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.
Animals ; Humans ; Nasopharyngeal Carcinoma/genetics* ; Epithelial-Mesenchymal Transition ; Zebrafish ; Cell Proliferation ; Cell Line, Tumor ; Nasopharyngeal Neoplasms/radiotherapy* ; Cell Movement ; Gene Expression Regulation, Neoplastic

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.
Humans ; Radiotherapy, Intensity-Modulated ; Immune Tolerance ; Nasopharyngeal Carcinoma ; ROC Curve ; Nasopharyngeal Neoplasms/radiotherapy*

Objective: To study the effect of circ-WHSC1 on the growth, metastasis and radiosensitivity of nasopharyngeal carcinoma cells and its molecular mechanism. Methods: Cancerous tissues and adjacent tissues were collected from 23 patients with nasopharyngeal carcinoma, and real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the expression levels of circ-WHSC1, miR-338-3p, and ELAVL1 mRNA. Western blot was used to detect the expression of ELAVL1 protein. Nasopharyngeal carcinoma cells 5-8F and SUNE1 were divided into si-NC group, si-circ-WHSC1 group, pCD5-ciR group, circ-WHSC1 group, anti-miR-NC group, anti-miR-338-3p group, miR-NC group, miR-338-3p group, si-circ-WHSC1+ anti-miR-NC group, si-circ-WHSC1+ anti-miR-338-3p group, miR-338-3p+ pcDNA group, miR-338-3p+ ELAVL1 group. Tetramethylazolium salt colorimetric method (MTT) was used to detect cell viability. Clone formation test was used to detect cell clone formation and cell radiosensitivity. Flow cytometry was used to detect cell apoptosis. Transwell was used to detect cell migration and invasion. Dual luciferase assay was used to detect the targeting relationship between circ-WHSC1 and miR-338-3p, miR-338-3p and ELAVL1. The SUNE1 cells stably transfected with sh-circ-WHSC1 were injected into nude mice and irradiated with radiation, and then the tumor volume and weight of mice were detected. Results: The expressions of circ-WHSC1 (1.57±0.94 vs 3.78±1.18, 1.00±0.10 vs 1.64±0.14/2.00±0.21/2.81±0.26/3.36±0.34) and ELAVL1 (1.28±0.74 vs 3.36±0.77, 1.00±0.08 vs 2.51±0.19/3.27±0.27) in nasopharyngeal carcinoma tissues and cells were increased, and the expression of miR-338-3p (3.13±0.96 vs 1.37±0.98, 1.00±0.08 vs 0.48±0.08/0.38±0.07) was decreased (P<0.05). After knockdown of circ-WHSC1, the activity of nasopharyngeal carcinoma cells was decreased [(100.00±8.00)% vs (51.33±8.62)%, (100.00±10.10)% vs (41.02±7.31)%], the number of clone-forming cells was decreased (101.00±8.54 vs 50.33±8.02, 114.00±14.10 vs 42.33±10.01), the rate of apoptosis was increased [(5.37±1.20)% vs (18.3±1.01)%, (6.5±1.18)% vs (22.43±1.40)%], and the numbers of migration (136.00±13.00 vs 72.33±9.50, 154.00±14.10 vs 62.67±11.50) and invasion (113.67±11.59 vs 60.67±9.07, 124.33±15.57 vs 50.33±9.01) were decreased; after different doses of radiation, the cell survival score was decreased (0.23±0.04 vs 0.06±0.01, 0.32±0.07 vs 0.05±0.02) (P<0.05). Circ-WHSC1 targeted and negatively regulated miR-338-3p. Inhibition of miR-338-3p affected the effect of knockdown of circ-WHSC1 on the proliferation, apoptosis, migration, invasion and radiosensitivity of nasopharyngeal carcinoma cells. MiR-338-3p targeted and negatively regulated ELAVL1; ELAVL1 overexpression affected the effects of miR-338-3p on the proliferation, apoptosis, migration, invasion and radiosensitivity of nasopharyngeal carcinoma cells. After the cells stably transfected with sh-circ-WHSC1 were injected into nude mice, the tumor volume [(884.67±95.63)mm(3) vs (487.33±76.51)mm(3)] and weight [(899.01±88.54)mg vs (558.67±75.04) mg] of the nude mice were reduced; after further irradiation, the tumor volume [(395.00±73.50)mm(3) vs 243.13±42.51)mm(3)] and weight[ (452.33±67.30)mg vs (211.09±57.51)mg] of the nude mice were reduced (P<0.05). Circ-WHSC1 regulated the expression of ELAVL1 by targeting miR-382. Conclusion: Knockdown of circ-WHSC1 can inhibit the growth and metastasis of nasopharyngeal carcinoma cells by targeting miR-338-3p/ELAVL1 axis, and enhances the radiosensitivity of nasopharyngeal carcinoma cells.
Mice ; Animals ; Nasopharyngeal Carcinoma/radiotherapy* ; Mice, Nude ; MicroRNAs/genetics* ; Antagomirs ; Cell Line, Tumor ; Radiation Tolerance/genetics* ; Nasopharyngeal Neoplasms/pathology* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic

OBJECTIVE: To investigate the accuracy of automatic segmentation of organs at risk (OARs) in radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: The CT image data of 147 NPC patients with manual segmentation of the OARs were randomized into the training set (115 cases), validation set (12 cases), and the test set (20 cases). An improved network based on three-dimensional (3D) Unet was established (named as AUnet) and its efficiency was improved through end-to-end training. Organ size was introduced as a priori knowledge to improve the performance of the model in convolution kernel size design, which enabled the network to better extract the features of different organs of different sizes. The adaptive histogram equalization algorithm was used to preprocess the input CT images to facilitate contour recognition. The similarity evaluation indexes, including Dice Similarity Coefficient (DSC) and Hausdorff Distance (HD), were calculated to verify the validity of segmentation. RESULTS: DSC and HD of the test dataset were 0.86±0.02 and 4.0±2.0 mm, respectively. No significant difference was found between the results of AUnet and manual segmentation of the OARs ( CONCLUSIONS AUnet, an improved deep learning neural network, is capable of automatic segmentation of the OARs in radiotherapy for NPC based on CT images, and for most organs, the results are comparable to those of manual segmentation.
Databases, Factual ; Humans ; Image Processing, Computer-Assisted ; Nasopharyngeal Carcinoma/radiotherapy* ; Nasopharyngeal Neoplasms/radiotherapy* ; Organs at Risk ; Tomography, X-Ray Computed

Modern pharmacological studies have shown that Shengmai San has the effects of enhancing immunity and improving blood circulation, and Curcumae Longae Rhizoma(Jianghuang) has anti-inflammatory, anti-cancer, anti-oxidation and other functions. Shengmai San combined with Jianghuang is a new research direction in the study of anti-tumor of traditional Chinese medicines. The main treatment for nasopharyngeal carcinoma is radiation therapy, but radiation therapy can cause a variety of side effects, and it also changes the composition of the intestinal flora. In this study, the 16 s rDNA sequencing platform was used to perform macro-sequence sequencing of the intestinal flora samples of nude mice bearing the veins of Shengmai Jianghuang San, and then the results of intestinal flora data were analyzed to investigate the effect of Shengmai Jianghuang San on tumors. The results showed that Shengmai Jianghuang San combined with irradiation could enhance the therapeutic effect of tumor treatment. Radiation therapy would reduce the total number and diversity of intestinal flora in nude mice, and also change the structure of the flora. Shengmai Jianghuang San could protect the diversity of colonies, and also partially restore the colony imbalance caused by irradiation. This study provides a research idea for Shengmai Jianghuang San as a sensitizing adjuvant for radiotherapy of nasopharyngeal carcinoma.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Gastrointestinal Microbiome ; drug effects ; Mice ; Mice, Nude ; Nasopharyngeal Carcinoma ; radiotherapy ; Radiation Tolerance ; Radiation-Sensitizing Agents ; pharmacology

To explore the correlation of quality of life with self-care efficacy and social support in patients with nasopharyngeal carcinoma after radiotherapy.
 Methods: A total of 179 patients with nasopharyngeal carcinoma at 3 months after radiotherapy were surveyed using self-designed general information questionnaire, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30 V3.0), Chinese-version of Strategies Used by People to Promote Health (C-SUPPH), and Perceived Social Support Scale (PSSS).
 Results: The score of cognitive function was the highest, while the score of social function was the lowest. The score of related symptoms was 22.21±10.24, the overall score for quality of life was 52.46±17.96, the score of self-care efficacy was 62.14±14.50, and the score of social support was 56.03±7.63. Self-care efficacy of patients with nasopharyngeal cancer after radiotherapy was positively correlated with 5 functional areas of quality of life and overall quality of life, and negatively correlated with relevant symptoms (P<0.01). Social support was positively correlated with physical function, social function and overall quality of life (P<0.01), and negatively correlated with relevant symptoms (P<0.05). Multiple regression analysis showed that self-care efficacy could predict 5 functional areas of life quality, relevant symptoms, overall quality of life and social support predicted social function in quality of life.
 Conclusion: Self-care efficacy and social support for patients with nasopharyngeal cancer after radiotherapy can affect their quality of life. Nursing staff should pay attention to improving the self-care efficacy of patients, guide them to actively seek or obtain social support, and in turn to improve their quality of life.
Humans ; Nasopharyngeal Carcinoma ; radiotherapy ; Nasopharyngeal Neoplasms ; radiotherapy ; Quality of Life ; Self Care ; Social Support

OBJECTIVETo investigate the method of surgical treatment via trans-nasal endoscopic approach in osteoradionecrosis of skull base after radiotherapy for nasopharyngeal carcinoma.

METHODSFifteen patients with osteoradionecrosis of skull base after radiotherapy for nasopharyngeal carcinoma who underwent operation via trans-nasal endoscopic approach from 2008 to 2013 were retrospectively reviewed. The typical clinical manifestations included headache (NRS 6-9: 11 cases), foul odor (10 cases), epistaxis (4 cases), hearing loss (5 cases, 7 ears), tinnitus (4 cases, 5 ears). All patients underwent operation via trans-nasal endoscopic approach. During the operation, the diseased region was fully exposed, the necrotic tissue was resected, the necrotic bone was removed by high-speed electric drill, and the drainage was made unobstructed. The perioperative treatment and follow-up were carried out.

RESULTSAfter operation, all patients were diagnosed pathologically as osteoradionecrosis and mucosal chroinic inflammation, 1 case combined with fungal sphenoid sinusitis. Headache (9 cases) and foul odor (9 cases) resolved after operation. The follow-up was lasted 18-82 months, 13 cases were survival, 1 case lost to follow-up, 1 case died of cerebral hemorrhage.

CONCLUSIONSurgical treatment via trans-nasal endoscopic approach is safe and effective in osteoradionecrosis of skull base after radiotherapy for nasopharyngeal carcinoma, and is helping to improve the survival rate and survival quality.

Carcinoma ; Endoscopy ; Humans ; Nasopharyngeal Neoplasms ; radiotherapy ; Osteoradionecrosis ; surgery ; Retrospective Studies ; Skull Base ; surgery ; Survival Rate

OBJECTIVETo evaluate the efficacies of different treatments for recurrent cervical lymph nodes and the factors contributing to prognosis in patients with nasopharyngeal carcinoma after radiotherapy.

METHODSClinical data of 79 patients with nasopharyngeal carcinoma after radiotherapy were retrospectively analyzed, and all cases were diagnosed as having recurrent cervical lymph nodes by pathological examination. The factors including sex, age, the interval between completion of radiotherapy and recurrence, rN stage, treatment methods, and the location relationship between recurrent lesion and primary tumor in the neck were analyzed for prognosis. Kaplan-Meier curves, Log-rank test and Cox's proportional hazards regression mode were used in the statistical analysis.

RESULTSThe median recurrence time was 26 months, and the 1- , 3- and 5-year overall survival rates were 77.9%, 53.4% and 39.7%. Cox's proportional hazards regression mode analysis indicated that age, rN stage, treatment methods, and the location relationship between recurrent lesion and primary tumor were significantly prognostic factors.

CONCLUSIONSNeck dissection is superior to re-radiotherapy in treatment of recurrent cervical lymph nodes in nasopharyngeal carcinoma after radiotherapy. The patients younger than 45 years old, in early rN stage and for recurrence in the center region of primary tumor have a better prognosis.

Carcinoma ; Humans ; Kaplan-Meier Estimate ; Lymph Nodes ; pathology ; Nasopharyngeal Neoplasms ; radiotherapy ; Neck ; Neck Dissection ; Neoplasm Recurrence, Local ; surgery ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Treatment Outcome

OBJECTIVETo evaluate the effect of cervical esophagostomy for the treatment of patients with dysphagia induced by radiotherapy, in order to improve the therapeutic effects.

METHODSA retrospective study was performed on 53 nasopharyngeal carcinoma (NPC) patients with dysphagia, who received cervical esophagostomy. The nutritional status of these patients was measured at five given time before and after operation. The occurrence of pneumonia and reflux esophagitis before and after operation was recorded, and the quality of life based on SF-36 quality of life (QOL) scale was studied.

RESULTSAfter operation, the nutritional status of these patients improved substantially, including the weight, levels of hemoglobin, total protein, albumin and transferring (P<0.05). The pneumonia-infection decreased from 60.38% (32/53) before operation to 15.22% (7/46) after operation (χ(2)=21.04, P<0.01). The incidences of reflux esophagitis decreased from 26.42% (14/53)without operation to 6.52% (3/46) after operation (χ(2)=5.00, P<0.01). Meanwhile, the status of physical health, mental health as well as physical function and social function of these patients were improved significantly at 1 month, 6 months, 1 year and 2 years after operation (P<0.05).

CONCLUSIONCervical esophagostomy can improve the life quality of patients with dysphagia induced by radiotherapy for nasopharyngeal carcinoma.

Carcinoma ; Deglutition Disorders ; complications ; surgery ; Esophagitis, Peptic ; complications ; Esophagostomy ; Humans ; Incidence ; Nasopharyngeal Neoplasms ; complications ; radiotherapy ; Pneumonia ; complications ; Quality of Life ; Radiotherapy ; adverse effects ; Retrospective Studies

OBJECTIVETo study the changes in quantitative kinetic parameters in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during radiotherapy and their value for efficacy evaluation in patients with nasopharyngeal carcinoma (NPC).

METHODSTwenty-four patients with NPC that had been pathologically confirmed as poorly differentiated squamous cell carcinoma underwent conventional MRI and DCE-MRI scans 1-2 days before radiotherapy (Pre-RT), during radiotherapy (RT 50 Gy), and upon completion of radiotherapy (RT 70 Gy). Based on the two-compartment model and using the arterial input function deconvolution technique, we calculated the quantitative kinetic parameters of DCE-MRI (K(trans), kep, and Ve) of the tumor tissues, examined the correlation between the tumor regression rate (RS0-50) and the parameters on Pre-RT and RT 50 Gy, and compared the parameters for RT 70 Gy among the groups with different prognosis.

RESULTSThe K(trans) value of the tumor tissue decreased after radiotherapy and showed a significant difference between Pre-RT and RT 70 Gy, but not between Pre-RT and RT 50 Gy. The kep value decreased and Ve value increased after radiotherapy. The tumor regression rate was found to be positively correlated with the K(trans) value for Pre-RT (P=0.005) but negatively with the K(trans) value for RT 50 Gy (P=0.001). During the follow-up for 3 years, 5 patients died and 3 patients had distant metastases. No statistical differences in K(trans), kep, or Ve were found between the groups with different prognosis.

CONCLUSIONSThe kinetic parameters in DCE-MRI, which vary significantly during radiotherapy, allow monitoring of tumor angiogenesis and vascular permeability and quantitative assessment of treatment efficacy for NPC. K(trans) value for Pre-RT and RT 50 Gy can serve as an indicator for early efficacy assessment of radiotherapy and for treatment adjustment, but its relation with the long-term outcomes awaits further study.

Algorithms ; Capillary Permeability ; Carcinoma ; Carcinoma, Squamous Cell ; diagnosis ; Humans ; Magnetic Resonance Imaging ; Nasopharyngeal Neoplasms ; blood supply ; radiotherapy ; Neovascularization, Pathologic ; Prognosis ; Treatment Outcome