Familial intrahepatic cholestasis(FIC) comprises a group of rare cholestatic liver diseases associated with canalicular transport defects resulting predominantly from mutations in ATP8B1, ABCB11 and ABCB4. Phe-notypes...Familial intrahepatic cholestasis(FIC) comprises a group of rare cholestatic liver diseases associated with canalicular transport defects resulting predominantly from mutations in ATP8B1, ABCB11 and ABCB4. Phe-notypes range from benign recurrent intrahepatic cholestasis(BRIC), associated with recurrent cholestatic attacks, to progressive FIC(PFIC). Patients often suffer from severe pruritus and eventually progressive cholestasis results in liver failure. Currently, first-line treatment includes ursodeoxycholic acid in patients with ABCB4 deficiency(PFIC3) and partial biliary diversion in patients with ATP8B1 or ABCB11 deficiency(PFIC1 and PFIC2). When treatment fails, liver transplantation is needed which is associated with complications like rejection, post-transplant hepatic steatosis and recurrence of disease. Therefore, the need for more and better therapies for this group of chronic diseases remains. Here, we discuss new symptomatic treatment options like total biliary diversion, pharmacological diversion of bile acids and hepatocyte transplantation. Furthermore, we focus on emerging mutation-targeted therapeutic strategies, providing an outlook for future personalized treatment for inherited cholestatic liver diseases.展开更多
Objective： The aim of this study was to evaluate the safety and efficiency of combination of trastuzumab and chemotherapy as first line regimen in Her-2 overexpressing metastatic breast cancer （MBC） patients. The p...Objective： The aim of this study was to evaluate the safety and efficiency of combination of trastuzumab and chemotherapy as first line regimen in Her-2 overexpressing metastatic breast cancer （MBC） patients. The primary endpoint was overall response rate （ORR） and the second endpoint was clinical benefit rate （CBR） and toxcities. Methods： Estrogen recep- tor （ER） （-）, progesterone receptor （PR） （-）, Her-2 （＋＋＋） patients were included in the study. 126 eligible patients were divided into 2 groups, 51 of them were assigned to the Herceptin group （H group） and 75 of them were assigned to the Control group （C group）. They were treated by commonly used chemotherapy regimens with or without trastuzumab. Results： Response rate （RR） of the H group and the C group were 51.0% and 24.0% separately, and the difference were statistically significant （P 〈 0.05）. CBR of the two groups were 76.4% （H group） and 64.0% （C group）, had significant difference （P 〈 0.05）. Complete response rate （CRR） of the two groups were 21.5% and 6.6%, there were no significant difference between the two groups （P = 0.055）. Grade 3-4 cardiac toxicity were recorded in 9 patients with trastuzumab plus chemotherapy （17.6%） and 4 patients with chemotherapy （5.4%）, with no statistical significance （P = 0.054）. In the subgroup of antharcycline-containing regimens, Grade 1-4 cardiac toxicity occurred in 9 patients in the trasutuzumab combining with antharcycline-containing regimens arm [herceptin plus anthracyciine contained chemotherapy （H ＋ ACCT arm; 40.9%, g/22）], and 4 patients in the antharcycline- containing chemotherapy arm （ACCT arm; 12.5%, 4/32）. There was statistical significant difference between the two arms （P 〈 0.05）. Grade 3--4 cardiac toxicity, the occurance rates were 18.1% （4/22） in H ＋ ACCT arm and 6.3% （2/32） in ACCT arm, and there was no significant statistical difference （P = 0.352）. Grade 3-4 granulocytopenia in the H group and C group were 27.5% （14/51） and 26.7% （20/75）, with no significant difference （P = 0.922）. Conclusion： The efficiency of trastuzumab combining with chemotherapy using as first line regimen in Her-2 overexpressing MBC patients were exact. However, the long-term cardiac toxicity can be hidden troubles of trastuzumab using.展开更多
文摘Familial intrahepatic cholestasis(FIC) comprises a group of rare cholestatic liver diseases associated with canalicular transport defects resulting predominantly from mutations in ATP8B1, ABCB11 and ABCB4. Phe-notypes range from benign recurrent intrahepatic cholestasis(BRIC), associated with recurrent cholestatic attacks, to progressive FIC(PFIC). Patients often suffer from severe pruritus and eventually progressive cholestasis results in liver failure. Currently, first-line treatment includes ursodeoxycholic acid in patients with ABCB4 deficiency(PFIC3) and partial biliary diversion in patients with ATP8B1 or ABCB11 deficiency(PFIC1 and PFIC2). When treatment fails, liver transplantation is needed which is associated with complications like rejection, post-transplant hepatic steatosis and recurrence of disease. Therefore, the need for more and better therapies for this group of chronic diseases remains. Here, we discuss new symptomatic treatment options like total biliary diversion, pharmacological diversion of bile acids and hepatocyte transplantation. Furthermore, we focus on emerging mutation-targeted therapeutic strategies, providing an outlook for future personalized treatment for inherited cholestatic liver diseases.
基金Supported by grants from the Sub-topics of Major Drug Discovery Platform in the Twelfth-Five Year Research Program of China(No.2012ZX09303016-002)Liaoning Province Science & Technology Development Funds(No.2012225019)
文摘Objective： The aim of this study was to evaluate the safety and efficiency of combination of trastuzumab and chemotherapy as first line regimen in Her-2 overexpressing metastatic breast cancer （MBC） patients. The primary endpoint was overall response rate （ORR） and the second endpoint was clinical benefit rate （CBR） and toxcities. Methods： Estrogen recep- tor （ER） （-）, progesterone receptor （PR） （-）, Her-2 （＋＋＋） patients were included in the study. 126 eligible patients were divided into 2 groups, 51 of them were assigned to the Herceptin group （H group） and 75 of them were assigned to the Control group （C group）. They were treated by commonly used chemotherapy regimens with or without trastuzumab. Results： Response rate （RR） of the H group and the C group were 51.0% and 24.0% separately, and the difference were statistically significant （P 〈 0.05）. CBR of the two groups were 76.4% （H group） and 64.0% （C group）, had significant difference （P 〈 0.05）. Complete response rate （CRR） of the two groups were 21.5% and 6.6%, there were no significant difference between the two groups （P = 0.055）. Grade 3-4 cardiac toxicity were recorded in 9 patients with trastuzumab plus chemotherapy （17.6%） and 4 patients with chemotherapy （5.4%）, with no statistical significance （P = 0.054）. In the subgroup of antharcycline-containing regimens, Grade 1-4 cardiac toxicity occurred in 9 patients in the trasutuzumab combining with antharcycline-containing regimens arm [herceptin plus anthracyciine contained chemotherapy （H ＋ ACCT arm; 40.9%, g/22）], and 4 patients in the antharcycline- containing chemotherapy arm （ACCT arm; 12.5%, 4/32）. There was statistical significant difference between the two arms （P 〈 0.05）. Grade 3--4 cardiac toxicity, the occurance rates were 18.1% （4/22） in H ＋ ACCT arm and 6.3% （2/32） in ACCT arm, and there was no significant statistical difference （P = 0.352）. Grade 3-4 granulocytopenia in the H group and C group were 27.5% （14/51） and 26.7% （20/75）, with no significant difference （P = 0.922）. Conclusion： The efficiency of trastuzumab combining with chemotherapy using as first line regimen in Her-2 overexpressing MBC patients were exact. However, the long-term cardiac toxicity can be hidden troubles of trastuzumab using.
