Cancer pharmacogenetics implies a complex combination of germline variants from the patient and somatic mutations in tumor cells.Somatic mutations meanwhile have become drugable targets or biomarkers,whereas germline ...Cancer pharmacogenetics implies a complex combination of germline variants from the patient and somatic mutations in tumor cells.Somatic mutations meanwhile have become drugable targets or biomarkers,whereas germline mutations potentially predict adverse drug effects or drug response.Here,we evaluate hereditary variants in biotransforming enzymes and drug transporters,such as thiopurine S-methyltransferase,UDP-glucuronosyltransferase(UGT1A1),dihydropyrimidine dehydrogenase(DPD),as well as ABC transporters(ABCB1,ABCG2 and ABCC subfamily)with respect to cytostatics and targeted therapies.Furthermore,gene expression regulation with regards to epigenetics and posttranscriptional modification are discussed.展开更多
Antibody‐drug conjugates(ADCs)are targeted biological agents composed of a cytotoxic drug linked to a monoclonal antibody through a linker.The monoclonal antibody targets tumor cells and transports small‐molecule cy...Antibody‐drug conjugates(ADCs)are targeted biological agents composed of a cytotoxic drug linked to a monoclonal antibody through a linker.The monoclonal antibody targets tumor cells and transports small‐molecule cytotoxic drugs for specific delivery and minimal off‐target side effects.It is necessary for clinicians to understand the molecular characteristics and mechanisms of ADCs.Patients'survival mainly depends on the appropriate dose and course of treatment and also on proper management of adverse reactions.This consensus provides a systematic review of commercially available ADCs and further discusses the clinical application and management of ADCs.展开更多
The cationic folic acid（CFA） was prepared by introducing triethylenetetramine into folic acid with EDCI/NHS and characterized by IR, NMR and mass spectra. It was found that approximately one of two carboxyls in the ...The cationic folic acid（CFA） was prepared by introducing triethylenetetramine into folic acid with EDCI/NHS and characterized by IR, NMR and mass spectra. It was found that approximately one of two carboxyls in the folic acid molecule was substituted to form CFA. The conversion of γ-carboxyl is found to be 59% higher than 30% of γ-carboxyl. The CFA and doxorubicin hydrochloride can be loaded on the ionic shell of PTX-encapsulated micelle to form CFA loaded binary drug carrier via static interaction in aqueous solutions. The successful loading was demonstrated by zeta potential measurement and the drug load amount（DLA） of CFA was measured by HPLC. In vitro cytotoxicity results revealed the CFA drug carrier showed higher cytotoxicity to cancer cell MDA-MB-321 than the binary drug carrier without CFA and the positive control, while it showed lower cytotoxicity to normal cell HUVEC than the positive control, and similar cytotoxicity with the binary drug carrier without CFA. These results as well as confocal laser scanning microscopy observation indicate the synthesized CFA drug carrier possesses active tumor-targeting property.展开更多
文摘Cancer pharmacogenetics implies a complex combination of germline variants from the patient and somatic mutations in tumor cells.Somatic mutations meanwhile have become drugable targets or biomarkers,whereas germline mutations potentially predict adverse drug effects or drug response.Here,we evaluate hereditary variants in biotransforming enzymes and drug transporters,such as thiopurine S-methyltransferase,UDP-glucuronosyltransferase(UGT1A1),dihydropyrimidine dehydrogenase(DPD),as well as ABC transporters(ABCB1,ABCG2 and ABCC subfamily)with respect to cytostatics and targeted therapies.Furthermore,gene expression regulation with regards to epigenetics and posttranscriptional modification are discussed.
文摘Antibody‐drug conjugates(ADCs)are targeted biological agents composed of a cytotoxic drug linked to a monoclonal antibody through a linker.The monoclonal antibody targets tumor cells and transports small‐molecule cytotoxic drugs for specific delivery and minimal off‐target side effects.It is necessary for clinicians to understand the molecular characteristics and mechanisms of ADCs.Patients'survival mainly depends on the appropriate dose and course of treatment and also on proper management of adverse reactions.This consensus provides a systematic review of commercially available ADCs and further discusses the clinical application and management of ADCs.
基金financially supported by National Undergraduate Training Programs for Innovation and Entrepreneurship(201310007048)the Basic Research Foundation of Beijing Institute of Technology(No.20120942005)the National Natural Science Foundation of China(No.21104005)
文摘The cationic folic acid（CFA） was prepared by introducing triethylenetetramine into folic acid with EDCI/NHS and characterized by IR, NMR and mass spectra. It was found that approximately one of two carboxyls in the folic acid molecule was substituted to form CFA. The conversion of γ-carboxyl is found to be 59% higher than 30% of γ-carboxyl. The CFA and doxorubicin hydrochloride can be loaded on the ionic shell of PTX-encapsulated micelle to form CFA loaded binary drug carrier via static interaction in aqueous solutions. The successful loading was demonstrated by zeta potential measurement and the drug load amount（DLA） of CFA was measured by HPLC. In vitro cytotoxicity results revealed the CFA drug carrier showed higher cytotoxicity to cancer cell MDA-MB-321 than the binary drug carrier without CFA and the positive control, while it showed lower cytotoxicity to normal cell HUVEC than the positive control, and similar cytotoxicity with the binary drug carrier without CFA. These results as well as confocal laser scanning microscopy observation indicate the synthesized CFA drug carrier possesses active tumor-targeting property.
