ABSTRACT
CLDN6 is a member of the CLDNs family that is specifically and highly expressed in cancers such as ovarian, testicular, endocervical, liver and lung adenocarcinoma, but hardly expressed in adult normal tissues. CLDN6 is able to activate multiple signaling pathways, which take part in the development and progression of cancer, including promoting tumor growth, migration and invasion, and promoting chemoresistance in cancer. In recent years, CLDN6 has received much attention as a novel target for cancer therapeutics. Many types of anticancer drugs targeting CLDN6 have been developed, including antibody-conjugated drugs (ADC), monoclonal antibodies, bispecific antibodies, and chimeric antigen receptor T-cell immunotherapy (CAR-T). This paper briefly summarizes the structure, expression and function of CLDN6 in tumors, and reviews the current status and ideas of developing targeted CLDN6 anticancer drugs.
Subject(s)
Signal Transduction , Immunotherapy , Antibodies, Monoclonal , Neoplasms/drug therapyABSTRACT
Xiao Ke Qing (XKQ) granule has been clinically used to treat type 2 diabetes mellitus (T2DM) for 10 years in Chinese traditional medication. However, its mechanisms against hyperglycemia remain poorly understood. This study aims to investigate XKQ mechanisms on diabetes and diabetic liver disease by using the KKAy mice model. Our results indicate that XKQ can significantly reduce food and water intake. XKQ treatment also remarkably decreases both the fasting blood glucose and blood glucose in the oral glucose tolerance test. Additionally, XKQ can significantly decrease the serum alanine aminotransferase level and liver index and can alleviate the fat degeneration in liver tissues. Moreover, XKQ can ameliorate insulin resistance and upregulate the expression of IRS-1, PI3K (p85), p-Akt, and GLUT4 in the skeletal muscle of KKAy mice. XKQ is an effective drug for T2DM by ameliorating insulin resistance and regulating the PI3K/Akt signaling pathway in the skeletal muscle.
Subject(s)
Animals , Female , Mice , Blood Glucose , Metabolism , Diabetes Mellitus, Type 2 , Drug Therapy , Metabolism , Disease Models, Animal , Drugs, Chinese Herbal , Pharmacology , Glucose Tolerance Test , Glucose Transporter Type 4 , Metabolism , Hypoglycemic Agents , Pharmacology , Insulin , Blood , Insulin Resistance , Liver , Pathology , Mice, Inbred C57BL , Phosphatidylinositol 3-Kinases , Metabolism , Proto-Oncogene Proteins c-akt , Metabolism , Signal TransductionABSTRACT
Compound Traditional Chinese Medicine (CTCM) applying for FDA approval as botanical drug is a systemic and innovative work.Compound Danshen Dripping Pill (T89) is the first CTCM completed FDA global multi-center Phase Ⅲ clinical trial,which has become a benchmark for TCM globalization.Extensive experiences have been accumulated through the 20 years' research and development.Tasly fully considered the characteristics of CTCM while complying with FDA regulations during the entire application process.In which,product indication was clearly defined and agreed,clinical trial protocol was scientifically and innovatively designed with gold standard,phase Ⅱ study was well completed,SPA for phase Ⅲ study was obtained,and eventually the global multi-center phase Ⅲ study was successfully completed.In order to better support T89's application,Tasly conducted series of additional studies and introduced many innovations,such as drug-drug interaction study for TCM,finger printing study for CTCM,quality consistency study,biological assay study and etc.Globalization of T89 is not only a product creating history,but also a process for Tasly and the US FDA working together to continuously innovate and create history in innovating modern TCM standards,improving industrial chain GMP system for botanical drugs,making technical breakthroughs,exploring regulatory pathways and increasing product value.It represents the national power and historical progress in medicine.