ABSTRACT
ABSTRACT Purpose: We aimed to study reported cases of nasopharyngeal carcinoma presenting with ophthalmic manifestations with and without a prior diagnosis of nasopharyngeal carcinoma. Methods: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A literature search was conducted using the MEDLINE database in PubMed and Google Scholar. We included patients with a previous diagnosis of nasopharyngeal carcinoma in Group I and those without a prior diagnosis of nasopharyngeal carcinoma in Group II. Data included demographics, clinical presentation, history of nasopharyngeal carcinoma, treatment, histopathological description, World Health Organization classification, and outcome. Results: Fifty-eight patients (26 in Group I and 32 in Group II) were included. The male-to-female ratio was 3:1. The mean age of the patients (53.3 ± 11.7 years and 54.8 ± 16.2 years, respectively) and gender did not differ significantly between the two groups. The most common ocular presentations were diplopia and proptosis in the first group (each in 34.6%), whereas visual disturbance was most common in the second group (46.9%). Treatment options and World Health Organization grading were comparable. The outcome in 38 patients (after a comparable follow-up period) was significantly better in group II (p=0.003). There was no statistically significant difference in the outcome of 23 patients in correlation with World Health Organization grades II versus III irrespective of group (p=0.094). Conclusions: The demographics of patients with nasopharyngeal carcinoma presenting with ophthalmic manifestations were similar between the two study groups, with a wide age range and male predominance. Patients presenting initially to ophthalmologists with no history of nasopharyngeal carcinoma have a more favorable outcome. World Health Organization grading may have less value as a prognostic indicator.
ABSTRACT
Abstract Objectives Nasopharyngeal Carcinoma (NPC) is a common malignant tumor of nasopharyngeal mucosal epithelium in clinical practice. Radiotherapy and chemotherapy are the main treatment methods at present, but the therapeutic effect is still unsatisfactory. Studies have shown that exosomes and microRNAs (miRNAs) play an important role in the development of cancer. Therefore, this study aimed to investigate the effects of NPC derived exosomes on NPC and their molecular mechanisms. Methods Serum was collected from healthy subjects, Epstein-Barr Virus (EBV) infected patients and NPC patients (n = 9 group) and exosomes were extracted separately. High-throughput sequencing of exosomes was performed to screen differentially expressed miRNAs. The function of the screened miRNA was identified by treating NPC cells with exosomes. The target gene of miRNA was identified using the dual-luciferase assay. Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) was used to determine the levels of miR-99a-5p and Bromodomain Adjacent Tozinc finger domain protein 2A (BAZ2A). Cell Counting Kit-8 assay, flow cytometry, and wound healing assay were utilized to detect cell viability, cell cycle and apoptosis, and migration ability. The protein levels were evaluated by Western blot. Results MiR-99a-5p was identified as the most significant differentially expressed miRNA in exosomes (p< 0.05). The proliferation and migration of NPC cells were extremely facilitated by exosomes, accompanied by the suppressed apoptosis, upregulated BAZ2A, Monocyte Chemotactic Protein-1 (MCP1), and Vascular Endothelial Growth Factor A (VEGFA), and downregulation of Interleukin (IL)-1β and Nuclear Transcription Factor-κB (NF-κB) (p< 0.05). BAZ2A was a target gene of miR-99a-5p. Furthermore, the regulatory effect of exosomes on the proliferation, migration, and apoptosis was significantly abolished by overexpression of miR-99a-5p or downregulation of BAZ2A (p< 0.05). Conclusion NPC derived exosomes facilitated the proliferation and migration of NPC through regulating the miR-99a-5p/BAZ2A axis.
ABSTRACT
Abstract Objectives Nasopharyngeal carcinoma (NPC) is an aggressive epithelial cancer. The expression of miR-186 is decreased in a variety of malignancies and can promote the invasion and metastasis of cancer cells. This study aimed to explore the role and possible mechanism of miR-186 in the metastasis and epithelial-mesenchymal transformation (EMT) of NPC. Methods The expression of miR-186 in NPC tissues and cells was detected by RT-PCR. Then, miR-186 mimic was used to transfect NPC cell lines C666-1 and CNE-2, and cell activity, invasion and migration were detected by CCK8, transwell and scratch assay, respectively. The expression of EMT-related proteins was analyzed by western blotting analysis. The binding relationship between miR-186 and target gene Zinc Finger E-Box Binding Homeobox 1 (ZEB1) was confirmed by double luciferase assay. Results The expression of miR-186 in NPC was significantly decreased, and transfection of miR-186 mimic could significantly inhibit the cell activity, invasion, and migration, and regulate the protein expressions of E-cadherin, N-cadherin and vimentin in C666-1 and CNE-2 cells. Further experiments confirmed that miR-186 could directly target ZEB1 and negatively regulate its expression. In addition, ZEB1 has been confirmed to be highly expressed in NPC, and inhibition of ZEB1 could inhibit the activity, invasion, metastasis and EMT of NPC cells. And co-transfection of miR-186 mimic and si-ZEB1 could further inhibit the proliferation and metastasis of NPC. Conclusion miR-186 may inhibit the proliferation, metastasis and EMT of NPC by targeting ZEB1, and the miR-186/ZEB1 axis plays an important role in NPC.
ABSTRACT
Abstract Objective Nasopharyngeal Carcinoma (NPC) is a malignancy of epithelium of epithelium of the nasopharynx, with the highest incidence of otolaryngeal malignancies. A growing number of studies confirm that Circular RNA (circRNA) plays an important role in tumor development, including Hsa_circ_0013561. This study aims to elucidate the process and mechanism of NPC regulation hsa_circ_0013561. Methods In this study, circRNA expression nodes and subcellular localization in NPC tissues were analyzed by fluorescence in situ hybridization. The expression of hsa_circ_0013561 in NPC cells was further clarified by RT-qPCR. At the same time, the lentivirus vector interfered by hsa_circ_0013561 was constructed and transfected. The cell proliferation was detected by CCK-8 method, EdU assay and plate cloning assay. The cell cycle and apoptosis were detected by flow cytometry, and the cell migration ability was detected by wound healing assay and Transwell assay. Western blotting examined the expression of apoptosis, Epithelial-Mesenchymal Transition (EMT)-associated proteins, and Janus Kinase/Signal Transductor and Activator of Transcription (JAK/STAT) signaling pathway-related proteins. Results The results showed that the expression of hsa_circ_0013561 in NPC samples was significantly upregulated and hsa_circ_0013561 localized in the cytoplasm. After down-regulating hsa_circ_0013561 expression, it significantly inhibited the proliferation and metastasis ability of NPC, inhibited EMT progression, and promoted apoptosis. Further studies showed that interference hsa_circ_0013561 significantly inhibited JAK2/STAT3 signaling pathway activation and induced the expression of apoptosis-related proteins. Conclusion In summary, we found that hsa_circ_0013561 is a pro-tumor circRNA in NPC, which can reduce the activation of JAK2/STAT3 pathway by knocking down hsa_circ_0013561, thereby slowing down the malignant progression of NPC. Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence Level 4.
ABSTRACT
Abstract Introduction Finding biomarkers for highly lethal cancers is a priority. Objective The current study was designed to understand the clinical significance of vascular endothelial growth factor (VEGF), latent membrane protein 1 (LMP1), and tumor necrosis factor-α (TNF-α) expression as the biomarkers, and evaluate their correlation with each other, in nasopharyngeal carcinoma (NPC) in the province of Guilan, North of Iran. Methods Gene expression was evaluated in 25 formalin-fixed paraffin-embedded (FFPE) blocks from cases of confirmed NPC and 20 FFPE samples of non-NPC by quantifying messenger ribonucleic acid (mRNA) and protein levels, using real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC) methods, respectively. Furthermore, the correlations among the protein levels of different genes, along with the patients' demographic characteristics were assessed. Results Our findings on mRNA and protein levels demonstrated that the expression of the LMP1 gene in the NPC group was significantly elevated compared with that of the non-NPC group. In addition, the protein levels in the NPC group indicated a positive and significant correlation between LMP1 and VEGF expression. It was noted that both protein and mRNA levels showed no significant differences in the expression of TNF-α and VEGF genes between the NPC and control groups. Furthermore, there was no significant relationship between the expression of these proteins and the demographic characteristics of NPC patients. Conclusion Overall, a significant increase in LMP1 expression was observed in NPC patients, which may serve as a diagnostic biomarker for NPC. Also, LMP1 might be involved in NPC progression by inducing VEGF gene expression.
ABSTRACT
Abstract Objective To evaluate the efficacy and safety of Alternating Chemoradiotherapy (ACRT) using cisplatin and 5-Fluorouracil (5-FU) in patients with nasopharyngeal carcinoma. Methods This was a retrospective study in which patients' clinical records were reviewed to identify patients with a new diagnosis of nasopharyngeal carcinoma at our institution between January 2005 and January 2019. Thirty-seven eligible patients were identified; of these, the clinical details of 27 patients treated with ACRT were evaluated. Patient outcomes, including overall survival and progression-free survival, and adverse events were assessed. Results Of these initial 37 patients, 1, 10, 13, 10, and 3 were staged as I, II, III, IVA, and IVB, respectively, as defined by the 8th edition of the TNM classification system. Twenty-seven patients received ACRT comprising sequential administration of chemotherapy, radiotherapy (wide field), chemotherapy, radiotherapy (shrinking field), and chemotherapy. The 5-year overall survival and progression-free survival rates were 83.7% and 88.9%, respectively. Treatment compliance was 93%, which is comparable to that of previous reports. Conclusion ACRT using cisplating and 5-fluorouracil was well tolerated with acceptable efficacy. Level of Evidence IVa
ABSTRACT
Abstract Objectives The aim of this study was to examine the changes in gray matter in nasopharyngeal carcinoma patients with normal hearing (Group 1) and nasopharyngeal carcinoma patients with hearing loss (Group 2) after radiotherapy using voxel-based morphological analysis and to analyze the relationship with the radiation doses of the temporal lobe. Methods 21 patients in Group 1, 14 patients in Group 2, and 21 healthy volunteers were selected. All participants underwent an otologic examination and three-dimensional magnetization preparatory rapid acquisition gradient echo sequence scan. The correlation between the variation of whole brain gray matter volume and the doses of the temporal lobe was analyzed by Data Processing & Analysis for Brain Imaging software. Results Compared with the normal control group, the brain areas with reduced gray matter volume in nasopharyngeal carcinoma patients after radiotherapy were mainly in the left posterior cerebellar lobe (T = −8.797), left insular lobe (T = −7.96), and the right insular lobe (T = −6.632). Compared to Group 1, the brain areas of Group 2 patients with reduced gray matter volume were mainly in the left superior temporal gyrus (T = −2.366), left olfactory bulb (T = −2.52), left Rolandic operculum (T = −2.431), and right olfactory bulb (T = −3.100). Compared with Group 1, the brain areas of Group 2 patients with increased gray matter volume were mainly in the left calcarine sulcus (T = 3.425) and right calcarine sulcus (T = 3.169). There were no correlations between the changes of brain gray matter volume and the radiation doses of the temporal lobe in both Group 1 and Group 2. Conclusions The radiotherapy may cause the changes of brain areas associated with cognitive function in nasopharyngeal carcinoma in a long-term follow-up. At the same time, nasopharyngeal carcinoma patients with the radiation-induced hearing loss had abnormal gray matter volumes in the auditory center and other sensory centers. Our findings might provide new understanding into the pathogenesis of radiation-induced brain damage in normal-appearing brain tissue. Yet this exploratory study should be taken with caution.
ABSTRACT
Abstract Objective The role of Primary Tumor Volume (PTV) in Nasopharyngeal Carcinoma (NPC) treated with Volumetric Modulated Arc Therapy (VMAT) is still unclear. The aim of this study was to access the effect of PTV in prognosis prediction of nasopharyngeal carcinoma in era of VMAT. Methods Between January 20 and November 2011, 498 consecutive NPC patients with stage I-IVA disease who received VMAT at a single center were retrospectively analyzed. Receiver Operating Characteristic (ROC) was performed to access the cut-off point of PTV. Univariate Kaplan-Meier and multivariate Cox regression analyses were used to evaluate prognostic value for PTV. The Propensity Score Matching (PSM) was used to adjust baseline potential confounders. Results The 5-year Locol-Regional Failure-Free (L-FFR), Distant Failure-Free Survival (D-FFR), Disease-Free Survival (DFS) and Overall Survival (OS) were 90.6%, 83.7%, 71.5% and 79.3%, respectively. Before PSM, the 5-year L-FFR, D-FFR, DFS, OS rates for NPC patients with PTV ≤ 38 mL vs. PTV > 38 mL were 94.1% vs. 90.4% (p= 0.063), 87.9% vs. 76.3% (p< 0.001), 78.5% vs. 58.5% (p< 0.001) and 86.3% vs. 66.7% (p< 0.001) respectively. Multivariate analysis showed PTV was an independent prognostic factor for D-FFS (p= 0.034), DFS (p= 0.002) and OS (p= 0.001). PTV classified was still an independent prognostic factor for OS after PSM (HR = 2.034, p= 0.025. Conclusions PTV had a substantial impact on the prognosis of NPC patients treated with VMAT before and after PSM simultaneously. PTV > 38 mL may be considered as an indicator of the clinical stage of nasopharyngeal carcinoma. Level of evidence III.
ABSTRACT
Objective:To construct a comprehensive nutritional index after treatment of nasopharyngeal carcinoma patients with intensity-modulated radiation therapy (IMRT), and to analyze its relationship with quality of life and 3-year survival period, and aimed to provide some reference for the management of nasopharyngeal carcinoma patients.Methods:This was a prospective cohort study. The clinical data of 431 nasopharyngeal carcinoma patients who admitted to Beijing Tongren Hospital Affiliated to Capital Medical University from January 2017 to December 2021 were collected using convenience sampling method. To evaluate the nutritional status of the patients, the BMI, change in body weight, hemoglobin, lymphocyte count, and albumin level and other clinical data of the patients were collected before and after intensity-modulated radiation therapy. The comprehensive nutrition index after IMRT was constructed by principal component analysis. The Chinese version of European Organization for Reasearch and Treatment of Cancer quality of life questionnare-Core 30 (EORTC QLQ-C30) and Quality of life questionnaire head and neck cancer module(QLQ-H&N35) were used to evaluate the patients′ quality of life. The best diagnostic cutoff point for predicting patient death within 3 years using ROC, and based on the determined optimal diagnostic cutoff point, all patients were divided into a low comprehensive nutritional index group and a high comprehensive nutritional index group. And analyzed the Pearson correlation between comprehensive nutritional index and quality of life.Differences in 3-year survival between the two groups were compared using the Kaplan-Meier method and Log-rank test.Results:Using the diagnostic threshold of receiver operating characteristic, all patients were divided into low comprehensive nutrition index group ( n=280) and high comprehensive nutrition index group ( n=151).The BMI, percentage of weight change, albumin, hemoglobin, and lymphocyte count of nasopharyngeal carcinoma patients before intensity-modulated radiation therapy were (23.14 ± 2.87) kg/m 2, (1.08 ± 0.14)%, (44.02 ± 4.52) g/L, (147.28 ± 15.57)g/L, (1.76 ± 0.56)×10 9/L, and higher than after intensity-modulated radiation therapy (21.14 ± 4.07) kg/m 2, (0.97 ± 0.16)%, ( 38.99 ± 5.12) g/L, (113.87 ± 18.24)g/L, (0.50 ± 0.18)×10 9/L, respectively, the difference were statistically significant ( t values were 8.34 to 44.47, all P<0.05).The comprehensive nutritional index constructed using principal component analysis was correlated with multiple dimensions of EORTC QLQ-C30) and QLQ-H&N35, with statistically significant differences ( r values were -0.169 - 0.245, all P<0.05). Kaplan-Meier curves indicated that the 3-year survival rate of the high comprehensive nutritional index group was higher than that of the low comprehensive nutritional index group, with 87.42% and 79.29% respectively, and the difference was statistically significant ( χ2=4.53, P<0.05). Conclusions:The constructed comprehensive nutritional index could reflect the comprehensive nutritional status of nasopharyngeal carcinoma patients. Nasopharyngeal carcinoma patients with a low comprehensive nutritional index score had a worse quality of life and shorter 3-year survival. Active intervention and improvement of malnutrition in nasopharyngeal carcinoma patients should be undertaken to improve patient quality of life and improve survival.
ABSTRACT
Radiotherapy is the first treatment choice for nasopharyngeal carcinoma. With the rapid development of image-guided radiotherapy, adaptive radiotherapy (ART) has become widely available in clinical practice. ART may be implemented to monitor the anatomical or physiological variations of patients using dynamic imaging technology and feedback information during the treatment course, including geometric changes (size, shape, and position) of tumor and normal organs. ART also allows the modification of the treatment plan to accurately deliver the maximize dose to target and minimize normal tissue explosion. This review discusses the physics basis of ART and its state-of-art application and potential pitfalls.
ABSTRACT
Metastasis is the main cause of cancer-related death. Growing evidence has shown that changes in glucose metabolism in nasopharyngeal carcinoma cells affect the invasion and metastasis of nasopharyngeal carcinoma through many pathways. This review summarizes the molecular mechanism underlying abnormal glucose metabolism in nasopharyngeal carcinoma cells and analyzes its relationship with the invasion and metastasis of nasopharyngeal carcinoma, including aerobic glycolysis, aerobic oxidation, and pentose phosphate pathway. The aim is to provide novel approaches using the relationships among glucose metabolism, invasion, and metastasis in the targeted therapy of nasopharyngeal carcinoma.
ABSTRACT
Objective To explore the prognostic value of pretreatment hematological indicators in children and adolescents with nasopharyngeal carcinoma. Methods We performed a retrospective analysis on the medical records of 79 children and adolescents (≤20 years old) with nasopharyngeal carcinoma. Before treatment, all patients underwent hematological tests, and patients received intensity-modulated radiotherapy alone or intensity-modulated radiotherapy combined with chemotherapy, targeted, and other comprehensive treatment modes. The follow-up endpoints were overall survival (OS) and progression-free survival (PFS). Results Age≤14 years, no concurrent chemotherapy, pretreatment hematological indicators (high NLR, high PLR, high LDH, and high LAR) were associated with poor OS and PFS in children and adolescents with nasopharyngeal carcinoma (all P < 0.05). No concurrent chemotherapy and high LAR before treatment were independent adverse prognostic factors for OS in children and adolescents with nasopharyngeal carcinoma. Conclusion High NLR, high PLR, high LDH, and high LAR of pretreatment hematological indicators are associated with poor OS and PFS. Meanwhile, high LAR before treatment is an independent adverse prognostic factor for OS in children and adolescents with nasopharyngeal carcinoma.
ABSTRACT
ObjectiveThis study aimed to analyze the difference in setup error before and after correction of systematic error. To determine the most appropriate image-guided strategy during HT treatment， we use different scanning ranges and image-guidance frequencies in patients with nasopharyngeal carcinoma （NPC） treated with helical tomotherapy （HT）. MethodsFifteen patients with NPC who received HT treatment in Sun Yat-sen University Cancer Center from October 2019 to February 2020 were selected. Megavoltage computed tomography （MVCT） scanning was performed before each treatment. After five times of radiotherapy， system-error correction was performed to adjust the setup center. The setup errors before and after the correction of systematic errors， as well as the setup errors of different scanning ranges and different scanning frequencies， were collected for analysis and comparison. ResultsWhen comparing the setup errors before and after the correction of systematic error， the differences in setup errors in the left–right （LR）， superior–inferior （SI）， and anterior–posterior （AP） directions were statistically significant （P<0.05）.The different scanning ranges of "nasopharynx + neck" and "nasopharynx" were compared， and a statistically significant difference was found in yaw rotational errors （P<0.05）. In the comparison of daily and weekly scan frequency after system-error correction， a significant difference was found in AP direction （P<0.05）. ConclusionDuring radiotherapy for NPC， the systematic error can be corrected according to the first five setup errors， and then small-scale scanning was selected for image-guided radiotherapy every day.
ABSTRACT
Objective:To evaluate the diagnostic accuracy of the convolutional neural network（CNN） in diagnosing nasopharyngeal carcinoma using endoscopic narrowband imaging. Methods:A total of 834 cases with nasopharyngeal lesions were collected from the People's Hospital of Guangxi Zhuang Autonomous Region between 2014 and 2016. We trained the DenseNet201 model to classify the endoscopic images, evaluated its performance using the test dataset, and compared the results with those of two independent endoscopic experts. Results:The area under the ROC curve of the CNN in diagnosing nasopharyngeal carcinoma was 0.98. The sensitivity and specificity of the CNN were 91.90% and 94.69%, respectively. The sensitivity of the two expert-based assessment was 92.08% and 91.06%, respectively, and the specificity was 95.58% and 92.79%, respectively. There was no significant difference between the diagnostic accuracy of CNN and the expert-based assessment （P=0.282, P=0.085）. Moreover, there was no significant difference in the accuracy in discriminating early-stage and late-stage nasopharyngeal carcinoma（P=0.382）. The CNN model could rapidly distinguish nasopharyngeal carcinoma from benign lesions, with an image recognition time of 0.1 s/piece. Conclusion:The CNN model can quickly distinguish nasopharyngeal carcinoma from benign nasopharyngeal lesions, which can aid endoscopists in diagnosing nasopharyngeal lesions and reduce the rate of nasopharyngeal biopsy.
Subject(s)
Humans , Nasopharyngeal Carcinoma , Narrow Band Imaging , China , Neural Networks, Computer , Nasopharyngeal Neoplasms/diagnostic imagingABSTRACT
The abnormal activation of HER family kinase activity is closely related to the development of human malignancies. In this study, we used HER kinases as targets for the treatment of nasopharyngeal carcinoma (NPC) and explored the anti-tumor effects of the novel pan-HER inhibitor HM781-36B, alone or in combination with cisplatin. We found that HER family proteins were positively expressed in tumor tissues of some NPC patients, and the high levels of those proteins were significantly related to poor prognosis. HM781-36B inhibited NPC in vitro and in vivo. HM781-36B exerted synergistic effects with cisplatin on inhibiting proliferation and promoting apoptosis of NPC cells. In NPC xenograft models in nude mice, HM781-36B and cisplatin synergistically inhibited tumor growth. Downregulating the activity of HER family proteins and their downstream signaling pathways and regulating tumor microenvironment may explain the synergistic anti-tumor effects of HM781-36B and cisplatin. In conclusion, our study provides evidence for HER family proteins as prognostic biomarkers and potential therapeutic targets for NPC. The pan-HER inhibitor HM781-36B alone or in combination with cisplatin represents promising therapeutic effects for the treatment of NPC patients, which provides a new idea for the comprehensive treatment of NPC.
Subject(s)
Humans , Animals , Mice , Cisplatin/therapeutic use , Antineoplastic Agents/therapeutic use , Nasopharyngeal Carcinoma/drug therapy , Mice, Nude , Nasopharyngeal Neoplasms/pathology , Tumor MicroenvironmentABSTRACT
Objective To investigate the effect of TES gene on the radiosensitivity of nasopharyngeal carcinoma 5-8F cells. Methods Specimens of 5-8F cells (unprocessed group) and 5-8F cells with high TES expression (TES group) were irradiated at 0, 2, 4, 6, and 8 Gy radiation dose points.Cell clone formation experiment was conducted to draw the survival curve.Twenty-four BALB/c nude mice were randomly divided into four groups: nontransfection group, TES group, irradiation group, and TES irradiation group.A nude mouse model of nasopharyngeal carcinoma 5-8F cells was established.The length and diameter of the transplanted tumor were measured every three days, the tumor volume was calculated, and the growth curve of the transplanted tumor was drawn.After the mice were killed one month later, the tumor block was taken and weighed.The apoptosis of the transplanted tumor cells in each group was detected by flow cytometry. Results Compared with that in the unprocessed group, the survival rate of cells in the TES group was significantly lower (P < 0.01).The tumor growth rate and tumor mass of all four groups decreased in turn, while the apoptosis rate increased in turn.The TES irradiation group had the slowest tumor growth rate, greatest decrease in tumor weight, and highest apoptosis rate among the four groups.Multiple comparison revealed statistically significant differences between the groups (P < 0.05). Conclusion The testin gene can effectively improve the radiosensitivity of nasopharyngeal carcinoma 5-8F cells cultured in vitro.
ABSTRACT
Abstract Objective: Nasopharyngeal Carcinoma (NPC) is lethal cancer. Typically, relapse and metastasis are the outcomes of most patients. Against this backdrop, this study aimed to investigate the correlation between Circulating Tumor Cell (CTC) profiles and clinicopathological features in patients with NPC. Patients and methods: A total of 119 blood samples from 79 patients were collected from patients with NPC during treatment. CanPatrol™ CTC enrichment and RNA In Situ Hybridization (RNA-ISH) were used to characterize CTCs, including epithelial, Mesenchymal (MCTCs), and epithelial/mesenchymal mixed types according to their surface markers. Results: The number of CTCs and MCTCs in the pre-treatment group was significantly higher than that in the post-treatment group (p < 0.05). The total number of CTCs and MCTCs cell numbers was significant correlation with Tumor-Node-Metastasis (TNM) staging (p < 0.05), Progression-Free Survival (PFS), and Overall Survival (OS). The PFS of patients with > 7 CTCs or > 5 MCTCs per 5 mL blood was significantly shorter PFS than those patients with ≤ 7 CTCs or ≤ 5 MCTCs (p < 0.05). Patients treated with targeted therapy combined with chemoradiother-apy had poorer PFS and OS rates than those treated with chemoradiotherapy (p < 0.05). The Kaplan-Meier survival analysis also demonstrated that patients with changes in CTC > 4 were strongly associated with PFS and OS rates (p < 0.05). Conclusion: CTC and MCTC number detection in patients with NPC is a useful biomarker for predicting patient progress. Patients with more than 7 CTCs or 5 MCTCs in 5 mL of blood had shorter PFS and OS rates. CTC and MCTC count changes were also significantly associated with the patient's therapy.
ABSTRACT
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
Subject(s)
Humans , Herpesvirus 4, Human/physiology , Epstein-Barr Virus Infections/complications , Stomach Neoplasms/physiopathology , Stomach Neoplasms/virology , Hodgkin Disease/physiopathology , Hodgkin Disease/virology , Nasopharyngeal Neoplasms/physiopathology , Nasopharyngeal Neoplasms/virology , Burkitt Lymphoma/physiopathology , Burkitt Lymphoma/virology , Carcinogenesis , Nasopharyngeal Carcinoma/physiopathology , Nasopharyngeal Carcinoma/virology , Multiple Sclerosis/physiopathology , Multiple Sclerosis/virologyABSTRACT
RNA interference (RNAi) treatment has been proven to be an important therapeutic approach in cancer based on downregulation of target-oncogenes, but its clinical efficacy still needs further investigation. LMP1 is usually presented by Epstein-Barr virus (EBV)-positive tumor cells like EBV-associated nasopharyngeal carcinoma (NPC) and acts as an oncogene in tumorigenesis. However, the mechanism of LMP1 as a proto-oncogene in nasopharyngeal carcinoma is still unclear. Two sequence-specific shRNAs 1 and 2 were designed to target the different nucleotide loci of EBV latent antigen LMP1 gene and a series of in vivo and in vitro experiments were performed to investigate the therapeutic effect of sequence-specific shRNAs targeting LMP1 and its related molecular mechanisms in EBV-positive NPC. LMP1-shRNA2 generated a truncated LMP1 mRNA and protein, whereas LMP1-shRNA1 completely blocked LMP1 mRNA and protein expression. Both LMP1-shRNAs inhibited the proliferation and migration of NPC cells overexpressing LMP1 (NPC-LMP1) as well as the NPC-associated myeloid-derived suppressor cell (MDSC) expansion in vitro. However, LMP1-shRNA2 maintained the immunogenicity of NPC-LMP1 cells, which provoked MHC-class I-dependent T cell recognition. LMP1-shRNAs inhibited tumor growth in nude mice but did not reach statistical significance compared to control groups, while the LDH nanoparticle loaded LMP1-shRNAs and the antigen-specific T cells induced by NPC-LMP1 cells treated with LMP1-shRNA2 significantly reduced tumor growth in vivo. LMP1-RNAi-based anti-tumor therapy could be a new hope for the clinical efficacy of RNAi treatment of tumors like NPC.
ABSTRACT
@#Multi-leaf collimators are devices to block rays from medical linear accelerators, which directly affect doses to targets and organs at risk by adjusting field shape and dose distribution in radiation therapy. As multi-leaf collimators are diversified in structure, there has been growing research on dosimetric comparison of various multi-leaf collimators. In this paper, we introduced the classifications of multi-leaf collimators according to their basic components, as well as the hardware structure and design features of the products of main accelerator manufacturers, including Varian’s Millennium MLC, HD120 MLC, and Halcyon, Elekta’s MLCi/i2 and Agility, and Accuray’s InCise 2 MLC and TomoTherapy. In terms of clinical application evaluation, focusing on radiotherapy plans for nasopharyngeal carcinoma, we reviewed comparative studies on the dosimetry performance of multi-leaf collimators and the effects of relevant parameters on dose distribution. We hope this review on the design and application evaluation of multi-leaf collimators can provide a reference for more innovative design and accelerator selection and parameter setting in clinical individualized treatment.