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 Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for ...BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer.As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients,we examined American College of Surgeons National Surgical Quality Improvement Program(NSQIP)database to determine if there was higher morbidity among the neo-adjuvant group within the 30-day post-operative period.We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity.AIM To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery.METHODS A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity(bile leak,infection rate,rate of converting to open surgery,etc.)compared to the group who only had surgery.To calculate the odds ratio for the primary and secondary outcomes,a crude logistic regression was performed.RESULTS Of the 452 patients,52 patients received NACT prior to surgery.There were no statistically significant differences in the odds of morbidity between the two groups,including bile leak[odds ratio(OR),0.69;95%confidence interval(95%CI):0.16-2.10;P=0.55],superficial wound infection(OR,0.58;95%CI:0.03-3.02;P=0.61),and organ space wound infection(OR,0.63;95%CI:0.18-1.63;P=0.61).CONCLUSION There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.展开更多
BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,i...BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.展开更多
BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.Howev...BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.展开更多
Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a ca...Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.展开更多
BACKGROUND Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib(TRIPLET protocol)is promising for advanced hepatocellular carcinoma(Ad-HCC).However,the usefulness of microwave ablation(MWA)after TRIPL...BACKGROUND Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib(TRIPLET protocol)is promising for advanced hepatocellular carcinoma(Ad-HCC).However,the usefulness of microwave ablation(MWA)after TRIPLET is still controversial.AIM To compare the efficacy and safety of TRIPLET alone(T-A)vs TRIPLET-MWA(TM)for Ad-HCC.METHODS From January 2018 to March 2022,217 Ad-HCC patients were retrospectively enrolled.Among them,122 were included in the T-A group,and 95 were included in the T-M group.A propensity score matching(PSM)was applied to balance bias.Overall survival(OS)was compared using the Kaplan-Meier curve with the log-rank test.The overall objective response rate(ORR)and major complications were also assessed.RESULTS After PSM,82 patients were included both the T-A group and the T-M group.The ORR(85.4%)in the T-M group was significantly higher than that(65.9%)in the T-A group(P<0.001).The cumulative 1-,2-,and 3-year OS rates were 98.7%,93.4%,and 82.0%in the T-M group and 85.1%,63.1%,and 55.0%in the T-A group(hazard ratio=0.22;95%confidence interval:0.10-0.49;P<0.001).The incidence of major complications was 4.9%(6/122)in the T-A group and 5.3%(5/95)in the T-M group,which were not significantly different(P=1.000).CONCLUSION T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.展开更多
BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal t...BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.展开更多
Objective:To investigate the effects of different chemotherapy regimens before radical operation for lung cancer on cancer cell growth and antitumor immune response.Methods: A total of 180 patients with primary lung c...Objective:To investigate the effects of different chemotherapy regimens before radical operation for lung cancer on cancer cell growth and antitumor immune response.Methods: A total of 180 patients with primary lung cancer who underwent surgery in this hospital between February 2013 and August 2017 were divided into the cisplatin group (n=93) who received cisplatin & paclitaxel chemotherapy and the lobaplatin group (n=87) who received lobaplatin & paclitaxel chemotherapy according to different preoperative neoadjuvant chemotherapy regimens. The differences among the expression of proliferation genes and apoptosis genes in tumor tissues as well as the contents of Th1/Th2 cytokines in serum were compared between the two groups.Results: Proliferation genes DDX17, GPx1, MACC1, RACK1 and SIRT1 mRNA expression levels in tumor tissue of lobaplatin group were lower than those of cisplatin group whereas LRRC3B mRNA expression level was higher than that of cisplatin group;apoptosis gene Fas, FasL and Caspase-3 mRNA expression levels were higher than those of cisplatin group whereas Survivin and Bcl-2 mRNA expression levels were lower than those of cisplatin group;serum Th1 cytokines IFN-γ and IL-12 contents were higher than those of cisplatin group whereas Th2 cytokines IL-5 and IL-10 contents were lower than those of cisplatin group.Conclusion: Lobaplatin chemotherapy before radical operation for lung cancer is more effective than cisplatin chemotherapy to inhibit the proliferation activity and enhance the apoptosis activity of lung cancer cells and optimize the anti-tumor immune response.展开更多
Objective: To study the effect of negative emotion on tumor load and anti-tumor immune response in bladder cancer infusion chemotherapy. Methods: Patients with advanced bladder cancer who received bladder infusion che...Objective: To study the effect of negative emotion on tumor load and anti-tumor immune response in bladder cancer infusion chemotherapy. Methods: Patients with advanced bladder cancer who received bladder infusion chemotherapy in the First People's Hospital of Ziyang between May 2014 and December 2016 were selected and divided into the control group without negative emotions, the anxiety group with anxiety, the depression group with depression and the anxiety depression group with both anxiety and depression according to the assessment results of HAMA scale and HAMD scale. The contents of tumor markers in serum, the contents of immune cells in peripheral blood and the expression of apoptosis genes in urine were detected during chemotherapy. Results: DKK-1, DKK-3, OPN and CYFRA21-1 contents in serum as well as PD-1+CD4+T cell, PD-1+CD8+T cell and B7-H1+CD11c+DC cell contents in peripheral blood of anxiety group, depression group and anxiety depression group were significantly higher than those of control group while DAP2IP, Fas, FasL, Caspase-8 and PTEN protein expression in urine were significantly lower than those of control group, and DKK-1, DKK-3, OPN and CYFRA21-1 contents in serum as well as PD-1+CD4+T cell, PD-1+CD8+T cell and B7-H1+CD11c+DC cell contents in peripheral blood of anxiety depression group were significantly higher than those of anxiety group and depression group while DAP2IP, Fas, FasL, Caspase-8 and PTEN protein expression in urine were significantly lower than those of anxiety group and depression group. Conclusion: The anxiety and depression in bladder cancer infusion chemotherapy can suppress the expression of apoptosis genes and the anti-tumor immune response to lead to more vigorous proliferation of cancer cells.展开更多
BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare autosomal dominant disorder,and female patients may develop gynecologic tumours.The prognosis for such patients is poor and the specific pathogenesis remains uncertain.T...BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare autosomal dominant disorder,and female patients may develop gynecologic tumours.The prognosis for such patients is poor and the specific pathogenesis remains uncertain.Therefore,there are currently no uniform treatment options.CASE SUMMARY Herein,we introduce the case of a 45-year-old female who was diagnosed with PJS for 45 years and cervical cancer for 3 years.Postoperative pathological examination showed metastases in the right external iliac lymph nodes.The patient was initially treated with a combination of doxorubicin and carboplatin chemotherapy and pelvic magnetic resonance showed that the metastases had grown.Subsequently,we performed whole exome sequencing in this patient and identified the relevant causative gene.In addition to the chemotherapy regimen,sindilizumab was administered and the patient was followed up.After 4 cycles of treatment,the metastases were substantially reduced and were not enlarged after six months of follow-up.This case report suggests that patients with PJS combined with cervical cancer may have a sustained response to immunecombination chemotherapy regimens.CONCLUSION Clinicians should be aware of the importance of immunotherapy in patients with PJS combined with advanced cervical cancer.展开更多
目的评价程序性死亡受体1(PD-1)抑制剂联合化疗一线治疗人表皮生长因子受体2(HER2)阴性晚期胃或胃食管交界部癌(G/GEJC)的有效性及安全性。方法检索中国知网、万方、Pubmed、Cochrane、Embase、Web of Science、Clinical Trials.gov等...目的评价程序性死亡受体1(PD-1)抑制剂联合化疗一线治疗人表皮生长因子受体2(HER2)阴性晚期胃或胃食管交界部癌(G/GEJC)的有效性及安全性。方法检索中国知网、万方、Pubmed、Cochrane、Embase、Web of Science、Clinical Trials.gov等数据库和中国抗癌协会、韩国临床肿瘤学会、日本临床肿瘤学会等会议摘要中有关PD-1抑制剂联合化疗一线治疗HER2阴性晚期G/GEJC患者的临床随机对照试验(RCT),筛选文献,提取资料,采用R 4.3.1进行Meta分析。结果纳入5篇RCT共5297例HER2阴性晚期G/GEJC的成年患者。PD-1抑制剂联合化疗一线治疗可延长患者的总生存期(OS)(HR=0.79,95%CI:0.74~0.85,P<0.001)及无进展生存期(PFS)(HR=0.74,95%CI:0.69~0.80,P<0.001),并提高客观有效率(ORR)(RR=1.23,95%CI:1.15~1.31,P<0.001)。亚组分析结果显示:在综合阳性分数(CPS)≥1、CPS≥5、CPS≥10的患者中,PD-1抑制剂联合化疗一线治疗方案的OS、PFS、ORR均获益,且程序性死亡配体1表达程度越高,疗效获益均更佳。此外,微卫星高度不稳定性(MSI-H)的患者PD-1抑制剂联合化疗一线治疗方案延长OS更为显著(HR=0.35,95%CI:0.21~0.59,P<0.001)。与化疗组相比,PD-1抑制剂联合化疗一线治疗方案未增加治疗相关不良反应的发生率(P>0.05)。结论PD-1抑制剂联合化疗一线治疗HER2阴性晚期G/GEJC的疗效优于化疗,且高CPS或MSI-H患者获益更大,具有良好的安全性。展开更多
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.
文摘BACKGROUND Gallbladder cancer is the most common malignancy of the biliary tract.Neo-adjuvant chemotherapy(NACT)has improved overall survival by enabling R0 resection.Currently,there is no consensus of guidelines for neoadjuvant therapy in gallbladder cancer.As investigations continue to analyze the regimen and benefit of NACT for ongoing care of gallbladder cancer patients,we examined American College of Surgeons National Surgical Quality Improvement Program(NSQIP)database to determine if there was higher morbidity among the neo-adjuvant group within the 30-day post-operative period.We hypothesized patients who underwent NACT were more likely to have higher post-operative morbidity.AIM To investigate the 30-day post-operative morbidity outcomes between patients who received NACT and underwent surgery and patients who only had surgery.METHODS A retrospective analysis of the targeted hepatectomy NSQIP data between 2015 and 2019 was performed to determine if NACT in gallbladder cancer increased the risk for post-operative morbidity(bile leak,infection rate,rate of converting to open surgery,etc.)compared to the group who only had surgery.To calculate the odds ratio for the primary and secondary outcomes,a crude logistic regression was performed.RESULTS Of the 452 patients,52 patients received NACT prior to surgery.There were no statistically significant differences in the odds of morbidity between the two groups,including bile leak[odds ratio(OR),0.69;95%confidence interval(95%CI):0.16-2.10;P=0.55],superficial wound infection(OR,0.58;95%CI:0.03-3.02;P=0.61),and organ space wound infection(OR,0.63;95%CI:0.18-1.63;P=0.61).CONCLUSION There was no significant difference in the risk of 30-day post-operative morbidity between the NACT and surgery group and the surgery only group.
文摘BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.
基金Supported by Natural Science Foundation of Guangdong Province,No.2020A1515011539.
文摘BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.
基金was supported by National Natural Science Foundation of China(81972893,82172719)Natural Science Foundation of Henan(212300410071)Training program for young key teachers in Henan Province(2020GGJS019).
文摘Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy,but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration.Herein,we designed a cancer-associated fibroblasts(CAFs)triggered structure-transformable nano-assembly(HSD-P@V),which can directionally deliver valsartan(Val,CAFs regulator)and doxorubicin(DOX,senescence inducer)to the specific targets.In detail,DOX is conjugated with hyaluronic acid(HA)via diselenide bonds(Se-Se)to form HSD micelles,while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer,which is coated on Val nanocrystals(VNs)surface for improving the stability and achieving responsive release.Once arriving at tumor microenvironment and touching CAFs,HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment.VNs can degrade the extracellularmatrix,leading to the enhanced penetration of HSD.HSD targets tumor cells,releases DOX to induce senescence,and recruits effector immune cells.Furthermore,senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy.In vitro and in vivo results show that the nanoassembly remarkably inhibits tumor growth as well as lungmetastasis,and extends tumorbearing mice survival.This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.
文摘BACKGROUND Hepatic arterial infusion chemotherapy and camrelizumab plus apatinib(TRIPLET protocol)is promising for advanced hepatocellular carcinoma(Ad-HCC).However,the usefulness of microwave ablation(MWA)after TRIPLET is still controversial.AIM To compare the efficacy and safety of TRIPLET alone(T-A)vs TRIPLET-MWA(TM)for Ad-HCC.METHODS From January 2018 to March 2022,217 Ad-HCC patients were retrospectively enrolled.Among them,122 were included in the T-A group,and 95 were included in the T-M group.A propensity score matching(PSM)was applied to balance bias.Overall survival(OS)was compared using the Kaplan-Meier curve with the log-rank test.The overall objective response rate(ORR)and major complications were also assessed.RESULTS After PSM,82 patients were included both the T-A group and the T-M group.The ORR(85.4%)in the T-M group was significantly higher than that(65.9%)in the T-A group(P<0.001).The cumulative 1-,2-,and 3-year OS rates were 98.7%,93.4%,and 82.0%in the T-M group and 85.1%,63.1%,and 55.0%in the T-A group(hazard ratio=0.22;95%confidence interval:0.10-0.49;P<0.001).The incidence of major complications was 4.9%(6/122)in the T-A group and 5.3%(5/95)in the T-M group,which were not significantly different(P=1.000).CONCLUSION T-M can provide better survival outcomes and comparable safety for Ad-HCC than T-A.
文摘BACKGROUND SMARCA4 is a component of chromatin remodeling of SWItch/sucrose-nonfermenting(SWI/SNF)complexes and plays an essential role in oncogenesis.SMARCA4-deficient malignancies arising from the gastrointestinal tract are rare and have a poor prognosis.There is no standard treatment for advanced and undifferentiated SMARCA4-deficient duodenal malignancies.Programmed death 1(PD-1)antibodies,known as immune checkpoint inhibitor antibodies,potentially play a role in treating gastrointestinal tract malignancies.CASE SUMMARY We present two patients with SMARCA4 deficiency and TP53 gene mutation in advanced undifferentiated carcinomas of the duodenum.For both patients,SMARCA4 deficiency was confirmed by immunohistochemical staining for the BRG1 protein,while TP53 gene mutations were observed via next-generation sequencing.Both patients were administered chemotherapy in combination with an anti-PD-1 antibody.The two patients exhibited completely different responses to treatment and had different prognoses.Case 1 experienced rapid progression after PD-1 infusion and chemotherapy,case 2 experienced a remarkable response after treatment,and the progression-free survival was more than 6 months.CONCLUSION This study described our clinical and pathological observations of SMARCA4-deficient advanced undifferentiated carcinoma of the duodenum.PD-1 combined with chemotherapy showed a certain efficacy in select patients,providing options for treating these highly malignant tumors.Patients with liver metastases had a worse prognosis than did those with only lymph node metastasis.
文摘Objective:To investigate the effects of different chemotherapy regimens before radical operation for lung cancer on cancer cell growth and antitumor immune response.Methods: A total of 180 patients with primary lung cancer who underwent surgery in this hospital between February 2013 and August 2017 were divided into the cisplatin group (n=93) who received cisplatin & paclitaxel chemotherapy and the lobaplatin group (n=87) who received lobaplatin & paclitaxel chemotherapy according to different preoperative neoadjuvant chemotherapy regimens. The differences among the expression of proliferation genes and apoptosis genes in tumor tissues as well as the contents of Th1/Th2 cytokines in serum were compared between the two groups.Results: Proliferation genes DDX17, GPx1, MACC1, RACK1 and SIRT1 mRNA expression levels in tumor tissue of lobaplatin group were lower than those of cisplatin group whereas LRRC3B mRNA expression level was higher than that of cisplatin group;apoptosis gene Fas, FasL and Caspase-3 mRNA expression levels were higher than those of cisplatin group whereas Survivin and Bcl-2 mRNA expression levels were lower than those of cisplatin group;serum Th1 cytokines IFN-γ and IL-12 contents were higher than those of cisplatin group whereas Th2 cytokines IL-5 and IL-10 contents were lower than those of cisplatin group.Conclusion: Lobaplatin chemotherapy before radical operation for lung cancer is more effective than cisplatin chemotherapy to inhibit the proliferation activity and enhance the apoptosis activity of lung cancer cells and optimize the anti-tumor immune response.
文摘Objective: To study the effect of negative emotion on tumor load and anti-tumor immune response in bladder cancer infusion chemotherapy. Methods: Patients with advanced bladder cancer who received bladder infusion chemotherapy in the First People's Hospital of Ziyang between May 2014 and December 2016 were selected and divided into the control group without negative emotions, the anxiety group with anxiety, the depression group with depression and the anxiety depression group with both anxiety and depression according to the assessment results of HAMA scale and HAMD scale. The contents of tumor markers in serum, the contents of immune cells in peripheral blood and the expression of apoptosis genes in urine were detected during chemotherapy. Results: DKK-1, DKK-3, OPN and CYFRA21-1 contents in serum as well as PD-1+CD4+T cell, PD-1+CD8+T cell and B7-H1+CD11c+DC cell contents in peripheral blood of anxiety group, depression group and anxiety depression group were significantly higher than those of control group while DAP2IP, Fas, FasL, Caspase-8 and PTEN protein expression in urine were significantly lower than those of control group, and DKK-1, DKK-3, OPN and CYFRA21-1 contents in serum as well as PD-1+CD4+T cell, PD-1+CD8+T cell and B7-H1+CD11c+DC cell contents in peripheral blood of anxiety depression group were significantly higher than those of anxiety group and depression group while DAP2IP, Fas, FasL, Caspase-8 and PTEN protein expression in urine were significantly lower than those of anxiety group and depression group. Conclusion: The anxiety and depression in bladder cancer infusion chemotherapy can suppress the expression of apoptosis genes and the anti-tumor immune response to lead to more vigorous proliferation of cancer cells.
文摘BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare autosomal dominant disorder,and female patients may develop gynecologic tumours.The prognosis for such patients is poor and the specific pathogenesis remains uncertain.Therefore,there are currently no uniform treatment options.CASE SUMMARY Herein,we introduce the case of a 45-year-old female who was diagnosed with PJS for 45 years and cervical cancer for 3 years.Postoperative pathological examination showed metastases in the right external iliac lymph nodes.The patient was initially treated with a combination of doxorubicin and carboplatin chemotherapy and pelvic magnetic resonance showed that the metastases had grown.Subsequently,we performed whole exome sequencing in this patient and identified the relevant causative gene.In addition to the chemotherapy regimen,sindilizumab was administered and the patient was followed up.After 4 cycles of treatment,the metastases were substantially reduced and were not enlarged after six months of follow-up.This case report suggests that patients with PJS combined with cervical cancer may have a sustained response to immunecombination chemotherapy regimens.CONCLUSION Clinicians should be aware of the importance of immunotherapy in patients with PJS combined with advanced cervical cancer.
文摘目的评价程序性死亡受体1(PD-1)抑制剂联合化疗一线治疗人表皮生长因子受体2(HER2)阴性晚期胃或胃食管交界部癌(G/GEJC)的有效性及安全性。方法检索中国知网、万方、Pubmed、Cochrane、Embase、Web of Science、Clinical Trials.gov等数据库和中国抗癌协会、韩国临床肿瘤学会、日本临床肿瘤学会等会议摘要中有关PD-1抑制剂联合化疗一线治疗HER2阴性晚期G/GEJC患者的临床随机对照试验(RCT),筛选文献,提取资料,采用R 4.3.1进行Meta分析。结果纳入5篇RCT共5297例HER2阴性晚期G/GEJC的成年患者。PD-1抑制剂联合化疗一线治疗可延长患者的总生存期(OS)(HR=0.79,95%CI:0.74~0.85,P<0.001)及无进展生存期(PFS)(HR=0.74,95%CI:0.69~0.80,P<0.001),并提高客观有效率(ORR)(RR=1.23,95%CI:1.15~1.31,P<0.001)。亚组分析结果显示:在综合阳性分数(CPS)≥1、CPS≥5、CPS≥10的患者中,PD-1抑制剂联合化疗一线治疗方案的OS、PFS、ORR均获益,且程序性死亡配体1表达程度越高,疗效获益均更佳。此外,微卫星高度不稳定性(MSI-H)的患者PD-1抑制剂联合化疗一线治疗方案延长OS更为显著(HR=0.35,95%CI:0.21~0.59,P<0.001)。与化疗组相比,PD-1抑制剂联合化疗一线治疗方案未增加治疗相关不良反应的发生率(P>0.05)。结论PD-1抑制剂联合化疗一线治疗HER2阴性晚期G/GEJC的疗效优于化疗,且高CPS或MSI-H患者获益更大,具有良好的安全性。