EBioMedicine
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2022
·
IF 11.205
Ruo-Wen Xiao,Fang Wang,Tong-Min Wang,Jiang-Bo Zhang,Zi-Yi Wu,Chang-Mi Deng,Ying Liao,Ting Zhou,Da-Wei Yang,Si-Qi Dong,Wen-Qiong Xue,Yong-Qiao He,Xiao-Hui Zheng,Xi-Zhao Li,Pei-Fen Zhang,Shao-Dan Zhang,Ye-Zhu Hu,Yu-Ying Liu,Yun-Fei Xia,Song Gao,Jian-Bing Mu,Lin Feng,Wei-Hua Jia
Summary Background Nasopharyngeal carcinoma (NPC) exhibits significant familial aggregation; however, its susceptibility genes are largely unknown. Thus, this study aimed to identify germline mutations that might contribute to the risk of familial NPC, and explore their biological functions. Methods Whole-exome sequencing was performed in 13 NPC pedigrees with multiple cases. Mutations co-segregated with disease status were further validated in a cohort composed of 563 probands from independent families, 2,953 sporadic cases, and 3,175 healthy controls. Experimental studies were used to explore the functions of susceptibility genes and their disease-related mutations. Findings The three rare missense mutations in POLN (DNA polymerase nu) gene, P577L, R303Q, and F545C, were associated with familial NPC risk (5/576 [0·87%] in cases vs. 2/3374 [0·059%] in healthy controls with an adjusted OR of 44·84 [95% CI:3·91-514·34, p = 2·25 × 10 −3 ]). POLN was involved in Epstein-Barr virus (EBV) lytic replication in NPC cells in vitro. POLN promoted viral DNA replication, immediate-early and late lytic gene expression, and progeny viral particle production, ultimately affecting the proliferation of host cells. The three mutations were located in two pivotal functional domains and were predicted to alter the protein stability of POLN in silico . Further assays demonstrated that POLN carrying any of the three mutations displayed reduced protein stability and decreased expression levels, thereby impairing its ability to promote complete EBV lytic replication and facilitate cell survival. Interpretation We identified a susceptibility gene POLN for familial NPC and elucidated its function. Funding This study was funded by the National Key Research and Development Program of China (2021YFC2500400); the National Key Research and Development Program of China (2020YFC1316902); the Basic and Applied Basic Research Foundation of Guangdong Province, China (2021B1515420007); the National Natural Science Foundation of China (81973131); the National Natural Science Foundation of China (82003520); the National Natural Science Foundation of China (81903395).
研究领域:
肿瘤学
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分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioscience-Landmark
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2025
·Vol. 30
·期 4
·26038
·
IF 3.1
Deqiang An,Xianyao Jiang,Yucheng Yang
Background:Sesamin can suppress many cancers, but its effect on nasopharyngeal carcinoma (NPC) is unclear. Herein, we set out to pinpoint the possible changes in NPC due to Sesamin.Methods:The biological function of NPC cells exposed to Sesamin/N-acetyl-L-cysteine (NAC)/3-Methyladenine (3-MA) was detected, followed by evaluation of reactive oxygen species (ROS) production (dichlorodihydrofluorescein diacetate staining) and mitochondrial membrane potential (MMP) (flow cytometry). Proteins pertinent to apoptosis (cleaved caspase-3, cleaved poly (ADP-ribose) polymerase 1 (PARP1)), cell cycle (Cyclin B1), and autophagy (microtubule-associated protein light chain 3 (LC3)-I, LC3-II, Beclin-1, P62) were quantified by Western blot. After the xenografted tumor model in mice was established, the tumor volume and weight were recorded, and Ki-67 and cleaved caspase-3 levels were determined by immunohistochemical analysis.Results:Sesamin inhibited viability, proliferation, cell cycle progression and migration, induced apoptosis, increased ROS production, and decreased MMP in NPC cells. Sesamin elevated cleaved caspase-3/caspase-3, cleaved PARP1/PARP1, and Beclin-1 expressions as well as LC3-II/LC3-I ratio, while diminishing Cyclin B1 and P62 levels. NAC and 3-MA abrogated Sesamin-induced changes as above in NPC cells. Sesamin inhibited the increase of the xenografted tumor volume and weight, down-regulated Ki-67, and up-regulated cleaved caspase-3 in xenografted tumors.Conclusion:Sesamin exerts anti-tumor activity in NPC, as demonstrated by attenuated tumor proliferation and xenografted tumor volume and weight, as well as induced apoptosis in tumor tissues, consequent upon the promotion of autophagy and reactive oxygen species production.
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
Cancer Biomarkers
·
2018
·Vol. 23
·期 4
·603-613
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IF 2.392
Liu Zhi-Biao,Tang Chen,Jin Xin,Liu Shou-Hou,Pi Wen
BACKGROUND: Small nucleolar RNA host gene 12 (SNHG12) has been shown to be a long noncoding RNA (lncRNA) that facilitates the progression of a number of malignancies. However, the expression pattern and biological function of SNHG12 in nasopharyngeal carcinoma (NPC) have not been investigated. OBJECTIVE: The aim of our study is to investigate the expression, clinical significance and function of SNHG12 in NPC. METHODS: RT-PCR was used to detect the expression of SNHG12 in NPC cell lines and primary tumor tissues. The correlation of SNHG12 with clinicopathological features and patient prognosis was analyzed. The biologic functions of SNHG12 in NPC were explored by MTT assay, colony formation assay, wound healing assays, transwell assay and flow cytometric analysis in vitro. The expression of EMT markers and Notch signal pathway markers were determined by western blotting. RESULTS: The expression levels of SNHG12 were up-regulated in both NPC tissues and cell lines. High SNHG12 expression was significantly associated with clinical stage, grade and poor prognosis. Multivariate analysis demonstrated that high lncRNA SNHG12 expression was an independent poor prognostic factor for NPC patients. Functionally, knockdown of SNHG12 suppressed NPC cells proliferation, migration and invasion. Mechanistic investigations showed that knockdown of SNHG12 suppressed the activation of EMT and Notch-1 signal pathway. CONCLUSIONS: Our data suggest that SNHG12 promotes the progression of NPC and is a potential therapeutic target for NPC intervention.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
BIOLOGICAL & PHARMACEUTICAL BULLETIN
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2025
·Vol. 48
·期 7
·1096-1106
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IF 1.7
Tao Feng,Guofang Hu,Yinjun Luo,Xin Zhang,Hong Chen,Zuoren Liang,Xianjiao He,Shijing Ma,Jinting Wei,Xiaoyan Fang,Biao Li,Jinhua Wang,Suchan Liao
Nasopharyngeal carcinoma (NPC) is a highly invasive form of head and neck cancer that arises from nasopharyngeal epithelial cells. Celastrol and curcumin, both derived from traditional Chinese medicine, have demonstrated antitumor potential. However, the clinical application of these compounds is limited by their low bioavailability and/or toxicity. Cancer cell viability, apoptosis, autophagy, ferroptosis, and mitochondrial fission- and fusion-related proteins were evaluated following treatment with celastrol alone, curcumin alone, and their combination. The results indicated that low doses of celastrol (0.7 μM) alone do not inhibit proliferation in NPC cells. However, when combined with curcumin, there is a significant enhancement of the antiproliferative effect. There was no significant alteration in the expression levels of the apoptosis-related proteins BCL2-associated X and cleaved caspase 3 in either the curcumin alone or the combined treatment groups compared to the control group. Interestingly, the combined treatment significantly increased the ferroptosis contributor acyl-CoA synthetase long-chain family member 4 while notably decreasing solute carrier family 7 member 11 and glutathione peroxidase 4, accompanied by increased phosphorylation of dynamin-related protein 1. Furthermore, the combined treatment exhibited significant antitumor efficacy with low toxic side effects in a xenograft model. In conclusion, our study provides new insights into combination therapies to enhance anti-NPC efficacy.
研究领域:
肿瘤学
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药理学
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分子生物学
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传统中医药学
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转化医学
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产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2023
·Vol. 15
·期 7
·3475-3481
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IF 6.7
Rui Gong,Chenyang Yang,Ghulam Abbas,Dianbing Wang,Xianen Zhang,Guohui Nie,Hui Ding
The detection of the antibody of Epstein–Barr virus (EBV) is critical for the diagnosis of nasopharyngeal carcinoma (NPC). An accurate and scalable point-of-care detection method would support the screening, diagnosis, and monitoring of NPC patients. In this study, firstly, we made an antibody enrichment element, antigen-MNPs, which can screen out specific antibodies in a complex sample. Secondly, signal-amplifying elements were synthesized by labelling inorganic quantum dots (QDs) and anti-antibodies on the surface of flop-ferritin. A sandwich structure is formed among antigen-MNPs, target-antibodies, and anti-antibodies-flop-ferritin@QDs. The antibodies are quantified by fluorescence intensity with a limit of detection (LOD) as low as 10−11 g mL−1. Moreover, the method can detect different types of antibodies and was employed to examine 10 sera from NPC patients and 10 sera from healthy individuals. The result indicates that the simultaneous detection of anti-EBNA-IgG and anti-EBNA-IgA provides an efficient route for early diagnosis of NPC.
研究领域:
医学
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免疫学
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DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2017
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IF 4.164
Xin Ji,Huilong Guo,Qiao Tang,Dong Ma,Wei Xue
Antitumor efficacy of methotrexate (MTX) is seriously limited due to its poor water solubility, nonspecific tumor distribution and low bioavailability. To overcome these obstacles, polyspermine (PSP) conjugated with MTX and folic acid (FA) as a novel targeted prodrug was designed and has been successfully synthesized using the amidation reaction. The strong hydrophilic properties of PSP made MTX well dispersed in water and the cellular uptake study indicated that the presence of FA enhanced uptake of the FA-PSP-MTX in folate receptor (FR) over-expressing human nasopharyngeal carcinoma HNE-1 cells. 1 H NMR spectra and UV–Vis spectral analysis were carried out to confirm the MTX and FA content in FA-PSP-MTX, respectively. In CCK-8 assay and apoptosis analysis, the prodrug showed significantly enhanced anticancer efficacy than free MTX in HNE-1 cells. These results suggested that the prodrug has the potential for targeted delivery of MTX into cancer cells to improve its anti-tumor efficacy.
研究领域:
药理学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
Oncotarget
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2016
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IF 5.008
Tao Liu,Xidong Wu,Yigang Wang,Tao Zhang,Ting Wu,Fang Liu,Wansong Wang,Gang Jiang,Minqiang Xie
The co-delivery of drug and gene has become the primary strategy in cancer therapy. Based on our previous work, to co-deliver docetaxel (DOC) and MMP-9 siRNA more efficiently for HNE-1 nasopharyngeal carcinoma therapy, a folate-modified star-shaped copolymer (FA-CD-PLLD) consisting of β-cyclodextrin (CD) and poly(L-lysine) dendron (PLLD) was synthesized, and then used for DOC and MMP-9 co-delivery. Different from commonly used amphiphilic copolymers micelles, the obtained CD derivative could be used directly for the combinatorial delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vitro and in vivo assays are carried out to confirm the effectiveness of the target strategy and combined treatment. It was found that the conjugation of CD-PLLD with FA could enhance the DOC/MMP-9 delivery effect obviously, inducing a more significant apoptosis and decreasing invasive capacity of HEN-1 cells. In vivo assays showed that FA-CD-PLLD/DOC/MMP-9 could inhibit HNE-1 tumor growth and decrease PCNA expression effectively, indicating a promising strategy for nasopharyngeal carcinoma therapy. Moreover, the in vivo distribution of DOC and MMP-9, blood compatibility and toxicity are also explored.
研究领域:
药剂学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2024
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IF 18.5
Qianyu Yang,Gang Wu,Yefeng Yang,Yang Zhou,Jiali Song,Huile Gao,Weiyuan Huang
Based on the properties of photodynamic therapy (PDT) and magnetic resonance imaging (MRI), combining them to construct multifunctional nanotheranostics can leverage strengths and avoid weaknesses for tumor diagnosis and treatment. However, certain problems remain unsolved, notably the short observation window caused by insufficient retention time. In this study, a GSH-responsive shape-transformable nanotheranostics Gd-Ce6-FFVLGGGC-SS-PEG are designed (abbreviated as GdCFS) by combining a single metal Gd with Ce6, and peptide (Phe-Phe-Val-Leu-Gly-Gly-Gly-Cys) disulfide-conjugated with polyethylene glycol (PEG) to perform dual-modal T 1 /T 2 MRI specifically at the tumor site. Due to its amphiphilic features, GdCFS can self-assemble to spherical nanoparticles, while transforming to nanofibers (NFs) in the presence of intracellular overexpressed GSH stimuli. After NFs formation, the hydrophobic core of GdCFS is exposed, resulting in T 1 positive contrast enhancement, whereas NFs can simultaneously achieve T 2 negative contrast enhancement. Furthermore, GSH depletion can cause imbalance in intracellular redox state, ultimately improving PDT efficacy. GdCFS benefits from the shape-transformation in terms of sufficient retention time, thus positively minimizing the toxicity risk. On the tumor model of nasopharyngeal carcinoma, in vivo and in vitro outcomes confirm that GdCFS can be a promising candidate for early diagnosis, real-time monitoring, and precise treatment of tumors with great biocompatibility.
研究领域:
医学
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纳米医学
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肿瘤学
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影像学
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产品关联
DOI
高影响因子
Molecular Medicine Reports
·
2019
·Vol. 19
·期 5
·3658-3666
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IF 1.851
Jin Xu,Yin Ying,Gaoyun Xiong,Liqin Lai,Qingliang Wang,Yue Yang
Nasopharyngeal carcinoma (NPC) is a type of cancer originating in the nasopharynx. There are no NPC‑specific treatments available at present. Serpin peptidase inhibitor clade C member 1 (SERPINC1) serves roles in anticoagulation and anti‑inflammation. The aim of the present study was to investigate the role of SERPINC1 in the proliferation and apoptosis of NPC cells. Tumor and adjacent healthy tissue samples were collected from patients with NPC. Additionally, the SERPINC1 gene was silenced in the HNE3 cell line using short interfering RNA targeted against SERPINC1 (SERPINC1‑siRNA). Cell viability was determined via a Cell Counting Kit‑8 assay; furthermore, proliferation and apoptosis were investigated via flow cytometry. Western blotting and reverse transcription‑quantitative polymerase chain reaction analysis were performed to determine the expression levels of protein and mRNA. It was revealed that the expression levels of SERPINC1 mRNA and protein were increased in NPC tumor tissues compared with in adjacent healthy tissues. The expression of SERPINC1 mRNA and protein in HNE3 cells decreased following SERPINC1‑siRNA transfection. Furthermore, knockdown of SERPINC1 promoted apoptosis and inhibited proliferation. It was also demonstrated that silencing SERPINC1 upregulated the expression of B‑cell lymphoma-2 (Bcl‑2)‑associated X protein and p53 mRNA and protein, and downregulated that of Bcl‑2, survivin and cyclin D1. Downregulation of SERPINC1 reduced the phosphorylation of phosphatidylinositol 3‑kinase (PI3K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR). Thus, SERPINC1 knockdown may promote the apoptosis of HNE3 cells and inhibit proliferation via the suppression of the PI3K/Akt/mTOR signaling pathway.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2019
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IF 3.829
Tao Liu,Xidong Wu,Shaohua Chen,Peina Wu,Hong Han,Hongbin Zhang,Junzheng Li,Guanxue Li,Siyi Zhang
To obtain a high-efficiency drug and gene co-delivery system to HNE-1 tumor therapy, a polymeric prodrug (PAAs-MTX) with chemotherapeutic sensibilization was synthesized consisting of a GSH-response hyperbranched poly(amido amine) (PAAs) and an antitumor drug of methotrexate (MTX). Then, the targeting molecule to HNE-1 cells, transferrin (Tf), was conjugated to form the Tf-PAAs-MTX. This polymeric prodrug could deliver MMP-9 shRNA plasmid (pMMP-9) again to form the drug and gene co-delivery system of Tf-PAAs-MTX/pMMP-9. The co-delivery system showed the effective drug and gene delivery ability with high cytotoxicity and gene transfection efficiency to HNE-1 cells. Besides that, Tf-PAAs-MTX also showed the chemotherapeutic sensibilization effect, the formulation containing PAAs segments showed much higher cytotoxicity than that of free MTX. Benefiting from the sensibilization effect and MTX/pMMP-9 co-delivery strategy, this Tf-PAAs-MTX/pMMP-9 co-delivery system exhibited the significantly improved therapeutic efficacy to HNE-1 tumor in a combined manner which was confirmed by in vitro and in vivo assays. Moreover, its biocompatibility, especially the blood compatibility was analyzed. This polymeric prodrug provided an easily delivery system combining the drug/gene co-delivery, chemotherapeutic sensibilization and targeting into one single platform, which showed a promising application in nasopharyngeal carcinoma therapy.
研究领域:
肿瘤学
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药剂学
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分子生物学
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DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Hui-Qin Liu,Xi-Dong Wu,Xue-Wen Fang,Yun-Song An,Meng Xia,Xiao-Hua Luo,Jun-Zheng Li,Guan-Hai Wang,Tao Liu
Nasopharyngeal carcinoma (NPC) is prevalent in Southern China. Unfortunately, current treatments encounter multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), resulting in the efflux of chemotherapy drugs, is one of the significant mechanisms causing MDR. d-α-Tocopheryl poly(ethylene glycol) 1000 succinate (TPGS) has been demonstrated to effectively inhibit P-gp expression. The objectives of this study are to improve tumor MRI imaging, optimize docetaxel (DOC) administration, and target P-gp to overcome NPC resistance. Multifunctional micelles of TPGS (MM@DOC), loaded with magnetic nanoparticles, were synthesized for the targeted delivery of the first-line anticancer drug. MM@DOC exhibited greater toxicity and induced higher levels of apoptosis in DOC-resistant NPC cells (C666–1/DOC) compared to DOC. MM@DOC loaded with magnetic nanoparticles improved the quality of tumor MRI imaging. MM@DOC also demonstrated significant antitumor effects in nude mice with C666–1/DOC NPC. In conclusion, MM@DOC exhibited promising inhibitory effects on resistant tumors both in vitro and in vivo, optimized tumor MRI imaging, and showed great potential in drug delivery and overcoming resistance.
研究领域:
肿瘤学
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医学影像学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2025
·
IF 6
Ruiying Lin,Zhangying Jiang,Jinyong Lin,Feifei Tong,Yangmin Wu,Jinquan Hong,Sufang Qiu,Qiong Wu
Background In recent years, significant progress has been made in the treatment of nasopharyngeal carcinoma (NPC). The application of immunotherapy, especially the use of Programmed Cell Death Protein 1 inhibitors, has demonstrated excellent therapeutic effects. However, inconsistent immunotherapy outcomes due to individual differences in patients remain a major challenge, making the search for specific biomarkers to screen for the population who may benefit from immunotherapy a priority. Surface-enhanced Raman spectroscopy (SERS) has shown great potential as a highly sensitive and specific optical analytical tool for identifying and monitoring tumor-related markers in NPC. Results In this study, plasma samples from Nasopharyngeal cancer patients before and after immunotherapy, along with those from healthy volunteers, were tested using label-free SERS combined with plasmapheresis. Especially, the components with varying molecular weight sizes were analyzed via the separation process, thereby preventing the potential loss of diagnostic information that could result from competitive adsorption. Subsequently, a robust machine learning algorithm based on principal component analysis and linear discriminant analysis (PCA-LDA) was used to extract features from plasma SERS data and establish an effective discriminant model. The results showed that in the upper plasma layer, the most optimal discrimination was found between normal patients and those post-treatment, with sensitivity and specificity of 88.5% and 92.3%, respectively. In the lower plasma layer, the most optimal discrimination was found between the pre-treatment and post-treatment patients, with sensitivity and specificity of 84.6% and 80.8%, respectively. Significance and novelty Plasmapheresis can reveal latent diagnostic information in the plasma and holds promise for treating NPC, the screening of the population who may benefit from immunotherapy, and the postoperative evaluation of immunotherapy. Further exploration of the feasibility of using SERS to detect tumor markers in the population who may benefit from immunotherapy for NPC will help improve the therapeutic efficacy, optimize clinical practice, and promote the development of individualized treatment strategies.
研究领域:
肿瘤学
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医学诊断
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生物信息学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）