Recent pharmacokinetic studies have demonstrated that gastric acid suppression(AS)reduces exposure of gefitinib.However,the clinical significance of this drug-drug interaction(DDI)has not been determined.We,therefore,...Recent pharmacokinetic studies have demonstrated that gastric acid suppression(AS)reduces exposure of gefitinib.However,the clinical significance of this drug-drug interaction(DDI)has not been determined.We,therefore,evaluated it in this real-world study.A total of 200 NSCLC patients who received gefitinib from 2016 to 2018 at Fudan University Shanghai Cancer Center(FUSCC)were randomly selected.The patients were divided into two groups according to whether AS was used.The clinical characteristics of the patients were collected,and the efficacy and safety of gefitinib were compared between the two groups.We showed that 188 patients were considered eligible for this retrospective analysis,49 received AS(AS user group),while 139 patients did not(AS non-user group).Objective response rate(ORR)and disease control rate(DCR)in the AS user group versus AS non-user group were 69.4%versus 73.4%(P=0.591)and 89.8%versus 90.6%(P=0.486),respectively,while the progression-free survival(PFS)were 9.7 versus 12.2 months(P=0.0644).No significant difference in ORR,DCR or PFS was observed between the two groups.Further study showed that the PFS was related to the time of co-administration,and the patients receiving over 50%AS prescription overlap with gefitinib was significantly less compared with the other people(8.4 vs 12.6 months,P=0.0004).The frequencies of rash(8.2%vs 15.1%,P=0.281),diarrhea(4.1%vs 6.5%,P=0.539)and elevated ALT or AST level(6.1%vs 10.1%,P=0.407)were similar for both groups.Therefore,concomitant use of AS and gefitinib might affect the efficacy of gefitinib,which should be avoided if possible.展开更多
Hypoxia-inducible factor-1(HIF-1)is a key heterodimeric transcription factor for the cellular adaptive response to hypoxia,a common feature of the microenvironment in solid tumors.The transcriptional activity,protein ...Hypoxia-inducible factor-1(HIF-1)is a key heterodimeric transcription factor for the cellular adaptive response to hypoxia,a common feature of the microenvironment in solid tumors.The transcriptional activity,protein stabilization,protein-protein interactions and cellular localization of HIF-1α,an oxygen-sensitive subunit of HIF-1,are mainly modulated by various post-translational modifications.Recently,we reported that polycomb chromobox 4(Cbx4)governs the transcriptional activity of HIF-1αby enhancing its sumoylation at K391 and K477,through which Cbx4 potentiates angiogenesis of hepatocellular carcinoma.This review summarizes the current knowledge of HIF-1α sumoylation and its roles in the pathogenesis of cancer.展开更多
文摘Recent pharmacokinetic studies have demonstrated that gastric acid suppression(AS)reduces exposure of gefitinib.However,the clinical significance of this drug-drug interaction(DDI)has not been determined.We,therefore,evaluated it in this real-world study.A total of 200 NSCLC patients who received gefitinib from 2016 to 2018 at Fudan University Shanghai Cancer Center(FUSCC)were randomly selected.The patients were divided into two groups according to whether AS was used.The clinical characteristics of the patients were collected,and the efficacy and safety of gefitinib were compared between the two groups.We showed that 188 patients were considered eligible for this retrospective analysis,49 received AS(AS user group),while 139 patients did not(AS non-user group).Objective response rate(ORR)and disease control rate(DCR)in the AS user group versus AS non-user group were 69.4%versus 73.4%(P=0.591)and 89.8%versus 90.6%(P=0.486),respectively,while the progression-free survival(PFS)were 9.7 versus 12.2 months(P=0.0644).No significant difference in ORR,DCR or PFS was observed between the two groups.Further study showed that the PFS was related to the time of co-administration,and the patients receiving over 50%AS prescription overlap with gefitinib was significantly less compared with the other people(8.4 vs 12.6 months,P=0.0004).The frequencies of rash(8.2%vs 15.1%,P=0.281),diarrhea(4.1%vs 6.5%,P=0.539)and elevated ALT or AST level(6.1%vs 10.1%,P=0.407)were similar for both groups.Therefore,concomitant use of AS and gefitinib might affect the efficacy of gefitinib,which should be avoided if possible.
基金supported by grants from the National Natural Science Foundation of China (91213304,31101044)the National Basic Research Program of China (NO2009CB918404)+1 种基金Shanghai Science & Technology Committee (11JC1406800)Shanghai Committee of Education and Doctoral Innovation Fund Projects from Shanghai Jiao Tong University School of Medicine
文摘Hypoxia-inducible factor-1(HIF-1)is a key heterodimeric transcription factor for the cellular adaptive response to hypoxia,a common feature of the microenvironment in solid tumors.The transcriptional activity,protein stabilization,protein-protein interactions and cellular localization of HIF-1α,an oxygen-sensitive subunit of HIF-1,are mainly modulated by various post-translational modifications.Recently,we reported that polycomb chromobox 4(Cbx4)governs the transcriptional activity of HIF-1αby enhancing its sumoylation at K391 and K477,through which Cbx4 potentiates angiogenesis of hepatocellular carcinoma.This review summarizes the current knowledge of HIF-1α sumoylation and its roles in the pathogenesis of cancer.
