BACKGROUND This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer.It presents a unique case of a woman with estr...BACKGROUND This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer.It presents a unique case of a woman with estrogen receptor-positive,HER2-negative breast cancer who developed brain metastasis.The report highlights her initial favorable response to abemaciclib and letrozole therapy prior to the discon-tinuation due to drug-induced lung damage(DILD).CASE SUMMARY In this comprehensive case summary,we present the clinical course of a woman in her 60s,who 11 years following primary breast cancer surgery,was diagnosed with multiple brain metastases.As a third-line systemic therapy,she underwent treatment with abemaciclib and letrozole.This treatment approach yielded a near-partial response in her metastatic brain lesions.However,abemaciclib adminis-tration ceased due to the emergence of DILD,as confirmed by a computed tomography scan.The DILD improved after 1 mo of cessation.Despite ongoing therapeutic efforts,the patient’s condition progressively deteriorated,ultimately resulting in death due to progression of the brain metastases.CONCLUSION This case underscores the challenge of managing adverse events in responsive brain metastasis patients,given the scarcity of therapeutic options.展开更多
Drug-induced liver injury(DILI)is one of the leading causes of liver failure and withdrawal of drugs from the market.A poor understanding of the precipitating event aetiology and mechanisms of disease progression has ...Drug-induced liver injury(DILI)is one of the leading causes of liver failure and withdrawal of drugs from the market.A poor understanding of the precipitating event aetiology and mechanisms of disease progression has rendered the prediction and subsequent treatment intractable.Recent literature suggests that some drugs can alter the liver’s repair systems resulting in injury.The pathophysiology of DILI is complex,and immune dysfunction plays an important role in determining the course and severity of the disease.Immune dysfunction is influenced by the host response to drug toxicity.A deeper understanding of these processes may be beneficial in the management of DILI and aid in drug development.This review provides a structured framework presenting DILI in three progressive stages that summarize the interplay between drugs and the host defence networks.展开更多
Idiosyncratic drug-induced liver injury(iDILI) encompasses the unexpected harms that prescription and non-prescription drugs,herbal and dietary supplements can cause to the liver.iDILI remains a major public health pr...Idiosyncratic drug-induced liver injury(iDILI) encompasses the unexpected harms that prescription and non-prescription drugs,herbal and dietary supplements can cause to the liver.iDILI remains a major public health problem and a major cause of drug attrition.Given the lack of biomarkers for iDILI prediction,diagnosis and prognosis,searching new models to predict and study mechanisms of iDILI is necessary.One of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant iDILI.Thus,major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI patients.However,there are many gaps for explaining all the complexity of iDILI susceptibility and mechanisms.Therefore,there is a need to optimize preclinical human in vitro models to reduce the risk of iDILI during drug development.Here,the current experimental models and the future directions in iDILI modelling are thoroughly discussed,focusing on the human cellular models available to study the pathophysiological mechanisms of the disease and the most used in vivo animal iDILI models.We also comment about in silico approaches and the increasing relevance of patient-derived cellular models.展开更多
OBJECTIVE:To investigate the inhibitory effect of Yiguanjian decoction(YD) on DNA damage in Concanavalin A(Con A)-induced liver injury mice model and to explain the possible mechanism.METHODS:Totally 120 male BALB/c m...OBJECTIVE:To investigate the inhibitory effect of Yiguanjian decoction(YD) on DNA damage in Concanavalin A(Con A)-induced liver injury mice model and to explain the possible mechanism.METHODS:Totally 120 male BALB/c mice were randomly divided into 6 groups,20 mice each:normal group,model group,Bifendate group,YD low dose group,YD middle dose group and YD high dose group.Except normal group,liver injury model induced by Con A was established.While modeling,each mouse in YD group was given YD(0.4 m L/20 g per day) by intragastric administration(0.13 g YD for YD low dose group;0.26 g for YD middle dose group;0.52 g for YD high dose group).Bifendate group was given Bifendate(0.2 gnd model·kg-1 grou·d-1) by gavage.Normal group ap were fed with same volume of physiological saline daily.After 8 weeks,the serum alanine transaminase(ALT)and aspartate transaminase(AST) were tested.The hematoxylin-eosin staining was used to evaluate the grade of liver inflammation and liver fibrosis stage.Hepatocellular DNA damage was detected by single cell gel electrophoresis technology.The protein expression of tumor necrosis factor-α(TNF-α),Bax and Mut T Homolog 1(MTH1) was detected by western blotting and enzyme linked immunosorbent assay.Bax m RNA and MTH1 m RNA were detected by Real-time Polymerase Chain Reaction(PCR).RESULTS:YD can improve the degree of liver inflammation and fibrosis in the liver of chronic hepatitis mice,the dose effect relationship is remarkable(P < 0.05).YD can reduce liver cell DNA damage.The difference between YD middle dose group and model group was statistically significant(P < 0.05).YD middle dose group had decreased the protein expression of TNF-α in the mice liver of immunological liver injury(P < 0.05).YD can increase the protein expression of Bax(P < 0.05).Compared with normal group,the protein expression of MTH1 was decreased(P < 0.05),but there was no statistical significance between YD group and model group(P >0.05).YD can increase the m RNA expression of Bax and MTH1(both P < 0.05).CONCLUSION:YD can effectively inhibit the DNA damage in immunological liver injury mice,the mechanism may be that it can decrease the TNF-αand increase the Bax and MTH1 expression.展开更多
文摘BACKGROUND This case report addresses the dearth of effective therapeutic interventions for central nervous system metastases in patients with HER2-negative breast cancer.It presents a unique case of a woman with estrogen receptor-positive,HER2-negative breast cancer who developed brain metastasis.The report highlights her initial favorable response to abemaciclib and letrozole therapy prior to the discon-tinuation due to drug-induced lung damage(DILD).CASE SUMMARY In this comprehensive case summary,we present the clinical course of a woman in her 60s,who 11 years following primary breast cancer surgery,was diagnosed with multiple brain metastases.As a third-line systemic therapy,she underwent treatment with abemaciclib and letrozole.This treatment approach yielded a near-partial response in her metastatic brain lesions.However,abemaciclib adminis-tration ceased due to the emergence of DILD,as confirmed by a computed tomography scan.The DILD improved after 1 mo of cessation.Despite ongoing therapeutic efforts,the patient’s condition progressively deteriorated,ultimately resulting in death due to progression of the brain metastases.CONCLUSION This case underscores the challenge of managing adverse events in responsive brain metastasis patients,given the scarcity of therapeutic options.
文摘Drug-induced liver injury(DILI)is one of the leading causes of liver failure and withdrawal of drugs from the market.A poor understanding of the precipitating event aetiology and mechanisms of disease progression has rendered the prediction and subsequent treatment intractable.Recent literature suggests that some drugs can alter the liver’s repair systems resulting in injury.The pathophysiology of DILI is complex,and immune dysfunction plays an important role in determining the course and severity of the disease.Immune dysfunction is influenced by the host response to drug toxicity.A deeper understanding of these processes may be beneficial in the management of DILI and aid in drug development.This review provides a structured framework presenting DILI in three progressive stages that summarize the interplay between drugs and the host defence networks.
基金supported by grants of Instituto de Salud Carlos Ⅲ cofounded by Fondo Europeo de Desarrollo Regional-FEDER (contract numbers: PI18/01804, PI19-00883, PT20/00127,UMA18-FEDERJA-194, PY18-3364, Spain)Consejería de Salud de Andalucía cofounded by FEDER (contract number: PEMP-0127-2020, Spain)+1 种基金SCReN and CIBERehd are funded by ISCⅢ (Spain)based upon work from COST Action “CA17112d Prospective European Drug-Induced Liver Injury Network” supported by COST (European Cooperation in Science and Technology)。
文摘Idiosyncratic drug-induced liver injury(iDILI) encompasses the unexpected harms that prescription and non-prescription drugs,herbal and dietary supplements can cause to the liver.iDILI remains a major public health problem and a major cause of drug attrition.Given the lack of biomarkers for iDILI prediction,diagnosis and prognosis,searching new models to predict and study mechanisms of iDILI is necessary.One of the major limitations of iDILI preclinical assessment has been the lack of correlation between the markers of hepatotoxicity in animal toxicological studies and clinically significant iDILI.Thus,major advances in the understanding of iDILI susceptibility and pathogenesis have come from the study of well-phenotyped iDILI patients.However,there are many gaps for explaining all the complexity of iDILI susceptibility and mechanisms.Therefore,there is a need to optimize preclinical human in vitro models to reduce the risk of iDILI during drug development.Here,the current experimental models and the future directions in iDILI modelling are thoroughly discussed,focusing on the human cellular models available to study the pathophysiological mechanisms of the disease and the most used in vivo animal iDILI models.We also comment about in silico approaches and the increasing relevance of patient-derived cellular models.
基金Supported by Beijing Natural Science Foundation-funded Project(Yiguanjian on the Regulation of Microenvironment and Signal Pathway of Reactive Oxygen Species in Mouse with Immunological Liver Injury,No.7122024)
文摘OBJECTIVE:To investigate the inhibitory effect of Yiguanjian decoction(YD) on DNA damage in Concanavalin A(Con A)-induced liver injury mice model and to explain the possible mechanism.METHODS:Totally 120 male BALB/c mice were randomly divided into 6 groups,20 mice each:normal group,model group,Bifendate group,YD low dose group,YD middle dose group and YD high dose group.Except normal group,liver injury model induced by Con A was established.While modeling,each mouse in YD group was given YD(0.4 m L/20 g per day) by intragastric administration(0.13 g YD for YD low dose group;0.26 g for YD middle dose group;0.52 g for YD high dose group).Bifendate group was given Bifendate(0.2 gnd model·kg-1 grou·d-1) by gavage.Normal group ap were fed with same volume of physiological saline daily.After 8 weeks,the serum alanine transaminase(ALT)and aspartate transaminase(AST) were tested.The hematoxylin-eosin staining was used to evaluate the grade of liver inflammation and liver fibrosis stage.Hepatocellular DNA damage was detected by single cell gel electrophoresis technology.The protein expression of tumor necrosis factor-α(TNF-α),Bax and Mut T Homolog 1(MTH1) was detected by western blotting and enzyme linked immunosorbent assay.Bax m RNA and MTH1 m RNA were detected by Real-time Polymerase Chain Reaction(PCR).RESULTS:YD can improve the degree of liver inflammation and fibrosis in the liver of chronic hepatitis mice,the dose effect relationship is remarkable(P < 0.05).YD can reduce liver cell DNA damage.The difference between YD middle dose group and model group was statistically significant(P < 0.05).YD middle dose group had decreased the protein expression of TNF-α in the mice liver of immunological liver injury(P < 0.05).YD can increase the protein expression of Bax(P < 0.05).Compared with normal group,the protein expression of MTH1 was decreased(P < 0.05),but there was no statistical significance between YD group and model group(P >0.05).YD can increase the m RNA expression of Bax and MTH1(both P < 0.05).CONCLUSION:YD can effectively inhibit the DNA damage in immunological liver injury mice,the mechanism may be that it can decrease the TNF-αand increase the Bax and MTH1 expression.
