EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment

<p>Abstract</p> <p>Purpose</p> <p>There are conflicting reports regarding the function of EFEMP1 in different cancer types. In this study, we sought to evaluate the role of EFEMP1 in malignant glioma biology.</p> <p>Experimental Design</p> <p>Real-time qRT-PCR was used to quantify <it>EFEMP1 </it>expression in 95 glioblastoma multiforme (GBM). Human high-grade glioma cell lines and primary cultures were engineered to express ectopic EFEMP1, a small hairpin RNA of EFEMP1, or treated with exogenous recombinant EFEMP1 protein. Following treatment, growth was assayed both <it>in vitro </it>and <it>in vivo </it>(subcutaneous (s.c.) and intracranial (i.c.) xenograft model systems).</p> <p>Results</p> <p>Cox regression revealed that EFEMP1 is a favorable prognostic marker for patients with GBM. Over-expression of EFEMP1 eliminated tumor development and suppressed angiogenesis, cell proliferation, and VEGFA expression, while the converse was true with knock-down of endogenous EFEMP1 expression. The EFEMP1 suppression of tumor onset time was nearly restored by ectopic VEGFA expression; however, overall tumor growth rate remained suppressed. This suggested that inhibition of angiogenesis was only partly responsible for EFEMP1's impact on glioma development. In glioma cells that were treated by exogenous EFEMP1 protein or over-expressed endogenous EFEMP1, the EGFR level was reduced and AKT signaling activity attenuated. Mixing of EFEMP1 protein with cells prior to s.c. and i.c. implantations or injection of the protein around the established s.c. xenografts, both significantly suppressed tumorigenicity.</p> <p>Conclusions</p> <p>Overall, our data reveals that EEFEMP1 suppresses glioma growth <it>in vivo</it>, both by modulating the tumor extracellular microenvironment and by altering critical intracellular oncogenic signaling pathways.</p

Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion

The soluble and membrane-anchored isoforms of Mgm1 are only active when they work together (in trans)

African Socialism

(Statement of Responsibility) by Jodi Siegel(Thesis) Thesis (B.A.) -- New College of Florida, 1982(Electronic Access) RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE(Bibliography) Includes bibliographical references.(Source of Description) This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.(Local) Faculty Sponsor: Bates, Margare

Can we predict failure of percutaneous fixation of femoral neck fractures

PURPOSE: This study evaluated a series of geriatric femoral neck fracture treated with closed reduction percutaneous pinning (CRPP) at a single level-1 trauma center to determine if there are any simple, reliable, radiographic characteristics that can be used to predict increased risk of post-operative failure in nondisplaced and valgus impacted fracture patterns. METHODS: We conducted a retrospective cohort study of all patients with femoral neck fractures (AO/OTA 31B) who underwent CRPP over a 12-year period at a single Level 1 trauma center. Failure was defined as radiographic failure within the first year after the index operation requiring revision surgery. Common patterns identified on initial review were the presence of a visible medial transcervical line (MTL) felt to indicate a tension-sided failure, a straight inferior calcar (SIC) indicating severe valgus impaction, and quality of intra-operative screw positioning. X-rays of patients were then reviewed for these characteristics in a blinded manner by three different trauma-fellowship trained orthopedic surgeons. Inter-rater reliability was calculated using Fleiss\u27 Kappa Coefficient. Comparisons of failure rates between groups were made using a Fisher\u27s Exact test. RESULTS: 139 patients who underwent CRPP for a femoral neck fracture and follow-up for at least 90 days were identified and reviewed. There were a total of 19 failures (13.6%) within one year. The patients with a varus fracture had a failure rate of 9/24 (37.5%). Of the valgus/nondisplaced fractures, MTL was identified in 42/115 (36%) patients. Inter-rater agreement was high for the presence of an MTL (84%, Kappa 0.69). Patients with an MTL had a fourfold increase in risk of failure (7/42=17% with an MTL vs. 3/73=4% without, p 0.03). The presence of a SIC and quality of screw placement were not predictive of failure. CONCLUSION: Varus femoral neck fractures fixed with CRPP have a high rate of failure (37.5%). Nondisplaced or valgus impacted fractures with the presence of a visible medial transcervical line on pre-operative radiographic imaging resulted in a fourfold increase in the risk of failure after CRPP. Identification of the MTL will help treating surgeons better council patients when making pre-operative decisions between arthroplasty and CRPP

Reuse of external fixation components: a randomized trial

OBJECTIVES: External fixation devices are sold in the United States as single-use devices and can be costly. Approved processes for refurbishment of nonimplantable components are available. We evaluated one such program for safety, efficacy, and fiscal ramifications. DESIGN: Randomized clinical trial SETTING: Single center, Level I trauma center PATIENTS/PARTICIPANTS: During the 30-month enrollment period (November 16, 2001 to May 16, 2004), 41 patients (13%) of 315 patients were not able to consent and were excluded. A total of 178 (65%) of the 274 eligible patients who were offered entry into a randomized trial of new versus refurbished external fixation components for their injury refused to participate, leaving 96 (35%) of the 274 eligible patients entered into the study. INTERVENTION: Consented patients were entered into a trial of new versus refurbished nonimplantable external fixation components for their injury (all pins were new). MAIN OUTCOME MEASUREMENTS: The frames were evaluated at the time of removal for efficacy and the complications of pin tract infections, loss of fixation, or loosening of components. RESULTS: A total of 48 distal radius fractures, 29 pilon fractures, and 19 tibial plateau fractures were entered into the study. With the 96 fractures treated in our study (50 new frames, 46 reused frames), we found no statistical differences in the incidence of pin tract infections (46% versus 52%, P=0.32), loss of fixation (4% versus 4%, P=0.70), or loosening of the components (1% versus 1%, P=1.0). CONCLUSIONS: Sixty-five percent of consentable patients did not wish to have an external fixation frame with refurbished clamps. Our study demonstrated that this type of program is safe and effective with an actual cost savings of $65,452. The potential savings of such a program is 25% of the cost of all new frames

Transcatheter aortic-valve replacement for inoperable severe aortic stenosis.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) is the recommended therapy for patients with severe aortic stenosis who are not suitable candidates for surgery. The outcomes beyond 1 year in such patients are not known. METHODS: We randomly assigned patients to transfemoral TAVR or to standard therapy (which often included balloon aortic valvuloplasty). Data on 2-year outcomes were analyzed. RESULTS: A total of 358 patients underwent randomization at 21 centers. The rates of death at 2 years were 43.3% in the TAVR group and 68.0% in the standard-therapy group (P<0.001), and the corresponding rates of cardiac death were 31.0% and 62.4% (P<0.001). The survival advantage associated with TAVR that was seen at 1 year remained significant among patients who survived beyond the first year (hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.92; P=0.02 with the use of the log-rank test). The rate of stroke was higher after TAVR than with standard therapy (13.8% vs. 5.5%, P=0.01), owing, in the first 30 days, to the occurrence of more ischemic events in the TAVR group (6.7% vs. 1.7%, P=0.02) and, beyond 30 days, to the occurrence of more hemorrhagic strokes in the TAVR group (2.2% vs. 0.6%, P=0.16). At 2 years, the rate of rehospitalization was 35.0% in the TAVR group and 72.5% in the standard-therapy group (P<0.001). TAVR, as compared with standard therapy, was also associated with improved functional status (P<0.001). The data suggest that the mortality benefit after TAVR may be limited to patients who do not have extensive coexisting conditions. Echocardiographic analysis showed a sustained increase in aortic-valve area and a decrease in aortic-valve gradient, with no worsening of paravalvular aortic regurgitation. CONCLUSIONS: Among appropriately selected patients with severe aortic stenosis who were not suitable candidates for surgery, TAVR reduced the rates of death and hospitalization, with a decrease in symptoms and an improvement in valve hemodynamics that were sustained at 2 years of follow-up. The presence of extensive coexisting conditions may attenuate the survival benefit of TAVR. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.)