Immunotherapy offers significant potential but is often hampered by the immunosuppressive environment in oral squamous cell carcinoma(OSCC).To address this,we propose an enhanced immunotherapeutic strategy that revita...Immunotherapy offers significant potential but is often hampered by the immunosuppressive environment in oral squamous cell carcinoma(OSCC).To address this,we propose an enhanced immunotherapeutic strategy that revitalizes the tumor immune microenvironment(TIME)in OSCC by integrating upconversion-based photodynamic therapy(PDT)with chemotherapy.Using a red blood cell membraneinspired biomimetic nanoplatform,our approach concurrently delivers chlorin e6@upconversion nanoparticles(Ce6@UCNP)and doxorubicin(DOX).By leveraging fluorescence resonance energy transfer(FRET)for 980 nm to 660 nm upconversion excitation,we address challenges such as limited tissue penetration and tissue damage,as well as nanoplatform issues including immunogenicity and targeting inaccuracy Our integrated approach enhances PDT and chemotherapy with the goal of transforming immunologically“cold”tumors into“hot”ones through a cascaded therapy,thereby revitalizing the tumor immune microenvironment in OSCC.展开更多
Oral squamous cell carcinoma(OSCC)progresses from preneoplastic precursors via genetic and epigenetic alterations.Previous studies have focused on the treatment of terminally developed OSCC.However,the role of epigene...Oral squamous cell carcinoma(OSCC)progresses from preneoplastic precursors via genetic and epigenetic alterations.Previous studies have focused on the treatment of terminally developed OSCC.However,the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied.Our study identified lysine-specific demethylase 1(LSD1)as a crucial promoter of OSCC,demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia.LSD1 inhibition by SP2509 disrupted cell cycle,reduced immunosuppression,and enhanced CD4+and CD8+T-cell infiltration.In a feline model of spontaneous OSCC,a clinical LSD1 inhibitor(Seclidemstat or SP2577)was found to be safe and effectively inhibit the STAT3 network.Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling,which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4.Notably,LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422,offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition.This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.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
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
Introduction: As a chaperone, heat shock protein acts as central integrators of protein homeostasis in cell. The form of these functions is to help setting up a complex protein molecular fold (folded protein) in many ...Introduction: As a chaperone, heat shock protein acts as central integrators of protein homeostasis in cell. The form of these functions is to help setting up a complex protein molecular fold (folded protein) in many important settings, such as growth, differentiation, and the ability to live. It has become clear that the control system plays an important role if the folding process fails or an error occurs, causing folding abnormalities and targeted functionality to accumulate. The accumulation of faulty protein folding would harm cells and can result in death. Apparently, there is a correlation between protein folding error with various diseases, such as diabetes mellitus and cancer. Method: We examined protein levels in all samples using Dotblott with monoclonal antibody anti-Hsp40 and anti-Hsp70. Levels of the protein content was read using a densitometer. Modification of Dot Blot was as follows: treatment was conducted with 3 × SSC, added with 20 mL blocking solution, add with total protein samples of 10 mg/ml on nitrocellulose paper, prehybridized, incubated at 70° for 30 seconds, incubated at 70° for 30 seconds with primary antibody anti-Hsp40 or Hsp70 protein and then added with second antibody HRP anti-Hsp40 or Hsp70 protein, treated with 3 × SSC and visualized with TSA HRP, and then administered with streptavidin, biothynil tyramide, and, finally, added with chromogen (DAB) in a confined space. Result: From the analysis of the data using Manova test with Wilk’s Lambda, there were significant differences in the levels of Hsp40 between Benign Oral Lesion (mean 688.31 area) and OSCC (mean 1354.59 area) patients (p 0.070), there was also a highly significant difference in Hsp70 levels between patients who experienced Benign Oral Lesion (mean 529.82 area) and OSCC (mean 1346.32 area) patients (p 0.006). Conclusion: OSCC patients have increased Hsp70 levels, so it is possible that something is going wrong in protein folding. Errors in protein folding result in a new homeostasis or inhibition of apoptosis and increasing cell proliferation that triggers carcinogenesis. Hsp40 acts as co-chaperones.展开更多
基金supported by the National Natural Science Foundation of China(No.81802709)the Shandong Provincial Natural Science Foundation,China(Nos.ZR2023MH230,ZR2023MH096)+1 种基金the Shandong Provincial Postdoctoral Innovative Talents Funded SchemePlan of Young Scholars of Shandong University。
文摘Immunotherapy offers significant potential but is often hampered by the immunosuppressive environment in oral squamous cell carcinoma(OSCC).To address this,we propose an enhanced immunotherapeutic strategy that revitalizes the tumor immune microenvironment(TIME)in OSCC by integrating upconversion-based photodynamic therapy(PDT)with chemotherapy.Using a red blood cell membraneinspired biomimetic nanoplatform,our approach concurrently delivers chlorin e6@upconversion nanoparticles(Ce6@UCNP)and doxorubicin(DOX).By leveraging fluorescence resonance energy transfer(FRET)for 980 nm to 660 nm upconversion excitation,we address challenges such as limited tissue penetration and tissue damage,as well as nanoplatform issues including immunogenicity and targeting inaccuracy Our integrated approach enhances PDT and chemotherapy with the goal of transforming immunologically“cold”tumors into“hot”ones through a cascaded therapy,thereby revitalizing the tumor immune microenvironment in OSCC.
基金NIH/NIDCR grant R01 DE031413 and CTSA pilot grant UL1TR001430 to Manish V.Bais.
文摘Oral squamous cell carcinoma(OSCC)progresses from preneoplastic precursors via genetic and epigenetic alterations.Previous studies have focused on the treatment of terminally developed OSCC.However,the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied.Our study identified lysine-specific demethylase 1(LSD1)as a crucial promoter of OSCC,demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia.LSD1 inhibition by SP2509 disrupted cell cycle,reduced immunosuppression,and enhanced CD4+and CD8+T-cell infiltration.In a feline model of spontaneous OSCC,a clinical LSD1 inhibitor(Seclidemstat or SP2577)was found to be safe and effectively inhibit the STAT3 network.Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling,which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4.Notably,LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422,offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition.This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.
基金Fertilization-independent formation of embryo,endospermand pericarpfor apomictic hybrid ricesupported by Australian Centre for International Agricultural Research(CIM/2002/106)
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Introduction: As a chaperone, heat shock protein acts as central integrators of protein homeostasis in cell. The form of these functions is to help setting up a complex protein molecular fold (folded protein) in many important settings, such as growth, differentiation, and the ability to live. It has become clear that the control system plays an important role if the folding process fails or an error occurs, causing folding abnormalities and targeted functionality to accumulate. The accumulation of faulty protein folding would harm cells and can result in death. Apparently, there is a correlation between protein folding error with various diseases, such as diabetes mellitus and cancer. Method: We examined protein levels in all samples using Dotblott with monoclonal antibody anti-Hsp40 and anti-Hsp70. Levels of the protein content was read using a densitometer. Modification of Dot Blot was as follows: treatment was conducted with 3 × SSC, added with 20 mL blocking solution, add with total protein samples of 10 mg/ml on nitrocellulose paper, prehybridized, incubated at 70° for 30 seconds, incubated at 70° for 30 seconds with primary antibody anti-Hsp40 or Hsp70 protein and then added with second antibody HRP anti-Hsp40 or Hsp70 protein, treated with 3 × SSC and visualized with TSA HRP, and then administered with streptavidin, biothynil tyramide, and, finally, added with chromogen (DAB) in a confined space. Result: From the analysis of the data using Manova test with Wilk’s Lambda, there were significant differences in the levels of Hsp40 between Benign Oral Lesion (mean 688.31 area) and OSCC (mean 1354.59 area) patients (p 0.070), there was also a highly significant difference in Hsp70 levels between patients who experienced Benign Oral Lesion (mean 529.82 area) and OSCC (mean 1346.32 area) patients (p 0.006). Conclusion: OSCC patients have increased Hsp70 levels, so it is possible that something is going wrong in protein folding. Errors in protein folding result in a new homeostasis or inhibition of apoptosis and increasing cell proliferation that triggers carcinogenesis. Hsp40 acts as co-chaperones.
