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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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Comprehensive insights into the effects and regulatory mechanisms of immune cells expressing programmed death-1/programmed death ligand 1 in solid tumors 认领 引用 被引量：11
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作者 Min Liu Qian Sun +1 位作者 Feng Wei Xiubao Ren 《Cancer Biology & Medicine》 SCIE CAS CSCD 2020年第3期626-639,共14页
The programmed cell death-1(PD-1)/programmed cell death ligand 1(PD-L1)signaling pathway is an important mechanism in tumor immune escape,and expression of PD-L1 on tumor cells has been reported more frequently.Howeve... The programmed cell death-1(PD-1)/programmed cell death ligand 1(PD-L1)signaling pathway is an important mechanism in tumor immune escape,and expression of PD-L1 on tumor cells has been reported more frequently.However,accumulating evidence suggests that PD-1/PD-L1 is also widely expressed on immune cells,and that regulation is also critical for tumor immune responses.In this review,we emphasized that under solid tumor conditions,the immunoregulatory effects of immune cells expressing PD-1 or PD-L1,affected the prognoses of cancer patients.Therefore,a better understanding of the mechanisms that regulate PD-1 or PD-L1 expression on immune cells would provide clear insights into the increased efficacy of anti-PD antibodies and the development of novel tumor immunotherapy strategies. 展开更多
关键词 Immune cell immunotherapy programmed cell death ligand 1 programmed cell death-1 solid tumor
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Research progress regarding programmed cell death 1/programmed cell death ligand 1 inhibitors combined with targeted therapy for treating hepatocellular carcinoma 认领 引用
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作者 Lin-Lin Zheng Chang-Cheng Tao +4 位作者 Zong-Gui Tao Kai Zhang An-Ke Wu Jian-Xiong Wu Wei-Qi Rong 《World Journal of Gastrointestinal Surgery》 SCIE 2021年第10期1136-1148,共13页
In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is... In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is considered to be an effective treatment for advanced HCC.Immune checkpoint inhibitors targeting programmed cell death 1(PD-1)/programmed cell death ligand 1(PDL1)are important antitumor immunotherapy agents that represent breakthroughs in the treatment of advanced HCC.However,treating advanced HCC is still a great challenge,and the need for new treatments remains urgent.This review briefly summarizes the research progress in the use of PD-1/PD-L1 inhibitors combined with targeted therapy for treating HCC. 展开更多
关键词 Programmed cell death 1/programmed cell death ligand 1 inhibitors Targeted therapy Hepatocellular carcinoma Programmed cell death 1 Programmed cell death ligand 1
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Programmed death-1/programmed death-L1 signaling pathway and its blockade in hepatitis C virus immunotherapy 认领 引用 被引量：10
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作者 Mohamed L Salem Ahmed El-Badawy 《World Journal of Hepatology》 2015年第23期2449-2458,共10页
Chronic hepatitis C virus(HCV) infection is a public health issue that often progresses to life-threatening complications, including liver cirrhosis, fibrosis, and hepatocellular carcinoma. Impaired immune responses t... Chronic hepatitis C virus(HCV) infection is a public health issue that often progresses to life-threatening complications, including liver cirrhosis, fibrosis, and hepatocellular carcinoma. Impaired immune responses to HCV are key features of chronic HCV infection. Therefore, intervention strategies usually involve enhancing the immune responses against HCV. Cytotoxic CD8+ T lymphocytes(CTLs) play a critical role in the control of HCV infection. However, their cytolytic function can be impaired by the expression of co-inhibitory molecules. Programmed death-1(PD-1) receptor and its ligand PD-L1 function in a T cell co-inhibitory pathway, which either blocks the function of CTLs or the differentiation of CD8+ T cells. During chronic HCV infection, the immune inhibitory receptor PD-1 is upregulated on dysfunctional HCV-specific CD8+ T cells. As such, blockade of the PD-1/PD-L1 pathway in these CD8+ T cells might restore their functional capabilities. Indeed, clinical trials using therapies to block this pathway have shown promise in the fostering of anti-HCV immunity. Understanding how chronic HCV infection induces upregulation of PD-1 on HCV specific T cells and how the PD-1/PD-L1 interaction develops HCV specific T cell dysfunction will accelerate the development of an efficacious prophylactic and therapeutic vaccination against chronic HCV infections, which will significantly improve HCV treatments and patient survival. In this review, we discuss the relationship between PD-1 expression and clinical responses and the potential use of PD-1 blockade for anti-HCV therapy. 展开更多
关键词 Hepatitis C virus Programmed death-1 Hepatitis C v
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Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells 认领 引用
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作者 Caecilia H C Sukowati Korri Elvanita El-Khobar Claudio Tiribelli 《World Journal of Stem Cells》 SCIE 2021年第7期795-824,共30页
Hepatocellular carcinoma(HCC)is a heterogeneous malignancy related to diverse etiological factors.Different oncogenic mechanisms and genetic variations lead to multiple HCC molecular classifications.Recently,an immune... Hepatocellular carcinoma(HCC)is a heterogeneous malignancy related to diverse etiological factors.Different oncogenic mechanisms and genetic variations lead to multiple HCC molecular classifications.Recently,an immune-based strategy using immune checkpoint inhibitors(ICIs)was presented in HCC therapy,especially with ICIs against the programmed death-1(PD-1)and its ligand PD-L1.However,despite the success of anti-PD-1/PD-L1 in other cancers,a substantial proportion of HCC patients fail to respond.In this review,we gather current information on biomarkers of anti-PD-1/PD-L1 treatment and the contribution of HCC heterogeneity and hepatic cancer stem cells(CSCs).Genetic variations of PD-1 and PD-L1 are associated with chronic liver disease and progression to cancer.PD-L1 expression in tumoral tissues is differentially expressed in CSCs,particularly in those with a close association with the tumor microenvironment.This information will be beneficial for the selection of patients and the management of the ICIs against PD-1/PD-L1. 展开更多
关键词 Hepatocellular carcinoma Programmed death-1 Programmed death ligand 1 Cancer stem cells Cancer heterogeneity Genetic variants
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Clinical significance of programmed death 1/programmed death ligand 1 pathway in gastric neuroendocrine carcinomas 认领 引用 被引量：5
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作者 Min-Wei Yang Xue-Liang Fu +12 位作者 Yong-Sheng Jiang Xiao-Jing Chen Ling-Ye Tao Jian-Yu Yang Yan-Miao Huo Wei Liu Jun-Feng Zhang Pei-Feng Liu Qiang Liu Rong Hua Zhi-Gang Zhang Yong-Wei Sun De-Jun Liu 《World Journal of Gastroenterology》 SCIE CAS 2019年第14期1684-1696,共13页
BACKGROUND Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1(PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, t... BACKGROUND Recently, more and more studies have demonstrated the pivotal role of programmed death 1/programmed death ligand 1(PD-1/PD-L1) pathway in the immune evasion of tumors from the host immune system. However, the role of PD-1/PD-L1 pathway in gastric neuroendocrine carcinomas(G-NECs) remains unknown.AIM To investigate the expression of PD-1/PD-L1 and role of PD-1/PD-L1 pathway in G-NECs, which occur rarely but are highly malignant and clinically defiant.METHODS We investigated the expression of PD-L1 on tumor cells and PD-1^+, CD8^+, and FOXP3^+ T cell infiltration by immunohistochemistry in 43 resected G-NEC tissue specimens. The copy number alterations of PD-L1 were assessed by qRT-PCR.RESULTS Most of the G-NECs tumor cells exhibited a near-uniform expression pattern of PD-L1, while some showed a tumor-stromal interface enhanced pattern. Of the 43G-NECs, 21(48.8%) were classified as a high PD-L1 expression group, and the high expression of PD-L1 was associated with poor overall survival(OS). The high expression of PD-L1 was correlated with abundant PD-1^+ tumor infiltrating lymphocytes(TILs) instead of CD8^+ TILs and FOXP3^+ regulatory T cells(Tregs).Our analysis also suggested that the infiltration of CD8^+ TILs tended to be a favorable factor for OS, although the difference did not reach the statistical significance(P = 0.065). Meanwhile, PD-L1 was significantly overexpressed in cases with copy number gain as compared with those without.CONCLUSION Our data demonstrated for the first time that high expression of PD-L1 in GNECs is associated with a poor prognosis, while the high expression may be due to the copy number variation of PD-L1 gene or stimulation of TILs. These results provide a basis for the immunotherapy targeting PD-1/PD-L1 pathway in GNECs. 展开更多
关键词 Programmed death 1 Programmed death ligand 1 Gastric neuroendocrine carcinomas Prognosis Tumor infiltrating lymphocytes
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Current situation of programmed cell death protein 1/programmed cell death ligand 1 inhibitors in advanced triple-negative breast cancer 认领 引用 被引量：5
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作者 Yuehua Liang Xiaoran Liu +1 位作者 Kun Li Huiping Li 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2022年第2期117-130,共14页
Triple-negative breast cancer(TNBC)has the worst prognosis among all molecular types of breast cancer.Because of the strong immunogenicity of TNBC cells,programmed death 1/programmed death ligand 1(PD-1/PD-L1)inhibito... Triple-negative breast cancer(TNBC)has the worst prognosis among all molecular types of breast cancer.Because of the strong immunogenicity of TNBC cells,programmed death 1/programmed death ligand 1(PD-1/PD-L1)inhibitors,two kinds of immune checkpoint blockade agents,might help improve the prognosis of TNBC.However,how to better use PD-1/PD-L1 inhibitors and select patients who may benefit from treatment options remains controversial.This article summarizes published clinical studies in which PD-1/PD-L1 inhibitors were used in patients with advanced TNBC to explore how to maximize effectiveness of these medications. 展开更多
关键词 TNBC PD-L1/PD-1 PD-L1/PD-1 inhibitor immune checkpoint block
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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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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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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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FTCSEM—A FORTRAN-based parallelized 1D CSEM forward and inversion program for arbitrary source-receiver geometry 认领 引用
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作者 Wei-ying Chen Si-xu Han +2 位作者 Wan-ting Song Yu-lian Zhu Zheng Liu 《Applied Geophysics》 SCIE CSCD 2026年第2期693-709,870,共17页
This study introduces FTCSEM,a FORTRAN-based,parallelized one-dimensional controlledsource electromagnetic(CSEM)forward modeling and inversion software capable of accommodating arbitrary source-receiver confi guration... This study introduces FTCSEM,a FORTRAN-based,parallelized one-dimensional controlledsource electromagnetic(CSEM)forward modeling and inversion software capable of accommodating arbitrary source-receiver confi gurations.In comparison to existing one-dimensional CSEM tools,FTCSEM incorporates several signifi cant enhancements:it supports transmitters of diverse shapes,quantities,and spatial locations;permits receivers to be positioned flexibly on the surface,subsurface,or in the atmosphere;facilitates simulations and inversions in both frequency and time domains;integrates an adaptive regularized inversion algorithm with multiple model constraints;and leverages GPU-accelerated parallel computing to attain high computational efficiency.Validation through numerical experiments and field data inversion confirms the program’s accuracy and practical applicability.The findings indicate that FTCSEM performs robustly in complex geoelectric environments,multi-source and multi-receiver arrangements,as well as multi-component joint inversion scenarios,thereby offering a versatile and powerful tool for advancing CSEM research and applications. 展开更多
关键词 CSEM forward modeling regularized inversion parallel computing program
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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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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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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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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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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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Coordinated DNA methyltransferase 3A and methyltransferase-like 7A activity reprograms the tumor microenvironment through discoidin domain receptor 1 signaling 认领 引用
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作者 Zhengyang Bai Dan Yang +3 位作者 Jiayi Li Yaobang Liu Bin Lian Jinping Li 《Cancer Biology & Medicine》 SCIE CAS CSCD 2026年第1期107-132,共26页
Objective:Breast cancer is the most common malignancy in women and is characterized by a high recurrence rate that severely impacts patient survival.Regulatory T cells(Tregs)in the tumor microenvironment(TME)promote i... Objective:Breast cancer is the most common malignancy in women and is characterized by a high recurrence rate that severely impacts patient survival.Regulatory T cells(Tregs)in the tumor microenvironment(TME)promote immune evasion and metastasis,increasing recurrence risk.This study determined how the epigenetic regulators,DNMT3A and METTL7A,modulate Treg infiltration via the DDR1/STAT3/CXCL5 axis and influence breast cancer recurrence and prognosis.Methods:RNA sequencing(RNA-seq)was used to identify differentially expressed genes(DEGs),followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.Machine learning algorithms,including least absolute shrinkage and selection operator(LASSO),supported vector machine-recursive feature elimination(SVM-RFE)and ElasticNet identified DDR1 as a key gene.Validation included RT-qPCR,western blot,MSP,MeRIP-qPCR,and Co-IP to assess epigenetic regulation.Functional assays(CCK-8,Transwell,and Treg differentiation/chemotaxis)and xenograft models evaluated the role of DDR1 in tumor progression and recurrence.Results:DNMT3A upregulated DDR1 via DNA methylation,while METTL7A enhanced DDR1 mRNA stability via m6A modification.Co-regulation activated the DDR1/STAT3/CXCL5 axis,which boosted cancer cell proliferation,migration,and invasion.CXCL5 secretion increased Treg infiltration and accelerated tumor growth in vivo.DDR1 silencing reversed these effects,confirming that DDR1 has a pivotal role in breast cancer recurrence.Conclusion:DNMT3A and METTL7A were shown to cooperatively regulate DDR1 via DNA/m6A methylation,which drives Tregmediated immune suppression and recurrence.This study provided novel insights and therapeutic targets for breast cancer prognosis and treatment. 展开更多
关键词 Tumor microenvironment DNMT3A METTL7A DDR1/STAT3/CXCL5 axis Discoidin domain receptor 1
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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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