Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is related to numerous pathophysiological events. We previously reported that a RING ubiquitin ligase complex scaffold protein, cullin-3 (CUL3), and one of its adaptor proteins, BAZF, regulated angiogenesis in the mouse retina by suppressing Notch signaling. However, the degree of inhibition of angiogenesis was made greater by CUL3 depletion than by BAZF depletion, suggesting other roles of CUL3 in angiogenesis besides the regulation of Notch signaling. In the present study, we found that CUL3 was critical for the cell surface level of integrin β1, an essential cell adhesion molecule for angiogenesis in HUVECs. By siRNA screening of 175 BTBPs, a family of adaptor proteins for CUL3, we found that ANKFY1/Rabankyrin-5, an early endosomal BTBP, was also critical for localization of surface integrin β1 and angiogenesis. CUL3 interacted with ANKFY1 and was required for the early endosomal localization of ANKFY1. These data suggest that CUL3/ANKFY1 regulates endosomal membrane traffic of integrin β1. Our results highlight the multiple roles of CUL3 in angiogenesis, which are mediated through distinct CUL3-adaptor proteins.
LADG seems to be safe and effective even for elderly patients, and their prognosis was satisfactory. However, careful monitoring for cardiovascular and pulmonary disease should be observed during the follow-up period.
Angiogenesis, the formation of new blood vessels, is involved in a variety of diseases including the tumor growth. In response to various angiogenic stimulations, a number of proteins on the surface of vascular endothelial cells are activated to coordinate cell proliferation, migration, and spreading processes to form new blood vessels. Plasma membrane localization of these angiogenic proteins, which include vascular endothelial growth factor receptors and integrins, are warranted by intracellular membrane trafficking. Here, by using a siRNA library, we screened for the sorting nexin family that regulates intracellular trafficking and identified sorting nexin 9 (SNX9) as a novel angiogenic factor in human umbilical vein endothelial cells (HUVECs). SNX9 was essential for cell spreading on the Matrigel, and tube formation that mimics in vivo angiogenesis in HUVECs. SNX9 depletion significantly delayed the recycling of integrin β1, an essential adhesion molecule for angiogenesis, and reduced the surface levels of integrin β1 in HUVECs. Clinically, we showed that SNX9 protein was highly expressed in tumor endothelial cells of human colorectal cancer tissues. High‐level expression of SNX9 messenger RNA significantly correlated with poor prognosis of the patients with colorectal cancer. These results suggest that SNX9 is an angiogenic factor and provide a novel target for the development of new antiangiogenic drugs.
Primary mediastinal liposarcomas are rare malignancies, comprising fewer than 1% of all mediastinal tumors. We herein report a radical resection of a massive liposarcoma arising from the anterior mediastinum. A 63-year-old male patient presented with a 4-week history of dyspnea that had worsened over the previous several days. The patient had also experienced hoarseness for 2 weeks. Chest X-ray and computed tomography revealed a huge tumor occupying the entire left thoracic cavity. Anesthesia was induced when the patient was in the left semilateral position. The patient was moved into the right lateral position after initially stabilizing anesthesia with separate lung ventilation. The fourth rib was initially resected for thoracotomy, but there was no clearance between the tumor and the adjacent mediastinal structures, and two more ribs were therefore removed. The tumor had not invaded the other structures such as the chest wall, lung, or mediastinum. To reduce the tumor blood flow, the left internal mammary artery was ligated before the tumor was resected en bloc. The tumor was diagnosed as a liposarcoma arising from the thymus. The patient remains alive with no evidence of disease recurrence at 22 months after the operation.
Wilms tumor (WT) is the most common malignant kidney tumor in children. High blood pressure is seen in up to 55% of children with WT. However, hypertensive cardiomyopathy with congestive heart failure due to WT is remarkably rare, with only several cases reported worldwide. In this report, a pediatric case of WT with hypertension causing hypertensive cardiomyopathy and congestive heart failure is presented. An 8-month-old male child with abdominal distension was seen by his primary physician. He was referred to our hospital for further examination and treatment. Abdominal contrast-enhanced computed tomography demonstrated a weakly enhancing, large abdominal mass, which was larger than 12 cm. Two-dimensional transthoracic echocardiography showed a diffuse hypokinetic left ventricle. The patient was diagnosed with cardiomyopathy caused by hypertension. Open surgical resection of the mass was successfully performed. His postoperative course was uncomplicated, and the patient was successfully discharged. The plasma renin activity was maintained at a high level even after left nephrectomy, suggesting that the right kidney was likely the source of renin secretion. Mechanical compression of the right renal blood vessels by a greatly enlarged left kidney can cause right renal ischemia, which activates renin excretion. Nephrectomy can be an effective treatment for a WT patient with hypertension causing hypertensive cardiomyopathy, and then cardiac function will be improved within several weeks. We recommend routine echocardiography surveillance in patients with WT. This report can help pediatric surgeons become more familiar with cardiomyopathy caused by WT.
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