Search

Objective To explore the application value of transnasal endoscopy combined with endovascular treatment in the operation of skull base tumors. Methods A retrospective analysis was conducted on the clinical data of 9 patients who underwent endoscopic transnasal resection of skull base tumors and received endovascular treatment at Tianjin Huanhu Hospital from January 2017 to July 2022. To observe the tumor resection and evaluate the postoperative efficacy of nasopharyngeal carcinoma according to the World Health Organization (WHO) solid tumor measurement standards. During the follow- up period, Glasgow Outcome Scale (GOS) was used to assess postoperative neurological function recovery, and record tumor recurrence or progression. Complications related to endovascular treatment, such as pseudoaneurysm, spontaneous cerebral hemorrhage and cerebral infarction, were also recorded. Results Among 9 patients, there were 4 patients confirmed donor artery or internal carotid artery (ICA) rupture by DSA before operation, one case underwent spring coil embolization before operation, one case had a carotid catheter sheath inserted in advance during operation, one case had successful hemostasis with spring coil embolization during operation, one case had successful hemostasis with covered stent implantation during operation, 4 cases had ICA rupture confirmed by DSA during operation, and one case had successful hemostasis with spring coil embolization after DSA confirmation of ICA rupture. The total resection rate was 8/9. During a follow - up of 32.00 (25.00, 48.50) months, all patients did not experience tumor recurrence or progression. At the last follow -up, the GOS scores were 4-5, indicating good recovery of neurological function. A patient with recurrent nasopharyngeal carcinoma who underwent immunotherapy had a recurrent pseudoaneurysm at the distal end of the ICA covered with a stent implanted in the petrous segment. Three months after the stent implantation, the patient underwent external carotid artery - radial artery - middle cerebral artery bypass surgery to successfully stop the bleeding without any postoperative complications. The remaining 8 patients did not experience complications such as spontaneous cerebral hemorrhage or pseudoaneurysm. All patients did not experience complications such as cerebral infarction. Conclusions Evdovascular treatment is helpful in evaluating the relationship between skull base tumors and surrounding blood vessels before endoscopic transnasal resection of skull base tumors. It can effectively block the donor artery, reduce the probability of intraoperative bleeding, effectively treat the rupture of large blood vessels, and reduce the occurrence of serious complications. The efficacy and safety are both high. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) has a unique geographic distribution. It is unknown whether meteorological factors are related to the incidence of NPC. To investigate the effect of ambient temperature, relative humidity (RH), and absolute humidity (AH) on the incidence of NPC, we collected the incidence rate of NPC in 2016 and meteorological data from 2006 to 2016 from 484 cities and counties across 31 provinces in China. Generalized additive models with quasi‐Poisson regression and generalized linear models with natural cubic splines were employed respectively to elucidate the nonlinear relationships and specify the partial linear relationships. Subgroup and interactive analysis were also conducted. Temperature (R2 = 0.68, p <.001), RH (R2 = 0.47, p <.001), and AH (R2 = 0.70, p <.001) exhibited nonlinear correlations with NPC incidence rate. The risk of NPC incidence increased by 20.3% (95% confidence intervals [CI]: [18.9%, 21.7%]) per 1°C increase in temperature, by 6.3% (95% CI: [5.3%, 7.2%]) per 1% increase in RH, and by 32.2% (95% CI: [30.7%, 33.7%]) per 1 g/m3 increase in AH, between their the 25th and the 99th percentiles. In addition, the combination of low temperature and low RH was also related to increased risk (relative risk: 1.60, 95% CI: [1.18, 2.17]). Males and eastern or rural populations tended to be more vulnerable. In summary, this study suggests that ambient temperature, RH, and particularly AH are associated with the risk of NPC incidence. [ABSTRACT FROM AUTHOR]

Background Epstein–Barr virus (EBV) is a major cause of nasopharyngeal carcinoma (NPC) and measurement of different EBV antibodies in blood may improve early detection of NPC. Prospective studies can help assess the roles of different EBV antibodies in predicting NPC risk over time. Methods A case-cohort study within the prospective China Kadoorie Biobank of 512 715 adults from 10 (including two NPC endemic) areas included 295 incident NPC cases and 745 subcohort participants. A multiplex serology assay was used to quantify IgA and IgG antibodies against 16 EBV antigens in stored baseline plasma samples. Cox regression was used to estimate adjusted hazard ratios (HRs) for NPC and C-statistics to assess the discriminatory ability of EBV-markers, including two previously identified EBV-marker combinations, for predicting NPC. Results Sero-positivity for 15 out of 16 EBV-markers was significantly associated with higher NPC risk. Both IgA and IgG antibodies against the same three EBV-markers showed the most extreme HRs, i.e. BGLF2 (IgA: 124.2 (95% CI: 63.3–243.9); IgG: 8.6 (5.5–13.5); LF2: [67.8 (30.0–153.1), 10.9 (7.2–16.4)]); and BFRF1: 26.1 (10.1–67.5), 6.1 (2.7–13.6). Use of a two-marker (i.e. LF2/BGLF2 IgG) and a four-marker (i.e. LF2/BGLF2 IgG and LF2/EA-D IgA) combinations yielded C-statistics of 0.85 and 0.84, respectively, which persisted for at least 5 years after sample collection in both endemic and non-endemic areas. Conclusions In Chinese adults, plasma EBV markers strongly predict NPC occurrence many years before clinical diagnosis. LF2 and BGLF2 IgG could identify NPC high-risk individuals to improve NPC early detection in community and clinical settings. [ABSTRACT FROM AUTHOR]

Background Few studies have assessed the comprehensive associations among comorbid diseases in elderly patients with nasopharyngeal carcinoma (NPC). This study sought to identify potential comorbidity patterns and explore the relationship of comorbidity patterns with the mortality risk in elderly patients with NPC. Methods A total of 452 elderly patients with NPC were enrolled in the study. The network analysis and latent class analysis were applied to mine comorbidity patterns. Propensity score matching was used for adjusting confounders. A restricted cubic spline model was used to analyze the nonlinear association between age and the risk of all-cause mortality. Results We identified 2 comorbidity patterns, metabolic disease-related comorbidity (MDRC) and organ disease-related comorbidity (ODRC) in elderly patients with NPC. Patients in MDRC showed a significantly higher risk of all-cause mortality (71.41% vs 87.97%, HR 1.819 [95% CI, 1.106-2.994], P  = .031) and locoregional relapse (68.73% vs 80.88%, HR 1.689 [95% CI, 1.055-2.704], P  = .042). Moreover, in patients with MDRC pattern, we observed an intriguing inverted S-shaped relationship between age and all-cause mortality among patients aged 68 years and older. The risk of mortality up perpetually with age increasing in ODRC group, specifically within the age range of 68-77 years (HR 4.371, 1.958-9.757). Conclusion Our study shed light on the potential comorbidity patterns in elderly patients with NPC, thereby providing valuable insights into the development of comprehensive health management strategies for this specific population. [ABSTRACT FROM AUTHOR]

Objective: Recent studies have indicated that HOTTIP and MEG3 are associated with the initiation and progression of various types of tumors, including nasopharyngeal carcinoma (NPC). This investigation aimed to elucidate the impact of HOTTIP and MEG3 polymorphisms on the susceptibility and clinicopathologic characteristics of NPC. Methods: This research employed next-generation sequencing and multiplex PCR to assess the polymorphisms of HOTTIP rs1859168 and MEG3 rs7158663 in 200 NPC and 200 healthy individuals respectively. HOTTIP and MEG3 expression were assessed via qRT-PCR assessment. Furthermore, the genotypes and alleles frequency of rs1859168 and rs7158663 were compared between healthy and NPC individuals to elucidate their influence on NPC susceptibility and relation with clinicopathologic characteristics. Results: In comparison with the healthy cohort, the presence of HOTTIP rs1859168 CC genotype and the C allele were markedly linked with increased NPC incidence (p < 0.05). Furthermore, the MEG3 rs7158663 AA genotype and the A allele also indicated an increased risk of NPC (p < 0.05). The subgroup analysis of age, EBV infection, gender, nationality, smoking, and drinking status revealed no marked association between rs1859168 and rs7158663 genotypes and these potential confounding factors. Moreover, it was observed that rs1859168 CC and rs7158663 AA genotypes were related to local tumor invasion and lymph node metastasis. Additionally, HOTTIP indicated a marked elevation, while MEG3 substantially reduced in NPC samples than the normal nasopharyngeal biospecimens. Patients who carried CC or CA genotypes rather than the HOTTIP rs1859168 AA genotype, had substantially higher HOTTIP levels, while patients with rs7158663 AA or GA genotypes indicated notably lower expression of MEG3 than GG genotype carriers. Conclusion: Individuals with genetic variants of HOTTIP rs1859168 and MEG3 rs7158663 might have an increased risk of NPC susceptibility and related clinicopathologic characteristics, potentially by affecting the expression of HOTTIP and MEG3. [ABSTRACT FROM AUTHOR]

Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18–65 years with newly diagnosed high-risk non-metastatic stage III–IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3–4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0–44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81–90] vs 76% [70–81]; stratified hazard ratio 0·59 [0·38–0·92]; p=0·019). Grade 3–4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3–4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. For the Chinese translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a highly prevalent head and neck malignancy in southern China frequently diagnosed at advanced stages owing to subtle early symptoms and associated metastasis. Angiogenesis emerges as a pivotal factor in NPC progression, with numerous angiogenesis-related factors showing aberrant expression and contributing to increased neovascularization within NPC tumors. These abnormal vessels not only nourish tumor growth but also facilitate metastasis, culminating in unfavorable patient outcomes. Multiple studies have demonstrated the applicability of various imaging techniques for assessing angiogenesis in NPC tumors, thus serving as a foundation for personalized treatment strategies and prognostic assessments. Anti-angiogenic therapies have exhibited significant potential for inhibiting NPC angiogenesis and exerting anti-tumor effects. To enhance efficacy, anti-angiogenic drugs are frequently combined with other treatment modalities to synergistically enhance anti-tumor effects while mitigating the side effects associated with single-agent therapies, consequently improving patient prognosis. Identifying the potential mechanisms and key targets underlying NPC angiogenesis and exploring more effective detection and treatment approaches holds promise for shaping the future of NPC diagnosis, treatment, and prognosis, thereby offering new avenues and perspectives for research and clinical practice. [ABSTRACT FROM AUTHOR]

Genetic variants in Epstein-Barr virus (EBV) have been strongly associated with nasopharyngeal carcinoma (NPC) in South China. However, different results regarding the most significant viral variants, with polymorphisms in EBER2 and BALF2 loci, have been reported in separate studies. In this study, we newly sequenced 100 EBV genomes derived from 61 NPC cases and 39 population controls. Comprehensive genomic analyses of EBV sequences from both NPC patients and healthy carriers in South China were conducted, totaling 279 cases and 227 controls. Meta-analysis of genome-wide association study revealed a 4-bp deletion downstream of EBER2 (coordinates, 7188–7191; EBER-del) as the most significant variant associated with NPC. Furthermore, multiple viral variants were found to be genetically linked to EBER-del forming a risk haplotype, suggesting that multiple viral variants might be associated with NPC pathogenesis. Population structure and phylogenetic analyses further characterized a high risk EBV lineage for NPC revealing a panel of 38 single nucleotide polymorphisms (SNPs), including those in the EBER2 and BALF2 loci. With linkage disequilibrium clumping and feature selection algorithm, the 38 SNPs could be narrowed down to 9 SNPs which can be used to accurately detect the high risk EBV lineage. In summary, our study provides novel insight into the role of EBV genetic variation in NPC pathogenesis by defining a risk haplotype of EBV for downstream functional studies and identifying a single high risk EBV lineage characterized by 9 SNPs for potential application in population screening of NPC. Author summary: Two genome-wide association studies (GWAS) of Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC) in South China have revealed different risk loci in EBER region and BALF2 gene of EBV, respectively. More EBV genomes isolated from healthy donors and NPC biopsies are included in this study. The meta-analysis of EBV genomes derived from 279 NPC cases and 227 healthy controls identifies a risk haplotype of EBV comprising of multiple genetic variants having strong linkage disequilibrium with each other. Furthermore, a high risk lineage of EBV characterized by 9 single nucleotide polymorphisms (SNPs) is found to be enriched in NPC of South China. The risk haplotype of EBV will be useful for downstream studies of disease mechanisms and the high risk EBV lineage may be included in screening protocol for early detection of NPC in the population. [ABSTRACT FROM AUTHOR]

Objective: Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma. Methods: An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study. Results: The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications. Conclusion: The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy. [ABSTRACT FROM AUTHOR]

Background: Compared with the conventional work‐up (CWU) including computed tomography (CT) of the chest and abdomen, MRI of the head and neck, and skeletal scintigraphy, positron emission tomography (PET)/MRI might improve diagnostic accuracy, shorten the work‐up time, and reduce false‐positive (FP) findings in patients with nasopharyngeal carcinoma (NPC). However, evidence of cost‐effectiveness is needed for the adoption of PET/MRI for the initial staging in NPC. Purpose: To evaluate the cost‐effectiveness and clinical value of PET/MRI as an initial staging procedure for NPC. Study Type: Retrospective cohort cost effectiveness study. Subjects: Three hundred forty‐three patients with a median age of 51 (13–81) years underwent PET/MRI before treatment (the PET/MRI group) and the remaining 677 patients with a median age of 55 (15–95) years only underwent CWU (the CWU group). There were 80 (23.3%) females and 193 (28.5%) females in the PET/MRI and CWU groups, respectively. Field Strength/Sequence: 3‐T integrated PET/MRI system, diffusion‐weighted echo‐planar imaging (b = 0 and 1000 s/mm2) and [18F] fluorodeoxyglucose PET. Assessment: The primary end point was the FP rate. Costs were determined as issued in 2021 by the Medical Insurance Administration Bureau of Zhejiang, China. Statistical Tests: Incremental cost effectiveness ratio (ICER) measured cost of using PET/MRI per percent of patients who avoided a FP. A P‐value <0.05 was considered statistically significant. Results: For the whole group, the de novo metastatic disease rate was 5.2% (53/1020). A total of 187 patients with FP results were observed. Significantly more patients with FP results were observed in the CWU group compared to the PET/MRI group (25.6% vs. 4.1%). The ICER was $54 for each percent of patients avoiding a FP finding. Data Conclusion: Compared with CWU, PET/MRI may reduce the FP risk. Furthermore, PET/MRI may be cost‐effective as an initial staging procedure for NPC. Evidence Level: 3 Technical Efficacy: Stage 6 [ABSTRACT FROM AUTHOR]

Air pollution is potentially leading to cancer mortality; however, there is little evidence for a link between nasopharyngeal carcinoma and air pollution. In particular, limited studies have examined the role of traffic and multiple chemical components on the prognosis of this carcinoma. Here, we hypothesized that fine particulate matter (PM2.5) and traffic-related compositions, i.e., black carbon and organic matter, and ozone (O3), might be associated with increased mortality. We collected individual-level data from a 10-year nasopharyngeal cohort in southern China. Time-varying Cox models were developed. Traffic proximity and road density were studied. Results show that The hazard ratios for each interquartile range elevation in O3, black carbon and organic matter were 1.14, 1.21, and 1.22, respectively, whereas hazards for PM2.5 were significant only at above 31.2 μ g / m 3 . Women and patients below 49 years were susceptible to PM2.5, while men and patients above 50 years were vulnerable to high levels of black carbon, organic matter, and O3. The mortality risks were 28–33% or 16–73% greater for those living near traffic or in high-road density areas. There were positive associations between multiple air pollutants and nasopharyngeal carcinoma mortality among various subgroups. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a malignant tumor originating in the nasopharyngeal epithelium with a high incidence in southern China and parts of Southeast Asia. The current treatment methods are mainly radiotherapy and chemotherapy. However, they often have side effects and are not suitable for long‐term exposure. Natural products have received more and more attention in cancer prevention and treatment because of their its high efficiency, low toxic side effects, and low toxicity. Natural products can serve as a viable alternative, and this study aimed to review the efficacy and mechanisms of natural products in the treatment of NPC by examining previous literature. Most natural products act by inhibiting cell proliferation, metastasis, inducing cell cycle arrest, and apoptosis. Although further research is needed to verify their effectiveness and safety, natural products can significantly improve the treatment of NPC. [ABSTRACT FROM AUTHOR]

Background: The combination of tislelizumab and gemcitabine plus cisplatin (GP) in the first‐line treatment of patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has yielded significant results. However, it is not clear whether this treatment option is cost‐effective in China. The purpose of this study is to evaluate the cost‐effectiveness of tislelizumab plus GP for the first‐line treatment of R/M NPC from the perspective of the Chinese healthcare system. Methods: A partitioned survival model with three discrete health states was constructed to evaluate the cost‐effectiveness of tislelizumab plus GP versus GP in patients with R/M NPC. The target population enrolled in the RATIONALE‐309 trial had previously not treated for R/M NPC. Drug costs were obtained from relevant databases, and the remaining cost and health utility data were collected from the literature. The main outcomes include the expected life years, quality‐adjusted life years (QALYs), total cost, and incremental cost–benefit ratio (ICER). Results: The tislelizumab plus GP regimen produced an additional cost ($18392.76) and additional 1.57 QALYs compared with GP used alone. The ICER was $18392.75/QALYs. Sensitivity analysis showed that the analysis was robust and the utility of PD status was most sensitive to the model results. The possibility of tislelizumab plus GP being cost‐effective at the willingness‐to‐pay (WTP) threshold of $37 653/QALY was 99.8%. Subgroup analysis showed that high PD‐L1 expression had little impact on the ICER of this regimen. Conclusion: In patients with R/M NPC, the regimen of tislelizumab plus GP, as the first‐line treatment, is more cost‐effective than the GP regimen in China. [ABSTRACT FROM AUTHOR]

Objective: Our research group in the early stage identified CD109 as the target of aptamer S3 in nasopharyngeal carcinoma (NPC). This study was to use S3 to connect DNA tetrahedron (DT) and load doxorubicin (Dox) onto DT to develop a targeted delivery system, and explore whether S3-DT-Dox can achieve targeted therapy for NPC. Methods: Aptamer S3-conjugated DT was synthesized and loaded with Dox. The effects of S3-DT-Dox on NPC cells were investigated with laser confocal microscopy, flow cytometry, and MTS assays. A nude mouse tumor model was established from NPC 5-8F cells, and the in vivo anti-tumor activity of S3-DT-Dox was examined by using fluorescent probe labeling and hematoxylin–eosin staining. Results: The synthesized S3-DT had high purity and stability. S3-DT specifically recognized 5-8F cells and NPC tissues in vitro. When the ratio of S3-DT to Dox was 1:20, S3-DT had the best Dox loading efficiency. The drug release rate reached the maximum (0.402 ± 0.029) at 48 h after S3-DT-Dox was prepared and mixed with PBS. S3-DT did not affect Dox toxicity to 5-8F cells, but reduced Dox toxicity to non-target cells. Meanwhile, S3-DT-Dox was able to specifically target the transplanted tumors and inhibit their growth in nude mice, with minor damage to normal tissues. Conclusion: Our study highlights the ability and safety of S3-DT-Dox to target NPC cells and inhibit the development NPC. [ABSTRACT FROM AUTHOR]

The nasopharyngeal epithelium, which is frequently found in Southeast Asia and Southern China, gives rise to nasopharyngeal carcinoma (NPC). Despite improvements in diagnostic tools and remedial modalities, the prognosis of NPC remains meager. Thus, innovative and effective anti-cancer agents are desirable. Voacangine (VCG) is a recognized alkaloid sequestered from the plant Voacanga foetida. Hence, the current research assessed the anti-proliferative and apoptotic action of VCG on HK-1 human NPC cells and its underlying molecular actions. The results exposed that VCG (20 and 25 µ/ml) avert the HK-1 cells proliferation, which stimulates apoptosis by the amelioration of Bcl-2-associated X protein (Bax) and caspases, while it lessens cyclin-D1, B-cell lymphoma 2 (Bcl-2), c-Myc, survivin in a dose-dependent way. Furthermore, VCG alleviates inflammation, cell proliferation, and augmented cell death through the attenuation of Nuclear factor kappa B (NF-κB) facilitated Phosphoinositide 3-kinase/Protein kinase B/Mammalian target of rapamycin (PI3K/AKT/mTOR) signaling. This creates a Bax/Bcl-2 proportion imbalance, which triggers caspases cascade, Cyt-c, and induces apoptosis. Our findings deliver novel perceptions into exploring VCG as a beneficial bioactive alkaloid for the handling of NPC. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC), predominant in Southern China and Southeast Asia, is a malignant tumor that arises from the epithelial lining of the nasopharynx. Current NPC treatments result in unfavorable side effects. Natural compounds with anti-proliferative capabilities are gaining popularity as a way to mitigate the toxicity of radiation and synthetic antitumor drugs. Ponicidin, an ent-kaurane diterpenoid, has been demonstrated to possess several pharmacological activities, including antitumor, antibacterial, immunoregulatory, antiviral, and anti-inflammatory properties. Materials and Methods: In the current investigation, the anti-carcinogenic activity of Ponicidin against nasopharyngeal cell line C666-1, has been investigated. The influence of Ponicidin on cell viability, apoptotic induction, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and apoptotic markers has been examined. Doxorubicin was selected as the positive control for the experiments. Results: The effect of Ponicidin on the viability of C666-1 cells revealed that its cytotoxic potential increased in a dose-dependent pattern and the optimum concentration chosen for further experiments was 7.5 µM. The Ponicidin-treated cells demonstrated a significant increase in the amount of TBARS, whereas it reduced the activity of superoxide dismutase (SOD) and glutathione (GSH) levels, indicating augmented oxidative stress and lower antioxidant activity in the C666-1 cells. The acridine orange/ethidium bromide (AO/EtBr) staining technique was used to assess morphological changes with respect to apoptosis, which confirmed its apoptotic nature. Furthermore, Ponicidin elevated the ROS generation, modified the mitochondrial membrane permeability, elevated the apoptotic marker levels (caspase-3, caspase-9, and Bax) and reduced the Bcl-2 expression in C666-1 cell lines. Conclusion: The findings suggest that Ponicidin successfully inhibited cancer cell proliferation by following the mitochondrial apoptotic pathway and thus could be effectively utilized as a potent anti-cancer agent for the treatment of nasopharyngeal cancer. [ABSTRACT FROM AUTHOR]

Background: Previous researches have demonstrated that adaptive replanning during intensity-modulated radiation therapy (IMRT) could enhance the prognosis of patients with nasopharyngeal carcinoma (NPC). However, the delineation of replanning target volumes remains unclear. This study aimed to evaluate the feasibility of reducing target volumes through adaptive replanning during IMRT by analyzing long-term survival outcomes and failure patterns of locoregional recurrence in NPC. Methods: This study enrolled consecutive NPC patients who received IMRT at our hospital between August 2011 and April 2018. Patients with initially diagnosed, histologically verified, non-metastatic nasopharyngeal cancer were eligible for participation in this study. The location and extent of locoregional recurrences were transferred to pretreatment planning computed tomography for dosimetry analysis. Results: Among 274 patients, 100 (36.5%) received IMRT without replanning and 174 (63.5%) received IMRT with replanning. Five-year rates of locoregional recurrence-free survival (LRFS) were 90.1% (95%CI, 84.8% to 95.4%) and 80.8% (95%CI, 72.0% to 89.6%) for patients with and without replanning, P = 0.045. There were 17 locoregional recurrences in 15 patients among patients with replanning, of which 1 (5.9%) was out-field and 16 (94.1%) were in-field. Among patients without replanning, 19 patients developed locoregional recurrences, of which 1 (5.3%) was out-field, 2 (10.5%) were marginal, and 16 (84.2%) were in-field. Conclusions: In-field failure inside the high dose area was the most common locoregional recurrent pattern for non-metastatic NPC. Adapting the target volumes and modifying the radiation dose prescribed to the area of tumor reduction during IMRT was feasible and would not cause additional recurrence in the shrunken area. [ABSTRACT FROM AUTHOR]

Introduction: The RATIONALE-309 trial confirmed the significant efficacy and safety of tislelizumab plus chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). However, the economic benefits of this regimen are unclear. Therefore, this study aimed to evaluate the cost-effectiveness of adding tislelizumab to chemotherapy for R/M NPC from the perspective of the Chinese healthcare system. Methods: A Markov model was established to simulate the costs and outcomes of tislelizumab plus chemotherapy versus chemotherapy. The survival data came from the RATIONALE-309 trial. Only direct medical costs were considered, and utility values were referred to the literature. The incremental cost-effectiveness ratio (ICER) was used as the main outcome measure. Sensitivity analysis was performed to assess the effect of parameter uncertainty on the model. Additionally, subgroup analyses were performed. Results: The basic analysis showed that the cost of tislelizumab plus chemotherapy ($33,693) was $17,711 higher than that of chemotherapy ($15,982), but it also gained 1.05 QALYs more (2.72 QALYs vs. 1.67 QALYs), with an ICER of $16,859/QALY, which was lower than the willing-to-pay (WTP) of $36,289/QALY. The factors that most influenced the model were the utility of PD, the cost of tislelizumab, and the risk of platelet count decreased in tislelizumab plus chemotherapy group. The subgroup analysis also demonstrated that tislelizumab plus chemotherapy was cost-effective in the whole population regardless of EBV DNA level and PD-L1 expression level. Conclusion: Compared with chemotherapy alone, tislelizumab plus chemotherapy was cost-effective for the treatment of R/M NPC in China. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with high propensity for lymphatic spread and distant metastasis. It is prominent as an endemic malignancy in Southern China and Southeast Asia regions. Studies on NPC pathogenesis mechanism in the past decades such as through Epstein Barr Virus (EBV) infection and oncogenic molecular aberrations have explored several potential targets for therapy and diagnosis. The EBV infection introduces oncoviral proteins that consequently hyperactivate many promitotic pathways and block cell-death inducers. EBV infection is so prevalent in NPC patients such that EBV serological tests were used to diagnose and screen NPC patients. On the other hand, as the downstream effectors of oncogenic mechanisms, the promitotic pathways can potentially be exploited therapeutically. With the apparent heterogeneity and distinct molecular aberrations of NPC tumor, the focus has turned into a more personalized treatment in NPC. Herein in this comprehensive review, we depict the current status of screening, diagnosis, treatment, and prevention in NPC. Subsequently, based on the limitations on those aspects, we look at their potential improvements in moving towards the path of precision medicine. The importance of recent advances on the key molecular aberration involved in pathogenesis of NPC for precision medicine progression has also been reported in the present review. Besides, the challenge and future outlook of NPC management will also be highlighted. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) patients usually presented malnutrition under chemoradiotherapy (CRT)/radiotherapy (RT). Few studies stratified by age to investigate the association of nutritional status with overall survival (OS) in NPC patients. This study aimed to explore the nutritional parameters related prognosis of NPC patients in different age. The total 1365 NPC patients were classified into young (18~45), middle-aged (46~60), and old groups (> 60). PG-SGA scores, NRS-2002 scores, Karnofsky performance status scores, anthropometric, and blood indicators (albumin, prealbumin, transferrin, C-reactive protein, hemoglobin, and total lymphocyte) were assessed. Cox regression analysis was performed to evaluate the association between risk factors of nutritional status and the overall survival in different age group of NPC patients. Kaplan-Meier (KM) survival analysis was used to estimate the effect of nutritional indexes on prognosis. The abnormal rate of albumin, prealbumin, hemoglobin, hand grip strength, and calf circumference increased with age. The malnutrition occurred in all age group and low calf circumference (HR, 4.427, 1.167–16.791) was an independent death risk in young adults. Distant metastasis (HR, 4.754, 2.737–8.260), low albumin (HR, 3.530, 1.708–7.296), hand grip strength (HR, 1.901, 1.160–3.115), and the nutritional intervention requirement (NRS-2002 ≥ 3) (HR, 2.802, 1.211–6.483) was significantly correlated with poor OS in NPC patients with middled age adults. Distant metastasis (HR, 2.546, 1.497–4.330), low albumin (HR, 1.824, 0.949–3.507), low hemoglobin (HR, 1.757, 1.015–3.044), low hand grip strength (HR, 1.771, 1.112–2.818), and low calf circumference (HR, 1.951, 1.074–3.545) were associated with increased risk of death in the elderly. KM analysis indicated that over 60 years, distant metastasis, low albumin, low hand grip strength, low calf circumference, and malnutritional risk (NRS-2002 ≥ 3) were correlated to prognosis of NPC patients. Low calf circumference could be a prognosis not only in elderly but also in young adults of NPC patients, whereas low albumin and distant metastasis were the prognostic factors in middle-aged and elderly patients. Patients aged over 60 years exhibited poorer OS compared with young and middle-aged adults. [ABSTRACT FROM AUTHOR]

Background: China has a high mortality from nasopharyngeal carcinoma (NPC). The NPC mortality trends in China from 2006 to 2020 were described and analyzed to understand its epidemiological characteristics by region and sex and to explore age, period, and cohort effects. Methods: This study utilized NPC mortality data from the China Health Statistical Yearbook. A joinpoint regression model was used to fit the standardized NPC mortality and age-specific mortality. The age-period-cohort model was applied to investigate age, period, and cohort effects on NPC mortality risk. Results: The results showed that the NPC mortality rate in China has been declining steadily. From 2006 to 2020, the standardized NPC mortality rate in most age groups showed a significant downward trend. The annual percentage change was smaller in rural areas than in urban areas. The mortality risks of rural males and rural females from 2016 to 2020 were 1.139 times and 1.080 times those from 2011 to 2015, respectively. Both urban males born in 1984–1988 and rural males born in 1979–1983 exhibited an increasing trend in NPC mortality risk. Conclusions: Our study confirmed the effectiveness of NPC prevention and treatment strategies in China from 2006 to 2020. However, it underscored the urgent need for targeted interventions in rural areas to further reduce NPC mortality rates. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is prevalent in Southern China. The expression profile and functions of kinesin family member 18B (KIF18B) remain unclear in NPC. Methods: Bulk and single-cell transcriptome data for NPC were downloaded. KIF18B expression differences in NPC and normal tissues and its prognostic value were validated by immunohistochemistry and Cox model. We performed multifaceted functional enrichment analysis on KIF18B. Immune infiltration was analyzed comprehensively by the CIBERSORT, EPIC, and quanTIseq algorithms and the BisqueRNA package and confirmed by immunofluorescence assay. The intercellular communication were investigated by the CellChat package. We explored the dynamics of KIF18B expression by pseudotime trajectory. M6A modification analysis rely on SRAMP platform. The treatment response were evaluated by Tumor Immune Dysfunction and Exclusion (TIDE) score, immunophenoscore and IC50 value. Results: KIF18B overexpression in NPC led to unfavorable prognosis, and significantly associated with advanced T, N, and stage classifications. Functional analysis demonstrated that KIF18B was involved in immune suppression, epithelial-mesenchymal transition (EMT), N6-methyladenosine (m6A) modification and therapeutic responses. The deconvolution algorithm indicated that activated regulatory T cells (Tregs) had the strongest positive correlation with KIF18B among immune cells (R = 0.631). Validated by immunofluorescence assay, the high KIF18B expression group displayed a notable rise in Tregs infiltration, accompanied by a substantial decrease in the infiltration of CD8+ T cells and macrophages. In the intercellular communication network, malignant cells with high KIF18B expression implicated in more interactions, and activated and recruited Tregs by modulating cytokines, chemokines, and immune checkpoints. KIF18B was upregulated in more advanced malignant cells and influenced EMT by regulating ITGA6, VIM, and ZEB1/2. KIF18B expression was positively related to m6A "writer" and "reader" genes, and negatively related to "eraser" genes. The KIF18B high expression group exhibited a higher TIDE score and elevated IC50 values for the commonly used chemotherapy drugs, gemcitabine, oxaliplatin, and 5-fluorouracil. Conclusion: KIF18B is a significant prognostic marker in NPC, and may modulate immune evasion and EMT. M6A modification may account for the aberrant overexpression of KIF18B in NPC. Furthermore, KIF18B may predict response to immunotherapy and chemotherapy. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma is a common and highly malignant cancer in southern China. It is important to accurately assess the illness perception of nasopharyngeal carcinoma according to the common-sense model of self-regulation. The purpose was to validate the Chinese version of the Revised Illness Perception Questionnaire for patients with Nasopharyngeal carcinoma. A cross-sectional survey of 631 patients with Nasopharyngeal carcinoma was conducted in Guangzhou, China. The reliability of the scale was evaluated using Cronbach's alpha. The factor structure was assessed using exploratory factor analysis (EFA) of each dimension. The EFA revealed that the 29-item self-rated scale has a seven-factor structure consistent with the original scale and explained 67.3% of the variance after extraction and rotation. The scale showed satisfactory reliability. The item–total correlations ranged from −0.16 to 0.64 (p < 0.05). The item–subscale correlations ranged from 0.46 to 0.91 (p < 0.05). The item–other subscale correlations ranged from −0.38 to 0.51 and from −0.21 to 0.56 (p < 0.05). Significant correlations were found between the timeline (acute/chronic) (r = 0.224, r = 0.166), consequences (r = 0.415, r = 0.338), timeline cyclical (r = 0.366, r = 0.284), emotional representations (r = 0.497, r = 0.465), personal control (r = −0.122, r = −0.134), treatment control (r = −0.135, r = −0.148), and illness coherence (r = −0.261, r = −0.213) subscales, and depression, anxiety (p < 0.05). The scale revealed acceptable reliability, factorial validity, and construct validity. It could be used to assess the illness representations of Chinese patients with nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a commonly diagnosed malignancy in southern China and southeast Asia. Previous studies have identified galactosamine-(N-acetyl)-6-sulfatase (GALNS) as a potential biomarker for multiple cancers. However, it is unknown whether GALNS plays a role in NPC development, and the underlying mechanisms remain unclear. In this study, we found that GALNS is overexpressed in NPC cell lines and tissues compared to the normal nasopharyngeal counterparts. Knocking down GALNS expression in the NPC cells significantly decreased their proliferation in vitro, and inhibited xenograft growth in a mouse model. Mechanistically, the anti-proliferative effect of GALNS silencing was the result of autophagy induction via the inhibition of PI3K–AKT–mTOR signaling pathway. Taken together, GALNS drives the progression of NPC via PI3K–AKT–mTOR signaling-mediated autophagy, and is therefore a promising therapeutic target. [ABSTRACT FROM AUTHOR]

Introduction and aims: Intensity-modulated radiotherapy (IMRT) is the most commonly used radiotherapy technology in oncology, which enables precise conformation of the radiation dose to the target volume and reduces the risk of radiation damage to the adjacent normal structures. Nevertheless, it is still inevitable for IMRT of head and neck cancer to cause radiation-related toxic and side effects, such as dry mouth, mucositis, oral dysarthria, taste disorder, osteonecrosis, and trismus. Trismus is one of the most common late side effects caused by radiotherapy of nasopharyngeal carcinoma (NPC), which seriously affects the quality of life for patients with NPC. However, the current clinical assessment and management of trismus after radiotherapy for NPC are still imperfect. This best practice implementation project aimed to implement an evidence-based practice in assessing and managing trismus for NPC patients who underwent radiotherapy, thereby improving the compliance of clinical practice with the best evidence and the quality of life of patients with NPC. Methods: This evidence-based audit and feedback project was implemented using a three-phase approach at a third-class hospital in China, following JBI's Practical Application of Clinical Evidence System (PACES) and GRiP evidence application. The first phase included a baseline audit with six evidence-based audit criteria derived from the best available evidence. The second phase included analyzing the results of the baseline audit, identifying barriers to compliance with best practice principles, and developing and implementing strategies to address the barriers identified in the baseline audit. The third phase involved a follow-up audit to assess the results of the interventions implemented to improve practice. Results: After evidence application, the compliance rate for audit criterion 1 increased from 0% at baseline audit to 70% at follow-up audit. The compliance rate for audit criterion 2 increased from 0% to 100%. The compliance rate for audit criterion 3 increased from 22 to 62%. The compliance rate for audit criterion 4 increased from 88 to 100%. The compliance rate for audit criterion 5 was 100% at baseline audit and follow-up audit. The compliance rate for audit criterion 6 increased from 0 to 55%. Conclusion: Implementation of the best evidence for the assessment and management of trismus of patients with NPC after radiotherapy is conducive to improving the compliance of clinical practice with the best evidence, standardizing clinical nursing practice, improving the quality of clinical nursing, and better preventing severe trismus in patients with NPC after radiotherapy. [ABSTRACT FROM AUTHOR]

BACKGROUND Population screening of asymptomatic persons with Epstein-Barr virus (EBV) DNA or antibodies has improved the diagnosis of nasopharyngeal carcinoma and survival among affected persons. However, the positive predictive value of current screening strategies is unsatisfactory even in areas where EBV is endemic. METHODS We designed a peptide library representing highly ranked B-cell epitopes of EBV coding sequences to identify novel serologic biornarkers for nasopharyngeal carcinoma. After a retrospective case-control study, the performance of the novel bio marker anti-BNLF2b total antibody (P85-Ab) was validated through a large-scale prospective screening program and compared with that of the standard two-anti-body-based screening method (EBV nuclear antigen 1 [EBNAl]-IgA and EBV-specific viral capsid antigen [VCA]-IgA), RESULTS P85-Ab was the most promising biomarker for nasopharyngeal carcinoma screening, with high sensitivity (94.4%; 95% confidence interval [CI], 86.4 to 9Z8) and specificity (99. 6°/0 ; 95% CI, 97. 8 to 99. 9). Among the 24, 852 eligible participants in the prospective cohort, 47 cases of nasopharyngeal carcinoma (38 at an early stage) were identified. P85-Ab showed higher sensitivity than the two-antibody method (97.9% vs. 72.3°6; ratio, 1.4 [95% CI, 1.1 to 1.6]), higher specificity (98.3% vs. 97.0°6; ratio, 1.01 [95% CI, 1.01 to 1.02]), and a higher positive predictive value (10.0% vs. 4.30/0; ratio, 2.3 [95% CI, 1.8 to 2.8]). The combination of P85-Ab and the two-antibody method markedly increased the positive predictive value to 44.6% (95% CI, 33.8 to 55.9), with sensitivity of 70.2% (95% CI, 56.0 to 81.4). CONCLUSIONS Our results suggest that P85-Ab is a promising novel biomarker for nasopharyngeal carcinoma screening, with higher sensitivity, specificity, and positive predictive value than the standard two-antibody method. (Funded by the National Key Research and Development Program of China and others; ClinicalTrials.gov number, NCT04085900.) [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal cancer (NPC) has a high incidence in Southern China and Asia, and its survival is extremely poor in advanced patients. MiRNAs play critical roles in regulating gene expression and serve as therapeutic targets in cancer. This study sought to disclose key miRNAs and target genes responsible for NPC prognosis and endocrine metabolism. Materials and methods: Three datasets (GSE32960, GSE70970, and GSE102349) of NPC samples came from Gene Expression Omnibus (GEO). Limma and WGCNA were applied to identify key prognostic miRNAs. There were 12 types of miRNA tools implemented to study potential target genes (mRNAs) of miRNAs. Univariate Cox regression and stepAIC were introduced to construct risk models. Pearson analysis was conducted to analyze the correlation between endocrine metabolism and RiskScore. Single-sample gene set enrichment analysis (ssGSEA), MCP-counter, and ESTIMATE were performed for immune analysis. The response to immunotherapy was predicted by TIDE and SubMap analyses. Results: Two key miRNAs (miR-142-3p and miR-93) were closely involved in NPC prognosis. The expression of the two miRNAs was dysregulated in NPC cell lines. A total of 125 potential target genes of the key miRNAs were screened, and they were enriched in autophagy and mitophagy pathways. Five target genes (E2F1, KCNJ8, SUCO, HECTD1, and KIF23) were identified to construct a prognostic model, which was used to divide patients into high group and low group. RiskScore was negatively correlated with most endocrine-related genes and pathways. The low-risk group manifested higher immune infiltration, anticancer response, more activated immune-related pathways, and higher response to immunotherapy than the high-risk group. Conclusions: This study revealed two key miRNAs that were highly contributable to NPC prognosis. We delineated the specific links between key miRNAs and prognostic mRNAs with miRNA–mRNA networks. The effectiveness of the fivegene model in predicting NPC prognosis as well as endocrine metabolism provided a guidance for personalized immunotherapy in NPC patients. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is endemic in Southern China and Southeast Asia. Hyperthermia is widely used in combination with chemotherapy and radiotherapy to enhance therapeutic efficacy in NPC treatment, but the underlying anti-tumor mechanisms of hyperthermia remain unclear. Complement C3 has been reported to participate in the activation of immune system in the tumor microenvironment, leading to tumor growth inhibition. In this study, we aimed to explore the effect and mechanisms of hyperthermia and investigate the functional role of complement C3 in NPC hyperthermia therapy (HT). The serum levels of complement C3 before and after hyperthermia therapy in patients with NPC were analyzed. NPC cell lines SUNE1 and HONE1 were used for in vitro experiment to evaluate the function of complement C3 and HT on cell proliferation and apoptosis. SUNE1 xenograft mouse model was established and tumor-bearing mice were treated in water bath at a constant temperature of 43°C. Tumor samples were collected at different time points to verify the expression of complement C3 by immunohistochemical staining and western blot. The differential expressed genes after hyperthermia were analyzed by using RNA sequencing. We found that complement could enhance hyperthermia effect on suppressing proliferation and promoting apoptosis of tumor cells in NPC. Hyperthermia decreased the mRNA expression of complement C3 in tumor cells, but promoted the aggregation and activation circulating C3 in NPC tumor tissue. By using in vitro hyperthermia-treated NPC cell lines and SUNE1 xenograft tumor-bearing mice, we found that the expression of heat shock protein 5 (HSPA5) was significantly upregulated. Knockdown of HSPA5 abrogated the anti-tumor effect of hyperthermia. Moreover, we demonstrated that hyperthermia downregulated CD55 expression via HSPA5/NFκB (P65) signaling and activated complement cascade. Our findings suggest that therapeutic hyperthermia regulates complement C3 activation and suppresses tumor development via HSPA5/NFκB/CD55 pathway in NPC. Complement was involved in the anti-tumor effect of hyperthermia in vitro. Hyperthermia markedly increased the expression of heat shock protein 5 (HSPA5) and decreased the expression of CD55 which regulated the activation of complement C3 and complement cascade. Activation of HSPA5/NFκB (P65) signaling pathway resulted in a decrease in CD55 expression. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a highly recurrent and metastatic malignant tumor affecting a large number of individuals in southern China. Traditional Chinese herbal medicine has been found to be a rich source of natural compounds with mild therapeutic effects and minimal side effects, making them increasingly popular for treating various diseases. Trifolirhizin, a natural flavonoid derived from leguminous plants, has gained significant attention for its therapeutic potential. In this study, we confirmed that trifolirhizin could effectively inhibit the proliferation, migration and invasion of nasopharyngeal carcinoma 6–10B and HK1 cells. Furthermore, our findings demonstrated that trifolirhizin achieves this by suppressing the PI3K/Akt signaling pathway. The findings of the present study provides a valuable perspective on the potential therapeutic applications of trifolirhizin for the treatment of nasopharyngeal carcinoma. • The flavonoid compound TFL inhibits cell proliferation, migration and invasion in nasopharyngeal carcinoma cells while exhibiting minimal toxicity to normal cells. • TFL exhibits anti-tumor effects in vivo, inhibiting the growth of nasopharyngeal tumors without significant adverse effects. • TFL exerts its anti-tumor effects by inhibiting the PI3K/Akt signaling pathway in nasopharyngeal carcinoma cells. [ABSTRACT FROM AUTHOR]

In endemic areas, EBV DNA is used to guide diagnosis, detect recurrence and distant metastasis of NPC. Until now, the importance of EBV DNA in the prediction of NPC has received little attention in non-endemic regions. To explore the prognostic value of EBV DNA alone or in combination with PNI in NPC patients from a non-endemic area of China. In this retrospective study, 493 NPC patients were enrolled. Clinical pathologic data, pre-treatment plasma EBV DNA, and laboratory tests were all performed. A standard anticancer treatment was prescribed, and follow up data were collected. EBV DNA was found to be positively related to clinical stage (r = 0.357, P < 0.001), T stage (r = 0.193, P < 0.001), N stage (r = 0.281, P < 0.001), and M stage (r = 0.215, P < 0.001). The difference in EBV DNA loads between clinical stage, T, N and M stage was statistically significant (P < 0.001). In this study, the best cutoff value for EBV-DNA to distinguish the prognosis of NPC was 262.7 copies/ml. The 5-year OS of patients in the EBV-DNA ≤ 262.7 copies/ml group and EBV-DNA > 262.7 copies/ml group was 88% and 65.3%, respectively (P < 0.001). EBV-DNA and PNI were found to be independent prognostic factors for OS in multivariate analysis (P < 0.05). EBV-DNA was independent prognostic factors for PFS. In predicting NPC patients OS, the novel combination marker of EBV DNA and PNI outperformed TNM staging (AUC: 0.709 vs. 0.675). In addition, the difference between EBV + PNI and EBV + TNM was not statistically significant for OS or PFS (P > 0.05). This novel combination biomarker was a promising biomarker for predicting NPC survival and may one day guide treatment option. [ABSTRACT FROM AUTHOR]

Purpose: To explore the safety and role of tegafur/gimeracil/oteracil (S1) maintenance therapy (MT) in metastatic nasopharyngeal carcinoma (NPC) patients after response to first-line chemotherapy and to assess outcome-associated biomarkers. Methods: This was a multicentre, open-label, randomized controlled study involving metastatic NPC patients recruited (from May 2015 to May 2019) at five hospitals in China. The participants were randomized to S1-MT (receiving S1 MT until disease progression or intolerance) or non-MT (followed up until disease progression) groups. The primary endpoint was the progression-free survival (PFS). The secondary endpoints were the overall survival (OS), the correlation between EBV-DNA, serum amyloid A (SAA) status, and outcomes after the first-line chemotherapy, and safety. Results: The median follow-up was 24.3 months; 88 and 95 participants were evaluable in the S1-MT and non-MT groups, respectively. Compared with non-MT, S1-MT prolonged PFS (16.9 vs. 9.3 months, P < 0.001) and OS (33.6 vs. 20.6 months, P < 0.001). Regardless of their EBV-DNA status after first-line chemotherapy, participants were able to benefit from S1 MT, but EBV-DNA-positive participants benefited more significantly (PFS: HR = 0.600, 95% CI = 0.373–0.965, P = 0.035; OS: HR = 0.393, 95% CI = 0.227–0.681, P = 0.001). MT only improved PFS and OS in patients with an SAA decline after first-line chemotherapy (PFS: HR = 0.570, 95% CI = 0.350–0.919, P = 0.021; OS: HR = 0.404, 95% CI = 0.230–0.709, P = 0.002). The median S1 treatment was 23 cycles. Grade 1–2 skin pigmentation, oral mucositis, and hand and foot syndrome were the main adverse reactions. Conclusion: For metastatic NPC patients with first-line chemotherapy response, S1 MT can improve PFS and OS, with good tolerability. EBV-DNA and SAA can better help us identify patients who can benefit from MT after standard treatment. Trial registration: The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR-IOR-16007939). [ABSTRACT FROM AUTHOR]

A concern of reverse causation exists about the association between nasopharyngeal carcinoma (NPC) prognosis and body mass index (BMI) at diagnosis, while the prognostic impact of BMI measured years before diagnosis is unknown. Therefore, we investigated associations of prediagnosis and pretreatment BMI and body shape on NPC mortality. From a population‐based patient cohort in southern China between 2010 and 2013, we included 2526 incident NPC cases with prospective follow‐up through 2018. We assessed the associations of BMI and body shape at age 20 years, 10 years before diagnosis, and at diagnosis with NPC mortality, combining strategies of stratification and statistical adjustment to minimize reverse causation. We observed 25% lower all‐cause mortality (hazard ratio [HR] 0.75, 95% confidence interval [CI]: 0.64‐0.89) and 25% lower NPC‐specific mortality (HR 0.75, 95% CI: 0.61‐0.91) among overweight vs normal‐weight NPC cases at diagnosis. Lean body shapes 1 and 2 at diagnosis were associated with 68% and 23% higher all‐cause mortality, respectively, compared to normal body shape 3. No effect modification by cancer stage was detected for associations with all‐cause or NPC‐specific mortality. Associations with BMI and body shape 10 years before diagnosis were similar but attenuated, while body size and shape at age 20 were not associated with mortality. Being overweight at diagnosis decreased mortality, and thinner body shape increased mortality, compared to normal weight/body shape. These associations may be due to poorer nutrition and treatment intolerance, resulting in treatment discontinuation and worse survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with high incidence in China. The molecular mechanisms of vasculogenic mimicry (VM) and angiogenesis are not fully elucidated in NPC. More specially, it has seldomly been reported that Epstein–Barr virus‐encoded miRNA can regulate VM and angiogenesis in NPC. The aim of this study was to investigate the function and molecular mechanism of a targeting exosome system (iRGD‐exo‐antagomiR) against VM and angiogenesis in NPC, and to provide new approaches for improving the comprehensive treatment of NPC. Methods: Exosomes were isolated by differential ultracentrifugation. Dynamic light scattering, transmission electron microscopy and western blotting were performed to characterize the exosomes. The 3D‐Culture assay, tube formation assay, chicken chorioallantoic membrane assay, Matrigel plug assay, mouse xenograft tumor modeling and immunohistochemical staining were applied to evaluate the anti‐VM and anti‐angiogenic effects of the targeting exosome system in vitro and in vivo. Western blot was performed to detect the changes of downstream regulated networks following interference and recovery of the target gene. Results: In vitro or in vivo treatment with iRGD‐tagged exosome containing antagomiR‐BART1‐5p specifically suppressed VM and angiogenesis in NPC. EBV‐miR‐BART1‐5p promoted VM and angiogenesis in vitro and in vivo by regulating VEGF, PI3K, Akt, mTOR and HIF1‐α in a Spry2‐dependent manner. Conclusions: Our findings demonstrated that targeting exosomes enveloped EBV‐miR‐BART1‐5p‐antagomiRs in a Spry2‐dependent manner for NPC therapy through both anti‐VM and anti‐angiogenesis in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Objective: To explore the impact of pyroptosis related gene GSDME on the prognosis of patients with nasopharyngeal carcinoma and its interaction with the immune microenvironment. Methods: Gene expression profile and clinical data of 548 patients with nasopharyngeal carcinoma were obtained from TCGA database. Differential expression analysis and GO-KEGG enrichment analysis of GSDME were conducted using R language. Immunohistochemical maps of GSDME protein in nasopharyngeal carcinoma tissues and corresponding para-carcinoma tissues were obtained from The Human Protein Atlas database. The interacting proteins of GSDME were explored by using STRING database. The correlation between GSDME expression and infiltration of 24 kinds of immune cells in nasopharyngeal carcinoma tissues was analyzed by ssGSEA algorithm, the correlation between GSDME expression and immune checkpoint molecules was analyzed by Spearman method, and the correlation between GSDME expression and cytokine expression was analyzed by using TISIDB database. Univariate and multivariate COX regression analyses were used to screen the risk factors for prognosis, based on which, the nomogram and calibration curve were drawn. Survival analysis and risk analysis were performed in nasopharyngeal carcinoma patients based on GSDME expression levels. The mRNA expression of GSDME and four chemokines in Chinese nasopharyngeal carcinoma tissues was verified by qPCR. Results: Analysis of database data showed that GSDME was highly expressed in nasopharyngeal carcinoma tissues compared with paraneoplastic tissues (P<0.01), GO-KEGG enrichment analysis showed that GSDME was involved in immune response, cell pyroptosis-related signaling pathways, and GSDME expression was correlated with immune cell infiltration, cytokine and immune checkpoint molecule expression. qPCR examination of Chinese nasopharyngeal carcinoma tissues verified the bioinformatics predictions; GSDME expression, N stage and M stage were risk factors for the prognosis of nasopharyngeal carcinoma patients, and the nomogram and calibration curve based on risk factors could better predict the OS of nasopharyngeal carcinoma patients, and patients with high GSDME expression in nasopharyngeal carcinoma tissues had poor prognosis. Conclusion: GSDME is highly expressed in nasopharyngeal carcinoma tissues and is associated with patient's poor prognosis. High GSDME expression is associated with the pro-cancer effect of the immune microenvironment in nasopharyngeal carcinoma, which may be a potential target for immunotherapy. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a common head and neck malignant with a high incidence in Southern China. Genetic aberrations play a vital role in the pathogenesis, progression and prognosis of NPC. In the present study, we elucidated the underlying mechanism of FAS-AS1 and its genetic variation rs6586163 in NPC. We demonstrated that FAS-AS1 rs6586163 variant genotype carriers were associated with lower risk of NPC (CC vs. AA, OR = 0.645, P = 0.006) and better overall survival (AC + CC vs. AA, HR = 0.667, P = 0.030). Mechanically, rs6586163 increased the transcriptional activity of FAS-AS1 and contributed to ectopic overexpression of FAS-AS1 in NPC. rs6586163 also exhibited an eQTL trait and the genes affected by rs6586163 were enriched in apoptosis related signaling pathway. FAS-AS1 was downregulated in NPC tissues and over-expression of FAS-AS1 was associated with early clinical stage and better short-term treatment efficacy for NPC patients. Overexpression of FAS-AS1 inhibited NPC cell viability and promoted cell apoptosis. GSEA analysis of RNA-seq data suggested FAS-AS1 participate in mitochondria regulation and mRNA alternative splicing. Transmission electron microscopic examination verified that the mitochondria was swelled, the mitochondrial cristae was fragmented or disappeared, and their structures were destroyed in FAS-AS1 overexpressed cells. Furthermore, we identified HSP90AA1, CS, BCL2L1, SOD2 and PPARGC1A as the top 5 hub genes of FAS-AS1 regulated genes involved in mitochondria function. We also proved FAS-AS1 could affect Fas splicing isoform sFas/mFas expression ratio, and apoptotic protein expression, thus leading to increased apoptosis. Our study provided the first evidence that FAS-AS1 and its genetic polymorphism rs6586163 triggered apoptosis in NPC, which might have a potential as new biomarkers for NPC susceptibility and prognosis. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is an interdisciplinary field that encompasses a wide range of computer science disciplines, including image recognition, machine learning, human−computer interaction, robotics and so on. Recently, AI, especially deep learning algorithms, has shown excellent performance in the field of image recognition, being able to automatically perform quantitative evaluation of complex medical image features to improve diagnostic accuracy and efficiency. AI has a wider and deeper application in the medical field of diagnosis, treatment and prognosis. Nasopharyngeal carcinoma (NPC) occurs frequently in southern China and Southeast Asian countries and is the most common head and neck cancer in the region. Detecting and treating NPC early is crucial for a good prognosis. This paper describes the basic concepts of AI, including traditional machine learning and deep learning algorithms, and their clinical applications of detecting and assessing NPC lesions, facilitating treatment and predicting prognosis. The main limitations of current AI technologies are briefly described, including interpretability issues, privacy and security and the need for large amounts of annotated data. Finally, we discuss the remaining challenges and the promising future of using AI to diagnose and treat NPC. [ABSTRACT FROM AUTHOR]

Background: Most nasopharyngeal carcinoma (NPC) protocols define primary gross tumor volume (GTVnx) plus a range from 2 to 5 mm as the high‐dose clinical target volume (hd‐CTV). However, in China, hd‐CTV is defined as GTVnx plus 0 mm. Methods: A total of 40 patients with newly diagnosed nonmetastatic NPC (T1–T4 ten cases each) treated with IMRT were consecutively enrolled. Real and virtual treatment plans were designed according to the definitions of hd‐CTV recommended by China and Radiation Therapy Oncology Group (RTOG), respectively. Results: The hd‐CTV in China was significantly smaller than that of RTOG. Exposure doses to 5 mm subclinical involvement and OARs as well as NTCP in the China treatment plan were significantly lower than those of RTOG. Conclusion: It could be recommended to divide the hd‐CTV into GTV and subclinical target volume and to prescribe different doses for the GTV and subclinical involvement in the IMRT plan of NPC. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia and Southern China. Laminin subunit beta-3 (LAMB3) has been validated to participate in diverse cancers. Nevertheless, the role and mechanism of LAMB3 in NPC remain unclear. In this study, LAMB3 expression is upregulated in NPC cells and tissues. Interestingly, knockdown of LAMB3 promoted apoptosis and reduced the radioresistance of NPC cells. Besides, shLAMB3 enhanced X-ray-induced reactive oxygen species (ROS) accumulation. Mechanically, knockdown of LAMB3 deactivated nuclear factor erythroid-2-related factor 2 (NRF2) signaling pathway via enhancing forkhead box 3 (FOXO3) expression. In rescue experiments, suppression of NRF2 signaling pathway abrogated shLAMB3-induced NPC cell apoptosis and ROS accumulation under X-ray treatment. Similarly, LAMB3 knockdown restrains NPC tumor growth and reduces radioresistance in vivo. Thus, these findings concluded that knockdown of LAMB3 enhanced apoptosis and ROS accumulation, and suppressed radioresistance in NPC via enhancing FOXO3 expression and deactivating NRF2 signaling pathway, facilitating the development of novel strategies for NPC radioresistance. [ABSTRACT FROM AUTHOR]

Background: To establish a novel model using radiomics analysis of pre-treatment and post-treatment magnetic resonance (MR) images for prediction of progression-free survival in the patients with stage II–IVA nasopharyngeal carcinoma (NPC) in South China. Methods: One hundred and twenty NPC patients who underwent chemoradiotherapy were enrolled (80 in the training cohort and 40 in the validation cohort). Acquiring data and screening features were performed successively. Totally 1133 radiomics features were extracted from the T2-weight images before and after treatment. Least absolute shrinkage and selection operator regression, recursive feature elimination algorithm, random forest, and minimum-redundancy maximum-relevancy (mRMR) method were used for feature selection. Nomogram discrimination and calibration were evaluated. Harrell's concordance index (C-index) and receiver operating characteristic (ROC) analyses were applied to appraise the prognostic performance of nomograms. Survival curves were plotted using Kaplan–Meier method. Results: Integrating independent clinical predictors with pre-treatment and post-treatment radiomics signatures which were calculated in conformity with radiomics features, we established a clinical-and-radiomics nomogram by multivariable Cox regression. Nomogram consisting of 14 pre-treatment and 7 post-treatment selected features has been proved to yield a reliable predictive performance in both training and validation groups. The C-index of clinical-and-radiomics nomogram was 0.953 (all P < 0.05), which was higher than that of clinical (0.861) or radiomics nomograms alone (based on pre-treatment statistics: 0.942; based on post-treatment statistics: 0.944). Moreover, we received Rad-score of pre-treatment named RS1 and post-treatment named RS2 and all were used as independent predictors to divide patients into high-risk and low-risk groups. Kaplan–Meier analysis showed that lower RS1 (less than cutoff value, − 1.488) and RS2 (less than cutoff value, − 0.180) were easier to avoid disease progression (all P < 0.01). It showed clinical benefit with decision curve analysis. Conclusions: MR-based radiomics measured the burden on primary tumor before treatment and the tumor regression after chemoradiotherapy, and was used to build a model to predict progression-free survival (PFS) in the stage II–IVA NPC patients. It can also help to distinguish high-risk patients from low-risk patients, thus guiding personalized treatment decisions effectively. [ABSTRACT FROM AUTHOR]

Background: A high prevalence of nasopharyngeal carcinoma (NPC) has been found in China, but it rarely occurs with syncope. Studies have demonstrated that syncope due to NPC may be related to carotid sinus syndrome, glossopharyngeal irritation, and parapharyngeal and retropharyngeal space lesions. Such patients require evaluation by nasopharyngoscopy and head magnetic resonance imaging/computed tomography. There is no known single effective treatment for these patients. Various interventions may be considered in an effort to relieve syncope, including vasoconstrictive drugs, cardiac pacemaker implantation, radiotherapy and chemotherapy, and surgical resection. Case presentation: This case report describes a 56-year-old man who developed recurrent syncope with atrial fibrillation, a long RR interval, and hypotension. A single chamber pacemaker was fitted, but it failed to relieve the symptom. Cranial magnetic resonance imaging and pathological tests led to a final diagnosis of NPC. After six courses of chemotherapy and 35 sessions of radiotherapy, the patient became asymptomatic. However, he died from a massive uncontrolled hemorrhage in the nasopharynx two years later. Conclusions: This case brings attention to the fact that syncope can be a symptom of NPC. Due to the insidiously malignant nature of this cancer, when a patient presents with syncope, clinicians should bear in mind this connection, albeit a rare one. There are at least two ways of treating NPC-associated syncope, but there is disagreement about which is the most effective. [ABSTRACT FROM AUTHOR]

Epstein‐Barr virus (EBV)‐encoded BamHI A rightward transcript (BART) microRNAs (miRNAs) play important roles in viral infection and tumorigenesis. The association of sequence variations in the BART miRNA cluster 1 region with diseases remains unclear. Herein, 6 types and 11 subtypes of BART cluster 1 were identified in 354 tumors and healthy donors (HDs) from nasopharyngeal carcinoma (NPC)‐endemic and nonendemic China (genotyped data), and 905 EBV genomes retrieved from GenBank from diseased and normal people from around the world (archived data). The distributions of BART cluster 1 types/subtypes between NPC‐endemic and nonendemic China; between Asian regions and Africa/Europe & Australia & United States; and among Asian regions (NPC‐endemic China, NPC‐nonendemic East Asia and Southeast Asia) were significantly different (p < 0.001). The subtype BART‐D2 was not found outside Asia and was only common in NPC‐endemic China. More importantly, BART‐D2 had a higher frequency in NPCs than in HDs in NPC‐endemic China (genotyped data, 78.0% vs. 44.1%, p < 0.001; achieved data, 89.3% vs. 43.7%, p < 0.001), and was also more frequent in NPCs than in HDs, gastric carcinomas, and lymphomas in NPC‐nonendemic China (genotyped data, 27.9% vs. 1.9%, 2.4%, and 0.0%, p < 0.001). BART‐D2 was preferentially linked with the high‐risk subtypes for NPC previously reported, 162476C or 163364T, in the BALF2 gene, and was associated with NPC risk (p < 0.01). In vitro experiments showed that BART‐D2 affected the expression of some mature BART miRNAs. These findings demonstrate geographically restricted variations of BART cluster 1 and identify distinct subtype that is confined to NPC‐endemic China and is associated with NPC. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC), especially the nonkeratinizing type, is a malignant tumor primarily occurring in southern China and Southeast Asia. Chemotherapy (CT) and combined radiotherapy (RT) is used to treat NPC. However, the mortality rate is high in recurrent and metastatic NPC. We developed a molecular marker, analyzed its correlation with clinical characteristics, and assessed the prognostic value among NPC patients with or without chemoradiotherapy. Methods: A total of 157 NPC patients were included in this study, with 120 undergoing treatment and 37 without treatment. EBER1/2 expression was investigated using in situ hybridization (ISH). Expression of PABPC1, Ki-67, and p53 was detected with immunohistochemistry. The correlations of EBER1/2 and the expression of the three proteins having clinical features and prognosis were evaluated. Results: The expression of PABPC1 was associated with age, recurrence, and treatment but not with gender, TNM classification, or the expression of Ki-67, p53, or EBER. High expression of PABPC1 was associated with poor overall survival (OS) and disease-free survival (DFS) and was an independent predictor depending on multivariate analysis. Comparatively, no significant correlation was observed between the expression of p53, Ki-67, and EBER and survival. In this study, 120 patients received treatments and revealed significantly better OS and DFS than the untreated 37 patients. PABPC1 high expression was an independent predictor of shorter OS in the treated (HR = 4.012 (1.238–13.522), 95% CI, p = 0.021) and the untreated groups (HR = 5.473 (1.051–28.508), 95% CI, p = 0.044). However, it was not an independent predictor of shorter DFS in either the treated or the untreated groups. No significant survival difference was observed between patients with docetaxel-based induction chemotherapy (IC) + concurrent chemoradiotherapy (CCRT) and those with paclitaxel-based IC + CCRT. However, when combined with treatment and PABPC1 expression, patients with paclitaxel-added chemoradiotherapy plus PABPC1 low expression had significantly better OS than those who underwent chemoradiotherapy (p = 0.036). Conclusions: High expression of PABPC1 is associated with poorer OS and DFS among NPC patients. Patients with PABPC1 having low expression revealed good survival irrespective of the treatment received, indicating that PABPC1 could be a potential biomarker for triaging NPC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Nasopharyngeal carcinoma (NPC) is extremely frequent in several regions of the world, particularly Southern China (known as the Cantonese cancer). Previous studies were often limited to small cohorts, and systematic comparison with other cancer types has not been explored. In this study, we collected the largest NPC cohort (n = 431) and provided the first integrative analysis of NPC genomes. We identified many novel drivers and mutational signatures in NPC. By comparing NPC with other cancer types, we discovered many unique processes driving a viral-positive cancer type. As one of few viral-positive cancers, nasopharyngeal carcinoma (NPC) is extremely rare across the world but very frequent in several regions of the world, including Southern China (known as the Cantonese cancer). Even though several genomic studies have been conducted for NPC, their sample sizes are relatively small and systematic comparison with other cancer types has not been explored. In this study, we collected four-hundred-thirty-one samples from six previous studies and provided the first integrative analysis of NPC genomes. Combining several statistical methods for detecting driver genes, we identified 25 novel drivers for NPC, including ATG14 and NLRC5. Many of these novel drivers are enriched in several important pathways, such as autophagy and immunity. By comparing NPC with many other cancer types, we found NPC is a unique cancer type in which a high proportion of patients (45.2%) do not have any known driver mutations (termed as "missing driver events") but have a preponderance of deletion events, including chromosome 3p deletion. Through signature analysis, we identified many known and novel signatures, including single-base signatures (n = 12), double-base signatures (n = 1), indel signatures (n = 9) and copy number signatures (n = 8). Many of these new signatures are involved in DNA repair and have unknown etiology and genome instability, implying an unprecedented dynamic mutational process possibly driven by complex interactions between viral and host genomes. By combining clinical, molecular and intra-tumor heterogeneity features, we constructed the first integrative survival model for NPC, providing a strong basis for patient prognosis and stratification. Taken together, we have performed one of the first integrative analyses of NPC genomes and brought unique genomic insights into tumorigenesis of a viral-driven cancer. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) is a common tumor in China. Accurate stages of NPC are crucial for treatment. We therefore aim to develop radiomics models for discriminating early-stage (I–II) and advanced-stage (III–IVa) NPC based on MR images. Methods: 329 NPC patients were enrolled and randomly divided into a training cohort (n = 229) and a validation cohort (n = 100). Features were extracted based on axial contrast-enhanced T1-weighted images (CE-T1WI), T1WI, and T2-weighted images (T2WI). Least absolute shrinkage and selection operator (LASSO) was used to build radiomics signatures. Seven radiomics models were constructed with logistic regression. The AUC value was used to assess classification performance. The DeLong test was used to compare the AUCs of different radiomics models and visual assessment. Results: Models A, B, C, D, E, F, and G were constructed with 13, 9, 7, 9, 10, 7, and 6 features, respectively. All radiomics models showed better classification performance than that of visual assessment. Model A (CE-T1WI + T1WI + T2WI) showed the best classification performance (AUC: 0.847) in the training cohort. CE-T1WI showed the greatest significance for staging NPC. Conclusion: Radiomics models can effectively distinguish early-stage from advanced-stage NPC patients, and Model A (CE-T1WI + T1WI + T2WI) showed the best classification performance. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC), is an Epstein-Barr virus (EBV) associated malignancy most common in Southern China and Southeast Asia. In southern China, it is one of the major causes of cancer-related death. Despite improvement in radiotherapy and chemotherapy techniques, locoregional recurrence and distant metastasis remains the major causes for failure of treatment in NPC patients. Therefore, finding new specific drug targets for treatment interventions are urgently needed. Here, we report three potential ZLMP1-C affibody molecules (ZLMP1-C15, ZLMP1-C114 and ZLMP1-C277) that showed specific binding interactions for recombinant and native EBV LMP1 as determined by epitope mapping, co-localization and co-immunoprecipitation assays. The ZLMP1-C affibody molecules exhibited high antitumor effects on EBV-positive NPC cell lines and displayed minimal cytotoxicity towards EBV-negative NPC cell line. Moreover, ZLMP1-C277 showed higher antitumor efficacy than ZLMP1-C15 and ZLMP1-C114 affibody molecules. The ability of ZLMP1-C277 decrease the phosphorylation levels of up-stream activator phospho-Raf-1(Ser338), phospho-MEK1/2(Ser217/Ser221), phospho-ERK1/2(Thr202/Thr204), thereby leading to downstream suppression of phospho-p90RSK(Ser380) and transcription factor c-Fos. Importantly, tumor growth was reduced in tumor-bearing mice treated with ZLMP1-C277 and caused no apparent toxicity. Taken together, our findings provide evidence that ZLMP1-C277 as a promising therapeutic agent in EBV-associated NPC. [ABSTRACT FROM AUTHOR]

Objective: We compared the clinical characteristics and survival outcomes after radical radiotherapy between nasopharyngeal carcinoma (NPC) with early and late metastases based on a relatively large cohort, which provides valuable data for the planning of clinical surveillance strategies. Methods: This was a single-center retrospective analysis of 10,566 patients who received radical radiotherapy in China from January 2000 to December 2016. Overall survival was the primary endpoint. Kaplan–Meier survival analysis and log-rank tests were applied to investigate the association between early or late metastasis and the endpoints. The prognostic value of clinicopathological features was identified using univariate and multivariate Cox proportional hazards models. Results: The cutoff value for time to metastasis was based on ROC analysis. A total of 559 (5.3%) patients developed distant metastases, 297 (53.1%) of which developed early metastatic disease, with the rest (46.9%) developing late metastatic disease. The K-M analysis showed that the patients with late metastatic foci had significantly better post-metastatic OS (P = 0.0056). Multivariate analysis indicated that age, liver metastasis, the number of metastatic foci and time to metastasis (P = 0.013) are independent prognostic factors for OS. After analyzing the impact of different treatment methods, we found that local treatment was an independent protective factor for LM, while local treatment was not associated with a survival benefit for EM disease. Conclusions: The time to metastasis after radical radiotherapy affected the prognosis of NPC patients and local treatment was an independent protective factor that could improve the survival of late metastatic NPC patients. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is an uncommon type of malignancy/cancer worldwide. However, NPC is an endemic disease in southeast Asia and southern China and the reasons behind the underlying for such changes are unclear. Even though the Epstein–Barr infection (EBV) has been suggested as an important reason for undistinguishable NPC, the EBV itself is not adequate to source this type of cancer. The risk factors, for example, genetic susceptibility, and environmental factors might be associated with EBV to undertake a part in the NPC carcinogenesis. Normal healthy people have a memory B cell pool where the EBV persists, and any disturbance of this connection leads to virus-associated B cell malignancies. Less is known about the relationship between EBV and epithelial cell tumors, especially the EBV-associated nasopharyngeal carcinoma (EBVaNPC) and EBV-associated gastric carcinoma (EBVaGC). Currently, it is believed that premalignant genetic changes in epithelial cells contribute to the aberrant establishment of viral latency in these tumors. The early and late phases of NPC patients' survival rates vary significantly. The presence of EBV in all tumor cells presents prospects for the development of innovative therapeutic and diagnostic techniques, despite the fact that the virus's exact involvement in the carcinogenic process is presently not very well known. EBV research continues to shed light on the carcinogenic process, which is important for a more comprehensive knowledge of tumor etiology and the development of targeted cancer therapeutics. In order to screen for NPC, EBV-related biomarkers have been widely used in a few high-incidence locations because of their close associations with the risks of NPC. The current review highlights the scientific importance of EBV and its possible association with NPC. [ABSTRACT FROM AUTHOR]

Background: To explore the short‐ and long‐term outcomes in patients with nasopharyngeal carcinoma (NPC) with magnetic resonance imaging (MRI)‐detected residual disease at 3 months post‐treatment who received intervention either promptly (0 month) or following observation (after an additional 3 months). Methods: A total of 272 patients with residual disease at 3 months post‐treatment (observation [observation for additional 3 months]: 122, intervention [prompt intervention]: 150) were analyzed. Univariate and multivariate analyses were performed to examine the survival. Adverse events were analyzed in all patients. Results: Patients in the observation group had a lower 3‐year overall survival (77.1% vs. 85.2%), progression‐free survival (10.2% vs. 18.1%), and locoregional relapse‐free survival (10.2% vs. 20.6%) (all p <.05), but not distant metastasis‐free survival (83.8% vs. 78.4%, p =.189), whereas patients in the intervention group achieved higher complete remission (CR) rates (43.3% vs. 21.2%, p =.003). Patients who achieved CR after prompt intervention had a better survival rate than those who achieved observation‐CR or non‐CR (p <.001). Multivariate analyses revealed that a wait‐and‐see policy was an independent prognostic factor for impaired survival (p <.001). No significant differences of acute or late toxicities were observed between the two groups. Conclusions: Patients with NPC with MRI‐detected residual disease 3 months post‐radiotherapy should be encouraged to undergo prompt intervention rather than adopting a passive wait‐and‐see policy. [ABSTRACT FROM AUTHOR]

Background: Nasopharyngeal carcinoma (NPC) has high incidence in Southern China and is derived from the mucosal epithelium of the nasopharynx. Accumulating evidence has revealed that peptidyl arginine deiminase 4 (PAD4) exerts carcinogenic effect on certain cancers. We designed this study to probe the specific role that PAD4 plays in NPC and its molecular mechanism. Methods: PAD4 expression in NPC cells was detected by RT-qPCR analysis. MTT, colony formation, flow cytometry, TUNEL staining, and LC3-II punctuation experiments were done to probe into the biological functions of PAD4 on NPC cellular behaviors in vitro. Subsequently, the upstream regulatory mechanism of PAD4 was investigated by luciferase reporter, RNA pull-down, and RIP assays. The impact of PAD4 on NPC tumor growth in mice was assessed by in vivo xenograft tumor assay. Results: PAD4 was upregulated in NPC cells. PAD4 knockdown suppressed proliferative ability and promoted apoptosis and autophagy in NPC cells. Additionally, PAD4 expression was negatively regulated by microRNA 3164 (miR-3164). LINC00324 positively upregulated PAD4 expression by interacting with miR-3164 and recruiting HuR protein. The LINC00324/miR-3164/PAD4 axis modulated the PI3K/AKT pathway in NPC cells. Moreover, PAD4 upregulation countervailed the influences of LINC00324 deficiency on NPC cell proliferation, apoptosis, and autophagy and on NPC tumor growth in mice. Conclusion: LINC00324 promoted NPC malignancy by upregulation of PAD4 to activate the PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Objective: Nasopharyngeal carcinoma (NPC) is prevailing in Southern China, characterized by distinct geographical distribution. Aimed to predict the overall survival (OS) of patients with nasopharyngeal carcinoma, this study developed and validated nomograms considering demographic variables, hematological biomarkers, and oncogenic pathogens in China. Methods: The clinicopathological and follow-up data of the nasopharyngeal carcinoma patients obtained from a prospective longitudinal cohort study in the Chongqing University Cancer Hospital between Jan 1, 2017 and Dec 31, 2019 ( n = 1635 ). Cox regression model was used to tested the significance of all available variables as prognostic factors of OS. And independent prognostic factors were identified based on multivariable analysis to model nomogram. Concordance index (C-index), area under the receiver operating characteristic (AUC), calibration curve, and decision curve analysis (DCA) were measured to assess the model performance of nomogram. Results: Data was randomly divided into a training cohort (1227 observers, about 70% of data) and a validation group (408 observers, about 30% of data). At multivariable analysis, the following were independent predictors of OS in NPC patients and entered into the nomogram: age (hazard ratio [HR]: 1.03), stage (stage IV vs. stage I–II, HR: 4.54), radiotherapy (Yes vs. No, HR: 0.43), EBV ( ≥ 1000 vs. < 1000 , HR: 1.92), LAR ( > 6.15 vs. ≤ 6.15 , HR: 2.05), NLR ( > 4.84 vs. ≤ 4.84 HR: 1.54), and PLR ( > 206.33 vs. ≤ 206.33 , HR: 1.79). The C-indexes for training cohort at 1-, 3- and 5-year were 0.73, 0.83, 0.80, respectively, in the validation cohort, the C-indexes were 0.74 (95% CI 0.63–0.86), 0.80 (95% CI 0.73–0.87), and 0.77 (95% CI 0.67–0.86), respectively. The calibration curve demonstrated that favorable agreement between the predictions of the nomograms and the actual observations in the training and validation cohorts. In addition, the decision curve analysis proved that the nomogram model had the highest overall net benefit. Conclusion: A new prognostic model to predict OS of patients with NPC was developed. This can offer clinicians treatment making and patient counseling. Furthermore, the nomogram was deployed into a website server for use. [ABSTRACT FROM AUTHOR]