Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

The impact of multimodality integrated positron emission tomography-computed tomography on improving the staging and management of head and neck malignancy: a cross- sectional study

ABSTRACT BACKGROUND: Clinical assessment of head and neck cancers is highly challenging owing to the complexity of regional anatomy and wide range of lesions. The diagnostic evaluation includes detailed physical examination, biopsy and imaging modalities for disease extent and staging. Appropriate imaging is done to enable determination of precise tumor extent and involvement of lymph nodes, and detection of distant metastases and second primary tumors. OBJECTIVE: To evaluate the initial staging discrepancy between conventional contrasted computed tomography (CT) and 18F-fluorodeoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) and its impact on management plans for head and neck malignancies. DESIGN AND SETTING: Prospective cross-sectional study in two tertiary-level hospitals. METHODS: This study included 30 patients with primary head and neck malignant tumors who underwent contrasted computed tomography and whole-body 18F-FDG PET/CT assessments. The staging and treatment plans were compared with the incremental information obtained after 18F-FDG PET/CT. RESULTS: 18F-FDG PET/CT was found to raise the stage in 33.3% of the cases and the treatment intent was altered in 43.3% of them, while there was no management change in the remaining 56.7%. 18F-FDG PET/CT had higher sensitivity (96% versus 89.2%) and accuracy (93% versus 86.7%) than conventional contrast-enhanced computed tomography. CONCLUSION: Our study demonstrated that 18F-FDG PET/CT had higher sensitivity and accuracy for detecting head and neck malignancy, in comparison with conventional contrast-enhanced computed tomography. 18F-FDG PET/CT improved the initial staging and substantially impacted the management strategy for head and neck malignancies.

Screening of active components of Euchresta japonica against nasopharyngeal carcinoma / 中国药房

OBJECTIVE To screen t he active component s of Euchresta japonica against nasopharyngeal carcinoma. METHODS Main chemical components of E. japonica were selected ，and their target proteins were predicted in Swiss Target Prediction database. The target proteins of nasopharyngeal cancer were obtained with GeneCards database. Protein-protein interaction（PPI）network was established after the target of chemical components of E. japonica was intersected with the target of nasopharyngeal carcinoma ；PPI network was analyzed by using Cytoscape 3.6.1 software，and the potential active components and key targets of E. japonica against nasopharyngeal carcinoma were screened. The molecular docking technology was used to evaluate binding ability of active component-key target ；active components of E. japonica against nasopharyngeal carcinoma were screened. The anti-nasopharyngeal cancer effect of potential active components of E. japonica was verified by cell proliferation experiment. RESULTS Seven potential active components （tonkinensisol，quercetin，sophoranone，matrine，genistein，coumarin，maackiain） and 10 core targets （SRC，PIK3CA，MAPK1，MAPK3，AKT1，MAPK8，MAP2K1，PTK2，EGFR，JAK3）of E. japonica against nasopharyngeal carcinoma were screened. The molecular docking results showed that above potential active components all possessed certain anti-nasopharyngeal cancer effect. Cell proliferation activity test showed that tonkinensisol ，sophoranone and maackiain had a very significant inhibitory activity on nasopharyngeal carcinoma cells CNE- 1. CONCLUSIONS Tonkinensisol， sophoranone and maackiain might be the main active components of E. japonica against nasopharyngeal carcinoma.

Effect of Wuzhishan Callicarpa nudiflora in Hainan Province on Cisplatin-induced Apoptosis of Nasopharyngeal Carcinoma Cells and Mechanism： Based on Nrf2/ARE Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of Wuzhishan Callicarpa nudiflora （LHZZ） on the sensitivity of nasopharyngeal carcinoma （NPC） cells to cisplatin （DDP） and the mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the survival rate of NPC HNE1 cells after treatment with different concentration of DDP （0，2，4，8，16，32 mg·L-1） and different concentration of LHZZ （0，25，50，75，100 mg·L-1）. The following groups were designed： control group （normal HNE1 cells），DDP group （8 mg·L-1 DDP，24 h），LHZZ group （50 mg·L-1 LHZZ，24 h），DDP + LHZZ group （8 mg·L-1 DDP + 50 mg·L-1 LHZZ，24 h），DDP + LHZZ + nuclear factor erythroid 2-related factor 2 （Nrf2） activator sulforaphane （SFN） group （8 mg·L-1 DDP + 50 mg·L-1 LHZZ，24 h， 10 μmol·L-1 SFN，24 h）. Then CCK-8 assay was employed to examine cell survival rate，colony formation test the colony-forming ability，flow cytometry and in situ terminal end-labeling（TUNEL） staining cell apoptosis，fluorescent probe 2'，7'-dichlorofluorescin diacetate （DCFH-DA） the level of reactive oxygen species （ROS） in cultured cells，Western blot the expression of apoptosis-related proteins in cells，such as B-cell lymphoma/leukemia-2 （Bcl-2），Bcl-2 associated X protein （Bax），and cysteinyl aspartate specific proteinase-3 （Caspase-3），and Real-time quantitative polymerase chain reaction （Real-time PCR） the expression of Nrf2 and antioxidant response element （ARE） mRNA in cells. ResultThe survival rates of cells treated with different concentration of DDP and different concentration of LHZZ decreased compared with that in the control group （P<0.05）. Compared with the DDP group and the LHZZ group，DDP + LHZZ group demonstrated decrease in cell survival rate，number of cell colonies，and Bcl-2 level，and increase in the apoptosis level and the expression of Bax and Caspase-3 （P<0.05）. However，after the addition of SFN，the Nrf2/ARE signaling pathway was activated and the above variation was inhibited （P<0.05）. In addition，the level of intracellular ROS in the LHZZ group was lower than that in the control group （P<0.05） and the level in the DDP + LHZZ group was lower than that in the DDP group （P<0.05）. Moreover，the ROS level in the DDP + LHZZ + SFN group was higher than that in the DDP+LHZZ group （P<0.05）. ConclusionLHZZ can enhance the sensitivity of DDP-induced NPC apoptosis，possibly by blocking the Nrf2/ARE signaling pathway and inhibiting the level of ROS.

Scutellariae Barbatae Herba Extract Promotes Cycle Arrest of Nasopharyngeal Carcinoma Cells by Inhibiting STAT3/SKP2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of Scutellariae Barbatae Herba extract on on the cycle arrest of nasopharyngeal carcinoma cells and the possible mechanism by adding different concentration of Scutellariae Barbatae Herba extract （0.25， 0.5， 1 g·L-1） in the culture medium， taking CNE1 （nasopharyngeal carcinoma cells） as the research object. MethodAfter the treatment of CNE1 by Scutellariae Barbatae Herba extract， cell counting kit-8 （CCK-8） was used to detect cell proliferation， and Giemsa staining was used to detect the clone formation rate. Flow cytometry was used to detect cell cycle distribution， and reverse transcription-polymerase chain reaction （ RT-PCR） assay and Western blot assay were used to detect the relative expression of messenger ribonucleic acid （mRNA） by small interfering RNA （siRNA） or overexpression. ResultAs compared with the blank group， the proliferation and colony formation rate of CNE1 in the Scutellariae Barbatae Herba extract group significantly decreased （P<0.05， P<0.01） in a dose and time-dependent manner， whereas the percentage of cells in the presynthetic phase （G0/G1） increased （P<0.05， P<0.01）. The expression level of S-phase kinase associated protein 2 （SKP2） in the Scutellariae Barbatae Herba extract group significantly decreased （P<0.01） as compared with the blank group. As compared with the Scutellariae Barbatae Herba extract group， the protein levels of p21 and p27 significantly decreased in the overexpressed SKP2+ Scutellariae Barbatae Herba extract group （P<0.01）. As compared with the blank group， the signal activation and the phosphorylation level of signal transducer and activator of transcription 3 （STAT3） of CNE1 in the S. barbata extract group significantly decreased （P<0.05， P<0.01）. ConclusionScutellariae Barbatae Herba extract effectively inhibits the proliferation of CNE1， and the mechanism may be related to its action on the STAT3/SKP2 pathway.

Scutellariae Barbatae Herba Extract Promotes Cycle Arrest of Nasopharyngeal Carcinoma Cells by Inhibiting STAT3/SKP2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of Scutellariae Barbatae Herba extract on on the cycle arrest of nasopharyngeal carcinoma cells and the possible mechanism by adding different concentration of Scutellariae Barbatae Herba extract （0.25， 0.5， 1 g·L-1） in the culture medium， taking CNE1 （nasopharyngeal carcinoma cells） as the research object. MethodAfter the treatment of CNE1 by Scutellariae Barbatae Herba extract， cell counting kit-8 （CCK-8） was used to detect cell proliferation， and Giemsa staining was used to detect the clone formation rate. Flow cytometry was used to detect cell cycle distribution， and reverse transcription-polymerase chain reaction （ RT-PCR） assay and Western blot assay were used to detect the relative expression of messenger ribonucleic acid （mRNA） by small interfering RNA （siRNA） or overexpression. ResultAs compared with the blank group， the proliferation and colony formation rate of CNE1 in the Scutellariae Barbatae Herba extract group significantly decreased （P<0.05， P<0.01） in a dose and time-dependent manner， whereas the percentage of cells in the presynthetic phase （G0/G1） increased （P<0.05， P<0.01）. The expression level of S-phase kinase associated protein 2 （SKP2） in the Scutellariae Barbatae Herba extract group significantly decreased （P<0.01） as compared with the blank group. As compared with the Scutellariae Barbatae Herba extract group， the protein levels of p21 and p27 significantly decreased in the overexpressed SKP2+ Scutellariae Barbatae Herba extract group （P<0.01）. As compared with the blank group， the signal activation and the phosphorylation level of signal transducer and activator of transcription 3 （STAT3） of CNE1 in the S. barbata extract group significantly decreased （P<0.05， P<0.01）. ConclusionScutellariae Barbatae Herba extract effectively inhibits the proliferation of CNE1， and the mechanism may be related to its action on the STAT3/SKP2 pathway.

Function of AXL and molecular mechanisms in regulation of nasopharyngeal carcinoma / 中南大学学报(医学版)

OBJECTIVES@#Nasopharyngeal carcinoma (NPC) is a highly invasive epithelial malignant tumor with unique geographical and ethnic distribution characteristics. NPC is mostly found in south China and Southeast Asia, and its treatment mainly depends on radiotherapy and chemotherapy. However, NPC is usually found in the late stage, and local recurrence and distant metastasis are common, leading to poor prognosis. The receptor tyrosine kinase AXL is up-regulated in various tumors and it is involved in tumor proliferation, migration, invasion, and other processes, which are associated with poor prognosis of tumors. This study aims to detect the expression of AXL in NPC cell lines and tissues, and to investigate its biological function of AXL and the underlying molecular mechanisms in regulation of NPC.@*METHODS@#The expression levels of AXL in normal nasopharyngeal epithelial tissues and NPC tissues were analyzed by GSE68799, GSE12452, and GSE53819 data sets based on Gene Expression Omnibus (GEO) database. The Cancer Genome Atlas (TCGA) database was used to analyze the relationship between AXL and prognosis of head and neck squamous cell carcinoma (HNSC). The indicators of prognosis included overall survival (OS), disease-free interval (DFI), disease-specific survival (DSS), and progression-free interval (PFI). Western blotting assay was used to detect the AXL protein expression levels in normal nasopharyngeal epithelial cell line and NPC cell lines. Immunohistochemical method was used to detect AXL expression levels in normal nasopharyngeal epithelial tissues and NPC tissues. Cell lines with stable AXL knockdown were established by infecting 5-8F and Fadu cells with lentivirus interference vector, and cell lines with stable AXL overexpression were established by infecting C666-1 and HK-1 cells with lentivirus expression vector. Real-time PCR and Western blotting were used to detect the efficiency of knockdown and overexpression in stable cell lines. The effects of AXL knockdown or overexpression on proliferation, migration, and invasion of NPC cells were detected by CCK-8, plate colony formation, and Transwell assays, and the effect of AXL knockdown on tumor growth in nude mice was detected by subcutaneous tumor formation assay. The sequence of AXL upstream 2.0 kb promoter region was obtained by UCSC online database. The PROMO online database was used to predict AXL transcription factors with 0% fault tolerance, and the JASPAR online database was used to predict the binding sites of ETS1 to AXL. Real-time PCR and Western blotting were used to detect the effect of ETS1 on AXL protein and mRNA expression. The AXL upstream 2.0 kb promoter region was divided into 8 fragments, each of which was 250 bp in length. Primers were designed for 8 fragments. The binding of ETS1 to AXL promoter region was detected by chromatin immuno-precipitation (ChIP) assay to determine the direct regulatory relationship between ETS1 and AXL. Rescue assay was used to determine whether ETS1 affected the proliferation, migration, and invasion of NPC cells through AXL.@*RESULTS@#Bioinformatics analysis showed that AXL was highly expressed in NPC tissues (P<0.05), and AXL expression was positively correlated with OS, DFI, DSS, and PFI in HNSC patients. Western blotting and immunohistochemical results showed that AXL was highly expressed in NPC cell lines and tissues compared with the normal nasopharyngeal epithelial cell line and tissues. Real-time PCR and Western blotting results showed that knockdown and overexpression efficiency in the stable cell lines met the requirements of subsequent experiments. The results of CCK-8, plate colony formation, Transwell assays and subcutaneous tumor formation in nude mice showed that down-regulation of AXL significantly inhibited the proliferation, migration, invasion of NPC cells and tumor growth (all P<0.05), and the up-regulation of AXL significantly promoted the proliferation, migration, and invasion of NPC cells (all P<0.05).As predicted by PROMO and JASPAR online databases, ETS1 was a transcription factor of AXL and had multiple binding sites in the AXL promoter region. Real-time PCR and Western blotting results showed that knockdown or overexpression of ETS1 down-regulated or up-regulated AXL protein and mRNA expression levels. ChIP assay result showed that ETS1 bound to AXL promoter region and directly regulate AXL expression. Rescue assay showed that AXL rescued the effects of ETS1 on proliferation, migration and invasion of NPC cells (P<0.05).@*CONCLUSIONS@#AXL is highly expressed in NPC cell lines and tissues, which can promote the malignant progression of NPC, and its expression is regulated by transcription factor ETS1.

Effects of albumin-bound paclitaxel combined with nedaplatin inductive chemotherapy on loco-regionally advanced nasopharyngeal carcinoma / 中国药房

OBJECTIVE To observe the clinical efficacy and safety of albumin-bound paclitaxel combined with nedaplatin inductive chemotherapy followed by concurrent radiochemotherapy in the treatment of loco-regionally advanced nasopharyngeal carcinoma. METHODS The clinical data of 45 patients （observation group ） with loco-regionally advanced nasopharyngeal carcinoma（Ⅲ/Ⅳa stage ）who received albumin-bound paclitaxel combined with nedaplatin inductive chemotherapy in our hospital from August 2017 to July 2018 were retrospectively analyzed. Propensity score was used to match 45 patients（control group ）with loco-regionally advanced nasopharyngeal carcinoma who received docetaxel combined with cisplatin and fluorouracil inductive chemotherapy. After inductive chemotherapy ，both groups received intensity-modulated radiochemotherapy （IMRT）；observation group was additionally given concurrent nedaplatin chemotherapy ，and control groups was given concurrent cisplatin chemotherapy. Clinical efficacy and the incidence of ADR were compared between 2 groups. RESULTS All patients completed treatment and 3-year follow-up. After inductive chemotherapy and 1，3 months after concurrent radiochemotherapy ，there was no statistical significance in short-term response between 2 groups（P＞0.05）. There was no significantly difference in 3-years local control rate and 3-years free from distant metastasis between 2 groups（P＞0.05）. The incidences of leucopenia （grade 3 or above ）in the observation group were significantly lower than those in the control group ，and the incidence of peripheral neuropathy in observation group was higher than that in control group （P＜0.05）. The incidences of thrombocytopenia （grade 2 or above ），rash and vomiting （grade 2 or above ）in the observation group were lower than those in the control group ，but the difference was not statistically significant （P＞0.05）. There was no significant difference in the incidence of other ADR between 2 groups（P＞0.05）. CONCLUSIONS Albumin-bound paclitaxel combined with nedaplatin inductive chemotherapy followed by concurrent chemoradiotherapy in the treatment of loco-regionally advanced nasopharyngeal carcinoma is effective and tolerable ．

Anxiety and depression among dysphagic persons after radiotherapy for nasopharyngeal carcinoma / 中华物理医学与康复杂志

Objective:To investigate the incidence of anxiety and depression after radiotherapy for nasopharyngeal carcinoma among persons suffering from dysphagia, and to analyze the related factors.Methods:A total of 143 persons with dysphagia after radiotherapy for nasopharyngeal carcinoma were studied. They completed a general information questionnaire and were evaluated using the hospital anxiety and depression scale.Results:Anxiety was detected in 52 of the subjects (36.3%) and depression in 61 (42.7%). Multivariate regression analysis showed that the average total anxiety score was significantly related to whether the respondent used a gastric tube and whether they lived in a religious household. The average total depression score was related to gastric tube use and to the respondent′s district of residence.Conclusion:Persons with dysphagia after radiotherapy for nasopharyngeal carcinoma often suffer anxiety and depression. The use of a gastric tube increases the risk. The depression of rural residents and those with religious beliefs tends to be milder.

Progress on delineation of clinical target volume of primary tumour of nasopharyngeal carcinoma / 中华放射肿瘤学杂志

Accurate delineation of clinical target volume (CTV) of nasopharyngeal carcinoma is of significance to prevent local recurrence and improve the survival rate of patients. When intensity-modulated radiotherapy (IMRT) was first introduced, CTV was delineated based on two-dimensional radiotherapy experience. The local recurrence-free survival is high, but the adverse reactions induced by radiotherapy are severe and the patients’ quality of life is poor. How to reduce CTV to alleviate acute and late radiotherapy-induced adverse reactions without deteriorating therapeutic effect has currently become a research hotspot. Despite the 2010 Chinese Nasopharyngeal Carcinoma IMRT Target and Dose Design Guideline Expert Consensus and the International Guideline for the Delineation of the CTV for Nasopharyngeal Carcinoma as references, the optimal individualized and standardized delineation of CTV remains controversial. This review summarizes the progress on the delineation of CTV of primary tumour of nasopharyngeal carcinoma, aiming to provide practical reference for clinicians.

MRI-based assessment of effects of radiotherapy on the onset and progression of mastoiditis in patients with nasopharyngeal carcinoma / 中华放射医学与防护杂志

Objective:To analyze the effects of radiotherapy on the onset and progression of mastoiditis in patients with nasopharyngeal carcinoma (NPC) using magnetic resonance imaging (MRI) and to explore the risk factors for the onset of mastoiditis after radiotherapy.Methods:The onset and progression of mastoiditis of 204 NPC patients 3, 12, and 24 months after radiotherapy were analyzed based on MRI images. The multi-factor logistic regression analysis was applied to explore the risk factors of the onset of mastoiditis after radiotherapy. The cross-sectional area of the tensor veli palatini muscle was measured and the relationship between the atrophy degrees of the tensor veli palatini muscle and the onset of mastoiditis was analyzed.Results:The incidence of mastoiditis before radiotherapy was 20.6% (84/408, ears), and was 41.1% (168/408, ears), 22.3% (91/408, ears), and 19.6% (80/408, ears), respectively 3, 12, and 24 months after radiotherapy. The incidence of radiotherapy-induced mastoiditis was 35.8% (116/324, ears), 18.2% (59/324, ears), and 16.4% (53/324, ears), respectively 3, 12, and 24 months after radiotherapy. The remission rate of 63 patients (83 ears) who developed mastoiditis 3 months after radiotherapy was 63.9% (53/83, ears) and 75.9% (63/83, ears), respectively 12 and 24 months after radiotherapy. The remission rate of 54 patients (60 ears) who suffered mastoiditis before radiotherapy was 43.3% (26/60, ears), 65.0% (39/60, ears), and 73.3% (44/60, ears) 3, 12, and 24 months after radiotherapy. The multivariate analysis showed that the independent risk factors for radiotherapy-induced mastoiditis included age ≥50, clinical stages Ⅲ-Ⅳ, radiotherapy dose > 70 Gy, and tumors invading pharyngeal ostium of the eustachian tube. In addition, the atrophy degree of tensor veli palatini muscle 12 and 24 months after radiotherapy correlated with the onset of mastoiditis.Conclusions:The incidence of mastoiditis significantly increased 3 months after radiotherapy and significantly decreased 12 months after radiotherapy for NPC patients. The natural remission rate of radiotherapy-induced mastoiditis 12 months after radiotherapy was over 70%. The independent risk factors for radiotherapy-induced mastoiditis include age ≥50, clinical stages Ⅲ-Ⅳ, radiotherapy dose >70 Gy, and tumor invading pharyngeal ostium of the eustachian tube. The atrophy degree of the tensor veli palatini muscle 12 and 24 months after radiotherapy correlates with the onset of mastoiditis.

A randomized controlled study on the prevention and treatment of radiation-induced oral mucositis by Chinese herbal compound prescription / 中华放射医学与防护杂志

Objective:To evaluate the efficacy and safety of the combination of conventional western medicine therapy and oral traditional Chinese medicine (TCM) compound in the prevention and treatment of radiotherapy-inducedoral mucositis (RTOM) of nasopharyngeal carcinoma patients treated with concurrent radiotherapy and chemotherapy.Methods:A randomized, single-center, and open-label controlled experiment was conducted. Software Stata was used to generate random numbers, and 100 subjects were randomly assigned to two groups ata 1∶1 ratio, namely the integrated Chinese and western medicine group(the integrated group) and the conventional western medicine group. This study focused on the incidence of level-ⅢRTOM, followed by these verity degree of RTOM, therisk of malnutrition, and safety.Results:The incidences of level-III RTOM in the integrated group and the conventional western medicine group were 18% and 46%, respectively, with a statistically significant difference ( χ2=9.007, P=0.003). Compared to the integrated group, the conventional western medicine group showed a significantly increase dseverity degree of RTOM ( OR=3.269, 95% CI: 1.627-6.567, P<0.001) and higher risk of malnutrition ( OR=3.021, 95% CI: 1.786-5.109, P<0.001). Moreover, compared to the integrated group, the conventional western medicine group showed decrease dincidence of thirst (48.97% and 72.00% respectively; χ2=5.493, P=0.019) and decreased incidence of neutrophilcount reduction(12.24% and 30.00%, respectively, χ2=4.668, P=0.031). The incidence of mild/moderate adverse events related to TCM compound was 4.08%(2/49), and no serious adverse events related to TCM compound were observed. Conclusions:Compared to the conventional western medicine regimen, the integrated Chinese and western medicine regimen IS more effective in the prevention and treatment of RTOM. Meanwhile, its clinical application is safe and reliable.

Relationship of PI3K-Akt/mTOR/AMPK signaling pathway genetic mutation with efficacy and prognosis in nasopharyngeal carcinoma / 中南大学学报(医学版)

OBJECTIVES@#Genetic mutation is one of the important causes for tumor genesis and development, but genetic mutation in nasopharyngeal carcinoma (NPC) has rarely been reported. This study explored the role of phosphatidylinositol 3 kinase-protein kinase B (PI3K-Akt), mammalian target of rapamycin (mTOR), and adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway in the efficacy and prognosis in patients with NPC.@*METHODS@#A total of 31 patients with advanced NPC, who came from the Affiliated Cancer Hospital of Xiangya School of Medicine of Central South University/Hunan Provincial Cancer Hospital, were enrolled. All of the exons of 288 genes, introns of 38 genes and promoters or fusion breakpoint regions from the nasopharyngeal biopsy tissues before treatment were detected by the gene sequencing platform Illumina NextSeq CN500. The coding regions of 728 genes were carried out a high-depth sequencing of target region capture, and the 4 variant types of tumor genes (including point mutations, insertion deletions of small fragments, copy number variations, and currently known fusion genes) were detected. All of 31 patients received platinum-based induction chemotherapy combined with concurrent chemoradiotherapy and were followed up for a long time.@*RESULTS@#The 3-year regional failure-free survival (RFFS) and disease-free survival (DFS) in patients with PI3K-Akt pathway mutation were significantly lower than those in unmutated patients (χ2=6.647, P<0.05). The 3-year RFFS and DFS in patients with mTOR pathway mutations were significantly lower than those in unmutated patients, and there was significant difference (χ2=5.570, P<0.05). The rate of complete response (CR) in patients with unmutated AMPK pathway was significantly higher than that in patients with mutation at 3 months after treatment (P<0.05), and the 3-year RFFS and DFS in patients with AMPK pathway mutation were significantly lower than those in unmutated patients (χ2=4.553, P<0.05). PI3K-Akt/mTOR/AMPK signaling pathway mutations and pre-treatment EB virus DNA copy numbers were independent prognostic factors for 3-year RFFS and DFS in patients with NPC (both P<0.05).@*CONCLUSIONS@#The NPC patients with PI3K-Akt/mTOR/AMPK signaling pathway mutation have poor prognosis, and the detection of PI3K-Akt, mTOR, AMPK driver genes and signaling pathways by next-generation sequencing is expected to provide new idea for basic research and targeted therapy of NPC.

Secondary primary tumor mimicking osteoradionecrosis

ABSTRACT Nasopharyngeal carcinoma (NPC) is a malignant tumor rarely found in the head and neck, representing about 1% of all malignancies. The main treatment for NPC is radiation therapy, which is often given in combination with chemotherapy. However, such treatment may lead to long‐term complications, including second primary tumors (SPTs) and osteoradionecrosis (ORN). Both complications have similar radiological characteristics, which can lead to erroneous diagnoses. This paper describes a case of a second primary tumor in a patient after 20 years of radiotherapy in the area where a previous extraction was performed, mimicking an osteoradionecrosis process.

Supraglottic stenosis as a late complication of radiotherapy: a case report

ABSTRACT Nasopharyngeal carcinoma is rare and affect mainly men between the fourth and sixth decades of life. The clinic is characterized to be nonspecific and the main complaints or findings related to this disease are: cervical mass, aural dysfunction, and headache. The basis of treatment is radiotherapy that involves a wide field of irradiation of normal tissues, which usually generates sequelae with direct implications for quality of life. We report a case of a nasopharyngeal carcinoma treated with radiotherapy and chemotherapy that evolved, after 8 years, into supraglottic stenosis. We emphasize the relevance of clinical follow-up after radiotherapy, particularly due to the late sequelae and the relevance of using radiotherapy devices with a more focal cancer field, in order to minimize complications.

Combining respiratory function training with balloon dilatation for the rehabilitation of cricopharyngeal achalasia after radiotherapy for nasopharyngeal carcinoma / 中华物理医学与康复杂志

Objective:To observe the rehabilitative effect of combining respiratory function training with balloon dilatation for persons with cricopharyngeal achalasia after radiotherapy for nasopharyngeal carcinoma.Methods:A total of 120 nasopharyngeal carcinoma patients with cricopharyngeal achalasia after radiotherapy were randomly divided into an observation group and a control group, each of 60. Both groups were treated with routine functional swallowing training and balloon dilatation, while the observation group was additionally provided with respiratory function training 5 days a week for 8 weeks. Before the treatment and after 4 and 8 weeks of treatment, the swallowing function of both groups was evaluated using video fluoroscopy (VFSS), a functional oral intake scale (FOIS), cricopharyngeal muscle functional status and the M. D. Anderson dysphagia inventory (MDADI).Results:After 4 weeks of treatment the average VFSS, FOIS and MDADI scores of both groups were significantly better than before the treatment, and significant improvement continued over the subsequent four weeks. After 8 weeks of treatment, the average VFSS, FOIS and MDADI scores of the observation group had again improved significantly. Physiology, functioning, and their emotional state were also adjudged to have improved compared with 4 weeks earlier and compared with the control group.Conclusion:Combining respiratory function training with balloon dilatation can improve swallowing and can significantly reduce or delay swallowing disorders among patients with cyclopharyngeal achalasia after radiotherapy.

Comparison of the prognosis of advanced T and N stage in patients with nasopharyngeal carcinoma / 中国肿瘤临床

Objective: To retrospectively compare the prognosis between patients with locally advanced T and N stage nasopharyngeal carcinoma (NPC), to provide a reference for the clinical treatment of NPC. Methods: A total of 264 NPC cases from December 2011 to November 2017 visiting The General Hospital of Western Theater Command were pathologically diagnosed and retrospectively analyzed. Of these, 102 and 162 were locally advanced T and N stage, respectively. Results: The two groups 5-year overall survival (OS), progression-free survival (PFS), local relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared. These were 82.8% and 75.8% (P=0.271), 73.7% and 62.8% (P=0.043), 87.6% and 91.6% (P=0.646), 87.7% and 79.5% (P=0.066), respectively. Conclusions: The DMFS, OS and PFS decreased in patients with locally advanced N stage NPC, although there was no statistical difference. The significance of systemic and stratified treatment should be emphasized in patients with locally advanced N stage NPC in order to achieve a higher OS rate and reduce distant metastasis.

Role of EphA2 in pathogenesis of nasopharyngeal carcinoma and its potential as a therapeutic target / 中国肿瘤临床

The erythropoietin-producing hepatocellular receptor (Eph) and its ligand ephrin are the largest of the receptor tyrosine kinases (RTKs) family in humans. Since ephrin ligands and Eph receptors are membrane-bound proteins, binding and activation of Eph/ephrin intracellular signaling pathways can only occur via direct cell-cell interaction. Eph-ephrin complexes emanate bidirectional signals that affect cells expressing Eph and ephrin, respectively. Its repulsive signaling effects include retraction, which plays an important role in many physiological and pathological processes. EphA2 has been found to have a strong association with tumors and is most widely studied. EphA2 signal transduction in tumor cells may promote or inhibit tumor, depending on the tumor microenvironment. EphA2 "canonical" signaling involves ligand binding and kinase activity; thus EphA2 "noncanonical" signaling is ligand independent and lacks kinase activity. This review summarizes the pathogenesis of EphA2 in nasopharyngeal carcinoma (NPC), including ligand independent signal and EBV infection receptor, furthermore evaluates the prospect of its potential utilization as a target for cancer therapeutics. This may provide a new method for the prevention and treatment of NPC.

Study of standardizing nomenclatures for organs at risk of nasopharyngeal carcinoma via the contouring content-based image retrieval method / 中华放射肿瘤学杂志

Objective:Based on the AAPM TG-263, a Content-Based Standardizing Nomenclatures (CBSN) was proposed to explore the feasibility of its standardization verification for organs at risk (OAR) of nasopharyngeal carcinoma (NPC).Methods:The radiotherapy structure files of 855 patients with nasopharyngeal carcinoma (NPC) receiving intensity-modulated radiotherapy (IMRT) from 2017 to 2019(15 of whom showed clinical anomalous structures) were retrospectively collected and processed. The Matlab self-developed software was used to obtain the image position, geometric features, first-order gray histogram, and the Gray-level Co-occurrence Matrix′s texture features of the OAR contour outlined by the doctor to establish the CBSN Location Verification model and CBSN Knowledge Library. Fisher discriminant analysis was employed to establish a CBSN OAR classification model, which was evaluated using self-validation, cross-validation, and external validation, respectively.Results:99%(69/70) of the simulated anomalous structures were outside the 90% reference range of the CBSN Knowledge Library and the characteristic parameters significantly differed among different OARs (all P<0.001). The accuracy rates of self-validation, cross-validation and external verification of the CBSN OAR classification model were 92.1%, 92.0% and 91.8%, respectively. Fourteen cases of clinical abnormal structures were successfully detected by CBSN with an accuracy rate of 93%(14/15). In the simulation test, the accuracy of the left and right location verification reached 100%, such as detecting the right eye lens named Len_L. Conclusion:CBSN can be used for OAR verification of NPC, providing reference for multi-center cooperation and standardized radiotherapy of NPC patients.