Casein kinase 2α regulates glioblastoma brain tumor-initiating cell growth through the ß-catenin pathway.

Glioblastoma (GBM) is the most common and fatal primary brain tumor in humans, and it is essential that new and better therapies are developed to treat this disease. Previous research suggests that casein kinase 2 (CK2) may be a promising therapeutic target for GBMs. CK2 has enhanced expression or activity in numerous cancers, including GBM, and it has been demonstrated that inhibitors of CK2 regressed tumor growth in GBM xenograft mouse models. Our studies demonstrate that the CK2 subunit, CK2α, is overexpressed in and has an important role in regulating brain tumor-initiating cells (BTIC) in GBM. Initial studies showed that two GBM cell lines (U87-MG and U138) transduced with CK2α had enhanced proliferation and anchorage-independent growth. Inhibition of CKα using siRNA or small-molecule inhibitors (TBBz, CX-4945) reduced cell growth, decreased tumor size, and increased survival rates in GBM xenograft mouse models. We also verified that inhibition of CK2α decreased the activity of a well-known GBM-initiating cell regulator, ß-catenin. Loss of CK2α decreased two ß-catenin-regulated genes that are involved in GBM-initiating cell growth, OCT4 and NANOG. To determine the importance of CK2α in GBM stem cell maintenance, we reduced CK2α activity in primary GBM samples and tumor spheres derived from GBM patients. We discovered that loss of CK2α activity reduced the sphere-forming capacity of BTIC and decreased numerous GBM stem cell markers, including CD133, CD90, CD49f and A2B5. Our study suggests that CK2α is involved in GBM tumorigenesis by maintaining BTIC through the regulation of ß-catenin.

Intravitreal steroids may facilitate treatment of Eales' disease (idiopathic retinal vasculitis): an interventional case series.

PURPOSE: Eales' disease is an idiopathic peripheral perivasculitis leading to proliferative vascular retinopathy, recurrent vitreous haemorrhages, and tractional retinal detachment. It is an elusive cause of blindness in young, otherwise healthy individuals. We studied the effects of intravitreal triamcinolone acetonide (IVTA) in patients of Eales' disease, which may eventually reduce the side effects and cost of management, with results equivalent to or better than oral steroids. METHODS: Ethics approval and prior patient consent were obtained. Fluorescein fundus angiograms (FFAs) of 12 eyes of 12 Eales' disease patients were taken before enrolment. These patients received 0.1 ml of 40 mg/ml (4 mg) intravitreal triamcinolone through pars plana under topical anaesthesia. Regular weekly follow-ups were initiated to ascertain Snellen visual acuity, intraocular pressure (IOP) with Goldman tonometer, and triple mirror examination. Fluorescein fundus angiography was again performed in the 8th week to monitor response to treatment. Decrease in areas of late perivascular dye extravasation on fluorescein angiography was used as marker for improvement. RESULTS: Ten out of a total of 12 (83.33%) eyes treated with IVTA showed significant reduction of late leakage from retinal vessels on fluorescein fundus angiography. Two out of 12 eyes (16.67%) did not show considerable decrease in late perivascular fluorescein dye leakage after 8 weeks of intravitreal triamcinolone injection. Two patients (16.67%) had a significant rise in IOP after IVTA. CONCLUSION: Intravitreal steroids may be advocated for management of idiopathic retinal vasculitis without complications of systemic steroids, and minimize need for more invasive procedures.

Thalidomide prevents donor corneal graft neovascularization in an alkali burn model of corneal angiogenesis.

OBJECTIVE: Thalidomide is a potent inhibitor of angiogenesis. We evaluated the effects of Thalidomide on corneal angiogenesis and on tissue survival of grafts in rabbit eyes with pre-existing neovascularization secondary to alkali burn. METHODS: Sixteen rabbits received alkali burns to one cornea. One month post-injury, assessments of corneal neovascularization were performed followed by corneal transplantation. Four rabbits received oral Thalidomide and ten got placebo (powdered sugar) for thirty days. Total corneal neovascularization (NV), clock hours (CH) involved in (NV), longest (NV) pedicle length (NVP) and the duration of time required for NV to develop were assessed. RESULTS: Thalidomide significantly decreased the total neovascularization (p<0.0072), the number of (CH) involved (p<0.0002) and the longest (NVP) length (p<0.0001). There was also a significant delay in the earliest development of NV in the test group (p<0.0064). The test group retained corneal clarity significantly longer than the control group (p<0.0008). CONCLUSION: Thalidomide is an effective inhibitor of corneal angiogenesis and prolongs graft survival as measured by graft clarity in donor corneas in eyes with previous neovascularization secondary to alkali injury. CLINICAL RELEVANCE: Thalidomide may be used as a modulator of corneal angiogenesis to prolong graft survival in eyes with pre-existing corneal neovascularization.

Distribution of serum apolipoproteins A-I and B and lipoprotein(a) in European elderly. The SENECA study.

The purpose of this study is to describe sex and geographic differences in apolipoproteins (apo) A-I and B and lipoprotein(a) [Lp(a)] concentrations in elderly Europeans. Subjects were 2164 elderly participants of the SENECA study from different regions of Europe. Sera for apo A-I, apo B, and Lp(a) measurement were available for 1703 individuals. In men, mean values ranged from 1.38 to 1.79 g/l for apo A-I, 1.03-1.36 g/l for apo B, and 0.26-0.67 g/l for Lp(a). In women, mean values ranged from 1.54 to 1.98, 1.20-1.51, and 0.26-0.68 g/l for apo A-I, apo B, and Lp(a), respectively. A comparison of northern (Norway, Denmark, Netherlands), middle (France, Switzerland), and southern (Portugal, Spain, Italy, Greece) communities showed a less atherogenic profile in the south, including lower LDL cholesterol, apo B, TC/HDL cholesterol ratio, and apoB/apo A-I ratio. Men, but not women, also had significantly higher HDL cholesterol and apo A-I concentrations in the South. Paradoxically, Lp(a) concentrations were generally high among all elderly and were significantly higher in the southern communities. These data show that the elderly in Europe are very heterogeneous with respect to plasma lipoproteins, including apo A-I, apo B, and Lp(a).