Drug Des Dev Ther
-
Review Meta Analysis
A meta-analysis for C-X-C chemokine receptor type 4 as a prognostic marker and potential drug target in hepatocellular carcinoma.
Chemokines (CKs), small proinflammatory chemoattractant cytokines that bind to specific G-protein coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. C-X-C chemokine receptor type 4 (CXCR4) has gained tremendous attention over the last decade, since it was found to be upregulated in a wide variety of cancer types, including hepatocellular carcinoma (HCC). The clinical relevance of expression of CXCR4 in HCC remains controversial; our aim was to identify the precise relationship of CXCR4 to prognosis and clinicopathological features. ⋯ These data indicate that CXCR4 expression correlates with an increased risk and worse survival in HCC patients. The aberrant CXCR4 expression plays an important role in the carcinogenesis and metastasis of HCC. Our conclusion also supports that the promise of CXCR4 signaling pathway blockade as a potential strategy for HCC patients.
-
The complexity of treating severe sepsis and septic shock has been elucidated in myriad studies, particularly in the past 10 years. The development of clinical guidelines, insight into the effect of bundle elements, and results of clinical trials have brought to light further opportunities and questions in the approach to pharmaceutical interventions for the global challenge to save lives and reduce healthcare costs. Therapeutic interventions including fluid resuscitation, hemodynamic monitoring, glycemic control, corticosteroids, and antimicrobial therapy and stewardship inform outcomes. Research on biomarkers, use of mesenchymal stem cells, blood purification, immunoglobulins, and antioxidative treatments apropos the immune response may soon yield viable therapies.
-
The efficacy of adding panitumumab to chemotherapy remains controversial in the treatment of metastatic colorectal cancer (mCRC). Thus, we conducted this meta-analysis to assess the efficacy and safety of this combination regimen in patients with mCRC. ⋯ This meta-analysis indicates that the combination of panitumumab and chemotherapy effectively improved PFS and ORR, but it did not prolong OS. However, as the number of studies in the meta-analysis was limited, more large-scale, better-designed RCTs are needed to assess the combination of panitumumab and chemotherapy.
-
Each year, despite optimal use of recommended acute and secondary prevention therapies, 4%-5% of patients with acute coronary syndrome (ACS) experience relapse of ACS or other cardiovascular events including stroke, heart failure, or sudden cardiac death after the index ACS. The sudden atherosclerotic plaque rupture leading to an ACS event is often accompanied by inflammation, which is thought to be a key pathogenic pathway to these excess cardiovascular events. Losmapimod is a novel, oral p38 mitogen-activated protein kinase (MAPK) inhibitor that targets MAPKs activated in macrophages, myocardium, and endothelial cells that occur as a part of global coronary vascular inflammation following plaque rupture. This review aims to 1) discuss the pathophysiological pathways through which p38 MAPKs may play key roles in initiation and progression of inflammatory disease and how losmapimod is thought to counteract these p38 MAPKs, and 2) to describe the efficacy and safety data for losmapimod obtained from preclinical studies and randomized controlled trials that support the hypothesis that it has promise as a treatment for patients with ACS.
-
Randomized Controlled Trial Comparative Study
A pharmacokinetic comparison of two voriconazole formulations and the effect of CYP2C19 polymorphism on their pharmacokinetic profiles.
SYP-1018 is a lyophilized polymeric nanoparticle formulation of voriconazole that is under development for intravenous dosing. This study compared the pharmacokinetic and tolerability profiles of SYP-1018 with those of Vfend(®), the marketed formulation of voriconazole. The effect of CYP2C19 polymorphism on the voriconazole pharmacokinetics was also evaluated. ⋯ SYP-1018 had comparable pharmacokinetic and tolerability profiles to Vfend(®) after a single intravenous infusion. CYP2C19 genotype affected not only the pharmacokinetics of voriconazole, but its intrasubject variability. SYP-1018 can be further developed as a clinically effective alternative to Vfend(®).