[Retracted] miR­663 promotes NPC cell proliferation by directly targeting CDKN2A.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell cycle assay data shown in Figs. 2D and 5C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 16: 4863­4870, 2017; DOI: 10.3892/mmr.2017.7129].

miR-663b promotes tumor cell proliferation, migration and invasion in nasopharyngeal carcinoma through targeting TUSC2.

[This retracts the article DOI: 10.3892/etm.2017.4608.].

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

OBJECTIVE: To study the potential effects of intensity modulated radiation therapy (IMRT) on clinical efficacy, oral mucosa reaction and immunological foundation; and to explore the effect of immunological changes on clinical efficacy and oral mucosa reaction in patients with nasopharyngeal carcinoma.
 Methods: A total of 200 patients with nasopharyngeal carcinoma, who came from First Department of Nasopharyngeal Radiotherapy, the First People's Hospital of Foshan from October 2008 to November 2011, were selected. The patients were treated with nasopharyngeal radiotherapy, and divided into an observation group and a control group (n=100 in each group). The control group underwent common conventional two-dimensional radiotherapy treatment, while the observation group underwent IMRT. The 5-year survival rates and recurrence rates were recorded at follow-up. After the radiotherapy, the oral mucosa in the patients were evaluated by the classification standard of acute radioactive mucositis by American Radiotherapy Oncology Group (RTOG), and the number of T lymphocyte subsets before and after treatment was detected.
 Results: There were significant difference in non-regional-recurrence survival rate, disease-free survival rate, local recurrence rate between the above 2 groups (all P<0.05), but no significant difference in the distant metastasis-free survival rate (P>0.05). The acute oral mucosa reactions of grade 1, 2, 3, 4 in the control group were 8.00%, 20.00%, 12.00%, 7.00%, respectively, and those were 7.00%, 22.00%, 15.00%, 1.00% respectively. There was no significant difference in the acute response of oral mucosa in grade 1, 2 and 3 in the 2 groups (all P>0.05), but there was significant difference in the grade 4 (P<0.05). There were significantly difference in CD8+, CD4+/ CD8+ and CD4+ T lymphocyte subsets before and after treatment in the above 2 groups (all P<0.01); there were also significantly difference after treatment between the observation group and the control group (all P<0.01).
 Conclusion: In the process of treatment in patients with nasopharyngeal carcinoma, the use of IMRT on the basis of chemotherapy is more effective than the conventional two-dimensional radiotherapy, which can reduce the proportion of grade 4 (severe) acute oral mucosa reaction. It may be related to the protective effect of IMRT on immune function in the patients.

miR-663 promotes NPC cell proliferation by directly targeting CDKN2A.

MicroRNAs (miRs) act as important regulators during the development and progression of human cancer; however, the regulatory mechanism of miR-663 in nasopharyngeal carcinoma (NPC) remains unclear. The present study demonstrated that serum miR­663 levels were significantly increased in patients with NPC compared with healthy controls. In addition, the serum levels of miR­663 were associated with the grade, lymph node metastasis and clinical stage of NPC. The expression of miR­663 was increased in NPC C666­1 cells, compared with normal nasopharyngeal epithelial NP69 cells. The knockdown of miR­663 markedly decreased the proliferation of C666­1 cells through the induction of cell cycle arrest at the G1 stage. Cyclin­dependent kinase inhibitor 2A (CDKN2A) was hypothesized to be a putative target of miR­663. Further investigation confirmed that miR­663 was able to directly bind to the 3' untranslated region of CDKN2A mRNA, and to negatively regulate CDKN2A protein expression in C666­1 cells. Inhibition of CDKN2A expression attenuated the suppressive effects of miR­663 knockdown on the proliferation and cell cycle progression of C666­1 cells. In addition, it was observed that the mRNA and protein levels of CDKN2A were decreased in C666­1 cells compared with NP69 cells. In conclusion, the results of the present study demonstrated that miR­663 promoted the proliferation and cell cycle progression of NPC cells by directly targeting CDKN2A, suggesting that miR­663 may become a potential therapeutic target for the treatment of NPC.

miR-663b promotes tumor cell proliferation, migration and invasion in nasopharyngeal carcinoma through targeting TUSC2.

The authors' previous study revealed that the serum levels of microRNA (miR)-663b are significantly increased in patients with nasopharyngeal carcinoma (NPC), and are associated with NPC progression and poor prognosis. However, the molecular mechanism of underlying NPC growth and metastasis remains unclear. In the present study, quantitative polymerase chain reaction and western blot analyses were performed to examine changes to mRNA and protein expression, respectively. MTT, wound healing and Transwell assays were used to examine cell proliferation, migration and invasion, respectively. Luciferase reporter gene assays were performed to identify target genes of miR-663b. It was demonstrated that miR-663b was significantly upregulated in NPC tissue compared with non-tumor nasopharyngeal epithelial tissue samples. Furthermore, miR-663b expression gradually increased with advancing stages of NPC, with the highest expression being observed in the latest stage IV. The increased expression of miR-663b was associated with advanced clinical stage and lymph node metastasis. In addition, miR-663b expression was increased in NPC cell lines compared with normal nasopharyngeal epithelial NP69 cells. Knockdown of miR-663b resulted in a significant reduction in the proliferation, migration and invasion of NPC CNE1 cells. Tumor suppressor candidate 2 (TUSC2) was identified as a novel target gene of miR-663b. It was further demonstrated that TUSC2 was significantly downregulated in NPC tissue samples and cell lines. miR-663b negatively regulated the expression of TUSC2 at the post-transcriptional level in CNE1 cells. Additionally, inhibition of TUSC2 expression attenuated the suppressive effects of miR-663b downregulation on the proliferation, migration and invasion of CNE1 cells. To the best of our knowledge, this is the first study to demonstrate that miR-663b, which is upregulated in NPC, promotes the proliferation, migration and invasion of NPC cells, partially through the inhibition of TUSC2 expression. Therefore, it is suggested that miR-663b is a promising therapeutic target for the treatment of patients with NPC.

Increased Serum Level of MicroRNA-663 Is Correlated with Poor Prognosis of Patients with Nasopharyngeal Carcinoma.

MicroRNAs (miRs) play crucial roles in the carcinogenesis and malignant progression of human cancers including nasopharyngeal carcinoma (NPC). In this study, we aimed to investigate the association of serum miR-663 levels with the clinical factors and prognosis of NPC patients. Real-time PCR was performed to examine the amount of miR-663 in serum in NPC patients and healthy controls. Our data showed that the amount of miR-663 in serum was significantly higher in NPC patients than in healthy controls. Moreover, the serum levels of miR-663 were significantly correlated with the grade, lymph node metastasis, and clinical stage of NPC. Furthermore, higher serum miR-663 levels were closely associated with worse 5-year overall survival (OS) and relapse-free survival (RFS) of patients with NPC, and the serum level of miR-663 was found to be an independent predicator for the prognosis of NPC. In addition, after receiving chemoradiotherapy, the serum levels of miR-663 were significantly reduced in NPC patients. In summary, miR-663 was upregulated in the serum of NPC patients, which was downregulated after chemoradiotherapy, and its increased levels were closely associated with malignant progression and poor prognosis in NPC patients. Therefore, the amount of miR-663 in serum may become a potential predicator for the clinical outcome of NPC patients.

[Association between CCND1 G870A polymorphism and radiotherapy response in high-risk human papillomavirus-related cervical cancer].

OBJECTIVE: To investigate the correlation of cyclin D1 (CCND1) G870A single nucleotide polymorphism (SNP) with radiotherapy response in patients with high risk human papillomavirus (HR-HPV) related cervical cancer.
 METHODS: A total of 273 patients with cervical cancer, who were confirmed by histopathology and hybrid capture 2 (HC-2) assay and treated by radiotherapy, were enrolled for this study. The correlation of CCND1 G870A polymorphism with tumor response in patients was assessed.
 RESULTS: Compared with patients with AA genotype, the patients with GG genotype and AA genotype showed lower sensitivity to radio-therapy treatment (adjusted ORGA=2.69, 95% CI 1.28-5.67 and adjusted ORGG=3.28, 95% CI 1.47-7.29, respectively), an increase in risks of recurrence/metastasis (adjusted ORGA=2.52, 95% CI 1.12-5.63 and adjusted ORGG=3.95, 95% CI 1.68-9.26, respectively), and shorter recurrence/metastasis-free survival (PGA=0.010 and PGG=0.045).
 CONCLUSION: G870A polymorphism is a frequent variation that could be used for evaluate the radio-sensitivity and prognosis for patients with HR-HPV related cervical cancer.

Pretreatment Epstein-Barr virus DNA load and cumulative cisplatin dose intensity affect long-term outcome of nasopharyngeal carcinoma treated with concurrent chemotherapy: experience of an institute in an endemic area.

BACKGROUND: We retrospectively compared the long-term efficacy of concurrent chemoradiotherapy (CCRT) regimens (docetaxel vs. cisplatin), total dose intensity of cisplatin (> 200 vs. ≤ 200 mg/m2) and pretreatment plasma levels of Epstein-Barr virus (EBV) DNA for nasopharyngeal carcinoma (NPC), and investigated the prognostic factors. METHODS: We enrolled 214 patients diagnosed with NPC and treated with CCRT. 41 patients received weekly docetaxel and 173 weekly cisplatin. 62 received cumulative cisplatin of ≤ 200 mg/m2 and 111, > 200 mg/m2. Pretreatment levels of EBV DNA were available for 155 patients. RESULTS: Patients receiving concurrent weekly docetaxel and cisplatin had similar 5-year rates for overall survival (OS) (p = 0.306), progression-free survival (PFS) (p = 0.133), distant failure-free survival (DFS) (p = 0.110), and locoregional failure-free survival (LFS) (p = 0.452). Cumulative cisplatin of > 200 mg/m2 improved the 5-year rates of PFS (p = 0.018) and DFS (p = 0.042) significantly in comparison with cumulative cisplatin of ≤ 200 mg/m2. EBV DNA levels of ≥ 1,500 copies/ml was closely associated with poor DFS (p = 0.011), PFS (p = 0.006), and OS (p = 0.004). CONCLUSIONS: Weekly cisplatin was well tolerated in CCRT, during which cumulative cisplatin of > 200 mg/m2 improved PFS and DFS. The long-term efficacy of concurrent docetaxel was similar to that of concurrent cisplatin. The EBV DNA level was the most significant prognostic factor.

Prognostic significance of maximum primary tumor diameter in nasopharyngeal carcinoma.

BACKGROUND: To evaluate the prognostic value of maximum primary tumor diameter (MPTD) in nasopharyngeal carcinoma (NPC). METHODS: Three hundred and thirty-three consecutive, newly-diagnosed NPC patients were retrospectively reviewed. Kaplan-Meier analysis and the log-rank test were used to estimate overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS) and local relapse-free survival (LRFS). Cox proportional hazards regression analysis was used to assess the prognostic value of MPTD. RESULTS: Median follow-up was 66 months (range, 2-82 months). Median MPTD in stage T1, T2, T3 and T4 was 27.9, 37.5, 45.0 and 61.3 mm, respectively. The proportion of T1 patients with a MPTD ≤ 30 mm was 62.3%; 72% and 62.9% of T2 and T3 patients had a MPTD > 30-50 mm, and 83.5% of T4 patients had a MPTD > 50 mm. For patients with a MPTD ≤ 30 mm, > 30-50 mm and > 50 mm, the 5-year OS, FFS, DMFS and LRFS rates were 85.2%, 74.2% and 56.3% (P < 0.001); 87%, 80.7% and 62.8% (P < 0.001); 88.7%, 86.4% and 72.5% (P = 0.003); and 98.2%, 93.2% and 86.3% (P = 0.012), respectively. In multivariate analysis, MPTD was a prognostic factor for OS, FFS and DMFS, and the only independent prognostic factor for LRFS. For T3-T4 patients with a MPTD ≤ 50 mm and > 50 mm, the 5-year OS, FFS and DMFS rates were 70.4% vs. 58.4% (P = 0.010), 77.5% vs. 65.2% (P = 0.013) and 83.6% vs. 73.6% (P = 0.047), respectively. In patients with a MPTD ≤ 30 mm, 5-year LRFS in T1, T2, T3 and T4 was 100%, 100%, 88.9% and 100% (P = 0.172). CONCLUSIONS: Our data suggest that MPTD is an independent prognostic factor in NPC, and incorporation of MPTD might lead to a further refinement of T staging.

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

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