate and poor prognostic scores were 100%, 42.5%, and 9.6%. The corresponding five-year overall survival rates were 100%, 51.1%, and 0%. Important factors that predicted tumor control and survival after radiosurgery were identified. Patients with good prognostic score should be treated by radiosurgery in view of the excellent results. Patients with intermediate prognostic score may also be treated by radiosurgery but those with poor prognostic score should receive other salvage treatments.

Nasopharyngeal Microbiome Diversity Changes over Time in Children with Asthma.

PubMed

Pérez-Losada, Marcos; Alamri, Lamia; Crandall, Keith A; Freishtat, Robert J

2017-01-01

The nasopharynx is a reservoir for pathogens associated with respiratory illnesses such as asthma. Next-generation sequencing (NGS) has been used to characterize the nasopharyngeal microbiome of infants and adults during health and disease; less is known, however, about the composition and temporal dynamics (i.e., longitudinal variation) of microbiotas from children and adolescents. Here we use NGS technology to characterize the nasopharyngeal microbiomes of asthmatic children and adolescents (6 to 18 years) and determine their stability over time. Two nasopharyngeal washes collected 5.5 to 6.5 months apart were taken from 40 children and adolescents with asthma living in the Washington D.C. area. Sequence data from the 16S-V4 rRNA gene region (~250 bp) were collected from the samples using the MiSeq platform. Raw data were processed in mothur (SILVA123 reference database) and Operational Taxonomic Units (OTU)-based alpha- and beta-diversity metrics were estimated. Relatedness among samples was assessed using PCoA ordination and Procrustes analyses. Differences in microbial diversity and taxon mean relative proportions were assessed using linear mixed effects models. Core microbiome analyses were also performed to identify stable and consistent microbes of the nasopharynx. A total of 2,096,584 clean 16S sequences corresponding to an average of 167 OTUs per sample were generated. Representatives of Moraxella*, Staphylococcus*, Dolosigranulum, Corynebacterium, Prevotella, Streptococcus*, Haemophilus*, Fusobacterium* and a Neisseriaceae genus accounted for 86% of the total reads. These nine genera have been previously found in the nasopharynxes of both infants and adults, but in different proportions. OTUs from the five genera highlighted (*) above defined the nasopharyngeal core microbiome at the 95% level. No significant differences in alpha- and beta-diversity were observed between seasons, but bacterial mean relative proportions of Haemophilus, Moraxella

Re-Evaluation of 6th Edition of AJCC Staging System for Nasopharyngeal Carcinoma and Proposed Improvement Based on Magnetic Resonance Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mao Yanping; Xie Fangyun; Liu Lizhi

2009-04-01

Purpose: To use magnetic resonance imaging to re-evaluate and improve the 6th edition of the International Union Against Cancer/American Joint Committee on Cancer staging system for nasopharyngeal carcinoma. Methods and Materials: We performed a retrospective review of the data from 924 biopsy-proven nonmetastatic nasopharyngeal carcinoma cases. All patients had undergone magnetic resonance imaging examinations and received radiotherapy as their primary treatment. Results: The T classification, N classification, and stage group were independent predictors. No significant differences in the local failure hazards between adjacent T categories were observed between Stage T2b and T1, Stage T2b and T2a, and Stage T2b andmore » T3. Although the disease failure hazards for Stage T1 were similar to those for Stage T2a, those for Stage T2b were similar to those for Stage T3. Survival curves of the different T/N subsets showed a better segregation when Stage T2a was downstaged to T1, T2b and T3 were incorporated into T2, and the nodal greatest dimension was rejected. The disease failure hazard for T3N0-N1 subsets were similar to those of the T1-T2N1 subsets belonging to Stage II; the same result was found for the T4N0-N2 subsets in the sixth American Joint Committee on Cancer staging system. However, the staging system we propose shows more consistent hazards within the same stage group and better survival discrimination among T categories, N categories, and overall stages. Conclusion: Using the 6th American Joint Committee on Cancer staging system produces an acceptable distribution of patient numbers and segregation of survival curves among the different stage groups. The prognostic accuracy of the staging system could be improved by recategorizing the T, N, and group stage criteria.« less

Radiation-induced functional connectivity alterations in nasopharyngeal carcinoma patients with radiotherapy

PubMed Central

Ma, Qiongmin; Wu, Donglin; Zeng, Ling-Li; Shen, Hui; Hu, Dewen; Qiu, Shijun

2016-01-01

Abstract The study aims to investigate the radiation-induced brain functional alterations in nasopharyngeal carcinoma (NPC) patients who received radiotherapy (RT) using functional magnetic resonance imaging (fMRI) and statistic scale. The fMRI data of 35 NPC patients with RT and 24 demographically matched untreated NPC patients were acquired. Montreal Cognitive Assessment (MoCA) was also measured to evaluate their global cognition performance. Multivariate pattern analysis was performed to find the significantly altered functional connections between these 2 groups, while the linear correlation level was detected between the altered functional connections and the MoCA scores. Forty-five notably altered functional connections were found, which were mainly located between 3 brain networks, the cerebellum, sensorimotor, and cingulo-opercular. With strictly false discovery rate correction, 5 altered functional connections were shown to have significant linear correlations with the MoCA scores, that is, the connections between the vermis and hippocampus, cerebellum lobule VI and dorsolateral prefrontal cortex, precuneus and dorsal frontal cortex, cuneus and middle occipital lobe, and insula and cuneus. Besides, the connectivity between the vermis and hippocampus was also significantly correlated with the attention score, 1 of the 7 subscores of the MoCA. The present study provides new insights into the radiation-induced functional connectivity impairments in NPC patients. The results showed that the RT may induce the cognitive impairments, especially the attention alterations. The 45 altered functional connections, especially the 5 altered functional connections that were significantly correlated to the MoCA scores, may serve as the potential biomarkers of the RT-induced brain functional impairments and provide valuable targets for further functional recovery treatment. PMID:27442663

Radiation-induced functional connectivity alterations in nasopharyngeal carcinoma patients with radiotherapy.

PubMed

Ma, Qiongmin; Wu, Donglin; Zeng, Ling-Li; Shen, Hui; Hu, Dewen; Qiu, Shijun

2016-07-01

The study aims to investigate the radiation-induced brain functional alterations in nasopharyngeal carcinoma (NPC) patients who received radiotherapy (RT) using functional magnetic resonance imaging (fMRI) and statistic scale.The fMRI data of 35 NPC patients with RT and 24 demographically matched untreated NPC patients were acquired. Montreal Cognitive Assessment (MoCA) was also measured to evaluate their global cognition performance. Multivariate pattern analysis was performed to find the significantly altered functional connections between these 2 groups, while the linear correlation level was detected between the altered functional connections and the MoCA scores.Forty-five notably altered functional connections were found, which were mainly located between 3 brain networks, the cerebellum, sensorimotor, and cingulo-opercular. With strictly false discovery rate correction, 5 altered functional connections were shown to have significant linear correlations with the MoCA scores, that is, the connections between the vermis and hippocampus, cerebellum lobule VI and dorsolateral prefrontal cortex, precuneus and dorsal frontal cortex, cuneus and middle occipital lobe, and insula and cuneus. Besides, the connectivity between the vermis and hippocampus was also significantly correlated with the attention score, 1 of the 7 subscores of the MoCA.The present study provides new insights into the radiation-induced functional connectivity impairments in NPC patients. The results showed that the RT may induce the cognitive impairments, especially the attention alterations. The 45 altered functional connections, especially the 5 altered functional connections that were significantly correlated to the MoCA scores, may serve as the potential biomarkers of the RT-induced brain functional impairments and provide valuable targets for further functional recovery treatment.

A novel Smac mimetic APG-1387 demonstrates potent antitumor activity in nasopharyngeal carcinoma cells by inducing apoptosis.

PubMed

Li, Ning; Feng, Lin; Han, Hui-Qiong; Yuan, Jing; Qi, Xue-Kang; Lian, Yi-Fan; Kuang, Bo-Hua; Zhang, Yu-Chen; Deng, Cheng-Cheng; Zhang, Hao-Jiong; Yao, You-Yuan; Xu, Miao; He, Gui-Ping; Zhao, Bing-Chun; Gao, Ling; Feng, Qi-Sheng; Chen, Li-Zhen; Yang, Lu; Yang, Dajun; Zeng, Yi-Xin

2016-10-10

Despite advances in the development of radiation against nasopharyngeal carcinoma (NPC), the management of advanced NPC remains a challenge. Smac mimetics are designed to neutralize inhibitor of apoptosis (IAP) proteins, thus reactivating the apoptotic program in cancer cells. In this study, we investigated the effect of a novel bivalent Smac mimetic APG-1387 in NPC. In vitro, APG-1387 in combination with TNF-α potently decreased NPC cell viability by inducing apoptosis in majority of NPC cell lines. The in vitro antitumor effect was RIPK1-dependent, whereas it was independent on IAPs, USP11, or EBV. Of note, the inhibition of NF-κB or AKT pathway rendered resistant NPC cells responsive to the treatment of APG-1387/TNF-α. In vivo, APG-1387 displayed antitumor activity as a single agent at well-tolerated doses, even in an in vitro resistant cell line. In summary, our results demonstrate that APG-1387 exerts a potent antitumor effect on NPC. These findings support clinical evaluation of APG-1387 as a potential treatment for advanced NPC. Copyright © 2016. Published by Elsevier Ireland Ltd.

Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection.

PubMed

de Steenhuijsen Piters, Wouter A A; Heinonen, Santtu; Hasrat, Raiza; Bunsow, Eleonora; Smith, Bennett; Suarez-Arrabal, Maria-Carmen; Chaussabel, Damien; Cohen, Daniel M; Sanders, Elisabeth A M; Ramilo, Octavio; Bogaert, Debby; Mejias, Asuncion

2016-11-01

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem. To assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection. We characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response, and clinical disease severity. We identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae- and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling. Our data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.

Reporting Quality of Randomized, Controlled Trials Evaluating Combined Chemoradiotherapy in Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yu-Pei; Chen, Lei; Li, Wen-Fei

Purpose: To comprehensively assess the reporting quality of randomized, controlled trials (RCTs) in nasopharyngeal carcinoma (NPC), and to identify significant predictors of quality. Methods and Materials: Two investigators searched MEDLINE and EMBASE for RCTs published between January 1988 and December 2015 that assessed the effect of combined chemoradiotherapy for NPC. The overall quality of each report was assessed using a 28-point overall quality score (OQS) based on the 2010 Consolidated Standards of Reporting Trials (CONSORT) statement. To provide baseline data for further evaluation, we also investigated the reporting quality of certain important issues in detail, including key methodologic items (allocationmore » concealment, blinding, intention-to-treat principle), endpoints, follow-up, subgroup analyses, and adverse events. Results: We retrieved 24 relevant RCTs including 6591 patients. Median 2010 OQS was 15.5 (range, 10-24). Half of the items in the 2010 OQS were poorly reported in at least 40% of trials. Multivariable regression models revealed that publication after 2010 and high impact factor were significant predictors of improved 2010 OQS. Additionally, many issues that we consider significant were not reported adequately. Conclusions: Despite publication of the CONSORT statement more than a decade ago, overall reporting quality for RCTs in NPC was unsatisfactory. Additionally, substantial selectivity and heterogeneity exists in reporting of certain crucial issues. This survey provides the first prompt for NPC trial investigators to improve reporting quality according to the CONSORT statement; increased scrutiny and diligence by editors and peer reviewers is also required.« less

CXCR6 and CCR5 localize T lymphocyte subsets in nasopharyngeal carcinoma.

PubMed

Parsonage, Greg; Machado, Lee Richard; Hui, Jan Wai-Ying; McLarnon, Andrew; Schmaler, Tilo; Balasothy, Meenarani; To, Ka-Fai; Vlantis, Alexander C; van Hasselt, Charles A; Lo, Kwok-Wai; Wong, Wai-Lap; Hui, Edwin Pun; Chan, Anthony Tak Cheung; Lee, Steven P

2012-03-01

The substantial T lymphocyte infiltrate found in cases of nasopharyngeal carcinoma (NPC) has been implicated in the promotion of both tumor growth and immune escape. Conversely, because malignant NPC cells harbor the Epstein-Barr virus, this tumor is a candidate for virus-specific T cell-based therapies. Preventing the accumulation of tumor-promoting T cells or enhancing the recruitment of tumor-specific cytotoxic T cells offers therapeutic potential. However, the mechanisms involved in T cell recruitment to this tumor are poorly understood. Comparing memory T cell subsets that have naturally infiltrated NPC tissue with their counterparts from matched blood revealed enrichment of CD8(+), CD4(+), and regulatory T cells expressing the chemokine receptor CXCR6 in tumor tissue. CD8(+) and (nonregulatory) CD4(+) T cells also were more frequently CCR5(+) in tumor than in blood. Ex vivo studies demonstrated that both receptors were functional. CXCL16 and CCL4, unique chemokine ligands for CXCR6 and CCR5, respectively, were expressed by the malignant cells in tumor tissue from the majority of NPC cases, as was another CCR5 ligand, CCL5. The strongest expression of CXCL16 was found on tumor-infiltrating cells. CCL4 was detected on the tumor vasculature in a majority of cases. These findings suggest that CXCR6 and CCR5 play important roles in T cell recruitment and/or retention in NPC and have implications for the pathogenesis and treatment of this tumor. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Xerostomia, salivary characteristics and gland volumes following intensity-modulated radiotherapy for nasopharyngeal carcinoma: a two-year follow up.

PubMed

Sim, Cpc; Soong, Y L; Pang, Epp; Lim, C; Walker, G D; Manton, D J; Reynolds, E C; Wee, Jts

2018-06-01

To evaluate changes in xerostomia status, salivary characteristics and gland volumes 2 years following radiotherapy in nasopharyngeal carcinoma patients. Xerostomia scores, salivary flow rates, pH and buffering capacity were measured at pre-radiotherapy, mid-radiotherapy, 2 weeks, 3 months and 2 years post-radiotherapy. Salivary gland volumes and their correlation with radiation dose were also assessed. Mean radiation dose to oral cavity, parotid and submandibular glands (SMG) was 44.5, 65.0 and 38.6 Gy respectively. Parotid and SMG volumes decreased 33% at 3 months post-radiotherapy; volumes at 2 years post-radiotherapy were 84% and 51% of pre-radiotherapy levels, respectively. Correlations were observed between parotid gland volume per cent reduction and its radiation dose and between resting salivary flow rate reduction and post-radiotherapy/pre-radiotherapy SMG volume ratio. Salivary flow rates and resting saliva pH remained significantly low at 2 years post-radiotherapy (both flow rates, P = 0.001; resting saliva pH, P = 0.005). Similarly, xerostomia scores remained significantly higher compared with pre-radiotherapy levels. Submandibular gland volumetric shrinkage persisted 2 years after radiotherapy. Xerostomia scores remained significantly higher, and salivary flow rates and resting saliva pH remained significantly lower, suggesting that study participants were still at risk for hyposalivation-related oral diseases. © 2018 Australian Dental Association.

HOXB homeobox gene expression in cervical carcinoma.

PubMed

López, R; Garrido, E; Piña, P; Hidalgo, A; Lazos, M; Ochoa, R; Salcedo, M

2006-01-01

The homeobox (HOX) genes are a family of transcription factors that bind to specific DNA sequences in target genes regulating gene expression. Thirty-nine HOX genes have been mapped in four conserved clusters: A, B, C, and D; they act as master genes regulating the identity of body segments along the anteroposterior axis of the embryo. The role played by HOX genes in adult cell differentiation is unclear to date, but growing evidence suggests that they may play an important role in the development of cancer. To study the role played by HOX genes in cervical cancer, in the present work, we analyzed the expression of HOXB genes and the localization of their transcripts in human cervical tissues. Reverse transcription-polymerase chain reaction analysis and nonradioactive RNA in situ hybridization were used to detect HOXB expression in 11 normal cervical tissues and 17 cervical carcinomas. It was determined that HOXB1, B3, B5, B6, B7, B8, and B9 genes are expressed in normal adult cervical epithelium and squamous cervical carcinomas. Interestingly, HOXB2, HOXB4, and HOXB13 gene expression was found only in tumor tissues. Our findings suggest that the new expression of HOXB2, HOXB4, and B13 genes is involved in cervical cancer.

Lack of death receptor 4 (DR4) expression through gene promoter methylation in gastric carcinoma.

PubMed

Lee, Kyung Hwa; Lim, Sang Woo; Kim, Ho Gun; Kim, Dong Yi; Ryu, Seong Yeob; Joo, Jae Kyun; Kim, Jung Chul; Lee, Jae Hyuk

2009-07-01

To determine the underlying mechanism for the differential expression, the extent of promoter methylation in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-related genes acting downstream of TRAIL was examined in early and advanced gastric carcinomas. The extent of promoter methylation in the DR4, DR5, DcR1, DcR2, and CASP8 genes was quantified using bisulfite modification and methylation-specific polymerase chain reaction. The promoters for DcR1, DcR2, and CASP8 were largely unmethylated in early gastric carcinoma, advanced gastric carcinoma, and controls, with no significant difference among them. Protein levels of DR4, DcR1, and DcR2 as revealed by immunohistochemistry correlated with the extent of the respective promoter methylation (P < 0.05 in all cases). Hypomethylation, rather than hypermethylation, of the DR4 promoter was noted in invasive gastric malignancies, with statistical significance (P = 0.003). The promoter methylation status of TRAIL receptors in gastric carcinoma may have clinical implications for improving therapeutic strategies in patients with gastric carcinoma.

Quantitative fucK gene polymerase chain reaction on sputum and nasopharyngeal secretions to detect Haemophilus influenzae pneumonia.

PubMed

Abdeldaim, Guma M K; Strålin, Kristoffer; Olcén, Per; Blomberg, Jonas; Mölling, Paula; Herrmann, Björn

2013-06-01

A quantitative polymerase chain reaction (PCR) for the fucK gene was developed for specific detection of Haemophilus influenzae. The method was tested on sputum and nasopharyngeal aspirate (NPA) from 78 patients with community-acquired pneumonia (CAP). With a reference standard of sputum culture and/or serology against the patient's own nasopharyngeal isolate, H. influenzae etiology was detected in 20 patients. Compared with the reference standard, fucK PCR (using the detection limit 10(5) DNA copies/mL) on sputum and NPA showed a sensitivity of 95.0% (19/20) in both cases, and specificities of 87.9% (51/58) and 89.5% (52/58), respectively. In a receiver operating characteristic curve analysis, sputum fucK PCR was found to be significantly superior to sputum P6 PCR for detection of H. influenzae CAP. NPA fucK PCR was positive in 3 of 54 adult controls without respiratory symptoms. In conclusion, quantitative fucK real-time PCR provides a sensitive and specific identification of H. influenzae in respiratory secretions. Copyright © 2013 Elsevier Inc. All rights reserved.

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

PubMed Central

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

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

PubMed

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

2016-10-01

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.

Capsaicin Induces Autophagy and Apoptosis in Human Nasopharyngeal Carcinoma Cells by Downregulating the PI3K/AKT/mTOR Pathway.

PubMed

Lin, Yu-Tsai; Wang, Hung-Chen; Hsu, Yi-Chiang; Cho, Chung-Lung; Yang, Ming-Yu; Chien, Chih-Yen

2017-06-23

Capsaicin is a potential chemotherapeutic agent for different human cancers. In Southeast China, nasopharyngeal carcinoma (NPC) has the highest incidence of all cancers, but final treatment outcomes are unsatisfactory. However, there is a lack of information regarding the anticancer activity of capsaicin in NPC cells, and its effects on the signaling transduction pathways related to apoptosis and autophagy remain unclear. In the present study, the precise mechanisms by which capsaicin exerts anti-proliferative effects, cell cycle arrest, autophagy and apoptosis were investigated in NPC-TW01 cells. Exposure to capsaicin inhibited cancer cell growth and increased G1 phase cell cycle arrest. Western blotting and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) were used to measure capsaicin-induced autophagy via involvement of the class III PI3K/Beclin-1/Bcl-2 signaling pathway. Capsaicin induced autophagy by increasing levels of the autophagy markers LC3-II and Atg5, enhancing p62 and Fap-1 degradation and increasing caspase-3 activity to induce apoptosis, suggesting a correlation of blocking the PI3K/Akt/mTOR pathway with the above-mentioned anticancer activities. Taken together, these data confirm that capsaicin inhibited the growth of human NPC cells and induced autophagy, supporting its potential as a therapeutic agent for cancer.

Chromatin remodelling and DNA repair genes are frequently mutated in endometrioid endometrial carcinoma.

PubMed

García-Sanz, Pablo; Triviño, Juan Carlos; Mota, Alba; Pérez López, María; Colás, Eva; Rojo-Sebastián, Alejandro; García, Ángel; Gatius, Sonia; Ruiz, María; Prat, Jaime; López-López, Rafael; Abal, Miguel; Gil-Moreno, Antonio; Reventós, Jaume; Matias-Guiu, Xavier; Moreno-Bueno, Gema

2017-04-01

In developed countries, endometrial carcinoma is the most common cancer that affects the female genital tract. Endometrial carcinoma is divided into two main histological types, type I or endometrioid and type II or non-endometrioid, each of which have characteristic, although not exclusive, molecular alterations and mutational profiles. Nevertheless, information about the implication and relevance of some of these genes in this disease is lacking. We sought here to identify new recurrently mutated genes in endometrioid cancers that play a role in tumourigenesis and that influence the clinical outcome. We focused on low-grade, non-ultramutated tumours as these tumours have a worse prognosis than the ultramutated POLE-positive endometrioid endometrial carcinomas (EECs). We performed exome-sequencing of 11 EECs with matched normal tissue and subsequently validated 15 candidate genes in 76 samples. For the first time, we show that mutations in chromatin remodelling-related genes (KMT2D, KMT2C, SETD1B and BCOR) and in DNA-repair-related genes (BRCA1, BRCA2, RAD50 and CHD4) are frequent in this subtype of endometrial cancer. The alterations to these genes occurred with frequencies ranging from 35.5% for KMT2D to 10.5% for BRCA1 and BCOR, with some showing a tendency toward co-occurrence (RAD50-KMT2D and RAD50-SETD1B). All these genes harboured specific mutational hotspots. In addition, the mutational status of KMT2C, KMT2D and SETD1B helps to predict the degree of myometrial invasion, a critical prognostic feature. These results highlight the possible implication of these genes in this disease, creating opportunities for new therapeutic approaches. © 2016 UICC.

A retrospective study of 606 cases of nasopharyngeal carcinoma with or without oropharyngeal candidiasis during radiotherapy

PubMed Central

Xia, Wei-Xiong; Yang, Jing; Yu, Ya-Hui; Liang, Hu; Huang, Xin-Jun; Liu, Guo-Ying; Li, Wang-Zhong; Xiang, Yan-Qun; Guo, Xiang; Lv, Xing

2017-01-01

Background To evaluate the clinical characteristics, treatment-related toxicities and survival in patients with nasopharyngeal carcinoma (NPC) with or without oropharyngealcandidiasis (OPC) during radiotherapy. Methods The current study was conducted with NPC patients undergoing radiotherapy at Sun Yat-Sen University Cancer Center between June 2011 and May 2012. A clinical diagnosis of candidiasis was determined on the basis of a positive potassium hydroxide (KOH) test and the presence of pseudomembranous (white) form of candidal overgrowth. The Cox proportional hazard regression model was used to test the association of OPC and related survival rates. Results Compared with the non-OPC group, the OPC group had significantly increased occurrence rates of grade 3–4 mucositis (14.5% vs. 7.4%, P = 0.049), anaemia (11.3% vs. 4.4%, P = 0.020), hepatotoxicity (4.8% vs. 1.1%, P = 0.021) and critical weight loss (85.5% vs. 56.6%, P<0.001) during radiotherapy. The OPC group had a significantly lower disease-free survival (DFS) (70.9% vs. 82.6%, P = 0.012), mainly as a result of a reduction in locoregional relapse-free survival (LRFS) (87.0%vs. 94.9%, P = 0.025). After stratification by T stage, the 5-year DFS in T3-4 patients were 82.0% and 68.8% in non-OPC and OPC groups, respectively (P = 0.022). Multivariate analyses indicated that OPC was a prognostic factor for LRFS and DFS. Conclusions OPC during radiotherapy may worsen the nutritional status of NPC patients according to weight loss and anaemia, leading to a negative impact on 5-year locoregional relapse-free survival and disease-specific survival. Further investigations are needed to explore whether prevention and treatment of OPC during radiotherapy will be useful. PMID:28797119

A retrospective study of 606 cases of nasopharyngeal carcinoma with or without oropharyngeal candidiasis during radiotherapy.

PubMed

Qiu, Wen-Ze; Ke, Liang-Ru; Xia, Wei-Xiong; Yang, Jing; Yu, Ya-Hui; Liang, Hu; Huang, Xin-Jun; Liu, Guo-Ying; Li, Wang-Zhong; Xiang, Yan-Qun; Guo, Xiang; Lv, Xing

2017-01-01

To evaluate the clinical characteristics, treatment-related toxicities and survival in patients with nasopharyngeal carcinoma (NPC) with or without oropharyngealcandidiasis (OPC) during radiotherapy. The current study was conducted with NPC patients undergoing radiotherapy at Sun Yat-Sen University Cancer Center between June 2011 and May 2012. A clinical diagnosis of candidiasis was determined on the basis of a positive potassium hydroxide (KOH) test and the presence of pseudomembranous (white) form of candidal overgrowth. The Cox proportional hazard regression model was used to test the association of OPC and related survival rates. Compared with the non-OPC group, the OPC group had significantly increased occurrence rates of grade 3-4 mucositis (14.5% vs. 7.4%, P = 0.049), anaemia (11.3% vs. 4.4%, P = 0.020), hepatotoxicity (4.8% vs. 1.1%, P = 0.021) and critical weight loss (85.5% vs. 56.6%, P<0.001) during radiotherapy. The OPC group had a significantly lower disease-free survival (DFS) (70.9% vs. 82.6%, P = 0.012), mainly as a result of a reduction in locoregional relapse-free survival (LRFS) (87.0%vs. 94.9%, P = 0.025). After stratification by T stage, the 5-year DFS in T3-4 patients were 82.0% and 68.8% in non-OPC and OPC groups, respectively (P = 0.022). Multivariate analyses indicated that OPC was a prognostic factor for LRFS and DFS. OPC during radiotherapy may worsen the nutritional status of NPC patients according to weight loss and anaemia, leading to a negative impact on 5-year locoregional relapse-free survival and disease-specific survival. Further investigations are needed to explore whether prevention and treatment of OPC during radiotherapy will be useful.

Potential Susceptibility Loci Identified for Renal Cell Carcinoma by Targeting Obesity-Related Genes.

PubMed

Shu, Xiang; Purdue, Mark P; Ye, Yuanqing; Tu, Huakang; Wood, Christopher G; Tannir, Nizar M; Wang, Zhaoming; Albanes, Demetrius; Gapstur, Susan M; Stevens, Victoria L; Rothman, Nathaniel; Chanock, Stephen J; Wu, Xifeng

2017-09-01

Background: Obesity is an established risk factor for renal cell carcinoma (RCC). Although genome-wide association studies (GWAS) of RCC have identified several susceptibility loci, additional variants might be missed due to the highly conservative selection. Methods: We conducted a multiphase study utilizing three independent genome-wide scans at MD Anderson Cancer Center (MDA RCC GWAS and MDA RCC OncoArray) and National Cancer Institute (NCI RCC GWAS), which consisted of a total of 3,530 cases and 5,714 controls, to investigate genetic variations in obesity-related genes and RCC risk. Results: In the discovery phase, 32,946 SNPs located at ±10 kb of 2,001 obesity-related genes were extracted from MDA RCC GWAS and analyzed using multivariable logistic regression. Proxies ( R 2 > 0.8) were searched or imputation was performed if SNPs were not directly genotyped in the validation sets. Twenty-one SNPs with P < 0.05 in both MDA RCC GWAS and NCI RCC GWAS were subsequently evaluated in MDA RCC OncoArray. In the overall meta-analysis, significant ( P < 0.05) associations with RCC risk were observed for SNP mapping to IL1RAPL2 [rs10521506-G: OR meta = 0.87 (0.81-0.93), P meta = 2.33 × 10 -5 ], PLIN2 [rs2229536-A: OR meta = 0.87 (0.81-0.93), P meta = 2.33 × 10 -5 ], SMAD3 [rs4601989-A: OR meta = 0.86 (0.80-0.93), P meta = 2.71 × 10 -4 ], MED13L [rs10850596-A: OR meta = 1.14 (1.07-1.23), P meta = 1.50 × 10 -4 ], and TSC1 [rs3761840-G: OR meta = 0.90 (0.85-0.97), P meta = 2.47 × 10 -3 ]. We did not observe any significant cis-expression quantitative trait loci effect for these SNPs in the TCGA KIRC data. Conclusions: Taken together, we found that genetic variation of obesity-related genes could influence RCC susceptibility. Impact: The five identified loci may provide new insights into disease etiology that reveal importance of obesity-related genes in RCC development. Cancer Epidemiol Biomarkers Prev; 26(9); 1436-42. ©2017 AACR . ©2017 American Association for

Concurrent chemoradiotherapy degrades the quality of life of patients with stage II nasopharyngeal carcinoma as compared to radiotherapy

PubMed Central

Pan, Xin-Bin; Huang, Shi-Ting; Chen, Kai-Hua; Jiang, Yan-Ming; Ma, Jia-Lin; Qu, Song; Li, Ling; Chen, Long; Zhu, Xiao-Dong

2017-01-01

The purpose of this study was to compare the quality of life (QoL) of stage II nasopharyngeal carcinoma (NPC) patients treated with radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT). In a cross-sectional study, these patients were treated with RT (n = 55) or CCRT (n = 51) between June 2008 and June 2013. For all subjects, disease-free survival was more than 3 years. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questions and the Head and Neck 35 (EORTC QLQ-H&N35) questions. RT had better outcomes than CCRT for global QoL, functional scales, symptom scales of fatigue and insomnia, financial problems, and weight gain. Survivors receiving 1 cycle of concurrent chemotherapy had worse QoL outcomes than survivors receiving 2 cycles of concurrent chemotherapy. Patients receiving 3 cycles of concurrent chemotherapy had the best QoL outcomes. Thus, CCRT adversely affects the QoL of patients with stage II NPC as compared to radiotherapy. PMID:28152511

MET inhibitor PHA-665752 suppresses the hepatocyte growth factor-induced cell proliferation and radioresistance in nasopharyngeal carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Tongxin; Li, Qi; Sun, Quanquan

2014-06-20

Highlights: • We demonstrated that irradiation induced MET overexpression and activation. • The aberrant MET signal mediated by HGF induced proliferation and radioresistance of NPC cells. • MET inhibitor PHA-665752 effectively suppressed HGF induced cell proliferation and radioresistance in NPC cells. • PHA-665752 suppressed the three downstream pathway of HGF/MET signal in a dose-dependent manner. - Abstract: Although ionizing radiation (IR) has provided considerable improvements in nasopharyngeal carcinoma (NPC), in subsets of patients, radioresistance is still a major problem in the treatment. In this study, we demonstrated that irradiation induced MET overexpression and activation, and the aberrant MET signal mediatedmore » by hepatocyte growth factor (HGF) induced radioresistance. We also found that MET inhibitor PHA-665752 effectively suppressed HGF induced cell proliferation and radioresistance in NPC cells. Further investigation indicated that PHA-665752 suppressed the phosphorylation of the Akt, ERK1/2, and STAT3 proteins in a dose-dependent manner. Our data indicated that the combination of IR with a MET inhibitor, such as PHA-665752, might be a promising therapeutic strategy for NPC.« less

Clinical Outcomes of 174 Nasopharyngeal Carcinoma Patients With Radiation-Induced Temporal Lobe Necrosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lam, Tai-Chung, E-mail: lamtaichung@gmail.com; Wong, Frank C.S.; Leung, To-Wai

Purpose: To retrospectively study the clinical outcomes of nasopharyngeal carcinoma patients with radiation-induced temporal lobe necrosis (TLN) treated with steroids, surgery, or observation only. Methods and Patients: We performed a retrospective analysis of 174 consecutive patients diagnosed with TLN between 1990 and 2008. Before 1998, symptomatic patients were treated with oral steroids, while asymptomatic patients were treated conservatively. After 1998, most symptomatic and asymptomatic patients with a large volume of necrosis were treated by intravenously pulsed-steroid therapy with a standardized protocol. We examined factors affecting grade 4 complication-free survival and overall survival. Outcomes of the three treatment groups, those receivingmore » conservative treatment, those receiving oral steroid, and those receiving intravenous pulse steroid, were compared. Results: The mean follow-up time was 115 months. Rates of grade 4 complication-free survival at 2 years and at 5 years after diagnosis of TLN were 72.2% and 54.1%, respectively. The 2-year and 5-year overall survival rates were 57.5% and 35.4%, respectively. Multivariate analysis revealed that being symptomatic at diagnosis (relative risk [RR], 4.5; p = 0.0001), re-irradiation of the nasopharynx (NP) (RR, 1.56; p = 0.008), salvage brachytherapy to the NP (RR, 1.75; p = 0.012), and a short latency period before the diagnosis of TLN (RR, 0.96, p < 0.0001) were independent prognosticators of poor grade 4 complication-free survival. Patients with all four factors had a 100% risk of developing grade 4 complications within 5 years; whereas if no factor was present, the risk was 12.5%. Intravenous pulse steroid therapy was associated with a higher clinical response rate compared with conventional steroid therapy (p < 0.0001); however, it did not affect complication-free survival in multivariate analysis. Conclusions: TLN patients with good prognosticators could be observed without active treatment

Surgical techniques in radiation induced temporal lobe necrosis in nasopharyngeal carcinoma patients.

PubMed

Alfotih, Gobran Taha Ahmed; Zheng, Mei Guang; Cai, Wang Qing; Xu, Xin Ke; Hu, Zhen; Li, Fang Cheng

2016-01-01

Radiation induced brain injury ranges from acute reversible edema to late, irreversible radiation necrosis. Radiation induced temporal lobe necrosis is associated with permanent neurological deficits and occasionally progresses to death. We present our experience with surgery on radiation induced temporal lobe necrosis (RTLN) in nasopharyngeal carcinoma (NPC) patients with special consideration of clinical presentation, surgical technique, and outcomes. This retrospective study includes 12 patients with RTLN treated by the senior author between January 2010 and December 2014. Patients initially sought medical treatment due to headache; other symptoms were hearing loss, visual deterioration, seizure, hemiparesis, vertigo, memory loss and agnosia. A temporal approach through a linear incision was performed for all cases. RTLN was found in one side in 7 patients, and bilaterally in 5. 4 patients underwent resection of necrotic tissue bilaterally and 8 patients on one side. No death occurred in this series of cases. There were no post-operative complications, except 1 patient who developed aseptic meningitis. All 12 patients were free from headache. No seizure occurred in patients with preoperative epilepsy. Other symptoms such as hemiparesis and vertigo improved in all patients. Memory loss, agnosia and hearing loss did not change post-operatively in all cases. The follow-up MR images demonstrated no recurrence of necrotic lesions in all 12 patients. Neurosurgical intervention through a temporal approach with linear incision is warranted in patients with radiation induced temporal lobe necrosis with significant symptoms and signs of increased intracranial pressure, minimum space occupying effect on imaging, or neurological deterioration despite conservative management. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Alteration of runt-related transcription factor 3 gene expression and biologic behavior of esophageal carcinoma TE-1 cells after 5-azacytidine intervention.

PubMed

Wang, Shuai; Liu, Hong; Akhtar, Javed; Chen, Hua-Xia; Wang, Zhou

2013-01-01

5-Azacytidine (5-azaC) was originally identified as an anticancer drug (NSC102876) which can cause hypomethylation of tumor suppressor genes. To assess its effects on runt-related transcription factor 3 (RUNX3), expression levels and the promoter methylation status of the RUNX3 gene were assessed. We also investigated alteration of biologic behavior of esophageal carcinoma TE-1 cells. MTT assays showed 5-azaC inhibited the proliferation of TE-1 cells in a time and dose-dependent way. Although other genes could be demethylated after 5-azaC intervention, we focused on RUNX3 gene in this study. The expression level of RUNX3 mRNA increased significantly in TE-1 cells after treatment with 5-azaC at hypotoxic levels. RT-PCR showed 5-azaC at 50 μM had the highest RUNX3-induction activity. Methylation-specific PCR indicated that 5-azaC induced RUNX3 expression through demethylation. Migration and invasion of TE-1 cells were inhibited by 5-azaC, along with growth of Eca109 xenografts in nude mice. In conclusion, we demonstrate that the RUNX3 gene can be reactivated by the demethylation reagent 5-azaC, which inhibits the proliferation, migration and invasion of esophageal carcinoma TE-1 cells.

Influence of CT contrast agent on dose calculation of intensity modulated radiation therapy plan for nasopharyngeal carcinoma.

PubMed

Lee, F K-H; Chan, C C-L; Law, C-K

2009-02-01

Contrast enhanced computed tomography (CECT) has been used for delineation of treatment target in radiotherapy. The different Hounsfield unit due to the injected contrast agent may affect radiation dose calculation. We investigated this effect on intensity modulated radiotherapy (IMRT) of nasopharyngeal carcinoma (NPC). Dose distributions of 15 IMRT plans were recalculated on CECT. Dose statistics for organs at risk (OAR) and treatment targets were recorded for the plain CT-calculated and CECT-calculated plans. Statistical significance of the differences was evaluated. Correlations were also tested, among magnitude of calculated dose difference, tumor size and level of enhancement contrast. Differences in nodal mean/median dose were statistically significant, but small (approximately 0.15 Gy for a 66 Gy prescription). In the vicinity of the carotid arteries, the difference in calculated dose was also statistically significant, but only with a mean of approximately 0.2 Gy. We did not observe any significant correlation between the difference in the calculated dose and the tumor size or level of enhancement. The results implied that the calculated dose difference was clinically insignificant and may be acceptable for IMRT planning.

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

PubMed Central

TAN, PINGQING; LIU, YONG; YU, CHANGYUN; SU, ZHONGWU; LI, GUO; ZHOU, XIAOJUAN; HUANG, DONGHAI; ZHANG, XIN; QIU, YUANZHENG; TIAN, YONGQUAN

2012-01-01

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

The apoptotic effect of Zoledronic acid on the nasopharyngeal carcinoma cells via ROS mediated chloride channel activation.

PubMed

Wang, Liang; Gao, Hong; Yang, Xiaoya; Liang, Xiechou; Tan, Qiuchan; Chen, Zhanru; Zhao, Chan; Gu, Zhuoyu; Yu, Meisheng; Zheng, Yanfang; Huang, Yanqing; Zhu, Linyan; Jacob, Tim J C; Wang, Liwei; Chen, Lixin

2018-06-08

Zoledronic acid (ZA), a third-generation bisphosphonate, has been applied for treatment of bone metastases caused by malignant tumors. Recent studies have found its anti-cancer effects on various tumor cells. One of the mechanisms of anti-cancer effects of ZA is induction of apoptosis. However, the mechanisms of ZA-induced apoptosis in tumor cells have not been clarified clearly. In this study, we investigated the roles of chloride channels in ZA-induced apoptosis in nasopharyngeal carcinoma CNE-2Z cells. Apoptosis and chloride current were induced by ZA and suppressed by chloride channel blockers. After the knockdown of ClC-3 expression by ClC-3 siRNA, ZA-induced chloride current and apoptosis were significantly suppressed, indicating that the chloride channel participated in ZA-induced apoptosis may be ClC-3. When reactive oxygen species (ROS) generation was inhibited by the antioxidant N-acetyl-L-cysteine (L-NAC), ZA-induced apoptosis and chloride current were blocked accordingly, suggesting that ZA induces apoptosis through promoting ROS production and subsequently activating chloride channel. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

MicroRNA-132 sensitizes nasopharyngeal carcinoma cells to cisplatin through regulation of forkhead box A1 protein.

PubMed

Li, Yun-Ling; Zhao, Yi-Gang; Chen, Bin; Li, Xiao-Feng

2016-12-01

Chemoresistance in cancer is one of the major hindrances in cisplatin (DPP) treatment for nasopharyngeal carcinoma (NPC). The mechanism of such resistance remains unknown. Therefore, the present study aimed to clarify the mechanism of DDP resistance and attempted to reduce chemoresistance. Here, we found that miR-132, as a tumor suppressor, was poorly expressed in a cisplatin resistant CNE2 cell line (CNE2/DPP) accompanied with a decreased expression of miR-132 and an increased expression of FOXA1 compared with the parental cells CNE2. Exogenous overexpression of miR-132 in CNE2/DPP could sensitize their reaction to the treatment of cisplatin. In addition, FOXA1 knockdown in CNE2/DPP cells increased the chemosensitivity to DPP, suggesting the dependence of FOXA1 regulation in miR-132 activity. Moreover, miR-132 can restore cisplatin treatment response in cisplatin-resistant xenografts in vivo, while FOXA1 protein levels were decreased. In summary, our results provide novel mechanistic insights into the role of miR-132/FOXA1 signaling in the cisplatin resistance of NPC cells. Targeting of miR-132 is a potential therapeutic approach for NPC.

Correlation of nasopharyngeal carcinoma with rare earth elements and the Epstein-Barr virus

PubMed Central

Zhang, Xiangmin; Zeng, Xiangfu; Liu, Lianbin; Lan, Xiaolin; Huang, Jing; Zeng, Hongxue; Li, Rong; Luo, Keqing; Wu, Wei; Zhou, Maohua; Li, Shaojin

2018-01-01

The concentration and distribution of rare earth elements (REE) in nasopharyngeal carcinoma (NPC) were measured to investigate connections with tumor size, lymph node metastasis, clinical stages, and Epstein-Barr virus (EBV) infection. There were 30 patients with NPC who met the criteria for inclusion in the present study. The EBV copy number, as well as the concentration and distribution of REE, was analyzed. EBV was detected using reverse transcription-polymerase chain reaction, with the concentrations of REE in NPC tissues measured using inductively coupled plasma-tandem mass spectrometry. The mean values were used when comparing concentrations of REE in NPC tissues as the standard deviation of this parameter was the lowest. Light REE had the highest concentrations, followed by medium, and then heavy REE. The concentrations of REE decreased with increasing tumor size and with the presence of lymph node metastasis. The concentrations of REE gradually increased between stage II and IVa, but markedly decreased thereafter. The elements that exhibited the greatest decreases were terbium, holmium and ytterbium. Furthermore, the concentrations of REE in NPC were not associated with sex (r=0.301, P=0.106) or age (r=−0.011, P=0.955), and were negatively associated with EBV (r=−0.744, P<0.001). By contrast, the EBV copy number increased alongside advancements in clinical stage. Changes in the concentrations of REE in NPC were more prominent for medium and heavy elements. Additionally, alterations in the concentrations of heavy REE may affect the occurrence and development of NPC. PMID:29541176

Correlation of nasopharyngeal carcinoma with rare earth elements and the Epstein-Barr virus.

PubMed

Zhang, Xiangmin; Zeng, Xiangfu; Liu, Lianbin; Lan, Xiaolin; Huang, Jing; Zeng, Hongxue; Li, Rong; Luo, Keqing; Wu, Wei; Zhou, Maohua; Li, Shaojin

2018-04-01

The concentration and distribution of rare earth elements (REE) in nasopharyngeal carcinoma (NPC) were measured to investigate connections with tumor size, lymph node metastasis, clinical stages, and Epstein-Barr virus (EBV) infection. There were 30 patients with NPC who met the criteria for inclusion in the present study. The EBV copy number, as well as the concentration and distribution of REE, was analyzed. EBV was detected using reverse transcription-polymerase chain reaction, with the concentrations of REE in NPC tissues measured using inductively coupled plasma-tandem mass spectrometry. The mean values were used when comparing concentrations of REE in NPC tissues as the standard deviation of this parameter was the lowest. Light REE had the highest concentrations, followed by medium, and then heavy REE. The concentrations of REE decreased with increasing tumor size and with the presence of lymph node metastasis. The concentrations of REE gradually increased between stage II and IVa, but markedly decreased thereafter. The elements that exhibited the greatest decreases were terbium, holmium and ytterbium. Furthermore, the concentrations of REE in NPC were not associated with sex (r=0.301, P=0.106) or age (r=-0.011, P=0.955), and were negatively associated with EBV (r=-0.744, P<0.001). By contrast, the EBV copy number increased alongside advancements in clinical stage. Changes in the concentrations of REE in NPC were more prominent for medium and heavy elements. Additionally, alterations in the concentrations of heavy REE may affect the occurrence and development of NPC.

Identification of key target genes and pathways in laryngeal carcinoma

PubMed Central

Liu, Feng; Du, Jintao; Liu, Jun; Wen, Bei

2016-01-01

The purpose of the present study was to screen the key genes associated with laryngeal carcinoma and to investigate the molecular mechanism of laryngeal carcinoma progression. The gene expression profile of GSE10935 [Gene Expression Omnibus (GEO) accession number], including 12 specimens from laryngeal papillomas and 12 specimens from normal laryngeal epithelia controls, was downloaded from the GEO database. Differentially expressed genes (DEGs) were screened in laryngeal papillomas compared with normal controls using Limma package in R language, followed by Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Furthermore, the protein-protein interaction (PPI) network of DEGs was constructed using Cytoscape software and modules were analyzed using MCODE plugin from the PPI network. Furthermore, significant biological pathway regions (sub-pathway) were identified by using iSubpathwayMiner analysis. A total of 67 DEGs were identified, including 27 up-regulated genes and 40 down-regulated genes and they were involved in different GO terms and pathways. PPI network analysis revealed that Ras association (RalGDS/AF-6) domain family member 1 (RASSF1) was a hub protein. The sub-pathway analysis identified 9 significantly enriched sub-pathways, including glycolysis/gluconeogenesis and nitrogen metabolism. Genes such as phosphoglycerate kinase 1 (PGK1), carbonic anhydrase II (CA2), and carbonic anhydrase XII (CA12) whose node degrees were >10 were identified in the disease risk sub-pathway. Genes in the sub-pathway, such as RASSF1, PGK1, CA2 and CA12 were presumed to serve critical roles in laryngeal carcinoma. The present study identified DEGs and their sub-pathways in the disease, which may serve as potential targets for treatment of laryngeal carcinoma. PMID:27446427

Leptin acts on neoplastic behavior and expression levels of genes related to hypoxia, angiogenesis, and invasiveness in oral squamous cell carcinoma.

PubMed

Sobrinho Santos, Eliane Macedo; Guimarães, Talita Antunes; Santos, Hércules Otacílio; Cangussu, Lilian Mendes Borborema; de Jesus, Sabrina Ferreira; Fraga, Carlos Alberto de Carvalho; Cardoso, Claudio Marcelo; Santos, Sérgio Henrique Souza; de Paula, Alfredo Maurício Batista; Gomez, Ricardo Santiago; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

2017-05-01

Leptin, one of the main hormones controlling energy homeostasis, has been associated with different cancer types. In oral cancer, its effect is not well understood. We investigated, through in vitro and in vivo assays, whether leptin can affect the neoplastic behavior of oral squamous cell carcinoma. Expression of genes possibly linked to the leptin pathway was assessed in leptin-treated oral squamous cell carcinoma cells and also in tissue samples of oral squamous cell carcinoma and oral mucosa, including leptin, leptin receptor, hypoxia-inducible factor 1-alpha, E-cadherin, matrix metalloproteinase-2, matrix metalloproteinase-9, Col1A1, Ki67, and mir-210. Leptin treatment favored higher rates of cell proliferation and migration, and reduced apoptosis. Accordingly, leptin-treated oral squamous cell carcinoma cells show decreased messenger RNA caspase-3 expression, and increased levels of E-cadherin, Col1A1, matrix metalloproteinase-2, matrix metalloproteinase-9, and mir-210. In tissue samples, hypoxia-inducible factor 1-alpha messenger RNA and protein expression of leptin and leptin receptor were high in oral squamous cell carcinoma cases. Serum leptin levels were increased in first clinical stages of the disease. In animal model, oral squamous cell carcinoma-induced mice show higher leptin receptor expression, and serum leptin level was increased in dysplasia group. Our findings suggest that leptin seems to exert an effect on oral squamous cell carcinoma cells behavior and also on molecular markers related to cell proliferation, migration, and tumor angiogenesis.

A pooled analysis of the IL-10-1082 A/G polymorphism and the nasopharyngeal carcinoma susceptibility.

PubMed

Ma, Liping; Li, Shan; Lu, Yu; Zhang, Xiaolian; Zhao, Jiangyang; Qin, Xue

2016-04-01

It has been reported that IL-10-1082 A/G polymorphism might influence the transcription and secretion of IL10 and tumor development. While many studies have been conducted to investigate the association between IL-10-1082 A/G polymorphism and risk of nasopharyngeal carcinoma (NPC) in various populations, the results of these studies are still controversial. We aimed to explore this relationship through a cumulative meta-analysis. A search of the literature was performed using the Cochrane Library, PubMed, and EMBASE databases. The odds ratio (OR) and corresponding 95 % confidence interval (CI) were calculated to assess this possible association. Six studies were included in the study. The meta-analysis reveals a significant effect in the allelic model (G vs. A: OR 1.516, 95 % CI 1.077-2.133, P heterogeneity = 0.003), dominant model (AG + GG vs. AA: OR = 1.770, 95 % CI 1.415-2.212, P heterogeneity = 0.169), and co-dominant model (AG vs. AA: OR = 1.747, 95 % CI 1.377-2.216, P heterogeneity = 0.491). Similarly, in the stratified analyses, significant effects were reported in studies of Asian populations. Our meta-analysis results suggest that the IL-10-1082 A/G variant is associated with increased risk of NPC in Asian populations.

[Mechanism of apoptosis of nasopharyngeal carcinoma cells induced by polysaccharides extracts from Hedyotic diffusa].

PubMed

Jing Yan; Kang Min; Liu Jin; Li Jingyu; Tang Anzhou

2015-04-01

To explore the proliferation inhibition and apoptosis of polysaccharides extracts from polysaccharides extracts from Hedyotic diffusa (PEHD) on Human Nasopharyngeal Carcinoma (NPC)cell line CNE2 cells in vitro. CNE2 cells treated with various concentrations of PEHD were detected by MTT assay at 24 h, 48 h, and 72 h. The apoptotic cells were analyzed by flow cytometry with Annexin V/PI staining. The expression levels of Bax, Bcl-2 and caspase-3 protein were examined by Western blotting method. The growth of CNE2 cells were suppressed after treatment with PEHD (P < 0.05), MTT assay showed that the highest cell inhibition rate reached to 76.5%, the inhibition in the doses from 2 to 6 mg/ml showed dose-and-time-dependent. The percent of apoptosis in 4 and 6 mg/ml PEHD treatment groups for 48 h were 31.32%, 46.28%, respectively, and significantly higher than that in control groups, 4.86% (P < 0.01). After the cells being treated with PEHD for 48 h, the expression of Bax and caspase-3 protein increased, and the expression of Bcl-2 protein decreased gradually. PEHD could inhibited the growth of CNE2 cells and was dose-and-time-dependent, the mechanism may involve induction of cell apoptosis, which was associated with the activation of Bax and caspase-3 protein and the down-regulation of Bcl-2 protein expression.

Berberine sensitizes nasopharyngeal carcinoma cells to radiation through inhibition of Sp1 and EMT.

PubMed

Wang, Jun; Kang, Min; Wen, Qin; Qin, Yu-Tao; Wei, Zhu-Xin; Xiao, Jing-Jian; Wang, Ren-Sheng

2017-04-01

Nasopharyngeal carcinoma (NPC) is a tumor of epithelial origin with radiotherapy as its standard treatment. However, radioresistance remains a critical issue in the treatment of NPC. This study aimed to investigate the effect of berberine on the proliferation, cell cycle regulation, apoptosis, radioresistance of NPC cells and whether specificity protein 1 (Sp1) is a functional target of berberine. Our results showed that treatment with berberine reduced the proliferation and viability of CNE-2 cells in a dose- and time‑dependent manner. Berberine induced cell cycle arrest in the G0/G1 phase and apoptosis. In CNE-2 cells exposed to gamma‑ray irradiation, berberine reduced cell viability at various concentrations (25, 50, 75 and 100 µmol/l). Berberine significantly decreased mRNA and protein expression of Sp1 in the CNE-2 cells. Mithramycin A, a selective Sp1 inhibitor, enhanced the radiosensitivity and the rate of apoptosis in the CNE-2 cells. Berberine inhibited transforming growth factor-β (TGF-β)-induced tumor invasion and suppressed epithelial-to-mesenchymal transition (EMT) process, as evidenced by increased E-cadherin and decreased vimentin proteins. Sp1 may be required for the TGF-β1-induced invasion and EMT by berberine. In conclusion, berberine demonstrated the ability to suppress proliferation, induce cell cycle arrest and apoptosis, and enhance radiosensitivity of the CNE-2 NPC cells. Sp1 may be a target of berberine which is decreased during the radiosensitization of berberine.

Dosimetric Comparison of Intensity-Modulated Stereotactic Radiotherapy With Other Stereotactic Techniques for Locally Recurrent Nasopharyngeal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kung, Shiris Wai Sum; Wu, Vincent Wing Cheung; Kam, Michael Koon Ming, E-mail: kamkm@yahoo.co

2011-01-01

Purpose: Locally recurrent nasopharyngeal carcinoma (NPC) patients can be salvaged by reirradiation with a substantial degree of radiation-related complications. Stereotactic radiotherapy (SRT) is widely used in this regard because of its rapid dose falloff and high geometric precision. The aim of this study was to examine whether the newly developed intensity-modulated stereotactic radiotherapy (IMSRT) has any dosimetric advantages over three other stereotactic techniques, including circular arc (CARC), static conformal beam (SmMLC), and dynamic conformal arc (mARC), in treating locally recurrent NPC. Methods and Materials: Computed tomography images of 32 patients with locally recurrent NPC, previously treated with SRT, were retrievedmore » from the stereotactic planning system for contouring and computing treatment plans. Treatment planning of each patient was performed for the four treatment techniques: CARC, SmMLC, mARC, and IMSRT. The conformity index (CI) and homogeneity index (HI) of the planning target volume (PTV) and doses to the organs at risk (OARs) and normal tissue were compared. Results: All four techniques delivered adequate doses to the PTV. IMSRT, SmMLC, and mARC delivered reasonably conformal and homogenous dose to the PTV (CI <1.47, HI <0.53), but not for CARC (p < 0.05). IMSRT presented with the smallest CI (1.37) and HI (0.40). Among the four techniques, IMSRT spared the greatest number of OARs, namely brainstem, temporal lobes, optic chiasm, and optic nerve, and had the smallest normal tissue volume in the low-dose region. Conclusion: Based on the dosimetric comparison, IMSRT was optimal for locally recurrent NPC by delivering a conformal and homogenous dose to the PTV while sparing OARs.« less

Evaluation and Integration of Genetic Signature for Prediction Risk of Nasopharyngeal Carcinoma in Southern China

PubMed Central

Winkler, Cheryl A.; Li, Ji; Guan, Li; Tang, Minzhong; Liao, Jian; Deng, Hong; de Thé, Guy; Zeng, Yi; O'Brien, Stephen J.

2014-01-01

Genetic factors, as well as environmental factors, play a role in development of nasopharyngeal carcinoma (NPC). A number of single nucleotide polymorphisms (SNPs) have been reported to be associated with NPC. To confirm these genetic associations with NPC, two independent case-control studies from Southern China comprising 1166 NPC cases and 2340 controls were conducted. Seven SNPs in ITGA9 at 3p21.3 and 9 SNPs within the 6p21.3 HLA region were genotyped. To explore the potential clinical application of these genetic markers in NPC, we further evaluate the predictive/diagnostic role of significant SNPs by calculating the area under the curve (AUC). Results. The reported associations between ITGA9 variants and NPC were not replicated. Multiple loci of GABBR1, HLA-F, HLA-A, and HCG9 were statistically significant in both cohorts (P combined range from 5.96 × 10−17 to 0.02). We show for the first time that these factors influence NPC development independent of environmental risk factors. This study also indicated that the SNP alone cannot serve as a predictive/diagnostic marker for NPC. Integrating the most significant SNP with IgA antibodies status to EBV, which is presently used as screening/diagnostic marker for NPC in Chinese populations, did not improve the AUC estimate for diagnosis of NPC. PMID:25180181

Evaluation and integration of genetic signature for prediction risk of nasopharyngeal carcinoma in Southern China.

PubMed

Guo, Xiuchan; Winkler, Cheryl A; Li, Ji; Guan, Li; Tang, Minzhong; Liao, Jian; Deng, Hong; de Thé, Guy; Zeng, Yi; O'Brien, Stephen J

2014-01-01

Genetic factors, as well as environmental factors, play a role in development of nasopharyngeal carcinoma (NPC). A number of single nucleotide polymorphisms (SNPs) have been reported to be associated with NPC. To confirm these genetic associations with NPC, two independent case-control studies from Southern China comprising 1166 NPC cases and 2340 controls were conducted. Seven SNPs in ITGA9 at 3p21.3 and 9 SNPs within the 6p21.3 HLA region were genotyped. To explore the potential clinical application of these genetic markers in NPC, we further evaluate the predictive/diagnostic role of significant SNPs by calculating the area under the curve (AUC). The reported associations between ITGA9 variants and NPC were not replicated. Multiple loci of GABBR1, HLA-F, HLA-A, and HCG9 were statistically significant in both cohorts (P(combined) range from 5.96 × 10(-17) to 0.02). We show for the first time that these factors influence NPC development independent of environmental risk factors. This study also indicated that the SNP alone cannot serve as a predictive/diagnostic marker for NPC. Integrating the most significant SNP with IgA antibodies status to EBV, which is presently used as screening/diagnostic marker for NPC in Chinese populations, did not improve the AUC estimate for diagnosis of NPC.

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

PubMed

Li, Feng; Li, Maoyu; Xiao, Zhiqiang; Zhang, Pengfei; Li, Jianling; Chen, Zhuchu

2006-01-11

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. 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. 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/.

Clinicopathologic Characteristics and Prognosis of Tongue Squamous Cell Carcinoma in Patients with and without a History of Radiation for Nasopharyngeal Carcinoma: A Matched Case-Control Study.

PubMed

Zhang, Peng; Zhang, Li; Liu, Hui; Zhao, Lei; Li, Yong; Shen, Jing-Xian; Liu, Qing; Liu, Meng-Zhong; Xi, Mian

2017-07-01

Previous studies reported an association between an increased risk of tongue cancer and radiation treatment for nasopharyngeal carcinoma (NPC). This study compared the clinicopathologic characteristics and outcomes of tongue squamous cell carcinoma (TSCC) in patients with and without a history of radiotherapy for NPC. From 1965 to 2009, a total of 73 patients were diagnosed with TSCC with a history of radiotherapy for NPC. The patients were matched in a 1:3 ratio with patients with sporadic TSCC according to age, sex, and year of the TSCC diagnosis. The primary endpoint was the overall survival. The median interval from NPC to TSCC was 82 months. The NPC survivors were more likely to be diagnosed with a more advanced T classification, less likely to have lymph node involvement, and more likely to have the tumor located in the dorsum of the tongue than sporadic TSCC. Regarding the histologic characteristics, the NPC survivors were more likely to have a weak lymphocytic host response, low tumor budding, and low risk of a worse pattern of invasion. The sporadic TSCC patients had a better overall survival (hazard ratio, 0.690; p=0.033) than the NPC survivors. In competing risks analysis, the cumulative incidence functions for the competing event (documented non-tongue cancer death) were significantly higher in the NPC survivors (Gray's test, p=0.001). TSCC patients with a history of radiotherapy for NPC appear to have particular clinicopathologic features, a poorer survival, and are more likely to die from non-tongue cancer causes than those with sporadic TSCC.

Sibship size, birth order and risk of nasopharyngeal carcinoma and infectious mononucleosis: a nationwide study in Sweden.

PubMed

Liu, Zhiwei; Fang, Fang; Chang, Ellen T; Adami, Hans-Olov; Ye, Weimin

2016-06-01

The aetiology of nasopharyngeal carcinoma (NPC) remains enigmatic in endemic and non-endemic areas. Early-life infection with Epstein-Barr virus (EBV) may predispose to NPC development, whereas delayed primary infection with EBV may cause infectious mononucleosis (IM). We used Swedish population and health registers to investigate whether potential indicators of early EBV infection, such as birth order, sibship size, maternal age and paternal age, are related to the subsequent risks for NPC and IM. We conducted two nested case-control studies, one for each health outcome, based on 251 NPC case patients, 11 314 IM case patients and five population control subjects per case matched by birth year and sex. We used conditional logistic regression modelling to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for NPC and IM. The multivariate-adjusted ORs of developing NPC increased with number of siblings; the ORs associated with having one, two and three or more siblings, compared with none, were 1.59 (95% CI = 0.97, 2.62), 1.94 (95% CI = 1.17, 3.22), and 2.03 (95% CI = 1.23, 3.35), respectively (Ptrend = 0.006). This increased risk of NPC was explained mainly by having older rather than younger siblings. In contrast, lower risks of IM were observed among individuals with an increasing number of older siblings, younger siblings and total siblings. Early-life social environment, possibly related to EBV infection, contributes to NPC pathogenesis in non-endemic areas. This hypothesis is further supported by the clearly contrasting findings between NPC and IM. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Lymphoepithelial carcinoma of the nasal cavity mimicking juvenile angiofibroma.

PubMed

Kim, Young Hyo; Kim, Beom Joon; Jang, Tae Young

2012-10-01

Juvenile angiofibroma, nasopharyngeal carcinoma (NPC) and lymphoepithelial carcinoma of the nasal cavity (LEC NC) all could be found as a hyper-vascular mass in the nasopharynx area. Performing biopsy for histopathologic confirmation is necessary in the case of NPC or LEC NC but could be fatal in the case of angiofibroma. In our case, a 21-year-old male who was suffering from unilateral nasal stuffiness and frequent epistaxis had a mass with an easily bleeding tendency in his right nasal cavity. Juvenile angiofibroma was suspected by clinical and radiologic examinations. We performed preoperative angiography and the feeding vessel from the right internal maxillary artery was obliterated with polyvinyl alcohol nanoparticle. The mass was completely removed endoscopically, and there was profound hemorrhage in spite of the preoperative embolization. The mass turned out to be LEC NC by postoperative histopathologic examination. To avoid this misdiagnosis, the authors suggest that we should perform biopsy under rigid endoscopy 24h after angiographic embolization. If the result of frozen biopsy is juvenile angiofibroma, we could perform surgery another 24h later. If the result is nasopharyngeal carcinoma or LEC NC, we could avoid unnecessary surgical removal and perform radiotherapy. In terms of treatment strategies, we suggest endoscopic removal of gross tumor and postoperative combination of chemoradiotherapy as the more curative regimen with less complications related with radiotherapy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Activation of RAS family genes in urothelial carcinoma.

PubMed

Boulalas, I; Zaravinos, A; Karyotis, I; Delakas, D; Spandidos, D A

2009-05-01

Bladder cancer is the fifth most common malignancy in men in Western society. We determined RAS codon 12 and 13 point mutations and evaluated mRNA expression levels in transitional cell carcinoma cases. Samples from 30 human bladder cancers and 30 normal tissues were analyzed by polymerase chain reaction/restriction fragment length polymorphism and direct sequencing to determine the occurrence of mutations in codons 12 and 13 of RAS family genes. Moreover, we used real-time reverse transcriptase-polymerase chain reaction to evaluate the expression profile of RAS genes in bladder cancer specimens compared to that in adjacent normal tissues. Overall H-RAS mutations in codon 12 were observed in 9 tumor samples (30%). Two of the 9 patients (22%) had invasive bladder cancer and 7 (77%) had noninvasive bladder cancer. One H-RAS mutation (11%) was homozygous and the remaining 89% were heterozygous. All samples were WT for K and N-RAS oncogenes. Moreover, 23 of 30 samples (77%) showed over expression in at least 1 RAS family gene compared to adjacent normal tissue. K and N-RAS had the highest levels of over expression in bladder cancer specimens (50%), whereas 27% of transitional cell carcinomas demonstrated H-RAS over expression relative to paired normal tissues. Our results underline the importance of H-RAS activation in human bladder cancer by codon 12 mutations. Moreover, they provide evidence that increased expression of all 3 RAS genes is a common event in bladder cancer that is associated with disease development.

HNdb: an integrated database of gene and protein information on head and neck squamous cell carcinoma

PubMed Central

Henrique, Tiago; José Freitas da Silveira, Nelson; Henrique Cunha Volpato, Arthur; Mioto, Mayra Mataruco; Carolina Buzzo Stefanini, Ana; Bachir Fares, Adil; Gustavo da Silva Castro Andrade, João; Masson, Carolina; Verónica Mendoza López, Rossana; Daumas Nunes, Fabio; Paulo Kowalski, Luis; Severino, Patricia; Tajara, Eloiza Helena

2016-01-01

The total amount of scientific literature has grown rapidly in recent years. Specifically, there are several million citations in the field of cancer. This makes it difficult, if not impossible, to manually retrieve relevant information on the mechanisms that govern tumor behavior or the neoplastic process. Furthermore, cancer is a complex disease or, more accurately, a set of diseases. The heterogeneity that permeates many tumors is particularly evident in head and neck (HN) cancer, one of the most common types of cancer worldwide. In this study, we present HNdb, a free database that aims to provide a unified and comprehensive resource of information on genes and proteins involved in HN squamous cell carcinoma, covering data on genomics, transcriptomics, proteomics, literature citations and also cross-references of external databases. Different literature searches of MEDLINE abstracts were performed using specific Medical Subject Headings (MeSH terms) for oral, oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinomas. A curated gene-to-publication assignment yielded a total of 1370 genes related to HN cancer. The diversity of results allowed identifying novel and mostly unexplored gene associations, revealing, for example, that processes linked to response to steroid hormone stimulus are significantly enriched in genes related to HN carcinomas. Thus, our database expands the possibilities for gene networks investigation, providing potential hypothesis to be tested. Database URL: http://www.gencapo.famerp.br/hndb PMID:27013077

A GWAS Meta-analysis and Replication Study Identifies a Novel Locus within CLPTM1L/TERT Associated with Nasopharyngeal Carcinoma in Individuals of Chinese Ancestry.

PubMed

Bei, Jin-Xin; Su, Wen-Hui; Ng, Ching-Ching; Yu, Kai; Chin, Yoon-Ming; Lou, Pei-Jen; Hsu, Wan-Lun; McKay, James D; Chen, Chien-Jen; Chang, Yu-Sun; Chen, Li-Zhen; Chen, Ming-Yuan; Cui, Qian; Feng, Fu-Tuo; Feng, Qi-Shen; Guo, Yun-Miao; Jia, Wei-Hua; Khoo, Alan Soo-Beng; Liu, Wen-Sheng; Mo, Hao-Yuan; Pua, Kin-Choo; Teo, Soo-Hwang; Tse, Ka-Po; Xia, Yun-Fei; Zhang, Hongxin; Zhou, Gang-Qiao; Liu, Jian-Jun; Zeng, Yi-Xin; Hildesheim, Allan

2016-01-01

Genetic loci within the major histocompatibility complex (MHC) have been associated with nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer, in several GWAS. Results outside this region have varied. We conducted a meta-analysis of four NPC GWAS among Chinese individuals (2,152 cases; 3,740 controls). Forty-three noteworthy findings outside the MHC region were identified and targeted for replication in a pooled analysis of four independent case-control studies across three regions in Asia (4,716 cases; 5,379 controls). A meta-analysis that combined results from the initial GWA and replication studies was performed. In the combined meta-analysis, rs31489, located within the CLPTM1L/TERT region on chromosome 5p15.33, was strongly associated with NPC (OR = 0.81; P value 6.3 × 10(-13)). Our results also provide support for associations reported from published NPC GWAS-rs6774494 (P = 1.5 × 10(-12); located in the MECOM gene region), rs9510787 (P = 5.0 × 10(-10); located in the TNFRSF19 gene region), and rs1412829/rs4977756/rs1063192 (P = 2.8 × 10(-8), P = 7.0 × 10(-7), and P = 8.4 × 10(-7), respectively; located in the CDKN2A/B gene region). We have identified a novel association between genetic variation in the CLPTM1L/TERT region and NPC. Supporting our finding, rs31489 and other SNPs in this region have been reported to be associated with multiple cancer sites, candidate-based studies have reported associations between polymorphisms in this region and NPC, the TERT gene has been shown to be important for telomere maintenance and has been reported to be overexpressed in NPC, and an EBV protein expressed in NPC (LMP1) has been reported to modulate TERT expression/telomerase activity. Our finding suggests that factors involved in telomere length maintenance are involved in NPC pathogenesis. ©2015 American Association for Cancer Research.

A GWAS meta-analysis and replication study identifies a novel locus within CLPTM1L/TERT associated with nasopharyngeal carcinoma in individuals of Chinese ancestry

PubMed Central

Yu, Kai; Chin, Yoon-Ming; Lou, Pei-Jen; Hsu, Wan-Lun; McKay, James D.; Chen, Chien-Jen; Chang, Yu-Sun; Chen, Li-Zhen; Chen, Ming-Yuan; Cui, Qian; Feng, Fu-Tuo; Feng, Qi-Shen; Guo, Yun-Miao; Jia, Wei-Hua; Khoo, Alan Soo-Beng; Liu, Wen-Sheng; Mo, Hao-Yuan; Pua, Kin-Choo; Teo, Soo-Hwang; Tse, Ka-Po; Xia, Yun-Fei; Zhang, Hongxin; Zhou, Gang-Qiao; Liu, Jian-Jun; Zeng, Yi-Xin; Hildesheim, Allan

2015-01-01

Background Genetic loci within the major histocompatibility complex (MHC) have been associated with nasopharyngeal carcinoma (NPC), an Epstein-Barr virus (EBV)-associated cancer, in several GWAS. Results outside this region have varied. Methods We conducted a meta-analysis of four NPC GWAS among Chinese individuals (2,152 cases;3,740 controls). 43 noteworthy findings outside the MHC region were identified and targeted for replication in a pooled analysis of 4 independent case-control studies across 3 regions in Asia (4,716 cases;5,379 controls). A meta-analysis that combined results from the initial GWA and replication studies was performed. Results In the combined meta-analysis, rs31489, located within the CLPTM1L/TERT region on chromosome 5p15.33, was strongly associated with NPC (OR=0.81;p-value 6.3*10−13). Our results also provide support for associations reported from published NPC GWAS - rs6774494 (p = 1.5*10−12;located in the MECOM gene region), rs9510787 (p = 5.0*10−10;located in the TNFRSF19 gene region), and rs1412829/rs4977756/rs1063192 (p = 2.8*10−8,p = 7.0*10−7,and p = 8.4*10−7 respectively;located in the CDKN2A/B gene region). Conclusion We have identified a novel association between genetic variation in the CLPTM1L/TERT region and NPC. Supporting our finding, rs31489 and other SNPs in this region have been reported to be associated with multiple cancer sites, candidate-based studies have reported associations between polymorphisms in this region and NPC, the TERT gene is important for telomere maintenance and has been reported to be over-expressed in NPC, and an EBV protein expressed in NPC (LMP1) modulates TERT expression/telomerase activity. Impact Our finding suggests that factors involved in telomere length maintenance are involved in NPC pathogenesis. PMID:26545403

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, YanLing; Chen, Xin; Ren, PeiRong

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); andmore » (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

3-Deazaneplanocin A suppresses aggressive phenotype-related gene expression in an oral squamous cell carcinoma cell line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hatta, Mitsutoki, E-mail: hatta@college.fdcnet.ac.jp; Naganuma, Kaori; Kato, Kenichi

In tumor tissues, alterations of gene expression caused by aberrant epigenetic modifications confer phenotypic diversity on malignant cells. Although 3-deazaneplanocin A (DZNep) has been shown to reactivate tumor suppressor genes in several cancer cells, it remains unclear whether DZNep attenuates the malignant phenotypes of oral squamous cell carcinoma (OSCC) cells. In this study, we investigated the effect of DZNep on the expression of genes related to aggressive phenotypes, such as epithelial–mesenchymal transition, in OSCC cells. We found that DZNep reduced the cellular levels of polycomb group proteins (EZH2, SUZ12, BMI1, and RING1A) and the associated trimethylation of Lys27 on histonemore » H3 and monoubiquitination of Lys119 on histone H2A in the poorly differentiated OSCC cell line SAS. Immunocytochemical staining demonstrated that DZNep induced the reorganization of filamentous actin and the membrane localization of E-cadherin associated with cell–cell adhesions. We also found an inhibitory effect of DZNep on cell proliferation using a WST assay. Finally, quantitative RT-PCR analysis demonstrated that genes involved in the aggressive phenotypes (TWIST2, EGFR, ACTA2, TGFB1, WNT5B, and APLIN) were down-regulated, whereas epithelial phenotype genes (CDH1, CLDN4, IVL, and TGM1) were up-regulated in SAS cells treated with DZNep. Collectively, our findings suggest that DZNep reverses the aggressive characteristics of OSCC cells through the dynamic regulation of epithelial plasticity via the reprogramming of gene expression patterns. - Highlights: • DZNep reduced PcG proteins and associated histone modifications in OSCC cells. • DZNep enhanced cell–cell adhesion indicative of epithelial phenotype in OSCC cells. • DZNep suppressed the aggressive phenotype-related gene expression in OSCC cells. • DZNep activated the gene expression of epithelial markers in OSCC cells.« less

Expression of protease-activated receptor-2 (PAR-2) in patients with nasopharyngeal carcinoma: correlation with clinicopathological features and prognosis.

PubMed

Li, Zhi; Bian, Li-Juan; Li, Yang; Liang, Ying-Jie; Liang, Hui-Zhen

2009-01-01

We aimed at determining whether the expression of protease-activated receptor 2 (PAR-2) is involved in the progression of nasopharyngeal carcinoma (NPC) and correlated with latent membrane protein 1 (LMP-1), matrix metalloproteinases-9 (MMP9), and angiogenesis of tumor. PAR-2, LMP-1, and MMP9 expressions were detected in 57 biopsies of primary NPC by immunohistochemistry. The presence of Epstein-Barr virus (EBV) was determined using EBER in situ hybridization, and intratumoral microvessels were highlighted by staining endothelial cells for anti-CD34. The correlations with immunostainings and clinicopathological factors, as well as the follow-up data of patients, were analyzed statistically. Strong expression of PAR-2 in 61.4% (35/57) of the biopsies was correlated with extensive lymph node metastasis and advanced stage of NPC. The patients with PAR-2/LMP-1 or PAR-2/MMP9 dual high-expression tumors had a significant worse prognosis than those with single protein high expression and dual low or negative expression tumors (P=0.013 and 0.004, respectively). Angiogenesis in the tumor is related to overall survival of NPC patients (P=0.001), and exhibits strong PAR-2 expression or LMP-1 expression in tumors associated with increased intratumoral microvessel density (P=0.026 and 0.006, respectively). PAR-2 is a possible mediator cooperating with LMP-1 and MMP9 to influence the progression of NPC by inducing angiogenesis and promoting lymph node metastasis.

Regulation of tumour related genes by dynamic epigenetic alteration at enhancer regions in gastric epithelial cells infected by Epstein-Barr virus.

PubMed

Okabe, Atsushi; Funata, Sayaka; Matsusaka, Keisuke; Namba, Hiroe; Fukuyo, Masaki; Rahmutulla, Bahityar; Oshima, Motohiko; Iwama, Atsushi; Fukayama, Masashi; Kaneda, Atsushi

2017-08-11

Epstein-Barr virus (EBV) infection is associated with tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancer. We previously showed that EBV(+) gastric cancer presents an extremely high-methylation epigenotype and this aberrant DNA methylation causes silencing of multiple tumour suppressor genes. However, the mechanisms that drive EBV infection-mediated tumorigenesis, including other epigenomic alteration, remain unclear. We analysed epigenetic alterations induced by EBV infection especially at enhancer regions, to elucidate their contribution to tumorigenesis. We performed ChIP sequencing on H3K4me3, H3K4me1, H3K27ac, H3K27me3, and H3K9me3 in gastric epithelial cells infected or not with EBV. We showed that repressive marks were redistributed after EBV infection, resulting in aberrant enhancer activation and repression. Enhancer dysfunction led to the activation of pathways related to cancer hallmarks (e.g., resisting cell death, disrupting cellular energetics, inducing invasion, evading growth suppressors, sustaining proliferative signalling, angiogenesis, and tumour-promoting inflammation) and inactivation of tumour suppressive pathways. Deregulation of cancer-related genes in EBV-infected gastric epithelial cells was also observed in clinical EBV(+) gastric cancer specimens. Our analysis showed that epigenetic alteration associated with EBV-infection may contribute to tumorigenesis through enhancer activation and repression.

A qualitative signature for early diagnosis of hepatocellular carcinoma based on relative expression orderings.

PubMed

Ao, Lu; Zhang, Zimei; Guan, Qingzhou; Guo, Yating; Guo, You; Zhang, Jiahui; Lv, Xingwei; Huang, Haiyan; Zhang, Huarong; Wang, Xianlong; Guo, Zheng

2018-04-23

Currently, using biopsy specimens to confirm suspicious liver lesions of early hepatocellular carcinoma are not entirely reliable because of insufficient sampling amount and inaccurate sampling location. It is necessary to develop a signature to aid early hepatocellular carcinoma diagnosis using biopsy specimens even when the sampling location is inaccurate. Based on the within-sample relative expression orderings of gene pairs, we identified a simple qualitative signature to distinguish both hepatocellular carcinoma and adjacent non-tumour tissues from cirrhosis tissues of non-hepatocellular carcinoma patients. A signature consisting of 19 gene pairs was identified in the training data sets and validated in 2 large collections of samples from biopsy and surgical resection specimens. For biopsy specimens, 95.7% of 141 hepatocellular carcinoma tissues and all (100%) of 108 cirrhosis tissues of non-hepatocellular carcinoma patients were correctly classified. Especially, all (100%) of 60 hepatocellular carcinoma adjacent normal tissues and 77.5% of 80 hepatocellular carcinoma adjacent cirrhosis tissues were classified to hepatocellular carcinoma. For surgical resection specimens, 99.7% of 733 hepatocellular carcinoma specimens were correctly classified to hepatocellular carcinoma, while 96.1% of 254 hepatocellular carcinoma adjacent cirrhosis tissues and 95.9% of 538 hepatocellular carcinoma adjacent normal tissues were classified to hepatocellular carcinoma. In contrast, 17.0% of 47 cirrhosis from non-hepatocellular carcinoma patients waiting for liver transplantation were classified to hepatocellular carcinoma, indicating that some patients with long-lasting cirrhosis could have already gained hepatocellular carcinoma characteristics. The signature can distinguish both hepatocellular carcinoma tissues and tumour-adjacent tissues from cirrhosis tissues of non-hepatocellular carcinoma patients even using inaccurately sampled biopsy specimens, which can aid early

Effects of silencing S100A8 and S100A9 with small interfering RNA on the migration of CNE1 nasopharyngeal carcinoma cells.

PubMed

Yan, Lin-Lin; Huang, Yuan-Jiao; Yi, Xiang; Yan, Xue-Min; Cai, Yan; He, Qin; Han, Zi-Jian

2015-06-01

The calcium-binding S100 proteins are involved in functions such as cell growth, differentiation, migration, adhesion and signal transduction. S100A8 and S100A9 are highly expressed in a variety of tumor cells, and are implicated in tumor development and progression. However, the role of S100A8 and S100A9 in nasopharyngeal carcinoma (NPC) cell migration is unclear. The present study investigated the effect of S100A8 and S100A9 on migration using a NPC cell line, CNE1. The CNE1 cells were transfected with S100A8 or S100A9 small interfering RNA (siRNA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect S100A8 and S100A9 gene expression. Following the downregulation of S100A8 or S100A9, the effects on cell migration were determined using wound-healing assays. The expression of matrix metalloproteinase-7 (MMP7), a member of the MMP family that is associated with tumor cell invasion and migration, was also detected by RT-qPCR. S100A8 and S100A9 siRNAs effectively suppressed S100A8 and S100A9 gene expression, and substantially inhibited the migration of the CNE1 cells. In addition, MMP7 expression was reduced to varying extents in S100A8 and S100A9 siRNA-treated cells compared with controls. Thus, S100A8 and S100A9 promoted the migration of CNE1 NPC cells.

Effects of silencing S100A8 and S100A9 with small interfering RNA on the migration of CNE1 nasopharyngeal carcinoma cells

PubMed Central

YAN, LIN-LIN; HUANG, YUAN-JIAO; YI, XIANG; YAN, XUE-MIN; CAI, YAN; HE, QIN; HAN, ZI-JIAN

2015-01-01

The calcium-binding S100 proteins are involved in functions such as cell growth, differentiation, migration, adhesion and signal transduction. S100A8 and S100A9 are highly expressed in a variety of tumor cells, and are implicated in tumor development and progression. However, the role of S100A8 and S100A9 in nasopharyngeal carcinoma (NPC) cell migration is unclear. The present study investigated the effect of S100A8 and S100A9 on migration using a NPC cell line, CNE1. The CNE1 cells were transfected with S100A8 or S100A9 small interfering RNA (siRNA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect S100A8 and S100A9 gene expression. Following the downregulation of S100A8 or S100A9, the effects on cell migration were determined using wound-healing assays. The expression of matrix metalloproteinase-7 (MMP7), a member of the MMP family that is associated with tumor cell invasion and migration, was also detected by RT-qPCR. S100A8 and S100A9 siRNAs effectively suppressed S100A8 and S100A9 gene expression, and substantially inhibited the migration of the CNE1 cells. In addition, MMP7 expression was reduced to varying extents in S100A8 and S100A9 siRNA-treated cells compared with controls. Thus, S100A8 and S100A9 promoted the migration of CNE1 NPC cells. PMID:26137102

Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

PubMed Central

2010-01-01

Background Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs

Mutational analysis of FLASH and PTPN13 genes in colorectal carcinomas.

PubMed

Jeong, Eun Goo; Lee, Sung Hak; Yoo, Nam Jin; Lee, Sug Hyung

2008-01-01

The Fas-Fas ligand system is considered a major pathway for induction of apoptosis in cells and tissues. FLASH was identified as a pro-apoptotic protein that transmits apoptosis signal during Fas-mediated apoptosis. PTPN13 interacts with Fas and functions as both suppressor and inducer of Fas-mediated apoptosis. There are polyadenine tracts in both FLASH (A8 and A9 in exon 8) and PTPN13 (A8 in exon 7) genes that could be frameshift mutation targets in colorectal carcinomas. Because genes encoding proteins in Fas-mediated apoptosis frequently harbor somatic mutations in cancers, we explored the possibility as to whether mutations of FLASH and PTPN13 are a feature of colorectal carcinomas. We analysed human FLASH in exon 8 and PTPN13 in exon 7 for the detection of somatic mutations in 103 colorectal carcinomas by a polymerase chain reaction (PCR)- based single-strand conformation polymorphism (SSCP). We detected two mutations in FLASH gene, but none in PTPN13 gene. However, the two mutations were not frameshift (deletion or insertion) mutations in the polyadenine tracts of FLASH. The two mutations consisted of a deletion mutation (c.3734-3737delAGAA) and a missense mutation (c.3703A>C). These data indicate that frameshift mutation in the polyadenine tracts in both FLASH and PTPN13 genes is rare in colorectal carcinomas. Also, the data suggest that both FLASH and PTPN13 mutations in the polyadenine tracts may not have a crucial role in the pathogenesis of colorectal carcinomas.

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

PubMed

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.

miR-491-5p suppresses cell growth and invasion by targeting Notch3 in nasopharyngeal carcinoma.

PubMed

Zhang, Qi; Li, Qiang; Xu, Tao; Jiang, Hui; Xu, Lin-Gen

2016-06-01

MicroRNAs (miRNAs) have critical roles in the progression of nasopharyngeal carcinoma (NPC), a highly invasive and metastatic cancer that is widely prevalent in Southern China. miR-491-5p has been implicated in multiple types of cancer; however, its biological role and underlying mechanism in NPC have not been fully explored. In the present study, we found that miR-491-5p was downregulated in NPC tissues and cell lines compared with the corresponding normal counterparts. Overexpression of miR-491-5p significantly inhibited cell proliferation, migration and invasion in vitro and suppressed tumor growth in vivo. Using miRNA target prediction algorithms and reporter assays, we showed that miR-491-5p suppressed Notch3 expression both at the mRNA and protein level through directly targeting the 3' untranslated region (3'-UTR) of Notch3 mRNA. Overexpression of Notch3 significantly reversed the tumor-suppressive effects of miR‑491-5p. Taken together, the present study reveals a mechanistic link between miR-491-5p and Notch3 in the pathogenesis of NPC and that miR-491-5p has potential as a therapeutic target for NPC.

Risk of hypothyroidism among patients with nasopharyngeal carcinoma treated with radiation therapy: A Population-Based Cohort Study.

PubMed

Fan, Chao-Yueh; Lin, Chun-Shu; Chao, Hsing-Lung; Huang, Wen-Yen; Su, Yu-Fu; Lin, Kuen-Tze; Tsai, I-Ju; Kao, Chia-Hung

2017-06-01

This study aimed to assess the incidence and risk of hypothyroidism among patients with nasopharyngeal carcinoma (NPC) after radiation therapy (RT). We identified 14,893 NPC patients and 16,105 other head and neck cancer (HNC) patients treated with RT without thyroidectomy from the National Health Insurance Research Database in Taiwan between 2000 and 2011. Each NPC patient was randomly frequency-matched with four individuals without NPC by age, sex, and index year. Competing-risk regression models were used to estimate hazard ratios (HRs) of hypothyroidism requiring thyroxin associated with NPC after RT. The risk of developing hypothyroidism was significantly higher in the NPC cohort than in the matched cohort (adjusted HR=14.35, 95% CI=11.85-17.37) and the HNC cohort (adjusted HR=2.06, 95% CI=1.69-2.52). Independent risk factors for hypothyroidism among NPC patients included younger age, female sex, higher urbanization level, autoimmune disease, and receipt of chemotherapy. The risk of hypothyroidism requiring thyroxin was significantly higher in NPC patients after RT than in the general Taiwanese population and HNC patients. Regular clinical and serum thyroid function tests are essential among NPC survivors after RT. Copyright © 2017 Elsevier B.V. All rights reserved.

Phase I study of icotinib, an EGFR tyrosine kinase inhibitor combined with IMRT in nasopharyngeal carcinoma.

PubMed

Hu, Wei; Wang, Wei; Yang, Peinong; Zhou, Chao; Yang, Weifang; Wu, Bo; Lu, Hongsheng; Yang, Haihua

2015-01-01

Epidermal growth factor receptor (EGFR) is a new target for nasopharyngeal carcinoma (NPC) therapy. This prospective phase I study sought to determine the safety and recommended phase II dose of icotinib, a novel highly selective oral EGFR tyrosine kinase inhibitor, in combination with intensity-modulated radiotherapy (IMRT) in patients with NPC. Eligible patients with NPC received escalating doses of icotinib during IMRT. We treated six patients at a particular dose level until the maximum tolerated dose (MTD) was determined. The starting dose was 125 mg, once-daily and the dose was escalated to another level 125 mg, twice- and thrice- daily, until dose-limiting toxicity (DLT) occurred in two or more patients at a dose level. Expression and mutation analysis of EGFR were performed in all cases. A total of twelve patients were enrolled. Three patients experienced DLT (250 mg/day cohort) and MTD was 125 mg/day. Mucositis toxicity appears to be the major DLT. While EGFR expression in tumor tissue was detected in 75% (9/12) patients, EGFR mutation was detected in 16.67% (1/6) patients in 125 mg/day cohort, and 50% (3/6) in 250 mg/day cohort. The combination of icotinib (125 mg/day) and IMRT in patients with locally NPC had an acceptable safety profile and was well tolerated.

Treatment of stage IV(A-B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Anne W.M.; Yau, T.K.; Wong, Dominique H.M.

Purpose: To explore a more effective strategy for treating nasopharyngeal carcinoma with extensive locoregional disease. Methods and Materials: Between October 1998 and January 2003, 49 patients with Stage IV(A-B) disease infiltrating or abutting neurologic structures were treated with induction-concurrent chemotherapy and accelerated radiotherapy (RT). A combination of cisplatin and 5-fluorouracil was used in the induction phase and single-agent cisplatin in the concurrent phase. All patients were irradiated with conformal techniques at 2 Gy/fraction, six daily fractions weekly, to a total dose of 70 Gy. Results: Although 92% of patients had one or more acute toxicities Grade 3 or worse, 96%more » completed the whole course of RT, and 92% had five or more cycles of chemotherapy. The great majority of toxicities were uneventful, but 1 patient died of neutropenic sepsis. With a median follow-up of 3.1 years, 20 patients had failure at one or more sites and 15 patients died. The 3-year locoregional and distant failure-free rate was 77% and 75%, respectively, and the overall survival rate was 71%. At last follow-up, 27% of patients had developed late Grade 3 or worse toxicity (24% were hearing impairments), but none had radiation-induced neurologic damage. Conclusion: The current strategy achieved encouraging results for this poor prognostic group, and confirmation of the therapeutic gain by a prospective randomized trial is warranted.« less

Apatinib inhibits VEGFR-2 and angiogenesis in an in vivo murine model of nasopharyngeal carcinoma.

PubMed

Peng, Qiu-Xia; Han, Yun-Wei; Zhang, Yan-Ling; Hu, Jie; Fan, Juan; Fu, Shao-Zhi; Xu, Shan; Wan, Qiang

2017-08-08

Angiogenesis is initiated by the activation of the vascular epidermal growth factor receptor-2 (VEGFR-2) by the vascular epidermal growth factor (VEGF) ligand. Overexpression of VEGFR-2 increases the growth of nasopharyngeal carcinomas (NPC). Apatinib (YN968D1) is a highly-selective inhibitor of VEGFR-2, but its effects on NPC have not been hitherto investigated. In the present study, CNE-2 NPC cells were xenografted into 132 nude mice, which were treated with one of 6 drug regimens of apatinib administered alone or in combination with cisplatin (DDP). The impact of treatment regimens on the growth, microvascularization, apoptosis, and metabolic response of tumors, as well as mouse survival was determined by histopathology, immunohistochemistry (VEGFR-2 and CD31), terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL), micro 18F-FDG PET/CT imaging and survival curves. Administration of apatinib alone inhibited tumor growth, reduced microvascular density, and facilitated the apoptosis of tumors. Tumors treated simultaneously with apatinib and cisplatin exhibited significantly-increased inhibition of tumor growth, prolonged survival time, decreased expression of VEGFR-2, reduced microvascular density, and frequency of apoptosis over standalone and sequential administration therapy. Tumors treated simultaneously with apatinib and cisplatin had the lowest uptake of FDG. Taken together, the simultaneous administration of apatinib and cisplatin improves the therapeutic efficacy over standalone treatments, which also led to improved efficacy over sequential administration regimens. VEGFR-2 is an important predictive marker for efficacy of apatinib treatment of NPC.

Filaggrin gene polymorphism associated with Epstein-Barr virus-associated tumors in China.

PubMed

Yang, Yang; Liu, Wen; Zhao, Zhenzhen; Zhang, Yan; Xiao, Hua; Luo, Bing

2017-08-01

Mutations of filaggrin gene (FLG) have been identified as the cause of ichthyosis vulgaris, while recently FLG mutations were found to be associated with gastric cancer. This study aimed to investigate the association of filaggrin polymorphism with Epstein-Barr virus-associated tumors in China. A total of 200 patients with three types of tumors and 117 normal control samples were genotyped at three common FLG mutation loci (rs3126085, K4671X, R501X) by using Sequenom MassARRAY technique. The χ 2 test was used to evaluate the relationship between the mutation and the three kinds of tumors. A two-sided P value of <0.05 was considered statistically significant. The results showed that two single-nucleotide polymorphism (SNP) loci (rs3126085, K4671X) were significantly associated with nasopharyngeal carcinoma in genetic model. In addition, the two SNPs K4671X and rs3126085 were related to Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) and EBV-negative gastric carcinoma (EBVnGC), respectively. Furthermore, allele distributions in EBVaGC and EBVnGC were verified to be different in both SNP loci.

Apoptosis and TRAF-1 cleavage in Epstein-Barr virus-positive nasopharyngeal carcinoma cells treated with doxorubicin combined with a farnesyl-transferase inhibitor.

PubMed

Vicat, Jean Michel; Ardila-Osorio, Hector; Khabir, Abdelmajid; Brezak, Marie Christine; Viossat, Isabelle; Kasprzyk, Philip; Jlidi, Rachid; Opolon, Paule; Ooka, Tadamassa; Prevost, Grégoire; Huang, Dolly P; Busson, Pierre

2003-02-01

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinomas (NPC) are much more sensitive to chemotherapy than other head and neck carcinomas. Spectacular regressions are frequently observed after induction chemotherapy. However, these favorable responses are difficult to predict and often of short duration. So far there have been only few experiments to investigate the mechanisms which underline the cytotoxic effects of anti-neoplastic drugs against NPC cells. In addition, these studies were performed almost entirely on EBV-negative cell lines therefore not truly representative of NPC cells. For the first time, we have used two EBV-positive NPC tumor lines derived from a North African (C15) and a Chinese (C666-1) patient as in vitro targets for a panel of anti-neoplastic agents. Doxorubicin, taxol and in a lesser extent cis-platinum efficiently inhibited NPC cell proliferation at clinically relevant concentrations, but all three agents failed to induce apoptosis. However, massive apoptosis of C15 cells was achieved when doxorubicin (1 microM) was combined with a farnesyl-transferase inhibitor, BIM 2001 (5 microM). Moreover, this apoptotic process was associated with a caspase-dependent early cleavage of the TNF-receptor associated factor 1 (TRAF-1) molecule, a signaling adaptor which is specifically expressed in latently EBV-infected cells. TRAF-1 cleavage might become a useful indicator of chemo-induced apoptosis in EBV-associated NPCs.

Carotid artery stiffness evaluated early by wave intensity in normal left ventricular function in post-radiotherapy patients with nasopharyngeal carcinoma.

PubMed

Zhang, Zhuo; Luo, Runlan; Tan, Bijun; Qian, Jing; Duan, Yanfang; Wang, Nan; Li, Guangsen

2018-04-01

This study aims to assess carotid elasticity early in normal left ventricular function in post-radiotherapy patients with nasopharyngeal carcinoma (NPC) by wave intensity. Sixty-seven post-radiotherapy patients all with normal left ventricular function were classified into group NPC1 and group NPC2 based on their carotid intima-media thickness. Thirty age- and sex-matched NPC patients without any history of irradiation and chemotherapy were included as a control group. Carotid parameters, including stiffness constant (β), pressure-strain elastic modulus (Ep), arterial compliance (AC), stiffness constant pulse wave velocity (PWVβ), and wave intensity pulse wave velocity (PWVWI) were measured. There were no significant differences in conventional echocardiographic variables among the three groups. In comparison with the control group, β, Ep, PWVβ, and PWVWI were significantly increased, while AC was significantly decreased in the NPC1 and NPC2 groups, and there were differences between the NPC1 group and NPC2 group (all P < 0.05). This study suggested that carotid artery stiffness increased with reduced carotid compliance in post-RT with NPC.

Phase 2 Sequential and Concurrent Chemoradiation for Advanced Nasopharyngeal Carcinoma (NPC)

ClinicalTrials.gov

2016-12-09

Stage II Lymphoepithelioma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage III Lymphoepithelioma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx

General Information about Nasopharyngeal Cancer

MedlinePlus

... Nasopharyngeal Cancer Treatment (Adult) (PDQ®)–Patient Version General Information About Nasopharyngeal Cancer Go to Health Professional Version ... the PDQ Adult Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

EBV latent membrane protein 1 abundance correlates with patient age but not with metastatic behavior in north African nasopharyngeal carcinomas

PubMed Central

Khabir, Abdelmajid; Karray, Hela; Rodriguez, Sandrine; Rosé, Mathieu; Daoud, Jamel; Frikha, Mounir; Boudawara, Tahia; Middeldorp, Jaap; Jlidi, Rachid; Busson, Pierre

2005-01-01

Background Undifferentiated nasopharyngeal carcinomas are rare in a majority of countries but they occur at a high incidence in South China and to a lesser extent in North Africa. They are constantly associated with the Epstein-Barr virus (EBV) regardless of patient geographic origin. In North Africa, the distribution of NPC cases according to patient age is bi-modal with a large group of patients being around 50 years old (80%) and a smaller group below 25 years old. We and others have previously shown that the juvenile form of NPC has distinct biological characteristics including a low amount of p53 and Bcl2 in the tumor tissue and a low level of anti-EBV IgG and IgA in the peripheral blood. Results To get more insight on potential oncogenic mechanisms specific of these two forms, LMP1 abundance was assessed in 82 NPC patients of both groups, using immuno-histochemistry and semi-quantitative evaluation of tissue staining. Serum levels of anti-EBV antibodies were simultaneously assessed. For LMP1 staining, we used the S12 antibody which has proven to be more sensitive than the common anti-LMP1 CS1-4 for analysis of tissue sections. In all NPC biopsies, at least a small fraction of cells was positively stained by S12. LMP1 abundance was strongly correlated to patient age, with higher amounts of the viral protein detected in specimens of the juvenile form. In contrast, LMP1 abundance was not correlated to the presence of lymph node or visceral metastases, nor to the risk of metastatic recurrence. It was also independent of the level of circulating anti-EBV antibodies. Conclusion The high amount of LMP1 recorded in tumors from young patients confirms that the juvenile form of NPC has specific features regarding not only cellular but also viral gene expression. PMID:15842731

EBV latent membrane protein 1 abundance correlates with patient age but not with metastatic behavior in north African nasopharyngeal carcinomas.

PubMed

Khabir, Abdelmajid; Karray, Hela; Rodriguez, Sandrine; Rosé, Mathieu; Daoud, Jamel; Frikha, Mounir; Boudawara, Tahia; Middeldorp, Jaap; Jlidi, Rachid; Busson, Pierre

2005-04-20

Undifferentiated nasopharyngeal carcinomas are rare in a majority of countries but they occur at a high incidence in South China and to a lesser extent in North Africa. They are constantly associated with the Epstein-Barr virus (EBV) regardless of patient geographic origin. In North Africa, the distribution of NPC cases according to patient age is bi-modal with a large group of patients being around 50 years old (80%) and a smaller group below 25 years old. We and others have previously shown that the juvenile form of NPC has distinct biological characteristics including a low amount of p53 and Bcl2 in the tumor tissue and a low level of anti-EBV IgG and IgA in the peripheral blood. To get more insight on potential oncogenic mechanisms specific of these two forms, LMP1 abundance was assessed in 82 NPC patients of both groups, using immuno-histochemistry and semi-quantitative evaluation of tissue staining. Serum levels of anti-EBV antibodies were simultaneously assessed. For LMP1 staining, we used the S12 antibody which has proven to be more sensitive than the common anti-LMP1 CS1-4 for analysis of tissue sections. In all NPC biopsies, at least a small fraction of cells was positively stained by S12. LMP1 abundance was strongly correlated to patient age, with higher amounts of the viral protein detected in specimens of the juvenile form. In contrast, LMP1 abundance was not correlated to the presence of lymph node or visceral metastases, nor to the risk of metastatic recurrence. It was also independent of the level of circulating anti-EBV antibodies. The high amount of LMP1 recorded in tumors from young patients confirms that the juvenile form of NPC has specific features regarding not only cellular but also viral gene expression.

HPV-related Multiphenotypic Sinonasal Carcinoma: An Expanded Series of 49 Cases of the Tumor Formerly Known as HPV-related Carcinoma With Adenoid Cystic Carcinoma-like Features.

PubMed

Bishop, Justin A; Andreasen, Simon; Hang, Jen-Fan; Bullock, Martin J; Chen, Tiffany Y; Franchi, Alessandro; Garcia, Joaquin J; Gnepp, Douglas R; Gomez-Fernandez, Carmen R; Ihrler, Stephan; Kuo, Ying-Ju; Lewis, James S; Magliocca, Kelly R; Pambuccian, Stefan; Sandison, Ann; Uro-Coste, Emmanuelle; Stelow, Edward; Kiss, Katalin; Westra, William H

2017-12-01

were positive for p16 by immunostaining and HPV by RNA in situ hybridization. Thirty-three (67%) were positive for HPV 33. No cases tested for MYB, MYBL1, or NFIB gene fusions were positive. In the 38 cases with follow-up data, (mean follow-up, 42 mo) 14 recurred locally and 2 metastasized (lung, finger). There were no regional lymph node metastases, and no tumor-related deaths. HMSC is a distinct sinonasal neoplasm characterized by myoepithelial differentiation, frequent surface epithelial involvement, and the presence of high-risk HPV (especially type 33). Although it classically exhibits a cribriforming pattern that closely resembles adenoid cystic carcinoma, our expanded series highlights a histologic spectrum that is much broader than previously recognized, warranting a change in terminology. HMSC usually presents as a large and destructive sinonasal mass with high-grade histologic features, but it paradoxically behaves in a relatively indolent manner, underscoring the importance of distinguishing HMSC from true adenoid cystic carcinoma, squamous cell carcinoma, and other histologic mimickers.

Prognostic value of pre-treatment 18F-FDG PET uptake for nasopharyngeal carcinoma.

PubMed

Aktan, Meryem; Kanyilmaz, Gul; Yavuz, Berrin Benli; Koc, Mehmet; Eryılmaz, Mehmet Akif; Adli, Mustafa

2017-11-25

To evaluate the prognostic value of maximal standardized uptake values (SUV max ) from serial fluor-18-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in patients with nasopharyngeal carcinoma (NPC). Fifty-two patients with NPC who underwent 18 F-FDG PET/CT scan before radiotherapy with/without chemotherapy were reviewed retrospectively. Twenty-seven patients (52%) were applied 3-D conformal radiotherapy and 25 patients (48%) applied intensity-modulated radiotherapy (IMRT). Fourteen (27%) patients were given neoadjuvant chemotherapy and forty-four (84.6%) patients were given concomitant and adjuvant chemotherapy. Median follow-up time was 34 months (range 5.6-66.4 months). Forty-four (84.6%) patients were alive at last follow-up and eight (15.4%) had died. The best cut-off value of the SUV max for the primary tumor site (SUV max -PT) was 13 and 9 for the lymph nodes (SUV max -LN). Patients with SUV max -PT ≥ 13.0 and SUV max -LN ≥ 9 had a significantly higher risk for the development of the distant metastases (p = 0.044 and p = 0.038). DFS was affected in patients with SUV max -PT ≥ 13 (log rank χ 2  = 2.54, p = 0.017) and was significantly lower in patients with SUV max -LN ≥ 9 for the lymph nodes (log rank χ 2  = 5.81, p = 0.013). OS was not affected by SUV levels. A multivariate Cox proportional hazard model of DFS included age (≥ 40), SUV max -LN (< 9), T stage (T1-2) and neoadjuvant chemotherapy are significantly better prognosis for the DFS. 18 F-FDG PET/CT uptake before treatment, as determined by SUV max , may be a valuable tool to evaluate prognosis in NPC patients.

Aichi Cancer Center Initial Experience of Intensity Modulated Radiation Therapy for Nasopharyngeal Cancer Using Helical Tomotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kodaira, Takeshi; Tomita, Natsuo; Tachibana, Hiroyuki

Purpose: To assess the feasibility of helical tomotherapy (HT) for patients with nasopharyngeal carcinoma. Methods and Materials: From June 2006 to June 2007, 20 patients with nasopharyngeal carcinoma were treated with HT with (n = 18) or without (n = 2) systemic chemotherapy. The primary tumor and involved lymph node (PTV1) were prescribed 70 Gy and the prophylactic region 54 Gy at D95, respectively. The majority of patients received 2 Gy per fraction for PTV1 in 35 fractions. Parotid function was evaluated using quantitative scintigraphy at pretreatment, and posttreatment at 3 months and 1 year later. Results: The median patientmore » age was 53 years, ranging from 15 to 83. Our cohort included 5, 8, 4, 2, and 1 patients with disease Stages IIB, III, IVA, IVB, and IVC, respectively. Histopathological record revealed two for World Health Organization Type I and 18 for Type 2 or 3. The median duration time for treatment preparation was 9.5 days, and all plans were thought to be acceptable regarding dose constraints of both the planning target volume and organ at risk. All patients completed their treatment procedure of intensity-modulated radiation therapy (IMRT). All patients achieved clinical remission after IMRT. The majority of patients had Grade 3 or higher toxicity of skin, mucosa, and neutropenia. At the median follow-up of 10.9 months, two patients recurred, and one patient died from cardiac disease. Parotid gland function at 1 year after completion of IMRT was significantly improved compared with that at 3 months. Conclusion: HT was clinically effective in terms of IMRT planning and utility for patients with nasopharyngeal cancer.« less

The distinctive profile of risk factors of nasopharyngeal carcinoma in comparison with other head and neck cancer types

PubMed Central

Abdulamir, AS; Hafidh, RR; Abdulmuhaimen, N; Abubakar, F; Abbas, KA

2008-01-01

Background Nasopharyngeal carcinoma (NPC) and other head and neck cancer (HNCA) types show a great epidemiological variation in different regions of the world. NPC has multifactorial etiology and many interacting risk factors are involved in NPC development mainly Epstein Barr virus (EBV). There is a need to scrutinize the complicated network of risk factors affecting NPC and how far they are different from that of other HNCA types. Methods 122 HNCA patients and 100 control subjects were studied in the region of the Middle East. Three types of HNCA were involved in our study, NPC, carcinoma of larynx (CL), and hypopharyngeal carcinoma (HPC). The risk factors studied were the level of EBV serum IgG and IgA antibodies measured by ELISA, age, sex, smoking, alcohol intake, histology, and family history of the disease. Results EBV serum level of IgG and IgA antibodies was higher in NPC than CL, HPC, and control groups (p < 0.01). NPC was associated with lymphoepithelioma (LE) tumors, males, regular alcohol intake, and regular smoking while CL and HPC were not (p < 0.05). CL and HPC were associated with SCC tumors (p < 0.05). Furthermore, NPC, unlike CL and HPC groups, was not affected by the positive family history of HNCA (p > 0.05). The serum levels of EBV IgG and IgA antibodies were higher in LE tumors, regular smokers, younger patients, and negative family history groups of NPC patients than SCC tumors, non-regular smokers, older patients and positive family history groups respectively (p < 0.05) while this was not found in the regular alcoholics (p > 0.05). Conclusion It was concluded that risk factors of NPC deviate much from that of other HNCA. EBV, smoking, alcohol intake, LE tumors, male patient, and age > 54 years were hot risk factors of NPC while SCC and positive family history of the disease were not. Earlier incidence, smoking, LE tumors, and negative family history of the disease in NPC patients were associated much clearly with EBV. It is proposed that

Combination Gene Therapy for Liver Metastasis of Colon Carcinoma in vivo

NASA Astrophysics Data System (ADS)

Chen, Shu-Hsai; Chen, X. H. Li; Wang, Yibin; Kosai, Ken-Ichiro; Finegold, Milton J.; Rich, Susan S.

1995-03-01

The efficacy of combination therapy with a "suicide gene" and a cytokine gene to treat metastatic colon carcinoma in the liver was investigated. Tumor in the liver was generated by intrahepatic injection of a colon carcinoma cell line (MCA-26) in syngeneic BALB/c mice. Recombinant adenoviral vectors containing various control and therapeutic genes were injected directly into the solid tumors, followed by treatment with ganciclovir. While the tumors continued to grow in all animals treated with a control vector or a mouse interleukin 2 vector, those treated with a herpes simplex virus thymidine kinase vector, with or without the coadministration of the mouse interleukin 2 vector, exhibited dramatic necrosis and regression. However, only animals treated with both vectors developed an effective systemic antitumoral immunity against challenges of tumorigenic doses of parental tumor cells inoculated at distant sites. The antitumoral immunity was associated with the presence of MCA-26 tumor-specific cytolytic CD8^+ T lymphocytes. The results suggest that combination suicide and cytokine gene therapy in vivo can be a powerful approach for treatment of metastatic colon carcinoma in the liver.

Prognosticators and risk grouping in patients with lung metastasis from nasopharyngeal carcinoma: a more accurate and appropriate assessment of prognosis.

PubMed

Cao, Xun; Luo, Rong-Zhen; He, Li-Ru; Li, Yong; Lin, Wen-Qian; Chen, You-Fang; Wen, Zhe-Sheng

2011-08-26

Lung metastases arising from nasopharyngeal carcinomas (NPC) have a relatively favourable prognosis. The purpose of this study was to identify the prognostic factors and to establish a risk grouping in patients with lung metastases from NPC. A total of 198 patients who developed lung metastases from NPC after primary therapy were retrospectively recruited from January 1982 to December 2000. Univariate and multivariate analyses of clinical variables were performed using Cox proportional hazards regression models. Actuarial survival rates were plotted against time using the Kaplan-Meier method, and log-rank testing was used to compare the differences between the curves. The median overall survival (OS) period and the lung metastasis survival (LMS) period were 51.5 and 20.9 months, respectively. After univariate and multivariate analyses of the clinical variables, age, T classification, N classification, site of metastases, secondary metastases and disease-free interval (DFI) correlated with OS, whereas age, VCA-IgA titre, number of metastases and secondary metastases were related to LMS. The prognoses of the low- (score 0-1), intermediate- (score 2-3) and high-risk (score 4-8) subsets based on these factors were significantly different. The 3-, 5- and 10-year survival rates of the low-, intermediate- and high-risk subsets, respectively (P < 0.001) were as follows: 77.3%, 60% and 59%; 52.3%, 30% and 27.8%; and 20.5%, 7% and 0%. In this study, clinical variables provided prognostic indicators of survival in NPC patients with lung metastases. Risk subsets would help in a more accurate assessment of a patient's prognosis in the clinical setting and could facilitate the establishment of patient-tailored medical strategies and supports.

International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma.

PubMed

Lee, Anne W; Ng, Wai Tong; Pan, Jian Ji; Poh, Sharon S; Ahn, Yong Chan; AlHussain, Hussain; Corry, June; Grau, Cai; Grégoire, Vincent; Harrington, Kevin J; Hu, Chao Su; Kwong, Dora L; Langendijk, Johannes A; Le, Quynh Thu; Lee, Nancy Y; Lin, Jin Ching; Lu, Tai Xiang; Mendenhall, William M; O'Sullivan, Brian; Ozyar, Enis; Peters, Lester J; Rosenthal, David I; Soong, Yoke Lim; Tao, Yungan; Yom, Sue S; Wee, Joseph T

2018-01-01

Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, and dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome. A review of the available literature addressing the natural behaviour of NPC and correlation between clinical and pathological aspects of the disease was conducted. Existing international guidelines as well as published protocols specified by clinical trials on contouring of clinical target volumes (CTV) were compared. This information was then summarized into a preliminary draft guideline which was then circulated to international experts in the field for exchange of opinions and subsequent voting on areas with the greatest controversies. Common areas of uncertainty and variation in practices among experts experienced in radiation therapy for NPC were elucidated. Iterative revisions were made based on extensive discussion and final voting on controversial areas by the expert panel, to formulate the recommendations on contouring of CTV based on optimal geometric expansion and anatomical editing for those structures with substantial risk of microscopic infiltration. Through this comprehensive review of available evidence and best practices at major institutions, as well as interactive exchange of vast experience by international experts, this set of consensus guidelines has been developed to provide a practical reference for appropriate contouring to ensure optimal target coverage. However, the final decision on the treatment volumes should be based on full consideration of individual patients' factors and facilities of an individual centre (including the quality of imaging methods and the precision of treatment delivery). Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed Central

Fogg, Mark; Murphy, John R.; Lorch, Jochen; Posner, Marshall; Wang, Fred

2013-01-01

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. PMID:23601786

Evaluation of non-viral risk factors for nasopharyngeal carcinoma in a high-risk population of Southern China

PubMed Central

Guo, Xiuchan; Johnson, Randall C.; Deng, Hong; Liao, Jian; Guan, Li; Nelson, George W.; Tang, Mingzhong; Zheng, Yuming; de The, Guy; O’Brien, Stephen J.; Winkler, Cheryl A.; Zeng, Yi

2015-01-01

To understand the role of environmental and genetic influences on nasopharyngeal carcinoma (NPC) in populations at high risk of NPC, we have performed a case-control study in Guangxi Province of Southern China in 2004-2005. NPC cases (n=1049) were compared to 785 NPC-free matched controls who were seropositive for IgA antibodies (IgA) to Epstein-Barr virus (EBV) capsid antigen (VCA)—a predictive marker for NPC in Chinese populations. A questionnaire was used to capture exposure and NPC family history data. Risk factors associated with NPC in a multivariant analysis model were the following: 1) a first, second or third degree relative with NPC [Attributable risk (AR)= 6%, Odds ratio (OR) = 3.1, 95%CI = 2.0-4.9, p < 0.001]; 2) consumption of salted fish 3 or more than 3 times per month (AR=3%, OR = 1.9, 95%CI = 1.1-3.5, p = 0.035); 3) exposure to domestic wood cooking fires for more than 10 years (AR=69%, OR = 5.8, 95%CI = 2.5-13.6, p < 0.001); and 4) exposure to occupational solvents for 10 or less years (AR=4%, OR = 2.6, 95%CI = 1.4-4.8, p = 0.002). Consumption of preserved meats or a history of tobacco smoking were not associated with NPC (P>0.05). We also assessed the contribution of EBV/IgA/VCA antibody serostatus to NPC risk—32.2% of NPC can be explained by IgA+ status. However, family history and environmental risk factors cumulatively explained only 2.7% of NPC development in NPC high risk population. These findings should have important public health implications for NPC risk reduction in endemic regions. PMID:19296536

[Phase II clinical trial of two different modes of administration of the induction chemotherapy for locally advanced nasopharyngeal carcinoma].

PubMed

Bi, Ting; Jin, Feng; Wu, Weili; Long, Jinhua; Li, Yuanyuan; Gong, Xiuyun; Luo, Xiuling; Li, Zhuoling; He, Qianyong; Qu, Bo

2015-09-01

To compare the therapeutic effects, toxic side effects and influence on the immune function in patients treated with TPF [docetaxel (DOC) + cisplatin (DDP) + 5-fluorouracil (5-Fu)] induction chronochemotherapy and conventional chemotherapy for locally advanced nasopharyngeal (NPC). Seventy patients with locally advanced nasopharyngeal carcinoma were treated in our department at their first visit from April 2013 to December 2013. They were divided randomly into two groups: the chronochemotherapy group (38 patients) and conventional chemotherapy group (32 patients). All of the patients were treated with TPF regimen with 2 cycles of induction chemotherapy in a 21-28-days/cycle. The chronochemotherapy group: DOC: 75 mg/m2, i. v. gtt, d1 (03: 30-04: 30); DDP: 75 mg/m2, 10 am-10 pm, c.i.v, d1-d5; 5-Fu: 750 mg·m(-2)·d(-1), 10 pm-10 am, c. i.v., d1-d5, both chemotherapies were administered by intravenous infusion using an automatic electric pump. The conventional chemotherapy group: Both DOC and DDP were administered intravenously at a dose of 75 mg/m2 on d1. 5-Fu was given at a dose of 750 mg/m2 for 24 hours from d1-d5 with continuous infusion in a total of 120 hours. In this procedure, prescribing the conventional intravenous infusion, intensity modulated radiation therapy was used after the induction chemotherapy. The prescribed nasopharyngeal lesion dose (GTVnx) was 69.96 Gy/33 fractions for the T1-T2 nasopharygeal cancer, while 73.92 Gy/33 fractions nasopharynx lesion dose (GTVnx) for the T3-T4 nasopharyngeal cancer. The planning target volume (PTV) of positive lymph node (PTVnd) dose was 69.96 Gy/33 fractions. Concurrent chemoradiotherapy: cisplatin 100 mg/m2, i. v. gtt. d1-d2, and there were two cycles in total and 21 days each cycle. Sixty-six patients were evaluable for the response assessment. There were 36 patients in the chronochemotherapy group and 30 patients in the conventional chemotherapy group. After the induction chemotherapy, no CR case was found in

MicroRNA-188 suppresses G1/S transition by targeting multiple cyclin/CDK complexes.

PubMed

Wu, Jiangbin; Lv, Qing; He, Jie; Zhang, Haoxiang; Mei, Xueshuang; Cui, Kai; Huang, Nunu; Xie, Weidong; Xu, Naihan; Zhang, Yaou

2014-10-11

Accelerated cell cycle progression is the common feature of most cancers. MiRNAs can act as oncogenes or tumor suppressors by directly modulating cell cycle machinery. It has been shown that miR-188 is upregulated in UVB-irradiated mouse skin and human nasopharyngeal carcinoma CNE cells under hypoxic stress. However, little is known about the function of miR-188 in cell proliferation and growth control. Overexpression of miR-188 inhibits cell proliferation, tumor colony formation and G1/S cell cycle transition in human nasopharyngeal carcinoma CNE cells. Using bioinformatics approach, we identify a series of genes regulating G1/S transition as putative miR-188 targets. MiR-188 inhibits both mRNA and protein expression of CCND1, CCND3, CCNE1, CCNA2, CDK4 and CDK2, suppresses Rb phosphorylation and downregulates E2F transcriptional activity. The expression level of miR-188 also inversely correlates with the expression of miR-188 targets in human nasopharyngeal carcinoma (NPC) tissues. Moreover, studies in xenograft mouse model reveal that miR-188 is capable of inhibiting tumor initiation and progression by suppressing target genes expression and Rb phosphorylation. This study demonstrates that miR-188 exerts anticancer effects, via downregulation of multiple G1/S related cyclin/CDKs and Rb/E2F signaling pathway.

Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma.

PubMed

Chai, San Jiun; Yap, Yoke Yeow; Foo, Yoke Ching; Yap, Lee Fah; Ponniah, Sathibalan; Teo, Soo Hwang; Cheong, Sok Ching; Patel, Vyomesh; Lim, Kue Peng

2015-01-01

Nasopharyngeal carcinoma (NPC) is highly prevalent in South East Asia and China. The poor outcome is due to late presentation, recurrence, distant metastasis and limited therapeutic options. For improved treatment outcome, immunotherapeutic approaches focusing on dendritic and autologous cytotoxic T-cell based therapies have been developed, but cost and infrastructure remain barriers for implementing these in low-resource settings. As our prior observations had found that four-jointed box 1 (FJX1), a tumor antigen, is overexpressed in NPCs, we investigated if short 9-20 amino acid sequence specific peptides matching to FJX1 requiring only intramuscular immunization to train host immune systems would be a better treatment option for this disease. Thus, we designed 8 FJX1-specific peptides and implemented an assay system to first, assess the binding of these peptides to HLA-A2 molecules on T2 cells. After, ELISPOT assays were used to determine the peptides immunogenicity and ability to induce potential cytotoxicity activity towards cancer cells. Also, T-cell proliferation assay was used to evaluate the potential of MHC class II peptides to stimulate the expansion of isolated T-cells. Our results demonstrate that these peptides are immunogenic and peptide stimulated T-cells were able to induce peptide-specific cytolytic activity specifically against FJX1-expressing cancer cells. In addition, we demonstrated that the MHC class II peptides were capable of inducing T-cell proliferation. Our results suggest that these peptides are capable of inducing specific cytotoxic cytokines secretion against FJX1-expressing cancer cells and serve as a potential vaccine-based therapy for NPC patients.

What's New in Nasopharyngeal Cancer Research and Treatment?

MedlinePlus

... and Treatment? Nasopharyngeal Cancer About Nasopharyngeal Cancer What's New in Nasopharyngeal Cancer Research and Treatment? Research into ... the world where this cancer is common. Treatment New surgical techniques Advances in the field of skull ...

Development of a normal tissue complication probability (NTCP) model for radiation-induced hypothyroidism in nasopharyngeal carcinoma patients.

PubMed

Luo, Ren; Wu, Vincent W C; He, Binghui; Gao, Xiaoying; Xu, Zhenxi; Wang, Dandan; Yang, Zhining; Li, Mei; Lin, Zhixiong

2018-05-18

The objectives of this study were to build a normal tissue complication probability (NTCP) model of radiation-induced hypothyroidism (RHT) for nasopharyngeal carcinoma (NPC) patients and to compare it with other four published NTCP models to evaluate its efficacy. Medical notes of 174 NPC patients after radiotherapy were reviewed. Biochemical hypothyroidism was defined as an elevated level of serum thyroid-stimulating hormone (TSH) value with a normal or decreased level of serum free thyroxine (fT4) after radiotherapy. Logistic regression with leave-one-out cross-validation was performed to establish the NTCP model. Model performance was evaluated and compared by the area under the receiver operating characteristic curve (AUC) in our NPC cohort. With a median follow-up of 24 months, 39 (22.4%) patients developed biochemical hypothyroidism. Gender, chemotherapy, the percentage thyroid volume receiving more than 50 Gy (V 50 ), and the maximum dose of the pituitary (P max ) were identified as the most predictive factors for RHT. A NTCP model based on these four parameters were developed. The model comparison was made in our NPC cohort and our NTCP model performed better in RHT prediction than the other four models. This study developed a four-variable NTCP model for biochemical hypothyroidism in NPC patients post-radiotherapy. Our NTCP model for RHT presents a high prediction capability. This is a retrospective study without registration.

Somatic alterations of the serine/threonine kinase LKB1 gene in squamous cell (SCC) and large cell (LCC) lung carcinoma.

PubMed

Strazisar, Mojca; Mlakar, Vid; Rott, Tomaz; Glavac, Damjan

2009-05-01

Somatic LKB1 serine/threonine kinase alterations are rare in sporadic cancers, with the exception lung adenocarcinoma, but no mutations in squamous cell or large cell primary carcinoma were discovered. We screened the LKB1 gene in 129 primary nonsmall cell lung carcinomas, adjacent healthy lung tissue, and control blood samples. Forty-five percent of nonsmall cell lung tumors harbored either intron or exon alterations. We identified R86G, F354L, Y272Y and three polymorphisms: 290+36G/T, 386+156G/T, and 862+145C/T (novel). R86G (novel) and F354L mutations were found in six squamous cell carcinomas and three large cell cancer carcinomas, but not in the adjacent healthy tissue or controls samples. The F354L mutation was found in advanced squamous cell carcinomas with elevated COX-2 expression, rare P53, and no K-RAS mutation. Results indicate that the LKB1 gene is changed in a certain proportion of nonsmall cell lung tumors, predominately in advanced squamous lung carcinoma. Inactivation of the gene takes place via the C-terminal domain and could be related to mechanisms influencing tumor initiation, differentiation, and metastasis.

[Diagnostic value of MYB protein expression in adenoid cystic carcinoma and status of MYB gene copy number].

PubMed

Huo, Zhen; Zeng, Xuan; Wu, Shafei; Wu, Huanwen; Meng, Yunxiao; Liu, Yuanyuan; Luo, Yufeng; Cao, Jinling; Liang, Zhiyong

2015-08-01

To explore the diagnostic value of MYB protein expression for adenoid cystic carcinoma and its differential diagnosis from other salivary gland tumors, and to further investigate the status of MYB gene copy number. MYB expression was studied by immunohistochemistry in 34 adenoid cystic carcinomas, 55 non-adenoid cystic carcinomas (other salivary gland tumors) including 10 pleomorphic adenomas, 10 basal cell adenomas, 10 epithelial-myoepithelial carcinomas, 9 basal cell adenocarcinomas, 8 mucoepidermoid carcinomas, 4 carcinoma in pleomorphic adenomas, and 4 polymorphous low-grade adenocarcinoma. MYB gene copy number status was detected by FISH in MYB protein-positive cases. 82.4% (28/34) of adenoid cystic carcinomas were MYB protein-positive, compared with 9.1% (5/55) of non-adenoid cystic carcinomas, and the difference between the two groups was statistically significant (P < 0.01). 2/18 of adenoid cystic carcinomas had duplication of MYB gene by FISH, and all non-adenoid cystic carcinomas were negative although the difference was not statistically significant (P = 0.435). MYB protein expression is a useful diagnostic marker for adenoid cystic carcinomas in its separation from other salivary gland tumors. In addition, duplication of MYB gene is no a major mechanism for the MYB protein overexpression.

An oncolytic adenovirus enhances antiangiogenic and antitumoral effects of a replication-deficient adenovirus encoding endostatin by rescuing its selective replication in nasopharyngeal carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Ran-yi, E-mail: liuranyi@mail.sysu.edu.cn; Zhou, Ling; Zhang, Yan-ling

2013-12-13

Highlights: •H101 promotes endostatin expression by Ad-Endo via rescuing Ad-Endo replication. •H101 rescued Ad-Endo replication by supplying E1A and E1B19k proteins. •Ad-Endo enhanced the cytotoxicity of H101 in NPC cells. •Ad-Endo and oncolytic Ad H101 have synergistic antitumor effects on NPC. -- Abstract: A replication-deficient adenovirus (Ad) encoding secreted human endostatin (Ad-Endo) has been demonstrated to have promising antiangiogenic and antitumoral effects. The E1B55k-deleted Ad H101 can selectively lyse cancer cells. In this study, we explored the antitumor effects and cross-interactions of Ad-Endo and H101 on nasopharyngeal carcinoma (NPC). The results showed that H101 dramatically promoted endostatin expression by Ad-Endomore » via rescuing Ad-Endo replication in NPC cells, and the expressed endostatin proteins significantly inhibited the proliferation of human umbilical vein endothelial cells. E1A and E1B19k products are required for the rescuing of H101 to Ad-Endo replication in CNE-1 and CNE-2 cells, but not in C666-1 cells. On the other hand, Ad-Endo enhanced the cytotoxicity of H101 by enhancing Ad replication in NPC cells. The combination of H101 and Ad-Endo significantly inhibited CNE-2 xenografts growth through the increased endostatin expression and Ad replication. These findings indicate that the combination of Ad-Endo gene therapy and oncolytic Ad therapeutics could be promising in comprehensive treatment of NPC.« less

Altered gene expression in conjunctival squamous cell carcinoma.

PubMed

Mahale, Alka; Alkatan, Hind; Alwadani, Saeed; Othman, Maha; Suarez, Maria J; Price, Antoinette; Al-Hussain, Hailah; Jastaneiah, Sabah; Yu, Wayne; Maktabi, Azza; Deepak, Edward P; Eberhart, Charles G; Asnaghi, Laura

2016-05-01

Conjunctival squamous cell carcinoma is a malignancy of the ocular surface. The molecular drivers responsible for the development and progression of this disease are not well understood. We therefore compared the transcriptional profiles of eight snap-frozen conjunctival squamous cell carcinomas and one in situ lesion with normal conjunctival specimens in order to identify diagnostic markers or therapeutic targets. RNA was analyzed using oligonucleotide microarrays, and a wide range of transcripts with altered expression identified, including many dysregulated in carcinomas arising at other sites. Among the upregulated genes, we observed more than 30-fold induction of the matrix metalloproteinases, MMP-9 and MMP-11, as well as a prominent increase in the mRNA level of a calcium-binding protein important for the intracellular calcium signaling, S100A2, which was induced over 20-fold in the tumor cohort. Clusterin was the most downregulated gene, with an approximately 180-fold reduction in the mRNA expression. These alterations were all confirmed by qPCR in the samples used for initial microarray analysis. In addition, immunohistochemical analysis confirmed the overexpression of MMP-11 and S100A2, as well as reductions in clusterin, in several independent in situ carcinomas of conjunctiva. These data identify a number of alterations, including upregulation of MMP-9, MMP-11, and S100A2, as well as downregulation of clusterin, associated with epithelial tumorigenesis in the ocular surface.

Gene expression profiling reveals two separate mechanisms regulating apoptosis in rectal carcinomas in vivo

PubMed Central

de Bruin, Elza C.; van de Pas, Simone; van de Velde, Cornelis J. H.; van Krieken, J. Han J. M.; Peltenburg, Lucy T. C.; Marijnen, Corrie A. M.

2007-01-01

The level of apoptosis in rectal carcinomas of patients treated by surgery only predicts local failure; patients with intrinsically high-apoptotic tumors develop less local recurrences than patients with low levels of apoptosis. To identify genes involved in this intrinsic apoptotic process in vivo, 47 rectal tumors with known apoptotic phenotype (24 low- and 23 high-apoptotic) were analyzed by oligonucleotide microarray technology. We identified several genes differentially expressed between low- and high-apoptotic tumors. Unsupervised clustering of the tumors based on expression levels of these genes separated the low-apoptotic from the high-apoptotic tumors, indicating a gene expression-dependent regulation. In addition, this clustering revealed two subgroups of high-apoptotic tumors. One high-apoptotic subgroup showed subtle differences in mRNA and protein expression of the known apoptotic regulators BAX, cIAP2 and ARC compared to the low-apoptotic tumors. The other subgroup of high-apoptotic tumors showed high expression of immune-related genes; predominantly HLA class II and chemokines, but also HLA class I and interferon-inducible genes were highly expressed. Immunohistochemistry revealed HLA-DR expression in epithelial tumor cells in 70% of these high-apoptotic tumors. The expression data suggest that high levels of apoptosis in rectal carcinoma patients can be the result of either slightly altered expression of known pro- and anti-apoptotic genes or high expression of immune-related genes. Electronic supplementary material The online version of this article (doi: 10.1007/s10495-007-0088-2) contains supplementary material, which is available to authorized users. PMID:17610066

Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

PubMed Central

Wang, Xue; Chen, Meng; Wu, Jing; Xu, Jian-Hua; Qian, Pu-Dong; Guo, Wen-Jie; Jiang, Xue-Song; Zhu, Huan-Feng; Gu, Jia-Jia; Wu, Jian-Feng; Zhang, Ye-wei; He, Xia

2015-01-01

Background N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Patients and Methods Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. Results With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. Conclusion IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute

The prognostic implications of growth-related gene product β in laryngeal squamous cell carcinoma.

PubMed

Tang, Mingming; Xu, Xinjiang; Chen, Juanjuan; Huang, Jiangfei; Jiang, Bin; Han, Liang

2017-09-01

Growth-related gene product β (GROβ) is an angiogenic chemokine that belongs to the CXC chemokine family, and a number of studies have suggested that GROβ is associated with tumor development and progression. However, a number of studies have investigated the association between GROβ expression and the clinical attributes of laryngeal squamous cell carcinoma (LSCC). In the present study, one-step quantitative polymerase chain reaction and immunohistochemistry analysis were used to detect GROβ expression and evaluate the association between its expression and the clinicopathological characteristics of LSCC. The results demonstrated that the GROβ mRNA and protein expression levels were significantly increased in LSCC compared with the corresponding non-cancerous tissues. GROβ protein expression in LSCC was associated with tumor-node-metastasis stage, lymph node metastasis and histopathological grade. The Kaplan-Meier method and Cox multi-factor analysis indicated that high GROβ expression, lymph node metastasis and histopathological grade were significantly associated with poor survival of patients with LSCC. These data indicated that GROβ may be a novel prognostic biomarker of LSCC.

FAMM Flap in Reconstructing Postsurgical Nasopharyngeal Airway Stenosis

PubMed Central

Nangole, Ferdinand Wanjala; Khainga, Stanley Ominde

2014-01-01

Introduction. Postsurgical nasopharyngeal airway stenosis can be a challenge to manage. The stenosis could be as a result of any surgical procedure in the nasopharyngeal region that heals extensive scarring and fibrosis. Objective. To evaluate patients with nasopharyngeal stenosis managed with FAMM flap. Study Design. Prospective study of patients with nasopharyngeal stenosis at the Kenyatta National Hospital between 2010 and 2013 managed with FAMM flap. Materials and Methods. Patients with severe nasopharyngeal airway stenosis were reviewed and managed with FAMM flaps at the Kenyatta National Hospital. Postoperatively they were assessed for symptomatic improvement in respiratory distress, patency of the nasopharyngeal airway, and donor site morbidity. Results. A total of 8 patients were managed by the authors in a duration of 4 years with nasopharyngeal stenosis. Five patients were managed with unilateral FAMM flaps in a two-staged surgical procedure. Four patients had complete relieve of the airway obstruction with a patent airway created. One patient had a patent airway created though with only mild improvement in airway obstruction. Conclusion. FAMM flap provides an alternative in the management of postsurgical severe nasopharyngeal stenosis. It is a reliable flap that is easy to raise and could provide adequate epithelium for the stenosed pharynx. PMID:25328699

Nasopharyngeal culture

MedlinePlus

Culture - nasopharyngeal; Swab for respiratory viruses; Swab for staph carriage ... test identifies viruses and bacteria that cause upper respiratory tract symptoms. These include: Bordetella pertussis Neisseria meningitidis ...

APC gene expression in gastric carcinoma: an immunohistochemical study.

PubMed

Grace, A; Butler, D; Gallagher, M; Al-Agha, R; Xin, Y; Leader, M; Kay, E

2002-09-01

Gastric carcinoma is one of the most common malignancies worldwide, particularly in Japan and China. Inactivation of the adenomatous polyposis coli ( ) gene, a tumor suppressor gene, has been shown to play a significant role in the development of colorectal carcinoma, and it has been suggested that it may play a role throughout the digestive tract, including the stomach. This study assesses gene expression in normal gastric mucosa and gastric adenocarcinoma using an antibody to the C-terminal region. One hundred twenty cases of gastric adenocarcinoma were examined from the files of Beaumont Hospital, Dublin, Ireland, and China Medical University, Shenyang, China. Ninety-one cases were informative. Of these, 78% revealed loss of staining. Loss of staining in adenocarcinoma showed no association with tumor type, tumor, stage or patient nationality. Loss of staining was also found in nine of 35 cases (26%) of intestinal metaplasia. In conclusion, loss of the gene, as determined by immunohistochemical staining, appears to be an early event in gastric carcinogenesis. Immunohistochemistry is a sensitive method for detection of this loss.

Tumor-specific cytolysis caused by an E1B55K-attenuated adenovirus in nasopharyngeal carcinoma is augmented by cisplatin.

PubMed

Liu, Ran-Yi; Peng, Ji-Lin; Li, Yong-Qiang; Huang, Bi-Jun; Lin, Huan-Xin; Zhou, Ling; Luo, Hui-Ling; Huang, Wenlin

2013-12-01

An E1B55K-attenuated adenovirus, dl1520, has been shown to replicate selectively in and lyse tumor cells. In this study, the antitumor activities of dl1520, alone or in combination with the chemotherapeutic agent cisplatin, were investigated in nasopharyngeal carcinoma (NPC) cells. The results demonstrated that dl1520 replicated in and destroyed NPC cells, and induced apoptosis in vitro. In a nude mouse xenograft model, dl1520 significantly inhibited the growth of NPC cell xenografts, and the viral replication was associated with tumor regression. Importantly, the antitumor activity of dl1520 was augmented by the addition of cisplatin both in vitro and in vivo, showing that dl1520 and cisplatin have a synergistic anti-NPC effect. These data suggest that dl1520 exerts an efficient anti-NPC activity through oncolysis and the induction of apoptosis, which is enhanced synergistically by cisplatin. These findings indicate that oncolytic viral therapeutics using the E1B55K-attenuated adenovirus dl1520 could be promising in the comprehensive treatment of NPC, especially in combination with platinum-based chemotherapy. Copyright © 2013 Wiley Periodicals, Inc.

Surrogate endpoints for overall survival in combined chemotherapy and radiotherapy trials in nasopharyngeal carcinoma: Meta-analysis of randomised controlled trials.

PubMed

Chen, Yu-Pei; Sun, Ying; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Zhang, Wen-Na; Zhou, Guan-Qun; Guo, Rui; Lin, Ai-Hua; Ma, Jun

2015-08-01

We used a literature-based meta-analysis to assess whether failure-free survival (FFS) or progression-free survival (PFS) could be reliable surrogate endpoints for overall survival (OS) in trials of combined chemotherapy and radiotherapy for nasopharyngeal carcinoma (NPC). We identified randomised trials that evaluated combined chemoradiotherapy strategies, and reported FFS or PFS and OS in NPC. We analysed the treatment effects on FFS or PFS, and OS. We used the coefficient of determination (R(2)), and the surrogate threshold effect (STE) to assess the trial-level correlation. Twenty-one trials (5212 patients), with sixteen treatment-control comparisons for FFS, and nine for PFS, were analysed. FFS was strongly correlated with OS (R(2)=0.88, STE=0.84), as was PFS (R(2)=0.90, STE=0.88). Moreover, FFS and PFS at 3 years were still strongly correlated with 5-year OS (R(2)=0.80, STE=0.83; R(2)=0.85, STE=0.84). Both FFS and PFS could be valid surrogate endpoints for OS in trials of combined chemotherapy and radiotherapy for NPC; PFS may be a more acceptable surrogate endpoint compared with FFS. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Associations of Nasopharyngeal Metabolome and Microbiome with Severity among Infants with Bronchiolitis. A Multiomic Analysis.

PubMed

Stewart, Christopher J; Mansbach, Jonathan M; Wong, Matthew C; Ajami, Nadim J; Petrosino, Joseph F; Camargo, Carlos A; Hasegawa, Kohei

2017-10-01

Bronchiolitis is the most common lower respiratory infection in infants; however, it remains unclear which infants with bronchiolitis will develop severe illness. In addition, although emerging evidence indicates associations of the upper-airway microbiome with bronchiolitis severity, little is known about the mechanisms linking airway microbes and host response to disease severity. To determine the relations among the nasopharyngeal airway metabolome profiles, microbiome profiles, and severity in infants with bronchiolitis. We conducted a multicenter prospective cohort study of infants (age <1 yr) hospitalized with bronchiolitis. By applying metabolomic and metagenomic (16S ribosomal RNA gene and whole-genome shotgun sequencing) approaches to 144 nasopharyngeal airway samples collected within 24 hours of hospitalization, we determined metabolome and microbiome profiles and their association with higher severity, defined by the use of positive pressure ventilation (i.e., continuous positive airway pressure and/or intubation). Nasopharyngeal airway metabolome profiles significantly differed by bronchiolitis severity (P < 0.001). Among 254 metabolites identified, a panel of 25 metabolites showed high sensitivity (84%) and specificity (86%) in predicting the use of positive pressure ventilation. The intensity of these metabolites was correlated with relative abundance of Streptococcus pneumoniae. In the pathway analysis, sphingolipid metabolism was the most significantly enriched subpathway in infants with positive pressure ventilation use compared with those without (P < 0.001). Enrichment of sphingolipid metabolites was positively correlated with the relative abundance of S. pneumoniae. Although further validation is needed, our multiomic analyses demonstrate the potential of metabolomics to predict bronchiolitis severity and better understand microbe-host interaction.

Cranial nerve involvement in nasopharyngeal carcinoma: response to radiotherapy and its clinical impact.

PubMed

Li, Jian-Cheng; Mayr, Nina A; Yuh, William T C; Wang, Jian Z; Jiang, Guo-Liang

2006-05-01

To evaluate the cranial nerve (CN) palsy associated with nasopharyngeal carcinoma (NPC), we studied factors that influenced the neurologic outcome of radiotherapy (RT), and the patterns and time course of neurologic recovery of CN palsy. Between July 1987 and July 1989, 93 patients who presented with CN palsy at the time of diagnosis of NPC were studied. All patients underwent external-beam RT with either cobalt-60 or 6-MV photon beams to a dose of 69 to 84 Gy at 2 Gy per fraction. The time course and pattern of neurologic recovery (complete, partial, or none) from CN palsy were evaluated. Age, sex, stage, histology, incidence and distribution of types of CNs involved, duration of CN palsy, and time course of tumor response during RT were correlated with the patterns and the time course of neurologic CN recovery by univariate and multivariate analyses. The cases of CN palsy most commonly involved CN V (38%), CN VI (26%), and CN XII (11%), which accounted for the majority of the cases (75%). The time course of CN recovery was variable and protracted. Most patients showed significant improvement upon completion of RT (51%, 19%, and 30% complete, partial, and no recovery, respectively) and further improvement 6 months after RT (58%, 17%, and 25%, respectively). Cranial nerves V, VI, and XII accounted for 75% of cases with no recovery. Recovery was best for CNs II, IX, and XI and the sympathetic nerve (100%, 87%, 100%, and 100%, respectively) and worst for CNs IV, VII, and XII (67%, 60%, and 40%, respectively, with no recovery). Neurologic CN recovery correlated significantly with the pretherapy duration (<3 months versus > or =3 months) of CN palsy (88% versus 62%; p = .002, multivariate analysis), the time course of clinical tumor regression, and neurologic symptom improvement during RT. Age, sex, T stage, N stage, histology, anterior versus posterior CN palsies, and base of skull involvement were not significant. According to our limited data, most patients with CN

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

PubMed Central

Fang, Chih-Yeu; Wu, Chung-Chun; Hsu, Hui-Yu; Chuang, Hsin-Ying; Huang, Sheng-Yen; Tsai, Ching-Hwa; Chang, Yao; Tsao, George Sai-Wah; Chen, Chi-Long; Chen, Jen-Yang

2015-01-01

(−)-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. PMID:25625511

A randomized phase III study between sequential versus simultaneous integrated boost intensity-modulated radiation therapy in nasopharyngeal carcinoma.

PubMed

Lertbutsayanukul, Chawalit; Prayongrat, Anussara; Kannarunimit, Danita; Chakkabat, Chakkapong; Netsawang, Buntipa; Kitpanit, Sarin

2018-05-01

This study was performed to compare the acute and late toxicities between sequential (SEQ) and simultaneous integrated boost (SIB) intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC). Stage I-IVB NPC patients were randomized to receive SEQ-IMRT or SIB-IMRT. SEQ-IMRT consisted of two plans: 2 Gy × 25 fractions to low-risk planning target volume (PTV) followed by a sequential boost (2 Gy × 10 fractions) to high-risk PTV, while SIB-IMRT treated low- and high-risk PTVs with doses of 56 and 70 Gy in 33 fractions. Toxicities and survival outcomes were analyzed. Between October 2010 and September 2015, of the 209 patients who completed treatment, 102 in the SEQ and 107 in the SIB arm were analyzed. The majority had undifferentiated squamous cell carcinoma (82%). Mucositis and dysphagia were the most common grade 3-5 acute toxicities. There were no statistically significant differences in the cumulative incidence of grade 3-4 acute toxicities between the two arms (59.8% in SEQ vs. 58.9% in SIB; P = 0.892). Common grade 3-4 late toxicities for SEQ and SIB included hearing loss (2.9 vs. 8.4%), temporal lobe injury (2.9 vs. 0.9%), cranial nerve injury (0 vs. 2.8%), and xerostomia (2 vs. 0.9%). With the median follow-up of 41 months, 3‑year progression-free and overall survival rates were 72.7 vs. 73.4% (P = 0.488) and 86.3 vs. 83.6% (P = 0.938), respectively. SEQ and SIB provide excellent survival outcomes with few late toxicities. According to our study, SIB with a satisfactory dose-volume constraint to nearby critical organs is the technique of choice for NPC treatment due to its convenience.

Phase I trial of adoptively transferred tumor-infiltrating lymphocyte immunotherapy following concurrent chemoradiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma

PubMed Central

Li, Jiang; Chen, Qiu-Yan; He, Jia; Li, Ze-Lei; Tang, Xiao-Feng; Chen, Shi-Ping; Xie, Chuan-Miao; Li, Yong-Qiang; Huang, Li-Xi; Ye, Shu-bio; Ke, Miao-La; Tang, Lin-Quan; Liu, Huai; Zhang, Lu; Guo, Shan-Shan; Xia, Jian-Chuan; Zhang, Xiao-Shi; Zheng, Li-Min; Guo, Xiang; Qian, Chao-Nan; Mai, Hai-Qiang; Zeng, Yi-Xin

2015-01-01

Adoptive cell therapy (ACT) for cancers using autologous tumor-infiltrating lymphocytes (TILs) can induce immune responses and antitumor activity in metastatic melanoma patients. Here, we aimed to assess the safety and antitumor activity of ACT using expanded TILs following concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Twenty-three newly diagnosed, locoregionally advanced NPC patients were enrolled, of whom 20 received a single-dose of TIL infusion following CCRT. All treated patients were assessed for toxicity, survival and clinical and immunologic responses. Correlations between immunological responses and treatment effectiveness were further studied. Only mild adverse events (AEs), including Grade 3 neutropenia (1/23, 5%) consistent with immune-related causes, were observed. Nineteen of 20 patients exhibited an objective antitumor response, and 18 patients displayed disease-free survival longer than 12 mo after ACT. A measurable plasma Epstein–Barr virus (EBV) load was detected in 14 patients at diagnosis, but a measurable EBV load was not found in patients after one week of ACT, and the plasma EBV load remained undetectable in 17 patients at 6 mo after ACT. Expansion and persistence of T cells specific for EBV antigens in peripheral blood following TIL therapy were observed in 13 patients. The apparent positive correlation between tumor regression and the expansion of T cells specific for EBV was further investigated in four patients. This study shows that NPC patients can tolerate ACT with TILs following CCRT and that this treatment results in sustained antitumor activity and anti-EBV immune responses. A larger phase II trial is in progress. PMID:25949875

Molecular Inversion Probe Analysis of Gene Copy Alterations Reveals Distinct Categories of Colorectal Carcinoma

PubMed Central

Ji, Hanlee; Kumm, Jochen; Zhang, Michael; Farnam, Kyle; Salari, Keyan; Faham, Malek; Ford, James M.; Davis, Ronald W.

2006-01-01

Genomic instability is a major feature of neoplastic development in colorectal carcinoma and other cancers. Specific genomic instability events, such as deletions in chromosomes and other alterations in gene copy number, have potential utility as biologically relevant prognostic biomarkers. For example, genomic deletions on chromosome arm 18q are an indicator of colorectal carcinoma behavior and potentially useful as a prognostic indicator. Adapting a novel genomic technology called molecular inversion probes which can determine gene copy alterations, such as genomic deletions, we designed a set of probes to interrogate several hundred individual exons of >200 cancer genes with an overall distribution covering all chromosome arms. In addition, >100 probes were designed in close proximity of microsatellite markers on chromosome arm 18q. We analyzed a set of colorectal carcinoma cell lines and primary colorectal tumor samples for gene copy alterations and deletion mutations in exons. Based on clustering analysis, we distinguished the different categories of genomic instability among the colorectal cancer cell lines. Our analysis of primary tumors uncovered several distinct categories of colorectal carcinoma, each with specific patterns of 18q deletions and deletion mutations in specific genes. This finding has potential clinical ramifications given the application of 18q loss of heterozygosity events as a potential indicator for adjuvant treatment in stage II colorectal carcinoma. PMID:16912164

A prospective protocol for nasopharyngeal carcinoma in children and adolescents: the Italian Rare Tumors in Pediatric Age (TREP) project.

PubMed

Casanova, Michela; Bisogno, Gianni; Gandola, Lorenza; Cecchetto, Giovanni; Di Cataldo, Andrea; Basso, Eleonora; Indolfi, Paolo; D'Angelo, Paolo; Favini, Francesca; Collini, Paola; Potepan, Paolo; Ferrari, Andrea

2012-05-15

Nasopharyngeal carcinoma (NPC) is very rare in childhood. It differs from its adult counterpart in the prevalence of the nonkeratinizing, undifferentiated subtype and by an advanced clinical stage at onset and better chances of survival. The risk of long-term treatment-related toxicity also may be a more important issue in younger individuals. A prospective chemoradiotherapy protocol for pediatric NPC was started in Italy in 2000 within the framework of the Rare Tumors in Pediatric Age (TREP) project. Three courses of cisplatin/5-fluorouracil induction chemotherapy were followed by radiotherapy (doses up to 65 grays) with concomitant cisplatin. Forty-six patients (ages 9-17 years) were considered eligible for the study over a 10-year period. The ratio of observed to expected cases based on epidemiological data was approximately 1 for both children and adolescents. All but 1 patient had lymph node involvement, and 5 patients had distant metastases. The rate of response to primary chemotherapy was 90%. The 5-year overall and progression-free survival rates were 80.9% and 79.3%, respectively (median follow-up, 62 months). The only statistically significant prognostic variable was the presence or absence of distant metastases. A 65% incidence of late sequelae was reported. This study demonstrates the feasibility and efficacy of a prospective protocol even for such rare tumors as pediatric NPC. The use of lower radiotherapy doses than those used in adults did not affect locoregional failure rates. Long-term follow-up will be needed to obtain more information on both survival and treatment sequelae. The next objective will be to establish broader, international prospective cooperation schemes. Copyright © 2011 American Cancer Society.

MicroRNA-130a-3p suppresses cell viability, proliferation and invasion in nasopharyngeal carcinoma by inhibiting CXCL12.

PubMed

Qu, Rongfeng; Sun, Yan; Li, Yarong; Hu, Chunmei; Shi, Guang; Tang, Yan; Guo, Dongrui

2017-01-01

Incidence of nasopharyngeal carcinoma (NPC) has remained high worldwide, posing a serious health problem. MicroRNAs (miRNAs) are a family of about 20-23 nucleotides small non-coding molecules, which play a significant role in NPC. In this study, we explored the molecular mechanisms of miR-130a-3p in inhibiting viability, proliferation, migration and invasion of NPC cells by suppressing CXCL12 . The relative expression of miR-130a-3p and CXCL12 mRNA expression in tissues and cells was measured by qRT-PCR. NPC cell line CNE-2Z was transfected with miR-130a-3p mimics, CXCL12 siRNA, cDNA- CXCL12 and negative control. Western Blot was performed to detect CXCL12 expression. The MTT assay was performed to study cell viability. The colony formation assay was done to test cell growth. Flow cytometry was conducted to analyze cell cycle and apoptosis. The Transwell assay was used to investigate cell migration and invasion. The results found that the up-regulation of miR-130a-3p or down-regulation of CXCL12 could inhibit viability, proliferation, migration and invasion of CNE-2Z cells. Luciferase-reporting system assay was performed to investigate miR-130a-3p could bind to the 3'UTR region of CXCL12 and the overexpression of miR-130a-3p could suppress CXCL12 expression. Collectively, our finding suggested demonstrated that miR-130a-3p could prohibit the progression of NPC by suppressing CXCL12 , which might serve as potential therapeutic targets for NPC.

3-Bromopyruvate enhances TRAIL-induced apoptosis in human nasopharyngeal carcinoma cells through CHOP-dependent upregulation of TRAIL-R2.

PubMed

Can, Zhou; Lele, Song; Zhirui, Zhang; Qiong, Pan; Yuzhong, Chen; Lingling, Liu; Surong, Zhao; Yiming, Sun; Pei, Zhang; Chenchen, Jiang; Liu, Hao

2017-08-01

Past reports have shown that the sensitivity of cancer cells to TRAIL-induced apoptosis is related to their expression of TRAIL-death receptors on the cell surface. However, the level of TRAIL-death receptors expression on cancer cells is always low. Our previous research showed that nasopharyngeal carcinoma (NPC) cells have a poor sensitivity to low doses of TRAIL. Here, we evaluated combined treatment with the energy inhibitor 3-bromopyruvate (3BP) and TRAIL as a method to produce an increased apoptotic response in NPC cells. The results showed that 3BP and TRAIL together produced higher cytotoxicity and increased TRAIL-R2 expression in NPC cells compared with the effects of either 3BP or TRAIL alone. These findings led us to hypothesize that 3BP may sensitize NPC cells to TRAIL. 3BP is a metabolic blocker that inhibits hexokinase II activity, suppresses ATP production, and induces endoplasmic reticulum (ER) stress. Our results showed that 3BP also activated AMP-activated protein kinase, which we found to play an important role in the induction of ER stress by 3BP. Furthermore, the induction of TRAIL-R2 expression and the sensitization of the NPC cells to TRAIL by 3BP were reduced when we inhibited the expression of CHOP. Taken together, our results showed that a low dose of 3BP sensitized NPC cells to TRAIL-induced apoptosis by the upregulation of CHOP, which was mediated by the activation of AMP-activated protein kinase and ER stress. The results showed that 3BP is a promising candidate agent for enhancing the therapeutic response to TRAIL in NPC.

miR-504 mediated down-regulation of nuclear respiratory factor 1 leads to radio-resistance in nasopharyngeal carcinoma

PubMed Central

Zhao, Luqing; Tang, Min; Hu, Zheyu; Yan, Bin; Pi, Weiwei; Li, Zhi; Zhang, Jing; Zhang, Liqin; Jiang, Wuzhong; Li, Guo; Qiu, Yuanzheng; Hu, Fang; Liu, Feng; Lu, Jingchen; Chen, Xue; Xiao, Lanbo; Xu, Zhijie; Tao, Yongguang; Yang, Lifang; Bode, Ann M.; Dong, Zigang; Zhou, Jian; Fan, Jia; Sun, Lunquan; Cao, Ya

2015-01-01

microRNAs (miRNAs) are involved in the various processes of DNA damage repair and play crucial roles in regulating response of tumors to radiation therapy. Here, we used nasopharyngeal carcinoma (NPC) radio-resistant cell lines as models and found that the expression of miR-504 was significantly up-regulated. In contrast, the expression of nuclear respiratory factor 1 (NRF1) and other mitochondrial metabolism factors, including mitochondrial transcription factor A (TFAM) and oxidative phosphorylation (OXPHOS) complex III were down-regulated in these cell lines. At the same time, the Seahorse cell mitochondrial stress test results indicated that the mitochondrial respiratory capacity was impaired in NPC radio-resistant cell lines and in a miR-504 over-expressing cell line. We also conducted dual luciferase reporter assays and verified that miR-504 could directly target NRF1. Additionally, miR-504 could down-regulate the expression of TFAM and OXPHOS complexes I, III, and IV and impaired the mitochondrial respiratory function of NPC cells. Furthermore, serum from NPC patients showed that miR-504 was up-regulated during different weeks of radiotherapy and correlated with tumor, lymph nodes and metastasis (TNM) stages and total tumor volume. The radio-therapeutic effect at three months after radiotherapy was evaluated. Results indicated that patients with high expression of miR-504 exhibited a relatively lower therapeutic effect ratio of complete response (CR), but a higher ratio of partial response (PR), compared to patients with low expression of miR-504. Taken together, these results demonstrated that miR-504 affected the radio-resistance of NPC by down-regulating the expression of NRF1 and disturbing mitochondrial respiratory function. Thus, miR-504 might become a promising biomarker of NPC radio-resistance and targeting miR-504 might improve tumor radiation response. PMID:26201446

Mutational Analysis of Mismatch Repair Genes, hMLH1 and hMSH2, in Sporadic Endometrial Carcinomas with Microsatellite Instability

PubMed Central

Kobayashi, Kanji; Matsushima, Mieko; Koi, Sumiko; Saito, Hiroko; Sagae, Satoru; Kudo, Ryuichi

1996-01-01

Microsatellite instability, monitored by replication error (RER), bas been observed in both sporadic and hereditary types of endometrial carcinoma. In the hereditary tumors, this instability is considered to be caused by a germline defect in the DNA mismatch‐repair system. We previously reported that nearly one‐quarter of sporadic endometrial carcinomas examined revealed an RER‐positive phenotype at multiple microsatellite loci. To investigate the role of genetic alterations of DNA mismatch‐repair genes in sporadic endometrial carcinomas, we screened 18 RER(+) endometrial carcinomas for mutations of hMLH1 and hMSH2. Although we found no germline mutations, we detected two somatic mutations of hMLH1 in a single endometrial cancer; these two mutations had occurred on different alleles, suggesting that two separate mutational events had affected both copies of hMLH1 in this particular tumor. These data implied that mutations of hMLH1 or hMSH2 play limited roles in the development of sporadic endometrial carcinomas, and that the tumors with genetic instability might have alterations of other mismatch‐repair genes, such as hPMS1 and hPMS2, or of unknown genes related to the mismatch‐repair system. PMID:8609062

Detection of nasopharyngeal cancer using confocal Raman spectroscopy and genetic algorithm technique

NASA Astrophysics Data System (ADS)

Li, Shao-Xin; Chen, Qiu-Yan; Zhang, Yan-Jiao; Liu, Zhi-Ming; Xiong, Hong-Lian; Guo, Zhou-Yi; Mai, Hai-Qiang; Liu, Song-Hao

2012-12-01

Raman spectroscopy (RS) and a genetic algorithm (GA) were applied to distinguish nasopharyngeal cancer (NPC) from normal nasopharyngeal tissue. A total of 225 Raman spectra are acquired from 120 tissue sites of 63 nasopharyngeal patients, 56 Raman spectra from normal tissue and 169 Raman spectra from NPC tissue. The GA integrated with linear discriminant analysis (LDA) is developed to differentiate NPC and normal tissue according to spectral variables in the selected regions of 792-805, 867-880, 996-1009, 1086-1099, 1288-1304, 1663-1670, and 1742-1752 cm-1 related to proteins, nucleic acids and lipids of tissue. The GA-LDA algorithms with the leave-one-out cross-validation method provide a sensitivity of 69.2% and specificity of 100%. The results are better than that of principal component analysis which is applied to the same Raman dataset of nasopharyngeal tissue with a sensitivity of 63.3% and specificity of 94.6%. This demonstrates that Raman spectroscopy associated with GA-LDA diagnostic algorithm has enormous potential to detect and diagnose nasopharyngeal cancer.

HLA-A SNPs and amino acid variants are associated with nasopharyngeal carcinoma in Malaysian Chinese.

PubMed

Chin, Yoon-Ming; Mushiroda, Taisei; Takahashi, Atsushi; Kubo, Michiaki; Krishnan, Gopala; Yap, Lee-Fah; Teo, Soo-Hwang; Lim, Paul Vey-Hong; Yap, Yoke-Yeow; Pua, Kin-Choo; Kamatani, Naoyuki; Nakamura, Yusuke; Sam, Choon-Kook; Khoo, Alan Soo-Beng; Ng, Ching-Ching

2015-02-01

Nasopharyngeal carcinoma (NPC) arises from the mucosal epithelium of the nasopharynx and is constantly associated with Epstein-Barr virus type 1 (EBV-1) infection. We carried out a genome-wide association study (GWAS) of 575,247 autosomal SNPs in 184 NPC patients and 236 healthy controls of Malaysian Chinese ethnicity. Potential association signals were replicated in a separate cohort of 260 NPC patients and 245 healthy controls. We confirmed the association of HLA-A to NPC with the strongest signal detected in rs3869062 (p = 1.73 × 10(-9)). HLA-A fine mapping revealed associations in the amino acid variants as well as its corresponding SNPs in the antigen peptide binding groove (p(HLA-A-aa-site-99) = 3.79 × 10(-8), p(rs1136697) = 3.79 × 10(-8)) and T-cell receptor binding site (p(HLA-A-aa-site-145) = 1.41 × 10(-4), p(rs1059520) = 1.41 × 10(-4)) of the HLA-A. We also detected strong association signals in the 5'-UTR region with predicted active promoter states (p(rs41545520) = 7.91 × 10(-8)). SNP rs41545520 is a potential binding site for repressor ATF3, with increased binding affinity for rs41545520-G correlated with reduced HLA-A expression. Multivariate logistic regression diminished the effects of HLA-A amino acid variants and SNPs, indicating a correlation with the effects of HLA-A*11:01, and to a lesser extent HLA-A*02:07. We report the strong genetic influence of HLA-A on NPC susceptibility in the Malaysian Chinese. © 2014 UICC.

Effect of beam arrangement on oral cavity dose in external beam radiotherapy of nasopharyngeal carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Vincent W.C.; Yang Zhining; Zhang Wuzhe

This study compared the oral cavity dose between the routine 7-beam intensity-modulated radiotherapy (IMRT) beam arrangement and 2 other 7-beam IMRT with the conventional radiotherapy beam arrangements in the treatment of nasopharyngeal carcinoma (NPC). Ten NPC patients treated by the 7-beam routine IMRT technique (IMRT-7R) between April 2009 and June 2009 were recruited. Using the same computed tomography data, target information, and dose constraints for all the contoured structures, 2 IMRT plans with alternative beam arrangements (IMRT-7M and IMRT-7P) by avoiding the anterior facial beam and 1 conventional radiotherapy plan (CONRT) were computed using the Pinnacle treatment planning system. Dose-volumemore » histograms were generated for the planning target volumes (PTVs) and oral cavity from which the dose parameters and the conformity index of the PTV were recorded for dosimetric comparisons among the plans with different beam arrangements. The dose distributions to the PTVs were similar among the 3 IMRT beam arrangements, whereas the differences were significant between IMRT-7R and CONRT plans. For the oral cavity dose, the 3 IMRT beam arrangements did not show significant difference. Compared with IMRT-7R, CONRT plan showed a significantly lower mean dose, V30 and V-40, whereas the V-60 was significantly higher. The 2 suggested alternative beam arrangements did not significantly reduce the oral cavity dose. The impact of varying the beam angles in IMRT of NPC did not give noticeable effect on the target and oral cavity. Compared with IMRT, the 2-D conventional radiotherapy irradiated a greater high-dose volume in the oral cavity.« less

Identification of Four-Jointed Box 1 (FJX1)-Specific Peptides for Immunotherapy of Nasopharyngeal Carcinoma

PubMed Central

Chai, San Jiun; Yap, Yoke Yeow; Foo, Yoke Ching; Yap, Lee Fah; Ponniah, Sathibalan; Teo, Soo Hwang; Cheong, Sok Ching; Patel, Vyomesh; Lim, Kue Peng

2015-01-01

Nasopharyngeal carcinoma (NPC) is highly prevalent in South East Asia and China. The poor outcome is due to late presentation, recurrence, distant metastasis and limited therapeutic options. For improved treatment outcome, immunotherapeutic approaches focusing on dendritic and autologous cytotoxic T-cell based therapies have been developed, but cost and infrastructure remain barriers for implementing these in low-resource settings. As our prior observations had found that four-jointed box 1 (FJX1), a tumor antigen, is overexpressed in NPCs, we investigated if short 9–20 amino acid sequence specific peptides matching to FJX1 requiring only intramuscular immunization to train host immune systems would be a better treatment option for this disease. Thus, we designed 8 FJX1-specific peptides and implemented an assay system to first, assess the binding of these peptides to HLA-A2 molecules on T2 cells. After, ELISPOT assays were used to determine the peptides immunogenicity and ability to induce potential cytotoxicity activity towards cancer cells. Also, T-cell proliferation assay was used to evaluate the potential of MHC class II peptides to stimulate the expansion of isolated T-cells. Our results demonstrate that these peptides are immunogenic and peptide stimulated T-cells were able to induce peptide-specific cytolytic activity specifically against FJX1-expressing cancer cells. In addition, we demonstrated that the MHC class II peptides were capable of inducing T-cell proliferation. Our results suggest that these peptides are capable of inducing specific cytotoxic cytokines secretion against FJX1-expressing cancer cells and serve as a potential vaccine-based therapy for NPC patients. PMID:26536470

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

PubMed

Seol, Ki Ho; Lee, Jeong Eun

2016-03-01

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.

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

PubMed Central

Seol, Ki Ho

2016-01-01

Purpose 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). Materials and Methods 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. Results 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. Conclusion 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. PMID:27104162

Intensity-modulated radiotherapy for nasopharyngeal carcinoma: Clinical correlation of dose to the pharyngo-esophageal axis and dysphagia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fua, Tsien F.; Corry, June; Milner, Alvin D.

2007-03-15

Purpose: The aim of this study was to quantify the dose delivered to the pharyngo-esophageal axis using different intensity-modulated radiation therapy (IMRT) techniques for treatment of nasopharyngeal carcinoma and to correlate this with acute swallowing toxicity. Methods and Materials: The study population consisted of 28 patients treated with IMRT between February 2002 and August 2005: 20 with whole field IMRT (WF-IMRT) and 8 with IMRT fields junctioned with an anterior neck field with central shielding (j-IMRT). Dose to the pharyngo-esophageal axis was measured using dose-volume histograms. Acute swallowing toxicity was assessed by review of dysphagia grade during treatment and enteralmore » feeding requirements. Results: The mean pharyngo-esophageal dose was 55.2 Gy in the WF-IMRT group and 27.2 Gy in the j-IMRT group, p < 0.001. Ninety-five percent (19/20) of the WF-IMRT group developed Grade 3 dysphagia compared with 62.5% (5/8) of the j-IMRT group, p = 0.06. Feeding tube duration was a median of 38 days for the WF-IMRT group compared with 6 days for the j-IMRT group, p = 0.04. Conclusions: Clinical vigilance must be maintained when introducing new technology to ensure that unanticipated adverse effects do not result. Although newer planning systems can reduce the dose to the pharyngo-esophageal axis with WF-IMRT, the j-IMRT technique is preferred at least in patients with no gross disease in the lower neck.« less

Prevertebral space effusion caused by the breaking of swollen lymphonodi retropharynici in nasopharyngeal carcinoma: A case report.

PubMed

Liu, Lian-Hua; Yang, Xiao-Feng

2016-06-01

A 20-year-old male presented to hospital with blood in the mucus, which had occurred for 6 months, and was diagnosed with nasopharyngeal carcinoma (NPC). Due to passive smoking, the patient developed a constant and violent cough, pain behind the right ear and swelling of the retropharynx. The results of a computed tomography scan, which was performed during re-examination of the patient, revealed that the right lymphonodi retropharynici had decreased in size and the hypodense shadow of the prevertebral space had become clear. Therefore, the retropharyngeal pressure was suspected to be increased due to the violent cough. Consequently, the increased pressure may have caused the swollen lymph nodes on the right side of the pharynx to break, which allowed the necrotic liquid to seep into the prevertebral space and result in effusion. Subsequent to 5 days of treatment with methylprednisolone (40 mg ivgtt qd, d1-5), the results from the cone bean computed tomography examination, which had been performed prior to radiotherapy, indicated that the retropharyngeal swelling had improved and the prevertebral space had returned to normal. To the best of our knowledge, the present study is the first reported case of effusion in the prevertebral space caused by the breaking of swollen lymphonodi retropharynici in NPC. The present study acts as a reminder of the possible delays in the treatments for head and neck tumor patients that demonstrate swollen retropharyngeal lymph nodes due to the occurrence of effusion in the prevertebral space.

Otitis Media and Nasopharyngeal Colonization in ccl3-/- Mice.

PubMed

Deniffel, Dominik; Nuyen, Brian; Pak, Kwang; Suzukawa, Keigo; Hung, Jun; Kurabi, Arwa; Wasserman, Stephen I; Ryan, Allen F

2017-11-01

We previously found CC chemokine ligand 3 (CCL3) to be a potent effector of inflammation during otitis media (OM): exogenous CCL3 rescues the OM phenotype of tumor necrosis factor-deficient mice and the function of macrophages deficient in several innate immune molecules. To further delineate the role of CCL3 in OM, we evaluated middle ear (ME) responses of ccl3 -/- mice to nontypeable Haemophilus influenzae (NTHi). CCL chemokine gene expression was evaluated in wild-type (WT) mice during the complete course of acute OM. OM was induced in ccl3 -/- and WT mice, and infection and inflammation were monitored for 21 days. Phagocytosis and killing of NTHi by macrophages were evaluated by an in vitro assay. The nasopharyngeal bacterial load was assessed in naive animals of both strains. Many CCL genes showed increased expression levels during acute OM, with CCL3 being the most upregulated, at levels 600-fold higher than the baseline. ccl3 -/- deletion compromised ME bacterial clearance and prolonged mucosal hyperplasia. ME recruitment of leukocytes was delayed but persisted far longer than in WT mice. These events were linked to a decrease in the macrophage capacity for NTHi phagocytosis and increased nasopharyngeal bacterial loads in ccl3 -/- mice. The generalized impairment in inflammatory cell recruitment was associated with compensatory changes in the expression profiles of CCL2, CCL7, and CCL12. CCL3 plays a significant role in the clearance of infection and resolution of inflammation and contributes to mucosal host defense of the nasopharyngeal niche, a reservoir for ME and upper respiratory infections. Therapies based on CCL3 could prove useful in treating or preventing persistent disease. Copyright © 2017 American Society for Microbiology.

Gene therapy for carcinoma of the breast

PubMed Central

Stoff-Khalili, MA; Dall, P; Curiel, DT

2007-01-01

In view of the limited success of available treatment modalities for breast cancer, alternative and complementary strategies need to be developed. The delineation of the molecular basis of breast cancer provides the possibility of specific intervention by gene therapy through the introduction of genetic material for therapeutic purposes. In this regard, several gene therapy approaches for carcinoma of the breast have been developed. These approaches can be divided into six broad categories: (1) mutation compensation, (2) molecular chemotherapy, (3) proapoptotic gene therapy, (4) antiangiogenic gene therapy, (5) genetic immunopotentiation, and (6) genetic modulation of resistance/sensitivity. Clinical trials for breast cancer have been initiated to evaluate safety, toxicity, and efficacy. Combined modality therapy with gene therapy and chemotherapy or radiation therapy has shown promising results. It is expected that as new therapeutic targets and approaches are identified and advances in vector design are realized, gene therapy will play an increasing role in clinical breast cancer treatment. PMID:16410823

[A lymphoepithelioma-like type of spinous-cell carcinoma of the cervix uteri].

PubMed

Pires, M A; Andrade, M J; Guerra, C; Silva, T S; de Oliveira, C; Beja, M

1999-01-01

Lymphoepithelioma-like carcinomas of the cervix uteri are very rare. They are poorly differentiated squamous cell carcinomas with intense stromal lymphocytic infiltration. These histologic features are similar to nasopharyngeal lymphoepithelioma and may have a better prognosis than other tumors of the cervix. A lymphoepithelioma-like lesion of the cervix uteri is described in a 33-year-old Caucasian woman who had an episode of vaginal bleeding. A review of the literature about these types of tumor is also presented.

Gene regulation is governed by a core network in hepatocellular carcinoma.

PubMed

Gu, Zuguang; Zhang, Chenyu; Wang, Jin

2012-05-01

Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and the mechanisms that lead to the disease are still relatively unclear. However, with the development of high-throughput technologies it is possible to gain a systematic view of biological systems to enhance the understanding of the roles of genes associated with HCC. Thus, analysis of the mechanism of molecule interactions in the context of gene regulatory networks can reveal specific sub-networks that lead to the development of HCC. In this study, we aimed to identify the most important gene regulations that are dysfunctional in HCC generation. Our method for constructing gene regulatory network is based on predicted target interactions, experimentally-supported interactions, and co-expression model. Regulators in the network included both transcription factors and microRNAs to provide a complete view of gene regulation. Analysis of gene regulatory network revealed that gene regulation in HCC is highly modular, in which different sets of regulators take charge of specific biological processes. We found that microRNAs mainly control biological functions related to mitochondria and oxidative reduction, while transcription factors control immune responses, extracellular activity and the cell cycle. On the higher level of gene regulation, there exists a core network that organizes regulations between different modules and maintains the robustness of the whole network. There is direct experimental evidence for most of the regulators in the core gene regulatory network relating to HCC. We infer it is the central controller of gene regulation. Finally, we explored the influence of the core gene regulatory network on biological pathways. Our analysis provides insights into the mechanism of transcriptional and post-transcriptional control in HCC. In particular, we highlight the importance of the core gene regulatory network; we propose that it is highly related to HCC and we believe further

21 CFR 882.1340 - Nasopharyngeal electrode.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasopharyngeal electrode. 882.1340 Section 882.1340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1340 Nasopharyngeal electrode...

21 CFR 882.1340 - Nasopharyngeal electrode.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasopharyngeal electrode. 882.1340 Section 882.1340 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1340 Nasopharyngeal electrode...

21 CFR 868.5100 - Nasopharyngeal airway.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway. (a...

21 CFR 868.5100 - Nasopharyngeal airway.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway. (a...

21 CFR 868.5100 - Nasopharyngeal airway.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway. (a...

21 CFR 868.5100 - Nasopharyngeal airway.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nasopharyngeal airway. 868.5100 Section 868.5100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5100 Nasopharyngeal airway. (a...

(68)Ga-DOTA-peptide: A novel molecular biomarker for nasopharyngeal carcinoma.

PubMed

Khor, Lih Kin; Loi, Hoi Yin; Sinha, Arvind Kumar; Tong, Kian Ti; Goh, Boon Cher; Loh, Kwok Seng; Lu, Suat-Jin

2016-04-01

Increased somatostatin receptor (SSTR) expression in patients with undifferentiated nasopharyngeal carcinoma (NPC) has been demonstrated with receptor autoradiography, (111) In-Octreotide scintigraphy, and (68) Ga-DOTA-TOC positron emission tomography (PET)/CT imaging. We sought to compare and correlate the uptake of fluorodeoxyglucose (FDG) and DOTA-NOC in undifferentiated NPC to ascertain the possible role of (68) Ga-DOTA-NOC PET/CT as a new imaging biomarker and to assess whether targeted peptide receptor radionuclide therapy is a feasible treatment option. After obtaining approval from our institutional review board, 4 patients with biopsy proven nonkeratinizing undifferentiated NPC who had just undergone routine staging/restaging (18) F-FDG PET/CT imaging were prospectively and consecutively recruited for (68) Ga-DOTA-NOC PET/CT imaging. Of these 4 patients, 3 were newly diagnosed with untreated NPC, whereas 1 patient was diagnosed with a case of recurrent NPC with previous treatment. These patients subsequently underwent (68) Ga-DOTA-NOC PET/CT within 10 days from the (18) F-FDG PET/CT to ensure lesion comparability. Tracer uptake in tumor lesions were assessed visually and semiquantitatively by measuring maximum standardized uptake values (SUVmax). There were 12 FDG-avid lesions of which 7 showed avid uptake of DOTA-NOC greater than liver uptake, whereas 5 showed low uptake of DOTA-NOC less than liver uptake. Subset analysis of the FDG-avid lesions at the primary and recurrent sites showed that all the FDG-avid primary tumors in the nasopharynx showed avid uptake of DOTA-NOC. On the contrary, the case of recurrent NPC showed avid FDG uptake but low DOTA-NOC uptake. Subset analysis of the suspicious FDG-avid cervical lymph nodes showed that 50% of them demonstrated avid DOTA-NOC uptake greater than liver uptake, whereas the remaining demonstrated low-grade DOTA-NOC uptake less than liver uptake. The 2 subcentimeter cervical lymph nodes that showed low

Anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related human papillary thyroid carcinoma after the Chernobyl accident.

PubMed

Arndt, Annette; Steinestel, Konrad; Rump, Alexis; Sroya, Manveer; Bogdanova, Tetiana; Kovgan, Leonila; Port, Matthias; Abend, Michael; Eder, Stefan

2018-04-06

Childhood radiation exposure has been associated with increased papillary thyroid carcinoma (PTC) risk. The role of anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related PTC remains unclear, but STRN-ALK fusions have recently been detected in PTCs from radiation exposed persons after Chernobyl using targeted next-generation sequencing and RNA-seq. We investigated ALK and RET gene rearrangements as well as known driver point mutations in PTC tumours from 77 radiation-exposed patients (mean age at surgery 22.4 years) and PTC tumours from 19 non-exposed individuals after the Chernobyl accident. ALK rearrangements were detected by fluorescence in situ hybridisation (FISH) and confirmed with immunohistochemistry (IHC); point mutations in the BRAF and RAS genes were detected by DNA pyrosequencing. Among the 77 tumours from exposed persons, we identified 7 ALK rearrangements and none in the unexposed group. When combining ALK and RET rearrangements, we found 24 in the exposed (31.2%) compared to two (10.5%) in the unexposed group. Odds ratios increased significantly in a dose-dependent manner up to 6.2 (95%CI: 1.1, 34.7; p = 0.039) at Iodine-131 thyroid doses >500 mGy. In total, 27 cases carried point mutations of BRAF or RAS genes, yet logistic regression analysis failed to identify significant dose association. To our knowledge we are the first to describe ALK rearrangements in post-Chernobyl PTC samples using routine methods such as FISH and IHC. Our findings further support the hypothesis that gene rearrangements, but not oncogenic driver mutations, are associated with ionizing radiation-related tumour risk. IHC may represent an effective method for ALK-screening in PTCs with known radiation aetiology, which is of clinical value since oncogenic ALK activation might represent a valuable target for small molecule inhibitors. © 2018 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and

Berberine inhibits the proliferation of human nasopharyngeal carcinoma cells via an Epstein-Barr virus nuclear antigen 1-dependent mechanism.

PubMed

Wang, Chao; Wang, Huan; Zhang, Yaqian; Guo, Wei; Long, Cong; Wang, Jingchao; Liu, Limei; Sun, Xiaoping

2017-04-01

Nasopharyngeal carcinoma (NPC) is a malignancy derived from the epithelial cells of the nasopharynx cavity, and is closely associated with Epstein-Barr virus (EBV) infection. In addition to NPC, EBV causes various human malignancies, such as gastric cancer, hematological tumors and lymphoepithelioma-like carcinomas. Epstein-Barr nuclear antigen 1 (EBNA1) encoded by EBV is indispensable for replication, partition, transcription and maintenance of viral genomes. Berberine, a naturally occurring isoquinoline alkaloid, shows anti-inflammatory, anticholinergic, antioxidative, and anticancer activities. In the present study, the antitumor effect of berberine was studied. Cell Counting Kit-8 (CCK-8) assays were performed to demonstrate whether the proliferation of EBV-positive NPC cells was inhibited by berberine. Flow cytometric results revealed that berberine induced cell cycle arrest and apoptosis. Quantitative-PCR and western blotting results indicated that berberine decreased the expression of EBNA1 at both the mRNA and protein levels in the EBV-positive NPC cells. The function of EBNA1 promoter Qp which is to drive EBNA1 transcription in type Ⅱ latent infection was strongly suppressed by berberine. Overexpression of EBNA1 attenuated this inhibitory effect. Berberine also suppressed the activity of signal transducer and activator of transcription 3 which is a new therapeutic target in a series of malignancies, including NPC. Viral titer experiments demonstrated that berberine decreased the production of virions in HONE1 and HK1-EBV cells. In a mouse xenograft model of NPC induced by HONE1 cells, berberine significantly inhibited tumor formation. Altogether, these results indicate that berberine decreases the expression of EBNA1 and exhibits an antitumor effect against NPC both in vitro and in vivo.

Folate, vitamin B6, vitamin B12 and methionine intakes and risk for nasopharyngeal carcinoma in Chinese adults: a matched case-control study.

PubMed

Zeng, Fang-fang; Liu, Yuan-ting; Lin, Xiao-ling; Fan, Yu-Ying; Zhang, Xing-lan; Xu, Chun-hua; Chen, Yu-ming

2016-01-14

Many studies have suggested that folate-related one-carbon metabolism-related nutrients may play a role in certain cancer risks, but few studies have assessed their associations with the risk for nasopharyngeal carcinoma (NPC). In this study, we investigated the association between four folate-related one-carbon metabolism-related nutrients (folate, vitamin B6, vitamin B12 and methionine) and NPC risk in Chinese adults. A total of 600 patients newly diagnosed (within 3 months) with NPC were individually matched with 600 hospital-based controls by age, sex and household type (urban v. rural). Folate, vitamin B6, vitamin B12 and methionine intakes were measured using a validated seventy-eight-item FFQ. A higher dietary folate or vitamin B6 intake was associated with a lower NPC risk after adjusting for potential confounders. The adjusted OR of NPC for quartiles 2-4 (v. 1) were 0·66 (95% CI 0·48, 0·91), 0·52 (95% CI 0·37, 0·74) and 0·34 (95% CI 0·23, 0·50) (P(trend)<0·001) for folate and 0·72 (95% CI 0·52, 1·00), 0·55 (95% CI 0·39, 0·78) and 0·44 (95% CI 0·30, 0·63) (P(trend)<0·001) for vitamin B6. No significant association with NPC risk was observed for dietary vitamin B12 or methionine intake. The risk for NPC with dietary folate intake was more evident in the participants who were not exposed to toxic substances than in those who were exposed (P(interaction)=0·014). This study suggests that dietary folate and vitamin B6 may be protective for NPC in a high-risk population.

Detection of the inferred interaction network in hepatocellular carcinoma from EHCO (Encyclopedia of Hepatocellular Carcinoma genes Online)

PubMed Central

Hsu, Chun-Nan; Lai, Jin-Mei; Liu, Chia-Hung; Tseng, Huei-Hun; Lin, Chih-Yun; Lin, Kuan-Ting; Yeh, Hsu-Hua; Sung, Ting-Yi; Hsu, Wen-Lian; Su, Li-Jen; Lee, Sheng-An; Chen, Chang-Han; Lee, Gen-Cher; Lee, DT; Shiue, Yow-Ling; Yeh, Chang-Wei; Chang, Chao-Hui; Kao, Cheng-Yan; Huang, Chi-Ying F

2007-01-01

Background The significant advances in microarray and proteomics analyses have resulted in an exponential increase in potential new targets and have promised to shed light on the identification of disease markers and cellular pathways. We aim to collect and decipher the HCC-related genes at the systems level. Results Here, we build an integrative platform, the Encyclopedia of Hepatocellular Carcinoma genes Online, dubbed EHCO , to systematically collect, organize and compare the pileup of unsorted HCC-related studies by using natural language processing and softbots. Among the eight gene set collections, ranging across PubMed, SAGE, microarray, and proteomics data, there are 2,906 genes in total; however, more than 77% genes are only included once, suggesting that tremendous efforts need to be exerted to characterize the relationship between HCC and these genes. Of these HCC inventories, protein binding represents the largest proportion (~25%) from Gene Ontology analysis. In fact, many differentially expressed gene sets in EHCO could form interaction networks (e.g. HBV-associated HCC network) by using available human protein-protein interaction datasets. To further highlight the potential new targets in the inferred network from EHCO, we combine comparative genomics and interactomics approaches to analyze 120 evolutionary conserved and overexpressed genes in HCC. 47 out of 120 queries can form a highly interactive network with 18 queries serving as hubs. Conclusion This architectural map may represent the first step toward the attempt to decipher the hepatocarcinogenesis at the systems level. Targeting hubs and/or disruption of the network formation might reveal novel strategy for HCC treatment. PMID:17326819

Treatment outcomes and feasibility of partial neck irradiation for patients with nasopharyngeal carcinoma with only retropharyngeal lymph node metastasis after intensity-modulated radiotherapy.

PubMed

Chen, Mo; Tang, Ling-Long; Sun, Ying; Mao, Yan-Ping; Li, Wen-Fei; Guo, Rui; Liu, Li-Zhi; Li, Li; Lin, Ai-Hua; Ma, Jun

2014-04-01

The purpose of this study was to summarize the treatment outcomes and evaluate the feasibility of partial neck irradiation in patients with nasopharyngeal carcinoma (NPC) with only retropharyngeal lymph nodes (RLNs) metastasis. Between January 2003 and December 2007, 54 patients with NPC who received partial neck irradiation to levels II, III, and VA and 100 patients who received whole neck irradiation were reviewed. The 5-year disease free survival (DFS), disease metastasis-free survival, (DMFS) local relapse-free survival (LRFS), and regional relapse-free survival (RRFS) rates were 81.8%, 87.7%, 94.8%, and 98.1%, respectively. The 5-year RRFS and DFS rates for the partial neck irradiation group and whole neck irradiation group were 98.1% versus 98.0% (p = .882), 87.0% vs 77.0% (p = .117), respectively. Partial neck irradiation was not considered a significant prognostic factor for any endpoint in univariate and multivariate analyses. Partial irradiation of neck levels II, III, and VA might be acceptable for patients with NPC with only RLN metastasis. Copyright © 2013 Wiley Periodicals, Inc.

Concurrent chemoradiotherapy versus radiotherapy alone for locoregionally advanced nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy: a meta-analysis.

PubMed

He, Yan; Guo, Tao; Guan, Hui; Wang, Jingjing; Sun, Yu; Peng, Xingchen

2018-01-01

In this study, we attempted to compare the efficacy and toxicity of concurrent chemoradiotherapy (CCRT) with radiotherapy alone (RT) for locoregionally advanced nasopharyngeal carcinoma (LANPC) in the era of intensity-modulated radiotherapy (IMRT) by meta-analysis. We searched databases, and all randomized controlled trials meeting the inclusion criteria were utilized for a meta-analysis with RevMan 5.3 based on the Cochrane methodology. Fifteen studies were found suitable based on the inclusion criteria. CCRT not only significantly improved the overall response rate (risk ratio [RR]=0.53, 95% CI 0.43-0.66) and the complete response rate (RR=0.60, 95% CI 0.51-0.71) but also contributed to longer overall survival. The incidence of grade 3-4 adverse events from CCRT group increased in hematologic toxicity (RR 2.25, 95% CI 1.54-3.29), radiation-induced oral mucositis (RR 1.64, 95% CI 1.14-2.35), and radiodermatitis (RR 1.80, 95% CI 1.13-2.88). Compared with IMRT alone, CCRT provided survival benefit with acceptable toxicity in patients with LANPC. However, we need multicenter randomized controlled trials and long-term follow-up to evaluate the eventual efficacy and toxicity of concurrent chemotherapy plus IMRT.

Temporal lobe injury after re-irradiation of locally recurrent nasopharyngeal carcinoma using intensity modulated radiotherapy: clinical characteristics and prognostic factors.

PubMed

Liu, Shuai; Lu, Taixiang; Zhao, Chong; Shen, Jingxian; Tian, Yunming; Guan, Ying; Zeng, Lei; Xiao, Weiwei; Huang, Shaomin; Han, Fei

2014-09-01

Temporal lobe injury (TLI) is a debilitating complication after radiotherapy for nasopharyngeal carcinoma (NPC), especially in patients who suffer treatment relapses and receive re-irradiation. We explored the clinical characteristics and prognostic factors of TLI in locally recurrent NPC (rNPC) patients after re-irradiation using intensity modulated radiotherapy (IMRT). A total of 454 temporal lobes (TLs) from 227 locally rNPC patients were reviewed. The clinical characteristics of TLI were analyzed. In the two radiotherapy courses, the equivalent dose in 2 Gy per fraction (EQD2) for the TLs was recalculated to facilitate comparison of the individual data. The median follow-up time was 31 (range, 3-127) months. After re-irradiation using IMRT, 31.3 % (71/227) of patients developed TLI. The median latency of TLI was 15 (range, 4-100) months. Univariate and multivariate analysis showed that the interval time (IT) between the two courses of radiotherapy and the summation of the maximum doses of the two radiotherapy courses (EQD2 - ∑max) were independent factors influencing TLI. The 5-year incidence of TLI for an IT ≤26 or >26 months was 35.9 and 53.7 % respectively (p = 0.024). The median maximum doses delivered to the injured TLs were significantly higher than was the case for the uninjured TLs after two courses of radiotherapy (135.3 and 129.8 Gy, respectively: p < 0.001). The incidence of TLI with an EQD2 - ∑max < 125 Gy was <5 %, and with an EQD2 - ∑max <145 Gy it was <50 %. A treatment mode limiting EQD2 - ∑max <125 Gy with a >2-year interval was found to be relatively safe.

ESR1 gene amplification in endometrial carcinomas: a clinicopathological analysis.

PubMed

Rahman, Mohammed Tanjimur; Nakayama, Kentaro; Rahman, Munmun; Ishikawa, Masako; Katagiri, Hiroshi; Katagiri, Atsuko; Ishibashi, Tomoka; Sato, Emi; Iida, Kouji; Ishikawa, Noriyuki; Nakayama, Naomi; Miyazaki, Kohji

2013-09-01

This study investigated the clinicopathological significance of estrogen receptor 1 (ESR1) gene amplification and its relationship to phosphatase and tensin homolog (PTEN), human epidermal growth factor receptor 2 (HER2), MutL homolog 1 (MLH1), p53, and AT rich interactive domain 1A (ARID1A) expression in endometrial carcinomas. ESR1 amplification and expression were assessed by fluorescence in situ hybridization and immunohistochemistry. Clinical data were collected by retrospective chart review. ESR1 amplification was identified in 13 out of 111 (11.7%) endometrial carcinomas. No significant association was observed between ESR1 amplification and International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.17), histological grade (p=0.35), lymph node metastasis (p=0.51), or deep myometrial invasion (p=0.46). ESR1 amplification was independent of PTEN, p53, HER2, MLH1, and ARID1A protein expression. Patients without estrogen receptor (ER) or progesterone receptor (PR) expression had shorter progression-free and overall survival than those with ER or PR expression (p<0.01). ESR1 amplification is independent of known clinicopathological factors related to poor prognosis and PTEN, p53, HER2, MLH1, and ARID1A protein expression, suggesting ESR1 amplification may be an early event in endometrial carcinoma development.

[Retroviral-mediated transfer of a hygromycin phosphotransferase-thymidine kinase fusion gene into human bladder carcinoma cell].

PubMed

Ye, C; Chen, S; Pei, X; Li, L; Feng, K

1999-08-01

To evaluate the therapeutic efficacy of retroviral-mediated hygromycin phosphotransferase-thymidine kinase fusion gene (HyTK)/GCV on human bladder carcinoma cell. A retroviral expression vector pL (HyTK) SN was constructed. By using FuGENE 6-mediated transfection and "ping-pong effect" technique, high-titer of retroviral supernatant was obtained and HyTK gene was transferred into EJ cells. A retroviral vector encoding, enhanced green fluorescent protein, EGFP was used to rapidly detect the transduction efficiency. Antitumor effects were observed after GCV treatment. In vitro experiments demonstrated the EJ cells transferred by HyTK gene were killed in the GCV treatment. Non-transduced parental cells were not sensitive to GCV, but they were dead by the bystander killing of neighboring cells when mixed with EJ/HyTK cells at various ratios. In addition, this not only affect wild-type EJ cells but also cells from different bladder carcinoma cell lines. Retroviral-mediated HyTK/GCV systems were a promising suicide gene therapy for bladder carcinoma. EGFP may act as a convenient and rapid reporter to monitor retroviral-mediated gene transfer and expression in bladder carcinoma cells.

Genome-wide analysis of Epstein-Barr virus identifies variants and genes associated with gastric carcinoma and population structure.

PubMed

Yao, Youyuan; Xu, Miao; Liang, Liming; Zhang, Haojiong; Xu, Ruihua; Feng, Qisheng; Feng, Lin; Luo, Bing; Zeng, Yi-Xin

2017-10-01

Epstein-Barr virus is a ubiquitous virus and is associated with several human malignances, including the significant subset of gastric carcinoma, Epstein-Barr virus-associated gastric carcinoma. Some Epstein-Barr virus-associated diseases are uniquely prevalent in populations with different geographic origins. However, the features of the disease and geographically associated Epstein-Barr virus genetic variation as well as the roles that the variation plays in carcinogenesis and evolution remain unclear. Therefore, in this study, we sequenced 95 geographically distinct Epstein-Barr virus isolates from Epstein-Barr virus-associated gastric carcinoma biopsies and saliva of healthy donors to detect variants and genes associated with gastric carcinoma and population structure from a genome-wide spectrum. We demonstrated that Epstein-Barr virus revealed the population structure between North China and South China. In addition, we observed population stratification between Epstein-Barr virus strains from gastric carcinoma and healthy controls, indicating that certain Epstein-Barr virus subtypes are associated with different gastric carcinoma risks. We identified that the BRLF1, BBRF3, and BBLF2/BBLF3 genes had significant associations with gastric carcinoma. LMP1 and BNLF2a genes were strongly geographically associated genes in Epstein-Barr virus. Our study provides insights into the genetic basis of oncogenic Epstein-Barr virus for gastric carcinoma, and the genetic variants associated with gastric carcinoma can serve as biomarkers for oncogenic Epstein-Barr virus.

Incidence and dosimetric parameters for brainstem necrosis following intensity modulated radiation therapy in nasopharyngeal carcinoma.

PubMed

Li, Yang-Chan; Chen, Fo-Ping; Zhou, Guan-Qun; Zhu, Jin-Han; Hu, Jiang; Kang, De-Hua; Wu, Chen-Fei; Lin, Li; Wang, Xiao-Ju; Ma, Jun; Sun, Ying

2017-10-01

To clarify the incidence of brainstem toxicity and perform a dose-volume analysis for the brainstem after long-term follow-up of a large cohort of nasopharyngeal carcinoma (NPC) patients who underwent intensity-modulated radiation therapy (IMRT). All patients with NPC treated with IMRT at Sun Yat-sen University Cancer Center between April 2009 and March 2012 were retrospectively reviewed. A total of 1544 patients with follow-up >12months and detailed treatment plan data were included. Radiotherapy was administered using the simultaneous integrated boost technique in 2.0-2.48Gy per fractions/28-33 fractions. Brainstem necrosis was defined as lesions with high signal intensity on T2-weighted images and low signal intensity on T1-weighted images, with or without enhancement after administration of contrast in follow-up MRI. After median follow-up of 79.7months (range, 12.2-85.6months), 2/1544 (0.13%) patients developed brainstem necrosis after intervals of 12.3 and 18.5months. Actuarial incidence of brainstem necrosis was 0.07%, 0.13%, 0.13% and 0.13% after 1, 2, 3 and 5years, respectively. Overall, 384 (24.9%), 153 (9.9%), 67 (4.3%), 39 (2.5%), 78 (5.1%), and 114 (7.4%) patients had excessive doses of D max ≥64Gy, D1cc>59Gy, D2cc>59Gy, aV50>5.9cc, aV55>2.7cc and aV60>0.9cc respectively, of whom only two developed brainstem necrosis. Brainstem necrosis is rare in NPC. The definitive criteria based on conventional radiotherapy cannot accurately predict the occurrence of brainstem necrosis after IMRT, thus more flexible definitive criteria with strict restrictions need to be defined. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hypofractionated Dose-Painting Intensity Modulated Radiation Therapy With Chemotherapy for Nasopharyngeal Carcinoma: A Prospective Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bakst, Richard L.; Lee, Nancy; Pfister, David G.

2011-05-01

Purpose: To evaluate the feasibility of dose-painting intensity-modulated radiation therapy (DP-IMRT) with a hypofractionated regimen to treat nasopharyngeal carcinoma (NPC) with concomitant toxicity reduction. Methods and Materials: From October 2002 through April 2007, 25 newly diagnosed NPC patients were enrolled in a prospective trial. DP-IMRT was prescribed to deliver 70.2 Gy using 2.34-Gy fractions to the gross tumor volume for the primary and nodal sites while simultaneously delivering 54 Gy in 1.8-Gy fractions to regions at risk of microscopic disease. Patients received concurrent and adjuvant platin-based chemotherapy similar to the Intergroup 0099 trial. Results: Patient and disease characteristics are asmore » follows: median age, 46; 44% Asian; 68% male; 76% World Health Organization III; 20% T1, 52% T2, 16% T3, 12% T4; 20% N0, 36% N1, 36% N2, 8% N3. With median follow-up of 33 months, 3-year local control was 91%, regional control was 91%, freedom from distant metastases was 91%, and overall survival was 89%. The average mean dose to each cochlea was 43 Gy. With median audiogram follow-up of 14 months, only one patient had clinically significant (Grade 3) hearing loss. Twelve percent of patients developed temporal lobe necrosis; one patient required surgical resection. Conclusions: Preliminary findings using a hypofractionated DP-IMRT regimen demonstrated that local control, freedom from distant metastases, and overall survival compared favorably with other series of IMRT and chemotherapy. The highly conformal boost to the tumor bed resulted low rates of severe ototoxicity (Grade 3-4). However, the incidence of in-field brain radiation necrosis indicates that 2.34 Gy per fraction is not safe in this setting.« less

Dosimetric Predictors of Hypothyroidism After Radical Intensity-modulated Radiation Therapy for Non-metastatic Nasopharyngeal Carcinoma.

PubMed

Lee, V; Chan, Sum-Yin; Choi, Cheuk-Wai; Kwong, D; Lam, Ka-On; Tong, Chi-Chung; Sze, Chun-Kin; Ng, S; Leung, To-Wai; Lee, A

2016-08-01

To investigate dosimetric predictors of hypothyroidism after radical intensity-modulated radiation therapy (IMRT) for non-metastatic nasopharyngeal carcinoma (NPC). Patients with non-metastatic NPC treated with radical IMRT from 2008 to 2013 were reviewed. Serum thyroid function tests before and after IMRT were regularly monitored. Univariable and multivariable analyses were carried out for predictors of biochemical and clinical hypothyroidism. In total, 149 patients were recruited. After a median follow-up duration of 3.1 years, 33 (22.1%) and 21 (14.1%) patients developed biochemical and clinical hypothyroidism, respectively. Eight (24.2%) patients who had biochemical hypothyroidism developed clinical hypothyroidism later. Univariable and multivariable analyses revealed that the volume of the thyroid (P=0.002, multivariable), VS60 (the absolute thyroid volume spared from 60 Gy or less) (P<0.001, multivariable) and VS45 (P<0.001, multivariable) of the thyroid were significant predictors of biochemical hypothyroidism. The freedom from biochemical hypothyroidism was longer for those whose VS60 ≥ 10 cm(3) (mean 90.9 versus 62.6 months; P<0.001) and VS45 ≥ 5 cm(3) (mean 91.9 versus 65.2 months; P=0.001). Similarly multivariable analyses revealed that VS60 (P=0.001) and VS45 (P=0.003) were significant predictors of clinical hypothyroidism. The freedom from clinical hypothyroidism was longer for those whose VS60 ≥ 10 cm(3) (91.5 versus 73.3 months; P=0.002) and VS45 ≥ 5 cm(3) (91.5 versus 75.9 months; P=0.007). VS60 and VS45 of the thyroid should be considered important dose constraints against hypothyroidism without compromising target coverage during IMRT optimisation for NPC. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Contrast-enhanced dynamic and diffusion-weighted magnetic resonance imaging at 3.0 T to assess early-stage nasopharyngeal carcinoma.

PubMed

Ni, Liangping; Liu, Ying

2018-04-01

The present study aimed to assess early-stage nasopharyngeal carcinoma (NPC) with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) at 3.0 T. A total of 44 patients newly diagnosed with NPC were included in the present study. All patients underwent MR examination at 3.0 T using DCE-MRI and DWI. The volume transfer constant ( K trans ), flux rate constant between extravascular extracellular space and plasma ( K ep ), the volume of extravascular extracellular space per unit volume of tissue ( V e ) and the apparent diffusion coefficient (ADC) of tumours were investigated. Furthermore, the correlation between clinical stages and ADC value and K trans were analysed. The diagnostic accuracy of K trans and ADC were estimated using receiver operating characteristic curves. NPC stage correlated positively with K trans and negatively with ADC values. Additionally, tumour K trans negatively correlated with ADC value. The sensitivity and accuracy of combined K trans and ADC in distinguishing between stage II and stage III and stage III and IV were higher than the values of either measurement used separately. The present study suggested that K trans and ADC derived from DCE-MRI and DWI may be useful to detect stage early NPC accurately. K trans and ADC in combination were superior than either alone.

Potential surrogate endpoints for overall survival in locoregionally advanced nasopharyngeal carcinoma: an analysis of a phase III randomized trial

PubMed Central

Chen, Yu-Pei; Chen, Yong; Zhang, Wen-Na; Liang, Shao-Bo; Zong, Jing-Feng; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Guo, Ying; Lin, Ai-Hua; Liu, Meng-Zhong; Sun, Ying; Ma, Jun

2015-01-01

The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS, and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice’s four criteria. The Spearman’s rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice’s second criterion. Being consistent with all Prentice’s criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival. PMID:26219568

Potential surrogate endpoints for overall survival in locoregionally advanced nasopharyngeal carcinoma: an analysis of a phase III randomized trial.

PubMed

Chen, Yu-Pei; Chen, Yong; Zhang, Wen-Na; Liang, Shao-Bo; Zong, Jing-Feng; Chen, Lei; Mao, Yan-Ping; Tang, Ling-Long; Li, Wen-Fei; Liu, Xu; Guo, Ying; Lin, Ai-Hua; Liu, Meng-Zhong; Sun, Ying; Ma, Jun

2015-07-29

The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS, and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice's four criteria. The Spearman's rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice's second criterion. Being consistent with all Prentice's criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival.

Establishment and Analysis of the 3-dimensional (3D) Spheroids Generated from the Nasopharyngeal Carcinoma Cell Line HK1.

PubMed

Muniandy, Kalaivani; Sankar, Prabu Siva; Xiang, Benedict Lian Shi; Soo-Beng, Alan Khoo; Balakrishnan, Venugopal; Mohana-Kumaran, Nethia

2016-11-01

Spheroids have been shown to recapitulate the tumour in vivo with properties such as the tumour microenvironment, concentration gradients, and tumour phenotype. As such, it can serve as a platform for determining the growth and invasion behaviour pattern of the cancer cells as well as be utilised for drug sensitivity assays; capable of exhibiting results that are closer to what is observed in vivo compared to two-dimensional (2D) cell culture assays. This study focused on establishing a three-dimensional (3D) cell culture model using the Nasopharyngeal Carcinoma (NPC) cell line, HK1 and analysing its growth and invasion phenotypes. The spheroids will also serve as a model to elucidate their sensitivity to the chemotherapeutic drug, Flavopiridol. The liquid overlay method was employed to generate the spheroids which was embedded in bovine collagen I matrix for growth and invasion phenotypes observation. The HK1 cells formed compact spheroids within 72 hours. Our observation from the 3 days experiments revealed that the spheroids gradually grew and invaded into the collagen matrix, showing that the HK1 spheroids are capable of growth and invasion. Progressing from these experiments, the HK1 spheroids were employed to perform a drug sensitivity assay using the chemotherapeutic drug, Flavopiridol. The drug had a dose-dependent inhibition on spheroid growth and invasion.

Industrial Pollutants and Nasopharyngeal Cancer: An Open Question.

PubMed

Menicagli, Roberto; Bolla, Gianni; Menicagli, Laura; Esseiridou, Anastassia

2017-05-01

Nasopharyngeal Carcinoma represents 0.7% of the total cancer cases in the world with an ASR index of 1.7 and is widely associated with Epstein-Barr virus. It is not common in Italy (ASR index of 0.5) while in China (ASR 1.9), one third of the clinical cases are observed in Guangdong (ASR index 11.3). It is also quite common in Malaysia and Indonesia. The activation of the cancerogenesis process happens after the exposure to some environmental parameters that epidemiological studies have indicated with various dietary habits, mainly for salted fish consumption. The purpose of this work is to highlight such as exposure to compounds, such as formaldehyde, which is present in the different working conditions of these countries and may lead to the real cause to establish the carcinogenic process. The most recent publications regarding the impact of various external factors on Pub Med, Google, TOXLINE, Chem Abstract, were analyzed with the radiological data that were found in Milan hospitals database. The relationship between food consumption and nasopharyngeal cancer are not clear and statistically insignificant in Indonesia. In Malaysia, the preparation of natural rubber for the use of formaldehyde is a dangerous environmental factor. The same exposure is a risk factor in Guangdong, where many workers are employed in the wood panel industry. Incidence of cancer in these Chinese ethnic groups decreases when they migrate to other countries. In the last 5 years, few cases were recorded in Italy, without any apparent change in ethnic environmental factors or HBV infection Discussion: In the production of natural rubber, a lot of people are exposed to formaldehyde during the various steps of preparation and production such as stripping, drying and coagulation without observing proper environmental hygiene precautions. The same working conditions are present in industrial production of wood panels in Guangdong, China. The relationship between exposure to formaldehyde and

Adulthood consumption of preserved and nonpreserved vegetables and the risk of nasopharyngeal carcinoma: a systematic review.

PubMed

Gallicchio, Lisa; Matanoski, Genevieve; Tao, Xuguang Grant; Chen, Liwei; Lam, Tram K; Boyd, Kristina; Robinson, Karen A; Balick, Lyssa; Mickelson, Stephanie; Caulfield, Laura E; Herman, James G; Guallar, Eliseo; Alberg, Anthony J

2006-09-01

The incidence rates of nasopharyngeal carcinoma (NPC) are dramatically higher in certain regions of Asia compared to the rest of the world. Few risk factors for NPC are known; however, in contrast to the hypothesized health benefits of nonpreserved vegetables, it is thought that preserved vegetable intake may play a role in contributing to the higher incidence of NPC in high-risk regions. Therefore, the purpose of this study was to systematically review the epidemiologic evidence on the associations between adulthood intake of preserved and nonpreserved vegetables and NPC risk. A search of the epidemiological literature from 1966 to 2004 was performed using several bibliographic databases, including PubMed and the Chinese Biomedical Literature Database System. There were no language restrictions. Meta-analysis was conducted to obtain pooled odds ratios (ORs) for the highest-versus-lowest categories of preserved and nonpreserved vegetable intake. A total of 16 case-control studies were identified in the search. Results showed that highest-versus-lowest preserved vegetable intake was associated with a 2-fold increase in the risk of NPC (Random Effects Odds Ratio (RE OR) 2.04; 95% Confidence Limits (CL) 1.43, 2.92). Conversely, high nonpreserved vegetable intake was associated with 36% decrease in the risk of NPC (RE OR 0.64; 95% CL 0.48, 0.85). Findings for both preserved and nonpreserved vegetables were consistent across vegetable type and by country of study. Further research in high-risk areas to gain insight into the risk associated with preserved vegetables and protection associated with nonpreserved vegetables may advance understanding of NPC and yield clues for prevention. Copyright 2006 Wiley-Liss, Inc.

Randomized controlled trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma

PubMed Central

Meng, Zhiqiang; Garcia, M. Kay; Hu, Chaosu; Chiang, Joseph; Chambers, Mark; Rosenthal, David I.; Peng, Huiting; Zhang, Ying; Zhao, Qi; Zhao, Genming; Liu, Luming; Spelman, Amy; Palmer, J. Lynn; Wei, Qi; Cohen, Lorenzo

2011-01-01

Background Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients and available treatments are of little benefit. The objective of this trial was to determine if acupuncture can prevent xerostomia among head/neck patients undergoing radiotherapy. Methods A randomized, controlled trial among patients with nasopharyngeal carcinoma was conducted comparing acupuncture to standard care. Participants were treated at Fudan University Shanghai Cancer Center, Shanghai, China. Forty patients were randomized to acupuncture treatment and 46 to standard care. Patients were treated 3 times/week on the same days they received radiotherapy. Subjective measures included the Xerostomia Questionnaire (XQ) and MD Anderson Symptom Inventory for Head/Neck (MDASI-HN). Objective measures were unstimulated and stimulated whole salivary flow rates (UWSFR; SSFR). Patients were followed for 6 months after the end of radiotherapy. Results XQ scores for acupuncture were statistically significantly lower than controls starting in week 3 through the 6-months(P=0.003 at week3, all other P’s < 0.0001), with clinically significant differences as follows: week 11- RR 0.63 [95% CI, 0.45, 0.87]; 6 months - RR 0.38 [95% CI, 0.19, 0.76]. Similar findings were seen for MDASI-HN scores. Group differences emerged as early as 3 weeks into treatment for saliva (UWSFR, P = 0.0004), with greater saliva flow in the acupuncture group at week 7 (UWSFR, P < 0.0001; SSFR, P = 0.002) and 11 (UWSFR, P < 0.02; SSFR, P < 0.03) and at 6 months (SSFR, P < 0.003). Conclusions Acupuncture given concurrently with radiotherapy significantly reduced xerostomia and improved QOL. PMID:22072272

Consumption of salted fish and other risk factors for nasopharyngeal carcinoma (NPC) in Tianjin, a low-risk region for NPC in the People's Republic of China.

PubMed

Ning, J P; Yu, M C; Wang, Q S; Henderson, B E

1990-02-21

The dietary habits, occupational exposures, use of tobacco and alcohol, and medical history were compared among 100 patients with histologically confirmed nasopharyngeal carcinoma (NPC) in Tianjin City, People's Republic of China, and 300 neighborhood controls who were individually matched to the patients with regard to age (within 5 yr), sex, and race (Han). Exposure to salted fish was significantly associated with an increased risk of NPC. Four characteristics of exposure to salted fish independently contributed to the increased risk: (a) earlier age at first exposure, (b) increasing duration of consumption, (c) increasing frequency of consumption, and (d) cooking the fish by steaming it rather than frying, grilling, or boiling it. In addition, significant associations were observed for consumption in childhood of salted shrimp paste (increased risk) and carrots (reduced risk), and the three dietary effects (i.e., those from consumption of salted fish, salted shrimp paste, and carrots) were independent of each other. None of the non-dietary factors studied were significantly associated with NPC risk.

Evaluation of the Dosimetric Feasibility of Hippocampal Sparing Intensity-Modulated Radiotherapy in Patients with Locally Advanced Nasopharyngeal Carcinoma

PubMed Central

Gan, Hua; Denniston, Kyle A.; Li, Sicong; Tan, Wenyong; Wang, Zhaohua

2014-01-01

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%, Dmean, Dmedian, D98% and Dmin) 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 Dmin (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. PMID:24587184

Classification of ductal carcinoma in situ by gene expression profiling.

PubMed

Hannemann, Juliane; Velds, Arno; Halfwerk, Johannes B G; Kreike, Bas; Peterse, Johannes L; van de Vijver, Marc J

2006-01-01

Ductal carcinoma in situ (DCIS) is characterised by the intraductal proliferation of malignant epithelial cells. Several histological classification systems have been developed, but assessing the histological type/grade of DCIS lesions is still challenging, making treatment decisions based on these features difficult. To obtain insight in the molecular basis of the development of different types of DCIS and its progression to invasive breast cancer, we have studied differences in gene expression between different types of DCIS and between DCIS and invasive breast carcinomas. Gene expression profiling using microarray analysis has been performed on 40 in situ and 40 invasive breast cancer cases. DCIS cases were classified as well- (n = 6), intermediately (n = 18), and poorly (n = 14) differentiated type. Of the 40 invasive breast cancer samples, five samples were grade I, 11 samples were grade II, and 24 samples were grade III. Using two-dimensional hierarchical clustering, the basal-like type, ERB-B2 type, and the luminal-type tumours originally described for invasive breast cancer could also be identified in DCIS. Using supervised classification, we identified a gene expression classifier of 35 genes, which differed between DCIS and invasive breast cancer; a classifier of 43 genes could be identified separating between well- and poorly differentiated DCIS samples.

Classification of ductal carcinoma in situ by gene expression profiling

PubMed Central

Hannemann, Juliane; Velds, Arno; Halfwerk, Johannes BG; Kreike, Bas; Peterse, Johannes L; van de Vijver, Marc J

2006-01-01

Introduction Ductal carcinoma in situ (DCIS) is characterised by the intraductal proliferation of malignant epithelial cells. Several histological classification systems have been developed, but assessing the histological type/grade of DCIS lesions is still challenging, making treatment decisions based on these features difficult. To obtain insight in the molecular basis of the development of different types of DCIS and its progression to invasive breast cancer, we have studied differences in gene expression between different types of DCIS and between DCIS and invasive breast carcinomas. Methods Gene expression profiling using microarray analysis has been performed on 40 in situ and 40 invasive breast cancer cases. Results DCIS cases were classified as well- (n = 6), intermediately (n = 18), and poorly (n = 14) differentiated type. Of the 40 invasive breast cancer samples, five samples were grade I, 11 samples were grade II, and 24 samples were grade III. Using two-dimensional hierarchical clustering, the basal-like type, ERB-B2 type, and the luminal-type tumours originally described for invasive breast cancer could also be identified in DCIS. Conclusion Using supervised classification, we identified a gene expression classifier of 35 genes, which differed between DCIS and invasive breast cancer; a classifier of 43 genes could be identified separating between well- and poorly differentiated DCIS samples. PMID:17069663

Analysis of genes involved in the PI3K/Akt pathway in radiation- and MNU-induced rat mammary carcinomas.

PubMed

Showler, Kaye; Nishimura, Mayumi; Daino, Kazuhiro; Imaoka, Tatsuhiko; Nishimura, Yukiko; Morioka, Takamitsu; Blyth, Benjamin J; Kokubo, Toshiaki; Takabatake, Masaru; Fukuda, Maki; Moriyama, Hitomi; Kakinuma, Shizuko; Fukushi, Masahiro; Shimada, Yoshiya

2017-03-01

The PI3K/AKT pathway is one of the most important signaling networks in human breast cancer, and since it was potentially implicated in our preliminary investigations of radiation-induced rat mammary carcinomas, our aim here was to verify its role. We included mammary carcinomas induced by the chemical carcinogen 1-methyl-1-nitrosourea to determine whether any changes were radiation-specific. Most carcinomas from both groups showed activation of the PI3K/AKT pathway, but phosphorylation of AKT1 was often heterogeneous and only present in a minority of carcinoma cells. The negative pathway regulator Inpp4b was significantly downregulated in both groups, compared with in normal mammary tissue, and radiation-induced carcinomas also showed a significant decrease in Pten expression, while the chemically induced carcinomas showed a decrease in Pik3r1 and Pdk1. Significant upregulation of the positive regulators Erbb2 and Pik3ca was observed only in chemically induced carcinomas. However, no genes showed clear correlations with AKT phosphorylation levels, except in individual carcinomas. Only rare carcinomas showed mutations in PI3K/AKT pathway genes, yet these carcinomas did not exhibit stronger AKT phosphorylation. Thus, while AKT phosphorylation is a common feature of rat mammary carcinomas induced by radiation or a canonical chemical carcinogen, the mutation of key genes in the pathways or permanent changes to gene expression of particular signaling proteins do not explain the pathway activation in the advanced cancers. Although AKT signaling likely facilitates cancer development and growth in rat mammary carcinomas, it is unlikely that permanent disruption of the PI3K/AKT pathway genes is a major causal event in radiation carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Analysis of genes involved in the PI3K/Akt pathway in radiation- and MNU-induced rat mammary carcinomas

PubMed Central

Showler, Kaye; Nishimura, Mayumi; Imaoka, Tatsuhiko; Nishimura, Yukiko; Morioka, Takamitsu; Blyth, Benjamin J.; Kokubo, Toshiaki; Takabatake, Masaru; Fukuda, Maki; Moriyama, Hitomi; Kakinuma, Shizuko; Fukushi, Masahiro

2017-01-01

Abstract The PI3K/AKT pathway is one of the most important signaling networks in human breast cancer, and since it was potentially implicated in our preliminary investigations of radiation-induced rat mammary carcinomas, our aim here was to verify its role. We included mammary carcinomas induced by the chemical carcinogen 1-methyl-1-nitrosourea to determine whether any changes were radiation-specific. Most carcinomas from both groups showed activation of the PI3K/AKT pathway, but phosphorylation of AKT1 was often heterogeneous and only present in a minority of carcinoma cells. The negative pathway regulator Inpp4b was significantly downregulated in both groups, compared with in normal mammary tissue, and radiation-induced carcinomas also showed a significant decrease in Pten expression, while the chemically induced carcinomas showed a decrease in Pik3r1 and Pdk1. Significant upregulation of the positive regulators Erbb2 and Pik3ca was observed only in chemically induced carcinomas. However, no genes showed clear correlations with AKT phosphorylation levels, except in individual carcinomas. Only rare carcinomas showed mutations in PI3K/AKT pathway genes, yet these carcinomas did not exhibit stronger AKT phosphorylation. Thus, while AKT phosphorylation is a common feature of rat mammary carcinomas induced by radiation or a canonical chemical carcinogen, the mutation of key genes in the pathways or permanent changes to gene expression of particular signaling proteins do not explain the pathway activation in the advanced cancers. Although AKT signaling likely facilitates cancer development and growth in rat mammary carcinomas, it is unlikely that permanent disruption of the PI3K/AKT pathway genes is a major causal event in radiation carcinogenesis. PMID:27738081

Trichostatin A Sensitizes Hepatocellular Carcinoma Cells to Enhanced NK Cell-mediated Killing by Regulating Immune-related Genes.

PubMed

Shin, Sangsu; Kim, Miok; Lee, Seon-Jin; Park, Kang-Seo; Lee, Chang Hoon

2017-01-01

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. The ability of HCC to avoid immune detection is considered one of the main factors making it difficult to cure. Abnormal histone deacetylation is thought to be one of the mechanisms for HCC immune escape, making histone deacetylases (HDACs) attractive targets for HCC treatment. Here, we investigated the effect of trichostatin A (TSA), a highly potent HDAC inhibitor, on HCC (HepG2) gene expression and function. A genome wide-transcriptional microarray was used to identify genes regulated by TSA in HepG2 cells. Gene Ontology was used to identify pathways regulated by TSA, and these changes were confirmed by qPCR. The effect of TSA on natural killer (NK) cell-mediated killing of HCC cell lines were analyzed by both flow cytometry and LDH cytotoxicity assay. A study was also conducted in a Balb/c nude mice xenograft model to assess the anti-tumor activity of TSA. TSA regulated the transcription of numerous innate immunity & tumor antigen recognition-associated genes, such as ULBP1 and RAET1G, in HCC cells. In vivo, TSA reduced tumor cell growth in an NK cell-dependent manner. In vitro, TSA treatment of HepG2 cells rendered them more susceptible to NK cell-mediated killing while increasing the expression of NKGD2 ligands, including ULBP1/2/3 and MICA/B. TSA also induced direct killing of HCC cells by stimulating apoptosis. TSA likely increases killing of HCC cells indirectly by increasing NK cell-directed killing and directly by increasing apoptosis. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Trichostatin A Sensitizes Hepatocellular Carcinoma Cells to Enhanced NK Cell-mediated Killing by Regulating Immune-related Genes

PubMed Central

SHIN, SANGSU; KIM, MIOK; LEE, SEON-JIN; PARK, KANG-SEO

2017-01-01

Background/Aim: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. The ability of HCC to avoid immune detection is considered one of the main factors making it difficult to cure. Abnormal histone deacetylation is thought to be one of the mechanisms for HCC immune escape, making histone deacetylases (HDACs) attractive targets for HCC treatment. Here, we investigated the effect of trichostatin A (TSA), a highly potent HDAC inhibitor, on HCC (HepG2) gene expression and function. Materials and Methods: A genome wide-transcriptional microarray was used to identify genes regulated by TSA in HepG2 cells. Gene Ontology was used to identify pathways regulated by TSA, and these changes were confirmed by qPCR. The effect of TSA on natural killer (NK) cell-mediated killing of HCC cell lines were analyzed by both flow cytometry and LDH cytotoxicity assay. A study was also conducted in a Balb/c nude mice xenograft model to assess the anti-tumor activity of TSA. Results: TSA regulated the transcription of numerous innate immunity & tumor antigen recognition-associated genes, such as ULBP1 and RAET1G, in HCC cells. In vivo, TSA reduced tumor cell growth in an NK cell-dependent manner. In vitro, TSA treatment of HepG2 cells rendered them more susceptible to NK cell-mediated killing while increasing the expression of NKGD2 ligands, including ULBP1/2/3 and MICA/B. TSA also induced direct killing of HCC cells by stimulating apoptosis. Conclusion: TSA likely increases killing of HCC cells indirectly by increasing NK cell-directed killing and directly by increasing apoptosis. PMID:28871002

Clinical Investigation Program.

DTIC Science & Technology

1985-10-01

Patients with Nasopharyngeal Carcinoma (NPC) and Determination of the Effect of IFN on Epstein - Barr Virus (EBV)-related Immunological Markers (0) (P...with Nasopharyngeal Carcinoma (NPC) and Determination of the Effect of IFN on Epstein - Barr virus (EBV)-related Immunological Markers Principal...Ribosomal Vaccine (0) (PR) (P) 12A/84 Lieberman, M. M. Relationship of the Immune 26 Response to the Heat Sensitivity of the Moloney Virus -Induced YAC

A Giant Juvenile Nasopharyngeal Angiofibroma

PubMed Central

Yüce, Salim; Uysal, İsmail Önder; Doğan, Mansur; Polat, Kerem; Şalk, İsmail; Müderris, Suphi

2012-01-01

Juvenile nasopharyngeal angiofibroma (JNA) are locally growing highly vascular tumours. They are treated primarily by surgical excision ranging from open approach to endoscopic approach. We presented a 20-year-old male with a giant nasopharyngeal juvenile angiofibroma obliterating the pterygopalatine fossa bilaterally, invasing the sphenoid bone and extending to the left nasal passage. His complaints were epistaxis and nasal obstruction. After embolization, the patient was treated surgically with endoscopic approach and discharged as cured without any complication. PMID:23714961

SU-F-T-200: Dosimetric Variation of Organs at Risk for Recurrent Nasopharyngeal Carcinoma (rNPC) Patients Treated by Carbon Ion Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, W; Sheng, Y; Shahnazi, K

2016-06-15

Purpose: Investigate the factors which affect the doses of organs at risk (OARs) for head and neck carbon ion therapy. Methods: Ten locally recurrent nasopharyngeal carcinoma cases with similar prescriptions were selected. All patients’ organs at risk (OARs) as well as CTVs were contoured by an experienced physician. Carbon ion treatment plans were created using a Syngo treatment planning system (Siemens, Germany). The CTVs were expanded to make optimized target volumes (OTVs) by considering treatment uncertainties and OAR protections. All plans were reviewed by this physician to be clinically acceptable. The OTV was expanded an additional 3mm to define themore » volume where beam spots could be put. A volume was also drawn 6 mm around the OTV to approximate the 50 % dose volume. The volumes where the OARs overlapped the OTV + 3 mm and OTV + 6 mm volumes, termed residual volumes, were then calculated. Results: The residual volumes within OTV + 3 mm were directly related to the OAR maximum dose. The percentage of the residual volume within the OTV + 6 mm with respect to the OAR volume was strongly related to the OAR mean doses. OAR mean doses also were affected by the beam setups. For example, if the OARs were in the beam entrance, the superior beams would sharply decrease the mean doses of the OARs hit by the lateral beams while increasing the mean doses of the OARs hit by the superior beam; the mean dose of the OARs which were hit by higher weight beams would be higher than the OARs hit by lower weight beams. Conclusion: Physicians should be cautious when contouring OARs, especially those close to CTVs and sensitive to large doses. Planners should set the OTV and beam parameters properly in order to save the OARs.« less

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

PubMed Central

Luo, Yangkun; Feng, Mei; Fan, Zixuan; Zhu, Xiaodong; Jin, Feng; Li, Rongqing; Wu, Jingbo; Yang, Xia; Jiang, Qinghua; Bai, Hongfang; Huang, Yecai; Lang, Jinyi

2016-01-01

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. PMID:27375766

Identification of surrogate endpoints in patients with locoregionally advanced nasopharyngeal carcinoma receiving neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone.

PubMed

Chen, Yu-Pei; Zhang, Wen-Na; Tang, Ling-Long; Mao, Yan-Ping; Liu, Xu; Chen, Lei; Zhou, Guan-Qun; Mai, Hai-Qiang; Shao, Jian-Yong; Jia, Wei-Hua; Kang, Tie-Bang; Zeng, Mu-Sheng; Sun, Ying; Ma, Jun

2015-11-24

In the era of intensity-modulated radiotherapy (IMRT), the efficacy of additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is currently being investigated in ongoing trials. Overall survival (OS) is the gold standard endpoint in NPC trials. We performed this analysis to identify surrogate endpoints for OS, which could shorten follow-up duration and speed up assessment of treatment effects. We retrospectively analysed 208 matched-pair patients with locoregionally advanced NPC receiving NACT+CCRT or CCRT. Progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) and locoregional failure-free survival (LR-FFS) at 2 and 3 years were assessed as surrogates for 5-year OS according to Prentice's criteria. The strength of the associations were assessed using Spearman's rank correlation coefficient. No significant differences were observed between treatment arms for any surrogate endpoint at 2 years, which rejected Prentice's second criterion. In contrast, 3-year LR-FFS, PFS, FFS and D-FFS were consistent with all four of Prentice's criteria; the rank correlation coefficient (0.730) between 3-year PFS and 5-year OS was highest. 3-year PFS, FFS and D-FFS could be valid surrogate endpoints for 5-year OS; 3-year PFS may be the most accurate.

Fine genetic mapping of the gene for nevoid basal cell carcinoma syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wicking, C.; Berkman, J.; Wainwright, B.

1994-08-01

Nevoid basal cell carcinoma syndrome (NBCCS, or Gorlin syndrome) is a cancer predisposition syndrome characterized by multiple basal cell carcinomas and diverse developmental defects. The gene responsible for NBCCS, which is most likely to be a tumor suppressor gene, has previously been mapped to 9q22.3-q31 in a 12-cM interval between the microsatellite marker loci D9S12.1 and D9S109. Combined multipoint and haplotype analyses of additional polymorphisms in this region in our collection of Australasian pedigrees have further refined the localization of the gene to between the markers D9S196 and D9S180, an interval reported to be approximately 2 cM. 27 refs., 4more » figs., 1 tab.« less

Nasopharyngeal Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Nasopharyngeal cancer treatment options include radiation therapy, chemoradiation followed by adjuvant chemotherapy, surgery, and chemotherapy. Get detailed information about the treatment of newly diagnosed and recurrent nasopharyngeal cancer in this summary for clinicians.

Aberrant DNA methylation of tumor-related genes in oral rinse: a noninvasive method for detection of oral squamous cell carcinoma.

PubMed

Nagata, Satoshi; Hamada, Tomofumi; Yamada, Norishige; Yokoyama, Seiya; Kitamoto, Sho; Kanmura, Yuji; Nomura, Masahiro; Kamikawa, Yoshiaki; Yonezawa, Suguru; Sugihara, Kazumasa

2012-09-01

The early detection of oral squamous cell carcinoma (OSCC) is important, and a screening test with high sensitivity and specificity is urgently needed. Therefore, in this study, the authors investigated the methylation status of tumor-related genes with the objective of establishing a noninvasive method for the detection of OSCC. Oral rinse samples were obtained from 34 patients with OSCC and from 24 healthy individuals (controls). The methylation status of 13 genes was determined by using methylation-specific polymerase chain reaction analysis and was quantified using a microchip electrophoresis system. Promoter methylation in each participant was screened by receiver operating characteristic analysis, and the utility of each gene's methylation status, alone and in combination with other genes, was evaluated as a tool for oral cancer detection. Eight of the 13 genes had significantly higher levels of DNA methylation in samples from patients with OSCC than in controls. The genes E-cadherin (ECAD), transmembrane protein with epidermal growth factor-like and 2 follistatin-like domains 2 (TMEFF2), retinoic acid receptor beta (RARβ), and O-6 methylguanine DNA methyltransferase (MGMT) had high sensitivity (>75%) and specificity for the detection of oral cancer. OSCC was detected with 100% sensitivity and 87.5% specificity using a combination of ECAD, TMEFF2, RARβ, and MGMT and with 97.1% sensitivity and 91.7% specificity using a combination of ECAD, TMEFF2, and MGMT. The aberrant methylation of a combination of marker genes present in oral rinse samples was used to detect OSCC with >90% sensitivity and specificity. The detection of methylated marker genes from oral rinse samples has great potential for the noninvasive detection of OSCC. Copyright © 2012 American Cancer Society.

Gene expression-based chemical genomics identifies potential therapeutic drugs in hepatocellular carcinoma.

PubMed

Chen, Ming-Huang; Yang, Wu-Lung R; Lin, Kuan-Ting; Liu, Chia-Hung; Liu, Yu-Wen; Huang, Kai-Wen; Chang, Peter Mu-Hsin; Lai, Jin-Mei; Hsu, Chun-Nan; Chao, Kun-Mao; Kao, Cheng-Yan; Huang, Chi-Ying F

2011-01-01

Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis. Currently, only sorafenib is approved by the FDA for advanced HCC treatment; therefore, there is an urgent need to discover candidate therapeutic drugs for HCC. We hypothesized that if a drug signature could reverse, at least in part, the gene expression signature of HCC, it might have the potential to inhibit HCC-related pathways and thereby treat HCC. To test this hypothesis, we first built an integrative platform, the "Encyclopedia of Hepatocellular Carcinoma genes Online 2", dubbed EHCO2, to systematically collect, organize and compare the publicly available data from HCC studies. The resulting collection includes a total of 4,020 genes. To systematically query the Connectivity Map (CMap), which includes 6,100 drug-mediated expression profiles, we further designed various gene signature selection and enrichment methods, including a randomization technique, majority vote, and clique analysis. Subsequently, 28 out of 50 prioritized drugs, including tanespimycin, trichostatin A, thioguanosine, and several anti-psychotic drugs with anti-tumor activities, were validated via MTT cell viability assays and clonogenic assays in HCC cell lines. To accelerate their future clinical use, possibly through drug-repurposing, we selected two well-established drugs to test in mice, chlorpromazine and trifluoperazine. Both drugs inhibited orthotopic liver tumor growth. In conclusion, we successfully discovered and validated existing drugs for potential HCC therapeutic use with the pipeline of Connectivity Map analysis and lab verification, thereby suggesting the usefulness of this procedure to accelerate drug repurposing for HCC treatment.

Does Harvey-Ras gene expression lead to oral squamous cell carcinoma? A clinicopathological aspect

PubMed Central

Krishna, Akhilesh; Singh, Shraddha; Singh, Vineeta; Kumar, Vijay; Singh, Uma Shankar; Sankhwar, Satya Narayan

2018-01-01

Background: Harvey-Ras (H-Ras) is an important guanosine triphosphatase protein for the regulation of cellular growth and survival. Altered Ras signaling has been observed in different types of cancer either by gene amplification and/or mutation. The H-Ras oncogene mutations are well reported, but expression of the H-Ras gene is still unknown. Objective: This study aimed to examine both protein and messenger-RNA (mRNA) expressions of H-Ras in oral squamous cell carcinoma (OSCC) and analyzed the association with risk habits and the clinicopathological profile of cases. Methodology: A total of 65 tissue specimens of OSCC (case group) and equal number of normal tissues (control group) were included in this study. H-Ras protein and mRNA expressions were analyzed using immunohistochemical and quantitative real time-polymerase chain reaction techniques, respectively. Results: The H-Ras protein was significantly overexpressed in the oral carcinoma group compared to the normal group (P = 0.03). Most of the OSCC cases showed positive staining with moderate expression, while negative and moderate staining was high in the control group. The majority of H-Ras positive cases were found in individuals with multiple risk habits including tobacco chewing. The risk of H-Ras positivity was 1.46 times higher in smokers than non-smokers. H-Ras positivity increased in cases affected with buccal mucosa site and higher grade of carcinoma. Relative mRNA level of H-Ras was significantly elevated in oral carcinoma as compared with the control group (P ≤ 0.001). Protein and mRNA levels of H-Ras in case group was poorly correlated. Conclusion: H-Ras oncogene expression was markedly higher in oral carcinoma, and it can be a prognostic marker and target for an effective molecular therapy. PMID:29731559