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Pharmacological mechanisms of natural products with antidepressant effects:A focus on the programmed cell death regulation 认领 引用
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作者 Guangheng Zhang Shimeng Lv +9 位作者 Shengchuan Bao Weijie Zhao Yunhao Yi Haonan Gao Xia Zhong Xiangyu Li Fengzhao Liu Yitong Lu Siyuan Sun Jing Teng 《Journal of Pharmaceutical Analysis》 SCIE CAS CSCD 2026年第1期120-141,共22页
Depression is a prevalent mental disorder characterized by persistent disinterest and a depressed mood,with severe cases potentially leading to suicide.In recent years,the incidence of depression has steadily increase... Depression is a prevalent mental disorder characterized by persistent disinterest and a depressed mood,with severe cases potentially leading to suicide.In recent years,the incidence of depression has steadily increased,making it the second-largest global health burden.The pathogenesis of depression involves a series of complex pathological mechanisms,although the key underlying causes remain unclear.Programmed cell death(PCD),including apoptosis,autophagy,pyroptosis,ferroptosis,and necroptosis,involves highly organized gene expression processes that may influence the occurrence and development of depression by regulating cellular fate.Furthermore,numerous studies have shown that natural products can modulate PCDs through various signaling pathways,presenting significant potential for managing depression.Natural products offer benefits such as cost-effectiveness,fewer side effects,and other advantages,making them viable supplements or alternatives to traditional antidepressant drugs.To explore this potential,we reviewed studies demonstrating the antidepressant effects of natural products through multi-target modulation of PCDs.In addition,we discussed the toxicity and clinical applications of these natural products.This study highlights that diverse core biological pathways and targets are involved in determining the fate of depression-associated brain cells,including the PI3K/Akt signaling pathway,caspase-8,GSDMD,and others.In conclusion,the multi-target mechanisms of PCD regulation by natural products may provide a promising foundation for the future development of novel antidepressant medications. 展开更多
关键词 Depression Pharmacological mechanism Programmed cell death Natural products Antidepressant
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CD44-targeting and ZIF-8 gated gold nanocage for programmed breast cancer therapy through Pt-induced immunogenic cell death 认领 引用
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作者 Xin Li Fei Xiong +7 位作者 Xudong Cao Wei Liu Haobo Chen Jiayu He Weina Zhang Longguang Tang Wei Huang Xikuang Yao 《Chinese Chemical Letters》 SCIE CAS CSCD 2026年第1期462-467,共6页
The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD... The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future. 展开更多
关键词 Programmed drug release ZIF-8-gated Gold nanocage Immunogenic cell death Cancer therapy
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Clinical characteristics of programmed death-1 inhibitors for older patients with advanced pancreatic cancer 认领 引用
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作者 Yun-Yun Lu Yi Lu Pan Chen 《World Journal of Gastrointestinal Oncology》 SCIE 2026年第2期192-206,共15页
BACKGROUND Pancreatic cancer(PC),a highly malignant gastrointestinal cancer,is generally diagnosed at an advanced stage.However,traditional therapies for advanced PC are limited and often unsuitable for older patients... BACKGROUND Pancreatic cancer(PC),a highly malignant gastrointestinal cancer,is generally diagnosed at an advanced stage.However,traditional therapies for advanced PC are limited and often unsuitable for older patients.AIM To identify clinical predictors in older patients with advanced PC to facilitate individualized treatment.METHODS This was a retrospective clinical analysis involving 99 patients aged≥65 years with advanced PC who received programmed death-1(PD-1)inhibitors at Ningbo Medical Center Lihuili Hospital from January 2019 to January 2025.Univariate and multivariate analyses were conducted to identify clinical predictors for survival outcomes,utilizing blood levels and other clinical information.RESULTS The median progression-free survival(PFS)was 4.6 months[95%confidence interval(CI):3.700-5.800],and the median overall survival(OS)was 6.5 months(95%CI:5.700-8.200).Multivariate analysis helped identify meaningful clinical differences in PFS and OS across subgroups,including factors such as Eastern Cooperative Oncology Group performance status,prognostic nutritional index,and triglyceride levels.Univariate analysis showed that factors such as the location of primary PC,carbohydrate antigen 199 levels,systemic immune-inflammation,neutrophil-to-lymphocyte ratio,and the combination therapy comprising PD-1 inhibitors and radiotherapy are of significant clinical relevance to both PFS and OS.CONCLUSION The treatment of advanced PC with PD-1 inhibitors presented several potential independent clinical predictive indicators of survival outcomes in older patients.This study highlighted the importance of pre-treatment clinical characteristics and hematological variables for predicting treatment outcomes in older patients with PC. 展开更多
关键词 Advanced pancreatic cancer Older adults Programmed death-1 inhibitors Eastern Cooperative Oncology Group performance status Prognostic nutritional index Triglyceride
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Patterns and mechanisms of programmed cell death in bloom-forming Microcystis aeruginosa induced by potent allelochemical juglone 认领 引用
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作者 Xu YANG Jinyuan CHEN +4 位作者 Ang GAO Jinting LI Yulu HU Haiying WANG Xin ZHANG 《Journal of Oceanology and Limnology》 SCIE CAS CSCD 2026年第3期1116-1131,共16页
Harmful algal blooms(HABs)caused by Microcystis aeruginosa are a major global threat to the aquatic environment and public health.Allelochemicals derived from aquatic and terrestrial plants are emerging weapons for er... Harmful algal blooms(HABs)caused by Microcystis aeruginosa are a major global threat to the aquatic environment and public health.Allelochemicals derived from aquatic and terrestrial plants are emerging weapons for eradicating these blooms.Here,juglone outperformed the most reported allelochemicals in terms of algicidal activity against M.aeruginosa,with a half-maximal inhibitory concentration(IC50)of 0.078 mg/L.The algal growth suppression resulted from the activation of programmed cell death(PCD)upon juglone treatment.Ultrastructural changes of juglone-induced cyanobacterial cells were characterized by marked cytoplasmic vacuolization,as indicated by transmission electron microscopy(TEM)and scanning electron microscope(SEM).Dose-and timedependent biochemical features of M.aeruginosa in response to juglone included the increase in DNA fragmentation,caspase-3-like and caspase-9-like activities,phosphatidylserine externalization and chromatin condensation.Morphological and biochemical analyses revealed two modes of cell death,including apoptotic-like and autophagic-like PCD.The juglone-induced PCD was associated with increased reactive oxygen species(ROS)and nitric oxide(NO)as potential signal molecules.The blockage of the electron flow beyond(primary quinone acceptor)QA at photosystem II(PSII)acceptor side mediated the generation of ROS in M.aeruginosa exposed to juglone.Cotreatments with sodium tungstate,a nitrate reductase(NR)inhibitor,with the juglone successfully reduced NO production,suggesting that NO production in M.aeruginosa cells was mainly through NR pathway.The current study sheds light on the inhibition and action mode of juglone on M.aeruginosa from the perspective of PCD,as well as its potential for controlling cyanobacterial blooms. 展开更多
关键词 juglone Microcystis aeruginosa programmed cell death(PCD) reactive oxygen species(ROS) nitric oxide(NO)
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Adjuvant programmed death-1 inhibition combined with chemotherapy in resected pancreatic cancer:A real-world cohort study 认领 引用
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作者 Tang Cao Xiang-Liang Deng +4 位作者 Jin Xiao Xiao-Hong Tao Xue-Lian Xiang Man Qiu Xiao-Yan Liang 《World Journal of Gastrointestinal Oncology》 SCIE 2026年第6期114-124,共11页
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)carries a high risk of early recurrence even after curative resection.Although programmed death-1(PD-1)inhibitors have shown limited efficacy in advanced PDAC-primarily... BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)carries a high risk of early recurrence even after curative resection.Although programmed death-1(PD-1)inhibitors have shown limited efficacy in advanced PDAC-primarily due to its profoundly immunosuppressive tumor microenvironment-the adjuvant setting may provide an immunologically favorable window for PD-1 blockade.In this context,this real-world cohort study aimed to explore the efficacy and safety of PD-1 inhibitors combined with adjuvant chemotherapy in patients with resected PDAC.AIM To evaluate the efficacy and safety of PD-1 inhibitor–based adjuvant therapy combined with chemotherapy in patients with resected PDAC.METHODS We conducted a retrospective,single-center,real-world cohort study of 57 patients who underwent R0 or R1 resection for PDAC between 2021 and 2023.Patients received either adjuvant chemotherapy alone(n=31)or chemotherapy combined with a PD-1 inhibitor(n=26).The primary endpoint was recurrencefree survival(RFS);secondary endpoints included distant metastasis-free survival(DMFS),overall survival(OS),and treatment-related adverse events(TRAEs).Survival outcomes were analyzed using Kaplan-Meier estimates and multivariable Cox proportional hazards models.RESULTS Compared with chemotherapy alone,the addition of a PD-1 inhibitor significantly prolonged median RFS[21.0 months vs 9.0 months;hazard ratio(HR)=0.37,95%confidence interval(CI):0.19-0.72;P=0.003]and DMFS(21.0 months vs 11.0 months;HR=0.33,95%CI:0.16-0.69;P=0.003).Although OS was numerically longer in the combination group(27.0 months vs 21.0 months),the difference was not statistically significant(P=0.293).Multivariable analysis identified PD-1 therapy,younger age,lower baseline creatinine,and early-stage disease as independent predictors of longer RFS.Subgroup analyses suggested a generally consistent RFS benefit across predefined clinical and biomarker-defined strata.Exploratory analyses indicated that dynamic reductions in carbohydrate antigen 19-9 levels and neutrophil-to-lymphocyte ratio were more frequently observed in the combination group.Grade≥3 TRAEs occurred in 19.2%of the combination group and 25.8%of the chemotherapy group.CONCLUSION Adjuvant PD-1 blockade combined with chemotherapy was associated with improved recurrence-related outcomes in patients with resected PDAC without an increase in severe toxicity.These real-world findings provide clinical rationale for further prospective evaluation of immunotherapy-based adjuvant strategies and highlight the need for biomarker-informed randomized trials to validate these observations and optimize patient selection. 展开更多
关键词 Pancreatic ductal adenocarcinoma Programmed death-1 inhibitor Adjuvant therapy Recurrence free survival Immunotherapy Real world study
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Predictive value of neutrophil-lymphocyte ratio for prognosis in patients with advanced hepatocellular carcinoma treated with programmed cell death 1 inhibitors 认领 引用
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作者 Rui Guo Meng Gao 《World Journal of Gastroenterology》 SCIE CAS 2026年第18期51-64,共14页
BACKGROUND The neutrophil-lymphocyte ratio(NLR)is an accessible inflammatory biomarker with emerging prognostic value in oncology.AIM To evaluate the predictive value of pretreatment NLR in patients with advanced hepa... BACKGROUND The neutrophil-lymphocyte ratio(NLR)is an accessible inflammatory biomarker with emerging prognostic value in oncology.AIM To evaluate the predictive value of pretreatment NLR in patients with advanced hepatocellular carcinoma(aHCC)undergoing therapy with programmed cell death 1(PD-1)inhibitors.METHODS This retrospective analysis included 234 patients with aHCC who received PD-1 inhibitor therapy between January 2022 and June 2024.The patients were categorized into good or poor prognosis groups according to overall survival relative to the median.The optimal NLR cutoff(3.165)was determined by receiver operator characteristic analysis,defining the low(≤3.165)and high(>3.165)NLR groups.Hematological parameters were measured from blood samples collected within 1 week before treatment initiation.Radiologic assessments were conducted every 6-9 weeks in accordance with Response Evaluation Criteria in Solid Tumors v1.1.Progression-free survival(PFS)and overall survival(OS)were assessed during follow-up.RESULTS The high NLR group had significantly worse tumor burden and more advanced disease compared with the low NLR group.Multivariate analysis identified high NLR as an independent risk factor for poor prognosis(odds ratio=4.365,P<0.001)with the highest predictive accuracy(area under the curve=0.785).The low NLR group demonstrated superior objective response rate(35.66%vs 16.19%,P=0.001)and disease control rate(71.32%vs 57.14%,P=0.024)and had significantly longer median progression-free survival(7.52 months vs 5.21 months,P<0.001)and overall survival(16.84 months vs 11.05 months,P<0.001).Cox regression confirmed that high NLR independently predicted poor PFS(hazard ratio=2.084)and OS(hazard ratio=2.421).CONCLUSION Pretreatment NLR is a powerful,independent prognostic biomarker for patients with aHCC receiving PD-1 inhibitor treatment. 展开更多
关键词 Neutrophil-lymphocyte ratio Hepatocellular carcinoma Programmed cell death 1 inhibitor Prognosis Biomarker Immunotherapy
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Lack of cytoplasmic expression of a new marker programmed cell death ligand-1 in tumor cells is significant 认领 引用
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作者 Marina A Senchukova Evgeniya Yu Zubareva +1 位作者 Natalia V Saidler Lyubov V Krivolapova 《World Journal of Experimental Medicine》 2025年第4期215-237,共23页
BACKGROUND Recent studies have indicated that an antibody against programmed cell death protein 1-ligand 1(PDCD1-LG1),a new marker of programmed cell death-ligand 1 expression,is promising for studying the mechanisms ... BACKGROUND Recent studies have indicated that an antibody against programmed cell death protein 1-ligand 1(PDCD1-LG1),a new marker of programmed cell death-ligand 1 expression,is promising for studying the mechanisms of breast cancer(BC)progression and resistance to chemotherapy.AIM To compare the features of PDCD1-LG1 expression in chemoresistant luminal A BC and BC with high Ki67 indices.METHODS This prospective single-center observational cohort study included 148 patients with newly diagnosed primary resectable BC.The tumor sections were stained with antibodies against PDCD1-LG1.The statistical calculations were performed using Statistica software version 12.0.P<0.05 was considered statistically significant.RESULTS Cytoplasmic PDCD1-LG1(cPDCD1-LG1)expression was detected in the nonneoplastic epithelium,tumor cells(TCs)and immune cells(ICs).A lack of cPDCD1-LG1 expression in≥20% of TCs and a PDCD1-LG1+IC score≥10%were associated with aggressive BC characteristics,including tumor G3,estrogen receptor-negative status,overexpression of human epidermal growth factor receptor 2(HER2+),luminal B HER2+BC,nonluminal HER2+BC and triplenegative BC.The lack of cPDCD1-LG1 expression in<20% of the TCs,in combination with a PDCD1-LG1+IC score<10% and G1,was characteristic of chemoresistant luminal A BC,whereas the lack of cPDCD1-LG1 expression in≥20% of the TCs,combined with a PDCD1-LG1+IC score≥10%,was a predictor of high BC sensitivity to chemotherapy.CONCLUSION These results indicate that both the lack of cPDCD1 LG1 in TCs and the PDCD1 LG1 IC score and their combination may be important for assessing BC prognosis and sensitivity to chemotherapy. 展开更多
关键词 Breast cancer Chemoresistance Programmed death-ligand 1 Programmed cell death protein 1-ligand 1 Сytoplasmic programmed cell death protein 1 ligand 1
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Up-regulated programmed cell death protein-1/its ligand 1 expression promotes metabolic dysfunction-associated steatotic liver disease malignant progression 认领 引用 被引量：1
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作者 Min Xu Tian-Tian Ruan +5 位作者 Hao Tang Rong-Fei Fang Wen-Li Sai Qun Xie Deng-Fu Yao Min Yao 《World Journal of Gastrointestinal Oncology》 SCIE 2025年第5期1-8,共8页
This editorial focuses on the recent article by Yang et al in the World Journal of Gastrointestinal Oncology,which highlights the role of interlukin-17A in promoting hepatocellular carcinoma(HCC)progression by up-regu... This editorial focuses on the recent article by Yang et al in the World Journal of Gastrointestinal Oncology,which highlights the role of interlukin-17A in promoting hepatocellular carcinoma(HCC)progression by up-regulated programmed cell death protein-1(PD-1)/programmed cell death protein ligand-1(PD-L1)expression.Previous,the high PD-1/PD-L1 level was due to hepatitis virus infection leading to systemic innate immune tolerance and cluster of differen-tiation 8+T cells exhaustion,ultimately leading to HCC.Recently,interesting studies have found that the malignant progression of metabolic dysfunction-associated steatotic/fatty liver disease(MASLD/MAFLD),that is former nonalcoholic fatty liver disease,was achieved by up-regulated PD-L1 level that was activated the cGAS-STING pathway under lipid accumulation with mito-chondrial DNA overflow and up-regulated PD-1/PD-L1 to promote MASLD malignant transformation via immune escape.These data suggested that PD-1 or PD-L1 should be a promising target for preventing or delaying non-viral liver disease malignant progression except of antiviral therapy for HCC. 展开更多
关键词 Hepatocytes Metabolic dysfunction-associated steatotic/fatty liver disease Programmed cell death protein-1 Programmed cell death protein ligand-1 Immune escape
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Concordance of programmed death-ligand 1 expression assessments determined via two immunohistochemical tests and the polymerase chain reaction method 认领 引用 被引量：1
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作者 Marina A Senchukova Natalia V Saidler +2 位作者 Evgeniya Yu Zubareva Alexander B Prokofiev Dmitry G Tagabilev 《World Journal of Experimental Medicine》 2025年第3期207-220,共14页
BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both brea... BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both breast cancer(BC)clinicopathological characteristics and tumor sensitivity to chemotherapy.However,the concordance of PDCD1 LG1 expression scoring with immunohistochemical(IHC)tests approved for clinical use and with the polymerase chain reaction(PCR)method has not been previously studied.AIM To evaluate the concordance of methods for assessing PD-L1 expression,IHC tests with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and PCR.METHODS This prospective single-center observational cohort study included 148 patients with BC.PD-L1 expression in immune cells was assessed by the IHC method with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and by PCR.The concordance of PD-L1 scores between tests was assessed with positive percentage agreement(PPA)and negative percentage agreement(NPA).The strength of the agreement between the methods was calculated via the Cohen kappa index.P<0.05 was considered statistically significant.RESULTS Regardless of the method used to assess marker expression,PD-L1 expression was significantly more often detected in patients with negative estrogen receptor status,human epidermal growth factor receptor-2-positive(HER2+)status,luminal B HER+BC,nonluminal HER+BC and triple-negative BC.PPA and NPA were 38.3%and 70.4%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(SP142);26.3%and 63.3%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(PCR);and 36.5%and 74.4%,respectively,for PD-L1(SP142)and PD-L1(PCR).Cohen's kappa index for PD-L1(PDCD1 LG1)and PD-L1(SP142)was 0.385(95%CI:0.304–0.466),that for PD-L1(PDCD1 LG1)and PD-L1(PCR)was 0.207(95%CI:0.127–0.287),and that for PD-L1(SP142)and PD-L1(PCR)was 0.389(95%CI:0.309–0.469).CONCLUSION Thus,all three markers of PD-L1 expression are associated with the characteristics of aggressive BC,demonstrating moderate concordance between the tests. 展开更多
关键词 Breast cancer Cohen kappa index Negative percentage agreement Positive percentage agreement Programmed death-ligand 1 Programmed cell death protein 1 ligand 1
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The assembly and activation of the PANoptosome promote porcine granulosa cell programmed cell death during follicular atresia 认领 引用 被引量：3
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作者 Hao Wu Yingxue Han +6 位作者 Jikang Liu Rong Zhao Shizhen Dai Yajun Guo Nan Li Feng Yang Shenming Zeng 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2025年第1期121-135,共15页
Background Follicular atresia significantly impairs female fertility and hastens reproductive senescence.Apoptosis of granulosa cells is the primary cause of follicular atresia.Pyroptosis and necroptosis,as additional... Background Follicular atresia significantly impairs female fertility and hastens reproductive senescence.Apoptosis of granulosa cells is the primary cause of follicular atresia.Pyroptosis and necroptosis,as additional forms of pro-grammed cell death,have been reported in mammalian cells.However,the understanding of pyroptosis and necrop-tosis pathways in granulosa cells during follicular atresia remains unclear.This study explored the effects of pro-grammed cell death in granulosa cells on follicular atresia and the underlying mechanisms.Results The results revealed that granulosa cells undergo programmed cell death including apoptosis,pyroptosis,and necroptosis during follicular atresia.For the first time,we identified the formation of a PANoptosome com-plex in porcine granulosa cells.This complex was initially identified as being composed of ZBP1,RIPK3,and RIPK1,and is recruited through the RHIM domain.Additionally,we demonstrated that caspase-6 is activated and cleaved,interacting with RIPK3 as a component of the PANoptosome.Heat stress may exacerbate the activation of the PANop-tosome,leading to programmed cell death in granulosa cells.Conclusions Our data identified the formation of a PANoptosome complex that promoted programmed cell death in granulosa cells during the process of follicular atresia.These findings provide new insights into the molecular mechanisms underlying follicular atresia. 展开更多
关键词 Follicular atresia Granulosa cells PANoptosome Programmed cell death
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Targeting Programmed Cell Death in Acquired Sensorineural Hearing Loss:Ferroptosis,Necroptosis,and Pyroptosis 认领 引用 被引量：1
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作者 Shasha Zhang Hairong Xiao +7 位作者 Yanqin Lin Xujun Tang Wei Tong Buwei Shao He Li Lei Xu Xiaoqiong Ding Renjie Chai 《Neuroscience Bulletin》 SCIE CAS CSCD 2025年第6期1085-1102,共18页
Sensorineural hearing loss(SNHL),the most commonly-occurring form of hearing loss,is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea.Numerous environmental and physiolog... Sensorineural hearing loss(SNHL),the most commonly-occurring form of hearing loss,is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea.Numerous environmental and physiological factors have been shown to cause acquired SNHL,such as ototoxic drugs,noise exposure,aging,infections,and diseases.Several programmed cell death(PCD)pathways have been reported to be involved in SNHL,especially some novel PCD pathways that have only recently been reported,such as ferroptosis,necroptosis,and pyroptosis.Here we summarize these PCD pathways and their roles and mechanisms in SNHL,aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways. 展开更多
关键词 Sensorineural hearing loss Programmed cell death Ferroptosis Necroptosis Pyroptosis
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Programmed death-ligand 1 regulates ameloblastoma growth and recurrence 认领 引用 被引量：1
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作者 Linzhou Zhang Hao Lin +6 位作者 Jiajie Liang Xuanhao Liu Chenxi Zhang Qiwen Man Ruifang Li Yi Zhao Bing Liu 《International Journal of Oral Science》 SCIE CAS CSCD 2025年第2期233-243,共11页
Tumor cell-intrinsic programmed death-ligand 1(PD-L1)signals mediate tumor initiation,progression and metastasis,but their effects in ameloblastoma(AM)have not been reported.In this comprehensive study,we observed mar... Tumor cell-intrinsic programmed death-ligand 1(PD-L1)signals mediate tumor initiation,progression and metastasis,but their effects in ameloblastoma(AM)have not been reported.In this comprehensive study,we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates.Notably,we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT+-AM cells,whereas genetic ablation of PD-L1 exerted opposing inhibitory effects.By performing highresolution single-cell profiling and thorough immunohistochemical analyses in AM patients,we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors.Our findings revealed that hTERT+-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial-mesenchymal transition.This phenotypic shift is induced by the activation of the PI3KAKT-mTOR signaling axis;thus,this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence.Importantly,targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patientderived tumor organoids,highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM. 展开更多
关键词 tumorigenic processes high resolution single cell profiling tumor cell intrinsic recurrence PI K AKT mTOR signaling axis programmed death ligand tumor growth immunohistochemical analyses
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Relationship between Helicobacter pylori infection and programmed death-ligand 1 in gastric cancer:A meta-analysis 认领 引用 被引量：1
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作者 Hong-Chang Yang Cheng-Feng Fu +3 位作者 Li-Jun Qiao Gen-He Long Li-Fen Yang Biao Yao 《World Journal of Clinical Oncology》 2025年第4期280-290,共11页
BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a ... BACKGROUND Gastric cancer(GC)is one of the most common malignancies worldwide,and Helicobacter pylori(HP)infection is a well-established risk factor for its development.Programmed death-ligand 1(PD-L1)expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment.While HP infection and PD-L1 expression in GC may be linked,the relationship between them remains unclear,in part because there have been conflicting results reported from various studies.AIM To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.METHODS A systematic literature review was conducted using PubMed,Embase,Cochrane Library,and Web of Science databases.Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included.Odds ratios and 95%confidence intervals were calculated to estimate the association.Heterogeneity was assessed using Cochrane’s Q test and I²statistic.A random-effects model was used due to significant heterogeneity across studies.RESULTS Fourteen studies involving a total of 3069 patients with GC were included.The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues(odd ratio=1.69,95%confidence interval:1.24-2.29,P<0.001,I2=59%).Sensitivity analyses confirmed the robustness of these findings.Subgroup analyses did not show significant variation based on geographic region,sample size,or method of PD-L1 assessment.Publication bias was minimal,as shown by funnel plots and Egger’s regression test.CONCLUSION HP infection is associated with increased PD-L1 expression in GC,suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy. 展开更多
关键词 Helicobacter pylori Gastric cancer Programmed cell death protein 1/programmed death-ligand 1 Immune checkpoint blockade therapy Pathogenesis
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Interleukin-17A facilitates tumor progression via upregulating programmed death ligand-1 expression in hepatocellular carcinoma 认领 引用 被引量：1
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作者 Zhong-Xia Yang Li-Ting Zhang +2 位作者 Xiao-Jun Liu Xue-Bin Peng Xiao-Rong Mao 《World Journal of Gastrointestinal Oncology》 SCIE 2025年第1期176-198,共23页
BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in th... BACKGROUND Hepatocellular carcinoma(HCC)is an inflammation-associated tumor with a dismal prognosis.Immunotherapy has become an important treatment strategy for HCC,as immunity is closely related to inflammation in the tumor microenvir-onment.Inflammation regulates the expression of programmed death ligand-1(PD-L1)in the immunosuppressive tumor microenvironment and affects im-munotherapy efficacy.Interleukin-17A(IL-17A)is involved in the remodeling of the tumor microenvironment and plays a protumor or antitumor role in different tumors.We hypothesized that IL-17A participates in tumor progression by affe-cting the level of immune checkpoint molecules in HCC.The upregulation of PD-L1 expression in HCC cells by IL-17A was assessed by reverse transcription PCR,western blotting,and flow cytometry.Mechanistic studies were conducted with gene knockout models and pathway inhibitors.The function of IL-17A in immune evasion was explored through coculture of T cells and HCC cells.The effects of IL-17A on the malignant biological behaviors of HCC cells were evaluated in vitro,and the antitumor effects of an IL-17A inhibitor and its synergistic effects with a PD-L1 inhibitor were studied in vivo.RESULTS IL-17A upregulated PD-L1 expression in HCC cells in a dose-dependent manner,whereas IL-17A receptor knockout or treatment with a small mothers against decapentaplegic 2 inhibitor diminished the PD-L1 expression induced by IL-17A.IL-17A enhanced the survival of HCC cells in the coculture system.IL-17A increased the viability,G2/M ratio,and migration of HCC cells and decreased the apoptotic index.Cyclin D1,VEGF,MMP9,and Bcl-1 expression increased after IL-17A treatment,whereas BAX expression decreased.The combination of IL-17A and PD-L1 inhibitors showed synergistic antitumor efficacy and increased cluster of differentiation 8+T lymphocyte infiltration in an HCC mouse model.CONCLUSION IL-17A upregulates PD-L1 expression via the IL-17A receptor/phosphorylation-small mothers against decapenta-plegic 2 signaling pathway in HCC cells.Blocking IL-17A enhances the therapeutic efficacy of PD-L1 antibodies in HCC in vivo. 展开更多
关键词 Interleukin-17A Programmed death ligand-1 Interleukin-17A receptor Small mothers against decapentaplegic 2 Hepatocellular carcinoma Immunotherapy
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Irreversible electroporation combined with anti-programmed cell death protein 1 therapy promotes tumor antigen-specific CD8+T cell response 认领 引用 被引量：1
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作者 Yang-Yang Ma Xiao-Hua Wang +2 位作者 Jian-Ying Zeng Ji-Bing Chen Li-Zhi Niu 《World Journal of Gastrointestinal Oncology》 SCIE 2025年第3期237-245,共9页
BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and com... BACKGROUND Irreversible electroporation(IRE)is a novel local tumor ablation approach with the potential to activate the host’s immune system.However,this approach is insufficient to prevent cancer progression,and complementary approaches are required for effective immunotherapy.AIM To assess the immunomodulatory effects and mechanism of IRE combined antiprogrammed cell death protein 1(PD-1)treatment in subcutaneous pancreatic cancer models.METHODS C57BL-6 tumor-bearing mice were randomly divided into four groups:Control group;IRE group;anti-PD-1 group;and IRE+anti-PD-1 group.Tumor-infiltrating T,B,and natural killer cell levels and plasma concentrations of T helper type 1 cytokines(interleukin-2,interferon-γ,and tumor necrosis factor-α)were evaluated.Real-time PCR was used to determine the expression of CD8(marker of CD8+T cells)in tumor tissues of the mice of all groups at different points of time.The growth curves of tumors were drawn.RESULTS The results demonstrated that the IRE+anti-PD-1 group exhibited significantly higher percentages of T lymphocyte infiltration,including CD4+and CD8+T cells compared with the control group.Additionally,the IRE+anti-PD-1 group showed increased infiltration of natural killer and B cells,elevated cytokine levels,and higher CD8 mRNA expression.Tumor volume was significantly reduced in the IRE+anti-PD-1 group,indicating a more pronounced therapeutic effect.CONCLUSION The combination of IRE and anti-PD-1 therapy promotes CD8+T cell immunity responses,leading to a more effective reduction in tumor volume and improved therapeutic outcomes,which provides a new direction for ablation and immunotherapy of pancreatic cancer. 展开更多
关键词 Irreversible electroporation Pancreatic cancer Programmed cell death protein 1 blockade CD8+T cell Anticancer immunity
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Chemotherapy plus bevacizumab with or without anti-programmed death 1 immunotherapy as the second-line therapy in colorectal cancer 认领 引用
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作者 Zhao Gao Xiao-Yan Wang +4 位作者 Zhi-Gang Shen Jia-Hua Liu Xiao-Yun Wang Shi-Kai Wu Xuan Jin 《World Journal of Gastroenterology》 SCIE CAS 2025年第21期31-46,共16页
BACKGROUND Patients with microsatellite stable(MSS)metastatic colorectal cancer(mCRC)typically exhibit an immunosuppressive tumor microenvironment and demonstrate a low response rate to immunotherapy.Reports suggest t... BACKGROUND Patients with microsatellite stable(MSS)metastatic colorectal cancer(mCRC)typically exhibit an immunosuppressive tumor microenvironment and demonstrate a low response rate to immunotherapy.Reports suggest that chemotherapy and anti-angiogenic therapy may have the potential to enhance the response to immunotherapy in these patients.This study aims to evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without antiprogrammed death 1(PD-1)immunotherapy as the second-line regimen for MSS mCRC.AIM To evaluate the effectiveness and safety of chemotherapy combined with bevacizumab with or without anti-PD-1 immunotherapy as the second-line regimen for MSS mCRC.METHODS A retrospective analysis was conducted on patients with MSS mCRC diagnosed at Peking University First Hospital and Jilin Cancer Hospital from January 2020 to December 2024.The patients were divided into two groups:The experimental group receiving second-line chemotherapy combined with bevacizumab and anti-PD-1 immunotherapy,and the control group receiving chemotherapy combined with bevacizumab.Propensity score matching was applied to balance potential prognostic factors,including age,gender,Eastern Cooperative Oncology Group score,number of metastases,and primary tumor site.The progression-free survival,overall survival,disease control rate,objective response rate,and treatment-related adverse reactions were compared between the two groups.Kaplan-Meier analysis and log-rank test were used to compare survival outcomes.Inverse probability of treatment weighting was used for sensitivity analysis.RESULTS Propensity score matching resulted in 103 matched eligible patients.The median follow-up period was 13.9 months in the matched cohort.The objective response rate was 11.5%and 9%for the experimental and control groups,respectively(P=0.710),while the disease control rate was 76.9%and 53.2%,respectively(P=0.058).The median progression-free survival in the experimental group was 8.27 months[95%confidence interval(CI):6.7-14.7 months],significantly higher than that in the control group,which was 4.63 months(95%CI:3.9-5.67 months)(hazard ratio=0.4143,95%CI:0.2462-0.6972,P=0.00066).There was a trend towards the higher median overall survival in the experimental group compared to the control group(hazard ratio=0.4504,95%CI:0.1897-1.07,P=0.064).The incidences of adverse events were similar between the two groups.CONCLUSION Compared with the standard second-line chemotherapy combined with bevacizumab regimen,second-line therapy that combines chemotherapy with bevacizumab and anti-PD-1 immunotherapy has demonstrated promising efficacy in the treatment of MSS mCRC,while exhibiting a similar safety profile. 展开更多
关键词 Microsatellite stable RAS mutation Metastatic colorectal cancer Immune checkpoint inhibitors Programmed death 1
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Programmed cell death receptor 1 inhibitor Pembrolizumab in the treatment of advanced gastric cancer 认领 引用
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作者 Xue-Mei Yi Hong-Qiao Cai Yan Jiao 《World Journal of Gastrointestinal Surgery》 SCIE 2025年第2期16-19,共4页
This editorial discusses Christodoulidis et al's article,which appeared in the most recent edition.The clinical trials have demonstrated the programmed cell death receptor 1(PD-1)inhibitor Pembrolizumab involved c... This editorial discusses Christodoulidis et al's article,which appeared in the most recent edition.The clinical trials have demonstrated the programmed cell death receptor 1(PD-1)inhibitor Pembrolizumab involved combination therapy can improve the efficacy of advanced gastric cancer(AGC).Pembrolizumab combined with chemotherapy can enhance its sensitivity,and further eliminate tumor cells that develop resistance to chemotherapy.The combination of Pembrolizumab and Trastuzumab targeting human epidermal growth factor receptor 2 showed improved prognosis.The overall toxic effects of Pembrolizumab are significantly lower than traditional chemotherapy,and the safety is controllable.PD-1 inhibitor Pembrolizumab sheds a light on the treatment of AGC and brings new hope to the clinical practice. 展开更多
关键词 Programmed cell death receptor 1 inhibitor Pembrolizumab Advanced gastric cancer Chemotherapy Trastuzumab
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Adding programmed death 1/programmed death ligand 1 inhibitors to first-line standard-of-care therapy for metastatic colorectal cancer:A meta-analysis 认领 引用
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作者 Ting Zheng Xing-Xing Li +1 位作者 Li Zhou Jian-Jiang Jin 《World Journal of Clinical Oncology》 2025年第8期230-242,共13页
BACKGROUND In recent years,emerging clinical research has prioritized assessment of combined therapeutic efficacy and safety parameters when programmed death 1 or its ligand(PD-1/L1)inhibitors are incorporated into fi... BACKGROUND In recent years,emerging clinical research has prioritized assessment of combined therapeutic efficacy and safety parameters when programmed death 1 or its ligand(PD-1/L1)inhibitors are incorporated into first-line standard-of-care(SOC)therapy for metastatic colorectal cancer(mCRC).However,data obtained from these trials demonstrated conflicting evidence concerning survival benefits and clinical outcomes.AIM To evaluate the therapeutic impact and safety parameters of combining PD-1/L1 inhibitors with SOC protocols as first-line treatment for mCRC.METHODS Four biomedical databases(PubMed,Embase,Cochrane Library,Web of Science)were systematically interrogated to identify eligible studies published up to October 12,2024.The analysis focused on evaluating the primary outcome of overall survival(OS)in the mCRC population with secondary outcomes of progression-free survival(PFS),overall response rate(ORR),and incidence rate of grade≥3 adverse events.Additionally,we performed exploratory analyses in the microsatellite stable/mismatch repair-proficient(MSS/pMMR)subpopulation,based on a subset of the included studies.Subgroup analyses according to PD-1/L1 inhibitor use were conducted in both the overall population and the MSS/pMMR subgroup.RESULTS This pooled analysis incorporated six randomized controlled trials involving 675 patients with mCRC receiving first-line therapy.The combination of PD-1/L1 inhibitors with SOC regimens demonstrated a significant PFS advantage over SOC monotherapy in intention-to-treat populations[hazard ratio(HR)=0.8,95%confidence interval(CI):0.65-0.98,P=0.033].Nevertheless,the MSS/pMMR subgroup showed no PFS benefit(HR=0.83,95%CI:0.67-1.03,P=0.091),and no cohort exhibited OS improvement(intention-to-treat:HR=0.84,95%CI:0.66-1.05,P=0.124;MSS/pMMR:HR=0.79,95%CI:0.60-1.03,P=0.083).Comparable outcomes were observed for ORR(risk ratio=1.03,95%CI:0.90-1.17,P=0.711)and incidence rate of grade≥3 adverse events(risk ratio=1.12,95%CI:0.93-1.36,P=0.245)between treatment arms.CONCLUSION The findings indicated that integrating PD-1/L1 blocking agents with SOC regimens for mCRC as first-line treatment failed to demonstrate significant improvements in ORR.Existing clinical data remain inadequate to establish OS advantages,particularly in patients with MSS/pMMR,despite exhibiting manageable toxicity profiles.Subsequent confirmation through rigorously designed phase III clinical trials remains essential to verify these therapeutic outcomes. 展开更多
关键词 Programmed death 1 Programmed death ligand 1 Standard-of-care Metastatic colorectal cancer First-line Metaanalysis
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Pescadillo ribosomal biogenesis factor 1 and programmed deathligand 1 in gastric and head and neck squamous cell carcinoma 认领 引用 被引量：1
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作者 Xiao-Nan Hu Chun-Feng Li +2 位作者 Si-Meng Huang Chun-Lei Nie Rui Pang 《World Journal of Gastroenterology》 SCIE CAS 2025年第19期100-108,共9页
BACKGROUND Gastric cancer(GC)and head and neck squamous cell carcinoma(HNSCC)are common malignancies with high morbidity and mortality rates.Traditional treatments often yield limited efficacy,especially in advanced c... BACKGROUND Gastric cancer(GC)and head and neck squamous cell carcinoma(HNSCC)are common malignancies with high morbidity and mortality rates.Traditional treatments often yield limited efficacy,especially in advanced cases.Recent advancements in immunotherapy,particularly immune checkpoint inhibitors targeting programmed death-ligand 1(PD-L1),have shown promise.However,the expression and interaction of pescadillo ribosomal biogenesis factor 1(PES1)and PD-L1 in these cancers remain unclear.Understanding their roles could provide new insights into tumor biology and improve therapeutic strategies.AIM To investigate the expression levels of PES1 and PD-L1 in tumor tissues of patients with GC and HNSCC.METHODS A total of 58 cases of GC and HNSCC undergoing surgical resection were selected from January 2022 to January 2024.Paraffin specimens of GC and HNSCC tissues were taken from the patients,and the sections were subjected to staining with immunohistochemistry and hematoxylin-eosin staining,and the protein expression of PES1 and PD-L1 was observed microscopically.RESULTS Among 58 GC and HNSCC tissues,30 cases were positive and 28 cases were negative for PES1 expression,and 34 cases were positive and 24 cases were negative for PD-L1 expression.The positive expression rates of PES1 and PDL1 were 51.72% and 58.62%,respectively.PES1 expression was correlated with the TNM stage,lymph node metastasis,and the depth of infiltration(P<0.05),and PD-L1 expression was correlated with the differentiation degree,lymph node metastasis,and infiltration depth(P<0.05).CONCLUSION PES1 and PD-L1 were positively expressed in GC and HNSCC tissues and correlated with clinical features.They may serve as potential biomarkers for immune-targeted therapies. 展开更多
关键词 Pescadillo ribosomal biogenesis factor 1 Programmed death-ligand 1 Gastric cancer Head and neck squamous cell carcinoma Expression level
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Cytoplasmic and nuclear programmed death ligand 1 expression in peritumoral stromal cells in breast cancer:Prognostic and predictive value 认领 引用 被引量：2
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作者 Evgeniya Yu Zubareva Marina A Senchukova Natalia V Saidler 《World Journal of Experimental Medicine》 2025年第2期150-170,共21页
BACKGROUND Breast cancer(BC)continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population.One of the promising markers associated with BC progression i... BACKGROUND Breast cancer(BC)continues to occupy a leading position in terms of morbidity and mortality from malignant neoplasms among the female population.One of the promising markers associated with BC progression is programmed death ligand 1(PD-L1).Previously,we investigated PD-L1 expression in BC via a new antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)and reported that high PDCD1 LG1 expression in tumor cells is an independent factor for a high risk of regional metastasis in patients with BC.However,the prognostic significance of PDCD1 LG1 expression in BC stromal cells has not been adequately studied.AIM To study the features of PDCD1 LG1 expression in BC stromal cells and its relationship with BC clinicopathological characteristics.METHODS In a prospective single-center observational study,tumor samples from 148 patients with newly diagnosed BC were examined.The tumor sections were immunohistochemically stained with antibodies against PDCD1 LG1.In the tumor samples,the PDCD1 LG1-positive lymphocyte(PDCD1 LG1+LF)score,presence of nuclear PDCD1 LG1 expression in the LFs,PDCD1 LG1 expression in polymorphic cell infiltrates(PDCD1 LG1+polymorphic cell infiltrates[PCIs]),and cells of the fibroblastic stroma and endothelial cells of the tumor microvessels were assessed.Statistical analyses were performed using Statistica 10.0 software.RESULTS A PDCD1 LG1+LF score≥3 was detected more often at stages N0 and N3 than at N1 and N2(P=0.03).Moderate and pronounced PDCD1 LG1+PCIs and the presence of PDCD1 LG1+fibroblastic stroma were associated with negative estrogen receptor status(P=0.0008 and P=0.03,respectively),human epidermal growth factor receptor 2-positive(HER2+)BC(P<0.00001 and P=0.0005),and luminal B HER2+,non-luminal HER2+and triple-negative BC(P<0.00001 and P=0.004).The risk of metastasis to regional lymph nodes(RLNs)depend on lymphovascular invasion(LVI)and the PDCD1 LG1+LF score.In the absence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were absent in 66.6%and 93.9%of patients with BC,respectively.In the presence of LVI and a PDCD1 LG1+LF score<3 or≥3,metastases in RLNs were detected in 82.6%and 92.7%of patients with BC,respectively.CONCLUSION The results indicated that the combined assessment of the PDCD1 LG1+LF score and LVI can improve the accuracy of predicting the risk of metastasis to RLNs in patients with BC. 展开更多
关键词 Breast cancer Programmed death-ligand 1 Regional metastasis Tumor stroma
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