ABSTRACT
Angiogenesis, the formation of new blood vessels, is critical for tumor growth and metastasis. Notably, tumors themselves can lead to angiogenesis by inducing vascular endothelial growth factor (VEGF), which is one of the most potent angiogenic factors. Inhibition of angiogenesis is currently perceived as one of the most promising strategies for the blockage of tumor growth. In this study, we investigated the effects of Acer tegmentosum maxim water extract (ATME) on angiogenesis and its underlying signal mechanism. We studied the antiangiogenic activity of ATME by using human umbilical vein endothelial cells (HUVECs). ATME strongly inhibited VEGF-induced endothelial cell proliferation, migration, invasion, and tube formation, as well as vessel sprouting in a rat aortic ring sprouting assay. Moreover, we found that the p44/42 mitogen activated protein (MAP) kinase signaling pathway is involved in the inhibition of angiogenesis by ATME. Moreover, when we performed the in vivo matrigel plug assay, VEGF-induced angiogenesis was potently reduced when compared to that for the control group. Taken together, these results suggest that ATME exhibits potent antiangiogenic activity in vivo and in vitro and that these effects are regulated by the extracellular regulated kinase (ERK) pathway.
Subject(s)
Animals , Humans , Mice , Rats , Acer/metabolism , Angiogenesis Inhibitors/pharmacology , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Survival , Extracellular Signal-Regulated MAP Kinases/metabolism , Hep G2 Cells , Human Umbilical Vein Endothelial Cells/drug effects , MAP Kinase Signaling System/drug effects , Mice, Inbred C57BL , Mitogen-Activated Protein Kinase 1/metabolism , Neoplasm Invasiveness/pathology , Neovascularization, Pathologic/drug therapy , Nitric Oxide Synthase Type III/metabolism , Phosphorylation/drug effects , Plant Extracts/pharmacology , Rats, Sprague-Dawley , Transcription Factors/metabolism , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
We report a patient with a previously undiagnosed spine metastasis that developed into paraplegia following a continuous epidural block. This is an uncommon and quite rare complication. A 52-year-old male hepatoma case with upper abdominal cancer pain was indicated for a celiac plexus block. A continuous epidural block was performed prior to the celiac plexus block. A Tuohy needle was introduced at the Tll-12 interspace and an epidural catheter was inserted about 15cm in length cephalad through the needle. During the procedure, a saline solution was infused through the Tuohy needle and epidural catheter. The tip of the catheter was expected to be near the T, level. The upper abdominal pain was subsided after the injection of 3 ml of 1% lidocaine and 3 ml of 0.5% bupivacaine via the epidural catheter around noon time. When we made ward rounds that evening, the patient complained of motor weakness and sensory change below T; however, the local anesthetics were injected continuously through the epidural catheter every 4 hours. Next morning, because the patient complained of paraplegia, the epidural injection was discontinued. Under the suspicion of spinal cord compression, a computed tomogram of the thoracic spine was taken. It showed an osteolytic destruction of the right pedicle of T, due to a metastatic tumor. This suggested subclinical tumor invasion to the epidural space. The infusion of saline and local anesthetics through the Tuohy needle and the epidural catheter may increase the epidural pressure and compress the spinal cord. A laminectomy was refused by the family and the patient was discharged from the hospital after 6 treatments of radiotherapy without any improvement. It is advisable to take a spine CT or bone acan in terminal cancer patients before an epidural block, and when paraplegia develops after an epidural block.