Interest in understanding the etiology and developing new treatments for anxiety disorders in children and adolescents has led to recent studies of neurotransmitters not traditionally associated with neural pathways f...Interest in understanding the etiology and developing new treatments for anxiety disorders in children and adolescents has led to recent studies of neurotransmitters not traditionally associated with neural pathways for fear and anxiety. The binding of the neurotransmitter substance P (SP) to its neurokinin-1 (NK1) receptor may be a crucial component in mediating the anxiety response. While previous studies using rodent models have documented the anxiolytic effects of SP antagonists, the role of individual differences in affective temperament has not yet been examined in studies of drug response. This study used intracerebroventricular injections of the NK1 antagonist Spantide II at concentrations of 10 and 100 pmol to examine the consequences of blocking the SP-NK1 pathway in high and low line rats selectively bred for high or low levels of ultrasonic distress calls after a brief maternal separation. Affective temperament was a significant factor in determining drug response. Spantide II resulted in a significant reduction of distress calls in subjects in the high anxiety line, while low line subjects with low anxiety were resistant to the drug. These data indicate that the SP-NK1 pathway could be an important therapeutic target for the treatment of various stress disorders, but drug response might be influenced by the individual’s state anxiety or history of chronic stress.展开更多
Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy. Neurokinin-1 receptor antagonists (NK1-RAs) have been incorporated in the contemporary management of CINV. However, clinica...Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy. Neurokinin-1 receptor antagonists (NK1-RAs) have been incorporated in the contemporary management of CINV. However, clinical studies on NK1-RAs have shown mixed results in reducing CINV risk. Most studies focused on the use of aprepitant (APR) and casopitant (CAS) in breast cancer patients receiving AC-type (doxorubicin and cyclophosphamide) chemotherapy. In this study, we compared the study design and clinical efficacies of these NK1-RAs in reducing CINV risk. Among the selected eight studies, 4 APR Randomized Controlled Trials (RCTs), 2 APR Observational Studies (OSs) and 2 CAS RCTs were identified. Patient-related characteristics such as the proportion of females (60.0% - 100.0%), age (46.5 - 59.5 years), histories of motion (5.6% - 47.0% in NK1-RA arms) and morning sicknesses (14.2% - 45.0% in NK1-RA arms) and types of antiemetic regimens;as well as chemotherapy-related characteristics such as the proportion of patients on AC chemotherapy (15.0% - 100.0%) varied greatly. In terms of efficacies, both APR and CAS improved overall CR and vomiting in majority of the studies. None of the studies, however, demonstrated that NK1-RA could provide adequate nausea control. To conclude, NK1-RAs are effective in improving vomiting and overall CR, but not useful in controlling nausea or attaining CC, the ideal CINV endpoint. A shift in paradigm is needed for future CINV research. As healthcare providers continue to strive for optimum CINV control in their patients, we hope this review can help them make better informed clinical decisions.展开更多
Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1-and5-year relative survival rates are 25%and 6%,respectively.Thus,it is urgent to investigate new antitumor drugs ...Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1-and5-year relative survival rates are 25%and 6%,respectively.Thus,it is urgent to investigate new antitumor drugs to improve the survival of pancreatic cancer patients.The peptide substance P(SP)has a widespread distribution throughout the body.After binding to the neurokinin-1(NK-1)receptor,SP regulates biological functions related to cancer,such as tumor cell proliferation,neoangiogenesis,the migration of tumor cells for invasion,infiltration and metastasis,and it exerts an antiapoptotic effects on tumor cells.It is known that the SP/NK-1 receptor system is involved in pancreatic cancer progression:(1)pancreatic cancer cells and samples express NK-1 receptors;(2)the NK-1 receptor is overexpressed in pancreatic cancer cells in comparison with non-tumor cells;(3)nanomolar concentrations of SP induce pancreatic cancer cell proliferation;(4)NK-1 receptor antagonists inhibit pancreatic cell proliferation in a concentration-dependent manner,at a certain concentration,these antagonists inhibit100%of tumor cells;(5)this antitumor action is medi-ated through the NK-1 receptor,and tumor cells die by apoptosis;and(6)NK-1 receptor antagonists inhibit angiogenesis in pancreatic cancer xenografts.All these data suggest that the SP/NK-1 receptor system could play an important role in the development of pancreatic cancer;that the NK-1 receptor could be a new promising therapeutic target in pancreatic cancer,and that NK-1 receptor antagonists could improve the treatment of pancreatic cancer.展开更多
文摘Interest in understanding the etiology and developing new treatments for anxiety disorders in children and adolescents has led to recent studies of neurotransmitters not traditionally associated with neural pathways for fear and anxiety. The binding of the neurotransmitter substance P (SP) to its neurokinin-1 (NK1) receptor may be a crucial component in mediating the anxiety response. While previous studies using rodent models have documented the anxiolytic effects of SP antagonists, the role of individual differences in affective temperament has not yet been examined in studies of drug response. This study used intracerebroventricular injections of the NK1 antagonist Spantide II at concentrations of 10 and 100 pmol to examine the consequences of blocking the SP-NK1 pathway in high and low line rats selectively bred for high or low levels of ultrasonic distress calls after a brief maternal separation. Affective temperament was a significant factor in determining drug response. Spantide II resulted in a significant reduction of distress calls in subjects in the high anxiety line, while low line subjects with low anxiety were resistant to the drug. These data indicate that the SP-NK1 pathway could be an important therapeutic target for the treatment of various stress disorders, but drug response might be influenced by the individual’s state anxiety or history of chronic stress.
文摘Chemotherapy-induced nausea and vomiting (CINV) are distressing side effects of chemotherapy. Neurokinin-1 receptor antagonists (NK1-RAs) have been incorporated in the contemporary management of CINV. However, clinical studies on NK1-RAs have shown mixed results in reducing CINV risk. Most studies focused on the use of aprepitant (APR) and casopitant (CAS) in breast cancer patients receiving AC-type (doxorubicin and cyclophosphamide) chemotherapy. In this study, we compared the study design and clinical efficacies of these NK1-RAs in reducing CINV risk. Among the selected eight studies, 4 APR Randomized Controlled Trials (RCTs), 2 APR Observational Studies (OSs) and 2 CAS RCTs were identified. Patient-related characteristics such as the proportion of females (60.0% - 100.0%), age (46.5 - 59.5 years), histories of motion (5.6% - 47.0% in NK1-RA arms) and morning sicknesses (14.2% - 45.0% in NK1-RA arms) and types of antiemetic regimens;as well as chemotherapy-related characteristics such as the proportion of patients on AC chemotherapy (15.0% - 100.0%) varied greatly. In terms of efficacies, both APR and CAS improved overall CR and vomiting in majority of the studies. None of the studies, however, demonstrated that NK1-RA could provide adequate nausea control. To conclude, NK1-RAs are effective in improving vomiting and overall CR, but not useful in controlling nausea or attaining CC, the ideal CINV endpoint. A shift in paradigm is needed for future CINV research. As healthcare providers continue to strive for optimum CINV control in their patients, we hope this review can help them make better informed clinical decisions.
文摘Pancreatic cancer is the fourth leading cause of cancer related-death for both men and women and the 1-and5-year relative survival rates are 25%and 6%,respectively.Thus,it is urgent to investigate new antitumor drugs to improve the survival of pancreatic cancer patients.The peptide substance P(SP)has a widespread distribution throughout the body.After binding to the neurokinin-1(NK-1)receptor,SP regulates biological functions related to cancer,such as tumor cell proliferation,neoangiogenesis,the migration of tumor cells for invasion,infiltration and metastasis,and it exerts an antiapoptotic effects on tumor cells.It is known that the SP/NK-1 receptor system is involved in pancreatic cancer progression:(1)pancreatic cancer cells and samples express NK-1 receptors;(2)the NK-1 receptor is overexpressed in pancreatic cancer cells in comparison with non-tumor cells;(3)nanomolar concentrations of SP induce pancreatic cancer cell proliferation;(4)NK-1 receptor antagonists inhibit pancreatic cell proliferation in a concentration-dependent manner,at a certain concentration,these antagonists inhibit100%of tumor cells;(5)this antitumor action is medi-ated through the NK-1 receptor,and tumor cells die by apoptosis;and(6)NK-1 receptor antagonists inhibit angiogenesis in pancreatic cancer xenografts.All these data suggest that the SP/NK-1 receptor system could play an important role in the development of pancreatic cancer;that the NK-1 receptor could be a new promising therapeutic target in pancreatic cancer,and that NK-1 receptor antagonists could improve the treatment of pancreatic cancer.
