9 research outputs found
CXCR2 Inhibition Combined with Sorafenib Improved Antitumor and Antiangiogenic Response in Preclinical Models of Ovarian Cancer
The authors thank Drs. Kar-Ming Fung and Muralidharan Jayaraman, and Ms. Sheeja Aravindan for their help with the IHC experiments. The authors also thank the OUHSC Histology and Molecular Imaging Cores for their service and technical assistance.Antiangiogenic therapy is important for the treatment of gynecological cancer. However, the therapeutic benefit derived from these treatments is transient, predominantly due to the selective activation of compensatory proangiogenic pathways that lead to rapid development of resistance. We aimed to identify and target potential alternative signaling to anti-vascular endothelial growth factor (VEGF) therapy, with a view toward developing a combination of antiangiogenic agents to provide extended therapeutic benefits. We developed a preclinical in vivo phenotypic resistance model of ovarian cancer resistant to antiangiogenic therapy. We measured dynamic changes in secreted chemokines and angiogenic signaling in tumors and plasma in response to anti-VEGF treatment, as tumors advanced from the initial responsive phase to progressive disease. In tumors that progressed following sorafenib treatment, gene and protein expression levels of proangiogenic CXC chemokines and their receptors were significantly elevated, compared with responsive tumors. The chemokine (C-X-C motif) ligand 8 (CXCL8), also known as interleukin-8 (IL-8) increase was time-dependent and coincided with the dynamics of tumor progression. We used SB225002, a pharmacological inhibitor of chemokine (C-X-C motif) receptor 2 (CXCR2), to disrupt the CXC chemokine-mediated functions of ovarian cancer cells in in vitro assays of cell growth inhibition, spheroid formation, and cell migration. The combination of CXCR2 inhibitor with sorafenib led to a synergistic inhibition of cell growth in vitro, and further stabilized tumor progression following sorafenib in vivo. Our results suggest that CXCR2-mediated chemokines may represent an important compensatory pathway that promotes resistance to antiangiogenic therapy in ovarian cancer. Thus, simultaneous blockage of this proangiogenic cytokine pathway using CXCR2 inhibitors and the VEGF receptor (VEGFR) pathway could improve the outcomes of antiangiogenic therapy.Yeshttp://www.plosone.org/static/editorial#pee
The right ventricle after cardiac surgery: Hypotheses, evidence, and the role of advanced echocardiography modalities
N/
Tripartite Assessment of Right Ventricular Systolic Function in Persistent Pulmonary Hypertension of the Newborn
Inverse changes in plasma tetranectin and titin levels in patients with type 2 diabetes mellitus: a potential predictor of acute myocardial infarction?
Transection of the cervical sympathetic trunk inhibits the progression of pulmonary arterial hypertension via ERK-1/2 Signalling
Chest X-ray in right heart disease
© Springer International Publishing AG, part of Springer Nature 2018. Right heart pathology receives less attention from clinicians than left-sided heart disease, and knowledge of the importance of right heart, in particular right ventricle in disease development lags behind that of the left ventricle. In recent years, increasing evidence shows that right heart disease has significant impact on morbidity and mortality, thus highlighting the importance of recognizing right heart disease in clinical practice. Although ultrasound and computed tomography are the most commonly used diagnostic image techniques in the diagnosis of right heart disease, chest radiography still remains the first line technique in many applications. Despite non-specific findings in most of the situations, chest X-ray provides useful information for further diagnostic imaging tests of assessing right heart disease. This chapter provides an overview of applications of chest X-ray in the diagnosis of various right heart diseases