ABSTRACT
Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.
Subject(s)
Humans , Cost-Benefit Analysis , Smoking Cessation , Cost-Effectiveness Analysis , Nasopharyngeal Neoplasms , Varenicline , China , Kidney Neoplasms , Pharmaceutical PreparationsABSTRACT
Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.
Subject(s)
Humans , Cost-Benefit Analysis , Smoking Cessation , Cost-Effectiveness Analysis , Nasopharyngeal Neoplasms , Varenicline , China , Kidney Neoplasms , Pharmaceutical PreparationsABSTRACT
Objective: To describe a technique of endoscopic transoral approach nasopharyngectomy for petroclival and jugular foramen nasopharyngeal carcinoma, based on anatomic studies and surgeries. Methods: Three dry human skulls and five fresh human cadaver heads were used for anatomic study of a endoscopic transoral approach to expose petroclival and jugular foramen. The anatomical landmarks and the extent of exposure were recorded. Six clinical cases who were treated in Eye & ENT Hospital, Fudan University from June 2020 to April 2022 were used to illustrate the technique and feasibility of this approach and to assess its indications and advantages, including 3 males and 3 females, aged 42 to 69 years old. Descriptive analysis was used in this research. Results: On the basis of the preservation of the internal pterygoid muscle and the external pterygoid muscle, this approach could fully expose the parapharyngeal, petrosal and paraclival segment internal carotid arteries, and safely deal with the lesions of jugular foramen and petroclival region. The 6 patients in our study tolerated the procedure well. Postoperative enhanced MRI showed complete resection of the tumor and no postoperative masticatory dysfunction. Conclusion: Endoscopic transoral approach is a safe, minimally invasive and effective surgical treatment for petroclival and jugular foramen recurrent nasopharyngeal carcinoma.
Subject(s)
Male , Female , Humans , Adult , Middle Aged , Aged , Nasopharyngeal Carcinoma , Jugular Foramina , Neoplasm Recurrence, Local , Endoscopy/methods , Nasopharyngeal Neoplasms/surgeryABSTRACT
Objective: To investigate the efficacy of the first-day suspension method for improving the success rate of construction of nasopharyngeal carcinoma-patient derived organoids (NPC-PDO). Methods: The tumor samples of 14 nasopharyngeal carcinoma(NPC) patients, i.e.,13 males and 1 female, with a mean age of 43.0±12.0 years old, were collected from the Affiliated Tumor Hospital of Guangxi Medical University and the First Affiliated Hospital of Guangxi Medical University from January 2022 to July 2022. The tumor samples of 3 patients were digested into single cell suspension and divided into 2 groups, for comparing the efficacy of NPC-PDO construction by the direct inoculation method and the first-day suspension method. The remaining 11 patients were randomized to receive either the direct inoculation method or the first-day suspension method for NPC-PDO construction. The diameter and the number of spheres of NPC-PDO constructed by the two methods were compared by optical microscope; the 3D cell viability detection kit was used to compare the cell viability; the survival rates were compared by trypan blue staining; the success rates of the two construction methods were compared; the number of cases which could be successfully passaged for more than 5 generations and were consistent with the original tissue by pathological examination was counted; and the dynamic changes of cells in suspension overnight were observed by live cell workstation. The independent sample t-test was applied to compare the measurement data of the two groups, and the chi-square test was used to compare the classification data. Results: Compared with the direct inoculation, the diameter and the number of spheres of NPC-PDO constructed by the first-day suspension method were increased, with a higher cell activity, and the success rate of construction was obviously improved (80.0% vs 16.7%, χ2=4.41, P<0.05). In the suspension state, some of the cells aggregated and increased their ability to proliferate. Conclusion: The first-day suspension method can improve the success rate of NPC-PDO construction, especially for those whose original tumor sample size is small.
Subject(s)
Male , Humans , Female , Adult , Middle Aged , Nasopharyngeal Carcinoma , China , Microscopy , Organoids , Nasopharyngeal NeoplasmsABSTRACT
OBJECTIVE@#To screen the risk factors for death in patients with nasopharyngeal carcinoma (NPC) using artificial intelligence (AI) technology and establish a risk prediction model.@*METHODS@#The clinical data of NPC patients obtained from SEER database (1973-2015). The patients were randomly divided into model building and verification group at a 7∶3 ratio. Based on the data in the model building group, R software was used to identify the risk factors for death in NPC patients using 4 AI algorithms, namely eXtreme Gradient Boosting (XGBoost), Decision Tree (DT), Least absolute shrinkage and selection operator (LASSO) and random forest (RF), and a risk prediction model was constructed based on the risk factor identified. The C-Index, decision curve analysis (DCA), receiver operating characteristic (ROC) curve and calibration curve (CC) were used for internal validation of the model; the data in the validation group and clinical data of 96 NPC patients (collected from First Affiliated Hospital of Bengbu Medical College) were used for internal and external validation of the model.@*RESULTS@#The clinical data of a total of 2116 NPC patients were included (1484 in model building group and 632 in verification group). Risk factor screening showed that age, race, gender, stage M, stage T, and stage N were all risk factors of death in NPC patients. The risk prediction model for NPC-related death constructed based on these factors had a C-index of 0.76 for internal evaluation, an AUC of 0.74 and a net benefit rate of DCA of 9%-93%. The C-index of the model in internal verification was 0.740 with an AUC of 0.749 and a net benefit rate of DCA of 3%-89%, suggesting a high consistency of the two calibration curves. In external verification, the C-index of this model was 0.943 with a net benefit rate of DCA of 3%-97% and an AUC of 0.851, and the predicted value was consistent with the actual value.@*CONCLUSIONS@#Gender, age, race and TNM stage are risk factors of death of NPC patients, and the risk prediction model based on these factors can accurately predict the risks of death in NPC patients.
Subject(s)
Humans , Nasopharyngeal Neoplasms , Nasopharyngeal Carcinoma , Artificial Intelligence , Algorithms , SoftwareABSTRACT
Nasopharyngeal carcinoma (NPC) is a malignant tumor that mainly occurs in East and Southeast Asia. Although patients benefit from the main NPC treatments (e.g., radiotherapy and concurrent chemotherapy), persistent and recurrent diseases still occur in some NPC patients. Therefore, investigating the pathogenesis of NPC is of great clinical significance. In the present study, replication factor c subunit 4 (RFC4) is a key potential target involved in NPC progression via bioinformatics analysis. Furthermore, the expression and mechanism of RFC4 in NPC were investigated in vitro and in vivo. Our results revealed that RFC4 was more elevated in NPC tumor tissues than in normal tissues. RFC4 knockdown induced G2/M cell cycle arrest and inhibited NPC cell proliferation in vitro and in vivo. Interestingly, HOXA10 was confirmed as a downstream target of RFC4, and the overexpression of HOXA10 attenuated the silencing of RFC4-induced cell proliferation, colony formation inhibition, and cell cycle arrest. For the first time, this study reveals that RFC4 is required for NPC cell proliferation and may play a pivotal role in NPC tumorigenesis.
Subject(s)
Humans , Nasopharyngeal Carcinoma/pathology , Carcinoma/pathology , Replication Protein C/metabolism , Nasopharyngeal Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Cell MovementABSTRACT
Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.
Subject(s)
Humans , Nasopharyngeal Carcinoma/pathology , Cell Line, Tumor , Cell Proliferation , Apoptosis , Signal Transduction , Nasopharyngeal Neoplasms/pathologyABSTRACT
High-risk human papillomavirus (HPV)-related cancers consist of cervical cancer, anal cancer, penile cancer, vulvar cancer, vaginal cancer, and head and neck cancer (HNC). Of these, the disease burden of HNC is second only to cervical cancer. HNC mostly originates from malignant lesions of squamous epithelial cells and mainly includes oral cavity cancer, pharyngeal cancer (including nasopharyngeal cancer, oropharyngeal cancer, and hypopharyngeal cancer), and laryngeal cancer. Tobacco use, alcohol abuse, and HPV infection are three primary risk factors. Recently, there is an upward trend of HNC incidence globally, especially in high-income countries. In China, the disease burden and trends of HPV-related HNC are still not clear. A few small sample size and single-center studies suggest a high HPV prevalence and increasing trend in HNC. Methodological differences in HPV testing and regional variabilities still exist among these studies. Among the anatomic sites, oropharyngeal cancer has been shown to be caused by HPV infection, but the association of HPV with other sites is still under debate. In addition, there is a paucity of relevant studies. Here, this review narrates the association between HPV infection and HNC, compares the differences between global and Chinese studies, and then explores the importance of HPV infection in various anatomical sites. The main objective is to highlight the research on HPV-related HNC and promote relevant prevention and treatment programs.
Subject(s)
Female , Humans , Papillomaviridae , Papillomavirus Infections/prevention & control , Uterine Cervical Neoplasms/complications , Nasopharyngeal Neoplasms/complications , Head and Neck Neoplasms/epidemiology , Oropharyngeal Neoplasms/epidemiology , PapillomaviridaeABSTRACT
To investigate the γ pass rate limit of plan verification equipment for volumetric modulated arc therapy (VMAT) plan verification and its sensitivity on the opening and closing errors of multi-leaf collimator (MLC), 50 cases of nasopharyngeal carcinoma VMAT plan with clockwise and counterclockwise full arcs were randomly selected. Eight kinds of MLC opening and closing errors were introduced in 10 cases of them, and 80 plans with errors were generated. Firstly, the plan verification was conducted in the form of field-by-field measurement and true composite measurement. The γ analysis with the criteria of 3% dose difference, distance to agreement of 2 mm, 10% dose threshold, and absolute dose global normalized conditions were performed for these fields. Then gradient analysis was used to investigate the sensitivity of field-by-field measurement and true composite measurement on MLC opening and closing errors, and the receiver operating characteristic curve (ROC) was used to investigate the optimal threshold of γ pass rate for identifying errors. Tolerance limits and action limits for γ pass rates were calculated using statistical process control (SPC) method for another 40 cases. The error identification ability using the tolerance limit calculated by SPC method and the universal tolerance limit (95%) were compared with using the optimal threshold of ROC. The results show that for the true composite measurement, the clockwise arc and the counterclockwise arc, the descent gradients of the γ passing rate with per millimeter MLC opening error are 10.61%, 7.62% and 6.66%, respectively, and the descent gradients with per millimeter MLC closing error are 9.75%, 7.36% and 6.37%, respectively. The optimal thresholds obtained by the ROC method are 99.35%, 97.95% and 98.25%, respectively, and the tolerance limits obtained by the SPC method are 98.98%, 97.74% and 98.62%, respectively. The tolerance limit calculated by SPC method is close to the optimal threshold of ROC, both of which could identify all errors of ±2 mm, while the universal tolerance limit can only partially identify them, indicating that the universal tolerance limit is not sensitive on some large errors. Therefore, considering the factors such as ease of use and accuracy, it is suggested to use the true composite measurement in clinical practice, and to formulate tolerance limits and action limits suitable for the actual process of the institution based on the SPC method. In conclusion, it is expected that the results of this study can provide some references for institutions to optimize the radiotherapy plan verification process, set appropriate pass rate limit, and promote the standardization of plan verification.
Subject(s)
Humans , Radiotherapy, Intensity-Modulated , Immune Tolerance , Nasopharyngeal Carcinoma , ROC Curve , Nasopharyngeal Neoplasms/radiotherapyABSTRACT
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 clinicopathological features, immunophenotype and gene alterations of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA). Methods: Fifteen case of TL-LGNPPA diagnosed at Zhejiang Cancer Hospital (5 cases) and the First Affiliated Hospital, Zhejiang University School of Medicine (10 cases) from November 2011 to August 2020 were collected. Clinical and pathological examinations, immunohistochemical staining and next-generation sequencing were performed. The clinicopathological and molecular characteristics were summarized, and relevant literature was reviewed. Results: Fifteen patients were identified and included. Their median age was 36 years (range, 20-60 years). The male-female ratio was 1.0∶1.1. The most common symptoms were epistaxis and nasal obstruction. The neoplasms were located on the roof of the nasopharynx or the posterior margin of the nasal septum. The pathological features included complex papillary and glandular structures mainly composed of single or pseudostratified cubic and columnar cells, with mild to moderate cytological atypia. In some cases, spindle cell features, nuclear grooves, ground glass nuclei, squamous metaplasia, or scattered psammoma bodies were identified. In addition, nuclear polar reversal cells, hobnail cells and micropapillary structures were found, but have not been reported in previous literature. Immunohistochemistry showed that the tumor cells were diffusely positive for TTF1, CK7, vimentin and CKpan; focally positive for p40, CK5/6 and p16; and negative for Tg, NapsinA, CK20, CDX2, S-100 and PAX8. The Ki-67 positive rates ranged from 1% to 20% and were≤10% in thirteen cases (13/15). EBER in situ hybridization was negative in all cases. DNA sequencing of 6 specimens was performed and all specimens were found harboring gene mutations (EWSR1, SMAD2, ROS1, JAK3, GRIN2A, ERRCC5, STAT3, and TET2), but no hot spot gene alterations were found. No MSI-H and MMR related gene changes were detected. All tumors showed low tumor mutation burden. All 15 patients underwent endoscopic surgery, and only 1 of them underwent radiotherapy postoperatively. All patients were recurrence free and alive at the end of follow-up periods (range: 23 to 129 months). Conclusions: TL-LGNPPA is a rare indolent tumor of the nasopharynx and exhibits a unique morphology and immunophenotype. Endoscopic resection is an effective treatment for TL-LGNPPA with excellent overall prognosis.
Subject(s)
Humans , Male , Female , Adult , Thyroid Gland/pathology , Adenocarcinoma, Papillary/pathology , Nasopharyngeal Neoplasms/pathology , Protein-Tyrosine Kinases , Proto-Oncogene Proteins , Nasopharynx/pathology , Biomarkers, TumorABSTRACT
Objective: To analyze the survival of nasopharyngeal carcinoma patients in Qidong from 1972 to 2016, and provide a basis for the prognosis evaluation and prevention for nasopharyngeal carcinoma patients. Methods: A total of 1 060 registered nasopharyngeal carcinoma patients were followed up for survival outcomes until December 31, 2021. Observed survival rate (OSR) and relative survival rate (RSR) was calculated by Hakulinen method in SURV3.01 software, and Hakulinen's likelihood ratio test was used for statistical difference comparison. Age-standardized relative survival rate (ARSR) was calculated according to the International Cancer Survival Standard (ICSS). Joinpoint 4.7.0.0 software was used to conduct the annual average percentage change (AAPC) in nasopharyngeal carcinoma survival rate. The period from 1972 to 2016 is divided into 9 periods for grouping processing according to 5 years. Results: The OSR of nasopharyngeal carcinoma at 1, 5, 10 years were 63.02%, 34.70% and 24.72%, the RSR at 1, 5, 10 years were 64.44%, 38.98% and 31.64%, respectively. The uptrends of RSR in the nine periods were statistically significant (χ(2)=112.16, P<0.001). The 1, 5, 10 years RSR for males were 62.66%, 35.89% and 27.94%, while the 1, 5, 10 years RSR for females were 68.30%, 45.67% and 39.68%, respectively. There was no statistically significant difference in RSR between males and females (χ(2)=14.16, P=0.656). The 5-year RSR for the age groups of 25-34, 35-44, 45-54, 55-64, 65-74, and over 75 years old were 52.83%, 40.92%, 42.64%, 38.65%, 27.23% and 28.88%, respectively. There was a statistically significant difference in RSR among different age groups (χ(2)=42.33, P=0.003). Moreover, the ARSR of nasopharyngeal carcinoma at 1, 5, 10 years were 63.64%, 37.33% and 27.10%, for males were 61.82%, 35.60% and 25.20%, for females were 68.36%, 43.12% and 32.93%. Period trend showed that the AAPC of 5-ARSR was 2.71% (t=7.47, P<0.001) from 1972 to 2016 in Qidong. The AAPC of 5-ARSR in males and females were 2.63% (t=4.98, P=0.002) and 2.71% (t=6.08, P=0.001). There was statistically significant increase in 5-year ARSR among both genders. Furthermore, the AAPC of 5-year RSR among 25-34, 35-44, 45-54, 55-64, 65-74 and 75+ years old were 2.16% (t=4.28, P=0.004), 3.38% (t=5.06, P=0.001), 1.99% (t=2.82, P=0.026), 2.82% (t=3.39, P=0.012), 2.20% (t=2.82, P=0.026) and -0.91% (t=-0.42, P=0.689), respectively. Except for the 75+ years old age group, the other age groups were significantly upward trend. Conclusions: The overall survival rate of nasopharyngeal carcinoma in Qidong from 1972 to 2016 has shown an upward trend. It is necessary to introduce standardized multi-disciplinary treatment mode to improve treatment effect and survival rate.
Subject(s)
Humans , Male , Female , Aged , Nasopharyngeal Carcinoma , Survival Rate , Prognosis , Software , Nasopharyngeal Neoplasms , China/epidemiology , IncidenceABSTRACT
Objective: To analyze the survival of nasopharyngeal carcinoma patients in Qidong from 1972 to 2016, and provide a basis for the prognosis evaluation and prevention for nasopharyngeal carcinoma patients. Methods: A total of 1 060 registered nasopharyngeal carcinoma patients were followed up for survival outcomes until December 31, 2021. Observed survival rate (OSR) and relative survival rate (RSR) was calculated by Hakulinen method in SURV3.01 software, and Hakulinen's likelihood ratio test was used for statistical difference comparison. Age-standardized relative survival rate (ARSR) was calculated according to the International Cancer Survival Standard (ICSS). Joinpoint 4.7.0.0 software was used to conduct the annual average percentage change (AAPC) in nasopharyngeal carcinoma survival rate. The period from 1972 to 2016 is divided into 9 periods for grouping processing according to 5 years. Results: The OSR of nasopharyngeal carcinoma at 1, 5, 10 years were 63.02%, 34.70% and 24.72%, the RSR at 1, 5, 10 years were 64.44%, 38.98% and 31.64%, respectively. The uptrends of RSR in the nine periods were statistically significant (χ(2)=112.16, P<0.001). The 1, 5, 10 years RSR for males were 62.66%, 35.89% and 27.94%, while the 1, 5, 10 years RSR for females were 68.30%, 45.67% and 39.68%, respectively. There was no statistically significant difference in RSR between males and females (χ(2)=14.16, P=0.656). The 5-year RSR for the age groups of 25-34, 35-44, 45-54, 55-64, 65-74, and over 75 years old were 52.83%, 40.92%, 42.64%, 38.65%, 27.23% and 28.88%, respectively. There was a statistically significant difference in RSR among different age groups (χ(2)=42.33, P=0.003). Moreover, the ARSR of nasopharyngeal carcinoma at 1, 5, 10 years were 63.64%, 37.33% and 27.10%, for males were 61.82%, 35.60% and 25.20%, for females were 68.36%, 43.12% and 32.93%. Period trend showed that the AAPC of 5-ARSR was 2.71% (t=7.47, P<0.001) from 1972 to 2016 in Qidong. The AAPC of 5-ARSR in males and females were 2.63% (t=4.98, P=0.002) and 2.71% (t=6.08, P=0.001). There was statistically significant increase in 5-year ARSR among both genders. Furthermore, the AAPC of 5-year RSR among 25-34, 35-44, 45-54, 55-64, 65-74 and 75+ years old were 2.16% (t=4.28, P=0.004), 3.38% (t=5.06, P=0.001), 1.99% (t=2.82, P=0.026), 2.82% (t=3.39, P=0.012), 2.20% (t=2.82, P=0.026) and -0.91% (t=-0.42, P=0.689), respectively. Except for the 75+ years old age group, the other age groups were significantly upward trend. Conclusions: The overall survival rate of nasopharyngeal carcinoma in Qidong from 1972 to 2016 has shown an upward trend. It is necessary to introduce standardized multi-disciplinary treatment mode to improve treatment effect and survival rate.
Subject(s)
Humans , Male , Female , Aged , Nasopharyngeal Carcinoma , Survival Rate , Prognosis , Software , Nasopharyngeal Neoplasms , China/epidemiology , IncidenceABSTRACT
OBJECTIVE@#To investigate the mechanism by which Chinese medicine Shengmai Yin (SMY) reverses epithelial-mesenchymal transition (EMT) through lipocalin-2 (LCN2) in nasopharyngeal carcinoma (NPC) cells CNE-2R.@*METHODS@#Morphological changes in EMT in CNE-2R cells were observed under a microscope, and the expressions of EMT markers were detected using quantitative real-time PCR (RT-qPCR) and Western blot assays. Through the Gene Expression Omnibus dataset and text mining, LCN2 was found to be highly related to radiation resistance and EMT in NPC. The expressions of LCN2 and EMT markers following SMY treatment (50 and 100 µ g/mL) were detected by RT-qPCR and Western blot assays in vitro. Cell proliferation, migration, and invasion abilities were measured using colony formation, wound healing, and transwell invasion assays, respectively. The inhibitory effect of SMY in vivo was determined by observing a zebrafish xenograft model with a fluorescent label.@*RESULTS@#The CNE-2R cells showed EMT transition and high expression of LCN2, and the use of SMY (5, 10 and 20 µ g/mL) reduced the expression of LCN2 and reversed the EMT in the CNE-2R cells. Compared to that of the CNE-2R group, the proliferation, migration, and invasion abilities of SMY high-concentration group were weakened (P<0.05). Moreover, SMY mediated tumor growth and metastasis in a dose-dependent manner in a zebrafish xenograft model, which was consistent with the in vitro results.@*CONCLUSIONS@#SMY can reverse the EMT process of CNE-2R cells, which may be related to its inhibition of LCN2 expression. Therefore, LCN2 may be a potential diagnostic marker and therapeutic target in patients with NPC.
Subject(s)
Animals , Humans , Nasopharyngeal Carcinoma/genetics , Epithelial-Mesenchymal Transition , Zebrafish , Cell Proliferation , Cell Line, Tumor , Nasopharyngeal Neoplasms/radiotherapy , Cell Movement , Gene Expression Regulation, NeoplasticABSTRACT
OBJECTIVES@#Nasopharyngeal cracinoma is a kind of head and neck malignant tumor with high incidence and high mortality. Due to the characteristics of local recurrence, distant metastasis, and drug resistance, the survival rate of patients after treatment is not high. Paclitaxel (PTX) is used as a chemotherapy drug in treating nasopharyngeal carcinoma, but nasopharyngeal carcinoma cells are easy to develop resistance to PTX. Inhibition of heat shock protein 90 (Hsp90) can overcome common signal redundancy and resistance in many cancers. This study aims to investigate the anti-tumor effect of ginkgolic acids C15꞉1 (C15:1) combined with PTX on nasopharyngeal carcinoma CNE-2Z cells and the mechanisms.@*METHODS@#This experiment was divided into a control group (without drug), a C15:1 group (10, 30, 50, 70 μmol/L), a PTX group (5, 10, 20, 40 nmol/L), and a combination group. CNE-2Z cells were treated with the corresponding drugs in each group. The proliferation of CNE-2Z cells was evaluated by methyl thiazolyl tetrazolium (MTT). Wound-healing assay and transwell chamber assay were used to determine the migration of CNE-2Z cells. Transwell chamber was applied to the impact of CNE-2Z cell invasion. Annexin V-FITC/PI staining was used to observe the effect on apoptosis of CNE-2Z cells. The changes of proteins involved in cell invasion, migration, and apoptosis after the combination of C15꞉1 and PTX treatment were analyzed by Western blotting.@*RESULTS@#Compared with the control group, the C15꞉1 group and the PTX group could inhibit the proliferation of CNE-2Z cells (all P<0.05). The cell survival rates of the C15꞉1 50 μmol/L combined with 5, 10, 20, or 40 nmol/L PTX group were lower than those of the single PTX group (all P<0.05), the combination index (CI) value was less than 1, suggesting that the combined treatment group had a synergistic effect. Compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the combination group significantly inhibited the invasion and migration of CNE-2Z cells (all P<0.05). The results of Western blotting demonstrated that the combination group could significantly down-regulate Hsp90 client protein matrix metalloproteinase (MMP)-2 and MMP-9. The results of double staining showed that compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the apoptosis ratio of CNE-2Z cells in the combination group was higher (both P<0.05). The results of Western blotting suggested that the combination group could decrease the Hsp90 client proteins [Akt and B-cell lymphoma-2 (Bcl-2)] and increase the Bcl-2-associated X protein (Bax).@*CONCLUSIONS@#The combination of C15꞉1 and PTX has a synergistic effect which can inhibit cell proliferation, invasion, and migration, and induce cell apoptosis. This effect may be related to the inhibition of Hsp90 activity by C15꞉1.
Subject(s)
Humans , Nasopharyngeal Carcinoma , Paclitaxel/therapeutic use , Nasopharyngeal Neoplasms/metabolism , Antineoplastic Agents/therapeutic use , Apoptosis , Cell Proliferation , Cell Line, TumorABSTRACT
Objective To screen out the potential prediction genes for nasopharyngeal carcinoma(NPC)from the gene microarray data of NPC samples and then verify the genes by cell experiments.Methods The NPC dataset was downloaded from Gene Expression Omnibus,and limma package was employed to screen out the differentially expressed genes.Weighted correlation network analysis package was used for weighted gene co-expression network analysis,and Venn diagram was drawn to find the common genes.The gene ontology annotation and Kyoto encyclopedia of genes and genomes pathway enrichment were then performed for the common genes.The biomarkers for NPC were further explored by protein-protein interaction network,LASSO regression,and non-parametric tests.Real-time quantitative PCR and Western blotting were employed to determine the mRNA and protein levels of key predictors of NPC,so as to verify the screening results.Results There were 622 up-regulated genes and 351 down-regulated genes in the GSE12452 dataset.A total of 116 common genes were obtained by limma analysis and weighted gene co-expression network analysis.The common genes were mainly involved in the biological processes of cell proliferation and regulation and regulation of intercellular adhesion.They were mainly enriched in Rap1,Ras,and tumor necrosis factor signaling pathways.Six key genes were screened out,encoding angiopoietin-2(ANGPT2),dual oxidase 2(DUOX2),coagulation factor Ⅲ(F3),interleukin-15(IL-15),lipocalin-2,and retinoic acid receptor-related orphan receptor B(RORB).Real-time quantitative PCR and Western blotting showed that the NPC cells had up-regulated mRNA and protein levels of ANGPT2 and IL-15 and down-regulated mRNA and protein levels of DUOX2,F3,and RORB,which was consistent with the results predicted by bioinformatics.Conclusion ANGPT2,DUOX2,F3,IL-15 and RORB are potential predictive molecular markers and therapeutic targets for NPC,which may be involved in Rap1,Ras,tumor necrosis factor and other signaling pathways.
Subject(s)
Humans , Nasopharyngeal Carcinoma/genetics , Interleukin-15 , Dual Oxidases , Computational Biology , Nasopharyngeal Neoplasms/geneticsABSTRACT
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
Objective:To investigate the surgical approach for the resection of juvenile nasopharyngeal angiofibroma(JNA) under nasal endoscopy. Methods:The clinical data of 87 patients undergoing endoscopic resection of nasopharyngeal fibroangioma were retrospectively analyzed. We classified JNA according to tumor site, size, invasion scope and anatomic position relationship between tumor and midline of pupil. Three endoscopic surgical approaches were selected according to the classification, and the postoperative symptoms, complications and recurrence were investigated and analyzed. Results:The tumor resection rate of 87 cases by nasal endoscopic surgery was 100%. Thirty-five cases were approached through the middle nasal passage(small tumors located in the nasal sinuses and pterygopalatine fossa), forty-five cases were approached through the lateral wall of the nasal cavity(tumor invaded the pterygopalatine fossa but did not exceed the midline of the pupil) , and seven cases were approached via the lateral wall of nasal cavity + ipsilateral anterior wall of maxillary sinus(tumor invaded the infratemporal fossa beyond the midline of pupil or invaded the cavernous sinus and the middle cranial fossa epidural), Postoperative patients with nasal congestion, nasal bleeding, headache, dizziness, vision loss and other symptoms showed varying degrees of improvement. No surgical death or intracranial infection occurred. The postoperative follow-up was 6-78 months, and the recurrence rate was 3.44%. Conclusion:Endoscopic resection of nasopharyngeal fibroangioma is the main treatment method for JNA. Selecting suitable endoscopic approach to resect JNA, To maximize the advantage of nasal endoscopic equipment according to the inherent anatomical space of the human nasal cavity, In order to achieve the purpose of JNA resection, reduce intraoperative and postoperative complications, reduce the recurrence rate and improve the prognosis.
Subject(s)
Humans , Angiofibroma/pathology , Retrospective Studies , Nasopharyngeal Neoplasms/pathology , Endoscopy/methods , PrognosisABSTRACT
Objective:To compare the clinical effects and complications of surgery + chemotherapy and radiotherapy + chemotherapy in patients with nasopharyngeal carcinoma recurrence, so as to compare the safety and efficacy of two different therapeutic methods. Methods:A retrospective analysis was performed on 40 patients with recurrent nasopharyngeal carcinoma after radiotherapy and chemotherapy admitted to our hospital from January 2016 to June 2020. Among them, 26 patients were treated with surgery. The recurrent tumor was removed under nasal endoscope, and the frozen resection margin was negative during the operation. Chemotherapy was continued for stage Ⅲ and Ⅳ patients from 3 to 5 weeks after surgery. Fourteen patients received secondary radiotherapy and chemotherapy. Postoperative complications and survival rate were observed. Results:There were 14 patients in the secondary chemoradiotherapy group(control group) and 26 patients in the nasal endoscopic surgery group(observation group). Among the 26 patients, 19 patients underwent nasal septal mucosal repair, 5 patients underwent temporal muscle flap repair, 2 patients underwent submental flap repair, 2 patients had nasal septal mucosal flap necrosis and cerebrospinal fluid leakage, and the temporal muscle flap was used for secondary repair in the second stage operation, and 8 patients needed cervical lymph node dissection. The patients recovered well after surgery, and the patients in stage Ⅲ and Ⅳ were treated with chemotherapy after 3 weeks to 5 weeks according to the patient's wound condition. There were significant differences in the incidence of complications and 1-, 2-, and 3-year survival rates between the two groups(P<0.05). Conclusion:Patients with recurrent nasopharyngeal carcinoma can be treated by nasal endoscopic surgery to remove the tumor, and the use of pedicled nasal septal mucosal flap or temporal muscle flap for skull base reconstruction, The operation can effectively prevent major complications such as internal carotid artery rupture and hemorrhage, and improve the survival rate and quality of life of patients. It provides a safe and effective treatment for patients with recurrent nasopharyngeal carcinoma.
Subject(s)
Humans , Plastic Surgery Procedures , Nasopharyngeal Carcinoma/surgery , Retrospective Studies , Quality of Life , Skull Base/surgery , Nose Diseases/pathology , Nasopharyngeal Neoplasms/pathologyABSTRACT
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