A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and D...A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and DOX （an antitumor drug） were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate （ALG-mOEG） for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. In addition, nanoparticles with a 1：1 （W：W） ratio of GA-ALG-mOEG and DOX-ALG-mOEG （NPs-3） showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 μg/g 3 h after injection, and AUC0-∞ and t1/2 of DOX in liver reached 4744.9 μg·h/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth （88.37% reduction in tumor weight） 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.展开更多
Human gastric cancer MKN-45 cells were transfectedwith pULB 3238, a plasmid carrying MVMp NS-1 genewith its original P4 promoter replaced by the glucocorticoid inducible promoter MMTV-LTR. After the integration and ex...Human gastric cancer MKN-45 cells were transfectedwith pULB 3238, a plasmid carrying MVMp NS-1 genewith its original P4 promoter replaced by the glucocorticoid inducible promoter MMTV-LTR. After the integration and expression of NS-1 gene, some of the transfectantsdied, while others remained alive, but the growth featuresof survived cells were changed. For further study on theantineoplastic function of parvoviral NS-1 protein in vivo,transgenic mice carrying NS-1 genes were established byconventional method. Among 4 founders, one of them wasfound to be able to transmit the transgene to around 50%of their offsprings. RT-PCR was performed to indicate theexpression of NS-1 gene in transgenic mice and its mRNAappeared in a variety of tissues. The expression of integrated NS-1 gene may correlate with the decreased incidence of tumor induced in vivo by chemical carcinogens.展开更多
BACKGROUND Cancer incidence remains a global challenge.The World Health Organization reported 19976499 new cases in 2022,including 1551060 in Latin America and the Caribbean.While chemotherapy advances have improved s...BACKGROUND Cancer incidence remains a global challenge.The World Health Organization reported 19976499 new cases in 2022,including 1551060 in Latin America and the Caribbean.While chemotherapy advances have improved survival,these treatments carry significant risks,particularly cardiovascular complications impacting morbidity and mortality.Early cardiotoxicity detection enables targeted interventions,guiding clinical decisions on treatment adjustments to mitigate damage and preserve function.Cardiac imaging and biomarkers assess cardiotoxicity before,during,and after therapy.Despite their importance,the lack of a structured multidisciplinary program hinders early detection and management in high-risk patients.AIM To evaluate the use of diagnostic tools for monitoring cardiotoxicity in cancer patients receiving high-risk chemotherapy at the National University Hospital of Colombia.METHODS This observational,retrospective cohort study included patients aged≥18 with cancer treated with potentially cardiotoxic chemotherapy at the National University Hospital of Colombia(2016-2019).Data from medical records included demographics,comorbidities,biomarkers,and echocardiographic parameters.Cardiotoxicity was defined by reduced left ventricular ejection fraction(LVEF)using Simpson’s method and biomarker abnormalities.Statistical analysis included descriptive methods to compare pre-and post-chemotherapy use of biomarkers and echocardiographic parameters.RESULTS From a total of 195 patients analyzed,8.7%(n=17)developed cardiotoxicity,predominantly mild(58.8%,n=10).Affected patients were mostly male(64.7%,n=11)with a mean age of 51.88±15.9 years.The median LVEF declined from 62%[interquartile range(IQR):58%–66%]at baseline to 46%(IQR:34%–56%)post-treatment.STRAIN longitudinal values also significantly decreased,from-18.38±4.62%at baseline to-14.22±4.93%posttreatment.Troponin was measured in 58.8%(n=10)of cardiotoxicity cases,while ProBNP was less frequently used(17.6%,n=3).CONCLUSION This study highlights the utility of echocardiography and biomarkers in assessing cardiotoxicity in oncology patients,emphasizing the need for standardized protocols to optimize early diagnosis and management.However,the retrospective nature of the study and the insufficient use of biomarkers may limit the generalizability of the findings.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.51073080 and 51273095)Natural Science Foundation of Tianjin(No.13JCYBJC25100)and PCSIRT(No.IRT1257)
文摘A series of drug delivery systems based on a sodium alginate derivative were prepared by mixing glycyrrhetinic acid （GA） and doxorubicin （DOX） conjugates at different ratios. GA （a liver-targeting ligand） and DOX （an antitumor drug） were both conjugated to oligomeric glycol monomethyl ether-modified sodium alginate （ALG-mOEG） for prolonged duration of action. These NP-based delivery systems exhibited active cell uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. In addition, nanoparticles with a 1：1 （W：W） ratio of GA-ALG-mOEG and DOX-ALG-mOEG （NPs-3） showed the highest cellular uptake and cytotoxicity in vitro and liver-targeted distribution and anti-tumor activity in vivo. Specifically, when mixed nanoparticles defined as NPs-3 were injected in mice, liver DOX concentration reached 61.9 μg/g 3 h after injection, and AUC0-∞ and t1/2 of DOX in liver reached 4744.9 μg·h/g and 49.5 h, respectively. In addition, mice receiving a single injection of NPs-3 exhibited much slower tumor growth （88.37% reduction in tumor weight） 16 days after injection compared with placebo. These results indicate that effective cancer treatment may be developed using mixed NP delivery systems with appropriate ratio of targeted ligand and drug.
文摘Human gastric cancer MKN-45 cells were transfectedwith pULB 3238, a plasmid carrying MVMp NS-1 genewith its original P4 promoter replaced by the glucocorticoid inducible promoter MMTV-LTR. After the integration and expression of NS-1 gene, some of the transfectantsdied, while others remained alive, but the growth featuresof survived cells were changed. For further study on theantineoplastic function of parvoviral NS-1 protein in vivo,transgenic mice carrying NS-1 genes were established byconventional method. Among 4 founders, one of them wasfound to be able to transmit the transgene to around 50%of their offsprings. RT-PCR was performed to indicate theexpression of NS-1 gene in transgenic mice and its mRNAappeared in a variety of tissues. The expression of integrated NS-1 gene may correlate with the decreased incidence of tumor induced in vivo by chemical carcinogens.
文摘BACKGROUND Cancer incidence remains a global challenge.The World Health Organization reported 19976499 new cases in 2022,including 1551060 in Latin America and the Caribbean.While chemotherapy advances have improved survival,these treatments carry significant risks,particularly cardiovascular complications impacting morbidity and mortality.Early cardiotoxicity detection enables targeted interventions,guiding clinical decisions on treatment adjustments to mitigate damage and preserve function.Cardiac imaging and biomarkers assess cardiotoxicity before,during,and after therapy.Despite their importance,the lack of a structured multidisciplinary program hinders early detection and management in high-risk patients.AIM To evaluate the use of diagnostic tools for monitoring cardiotoxicity in cancer patients receiving high-risk chemotherapy at the National University Hospital of Colombia.METHODS This observational,retrospective cohort study included patients aged≥18 with cancer treated with potentially cardiotoxic chemotherapy at the National University Hospital of Colombia(2016-2019).Data from medical records included demographics,comorbidities,biomarkers,and echocardiographic parameters.Cardiotoxicity was defined by reduced left ventricular ejection fraction(LVEF)using Simpson’s method and biomarker abnormalities.Statistical analysis included descriptive methods to compare pre-and post-chemotherapy use of biomarkers and echocardiographic parameters.RESULTS From a total of 195 patients analyzed,8.7%(n=17)developed cardiotoxicity,predominantly mild(58.8%,n=10).Affected patients were mostly male(64.7%,n=11)with a mean age of 51.88±15.9 years.The median LVEF declined from 62%[interquartile range(IQR):58%–66%]at baseline to 46%(IQR:34%–56%)post-treatment.STRAIN longitudinal values also significantly decreased,from-18.38±4.62%at baseline to-14.22±4.93%posttreatment.Troponin was measured in 58.8%(n=10)of cardiotoxicity cases,while ProBNP was less frequently used(17.6%,n=3).CONCLUSION This study highlights the utility of echocardiography and biomarkers in assessing cardiotoxicity in oncology patients,emphasizing the need for standardized protocols to optimize early diagnosis and management.However,the retrospective nature of the study and the insufficient use of biomarkers may limit the generalizability of the findings.
