Effect of FOLFOX regimen plus toripalimab on angiogenesis and the PD-1/PD-L1 signaling pathway in patients with advanced gastric cancer
Objective To investigate the efficacy and immunomodulatory mechanism of toripalimab combined with FOLFOX in the treatment of advanced gastric cancer.Methods A total of 97 patients with advanced gastric can-cer admitted to Zhumadian Central Hospital from June 2021 to June 2023 were enrolled and randomly assigned to groups according to random number table method.Among them,48 cases treated with FOLFOX regimen were included in the control group,and 49 cases treated with the FOLFOX regimen plus toripalimab were included in the observation group.One treatment cycle was defined as 21 days,with treatments continuing for six cycles.Therapeutic effects after six treatment cycles were compared between the two groups,alongside the programmed cell death receptor-1(PD-1)/programmed cell death ligand-1(PD-L1)pathway markers(PD-1 protein,PD-1 mRNA,PD-L1 protein,PD-L1 mRNA)and angiogenesis indicators(hypoxia-inducible factor 1α[HIF-1α],vascular endothelial growth factor[VEGF],angiopoietin-2[Ang-2],and cyclooxygenase-2[COX-2])before treatment,after three cycles,and after six cycles.Addi-tionally,the toxic side effects during treatment and the six-month follow-up survival rates were compared between the two groups.Results After 6 treatment cycles,the disease control rate in the observation group was 63.27%,signifi-cantly higher than 41.67%in the control group,with a statistically significant difference(P<0.05).After 3 and 6 treat-ment cycles,the PD-1 protein levels in the observation group were 5.83±1.12 and 5.77±1.26,respectively,which were lower than corresponding 6.84±1.25 and 7.11±1.36 in the control group;the PD-1 mRNA levels were 6.12±1.33 and 6.01±1.34,respectively,significantly lower than corresponding 6.91±1.34 and 7.20±1.30 in the control group;the PD-L1 protein levels were 6.30±1.05 and 6.19±1.11,respectively,significantly lower than corresponding 7.02±1.33 and 6.88±1.40 in the control group;the PD-1 mRNA levels were 6.41±1.24 and 6.33±1.25,respectively,significantly lower than corresponding 7.19±1.36 and 7.10±1.38 in the control group;the aboved differences were statistically significant(P<0.05).Regarding angiogenesis indices,after 3 and 6 treatment cycles,the levels of VEGF were(224.46±25.25)ng/mL and(150.10±14.14)ng/mL,respectively,significantly lower than corresponding(279.79±30.44)ng/mL and(191.65±16.63)ng/mL in the control group;the levels of HIF-1α were(135.51±16.67)μg/L and(100.10±12.28)μg/L,respective-ly,significantly lower than corresponding(175.53±18.48)μg/L and(153.53±14.88)μg/L in the control group;the levels of Ang-2 were(68.98±7.36)ng/mL and(46.68±5.13)ng/mL,respectively,significantly lower than corresponding(75.51±7.95)ng/mL and(56.64±6.11)ng/mL in the control group;the levels of COX-2 were(31.48±4.12)ng/mL and(20.24±3.38)ng/mL,respectively,significantly were lower than corresponding(36.64±4.20)ng/mL and(25.74±3.59)ng/mL in the control group;all the aboved differences statistically significant(P<0.05).No significant differences were ob-served between the two groups in the incidence of toxic side effects after six treatment cycles or in six-month follow-up survival rates(P>0.05).Conclusion The combination of toripalimab and FOLFOX regimen in the treatment of ad-vanced gastric cancer can effectively block the PD-1/PD-L1 signaling pathway,enhance tumor control effect,and exhib-it a favorable safety profile.
Advanced gastric cancerFOLFOX regimenToripalimabProgrammed cell death receptor-1Pro-grammed cell death ligand-1Disease control effectivenessToxic side effects
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