Oral squamous cell carcinoma(OSCC)is a prevalent malignancy with high morbidity and mortality.Globally,about 400000 people are affected,often with a poor quality of life.Its high mortality is mainly due to its aggress...Oral squamous cell carcinoma(OSCC)is a prevalent malignancy with high morbidity and mortality.Globally,about 400000 people are affected,often with a poor quality of life.Its high mortality is mainly due to its aggressive growth and tendency to spread.Epithelial-mesenchymal transition(EMT)is a central regulatory hub driving tumor cell migration and invasion by enabling changes in cell characteristics.During EMT,epithelial cells gradually take on mesenchymal traits,gaining mobility and spreading mo re easily.Recent multi-omics studies show that many cancer cells exist in a hybrid or partial-EMT state,which lies between the full epithelial and mesenchymal forms.Cells in this state are especially invasive and metastatic,with high plasticity that promotes tumor progression.This review summarizes the role of partial-EMT in OSCC,with a focus on how it alters the tumor microenvironment(TME),promotes invasion and metastasis,and influences cancer stem cells(CSCs).We also highlight the link between partial-EMT and treatment resistance in OSCC.Based on these insights,we discuss therapeutic strategies targeting partial-EMT to improve outcomes.Targeting partial-EMT may offer promising strategies to enhance treatment effectiveness and improve patient survival and quality of life.展开更多
Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-202 Promotes Cell Apoptosis in Esophageal Squamous Cell Carcinoma by Targeting HSF2”has been retracted from Oncology Rese...Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-202 Promotes Cell Apoptosis in Esophageal Squamous Cell Carcinoma by Targeting HSF2”has been retracted from Oncology Research,Vol.25,No.2,2017,pp.215-223.DOI:10.3727/096504016X14732772150541 URL:https://www.techscience.com/or/v25n2/56800.展开更多
This letter addresses challenges in the clinical translation of BIBR1532,a promising telomerase inhibitor,for the treatment of esophageal squamous cell carcinoma(ESCC).BIBR1532 exerts its anti-cancer effect by activat...This letter addresses challenges in the clinical translation of BIBR1532,a promising telomerase inhibitor,for the treatment of esophageal squamous cell carcinoma(ESCC).BIBR1532 exerts its anti-cancer effect by activating DNA damage response(ATR/CHK1 and ATM/CHK2)pathways and downregulating telomere-binding proteins.Although its therapeutic potential is limited by poor aqueous solubility,solid dispersion(SD)technology may overcome this obstacle.Systematic analysis using PubChem-derived simplified molecular input line entry system identifiers and artificial intelligence-driven FormulationDT platform evaluation(oral formulation feasibility index:0.38)revealed that the SD technology,with superior scalability(32 approved products by 2021)and lower production risks,outperforms lipid-based formulations as an optimal dissolution strategy.Material analysis revealed hydroxypropyl methylcellulose(HPMC)as the optimal carrier with lower hygroscopicity,higher temperature and no intestinal targeting,thus enabling ESCC therapy.HPMC-based SD enhances BIBR1532 solubility and bioavailability for effective ESCC treatment.Future studies should focus on pilot tests for SD fabrication.展开更多
Cutaneous squamous cell carcinoma(CSCC)is the second most common type of skin cancer and typically involves the head and neck.Systemic therapy is often required for patients with advanced CSCC to achieve optimal disea...Cutaneous squamous cell carcinoma(CSCC)is the second most common type of skin cancer and typically involves the head and neck.Systemic therapy is often required for patients with advanced CSCC to achieve optimal disease control.Immune checkpoint inhibitors(ICIs)are now the standard of care for these patients,with a 50%-60%response rate and sustainable remission for at least 30%of patients.Given the activity of ICIs in advanced head and neck CSCC,ICIs are being studied in early-stage disease or neoadjuvant situations.The purpose of this review is to provide an overview of the innovative perioperative strategies in resectable disease and discuss novel immunotherapeutic strategies designed to overcome treatment resistance.In conclusion,neoadjuvant ICIs have demonstrated impressive response rates with unclear survival benefit.The effectiveness of adjuvant ICIs is currently being explored.Emerging biomarkers,such as circulating tumor DNA(ctDNA),will be crucial for optimizing patient selection and improving treatment outcomes.展开更多
This narrative review examines recent advances in salivary biomarkers for oral squamous cell carcinoma(OSCC),a major subtype of oral cancer with persistently low five-year survival rates due to delayed diagnosis.Saliv...This narrative review examines recent advances in salivary biomarkers for oral squamous cell carcinoma(OSCC),a major subtype of oral cancer with persistently low five-year survival rates due to delayed diagnosis.Saliva has emerged as a noninvasive diagnostic medium capable of reflecting both local tumor activity and systemic physiological changes.Various salivary biomarkers,including microRNAs,cytokines,proteins,metabolites,and exosomes,have been linked to oncogenic signaling pathways involved in tumor progression,immune modulation,and therapeutic resistance.Advances in quantitative polymerase chain reaction,mass spectrometry,and next-generation sequencing have enabled comprehensive biomarker profiling,while point-of-care detection systems and saliva-based omics platforms are accelerating clinical translation.Remaining challenges include variability in salivary composition,lack of standardized collection protocols,and insufficient validation across large patient cohorts.This review highlights the mechanistic relevance,diagnostic potential,and translational challenges of salivary biomarkers in OSCC.展开更多
Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanism...Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC.Methods:Bioinformatics analysis was performed utilizing single-cell RNA-seq,bulk RNA-seq,and histone H3 lysine 27 acetylation(H3K27ac)Chromatin Immunoprecipitation(ChIP)-seq data obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4(ELK4)to the dihydrofolate reductase(DHFR)enhancer.In vitro VM formation and invasion of OSCC cells were assessed using Matrigel-based tube formation and Transwell assays,respectively.Results:Elevated expression of VM-related genes predicts unfavorable prognosis in OSCC patients.High-dimensional weighted gene co-expression network analysis(hdWGCNA)identified epithelial subcluster C4 as most strongly associated with VM and metastasis.Three co-expression modules within this subcluster exhibited significant positive correlations with both phenotypic traits.Among the 30 eigengenes from the three modules,DHFR emerged as a key regulator of VM and metastasis.Knockdown or inhibition of DHFR significantly suppressed VM formation and invasion in OSCC cells.Mechanistically,ELK4 activated DHFR transcription through direct binding to its enhancer.DHFR overexpression rescued VM and invasion impairment induced by ELK4 knockdown.Conclusion:DHFR was a pivotal enhancer-regulated gene driving VM and metastasis in OSCC.ELK4 directly binds to DHFR enhancer regions to activate its transcription,thereby promoting these malignant phenotypes.These findings identified the ELK4/DHFR axis as a promising therapeutic target for anti-angiogenic intervention in OSCC.展开更多
Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognost...Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognostic biomarker in LA-LSCC.Methods:miR-449a expression was analyzed in tumor tissues,adjacent normal tissues,and serum from 81 LA-LSCC patients and 50 controls using quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).We assessed the diagnostic accuracy by Receiver Operating Characteristic curve(ROC curves),clinicopathological associations,survival outcomes(Kaplan-Meier),and treatment response dynamics.Results:miR-449a was significantly downregulated in LA-LSCC tissues(p<0.0001)and serum(p<0.0001),with a strong tissue-serum correlation(R^(2)=0.988).Tissue miR-449a demonstrated a diagnostic accuracy(Area Under the Curve,AUC=0.857),while serum showed moderate accuracy(AUC=0.734).High miR-449a expression correlated with favorable clinicopathological features and improved survival(median overall survival:67.82 vs.23.74 months;p=0.0012).Multivariate analysis confirmed miR-449a as an independent prognostic factor(p<0.001).miR-449a levels increased post-treatment,particularly in responders to chemotherapy/radiation(p<0.0001).Conclusion:miR-449a serves as a non-invasive biomarker for LA-LSCC diagnosis,prognosis,and treatment monitoring.Its dynamic expression highlights potential for risk stratification and therapy response prediction,warranting further validation in larger cohorts.展开更多
Objective The aim of this study was to analyze the correlation between the levels of 12 cytokines in the cervical microenvironment and cervical intraepithelial neoplasia in patients with high-risk human papillomavirus...Objective The aim of this study was to analyze the correlation between the levels of 12 cytokines in the cervical microenvironment and cervical intraepithelial neoplasia in patients with high-risk human papillomavirus(HR-HPV)infection.Methods Female patients(n=73)with HR-HPV infection were enrolled and divided into a high-grade squamous intraepithelial lesion(HSIL)group(n=33)and a non-HSIL(N-HSIL)group(n=40),which include low-grade squamous intraepithelial lesions and inflammation.Healthy screening subjects(n=31)with negative HR-HPV results were enrolled as a control group.We examined contemporaneous plasma and secretory cytokines from 25 study subjects to investigate the difference between systemic cytokine profiles and the local microenvironment immunity using the Wilcoxon matched-pairs signed rank test.The 12 cytokines from cervical secretions were compared between the three groups using the Mann-Whitney test,and logistic regression was used to analyze HSIL and N-HSIL.Results There were statistical differences in eight cytokines(IL-2,IL-6,TNF-α,IFN-γ,IL-1β,IL-12p70,IFN-α,and IL-8)between cervical secretion and plasma of the same patient,and seven cytokines were statistically different between the control and other two groups.We selected four independent variables(TNF-α,IFN-γ,IL-12p70,and IFN-α)commonly identified by univariate regression analysis and non-parametric tests for multivariate logistic regression analysis.Based on this model,HSIL could be predicted in patients with HR-HPV infection,with the area under the curve being 0.76.Conclusion The systemic cytokine profile cannot reflect the local microenvironment immunity,and the occurrence of HSIL is related to the cytokine levels in the cervical microenvironment.展开更多
The presence of a positive deep surgical margin in tongue squamous cell carcinoma(TSCC)significantly elevates the risk of local recurrence.Therefore,a prompt and precise intraoperative assessment of margin status is i...The presence of a positive deep surgical margin in tongue squamous cell carcinoma(TSCC)significantly elevates the risk of local recurrence.Therefore,a prompt and precise intraoperative assessment of margin status is imperative to ensure thorough tumor resection.In this study,we integrate Raman imaging technology with an artificial intelligence(AI)generative model,proposing an innovative approach for intraoperative margin status diagnosis.This method utilizes Raman imaging to swiftly and non-invasively capture tissue Raman images,which are then transformed into hematoxylin-eosin(H&E)-stained histopathological images using an AI generative model for histopathological diagnosis.The generated H&E-stained images clearly illustrate the tissue’s pathological conditions.Independently reviewed by three pathologists,the overall diagnostic accuracy for distinguishing between tumor tissue and normal muscle tissue reaches 86.7%.Notably,it outperforms current clinical practices,especially in TSCC with positive lymph node metastasis or moderately differentiated grades.This advancement highlights the potential of AI-enhanced Raman imaging to significantly improve intraoperative assessments and surgical margin evaluations,promising a versatile diagnostic tool beyond TSCC.展开更多
Dear Editor,Local recurrence and cervical lymph node metastases are major causes of mortality in patients with head and neck squamous cell carcinoma(HNSCC).To date,none of the proposed strategies for predicting outcom...Dear Editor,Local recurrence and cervical lymph node metastases are major causes of mortality in patients with head and neck squamous cell carcinoma(HNSCC).To date,none of the proposed strategies for predicting outcomes in this disease have proven fully effective,and a comprehensive physical examination remains the primary method for early detection and monitoring of HNSCC.展开更多
Dear Editor,This letter proposes an end-to-end feature disentangled Transformer(FDTs)for entanglement-free and semantic feature representation to enable accurate and trustworthy pathology grading of squamous cell carc...Dear Editor,This letter proposes an end-to-end feature disentangled Transformer(FDTs)for entanglement-free and semantic feature representation to enable accurate and trustworthy pathology grading of squamous cell carcinoma(SCC).Existing vision transformers(ViTs)can implement representation learning for SCC grading,however,they all adopt the class-patch token fuzzy mapping for pattern prediction probability or window down-sampling to enhance the representation to contextual information.展开更多
Dear Editor,Esophageal cancer(EC)is a malignant tumor originating from esophageal epithelium and remains a leading cause of cancer incidence and mortality worldwide1,2.According to the 2020 World Health Organization s...Dear Editor,Esophageal cancer(EC)is a malignant tumor originating from esophageal epithelium and remains a leading cause of cancer incidence and mortality worldwide1,2.According to the 2020 World Health Organization statistics,there were approx-imately 604,000 new EC cases and 544,000 EC-related deaths globally with China reporting approximately 320,000 new cases and 300,000 deaths,mainly from esophageal squamous cell carcinoma(ESCC)3.Although there has been progress in the treatment of EC,the long-term prognosis of patients with R0 resection and lymph node-positive disease contin-ues to be suboptimal4.A retrospective analysis performed by our center suggested that the median overall survival(OS)of lymph node-positive patients with EC who received postoper-ative adjuvant radiotherapy(PART)was 29 months compared to 21 months for surgery alone with 3-year survival rates of 43%and 36%,respectively,indicating a potential survival ben-efit of PART5.展开更多
AIM:To investigate the pathological features of ocular surface squamous neoplasia(OSSN)and evaluate the synergistic therapeutic effects of interferon-α2b(IFNα2b)and 5-fluorouracil(5-FU)on cellular proliferation,migr...AIM:To investigate the pathological features of ocular surface squamous neoplasia(OSSN)and evaluate the synergistic therapeutic effects of interferon-α2b(IFNα2b)and 5-fluorouracil(5-FU)on cellular proliferation,migration,apoptosis,and cell cycle of human oral squamous carcinoma cell line Cal27.METHODS:Tissue specimens from OSSN were processed with hematoxylin-eosin(HE)and immunofluorescence(IF)staining to characterize pathological changes.We analyzed the expression levels of four pivotal proteins involved in 5-FU metabolism:interferon alpha receptor(IFNAR),thymidylate synthase(TS),thymidine phosphorylase(TP),and dihydropyrimidine dehydrogenase(DPD).Cal27 cell lines were treated with a spectrum of concentrations of IFNα2b and 5-FU,either in isolation or in combination.Then,cell activity was measured utilizing CCK-8 assay and dose-effect curves were calculated,while tumor cell migration was detected by cell scratch experiments.Cal27 cells were added with IFNα2b and 5-FU in a non-constant ratio drug combination design and the corresponding combination index(CI)and fraction affected(Fa)were calculated with CompuSyn software.Western blot assay was conducted to quantify the expression of TP,TS,and DPD.Cell cycle and apoptosis were measured with flow cytometry and terminal deoxynucleotidyl transferasemediated dUTP nick and labeling(TUNEL)assay.RESULTS:Treatment with both IFNα2b and 5-FU inhibited cell proliferation.Except for the lowest and highest doses of 5-FU,CI values for all other groups were below 1,suggesting a synergistic interaction.Low concentrations of IFNα2b and 5-FU both diminished the relative mobility of Cal27 cells,instead,a stronger inhibitory effect was observed when the two drugs were co-applied.The expression levels of TP and DPD in Cal27 cells were dose-dependently increased at a low concentration of IFNα2b.Low-dose IFNα2b combined with 5-FU significantly inhibited cell proliferation in G0/G1 phase compared to 5-FU monotherapy.Medium and high doses of IFNα2b and all concentrations of 5-FU could induce apoptosis in a concentration-dependent manner.The susceptibility to 5-FU treatment and apoptosis rates of tumor cells were elevated with low doses of IFNα2b.CONCLUSION:Both IFNα2b and 5-FU,when administered individually or in combination,effectively suppress the proliferation and migration of Cal27 tumor cells,induce cell apoptosis and arrest cell cycle.Low doses of IFNα2b increase the antitumor effects of 5-FU on Cal27 potentially through up-regulating the expression of TP,demonstrating a synergistic effect between IFNα2b and 5-FU.展开更多
AIM:To evaluate the demographics,clinical characteristics,treatments,and outcomes of patients with ocular surface squamous neoplasia(OSSN)at the Philippine General Hospital.METHODS:This was a single-center,11-year ret...AIM:To evaluate the demographics,clinical characteristics,treatments,and outcomes of patients with ocular surface squamous neoplasia(OSSN)at the Philippine General Hospital.METHODS:This was a single-center,11-year retrospective,cross sectional case series on 18 cases of OSSN seen between January 2012 to June 2023.The patient’s demographics,presenting symptoms,tumor characteristics,histopathologic diagnosis,treatment,outcomes,and duration of follow-up were reviewed.RESULTS:Out of 33 identified cases of OSSN,only 18 were eligible for inclusion in the study.Mean age was 60.78y(range 31 to 80),with male predominance(66.67%).The left eye was most commonly affected(61.11%)with most presenting with fleshy mass(83.33%).Most tumors were located nasally(66.67%)and were predominantly papilliform(44.44%)in morphology with associated hyperpigmentation(38.89%).Squamous cell carcinoma(SCCA)was the most common histopathologic diagnosis(72.22%).The main primary treatment was surgical excision(94.44%)with or without adjunctive therapy,with only 1 patient undergoing first-line topical chemotherapy.Only 3 recurrences(16.67%)were noted with a median followup of 7.5mo.A statistically significant recurrence-free odds leaning towards the utilization of cryotherapy was noted.CONCLUSION:OSSN seen at the Philippine General Hospital is presented as a limbal papilliform mass,most commonly affecting elderly males.Surgical excision with adjuvant cryotherapy and/or chemotherapy is the preferred mode of treatment.展开更多
BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanis...BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.展开更多
BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis th...BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.展开更多
BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors...BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors is their penetration of neighboring tissues,such as lymphatic and blood arteries,due to the tumor cells'capacity to break down the extracellular matrix(ECM).Matrix metalloproteinases(MMPs)constitute a family of proteolytic enzymes that facilitate tissue remodeling and the degradation of the ECM.MMP-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific functions.MMP-13,a collagenase family member,is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens,whereas MMP-9 is thought to accelerate the growth of tumors.Elevated MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant cases.AIM To assess the immunohistochemical expression of MMP-9 and MMP-13 in OSCC.METHODS A total of 40 cases with histologically confirmed OSCC by incisional biopsy were included in this cross-sectional retrospective study.The protocols for both MMP-9 and MMP-13 immunohistochemical staining were performed according to the manufacturer’s recommendations along with the normal gingival epithelium as a positive control.All the observations were recorded and Pearson’sχ²test with Fisher exact test was used for statistical analysis.RESULTS Our study showed no significant correlation between MMP-9 and MMP-13 staining intensity and tumor size.The majority of the patients were in advanced TNM stages(III and IV),and showed intense expression of MMP-9 and MMP-13.CONCLUSION The present study suggests that both MMP-9 and MMP-13 play an important and independent role in OSCC progression and invasiveness.Intense expression of MMP-9 and MMP-13,irrespective of histological grade of OSCC,correlates well with TNM stage.Consequently,it is evident that MMP-9 and MMP-13 are important for the invasiveness and progression of tumors.The findings may facilitate the development of new approaches for evaluating lymph node metastases and interventional therapy techniques,hence enhancing the prognosis of patients diagnosed with OSCC.展开更多
OBJECTIVE:To uncover the biological foundation of the prevailing TCM syndrome in individuals with Esophageal squamous cell carcinoma(ESCC),Zhengxu Xieshi(ZXXS),which is characterized by a deficiency in vital Qi and an...OBJECTIVE:To uncover the biological foundation of the prevailing TCM syndrome in individuals with Esophageal squamous cell carcinoma(ESCC),Zhengxu Xieshi(ZXXS),which is characterized by a deficiency in vital Qi and an excess in evil Qi.METHODS:We investigated shifts in vital Qi by quantifying systemic metabolic changes in the peripheral blood.Serum metabolomic profiling was conducted on the ESCC cohort 1 along with a matched healthy control cohort.Additionally,we assessed changes in evil Qi by examining metabolic perturbations in ESCC tissues.This analysis involved metabolomic and proteomic surveys of ESCC tissues and paired normal adjacent tissues as controls in an independent ESCC cohort 2.RESULTS:Serum metabolomic profiling highlighted the prevalent downregulation of differentially expressed metabolites in patient sera,in contrast to the upregulation observed in ESCC tissues,compared to their respective controls.Remarkably,the group of differential metabolites in the ESCC tissues was predominantly composed of amino acids.Thus,we focused on amino acid metabolism.Our integrative analysis showed the downregulation of a significant majority of disturbed amino acids in patient sera relative to the upregulation of an overwhelming proportion of perturbed amino acids within ESCC tissues.Enrichment analysis of these amino acids revealed seven metabolic pathways that contribute to the metabolism of antioxidants,energy intermediates,and biosynthetic precursors.Interestingly,these pathways displayed attenuation in patient sera but augmentation in ESCC tissues.Similarly,the proteomic data confirmed the activation of these pathways in ESCC tissues.CONCLUSION:This study presents a new perspective on the prevalence of ZXXS syndrome in patients with ESCC,contextualized within the realm of metabolic reprogramming.Specifically,diminished amino acid metabolism in the circulating blood corresponds to a deficiency in vital Qi.Conversely,hyperactive amino acid metabolism in ESCC tissues signifies an augmentation of local evil Qi.These findings hold potential to enrich the current medical framework and offer a deeper understanding of ESCC management by integrating the principles of ZXXS syndrome.展开更多
BACKGROUND Early detection of esophageal squamous neoplasms(ESN)is essential for improving patient prognosis.Optical diagnosis of ESN remains challenging.Probebased confocal laser endomicroscopy(pCLE)enables accurate ...BACKGROUND Early detection of esophageal squamous neoplasms(ESN)is essential for improving patient prognosis.Optical diagnosis of ESN remains challenging.Probebased confocal laser endomicroscopy(pCLE)enables accurate in vivo histological observation and optical biopsy of ESN.However,interpretation of pCLE images requires histopathological expertise and extensive training.Artificial intelligence(AI)has been widely applied in digestive endoscopy;however,AI for pCLE diagnosis of ESN has not been reported.AIM To develop a pCLE computer-aided diagnostic system for ESN and assess its diagnostic performance and assistant efficiency for nonexpert endoscopists.METHODS The intelligent confocal laser endomicroscopy(iCLE)system consists of image recognition(based on inception-ResNet V2),video diagnosis,and quality judgment modules.This system was developed using pCLE images and videos and evaluated through image and prospective video recognition tests.Patients between June 2020 and January 2023 were prospectively enrolled.Expert and nonexpert endoscopists and the iCLE independently performed diagnoses for pCLE videos,with histopathology as the gold standard.Thereafter,the non-expert endoscopists performed a second assessment with iCLE assistance.RESULTS A total of 25056 images from 2803 patients were selected for iCLE training and validation.Another 2442 images from 226 patients were used for testing.iCLE achieved a high accuracy of 98.3%,sensitivity of 95.3%and specificity of 98.8%for diagnosing ESN images.A total of 2581 patients underwent upper gastrointestinal pCLE examination and were prospectively screened;54 patients with suspected ESN were enrolled.Overall,187 videos from 67 lesions were assessed by iCLE,three nonexpert and three expert endoscopists.iCLE achieved a high accuracy,sensitivity and specificity of 90.9%,92.0%,and 90.2%,respectively.Compared to experts,iCLE showed significantly higher sensitivity(92.0%vs 80.4%;P<0.001)and negative predictive value(94.4%vs 87.7%;P=0.003).With iCLE assistance,nonexpert endoscopists showed significant improvements in accuracy(from 83.6%to 88.6%)and sensitivity(from 76.0%to 89.8%).CONCLUSION iCLE system demonstrated high diagnostic performance for ESN.It can assist nonexpert endoscopists in improving the diagnostic efficiency of pCLE for ESN and has the potential for reducing unnecessary biopsies.展开更多
Perineural invasion(PNI)by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma(OSCC).Since Schwann cells(SCs)and fibroblasts maintain the physiological homeostasis of the peripheral nervous ...Perineural invasion(PNI)by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma(OSCC).Since Schwann cells(SCs)and fibroblasts maintain the physiological homeostasis of the peripheral nervous system,and we have focused on cancer-associated fibroblasts(CAFs)for decades,it’s imperative to elucidate the impact of CAFs on SCs in PNI+OSCCs.We describe a disease progression-driven shift of PNI−towards PNI+during the progression of early-stage OSCC(31%,n=125)to late-stage OSCC(53%,n=97),characterized by abundant CAFs and nerve demyelination.CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro,and this involved up-regulated ER stress and decreased MAPK signals.Moreover,CAFs also aggravated the paralysis of the hind limb and PNI in vivo.Unexpectedly,leukemia inhibitory factor(LIF)was exclusively expressed on CAFs and up-regulated in metastatic OSCC.The LIF inhibitor EC330 restored CAF-induced SC inactivation.Thus,OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.展开更多
基金funded by JSPS KAKENHI to Y.K.(22K19629,22H03288,and 21KK0162)JSPS Program for Forming Japan's Peak Research Universities:J-PEAKS(JPJS00420240022)to Y.K.JST SPRING,Grant Number JPMJSP2113 to C.W.and C.S.
文摘Oral squamous cell carcinoma(OSCC)is a prevalent malignancy with high morbidity and mortality.Globally,about 400000 people are affected,often with a poor quality of life.Its high mortality is mainly due to its aggressive growth and tendency to spread.Epithelial-mesenchymal transition(EMT)is a central regulatory hub driving tumor cell migration and invasion by enabling changes in cell characteristics.During EMT,epithelial cells gradually take on mesenchymal traits,gaining mobility and spreading mo re easily.Recent multi-omics studies show that many cancer cells exist in a hybrid or partial-EMT state,which lies between the full epithelial and mesenchymal forms.Cells in this state are especially invasive and metastatic,with high plasticity that promotes tumor progression.This review summarizes the role of partial-EMT in OSCC,with a focus on how it alters the tumor microenvironment(TME),promotes invasion and metastasis,and influences cancer stem cells(CSCs).We also highlight the link between partial-EMT and treatment resistance in OSCC.Based on these insights,we discuss therapeutic strategies targeting partial-EMT to improve outcomes.Targeting partial-EMT may offer promising strategies to enhance treatment effectiveness and improve patient survival and quality of life.
文摘Oncology Research Editorial Office Published:19 January 2026 The published article titled“miR-202 Promotes Cell Apoptosis in Esophageal Squamous Cell Carcinoma by Targeting HSF2”has been retracted from Oncology Research,Vol.25,No.2,2017,pp.215-223.DOI:10.3727/096504016X14732772150541 URL:https://www.techscience.com/or/v25n2/56800.
基金Supported by“Continuation”Project of Excellent Doctors,Guangdong Basic and Applied Basic Research Foundation,No.2025A04J5082Guangdong Basic and Applied Basic Research Foundation,No.2024A1515011236.
文摘This letter addresses challenges in the clinical translation of BIBR1532,a promising telomerase inhibitor,for the treatment of esophageal squamous cell carcinoma(ESCC).BIBR1532 exerts its anti-cancer effect by activating DNA damage response(ATR/CHK1 and ATM/CHK2)pathways and downregulating telomere-binding proteins.Although its therapeutic potential is limited by poor aqueous solubility,solid dispersion(SD)technology may overcome this obstacle.Systematic analysis using PubChem-derived simplified molecular input line entry system identifiers and artificial intelligence-driven FormulationDT platform evaluation(oral formulation feasibility index:0.38)revealed that the SD technology,with superior scalability(32 approved products by 2021)and lower production risks,outperforms lipid-based formulations as an optimal dissolution strategy.Material analysis revealed hydroxypropyl methylcellulose(HPMC)as the optimal carrier with lower hygroscopicity,higher temperature and no intestinal targeting,thus enabling ESCC therapy.HPMC-based SD enhances BIBR1532 solubility and bioavailability for effective ESCC treatment.Future studies should focus on pilot tests for SD fabrication.
文摘Cutaneous squamous cell carcinoma(CSCC)is the second most common type of skin cancer and typically involves the head and neck.Systemic therapy is often required for patients with advanced CSCC to achieve optimal disease control.Immune checkpoint inhibitors(ICIs)are now the standard of care for these patients,with a 50%-60%response rate and sustainable remission for at least 30%of patients.Given the activity of ICIs in advanced head and neck CSCC,ICIs are being studied in early-stage disease or neoadjuvant situations.The purpose of this review is to provide an overview of the innovative perioperative strategies in resectable disease and discuss novel immunotherapeutic strategies designed to overcome treatment resistance.In conclusion,neoadjuvant ICIs have demonstrated impressive response rates with unclear survival benefit.The effectiveness of adjuvant ICIs is currently being explored.Emerging biomarkers,such as circulating tumor DNA(ctDNA),will be crucial for optimizing patient selection and improving treatment outcomes.
基金supported by the College of Oral Medicine,Taipei Medical University,Taipei,Taiwan(Grant No.TMUCOM202502)supported by Taipei Medical University Hospital,Taipei,Taiwan(Grant No.114TMUH-NE-05).
文摘This narrative review examines recent advances in salivary biomarkers for oral squamous cell carcinoma(OSCC),a major subtype of oral cancer with persistently low five-year survival rates due to delayed diagnosis.Saliva has emerged as a noninvasive diagnostic medium capable of reflecting both local tumor activity and systemic physiological changes.Various salivary biomarkers,including microRNAs,cytokines,proteins,metabolites,and exosomes,have been linked to oncogenic signaling pathways involved in tumor progression,immune modulation,and therapeutic resistance.Advances in quantitative polymerase chain reaction,mass spectrometry,and next-generation sequencing have enabled comprehensive biomarker profiling,while point-of-care detection systems and saliva-based omics platforms are accelerating clinical translation.Remaining challenges include variability in salivary composition,lack of standardized collection protocols,and insufficient validation across large patient cohorts.This review highlights the mechanistic relevance,diagnostic potential,and translational challenges of salivary biomarkers in OSCC.
基金supported by Hebei Natural Science Foundation(H2024206476)Medical Science Research Project of Hebei(20240101).
文摘Background:The regulatory mechanisms governing vasculogenic mimicry(VM)in oral squamous cell carcinoma(OSCC)remain largely undefined.This study aimed to identify critical factors and elucidate the epigenetic mechanisms underlying VM in OSCC.Methods:Bioinformatics analysis was performed utilizing single-cell RNA-seq,bulk RNA-seq,and histone H3 lysine 27 acetylation(H3K27ac)Chromatin Immunoprecipitation(ChIP)-seq data obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases.ChIP-qPCR was used to validate the binding of ETS transcription factor ELK4(ELK4)to the dihydrofolate reductase(DHFR)enhancer.In vitro VM formation and invasion of OSCC cells were assessed using Matrigel-based tube formation and Transwell assays,respectively.Results:Elevated expression of VM-related genes predicts unfavorable prognosis in OSCC patients.High-dimensional weighted gene co-expression network analysis(hdWGCNA)identified epithelial subcluster C4 as most strongly associated with VM and metastasis.Three co-expression modules within this subcluster exhibited significant positive correlations with both phenotypic traits.Among the 30 eigengenes from the three modules,DHFR emerged as a key regulator of VM and metastasis.Knockdown or inhibition of DHFR significantly suppressed VM formation and invasion in OSCC cells.Mechanistically,ELK4 activated DHFR transcription through direct binding to its enhancer.DHFR overexpression rescued VM and invasion impairment induced by ELK4 knockdown.Conclusion:DHFR was a pivotal enhancer-regulated gene driving VM and metastasis in OSCC.ELK4 directly binds to DHFR enhancer regions to activate its transcription,thereby promoting these malignant phenotypes.These findings identified the ELK4/DHFR axis as a promising therapeutic target for anti-angiogenic intervention in OSCC.
基金The authors extend their appreciation to Taif University,Saudi Arabia,for supporting this work through project No.(TU-DSPP-2024-54).
文摘Background:Locally advanced laryngeal squamous cell carcinoma(LA-LSCC)presents clinical challenges due to the lack of reliable non-invasive biomarkers.This study aimed to evaluate miR-449a as a diagnostic and prognostic biomarker in LA-LSCC.Methods:miR-449a expression was analyzed in tumor tissues,adjacent normal tissues,and serum from 81 LA-LSCC patients and 50 controls using quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).We assessed the diagnostic accuracy by Receiver Operating Characteristic curve(ROC curves),clinicopathological associations,survival outcomes(Kaplan-Meier),and treatment response dynamics.Results:miR-449a was significantly downregulated in LA-LSCC tissues(p<0.0001)and serum(p<0.0001),with a strong tissue-serum correlation(R^(2)=0.988).Tissue miR-449a demonstrated a diagnostic accuracy(Area Under the Curve,AUC=0.857),while serum showed moderate accuracy(AUC=0.734).High miR-449a expression correlated with favorable clinicopathological features and improved survival(median overall survival:67.82 vs.23.74 months;p=0.0012).Multivariate analysis confirmed miR-449a as an independent prognostic factor(p<0.001).miR-449a levels increased post-treatment,particularly in responders to chemotherapy/radiation(p<0.0001).Conclusion:miR-449a serves as a non-invasive biomarker for LA-LSCC diagnosis,prognosis,and treatment monitoring.Its dynamic expression highlights potential for risk stratification and therapy response prediction,warranting further validation in larger cohorts.
基金supported by the National Key Research and Development Program of China(2023YFC2308800)the Natural Science Foundation of Shanghai(25ZR1402053)the Key Discipline of Public Health of the Shanghai Municipal Health Commission(Grant No.GWVI-11.1-07).
文摘Objective The aim of this study was to analyze the correlation between the levels of 12 cytokines in the cervical microenvironment and cervical intraepithelial neoplasia in patients with high-risk human papillomavirus(HR-HPV)infection.Methods Female patients(n=73)with HR-HPV infection were enrolled and divided into a high-grade squamous intraepithelial lesion(HSIL)group(n=33)and a non-HSIL(N-HSIL)group(n=40),which include low-grade squamous intraepithelial lesions and inflammation.Healthy screening subjects(n=31)with negative HR-HPV results were enrolled as a control group.We examined contemporaneous plasma and secretory cytokines from 25 study subjects to investigate the difference between systemic cytokine profiles and the local microenvironment immunity using the Wilcoxon matched-pairs signed rank test.The 12 cytokines from cervical secretions were compared between the three groups using the Mann-Whitney test,and logistic regression was used to analyze HSIL and N-HSIL.Results There were statistical differences in eight cytokines(IL-2,IL-6,TNF-α,IFN-γ,IL-1β,IL-12p70,IFN-α,and IL-8)between cervical secretion and plasma of the same patient,and seven cytokines were statistically different between the control and other two groups.We selected four independent variables(TNF-α,IFN-γ,IL-12p70,and IFN-α)commonly identified by univariate regression analysis and non-parametric tests for multivariate logistic regression analysis.Based on this model,HSIL could be predicted in patients with HR-HPV infection,with the area under the curve being 0.76.Conclusion The systemic cytokine profile cannot reflect the local microenvironment immunity,and the occurrence of HSIL is related to the cytokine levels in the cervical microenvironment.
基金supported by the National Natural Science Foundation of China(Grant Nos.82272955 and 22203057)the Natural Science Foundation of Fujian Province(Grant No.2021J011361).
文摘The presence of a positive deep surgical margin in tongue squamous cell carcinoma(TSCC)significantly elevates the risk of local recurrence.Therefore,a prompt and precise intraoperative assessment of margin status is imperative to ensure thorough tumor resection.In this study,we integrate Raman imaging technology with an artificial intelligence(AI)generative model,proposing an innovative approach for intraoperative margin status diagnosis.This method utilizes Raman imaging to swiftly and non-invasively capture tissue Raman images,which are then transformed into hematoxylin-eosin(H&E)-stained histopathological images using an AI generative model for histopathological diagnosis.The generated H&E-stained images clearly illustrate the tissue’s pathological conditions.Independently reviewed by three pathologists,the overall diagnostic accuracy for distinguishing between tumor tissue and normal muscle tissue reaches 86.7%.Notably,it outperforms current clinical practices,especially in TSCC with positive lymph node metastasis or moderately differentiated grades.This advancement highlights the potential of AI-enhanced Raman imaging to significantly improve intraoperative assessments and surgical margin evaluations,promising a versatile diagnostic tool beyond TSCC.
文摘Dear Editor,Local recurrence and cervical lymph node metastases are major causes of mortality in patients with head and neck squamous cell carcinoma(HNSCC).To date,none of the proposed strategies for predicting outcomes in this disease have proven fully effective,and a comprehensive physical examination remains the primary method for early detection and monitoring of HNSCC.
基金supported by the National Natural Science Foundation of China(62272078)the Chongqing Natural Science Foundation(CSTB2023NSCQ-LZX0069).
文摘Dear Editor,This letter proposes an end-to-end feature disentangled Transformer(FDTs)for entanglement-free and semantic feature representation to enable accurate and trustworthy pathology grading of squamous cell carcinoma(SCC).Existing vision transformers(ViTs)can implement representation learning for SCC grading,however,they all adopt the class-patch token fuzzy mapping for pattern prediction probability or window down-sampling to enhance the representation to contextual information.
基金supported by the National Natural Science Foundation of China(Grant No.82172567)the Key R&D Plan of Jiangxi Province(Grant No.2021BBG71006)the Key Project of Science and Technology Innovation of Health Commission of Jiangxi Province(Grant Nos.2023ZD005 and 2024ZD008).
文摘Dear Editor,Esophageal cancer(EC)is a malignant tumor originating from esophageal epithelium and remains a leading cause of cancer incidence and mortality worldwide1,2.According to the 2020 World Health Organization statistics,there were approx-imately 604,000 new EC cases and 544,000 EC-related deaths globally with China reporting approximately 320,000 new cases and 300,000 deaths,mainly from esophageal squamous cell carcinoma(ESCC)3.Although there has been progress in the treatment of EC,the long-term prognosis of patients with R0 resection and lymph node-positive disease contin-ues to be suboptimal4.A retrospective analysis performed by our center suggested that the median overall survival(OS)of lymph node-positive patients with EC who received postoper-ative adjuvant radiotherapy(PART)was 29 months compared to 21 months for surgery alone with 3-year survival rates of 43%and 36%,respectively,indicating a potential survival ben-efit of PART5.
基金Supported by the National Natural Science Foundation of China(No.82070934,No.82171025).
文摘AIM:To investigate the pathological features of ocular surface squamous neoplasia(OSSN)and evaluate the synergistic therapeutic effects of interferon-α2b(IFNα2b)and 5-fluorouracil(5-FU)on cellular proliferation,migration,apoptosis,and cell cycle of human oral squamous carcinoma cell line Cal27.METHODS:Tissue specimens from OSSN were processed with hematoxylin-eosin(HE)and immunofluorescence(IF)staining to characterize pathological changes.We analyzed the expression levels of four pivotal proteins involved in 5-FU metabolism:interferon alpha receptor(IFNAR),thymidylate synthase(TS),thymidine phosphorylase(TP),and dihydropyrimidine dehydrogenase(DPD).Cal27 cell lines were treated with a spectrum of concentrations of IFNα2b and 5-FU,either in isolation or in combination.Then,cell activity was measured utilizing CCK-8 assay and dose-effect curves were calculated,while tumor cell migration was detected by cell scratch experiments.Cal27 cells were added with IFNα2b and 5-FU in a non-constant ratio drug combination design and the corresponding combination index(CI)and fraction affected(Fa)were calculated with CompuSyn software.Western blot assay was conducted to quantify the expression of TP,TS,and DPD.Cell cycle and apoptosis were measured with flow cytometry and terminal deoxynucleotidyl transferasemediated dUTP nick and labeling(TUNEL)assay.RESULTS:Treatment with both IFNα2b and 5-FU inhibited cell proliferation.Except for the lowest and highest doses of 5-FU,CI values for all other groups were below 1,suggesting a synergistic interaction.Low concentrations of IFNα2b and 5-FU both diminished the relative mobility of Cal27 cells,instead,a stronger inhibitory effect was observed when the two drugs were co-applied.The expression levels of TP and DPD in Cal27 cells were dose-dependently increased at a low concentration of IFNα2b.Low-dose IFNα2b combined with 5-FU significantly inhibited cell proliferation in G0/G1 phase compared to 5-FU monotherapy.Medium and high doses of IFNα2b and all concentrations of 5-FU could induce apoptosis in a concentration-dependent manner.The susceptibility to 5-FU treatment and apoptosis rates of tumor cells were elevated with low doses of IFNα2b.CONCLUSION:Both IFNα2b and 5-FU,when administered individually or in combination,effectively suppress the proliferation and migration of Cal27 tumor cells,induce cell apoptosis and arrest cell cycle.Low doses of IFNα2b increase the antitumor effects of 5-FU on Cal27 potentially through up-regulating the expression of TP,demonstrating a synergistic effect between IFNα2b and 5-FU.
文摘AIM:To evaluate the demographics,clinical characteristics,treatments,and outcomes of patients with ocular surface squamous neoplasia(OSSN)at the Philippine General Hospital.METHODS:This was a single-center,11-year retrospective,cross sectional case series on 18 cases of OSSN seen between January 2012 to June 2023.The patient’s demographics,presenting symptoms,tumor characteristics,histopathologic diagnosis,treatment,outcomes,and duration of follow-up were reviewed.RESULTS:Out of 33 identified cases of OSSN,only 18 were eligible for inclusion in the study.Mean age was 60.78y(range 31 to 80),with male predominance(66.67%).The left eye was most commonly affected(61.11%)with most presenting with fleshy mass(83.33%).Most tumors were located nasally(66.67%)and were predominantly papilliform(44.44%)in morphology with associated hyperpigmentation(38.89%).Squamous cell carcinoma(SCCA)was the most common histopathologic diagnosis(72.22%).The main primary treatment was surgical excision(94.44%)with or without adjunctive therapy,with only 1 patient undergoing first-line topical chemotherapy.Only 3 recurrences(16.67%)were noted with a median followup of 7.5mo.A statistically significant recurrence-free odds leaning towards the utilization of cryotherapy was noted.CONCLUSION:OSSN seen at the Philippine General Hospital is presented as a limbal papilliform mass,most commonly affecting elderly males.Surgical excision with adjuvant cryotherapy and/or chemotherapy is the preferred mode of treatment.
基金Supported by the National Research Foundation of Korea,No.2020R1A2C1100891Soonchunhyang University Research Fund,No.2024-05-014.
文摘BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations.
基金Supported by The National Natural Science Foundation of China,No.82350127 and No.82241013the Shanghai Natural Science Foundation,No.20ZR1411600+2 种基金the Shanghai Shenkang Hospital Development Center,No.SHDC2020CR4039the Bethune Ethicon Excellent Surgery Foundation,No.CESS2021TC04Xuhui District Medical Research Project of Shanghai,No.SHXH201805.
文摘BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.
文摘BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors is their penetration of neighboring tissues,such as lymphatic and blood arteries,due to the tumor cells'capacity to break down the extracellular matrix(ECM).Matrix metalloproteinases(MMPs)constitute a family of proteolytic enzymes that facilitate tissue remodeling and the degradation of the ECM.MMP-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific functions.MMP-13,a collagenase family member,is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens,whereas MMP-9 is thought to accelerate the growth of tumors.Elevated MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant cases.AIM To assess the immunohistochemical expression of MMP-9 and MMP-13 in OSCC.METHODS A total of 40 cases with histologically confirmed OSCC by incisional biopsy were included in this cross-sectional retrospective study.The protocols for both MMP-9 and MMP-13 immunohistochemical staining were performed according to the manufacturer’s recommendations along with the normal gingival epithelium as a positive control.All the observations were recorded and Pearson’sχ²test with Fisher exact test was used for statistical analysis.RESULTS Our study showed no significant correlation between MMP-9 and MMP-13 staining intensity and tumor size.The majority of the patients were in advanced TNM stages(III and IV),and showed intense expression of MMP-9 and MMP-13.CONCLUSION The present study suggests that both MMP-9 and MMP-13 play an important and independent role in OSCC progression and invasiveness.Intense expression of MMP-9 and MMP-13,irrespective of histological grade of OSCC,correlates well with TNM stage.Consequently,it is evident that MMP-9 and MMP-13 are important for the invasiveness and progression of tumors.The findings may facilitate the development of new approaches for evaluating lymph node metastases and interventional therapy techniques,hence enhancing the prognosis of patients diagnosed with OSCC.
基金Supported by Natural Science Foundation-funded Project:Establishment of Syndrome-Disease Warning System and Investigation of the Clinical Features and Evolution Patterns of Traditional Chinese Medicine Syndromes in Esophageal Cancer under Modern Medical Diagnosis and Treatment(2023YFC3503200,2023YFC3503201)Biological Basis of the Pathogenesis of Cancer Toxin in Traditional Chinese Medicine(2022YFC3500200,2022YFC3500202)+12 种基金Natural Science Foundation-funded Project:Mechanistic Study of the Nucleolar Methyltransferase Fibrillarin to Promote Neoplastic Growth of Esophageal Squamous Cell Carcinoma via Activating Nucleoside Synthesis(No.32170778)Mechanistic Study of Renal Cancer Neoplastic Growth Driven by Glucose Transporter 5-Mediated Fructose Metabolism Reprogramming(No.31970708)Mechanistic Study of Methionine Cycle Modulating the Growth of Esophageal Squamous Cell Carcinoma through"DNA Methylation-DNA Stability-p53/p21-cell Cycle"Pathway(No.82002953)the Antitumor Mechanism of Oleanolic Acid via Autophagy by Regulating Adenosine Monophosphate-Activated Protein Kinase-Mammalian Target of Rapamycin-Unc51 Like Kinase 1 Pathway and Inhibiting Purine Salvage Pathway(No.82004177)USP14 Cooperates with Ubiquitin C-Terminal Hydrolase L5 to Regulate Constitutive Photomorphogenic 9 Signalosome-mediated Programmed Death-Ligand 1 Deubiquitination and Promote Immune Evasion in Hepatocellular Carcinoma.(No.81972214)National Scientific and Technological Major Special Project of China:Shuang Huang Sheng Bai Oral Liquid:Efficacy and Safety Evaluation of Traditional Chinese Medicine Compound Based on Systems Biology Approaches(2019ZX09201004-002-013)A special clinical research initiative for the health business sponsored by the Shanghai Municipal Health Commission(No.202040155)Shanghai Municipal Science and Technology Commissions Special Biomedical Technology Support Plan(No.20S31904100)Shanghai"Science and Technology Innovation Action Plan"Medical Innovation Research Project--Shanghai Clinical Research Center of Traditional Chinese Medicine Oncology(21MC1930500)Shanghai 13th Five-Year Plan Key Specialty of Traditional Chinese Medicine Oncology(shslczdzk03701)Tracking Programme for Eastern Scholar at Shanghai Institutions of Higher LearningShanghai High-level Talent Leadership Programme of Traditional Chinese Medicine[ZY(2021-2023)-0403]Scientific Research Project of Industry Development Center of Shanghai University of Traditional Chinese Medicine(602076D)。
文摘OBJECTIVE:To uncover the biological foundation of the prevailing TCM syndrome in individuals with Esophageal squamous cell carcinoma(ESCC),Zhengxu Xieshi(ZXXS),which is characterized by a deficiency in vital Qi and an excess in evil Qi.METHODS:We investigated shifts in vital Qi by quantifying systemic metabolic changes in the peripheral blood.Serum metabolomic profiling was conducted on the ESCC cohort 1 along with a matched healthy control cohort.Additionally,we assessed changes in evil Qi by examining metabolic perturbations in ESCC tissues.This analysis involved metabolomic and proteomic surveys of ESCC tissues and paired normal adjacent tissues as controls in an independent ESCC cohort 2.RESULTS:Serum metabolomic profiling highlighted the prevalent downregulation of differentially expressed metabolites in patient sera,in contrast to the upregulation observed in ESCC tissues,compared to their respective controls.Remarkably,the group of differential metabolites in the ESCC tissues was predominantly composed of amino acids.Thus,we focused on amino acid metabolism.Our integrative analysis showed the downregulation of a significant majority of disturbed amino acids in patient sera relative to the upregulation of an overwhelming proportion of perturbed amino acids within ESCC tissues.Enrichment analysis of these amino acids revealed seven metabolic pathways that contribute to the metabolism of antioxidants,energy intermediates,and biosynthetic precursors.Interestingly,these pathways displayed attenuation in patient sera but augmentation in ESCC tissues.Similarly,the proteomic data confirmed the activation of these pathways in ESCC tissues.CONCLUSION:This study presents a new perspective on the prevalence of ZXXS syndrome in patients with ESCC,contextualized within the realm of metabolic reprogramming.Specifically,diminished amino acid metabolism in the circulating blood corresponds to a deficiency in vital Qi.Conversely,hyperactive amino acid metabolism in ESCC tissues signifies an augmentation of local evil Qi.These findings hold potential to enrich the current medical framework and offer a deeper understanding of ESCC management by integrating the principles of ZXXS syndrome.
基金Supported by the National Key Research and Development Program of China,No.2023YFC2413800the Taishan Scholars Program of Shandong Province,No.tsqn202306344the National Natural Science Foundation of China,No.82270580 and No.82070552.
文摘BACKGROUND Early detection of esophageal squamous neoplasms(ESN)is essential for improving patient prognosis.Optical diagnosis of ESN remains challenging.Probebased confocal laser endomicroscopy(pCLE)enables accurate in vivo histological observation and optical biopsy of ESN.However,interpretation of pCLE images requires histopathological expertise and extensive training.Artificial intelligence(AI)has been widely applied in digestive endoscopy;however,AI for pCLE diagnosis of ESN has not been reported.AIM To develop a pCLE computer-aided diagnostic system for ESN and assess its diagnostic performance and assistant efficiency for nonexpert endoscopists.METHODS The intelligent confocal laser endomicroscopy(iCLE)system consists of image recognition(based on inception-ResNet V2),video diagnosis,and quality judgment modules.This system was developed using pCLE images and videos and evaluated through image and prospective video recognition tests.Patients between June 2020 and January 2023 were prospectively enrolled.Expert and nonexpert endoscopists and the iCLE independently performed diagnoses for pCLE videos,with histopathology as the gold standard.Thereafter,the non-expert endoscopists performed a second assessment with iCLE assistance.RESULTS A total of 25056 images from 2803 patients were selected for iCLE training and validation.Another 2442 images from 226 patients were used for testing.iCLE achieved a high accuracy of 98.3%,sensitivity of 95.3%and specificity of 98.8%for diagnosing ESN images.A total of 2581 patients underwent upper gastrointestinal pCLE examination and were prospectively screened;54 patients with suspected ESN were enrolled.Overall,187 videos from 67 lesions were assessed by iCLE,three nonexpert and three expert endoscopists.iCLE achieved a high accuracy,sensitivity and specificity of 90.9%,92.0%,and 90.2%,respectively.Compared to experts,iCLE showed significantly higher sensitivity(92.0%vs 80.4%;P<0.001)and negative predictive value(94.4%vs 87.7%;P=0.003).With iCLE assistance,nonexpert endoscopists showed significant improvements in accuracy(from 83.6%to 88.6%)and sensitivity(from 76.0%to 89.8%).CONCLUSION iCLE system demonstrated high diagnostic performance for ESN.It can assist nonexpert endoscopists in improving the diagnostic efficiency of pCLE for ESN and has the potential for reducing unnecessary biopsies.
基金supported by the National Natural Science Foundation of China(82373037 and 82403486)the Natural Science Foundation of Jiangsu Province(BK20230054 and BK20230161)+1 种基金the China Postdoctoral Science Foundation(2023M741766)the Nanjing Medical Science and Technology Development Foundation,Nanjing Department of Health(YKK21182 and JQX23010).
文摘Perineural invasion(PNI)by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma(OSCC).Since Schwann cells(SCs)and fibroblasts maintain the physiological homeostasis of the peripheral nervous system,and we have focused on cancer-associated fibroblasts(CAFs)for decades,it’s imperative to elucidate the impact of CAFs on SCs in PNI+OSCCs.We describe a disease progression-driven shift of PNI−towards PNI+during the progression of early-stage OSCC(31%,n=125)to late-stage OSCC(53%,n=97),characterized by abundant CAFs and nerve demyelination.CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro,and this involved up-regulated ER stress and decreased MAPK signals.Moreover,CAFs also aggravated the paralysis of the hind limb and PNI in vivo.Unexpectedly,leukemia inhibitory factor(LIF)was exclusively expressed on CAFs and up-regulated in metastatic OSCC.The LIF inhibitor EC330 restored CAF-induced SC inactivation.Thus,OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
