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
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
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
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
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,I^(2)=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
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
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
BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment opti...BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.展开更多
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
Objective:To investigate the impact of programmed harmonious nursing combined with hierarchical management on nursing quality and satisfaction in a health management center.Methods:A total of 100 patients who received...Objective:To investigate the impact of programmed harmonious nursing combined with hierarchical management on nursing quality and satisfaction in a health management center.Methods:A total of 100 patients who received care at this health management center from January 2024 to January 2025 were selected as subjects.Using a random number table method,they were divided into an observation group(n=50)and a control group(n=50).The control group followed traditional methods,while the observation group integrated programmed harmonious nursing with hierarchical management.Comparative analysis was conducted on nursing quality scores,adverse event occurrence rates,and patient satisfaction between the two groups.Results:The observation group showed significantly improved nursing quality scores(P<0.05)and markedly reduced incidence of adverse events(P<0.05),with statistically significant differences compared to pre-treatment conditions(P<0.05).Conclusion:The combination of hierarchical management and programmed harmonious nursing demonstrates effectiveness in enhancing medical service quality,reducing adverse reactions,and improving patient satisfaction—a method worthy of promotion.展开更多
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
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
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
BACKGROUND Immune checkpoint inhibitors(ICIs)are a new class of antitumor agents.They enhance antitumor effects by blocking inhibitory receptors and related ligands expressed on T cells.ICIs also modulate regular immu...BACKGROUND Immune checkpoint inhibitors(ICIs)are a new class of antitumor agents.They enhance antitumor effects by blocking inhibitory receptors and related ligands expressed on T cells.ICIs also modulate regular immune cell activity,affecting the immune system and causing immune-related adverse events.The renal system is sometimes affected by these adverse events.Currently,the literature on ICIs-related glomerular injuries is scarce.CASE SUMMARY We present a patient who developed granulomatosis with polyangiitis(GPA)3 weeks after treatment with the anti-programmed cell death-1 inhibitor,tislel-izumab.The patient experienced proteinuria,hematuria,and acute kidney injury without pulmonary hemorrhage and tested positive for anti-neutrophil cyto-plasmic antibody(ANCA)-cytoplasmic type.Renal biopsy confirmed ANCA-associated vasculitis,and GPA was finally diagnosed.The patient received pulse treatment with glucocorticoids and cyclophosphamide,and renal function improved.After self-discontinuation of the drug,the disease recurred,and the original treatment regimen was continued.However,the patient’s renal function continued to deteriorate.CONCLUSION Glucocorticoids plus cyclophosphamide are effective for treating GPA induced by tislelizumab.However,follow-up and patient education are needed.展开更多
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
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
Programmed cell death(PCD)plays a crucial role in the biological processes of living organisms and occurs in various forms,such as apoptosis,necroptosis and ferroptosis.However,traditional methods for PCD analysis are...Programmed cell death(PCD)plays a crucial role in the biological processes of living organisms and occurs in various forms,such as apoptosis,necroptosis and ferroptosis.However,traditional methods for PCD analysis are time-consuming and complex.In this paper,we propose a facile surface-enhanced Raman spectroscopy(SERS)-based strategy for the real-time analysis of three PCD patterns utilizing black phosphorus–gold nanoparticles(BP–Au NPs)as the ultrasensitive unlabeled Raman probe.BP–Au NPs,which possess excellent biocompatibility,are capable of detecting dye molecules at concentrations as low as 5×10^(-8)M and remain stable for at least one week in different physiological environments.In view of this,BP–Au NPs-based SERS technique can distinguish the tiny differences in the molecular fingerprints of cancer cells undergoing three PCD patterns(apoptosis,necroptosis and ferroptosis)triggered by doxorubicin,shikonin and erastin,respectively.We also have real-time monitoring of the intracellular molecular events during PCD,which spy the fluctuations of some typical SERS bands assigned to protein,DNA and lipid,revealing the unique phenotypic characteristics of each PCD pattern.This strategy provides a detailed and comprehensive analysis of the mechanisms of drug-induced PCD at the Raman level.展开更多
BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated a...BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.展开更多
BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported ...BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.展开更多
BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blocka...BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.展开更多
文摘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.
基金Supported by Russian Science Foundation,No.23-25-00183.
文摘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.
基金Supported by National Natural Science Foundation of China,No.81673241 and No.32470985.
文摘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.
基金Supported by the Natural Science Foundation of Gansu Province,No.21JR7RA373 and No.24JRRA295.
文摘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.
文摘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,I^(2)=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.
基金Supported by Russian Science Foundation,No.23-25-00183.
文摘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.
基金Science and Technology Program of Guangzhou,No.202102010077International Science Foundation of Guangzhou Fuda Cancer Hospital,No.Y2020-ZD-03.
文摘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.
文摘BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly aggressive cancer with poor prognosis.When it metastasizes to the liver,treatment options become particularly limited and challenging.Current treatment options for liver metastatic PDAC are limited,and chemotherapy alone often proves insufficient.Immunotherapy,particularly programmed cell death 1(PD-1)inhibitors like sintilimab,shows potential efficacy for various cancers but has limited reports on PDAC.This study compares the efficacy and safety of sintilimab plus S-1 and gemcitabine vs S-1 and gemcitabine alone in liver metastatic PDAC.AIM To explore the feasibility and effectiveness of combined PD-1 inhibitor sintilimab and S-1 and gemcitabine(combination group)vs S-1 and gemcitabine used alone(chemotherapy group)for treating liver metastatic pancreatic adenocarcinoma.METHODS Eligible patients were those with only liver metastatic PDAC,an Eastern Cooperative Oncology Group performance status of 0-1,adequate organ and marrow functions,and no prior anticancer therapy.Participants in the combination group received intravenous sintilimab 200 mg every 3 weeks,oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle,and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles or until disease progression,death,or unacceptable toxicity.Participants in the chemotherapy group received oral S-140 mg/m²twice daily on days 1-14 of a 21-day cycle and intravenous gemcitabine 1000 mg/m²on days 1 and 8 of the same cycle for up to eight cycles.Between June 2020 and December 2021,66 participants were enrolled,with 32 receiving the combination treatment and 34 receiving chemotherapy alone.RESULTS The group receiving the combined therapy exhibited a markedly prolonged median overall survival(18.8 months compared to 10.3 months,P<0.05)and progression-free survival(9.6 months vs 5.4 months,P<0.05).compared to the chemotherapy group.The incidence of severe adverse events did not differ significantly between the two groups(P>0.05).CONCLUSION The combination of PD-1 inhibitor sintilimab with S-1 and gemcitabine demonstrated effectiveness and safety for treating liver metastatic PDAC,meriting further investigation.
基金supported by grants from the National Key Research and Development Program of China(2023YFA1801804,2022YFA0807000,2021YFA1101300,2021YFA1101800,and 2020YFA0112503)the National Natural Science Foundation of China(82171149,82371166,81970892,82330033,82030029,92149304,82071053,and 82171144)+5 种基金the Shenzhen Science and Technology Program(JCYJ20230807114700001,JCYJ20210324125608022,and JCYJ20190814093401920)the Guangdong Basic and Applied Basic Research Foundation(2024A1515010548)the Science and Technology Department of Sichuan Province(2021YFS0371)the Jiangsu Provincial Scientific Research Center of Applied Mathematics(BK20233002)the Open Research Fund of Guangdong Academy of Medical Sciences(YKY‐KF202201)the Taishan Scholars Project-Young Experts Program of Shandong Province(tsqn202211357).
文摘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.
文摘Objective:To investigate the impact of programmed harmonious nursing combined with hierarchical management on nursing quality and satisfaction in a health management center.Methods:A total of 100 patients who received care at this health management center from January 2024 to January 2025 were selected as subjects.Using a random number table method,they were divided into an observation group(n=50)and a control group(n=50).The control group followed traditional methods,while the observation group integrated programmed harmonious nursing with hierarchical management.Comparative analysis was conducted on nursing quality scores,adverse event occurrence rates,and patient satisfaction between the two groups.Results:The observation group showed significantly improved nursing quality scores(P<0.05)and markedly reduced incidence of adverse events(P<0.05),with statistically significant differences compared to pre-treatment conditions(P<0.05).Conclusion:The combination of hierarchical management and programmed harmonious nursing demonstrates effectiveness in enhancing medical service quality,reducing adverse reactions,and improving patient satisfaction—a method worthy of promotion.
基金Supported by Jilin Provincial Natural Science Foundation,No.YDZJ202401650ZYTS。
文摘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.
基金National Key Research and Development Program of China(2022YFD1300405)National Natural Science Foundation of China(32202671)Open project of State Key Laboratory of Animal Biotech Breeding(Grant No.2024SKLAB6-5).
文摘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.
基金Supported by the National High Level Hospital Clinical Research Funding(Multi-center Clinical Research Project of Peking University First Hospital),No.2022CR65.
文摘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.
文摘BACKGROUND Immune checkpoint inhibitors(ICIs)are a new class of antitumor agents.They enhance antitumor effects by blocking inhibitory receptors and related ligands expressed on T cells.ICIs also modulate regular immune cell activity,affecting the immune system and causing immune-related adverse events.The renal system is sometimes affected by these adverse events.Currently,the literature on ICIs-related glomerular injuries is scarce.CASE SUMMARY We present a patient who developed granulomatosis with polyangiitis(GPA)3 weeks after treatment with the anti-programmed cell death-1 inhibitor,tislel-izumab.The patient experienced proteinuria,hematuria,and acute kidney injury without pulmonary hemorrhage and tested positive for anti-neutrophil cyto-plasmic antibody(ANCA)-cytoplasmic type.Renal biopsy confirmed ANCA-associated vasculitis,and GPA was finally diagnosed.The patient received pulse treatment with glucocorticoids and cyclophosphamide,and renal function improved.After self-discontinuation of the drug,the disease recurred,and the original treatment regimen was continued.However,the patient’s renal function continued to deteriorate.CONCLUSION Glucocorticoids plus cyclophosphamide are effective for treating GPA induced by tislelizumab.However,follow-up and patient education are needed.
基金supported by the postdoctoral fellowship program of CPSF(GZC20241270)the China Postdoctoral Science Foundation(2024M762496).
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China(62175071 and 32071399)the Guangdong Basic and Applied Basic Research Foundation(2021A1515011988 and 2021A1515110265)+2 种基金the Project of the Education Department of Guangdong Province,China(2021KTSCX238 and 2022ZDZX2077)the Project of Guangdong Food and Drug Vocational College(2020ZR01,2022ZR02 and 2024GCZX01)the Open Foundation of Key Laboratory of Optoelectronic Science and Technology for Medicine(Fujian Normal University),Ministry of Education,China(JYG2008 and JYG2009).
文摘Programmed cell death(PCD)plays a crucial role in the biological processes of living organisms and occurs in various forms,such as apoptosis,necroptosis and ferroptosis.However,traditional methods for PCD analysis are time-consuming and complex.In this paper,we propose a facile surface-enhanced Raman spectroscopy(SERS)-based strategy for the real-time analysis of three PCD patterns utilizing black phosphorus–gold nanoparticles(BP–Au NPs)as the ultrasensitive unlabeled Raman probe.BP–Au NPs,which possess excellent biocompatibility,are capable of detecting dye molecules at concentrations as low as 5×10^(-8)M and remain stable for at least one week in different physiological environments.In view of this,BP–Au NPs-based SERS technique can distinguish the tiny differences in the molecular fingerprints of cancer cells undergoing three PCD patterns(apoptosis,necroptosis and ferroptosis)triggered by doxorubicin,shikonin and erastin,respectively.We also have real-time monitoring of the intracellular molecular events during PCD,which spy the fluctuations of some typical SERS bands assigned to protein,DNA and lipid,revealing the unique phenotypic characteristics of each PCD pattern.This strategy provides a detailed and comprehensive analysis of the mechanisms of drug-induced PCD at the Raman level.
文摘BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.
文摘BACKGROUND Bevacizumab,an anti-vascular endothelial growth factor(VEGF)monoclonal antibody,inhibits angiogenesis and reduces tumor growth.Serum VEGF-C,lactate dehydrogenase,and inflammatory markers have been reported as predictive markers related to bevacizumab treatment.Programmed cell death ligand 1(PD-L1)could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis.AIM To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer(CRC)according to the expression of PD-L1.METHODS This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24,2014 and February 28,2022,at Samsung Medical Center(Seoul,South Korea).Analysis of patient data included evaluation of PD-L1 expression by the combined positive score(CPS).We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC.RESULTS A total of 124 patients was included in this analysis.Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy.While 77%of patients received FOLFOX,23%received FOLFIRI as backbone first-line chemotherapy.The numbers of patients with a PD-L1 CPS of 1 or more,5 or more,or 10 or more were 105(85%),64(52%),and 32(26%),respectively.The results showed no significant difference in progression-free survival(PFS)and overall survival(OS)with bevacizumab treatment between patients with PDL1 CPS less than 1 and those with PD-L1 CPS of 1 or more(PD-L1<1%vs PD-L1≥1%;PFS:P=0.93,OS:P=0.33),between patients with PD-L1 CPS less than 5 and of 5 or more(PD-L1<5%vs PD-L1≥5%;PFS:P=0.409,OS:P=0.746),and between patients with PD-L1 CPS less than 10 and of 10 or more(PD-L1<10%vs PD-L1≥10%;PFS:P=0.529,OS:P=0.568).CONCLUSION Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.
基金Supported by Shaoxing Health Science and Technology Program,No.2022SY016,No.2022KY010.
文摘BACKGROUND In recent years,immune checkpoint inhibitors(ICIs)have demonstrated remarkable efficacy across diverse malignancies.Notably,in patients with advanced gastric cancer,the use of programmed death 1(PD-1)blockade has significantly prolonged overall survival,marking a pivotal advancement comparable to the impact of Herceptin over the past two decades.While the therapeutic benefits of ICIs are evident,the increasing use of immunotherapy has led to an increase in immune-related adverse events.CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis.Following sintilimab therapy,the patient developed severe rashes accompanied by cytokine release syndrome(CRS).Fortunately,effective management was achieved through the administration of glucocorticoid,tocilizumab,and acitretin,which resulted in favorable outcomes.CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.
