The luminous intensity of dark variant (S1) separated from photobacterium phosph oreum (A2) was 1/10 000 less than that of wild type. Ethidium bromide (EB) (0.6 mg/L), Mytomycin C (MC, 0.05 mg/L), 2 amino fluorene ...The luminous intensity of dark variant (S1) separated from photobacterium phosph oreum (A2) was 1/10 000 less than that of wild type. Ethidium bromide (EB) (0.6 mg/L), Mytomycin C (MC, 0.05 mg/L), 2 amino fluorene (2 AF, 1.0 mg/L) all cou ld strongly induce reversion mutation for S1 within 24 h and increase reversion ratio significantly. The results of experiments indicated that these revertants had stable genetic characteristic and the mutation may take place at gene levels . The mutagenesis to S1 caused by EB, MC and 2 AF was detected and it may be us ed as a new rapid, simple and sensitive method for gene toxicant monitoring.展开更多
BACKGROUND The poly(ADP-ribose)polymerase(PARP)inhibitor olaparib has displayed superior clinical effect in metastatic castration-resistant prostate cancer(mCRPC)patients with the homologous recombination repair(HRR)g...BACKGROUND The poly(ADP-ribose)polymerase(PARP)inhibitor olaparib has displayed superior clinical effect in metastatic castration-resistant prostate cancer(mCRPC)patients with the homologous recombination repair(HRR)genes mutations.However,when a patient’s tumor tissue volume is insufficient for genomic profiling of HRR gene mutations,circulating tumor DNA(ctDNA)may be useful in helping to determine and monitor the efficacy of olaparib,as well as in abiraterone-combination treatment,and for understanding any resistance mechanism related to such mutations.CASE SUMMARY A 61-year-old man who was diagnosed with metastatic prostate adenocarcinoma was initially hormone sensitivity,showing high Gleason score(5+5=10)and absolute positive rate(14/14 biopsied specimens).Following failure of several standard therapies,the patient progressed to mCRPC.Surprisingly,the patient showed good response to olaparib-abiraterone-prednisone combination treatment(an androgen-deprivation therapy,provided as the‘final choice’in China).Serum total prostate-specific antigen(TPSA)level reduced and symptoms remitted for 4 months.However,thereafter,serum TPSA levels began slowly increasing,indicating development of olaparib resistance.Subsequent comprehensive genomic profiling of ctDNA, screening 508 cancer-related genes by next-generation sequencing,identified 10 somatic variants as well as 3 copy number alterations. Two identified reversemissense mutations in partner and localizer of BRCA2 (PALB2) may have recovered the readingframe, restoring function of the primary germline PALB2 mutation and causing resistance to thePARP inhibitor olaparib.CONCLUSIONReverse mutations in PALB2, discovered via genomic profiling of ctDNA, may represent apotential resistance mechanism against olaparib in mCRPC.展开更多
Background:Ethylhexyl triazone(EHT)and diethylhexyl butamido triazone(HEB)both belong to the recently developed class of triazine ultraviolet filters.However,their toxicity profiles remain unclear.Objective:To assess ...Background:Ethylhexyl triazone(EHT)and diethylhexyl butamido triazone(HEB)both belong to the recently developed class of triazine ultraviolet filters.However,their toxicity profiles remain unclear.Objective:To assess the genotoxic and phototoxic effects of EHT and HEB.Methods:The genotoxicity of EHT and HEB was assessed using in vitro bacterial reverse mutation assays,chromosomal aberration assays,and micronucleus assays.Meanwhile,their phototoxicity was evaluated using in vitro 3T3 neutral red uptake(NRU)phototoxicity assays and in vivo skin phototoxicity tests.Results:In the bacterial reverse mutation assay,the number of bacterial colonies was not significantly higher in the EHT and HEB groups than in the solvent control group.Similarly,the chromosomal aberration assay revealed no increase in aberration rates after either EHT or HEB treatment.In the micronucleus assay,the frequency of micronuclei was comparable between the treatment and control groups.Finally,based on the 3T3 NRU phototoxicity assay,both EHT and HEB(photo-irritation factor<2 and mean photo effect value<0.1)were classified as non-phototoxic.The skin phototoxicity test in vivo showed the same results as in vitro.Conclusion:Results from a series of genotoxicity and phototoxicity assays indicate that EHT and HEB possess neither genotoxic nor phototoxic potential.These findings provide experimental evidence supporting the safety of EHT and HEB for topical applications.展开更多
文摘The luminous intensity of dark variant (S1) separated from photobacterium phosph oreum (A2) was 1/10 000 less than that of wild type. Ethidium bromide (EB) (0.6 mg/L), Mytomycin C (MC, 0.05 mg/L), 2 amino fluorene (2 AF, 1.0 mg/L) all cou ld strongly induce reversion mutation for S1 within 24 h and increase reversion ratio significantly. The results of experiments indicated that these revertants had stable genetic characteristic and the mutation may take place at gene levels . The mutagenesis to S1 caused by EB, MC and 2 AF was detected and it may be us ed as a new rapid, simple and sensitive method for gene toxicant monitoring.
基金Supported by the Natural Science Foundation of Chongqing,No. cstc2018jcyj AX0781the Major Project of Chongqing Health Committee,No. cstc2016 shmszx130033031+1 种基金the National Natural Science Foundation of China,No. 81302316the Chongqing technological innovation and application development-Major theme projects,No. cstc2019jscxfxydx0008
文摘BACKGROUND The poly(ADP-ribose)polymerase(PARP)inhibitor olaparib has displayed superior clinical effect in metastatic castration-resistant prostate cancer(mCRPC)patients with the homologous recombination repair(HRR)genes mutations.However,when a patient’s tumor tissue volume is insufficient for genomic profiling of HRR gene mutations,circulating tumor DNA(ctDNA)may be useful in helping to determine and monitor the efficacy of olaparib,as well as in abiraterone-combination treatment,and for understanding any resistance mechanism related to such mutations.CASE SUMMARY A 61-year-old man who was diagnosed with metastatic prostate adenocarcinoma was initially hormone sensitivity,showing high Gleason score(5+5=10)and absolute positive rate(14/14 biopsied specimens).Following failure of several standard therapies,the patient progressed to mCRPC.Surprisingly,the patient showed good response to olaparib-abiraterone-prednisone combination treatment(an androgen-deprivation therapy,provided as the‘final choice’in China).Serum total prostate-specific antigen(TPSA)level reduced and symptoms remitted for 4 months.However,thereafter,serum TPSA levels began slowly increasing,indicating development of olaparib resistance.Subsequent comprehensive genomic profiling of ctDNA, screening 508 cancer-related genes by next-generation sequencing,identified 10 somatic variants as well as 3 copy number alterations. Two identified reversemissense mutations in partner and localizer of BRCA2 (PALB2) may have recovered the readingframe, restoring function of the primary germline PALB2 mutation and causing resistance to thePARP inhibitor olaparib.CONCLUSIONReverse mutations in PALB2, discovered via genomic profiling of ctDNA, may represent apotential resistance mechanism against olaparib in mCRPC.
基金supported by the National Natural Science Foundation of China(No.81600459)National Natural Science Foundation of Hubei Province(No.2016CFB312)+3 种基金Talent Introduction Project of Hubei Polytechnic University(No.15xjz03R)Industry-University Collaboration(No.KY2023-269)Hubei Key Laboratory of Kidney Disease Pathogenesis and Intervention Foundation(No.SB202103)Provincial College Student Innovation and Entrepreneurship Training Program(No.S202210920011).
文摘Background:Ethylhexyl triazone(EHT)and diethylhexyl butamido triazone(HEB)both belong to the recently developed class of triazine ultraviolet filters.However,their toxicity profiles remain unclear.Objective:To assess the genotoxic and phototoxic effects of EHT and HEB.Methods:The genotoxicity of EHT and HEB was assessed using in vitro bacterial reverse mutation assays,chromosomal aberration assays,and micronucleus assays.Meanwhile,their phototoxicity was evaluated using in vitro 3T3 neutral red uptake(NRU)phototoxicity assays and in vivo skin phototoxicity tests.Results:In the bacterial reverse mutation assay,the number of bacterial colonies was not significantly higher in the EHT and HEB groups than in the solvent control group.Similarly,the chromosomal aberration assay revealed no increase in aberration rates after either EHT or HEB treatment.In the micronucleus assay,the frequency of micronuclei was comparable between the treatment and control groups.Finally,based on the 3T3 NRU phototoxicity assay,both EHT and HEB(photo-irritation factor<2 and mean photo effect value<0.1)were classified as non-phototoxic.The skin phototoxicity test in vivo showed the same results as in vitro.Conclusion:Results from a series of genotoxicity and phototoxicity assays indicate that EHT and HEB possess neither genotoxic nor phototoxic potential.These findings provide experimental evidence supporting the safety of EHT and HEB for topical applications.
