Anti-androgen therapy is the leading treatment for advanced prostate cancer and is commonly used for neoadjuvant or adjuvant treatment. Bicalutamide is a non-steroidal anti-androgen, used during the initiation of andr...Anti-androgen therapy is the leading treatment for advanced prostate cancer and is commonly used for neoadjuvant or adjuvant treatment. Bicalutamide is a non-steroidal anti-androgen, used during the initiation of androgen deprivation therapy along with a luteinizing hormone-releasing hormone agonist to reduce the symptoms of tumor-related flares in patients with advanced prostate cancer. As side effects, bicalutamide can cause fatigue, gynecomastia, and decreased libido through competitive androgen receptor blockade. Additionally, although not as common, drug-induced liver injury has also been reported. Herein, we report a case of hepatotoxicity secondary to bicalutamide use. Typically, bicalutamideinduced hepatotoxicity develops after a few days; however, in this case, hepatic injury occurred 5 mo after treatment initiation. Based on this rare case of delayed liver injury, we recommend careful monitoring of liver function throughout bicalutamide treatment for prostate cancer.展开更多
Anabolic androgenic steroids(AASs)are a group of molecules including endogenous testosterone and synthetic derivatives that have both androgenic and anabolic effects.These properties make them therapeutically benefici...Anabolic androgenic steroids(AASs)are a group of molecules including endogenous testosterone and synthetic derivatives that have both androgenic and anabolic effects.These properties make them therapeutically beneficial in medical conditions such as hypogonadism.However,they are commonly bought illegally and misused for their anabolic,skeletal muscle building,and performanceenhancing effects.Supraphysiologic and long-term use of AASs affects all organs,leading to cardiovascular,neurological,endocrine,gastrointestinal,renal,and hematologic disorders.Hepatotoxicity is one of the major concerns regarding AASs treatment and abuse.Testosterone and its derivatives have been most often shown to induce a specific form of cholestasis,peliosis hepatis,and hepatic benign and malignant tumors.It is currently believed that mechanisms of pathogenesis of these disorders include disturbance of antioxidative factors,upregulation of bile acid synthesis,and induction of hepatocyte hyperplasia.Most toxicity cases are treated with supportive measures and liver function normalizes with discontinuation of AAS.However,some long-term consequences are irreversible.AAS-induced liver injury should be taken in consideration in patients with liver disorders,especially with the increasing unintentional ingestion of supplements containing AAS.In this paper,we review the most current knowledge about AAS-associated adverse effects on the liver,and their clinical presentations,prevalence,and pathophysiological mechanisms.展开更多
AIM We have previously reported that inducible over-expresaion of Bak may prolong cell cycle in G1 phase and lead to apoptosis in HCC-9204 cells. This study is to investigate whether p27KIP1 plays an important role in...AIM We have previously reported that inducible over-expresaion of Bak may prolong cell cycle in G1 phase and lead to apoptosis in HCC-9204 cells. This study is to investigate whether p27KIP1 plays an important role in this process. MEHODS In order to elucidate the exact function of p27KIP1 in this process, a zinc inducible p27KIP1 stable transfectant and transient p27KIP1- GFP fusion transfectant were constructed. The effects of inducible p27KIP1 on cell growth, cell cycle arrest and apoptosis were examined in the mock, control pMD vector, and pMD-KIP1 transfected HCC-9204 cells. RESULTS This p27KIP1-GFP transfectant may transiently express the fusion gene. The cell growth was reduced by 35% at 48 h of p27KIP1 induction with zinc treatment as determined by trypan blue exclusion assay. These differences remained the same after 72 h of p27KIP1 expression, p27KIP1 caused cell cycle arrest after 24 h of induction, with 40% increase in G1 population. Prolonged p27KIP1 expression in this cell line induced apoptotic cell death reflected by TUNEL assay. Fourty-eight h and 72 h of p27KIP1 expression showed a characteristic DNA ladder on agarose gel electrophoresis.展开更多
AIM To investigate the expression of integrinsin rats liver during 3’-Me-DAB inducedhepatocarcinogenesis and to find out therelationship between integrins and liver cancermetastasis.METHODS The expressions of integri...AIM To investigate the expression of integrinsin rats liver during 3’-Me-DAB inducedhepatocarcinogenesis and to find out therelationship between integrins and liver cancermetastasis.METHODS The expressions of integrins α<sub>1</sub>,α<sub>2</sub>,α<sub>3</sub> and α<sub>5</sub> and epidermal keratin（EK）wereobserved by immunohistochemical PAP method.RESULTS In the normal liver tissues,hepatocytes express integrins α<sub>1</sub> and α<sub>5</sub> and inthe bile duct epithlium,EK.In liver cirrhosis,hepatocytes highly express integrins α<sub>1</sub>,α<sub>2</sub>,α<sub>3</sub>and α<sub>5</sub> and in hyperplastic bile duct epithelium,integrins α<sub>1</sub>,α<sub>5</sub> and EK.Expression of integrinsα<sub>1</sub>,α<sub>2</sub>,α<sub>3</sub> and α<sub>5</sub> were obviously decreased in thepreneoplastic nodules and primary carcinomabut expressions of integrins α<sub>1</sub> and α<sub>5</sub> inmetastasis in the lung and diaphragma werehigher than those in primary carcinoma.CONCLUSION Integrins α<sub>1</sub> and α<sub>5</sub> may play amajor role in chemically inducedhepatocarcinogenesis and metastasis in rats.展开更多
To examine the effect of transcatheter arterial embolization （TAE） of liver tumors on hypoxia-inducible factor-1α （HIF-1α） expression in the residual viable tumor, a total of 30 New Zealand White rabbits implant...To examine the effect of transcatheter arterial embolization （TAE） of liver tumors on hypoxia-inducible factor-1α （HIF-1α） expression in the residual viable tumor, a total of 30 New Zealand White rabbits implanted with VX2 liver tumor were divided into 2 groups. TAE-treated group animals （n=15） were subjected to TAE with 150–250 μm polyvinyl alcohol particles. Control group animals （n=15） underwent sham embolization with distilled water. Six hours, 3 days or 7 days after TAE, the animals were sacrificed, and samples of tumor and adjacent normal liver tissue were harvested. Expression of HIF-1α protein was examined immunohistochemically. Real-time PCR was performed to examine the HIF-1α mRNA levels. Our results showed that HIF-1α protein was expressed in the VX2 tumors but not in the adjacent normal liver tissue. The HIF-1α-positive tumor cells were located predominantly at the periphery of necrotic tumor regions. The mean levels of HIF-1α protein were significantly higher in TAE-treated tumors than those in control tumors （P=0.002）. Among the three sacrificing time points, the difference in increase in HIF-1α protein was significant between the two groups at the sacrificing time point of 6 h and 3 days after TAE （P=0.020, P=0.031, respectively）, whereas no significant increase was noted 7 days after TAE （P=0.502）. In contrast, although HIF-1α mRNA was expressed in TAE-treated and control VX2 tumors, there existed no significant difference in the HIF-1α mRNA level between the two groups （P=0.372）. It is concluded that TAE of liver tumors increases the expression of HIF-1α at protein level in the residual viable tumor, which could be attributed to hypoxia generated by the procedure.展开更多
Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019(COVID...Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019(COVID-19)vaccination protocols.All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations,e.g.,BNT162b2,mRNA-1273,and ChAdOx1-S,can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration.Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination.The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies.Novel vaccine delivery platforms,e.g.,mRNA-containing lipid nanoparticles and adenoviral vectors,contribute to the inflammatory background that leads to an exaggerated immune response,while patterns of molecular mimicry between the spike(S)protein and prominent liver antigens may account for the autoimmune presentation.Immune mediators triggered by vaccination or vaccine ingredients per se,including autoreactive antibodies,cytokines,and cytotoxic T-cell populations,may inflict hepatocellular damage through wellestablished pathways.We aim to review available data associated with immunemediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.展开更多
目的探讨药物性肝损伤(DILI)患者临床转归的影响因素,构建列线图模型并进行内部验证。方法回顾性分析哈尔滨工业大学附属黑龙江省医院2017年1月—2022年12月收治的188例DILI患者的一般资料和实验室数据,根据患者临床转归分为结局良好组(...目的探讨药物性肝损伤(DILI)患者临床转归的影响因素,构建列线图模型并进行内部验证。方法回顾性分析哈尔滨工业大学附属黑龙江省医院2017年1月—2022年12月收治的188例DILI患者的一般资料和实验室数据,根据患者临床转归分为结局良好组(n=146)和不良结局组(n=42)。正态分布计量资料两组间比较采用成组t检验;非正态分布计量资料两组间比较采用Mann-Whitney U检验。计数资料两组间比较采用χ^(2)检验。通过单因素和多因素Logistic回归分析筛选DILI患者临床转归相关的独立影响因素。R Studio 4.1.2软件构建列线图模型,通过校准曲线、受试者工作特征曲线(ROC曲线)和决策曲线分析(DCA)对模型进行内部验证。结果单因素Logistic回归分析结果显示,肝活检诊断DILI、PLT、ChE、Alb、PTA、IgM和IgG与DILI患者不良结局相关(P值均<0.05)。多因素Logistic回归分析结果显示,肝活检诊断DILI(OR=0.072,95%CI:0.022~0.213,P<0.001)、临床分型(OR=0.463,95%CI:0.213~0.926,P=0.039)、ALT(OR=0.999,95%CI:0.998~1.000,P=0.025)、PTA(OR=0.973,95%CI:0.952~0.993,P=0.011)和Ig M(OR=1.456,95%CI:1.082~2.021,P=0.015)是DILI患者临床转归的独立影响因素。构建列线图,经验证校准曲线接近参考曲线,ROC曲线下面积为0.829,决策曲线分析显示该模型具有良好的临床净收益。结论构建的列线图模型对评估DILI患者的临床转归具有较好的临床校准度、鉴别能力和应用价值。展开更多
基金Supported by Departments of Internal MedicineChungnam National University School of Medicine,Daejeon,South Korea
文摘Anti-androgen therapy is the leading treatment for advanced prostate cancer and is commonly used for neoadjuvant or adjuvant treatment. Bicalutamide is a non-steroidal anti-androgen, used during the initiation of androgen deprivation therapy along with a luteinizing hormone-releasing hormone agonist to reduce the symptoms of tumor-related flares in patients with advanced prostate cancer. As side effects, bicalutamide can cause fatigue, gynecomastia, and decreased libido through competitive androgen receptor blockade. Additionally, although not as common, drug-induced liver injury has also been reported. Herein, we report a case of hepatotoxicity secondary to bicalutamide use. Typically, bicalutamideinduced hepatotoxicity develops after a few days; however, in this case, hepatic injury occurred 5 mo after treatment initiation. Based on this rare case of delayed liver injury, we recommend careful monitoring of liver function throughout bicalutamide treatment for prostate cancer.
文摘Anabolic androgenic steroids(AASs)are a group of molecules including endogenous testosterone and synthetic derivatives that have both androgenic and anabolic effects.These properties make them therapeutically beneficial in medical conditions such as hypogonadism.However,they are commonly bought illegally and misused for their anabolic,skeletal muscle building,and performanceenhancing effects.Supraphysiologic and long-term use of AASs affects all organs,leading to cardiovascular,neurological,endocrine,gastrointestinal,renal,and hematologic disorders.Hepatotoxicity is one of the major concerns regarding AASs treatment and abuse.Testosterone and its derivatives have been most often shown to induce a specific form of cholestasis,peliosis hepatis,and hepatic benign and malignant tumors.It is currently believed that mechanisms of pathogenesis of these disorders include disturbance of antioxidative factors,upregulation of bile acid synthesis,and induction of hepatocyte hyperplasia.Most toxicity cases are treated with supportive measures and liver function normalizes with discontinuation of AAS.However,some long-term consequences are irreversible.AAS-induced liver injury should be taken in consideration in patients with liver disorders,especially with the increasing unintentional ingestion of supplements containing AAS.In this paper,we review the most current knowledge about AAS-associated adverse effects on the liver,and their clinical presentations,prevalence,and pathophysiological mechanisms.
文摘AIM We have previously reported that inducible over-expresaion of Bak may prolong cell cycle in G1 phase and lead to apoptosis in HCC-9204 cells. This study is to investigate whether p27KIP1 plays an important role in this process. MEHODS In order to elucidate the exact function of p27KIP1 in this process, a zinc inducible p27KIP1 stable transfectant and transient p27KIP1- GFP fusion transfectant were constructed. The effects of inducible p27KIP1 on cell growth, cell cycle arrest and apoptosis were examined in the mock, control pMD vector, and pMD-KIP1 transfected HCC-9204 cells. RESULTS This p27KIP1-GFP transfectant may transiently express the fusion gene. The cell growth was reduced by 35% at 48 h of p27KIP1 induction with zinc treatment as determined by trypan blue exclusion assay. These differences remained the same after 72 h of p27KIP1 expression, p27KIP1 caused cell cycle arrest after 24 h of induction, with 40% increase in G1 population. Prolonged p27KIP1 expression in this cell line induced apoptotic cell death reflected by TUNEL assay. Fourty-eight h and 72 h of p27KIP1 expression showed a characteristic DNA ladder on agarose gel electrophoresis.
基金The Ninth Five-Year Key Program of the Ministry of Health (JB02 96-906-01-15)
文摘AIM To investigate the expression of integrinsin rats liver during 3’-Me-DAB inducedhepatocarcinogenesis and to find out therelationship between integrins and liver cancermetastasis.METHODS The expressions of integrins α<sub>1</sub>,α<sub>2</sub>,α<sub>3</sub> and α<sub>5</sub> and epidermal keratin（EK）wereobserved by immunohistochemical PAP method.RESULTS In the normal liver tissues,hepatocytes express integrins α<sub>1</sub> and α<sub>5</sub> and inthe bile duct epithlium,EK.In liver cirrhosis,hepatocytes highly express integrins α<sub>1</sub>,α<sub>2</sub>,α<sub>3</sub>and α<sub>5</sub> and in hyperplastic bile duct epithelium,integrins α<sub>1</sub>,α<sub>5</sub> and EK.Expression of integrinsα<sub>1</sub>,α<sub>2</sub>,α<sub>3</sub> and α<sub>5</sub> were obviously decreased in thepreneoplastic nodules and primary carcinomabut expressions of integrins α<sub>1</sub> and α<sub>5</sub> inmetastasis in the lung and diaphragma werehigher than those in primary carcinoma.CONCLUSION Integrins α<sub>1</sub> and α<sub>5</sub> may play amajor role in chemically inducedhepatocarcinogenesis and metastasis in rats.
基金supported by grants from National Natural Sciences Foundation of China (No 30970804)863 Na-tional High Technology Research and Development Program of China (No 2006AA03Z332)
文摘To examine the effect of transcatheter arterial embolization （TAE） of liver tumors on hypoxia-inducible factor-1α （HIF-1α） expression in the residual viable tumor, a total of 30 New Zealand White rabbits implanted with VX2 liver tumor were divided into 2 groups. TAE-treated group animals （n=15） were subjected to TAE with 150–250 μm polyvinyl alcohol particles. Control group animals （n=15） underwent sham embolization with distilled water. Six hours, 3 days or 7 days after TAE, the animals were sacrificed, and samples of tumor and adjacent normal liver tissue were harvested. Expression of HIF-1α protein was examined immunohistochemically. Real-time PCR was performed to examine the HIF-1α mRNA levels. Our results showed that HIF-1α protein was expressed in the VX2 tumors but not in the adjacent normal liver tissue. The HIF-1α-positive tumor cells were located predominantly at the periphery of necrotic tumor regions. The mean levels of HIF-1α protein were significantly higher in TAE-treated tumors than those in control tumors （P=0.002）. Among the three sacrificing time points, the difference in increase in HIF-1α protein was significant between the two groups at the sacrificing time point of 6 h and 3 days after TAE （P=0.020, P=0.031, respectively）, whereas no significant increase was noted 7 days after TAE （P=0.502）. In contrast, although HIF-1α mRNA was expressed in TAE-treated and control VX2 tumors, there existed no significant difference in the HIF-1α mRNA level between the two groups （P=0.372）. It is concluded that TAE of liver tumors increases the expression of HIF-1α at protein level in the residual viable tumor, which could be attributed to hypoxia generated by the procedure.
文摘Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019(COVID-19)vaccination protocols.All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations,e.g.,BNT162b2,mRNA-1273,and ChAdOx1-S,can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration.Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination.The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies.Novel vaccine delivery platforms,e.g.,mRNA-containing lipid nanoparticles and adenoviral vectors,contribute to the inflammatory background that leads to an exaggerated immune response,while patterns of molecular mimicry between the spike(S)protein and prominent liver antigens may account for the autoimmune presentation.Immune mediators triggered by vaccination or vaccine ingredients per se,including autoreactive antibodies,cytokines,and cytotoxic T-cell populations,may inflict hepatocellular damage through wellestablished pathways.We aim to review available data associated with immunemediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.
文摘目的探讨药物性肝损伤(DILI)患者临床转归的影响因素,构建列线图模型并进行内部验证。方法回顾性分析哈尔滨工业大学附属黑龙江省医院2017年1月—2022年12月收治的188例DILI患者的一般资料和实验室数据,根据患者临床转归分为结局良好组(n=146)和不良结局组(n=42)。正态分布计量资料两组间比较采用成组t检验;非正态分布计量资料两组间比较采用Mann-Whitney U检验。计数资料两组间比较采用χ^(2)检验。通过单因素和多因素Logistic回归分析筛选DILI患者临床转归相关的独立影响因素。R Studio 4.1.2软件构建列线图模型,通过校准曲线、受试者工作特征曲线(ROC曲线)和决策曲线分析(DCA)对模型进行内部验证。结果单因素Logistic回归分析结果显示,肝活检诊断DILI、PLT、ChE、Alb、PTA、IgM和IgG与DILI患者不良结局相关(P值均<0.05)。多因素Logistic回归分析结果显示,肝活检诊断DILI(OR=0.072,95%CI:0.022~0.213,P<0.001)、临床分型(OR=0.463,95%CI:0.213~0.926,P=0.039)、ALT(OR=0.999,95%CI:0.998~1.000,P=0.025)、PTA(OR=0.973,95%CI:0.952~0.993,P=0.011)和Ig M(OR=1.456,95%CI:1.082~2.021,P=0.015)是DILI患者临床转归的独立影响因素。构建列线图,经验证校准曲线接近参考曲线,ROC曲线下面积为0.829,决策曲线分析显示该模型具有良好的临床净收益。结论构建的列线图模型对评估DILI患者的临床转归具有较好的临床校准度、鉴别能力和应用价值。
