BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and b...BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and bone resorption,as well as their potential to modulate immune functions and thereby enhance the efficacy of programmed cell death protein 1(PD-1)inhibitor therapy.CASE SUMMARY We present a case of a patient with NPC who developed sternal stalk metastasis and multiple bone metastases with soft tissue invasion following radical chemoradiotherapy and targeted therapy.Prior to chemotherapy,the patient experienced severe bone marrow suppression and opted out of further chemotherapy sessions.However,the patient received combination therapy,including RANKL inhibitors(denosumab)alongside PD-1,radiotherapy,and granulocyte-macrophage colonystimulating factor(PRaG)therapy(NCT05435768),and achieved 16 months of progression-free survival and more than 35 months of overall survival,without encountering any grade 2 or higher treatment-related adverse events.CONCLUSION Denosumab combined with PRaG therapy could be a new therapeutic approach for the second-line treatment in patients with bone metastases.展开更多
Objective:To investigate the chemical components of Semen podocarpi extract(SPE)and its effect on nasopharyngeal carcinoma cells and CNE-2R cells.Methods:Chemical components in SPE were identified by UPLC-MS/MS.CCK-8 ...Objective:To investigate the chemical components of Semen podocarpi extract(SPE)and its effect on nasopharyngeal carcinoma cells and CNE-2R cells.Methods:Chemical components in SPE were identified by UPLC-MS/MS.CCK-8 and cell cloning experiments were applied to evaluate the effects of SPE on the proliferation of CNE-2R cells,and a single-hit multitarget model was used to calculate the radiobiological parameters.Cell apoptosis and cell cycle were analyzed by flow cytometry,and the levels of genes and proteins of the Raf/MEK/ERK pathway were determined by RT-PCR and Western blotting.Results:A total of 37 compounds from SPE were identified,and SPE with or without irradiation inhibited the proliferation of CNE-2R cells.SPE also promoted apoptosis,arrested cells in the G_(2)/M phase,and presented radiosensitizing effects.Compared with irradiation alone,the effects of SPE+irradiation on apoptosis and cell cycle distribution were not significantly different.In addition,SPE had no significant effect on MEK gene expression.SPE significantly increased the gene expression of C-Raf and significantly reduced the protein expression of C-Raf,as well as the gene and protein expression of ERK1 and ERK2.The protein levels of C-Raf,ERK1,and ERK2 were also significantly lower in cells treated with SPE+irradiation than in cells treated with irradiation alone.Conclusions:The effects of SPE on inhibiting cell proliferation and promoting apoptosis are likely associated with cell cycle arrest and Raf/MEK/ERK pathway regulation,and the mechanism underlying radiosensitization by SPE may involve downregulating the protein expression of C-Raf,ERK1,and ERK2.展开更多
Various genetic association studies have identified numerous single nucleotide polymorphisms(SNPs)associated with nasopharyngeal carcinoma(NPC)risk.However,these studies have predominantly focused on common variants,l...Various genetic association studies have identified numerous single nucleotide polymorphisms(SNPs)associated with nasopharyngeal carcinoma(NPC)risk.However,these studies have predominantly focused on common variants,leaving the contribution of rare variants to the“missing heritability”largely unexplored.Here,we integrate genotyping data from 3925 NPC cases and 15,048 healthy controls to identify a rare SNP,rs141121474,resulting in a Glu510Lys mutation in KLHDC4 gene linked to increased NPC risk.Subsequent analyses reveal that KLHDC4 is highly expressed in NPC and correlates with poorer prognosis.Functional characterizations demonstrate that KLHDC4 acts as an oncogene in NPC cells,enhancing their migratory and metastatic capabilities,with these effects being further augmented by the Glu510Lys mutation.Mechanistically,the Glu510Lys mutant exhibits increased interaction with Vimentin compared to the wild-type KLHDC4(KLHDC4-WT),leading to elevated Vimentin protein stability and modulation of the epithelial-mesenchymal transition process,thereby promoting tumor metastasis.Moreover,Vimentin knockdown significantly mitigates the oncogenic effects induced by overexpression of both KLHDC4-WT and the Glu510Lys variant.Collectively,our findings highlight the critical role of the rare KLHDC4 variant rs141121474 in NPC progression and propose its potential as a diagnostic and therapeutic target for NPC patients.展开更多
Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for ...Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).A crucial question is whether concurrent chemo-radiotherapy(CCRT)could derive additional benefits to this recent“down-staging”subgroup of NPC patients.This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival(PFS)of stageⅡNPC treated with RT alone or CCRT.Methods:Imaging and clinical data of 166 stageⅡNPC(eighth edition AJCC/UICC)patients were collected.Data were allocated into training,internal testing,and external testing sets.For each case,851 radiomic features were extracted and 10 clinical features were collected.Radiomic and clinical features most associated with the 5-year PFS were selected separately.A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS.Model performances were evaluated by area under the receiver operating curve(AUC),prediction accuracy,and decision curve analysis.Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.Results:Thirteen radiomic features,three clinical features,and treatment option were considered for model development.The combined model showed higher prognostic performance than using either.For the merged testing set(internal and external testing sets),AUC is 0.76(combined)vs.0.56-0.80(clinical or radiomic alone)and accuracy is 0.75(combined)vs.0.62-0.73(clinical or radiomic alone).Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts(P<0.05).Conclusions:Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen,guiding individualized decisions of chemotherapy based on the predicted treatment outcome.展开更多
According to the International Cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and south...According to the International Cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and southern China.Recently,substantial progress has been made in the field of basic and translational research on NPC,enhancing our understanding of the molecular mechanisms underlying the disease and paving the way for precise therapeutic approaches.This review summarizes the advances in NPC research,focusing on key areas that include radiotherapy and chemotherapy resistance and tumor metastasis,microenvironment,metabolism,microbiome,and biomarkers.Additionally,future research directions in NPC are discussed to provide valuable insights to advance the field further.展开更多
Accurate cancer staging is the foundation of precision oncology and guides prognosis prediction and therapeutic decision-making. The conjoint TNM System by the American Joint Committee on Cancer (AJCC) and the Interna...Accurate cancer staging is the foundation of precision oncology and guides prognosis prediction and therapeutic decision-making. The conjoint TNM System by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) has served as the global standard for tumor classification since inception.展开更多
Objective Histamine N-methyltransferase(HNMT)is involved primarily in histamine metabolism,but emerging evidence suggests its potential role in cancer progression.This study investigated the role of HNMT in nasopharyn...Objective Histamine N-methyltransferase(HNMT)is involved primarily in histamine metabolism,but emerging evidence suggests its potential role in cancer progression.This study investigated the role of HNMT in nasopharyngeal carcinoma(NPC)and its impact on interferon(IFN)signaling,thioredoxin-interacting protein(TXNIP),and p53 tumor suppressor pathways.Methods HNMT expression in NPC tissues and cell lines was analyzed via qPCR and Western blotting.Functional assays,including cell proliferation,migration,invasion,and apoptosis,were performed after HNMT knockdown or overexpression.Transcriptomic sequencing was used to identify differentially expressed genes(DEGs).In addition,we examined the relationship between HNMT and the IFN/TXNIP/p53 axis via rescue experiments in vitro and in vivo models via qPCR and Western blotting.Results HNMT knockdown reduced cell proliferation,migration,and invasion,and promoted apoptosis in NPC tissues and cell lines.TXNIP was the most significantly upregulated gene following HNMT knockdown.Inhibition of the IFN pathway reversed these effects,confirming the role of HNMT in downregulating the IFN/TXNIP/p53 pathway.An in vivo study revealed that HNMT overexpression correlated with reduced expression of TXNIP and p53 in NCG mice.Conclusion In NPC,HNMT promotes tumor growth and progression by inhibiting the IFN/TXNIP/p53 axis.These findings suggest that targeting the HNMT axis or restoring its function could provide new therapeutic strategies for NPC.展开更多
BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitiv...BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitivity and specificity for identifying patients at high risk of recurrence.However,use of its results as a biomarker for guiding the treatment and predicting the prognosis of naso-pharyngeal carcinoma(NPC)has not been reported.CASE SUMMARY In this case study of a patient with stage IVb NPC,we utilized ctDNA as an independent biomarker to guide treatment.Chemotherapy was administered in the early stages of the disease,and local intensity-modulated radiation therapy was added when the patient tested positive for ctDNA,while radiation therapy was stopped and the patient was observed when the ctDNA test was negative.During the follow-up period,ctDNA signals became positive before tumor progression and became negative again at the end of treatment.We also explored the potential of ctDNA in combination with Epstein-Barr virus(EBV)DNA status to predict the prognosis of NPC patients,as well as the criteria for selecting genetic mutations and the testing cycle for ctDNA analysis.CONCLUSION The results of ctDNA-based liquid biopsy can serve as an independent biomarker,either independently or in conjunction with EBV DNA status,to guide the treatment and predict the prognosis of NPC.展开更多
It is hereby declared that the article entitled“miR-34c-3p Inhibits Nasopharyngeal Carcinoma Development via Inhibiting M2 Polarization of Macrophages”(Yuzi Ji,Yujie Wang,Jiqing Ma,Zhihua Yin,Fei Liu,Yanzi Zang,Guan...It is hereby declared that the article entitled“miR-34c-3p Inhibits Nasopharyngeal Carcinoma Development via Inhibiting M2 Polarization of Macrophages”(Yuzi Ji,Yujie Wang,Jiqing Ma,Zhihua Yin,Fei Liu,Yanzi Zang,Guangke Wang,and Yong Tai),published in Biomedical and Environmental Sciences February 2025,Volume 38(2),Page 219-229.展开更多
Objective miR-34c-3p is down-regulated in nasopharyngeal carcinoma(NPC).The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study.Methods Flow cytometry and imm...Objective miR-34c-3p is down-regulated in nasopharyngeal carcinoma(NPC).The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study.Methods Flow cytometry and immunohistochemical staining were employed to detect cluster of differentiation 86(CD86)and cluster of differentiation 206(CD206)expression;quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were employed to examine mRNA expression and protein levels;cell counting kit-8(CCK8)and transwell assays were employed to assess cell proliferation,migration,and invasion;and hematoxylin-eosin(HE)staining was employed to assess pathological changes in tumor tissues.Results Our results revealed that the miR-34c-3p mimic markedly inhibited M2 polarization of macrophages by targeting SLC7A11,and M2 macrophages transfected with the miR-34c-3p mimic inhibited the proliferation,migration,and invasion of NPC cells.The in vivo experiments further confirmed that miR-34c-3p mimics blocked tumor growth and reduced inflammatory infiltration in tumor tissues.Conclusion This study provides novel insights into the pathogenesis of NPC and a new treatment strategy.展开更多
Introduction: Acute otitis media is an acute inflammation of the mucosa of the middle ear cavities. It is often secondary to nasopharyngitis, which favors the passage of infection through the Eustachian tube to the mi...Introduction: Acute otitis media is an acute inflammation of the mucosa of the middle ear cavities. It is often secondary to nasopharyngitis, which favors the passage of infection through the Eustachian tube to the middle ear. The aim of our study was to improve the management of AOM in the Paediatric Department of the Hospital National Ignace Deen (Conakry). Patients and Methods: This was a prospective descriptive study lasting 6 months from 01 July to 31 December 2011;the study covered 525 cases out of a total of 6276 children, i.e. a frequency of 8.36%. Results: The most affected age group was 6 to 11 months. Males predominated (69.71%). 82.29% had a history of recurrent rhinopharyngitis. The most frequent reason for consultation was incessant crying (66.29%). Rhinopharyngitis and malaria were the most commonly associated pathologies (87.62% and 39.62% respectively). 72.19% of our patients were admitted with congestive AOM and received medical treatment. We recorded one case of otomastoiditis which was treated surgically. Conclusion: AOM is more common in children aged between 6 and 24 months. Good collaboration between paediatricians and ENT specialists is essential to reduce the morbidity of AOM.展开更多
Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collect...Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital.The expression of MUC1 was measured by real-time quantitative PCR(qPCR)in the patients with PNC.The 5-8F and HNE1 cells were transfected with siRNA control(si-control)or siRNA targeting MUC1(si-MUC1).Cell proliferation was analyzed by cell counting kit-8 and colony formation assay,and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells.The qPCR and ELISA were executed to analyze the levels of TNF-αand IL-6.Western blot was performed to measure the expression of MUC1,NFкB and apoptosis-related proteins(Bax and Bcl-2).Results The expression of MUC1 was up-regulated in the NPC tissues,and NPC patients with the high MUC1 expression were inclined to EBV infection,growth and metastasis of NPC.Loss of MUC1 restrained malignant features,including the proliferation and apoptosis,downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells.Conclusion Downregulation of MUC1 restrained biological characteristics of malignancy,including cell proliferation and apoptosis,by inactivating NF-κB signaling pathway in NPC.展开更多
Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal c...Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA_Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43%(43/87),higher than that of conventional MRI(30/87,34.48%,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19%(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85%,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CNⅨ—ⅪPNS in jugular foramen(P<0.05)and CNⅨ—ⅫPNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P<0.05),of PNS of CNⅢ—Ⅴin cavernous sinus were higher than that of T2WI-FS(P<0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P<0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.展开更多
Nasopharyngeal carcinoma(NPC)has been a focus of medical research for more than 100 years,with significant interest emerging over the last 58 years following the identification of the link between the disease and Epst...Nasopharyngeal carcinoma(NPC)has been a focus of medical research for more than 100 years,with significant interest emerging over the last 58 years following the identification of the link between the disease and Epstein-Barr virus(EBV)infection.NPC possesses several distinctive characteristics among human cancers,notably its well-documented global epidemiology,which reveals localized high-incidence regions primarily in Southeast Asia,particularly in the Southern provinces of China near the Pearl river,as well as in Greenland and North Africa.Epidemiological data indicate a marked male predominance,early disease onset,and a nearly 100%prevalence of latent EBV infection in the tumors.Due to lack of consistent pattern of cancer-related mutations in NPC genomes and excessive DNA-methylation in the tumor cells,NPC can be considered"an epigenetic cancer".Despite extensive researches,convincing biological explanations for these unique characteristics remain elusive.Recently,suggestive evidence has been published that specific local variants of EBV may represent major high risk factors.In spite of tumor and virus specific immunity,it has not been possible to use this for improved treatment.Ongoing studies on the role of the local microflora and tumor microenvironment are essential for a comprehensive understanding of host-EBV-tumor interactions.Ultimately,this knowledge aims to enhance diagnosis,disease fractionation,treatment strategies,and potentially prevention of NPC.展开更多
Nasopharyngeal carcinoma(NPC)is a malignancy originating from the nasopharyngeal epithelial cells.Although some studies have identified potential biomarkers for early diagnosis of NPC based on metabolomics data(Chen e...Nasopharyngeal carcinoma(NPC)is a malignancy originating from the nasopharyngeal epithelial cells.Although some studies have identified potential biomarkers for early diagnosis of NPC based on metabolomics data(Chen et al.,2023;Zhou et al.,2023)and Epstein-Barr virus subtypes(Xu et al.,2019),their effectiveness and applicability need further investigation,particularly when consideringthe roles of oral microbiota.展开更多
Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the...Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis.Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines,correlating with worse disease-free and overall survival in NPC patients.Functional assays further elucidate the oncogenic role of PLD1,demonstrating its pivotal promotion of critical tumorigenic processes such as cellproliferation and migration in vitro,as well as tumor growth in vivo.Notably,our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression.Specifically,PLD1 enhances NF-kB activity by facilitating the phosphorylation and nuclear translocation of RELA,which in turn binds to the promoter of PLD1,augmenting its expression.Moreover,RELA over-expression markedly rescues the inhibitory effects in PLD1-depleted NPC cells.Importantly,the application of the PLD1 inhibitor,VU0155069,substantially inhibits NPC tumorigenesis in a patient-derived xenograft model.Together,our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.展开更多
Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(...Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(GBCA).Methods Fifty patients with pathologically confirmed nasopharyngeal carcinoma and received intensity-modulated radiotherapy were retrospectively enrolled as the nasopharyngeal carcinoma group,and 50 patients with other malignant tumors and without history of brain radiotherapy were retrospectively enrolled as the control group.All patients received yearly GBCA enhanced MR examinations for the nasopharynx or the head.T1WI signal intensities of the dentate nucleus and the pons on same plane were measured based on images in the year of confirmed diagnosis(recorded as the first year)and in the second to the fifth years.T1WI signal intensity ratio of year i(ranging from 1 to 5)was calculated with values of dentate nucleus divided by values of the pons(ΔSI i),while the percentage of relative changes of year j(ranging from 2 to 5)was calculated withΔSI j compared toΔSI 1(Rchange j).The values of these two parameters were compared,and the correlation ofΔSI and GBCA injection year-time was evaluated within each group.Results No significant difference of gender,age norΔSI 1 was found between groups(all P>0.05).The second to the fifth yearΔSI and Rchange in nasopharyngeal carcinoma group were all higher than those in control group(all P<0.05).Within both groups,ΔSI was positively correlated with GBCA injection year-time(both P<0.05).Conclusion Patients with nasopharyngeal carcinoma who underwent radiotherapy and multiple times of intravenous injection of GBCA tended to be found with gradually worsening GBCA deposition in dentate nucleus,for which radiotherapy might be a risk factor.展开更多
基金Supported by The Suzhou Medical Center,No.Szlcyxzx202103The National Natural Science Foundation of China,No.82171828+15 种基金The Key R and D Plan of Jiangsu Province(Development of Social),No.BE2021652The Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011The Wu Jieping Medical Foundation,No.320.6750.2021-01-12The Special Project of"Technological Innovation"Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001The Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113 and No.Y-XD202002/zb-0015The Beijing Bethune Charitable Foundation,No.STLKY0016The Research Projects of China Baoyuan Investment Co.Ltd,No.270004The Suzhou Gusu Health Talent Program,No.GSWS2022028The Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302The New Medical Technology Project of the Second Affiliated Hospital of Soochow University,No.23zl001The Multi-center Clinical Research Project for Major Diseases in Suzhou,No.DZXYJ202304The Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.SJCX24_1814The Gusu Health Talent Research Fund,No.GSWS2022053The National Natural Science Foundation of China,No.82102824The Scientific Research Program for Young Talents of China National Nuclear Corporation。
文摘BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and bone resorption,as well as their potential to modulate immune functions and thereby enhance the efficacy of programmed cell death protein 1(PD-1)inhibitor therapy.CASE SUMMARY We present a case of a patient with NPC who developed sternal stalk metastasis and multiple bone metastases with soft tissue invasion following radical chemoradiotherapy and targeted therapy.Prior to chemotherapy,the patient experienced severe bone marrow suppression and opted out of further chemotherapy sessions.However,the patient received combination therapy,including RANKL inhibitors(denosumab)alongside PD-1,radiotherapy,and granulocyte-macrophage colonystimulating factor(PRaG)therapy(NCT05435768),and achieved 16 months of progression-free survival and more than 35 months of overall survival,without encountering any grade 2 or higher treatment-related adverse events.CONCLUSION Denosumab combined with PRaG therapy could be a new therapeutic approach for the second-line treatment in patients with bone metastases.
基金supported by the Project of Administration of Traditional Chinese Medicine of Guangxi Zhuang Autonomous Region(grant number GZSY22-69)the Middle/Young aged Teachers’Research Ability Improvement Project of Guangxi Higher Education(grant number 2024KY0120).
文摘Objective:To investigate the chemical components of Semen podocarpi extract(SPE)and its effect on nasopharyngeal carcinoma cells and CNE-2R cells.Methods:Chemical components in SPE were identified by UPLC-MS/MS.CCK-8 and cell cloning experiments were applied to evaluate the effects of SPE on the proliferation of CNE-2R cells,and a single-hit multitarget model was used to calculate the radiobiological parameters.Cell apoptosis and cell cycle were analyzed by flow cytometry,and the levels of genes and proteins of the Raf/MEK/ERK pathway were determined by RT-PCR and Western blotting.Results:A total of 37 compounds from SPE were identified,and SPE with or without irradiation inhibited the proliferation of CNE-2R cells.SPE also promoted apoptosis,arrested cells in the G_(2)/M phase,and presented radiosensitizing effects.Compared with irradiation alone,the effects of SPE+irradiation on apoptosis and cell cycle distribution were not significantly different.In addition,SPE had no significant effect on MEK gene expression.SPE significantly increased the gene expression of C-Raf and significantly reduced the protein expression of C-Raf,as well as the gene and protein expression of ERK1 and ERK2.The protein levels of C-Raf,ERK1,and ERK2 were also significantly lower in cells treated with SPE+irradiation than in cells treated with irradiation alone.Conclusions:The effects of SPE on inhibiting cell proliferation and promoting apoptosis are likely associated with cell cycle arrest and Raf/MEK/ERK pathway regulation,and the mechanism underlying radiosensitization by SPE may involve downregulating the protein expression of C-Raf,ERK1,and ERK2.
基金supported by the National Natural Science Foundation(82261160657,82102490,and 81572781)the Guangdong Basic and Applied Basic Research Foundation(2024A1515013061)+2 种基金the Sci-Tech Project Foundation of Guangzhou City(2023A04J2141)Chang Jiang Scholars Program(J.-X.B.)the Hong Kong Research Grant Council(RGC)Theme-based Research Scheme Funds(T12-703/22-R and T12-703/23-N).
文摘Various genetic association studies have identified numerous single nucleotide polymorphisms(SNPs)associated with nasopharyngeal carcinoma(NPC)risk.However,these studies have predominantly focused on common variants,leaving the contribution of rare variants to the“missing heritability”largely unexplored.Here,we integrate genotyping data from 3925 NPC cases and 15,048 healthy controls to identify a rare SNP,rs141121474,resulting in a Glu510Lys mutation in KLHDC4 gene linked to increased NPC risk.Subsequent analyses reveal that KLHDC4 is highly expressed in NPC and correlates with poorer prognosis.Functional characterizations demonstrate that KLHDC4 acts as an oncogene in NPC cells,enhancing their migratory and metastatic capabilities,with these effects being further augmented by the Glu510Lys mutation.Mechanistically,the Glu510Lys mutant exhibits increased interaction with Vimentin compared to the wild-type KLHDC4(KLHDC4-WT),leading to elevated Vimentin protein stability and modulation of the epithelial-mesenchymal transition process,thereby promoting tumor metastasis.Moreover,Vimentin knockdown significantly mitigates the oncogenic effects induced by overexpression of both KLHDC4-WT and the Glu510Lys variant.Collectively,our findings highlight the critical role of the rare KLHDC4 variant rs141121474 in NPC progression and propose its potential as a diagnostic and therapeutic target for NPC patients.
文摘Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).A crucial question is whether concurrent chemo-radiotherapy(CCRT)could derive additional benefits to this recent“down-staging”subgroup of NPC patients.This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival(PFS)of stageⅡNPC treated with RT alone or CCRT.Methods:Imaging and clinical data of 166 stageⅡNPC(eighth edition AJCC/UICC)patients were collected.Data were allocated into training,internal testing,and external testing sets.For each case,851 radiomic features were extracted and 10 clinical features were collected.Radiomic and clinical features most associated with the 5-year PFS were selected separately.A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS.Model performances were evaluated by area under the receiver operating curve(AUC),prediction accuracy,and decision curve analysis.Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.Results:Thirteen radiomic features,three clinical features,and treatment option were considered for model development.The combined model showed higher prognostic performance than using either.For the merged testing set(internal and external testing sets),AUC is 0.76(combined)vs.0.56-0.80(clinical or radiomic alone)and accuracy is 0.75(combined)vs.0.62-0.73(clinical or radiomic alone).Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts(P<0.05).Conclusions:Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen,guiding individualized decisions of chemotherapy based on the predicted treatment outcome.
基金supported by the National Natural Science Foundation of China(no.81930072 and no.82172870 to J.Ma)by the Key-Area Research and Development Program of Guangdong Province(no.2019B020230002 to J.Ma).
文摘According to the International Cancer Research Institute of the World Health Organization data,nasopharyngeal carcinoma(NPC)remains a significant health concern,particularly in regions such as Southeast Asia and southern China.Recently,substantial progress has been made in the field of basic and translational research on NPC,enhancing our understanding of the molecular mechanisms underlying the disease and paving the way for precise therapeutic approaches.This review summarizes the advances in NPC research,focusing on key areas that include radiotherapy and chemotherapy resistance and tumor metastasis,microenvironment,metabolism,microbiome,and biomarkers.Additionally,future research directions in NPC are discussed to provide valuable insights to advance the field further.
基金supported by the Sanming Project of Medicine in Shenzhen (SZSM202211017)。
文摘Accurate cancer staging is the foundation of precision oncology and guides prognosis prediction and therapeutic decision-making. The conjoint TNM System by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) has served as the global standard for tumor classification since inception.
基金supported by grants from Science Research Foundation of Yunnan Education Bureau(No.2023Y0631)Yunnan Provincial Science and Technology Project(No.202303AP140005).
文摘Objective Histamine N-methyltransferase(HNMT)is involved primarily in histamine metabolism,but emerging evidence suggests its potential role in cancer progression.This study investigated the role of HNMT in nasopharyngeal carcinoma(NPC)and its impact on interferon(IFN)signaling,thioredoxin-interacting protein(TXNIP),and p53 tumor suppressor pathways.Methods HNMT expression in NPC tissues and cell lines was analyzed via qPCR and Western blotting.Functional assays,including cell proliferation,migration,invasion,and apoptosis,were performed after HNMT knockdown or overexpression.Transcriptomic sequencing was used to identify differentially expressed genes(DEGs).In addition,we examined the relationship between HNMT and the IFN/TXNIP/p53 axis via rescue experiments in vitro and in vivo models via qPCR and Western blotting.Results HNMT knockdown reduced cell proliferation,migration,and invasion,and promoted apoptosis in NPC tissues and cell lines.TXNIP was the most significantly upregulated gene following HNMT knockdown.Inhibition of the IFN pathway reversed these effects,confirming the role of HNMT in downregulating the IFN/TXNIP/p53 pathway.An in vivo study revealed that HNMT overexpression correlated with reduced expression of TXNIP and p53 in NCG mice.Conclusion In NPC,HNMT promotes tumor growth and progression by inhibiting the IFN/TXNIP/p53 axis.These findings suggest that targeting the HNMT axis or restoring its function could provide new therapeutic strategies for NPC.
基金Supported by Beijing Bethune Charitable Foundation and Provincial Natural Science Foundation of Liaoning,No.2022-MS-190.
文摘BACKGROUND Circulating tumor DNA(ctDNA)-based liquid biopsy has been found to be effective for the detection of minimal residual disease and the evaluation of prognostic risk in various solid tumors,with good sensitivity and specificity for identifying patients at high risk of recurrence.However,use of its results as a biomarker for guiding the treatment and predicting the prognosis of naso-pharyngeal carcinoma(NPC)has not been reported.CASE SUMMARY In this case study of a patient with stage IVb NPC,we utilized ctDNA as an independent biomarker to guide treatment.Chemotherapy was administered in the early stages of the disease,and local intensity-modulated radiation therapy was added when the patient tested positive for ctDNA,while radiation therapy was stopped and the patient was observed when the ctDNA test was negative.During the follow-up period,ctDNA signals became positive before tumor progression and became negative again at the end of treatment.We also explored the potential of ctDNA in combination with Epstein-Barr virus(EBV)DNA status to predict the prognosis of NPC patients,as well as the criteria for selecting genetic mutations and the testing cycle for ctDNA analysis.CONCLUSION The results of ctDNA-based liquid biopsy can serve as an independent biomarker,either independently or in conjunction with EBV DNA status,to guide the treatment and predict the prognosis of NPC.
文摘It is hereby declared that the article entitled“miR-34c-3p Inhibits Nasopharyngeal Carcinoma Development via Inhibiting M2 Polarization of Macrophages”(Yuzi Ji,Yujie Wang,Jiqing Ma,Zhihua Yin,Fei Liu,Yanzi Zang,Guangke Wang,and Yong Tai),published in Biomedical and Environmental Sciences February 2025,Volume 38(2),Page 219-229.
文摘Objective miR-34c-3p is down-regulated in nasopharyngeal carcinoma(NPC).The biological role of miR-34c-3p in NPC and its underlying mechanisms are unknown and were explored in this study.Methods Flow cytometry and immunohistochemical staining were employed to detect cluster of differentiation 86(CD86)and cluster of differentiation 206(CD206)expression;quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were employed to examine mRNA expression and protein levels;cell counting kit-8(CCK8)and transwell assays were employed to assess cell proliferation,migration,and invasion;and hematoxylin-eosin(HE)staining was employed to assess pathological changes in tumor tissues.Results Our results revealed that the miR-34c-3p mimic markedly inhibited M2 polarization of macrophages by targeting SLC7A11,and M2 macrophages transfected with the miR-34c-3p mimic inhibited the proliferation,migration,and invasion of NPC cells.The in vivo experiments further confirmed that miR-34c-3p mimics blocked tumor growth and reduced inflammatory infiltration in tumor tissues.Conclusion This study provides novel insights into the pathogenesis of NPC and a new treatment strategy.
文摘Introduction: Acute otitis media is an acute inflammation of the mucosa of the middle ear cavities. It is often secondary to nasopharyngitis, which favors the passage of infection through the Eustachian tube to the middle ear. The aim of our study was to improve the management of AOM in the Paediatric Department of the Hospital National Ignace Deen (Conakry). Patients and Methods: This was a prospective descriptive study lasting 6 months from 01 July to 31 December 2011;the study covered 525 cases out of a total of 6276 children, i.e. a frequency of 8.36%. Results: The most affected age group was 6 to 11 months. Males predominated (69.71%). 82.29% had a history of recurrent rhinopharyngitis. The most frequent reason for consultation was incessant crying (66.29%). Rhinopharyngitis and malaria were the most commonly associated pathologies (87.62% and 39.62% respectively). 72.19% of our patients were admitted with congestive AOM and received medical treatment. We recorded one case of otomastoiditis which was treated surgically. Conclusion: AOM is more common in children aged between 6 and 24 months. Good collaboration between paediatricians and ENT specialists is essential to reduce the morbidity of AOM.
文摘Objective To investigate the effect of mucin 1(MUC1)on the proliferation and apoptosis of nasopharyngeal carcinoma(NPC)and its regulatory mechanism.Methods The 60 NPC and paired para-cancer normal tissues were collected from October 2020 to July 2021 in Quanzhou First Hospital.The expression of MUC1 was measured by real-time quantitative PCR(qPCR)in the patients with PNC.The 5-8F and HNE1 cells were transfected with siRNA control(si-control)or siRNA targeting MUC1(si-MUC1).Cell proliferation was analyzed by cell counting kit-8 and colony formation assay,and apoptosis was analyzed by flow cytometry analysis in the 5-8F and HNE1 cells.The qPCR and ELISA were executed to analyze the levels of TNF-αand IL-6.Western blot was performed to measure the expression of MUC1,NFкB and apoptosis-related proteins(Bax and Bcl-2).Results The expression of MUC1 was up-regulated in the NPC tissues,and NPC patients with the high MUC1 expression were inclined to EBV infection,growth and metastasis of NPC.Loss of MUC1 restrained malignant features,including the proliferation and apoptosis,downregulated the expression of p-IкB、p-P65 and Bcl-2 and upregulated the expression of Bax in the NPC cells.Conclusion Downregulation of MUC1 restrained biological characteristics of malignancy,including cell proliferation and apoptosis,by inactivating NF-κB signaling pathway in NPC.
文摘Objective To observe the value of isotropic volumetric MRI for displaying perineural spread(PNS)of cranial nerve(CN)in nasopharyngeal carcinoma.Methods Eighty-seven patients with pathologically proven nasopharyngeal carcinoma were prospectively enrolled.MR scanning,including three-dimensional liver acquisition with volume acceleration-flexible(3D LAVA_Flex)image,T2WI with fat suppression(T2WI-FS),T1WI,contrast enhancement(CE)T1WI-FS of nasopharynx and neck region were performed.The displaying rates of CN PNS were evaluated and compared between 3D LAVA_Flex and T2WI-FS,T1WI,CE-T1WI-FS at patient level,CN group level and neural level,respectively.Results The displaying rate of CN PNS in all 87 nasopharyngeal carcinoma patients by 3D LAVA_Flex sequence was 49.43%(43/87),higher than that of conventional MRI(30/87,34.48%,P=0.001).Among 59 patients with advanced nasopharyngeal carcinoma diagnosed with conventional sequences,the displaying rate of CN PNS was 71.19%(42/59)by 3D LAVA-Flex sequence,higher than that of conventional MRI(30/59,50.85%,P=0.001).At both patient level and posterior CN level,significant differences of the displaying rate of CN PNS were found between 3D LAVA-Flex sequence and T2WI-FS,T1WI,CE-T1WI-FS,while at CN level,the displaying rates of mandibular nerve PNS,CNⅨ—ⅪPNS in jugular foramen(P<0.05)and CNⅨ—ⅫPNS in carotid space of 3D LAVA_Flex sequence were all significantly higher than that of T2WI-FS,T1WI and CE-T1WI-FS(all P<0.05),of PNS of CNⅢ—Ⅴin cavernous sinus were higher than that of T2WI-FS(P<0.05),while of PNS of hypoglossal nerve were significantly higher than that of T2WI-FS and T1WI(both P<0.05).Conclusion 3D LAVA_Flex sequence could be used to effectively display CN PNS of nasopharyngeal carcinoma.
文摘Nasopharyngeal carcinoma(NPC)has been a focus of medical research for more than 100 years,with significant interest emerging over the last 58 years following the identification of the link between the disease and Epstein-Barr virus(EBV)infection.NPC possesses several distinctive characteristics among human cancers,notably its well-documented global epidemiology,which reveals localized high-incidence regions primarily in Southeast Asia,particularly in the Southern provinces of China near the Pearl river,as well as in Greenland and North Africa.Epidemiological data indicate a marked male predominance,early disease onset,and a nearly 100%prevalence of latent EBV infection in the tumors.Due to lack of consistent pattern of cancer-related mutations in NPC genomes and excessive DNA-methylation in the tumor cells,NPC can be considered"an epigenetic cancer".Despite extensive researches,convincing biological explanations for these unique characteristics remain elusive.Recently,suggestive evidence has been published that specific local variants of EBV may represent major high risk factors.In spite of tumor and virus specific immunity,it has not been possible to use this for improved treatment.Ongoing studies on the role of the local microflora and tumor microenvironment are essential for a comprehensive understanding of host-EBV-tumor interactions.Ultimately,this knowledge aims to enhance diagnosis,disease fractionation,treatment strategies,and potentially prevention of NPC.
基金supported by the National Key R&D Program of China(2022YFA1204000 to T.D.)the Guangdong Key Area Research and Development Program(2019B020228001 to T.D.)the National Natural Science Foundation of China(81971906 to T.D.).
文摘Nasopharyngeal carcinoma(NPC)is a malignancy originating from the nasopharyngeal epithelial cells.Although some studies have identified potential biomarkers for early diagnosis of NPC based on metabolomics data(Chen et al.,2023;Zhou et al.,2023)and Epstein-Barr virus subtypes(Xu et al.,2019),their effectiveness and applicability need further investigation,particularly when consideringthe roles of oral microbiota.
基金This work was supported by the Guangdong Basic and Applied Basic Research Foundation(2024A1515013061)the Sci-Tech Project Foundation of Guangzhou City(2023A04J2141)+2 种基金National Natural Science Foundation(82261160657)Chang Jiang Scholars Program(J.-X.B.)Special Support Program of Guangdong(J.-X.B.)。
文摘Phospholipase D(PLD)lipid-signaling enzyme superfamily has been widely implicated in various human malignancies,but its role and underlying mechanism remain unclear in nasopharyngeal carcinoma(NPC).Here,we analyze the expressions of 6 PLD family members between 87 NPC and 10 control samples through transcriptome analysis.Our findings reveal a notable upregulation of PLD1 in both NPC tumors and cell lines,correlating with worse disease-free and overall survival in NPC patients.Functional assays further elucidate the oncogenic role of PLD1,demonstrating its pivotal promotion of critical tumorigenic processes such as cellproliferation and migration in vitro,as well as tumor growth in vivo.Notably,our study uncovers a positive feedback loop between PLD1 and the NF-κB signaling pathway to render NPC progression.Specifically,PLD1 enhances NF-kB activity by facilitating the phosphorylation and nuclear translocation of RELA,which in turn binds to the promoter of PLD1,augmenting its expression.Moreover,RELA over-expression markedly rescues the inhibitory effects in PLD1-depleted NPC cells.Importantly,the application of the PLD1 inhibitor,VU0155069,substantially inhibits NPC tumorigenesis in a patient-derived xenograft model.Together,our findings identify PLD1/NF-κB signaling as a positive feedback loop with promising therapeutic and prognostic potential in NPC.
文摘Objective To observe changes of plain MR T1WI signal intensity of dentate nucleus in nasopharyngeal carcinoma patients after radiotherapy and multiple times of intravenous injection of gadolinium-based contrast agent(GBCA).Methods Fifty patients with pathologically confirmed nasopharyngeal carcinoma and received intensity-modulated radiotherapy were retrospectively enrolled as the nasopharyngeal carcinoma group,and 50 patients with other malignant tumors and without history of brain radiotherapy were retrospectively enrolled as the control group.All patients received yearly GBCA enhanced MR examinations for the nasopharynx or the head.T1WI signal intensities of the dentate nucleus and the pons on same plane were measured based on images in the year of confirmed diagnosis(recorded as the first year)and in the second to the fifth years.T1WI signal intensity ratio of year i(ranging from 1 to 5)was calculated with values of dentate nucleus divided by values of the pons(ΔSI i),while the percentage of relative changes of year j(ranging from 2 to 5)was calculated withΔSI j compared toΔSI 1(Rchange j).The values of these two parameters were compared,and the correlation ofΔSI and GBCA injection year-time was evaluated within each group.Results No significant difference of gender,age norΔSI 1 was found between groups(all P>0.05).The second to the fifth yearΔSI and Rchange in nasopharyngeal carcinoma group were all higher than those in control group(all P<0.05).Within both groups,ΔSI was positively correlated with GBCA injection year-time(both P<0.05).Conclusion Patients with nasopharyngeal carcinoma who underwent radiotherapy and multiple times of intravenous injection of GBCA tended to be found with gradually worsening GBCA deposition in dentate nucleus,for which radiotherapy might be a risk factor.
