Prognostic analysis of surgical treatment for T3 glottic laryngeal cancer based on different tumor extension patterns.

BACKGROUND AND OBJECTIVES: To investigate the prognostic impact of different tumor invasion patterns in the surgical treatment of T3 glottic laryngeal cancer. METHODS: We conducted a retrospective analysis of clinical data of 91 patients with T3 glottic laryngeal cancer. RESULTS: We found that the posterior invasion being significantly associated with involvement of the lamina of cricoid cartilage (P < 0.001), arytenoid cartilage (P = 0.001), and subglottic (P = 0.001). There was no statistical difference in survival outcomes between the total laryngectomy (TL) group and the partial laryngectomy (PL) group, but in the PL group, tumors with anterior invasion were associated with a better 5-year DFS than tumors with posterior invasion (HR: 4.681, 95% CI: 1.337-16.393, P = 0.016), and subglottic involvement was associated with worse LRRFS (HR: 3.931, 95% CI: 1.054-14.658, P = 0.041). At the same time, we found that involvement of the lamina of cricoid cartilage was an independent risk factor for postoperative laryngeal stenosis in PL patients (HR: 11.67, 95% CI: 1.89-71.98, P = 0.008). CONCLUSION: Selectively performed PL can also achieve favorable oncological outcomes comparable to those of TL. Posterior invasion and subglottic involvement are independent prognostic factors for recurrence after PL in T3 glottic laryngeal cancer, and involvement of the lamina of cricoid cartilage is associated with postoperative laryngeal stenosis. The tumor invasion pattern of patients with laryngeal cancer should be further subdivided to allow for selection of a more individualized treatment plan.

Robust Point Cloud Registration for Aircraft Engine Pipeline Systems.

Aircraft engine systems are composed of numerous pipelines. It is crucial to regularly inspect these pipelines to detect any damages or failures that could potentially lead to serious accidents. The inspection process typically involves capturing complete 3D point clouds of the pipelines using 3D scanning techniques from multiple viewpoints. To obtain a complete and accurate representation of the aircraft pipeline system, it is necessary to register and align the individual point clouds acquired from different views. However, the structures of aircraft pipelines often appear similar from different viewpoints, and the scanning process is prone to occlusions, resulting in incomplete point cloud data. The occlusions pose a challenge for existing registration methods, as they can lead to missing or wrong correspondences. To this end, we present a novel registration framework specifically designed for aircraft pipeline scenes. The proposed framework consists of two main steps. First, we extract the point feature structure of the pipeline axis by leveraging the cylindrical characteristics observed between adjacent blocks. Then, we design a new 3D descriptor called PL-PPFs (Point Line-Point Pair Features), which combines information from both the pipeline features and the engine assembly line features within the aircraft pipeline point cloud. By incorporating these relevant features, our descriptor enables accurate identification of the structure of the engine's piping system. Experimental results demonstrate the effectiveness of our approach on aircraft engine pipeline point cloud data.

Controlling photons by phonons via giant atom in a waveguide QED setup.

We investigate the single photon scattering in a phonon-photon hybrid system in the waveguide quantum electrodynamics (QED) scheme. In our consideration, an artificial giant atom, which is dressed by the phonons in a surface acoustic wave resonator, interacts with a coupled resonator waveguide (CRW) nonlocally via two connecting sites. Together with the interference effect by the nonlocal coupling, the phonon serves as a controller to the transport of the photon in the waveguide. On the one hand, the coupling strength between the giant atom and the surface acoustic wave resonator modulates the width of the transmission valley or window in the near resonant regime. On the other hand, the two reflective peaks induced by the Rabi splitting degrade into a single one when the giant atom is large detuned from the surface acoustic resonator, which implies an effective dispersive coupling. Our study paves the way for the potential application of giant atoms in the hybrid system.

Pedicled thoracoacromial artery compound flaps for circumferential hypopharyngeal reconstruction.

BACKGROUND: Total laryngeal and hypopharyngeal resection remained to be the mainly treatment option for advanced hypopharyngeal cancer, which resulted in complicated reconstructive challenge for circumferential hypopharyngeal defect. The pedicled thoracoacromial artery compound flaps included Thoracoacromial artery perforator (TAAP) flap and pectoralis major myocutaneous (PMMC) flap. This study is to evaluate the clinical application of the pedicled thoracoacromial artery compound flaps for circumferential hypopharyngeal reconstruction. METHODS: From May 2021 to April 2022, four hypopharyngeal cancer patients with circumferential hypopharyngeal defects were reconstructed by the pedicled thoracoacromial artery compound flaps. All patients were males. Patient age ranged from 35 to 62 years (average, 50 years). The Shoulder function were evaluated by SPADI. The average follow-up was 10.25 months (range from 4 to 18 months). RESULTS: All of the pedicled thoracoacromial artery compound flaps in our study survived. The defect length between tongue base and cervical esophagus ranged from 8 to 10 cm after total laryngeal and hypopharyngeal resection. The TAAP flap size ranged from 6 × 7 cm to 7 × 10 cm, and the PMMC flap size ranged from 6 × 7 cm to 9 × 12 cm. The pedicle length of TAAP and PMMC flaps varied, respectively, from 5 to 8 cm (mean 6.5 cm) and 7 cm to 11 cm (mean 8.75 cm). The mean time of TAAP and PMMC flaps harvest was, respectively, 82 min and 39 min. All patients were able to resume soft diet in the fourth week of postoperation, but one patient was operated by gastrostomy in the second month of postoperation because of pharyngeal cavity stenosis, and the patient successfully resumed oral soft diet by endoscopic balloon dilation after postoperation radiotherapy. All patients have resumed oral feeding at last. There were mild dysfunction for our patients according to SPADI during the mid-long follow-up. CONCLUSIONS: The pedicled thoracoacromial artery compound flaps have stable blood supply and provide adequate muscle coverage for greater protection during radiotherapy, and the microsurgical skills have no requirement. Therefore, the compound flaps provide a good choice for the reconstruction of circumferential hypopharyngeal defect, especially in the aged or patients with comorbidities who are not able to tolerate prolonged surgery.

Rolling Bearing Performance Degradation Assessment with Adaptive Sensitive Feature Selection and Multi-Strategy Optimized SVDD.

In light of the problems of a single vibration feature containing limited information on the degradation of rolling bearings, the redundant information in high-dimensional feature sets inaccurately reflecting the reliability of rolling bearings in service, and assessments of the degradation performance being disturbed by outliers and false fluctuations in the signal, this study proposes a method of assessing rolling bearings' performance in terms of degradation using adaptive sensitive feature selection and multi-strategy optimized support vector data description (SVDD). First, a high-dimensional feature set of vibration signals from rolling bearings was extracted. Second, a method combining the Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS) and K-medoids was used to comprehensively evaluate the features with multiple evaluation indicators and to adaptively select better degradation features to construct the sensitive feature set. Next, multi-strategy optimization of the SVDD model was carried out by introducing the autocorrelation kernel regression (AAKR) and a multi-kernel function to improve the ability of the evaluation model to overcome outliers and false fluctuations. Through validation, it could be seen that the method in this study uses samples of rolling bearings in the healthy early stage to establish the evaluation model, which can adaptively determine the starting point of the bearing's degradation. The stability and accuracy of the model were effectively improved.

Remaining Useful Life Prediction of Rolling Bearings Using GRU-DeepAR with Adaptive Failure Threshold.

Aiming at the problem that a single neural network model has difficulty in accurately predicting trends of the remaining useful life of a rolling bearing, a method of predicting the remaining useful life of rolling bearings using a gated recurrent unit-deep autoregressive model (GRU-DeepAR) with an adaptive failure threshold was proposed. First, time domain and frequency domain features were extracted from the rolling bearing vibration signal. Second, its operation process was divided into a smooth operation stage and degradation stage according to the trend of the accumulated root mean square of maximum. Then, the failure threshold for different bearings were determined adaptively by the maximum of the smooth operation data. The degradation dataset of a rolling bearing was subsequently obtained. In the meantime, a GRU-DeepAR model was built to obtain predictions of the failure time and failure probability. Appropriate model parameters were determined after a large number of tests to assure the effectiveness and prediction accuracy. Finally, the trend of time series and failure times were predicted by inputting the degradation dataset into the GRU-DeepAR model. Experiments showed that the proposed method can effectively improve the accuracy of the remaining useful life prediction of a rolling bearing with good stability.

Mexicanolide limonoids from the seeds of Khaya ivorensis with antimicrobial activity.

The methanol extract of the seeds of Khaya ivorensis afforded two new mexicanolide limonoids, ivorensines A and B (1 and 2), together with one known compound, ruageanin D (3). The structures of the isolated compounds were established based on 1 D and 2 D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated limonoids were tested in vitro for antimicrobial potentials against 5 pathogenic microorganisms. As a result, compounds 1-3 exhibited antimicrobial activity against the tested Gram negative bacteria at the minimum inhibitory concentration values less than 50 µg/ml.

RAF1 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating LAGE1: an experimental research.

BACKGROUND: Lymphatic metastasis was an independent prognostic risk factor for hypopharyngeal carcinoma and was the main cause of treatment failure. The purpose of this study was to screen the differential genes and investigate the mechanism of lymphatic metastasis in hypopharyngeal carcinoma. METHODS: Transcriptome sequencing was performed on primary tumors of patients, and differential genes were screened by bioinformatics analysis. The expression of differential genes was verified by qRT-PCR, western-blotting and immunohistochemical, and prognostic value was analyzed by Kaplan-Meier and log-rank test and Cox's test. Next, FADU and SCC15 cell lines were used to demonstrate the function of differential genes both in vitro by EdU, Flow cytometry, Wound Healing and Transwell assays and in vivo by a foot-pad xenograft mice model. Proteomic sequencing was performed to screen relevant targets. In addition, in vitro and in vivo experiments were conducted to verify the mechanism of lymphatic metastasis. RESULTS: Results of transcriptome sequencing showed that RAF1 was a significantly differential gene in lymphatic metastasis and was an independent prognostic risk factor. In vitro experiments suggested that decreased expression of RAF1 could inhibit proliferation, migration and invasion of tumor cells and promote apoptosis. In vivo experiments indicated that RAF1 could promote tumor growth and lymphatic metastasis. Proteomic sequencing and subsequent experiments suggested that LAGE1 could promote development of tumor and lymphatic metastasis, and was regulated by RAF1. CONCLUSIONS: It suggests that RAF1 can promote lymphatic metastasis of hypopharyngeal carcinoma by regulating LAGE1, and provide a basis for the exploring of novel therapeutic target and ultimately provide new guidance for the establishment of intelligent diagnosis and precise treatment of hypopharyngeal carcinoma.

CEACAM5 inhibits the lymphatic metastasis of head and neck squamous cell carcinoma by regulating epithelial-mesenchymal transition via inhibiting MDM2.

Lymph node (LN) metastasis affects both the management and prognosis of head and neck squamous cell carcinoma (HNSCC). Here, we explored the relationship between lymphatic metastasis and CEA family member 5 (CEACAM5), including its possible regulatory role in HNSCC. The levels of CEACAM5 in tissues from patients with HNSCC, with and without LN metastases, were assessed by transcriptome sequencing. The associations between CEACAM5 and the N stage of LN metastasis in HNSCC were predicted through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and a pan-cancer analysis of CEACAM5 expression in 33 common human tumors was conducted. CEACAM5 levels were analyzed in tumor and normal tissue specimens from HNSCC patients and the correlation between CEACAM5 levels and prognosis was evaluated. The influence of CEACAM5 on cell proliferation, invasion, migration, and apoptosis was investigated in HNSCC cell lines, as were the downstream regulatory mechanisms. A mouse model of LN metastasis was constructed. CEACAM5 levels were significantly higher in HNSCC tissue without LN metastasis than in that with LN metastasis. Similar findings were obtained for the clinical specimens. CEACAM5 levels were associated with better clinical prognosis. CEACAM5 was found to inhibit the proliferation and migration and promote the apoptosis of HNSCC cells. A mouse xenograft model showed that CEACAM5 inhibited LN metastasis. In conclusions, CEACAM5 inhibited epithelial-mesenchymal transition (EMT) in HNSCC by reducing murine double minute 2 (MDM2) expression and thereby suppressing LN metastasis. CEACAM5 has potential as both a prognostic marker and a therapeutic target in HNSCC.

Bi(OTf)3-Catalyzed Alkyl-Intercepted Meyer-Schuster Rearrangement of Propargylic Alcohols for the Synthesis of 1,2,3,5-Tetrasubstituted Pentane-1,5-diones.

An alkyl intercepted Meyer-Schuster rearrangement reaction with α,ß-unsaturated ketones as the electrophiles was first investigated, which provided a facile method to construct 2-methylene-pentane-1,5-diones. Then the in situ generated 2-methylene-pentane-1,5-diones underwent a Michael addition to give diverse 2-malononitrile methyl substituted pentane-1,5-diones in a one-pot fashion. This transformation was reliable on a gram scale. The high yield, convenient experimental operation, and 100% atom economy made it a valuable method for the construction of 1,2,3,5-tetrasubstituted pentane-1,5-dione derivatives.

Multi-Focus Image Fusion Based on Multi-Scale Generative Adversarial Network.

The methods based on the convolutional neural network have demonstrated its powerful information integration ability in image fusion. However, most of the existing methods based on neural networks are only applied to a part of the fusion process. In this paper, an end-to-end multi-focus image fusion method based on a multi-scale generative adversarial network (MsGAN) is proposed that makes full use of image features by a combination of multi-scale decomposition with a convolutional neural network. Extensive qualitative and quantitative experiments on the synthetic and Lytro datasets demonstrated the effectiveness and superiority of the proposed MsGAN compared to the state-of-the-art multi-focus image fusion methods.

Controllable optical response and tunable sensing based on self interference in waveguide QED systems.

We study the self interference effect of a resonator coupled with a bent waveguide at two separated ports. Such interference effects are shown to be similar for the cases of standing-wave and traveling-wave resonators, while in the system of two separated resonators indirectly coupled via a waveguide, the coupling forms and the related interference effects depend on which kind of resonators is chosen. Due to the self interference, controllable optical responses including tunable linewidth and frequency shift, and optical dark state can be achieved. Moreover, we consider a self-interference photon-magnon hybrid model and show phase-dependent Fano-like line shapes which have potential applications in frequency sensing. The photon-magnon hybridization can not only enhance the sensitivity and provide tunable working region, but also enables optical readout of the magnetic field strength in turn. The results in this paper provide a deeper insight into the self interference effect and its potential applications.

PARP inhibitor Olaparib increases the sensitization to radiotherapy in FaDu cells.

Radioresistance causes a major problem for improvement of outcomes of patients treated with radiation. Targeting for DNA repair deficient mechanisms is a hallmark of sensitization to resistance. We tested whether Olaparib, a (poly) ADP-ribose polymerase (PARP) inhibitor, can sensitize the radioresistant FaDu cells to radiotherapy. Radioresistant FaDu cells, called FaDu-RR cells, were used as the radioresistant hypopharyngeal cancer models. The expression of PARP1 was detected in both FaDu and FaDu-RR cells. The role of Olaparib in radiosensitization was analysed with several assays including clonogenic cell survival, cell proliferation and cell cycle, and radioresistant xenograft. High expression of PARP1 had a significant effect on enhancing radioresistance in FaDu-RR cells compared with FaDu cells. After treatment of Olaparib, FaDu-RR cells showed significantly less and smaller surviving colonies, lower proliferation ability and G2/M arrest than those in the group without treatment. Moreover, Olaparib significantly reduced growth of tumours in FaDu-RR cell xenografts treated with ionizing radiation. Olaparib can significantly inhibit PARP1 expression and consequently has significant effects on radiosensitization in FaDu-RR cells. These results indicate that Olaparib may help individualize treatment and improve their outcomes of hypopharyngeal cancer patients treated with radiation.

Supercorrelated Radiance in Nonlinear Photonic Waveguides.

We study the collective decay of two-level emitters coupled to a nonlinear waveguide, for example, a nanophotonic lattice or a superconducting resonator array with strong photon-photon interactions. Under these conditions, a new decay channel into bound photon pairs emerges, through which spatial correlations between emitters are established by regular interference as well as interactions between the photons. We derive an effective Markovian theory to model the resulting decay dynamics of an arbitrary distribution of emitters and identify collective effects beyond the usual phenomena of super- and subradiance. Specifically, in the limit of many close-by emitters, we find that the system undergoes a supercorrelated decay process where all the emitters are either in the excited state or in the ground state but not in any of the intermediate states. The predicted effects can be probed in state-of-the-art waveguide QED experiments and provide a striking example of how the dynamics of open quantum systems can be modified by many-body effects in a nonharmonic environment.

The Effects of Mobile Phone Radiofrequency Radiation on Cochlear Stria Marginal Cells in Sprague-Dawley Rats.

To investigate the possible mechanisms for biological effects of 1,800 MHz mobile radiofrequency radiation (RFR), the radiation-specific absorption rate was applied at 2 and 4 W/kg, and the exposure mode was 5 min on and 10 min off (conversation mode). Exposure time was 24 h short-term exposure. Following exposure, to detect cell DNA damage, cell apoptosis, and reactive oxygen species (ROS) generation, the Comet assay test, flow cytometry, DAPI (4',6-diamidino-2-phenylindole dihydrochloride) staining, and a fluorescent probe were used, respectively. Our experiments revealed that mobile phone RFR did not cause DNA damage in marginal cells, and the rate of cell apoptosis did not increase (P > 0.05). However, the production of ROS in the 4 W/kg exposure group was greater than that in the control group (P < 0.05). In conclusion, these results suggest that mobile phone energy was insufficient to cause cell DNA damage and cell apoptosis following short-term exposure, but the cumulative effect of mobile phone radiation still requires further confirmation. Activation of the ROS system plays a significant role in the biological effects of RFR. Bioelectromagnetics. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals, Inc.

15-hydroxy-6α,12-epoxy-7ß,10αH,11ßH-spiroax-4-ene-12-one sensitizes rectal tumor cells to anti-PD1 treatment through agonism of CD11b.

PURPOSE: Although immunotherapies have resulted in durable clinical responses, not all tumor types have seen substantial benefit. Extensive recruitment and accumulation of immunosuppressive myeloid cells into the tumor tissues has been postulated as a major mechanism of resistance to immunotherapies. Strategies targeting on single immunosuppressive cell type, in combination with checkpoint inhibitors, have resulted in promising outcomes in animal studies. However, compensatory actions by untargeted cells may limit the therapeutic efficacy. CD11b is highly expressed on the myeloid cell surface with an important role in their trafficking and cellular functions.In this study, we demonstrated that activation of CD11b with 15-hydroxy-6α,12-epoxy-7ß,10αH,11ßH-spiroax-4-ene-12-one (HESEO) enhanced the therapeutic efficacy of anti-PD1 treatment in the tumor model. MATERIALS AND METHODS: A syngeneic rectal tumor model was established. Different types of cells from the peripheral blood and tumor tissues were analyzed by flow cytometry. Real-time PCR was used to detect the gene expression. Therapeutic effects of HESEO combining with anti-PD1 antibody were assessed by the tumor model. RESULTS: Our data demonstrated that HESEO repolarized tumor-associated macrophages and reduced the number of tumor-infiltrating immunosuppressive myeloid cells. We further demonstrated that HESEO and immunotherapy combination promoted tumor growth control in a syngeneic tumor model. CONCLUSIONS: Our results showed that HESEO improved anti-tumor T cell immunity and rendered anti-PD1 treatment effective in unresponsive tumor models, providing proof of concept for a new combination strategy involving molecular agonism of CD11b to bypass the limitations of current clinical strategies to overcome resistance to immunotherapies.

Reconstruction of Periodic Band Limited Signals from Non-Uniform Samples with Sub-Nyquist Sampling Rate.

Important state parameters, such as torque and angle obtained from the servo control and drive system, can reflect the operating condition of the equipment. However, there are two problems with the information obtained through the network from the control and drive system: the low sampling rate, which does not meet the sampling theorem and the nonuniformity of the sampling points. By combing equivalent sampling and nonuniform signal reconstruction theory, this paper proposes a reconstruction method for signal obtained from servo system in periodic reciprocating motion. Equivalent sampling combines the low rate and nonuniform samples from multiple periods into one single period, so that the equivalent sampling rate is far increased. Then, the nonuniform samples with high density are further resampled to meet the reconstruction conditions. This step can avoid the amplitude error in the reconstructed signal and increase the possibility of successful reconstruction. Finally, the reconstruction formula derived from basis theory is applied to recover the signal. This method has been successfully verified by the simulation signal of the robot swing process and the actual current signal collected on the robot arm testbed.

Loss of NFBD1/MDC1 disrupts homologous recombination repair and sensitizes nasopharyngeal carcinoma cells to PARP inhibitors.

BACKGROUND: Nasopharyngeal carcinoma (NPC), a highly invasive tumor, exhibits a distinctive racial and geographic distribution. As options of agents for effective combination chemoradiotherapy for advanced NPC are limited, novel therapeutic approaches are desperately needed. Here the potential of silencing NFBD1 in combination with PARP inhibition as a novel therapeutic strategy for NPC was investigated. METHODS: To investigate the function of NFBD1, we created NFBD1-depleted NPC cell lines via lentivirus mediated shRNA, and the colony formation, MTS assay, comet assay and apoptosis analysis were used to evaluate the sensitivity of NFBD1 knockdown on PARP inhibition. The signaling change was assessed by western blot, Immunofluorescence and flow cytometry. Furthermore, Xenografts model was used to evaluate the role of silencing NFBD1 in combination with PARP inhibition. RESULTS: We find that silencing NFBD1 in combination with PARP inhibition significantly inhibits the cell proliferation and cell cycle checkpoint activity, and increases the apoptosis and DNA damage. Mechanistic studies reveal that NFBD1 loss blocks olaparib-induced homologous recombination repair by decreasing the formation of BRCA1, BRCA2 and RAD51 foci. Furthermore, the xenograft tumor model demonstrated significantly increases sensitivity towards PARP inhibition under NFBD1 deficiency. CONCLUSIONS: We show that NFBD1 depletion may possess sensitizing effects of PARP inhibitor, and consequently offers novel therapeutic options for a significant subset of patients.

RPA1 downregulation enhances nasopharyngeal cancer radiosensitivity via blocking RAD51 to the DNA damage site.

BACKGROUND/AIM: Nasopharyngeal cancer (NPC) has a high local recurrence rate due to its resistance to ionizing radiation (IR). Replication protein A1 (RPA1) is one of the main elements in the homologous repair (HR) pathway, which is closely associated with the repair of DNA double strand breaks (DDBs). Studies on the relationship between RPA1 and the radiosensitivity of NPC are substantially limited. It was hypothesized that RPA1 plays a crucial role in predicting the radiosensitivity of NPC. METHODS: The protein expression of RPA1 in 182 patients with NPC in the complete response (CR) and non-complete response (nCR) groups was evaluated using immunohistochemistry. Then, univariate and multivariate analysis were performed using SPSS software vision 22 to determine the relationship between the expression of RPA1 and the clinicopathological features. In addition, the mRNA expression of RPA1 was tested in 24 fresh samples using qRT-PCR. RPA1 was silenced in CNE-2R cell lines combined with IR to measure the radiosensitivity, proliferation, DNA damage repair and cell cycle of CNE-2R cells. Xenograft models in nude mice were used to determine the effect of RPA1 on tumor growth after IR. Immunoblotting and immunofluorescence staining were performed to identify proteins that interacted with RPA1. All statistical tests were two-sided. RESULTS: RPA1 protein was overexpressed in NPC patients with nCR (65.31%), and was an independent predictor of radiosensitivity (HR: 3.755, 95% CI: 1.990-7.085), in addition to Epstein-Barr virus (EBV; HR: 3.984; 95% CI: 1.524-10.410). The silencing of RPA1 increased the radiosensitivity of CNE-2R cells, blocked the repair of DNA, impaired cell proliferation, and contributed to G2/M cell cycle arrest. Furthermore, the xenograft models in nude mice revealed that silencing RPA1 combined with irradiation significantly retarded the growth of tumors. Moreover, the knockdown of RPA1 decreased Rad51 collection to the damage site and prolonged the time of DNA repair. CONCLUSION: RPA1 protein is frequently overexpressed in NPC patients with nCR. The silencing of RPA1 enhanced the radiosensitivity of CNE-2R cells. These present findings reveal that RPA1 is a potential biomarker for predicting the radiosensitivity in NPC.

Knockdown of NFBD1/MDC1 enhances chemosensitivity to cisplatin or 5-fluorouracil in nasopharyngeal carcinoma CNE1 cells.

Nasopharyngeal carcinoma (NPC) is a rare but highly invasive cancer that is prevalent among people of southern Chinese ancestry in southern China and Southeast Asia. Radiotherapy and cisplatin (CDDP)-based chemotherapy are the main treatment options. Unfortunately, disease response to concurrent chemoradiotherapy varies among patients with NPC, and many cases are resistant to CDDP and radiotherapy. NFBD1 functions in cell cycle checkpoint activation and DNA repair following DNA damage. In this study, we identified the NFBD1 as a tractable molecular target to chemosensitize NPC cells. NFBD1 expression in NPC CNE1 cell lines was depleted using lentivirus-mediated short hairpin RNA, and the elevated sensitivity of these NFBD1-inhibited NPC cells to therapeutic reagent CDDP and 5-fluorouracil (5-FU) was evaluated using MTS assays. Flow cytometry analysis also showed that NFBD1 knockdown led to an obvious induction of apoptosis in CDDP- or 5-FU-treated CNE1 cells. Furthermore, we implicated the involvement of NFBD1 in Rad51 and DNA-PKcs foci formation following CDDP or 5-FU chemotherapy. In conclusion, NFBD1 knockdown improves the chemosensitivity of NPC cells by inhibiting cell growth and promoting apoptosis through the impairment of DNA damage repair, suggesting NFBD1 as a novel therapeutic target for NPC.