Elevated tumor LDLR expression accelerates LDL cholesterol-mediated breast cancer growth in mouse models of hyperlipidemia.

Obesity is associated with an increase in cancer-specific mortality in women with breast cancer. Elevated cholesterol, particularly low-density lipoprotein cholesterol (LDL-C), is frequently seen in obese women. Here, we aimed to determine the importance of elevated circulating LDL, and LDL receptor (LDLR) expression in tumor cells, on the growth of breast cancer using mouse models of hyperlipidemia. We describe two novel immunodeficient mouse models of hyperlipidemia (Rag1-/-/LDLR-/- and Rag1-/-/ApoE (apolipoprotein E)-/- mice) in addition to established immunocompetent LDLR-/- and ApoE-/- mice. The mice were used to study the effects of elevated LDL-C in human triple-negative (MDA-MB-231) and mouse Her2/Neu-overexpressing (MCNeuA) breast cancers. Tumors derived from MCNeuA and MDA-MB-231 cells had high LDLR expression and formed larger tumors in mice with high circulating LDL-C concentrations than in mice with lower LDL-C. Silencing the LDLR in the tumor cells led to decreased growth of Her2/Neu-overexpressing tumors in LDLR-/- and ApoE-/- mice, with increased Caspase 3 cleavage. Additionally, in vitro, silencing the LDLR led to decreased cell survival in serum-starved conditions, associated with Caspase 3 cleavage. Examining publically available human data sets, we found that high LDLR expression in human breast cancers was associated with decreased recurrence-free survival, particularly in patients treated with systemic therapies. Overall, our results highlight the importance of the LDLR in the growth of triple-negative and HER2-overexpressing breast cancers in the setting of elevated circulating LDL-C, which may be important contributing factors to the increased recurrence and mortality in obese women with breast cancer.

Preparation and impact of multiple (water-in-oil-in-water) emulsions in meat systems.

The aim of this paper was to prepare and characterise multiple emulsions and assess their utility as pork backfat replacers in meat gel/emulsion model systems. In order to improve the fat content (in quantitative and qualitative terms) pork backfat was replaced by a water-in-oil-in-water emulsion (W1/O/W2) prepared with olive oil (as lipid phase), polyglycerol ester of polyricinoleic acid (PGPR) as a lipophilic emulsifier, and sodium caseinate (SC) and whey protein concentrate (WP) as hydrophilic emulsifiers. The emulsion properties (particle size and distribution, stability, microstructure) and meat model system characteristics (composition, texture, fat and water binding properties, and colour) of the W1/O/W2, as affected by reformulation, were evaluated. Multiple emulsions showed a well-defined monomodal distribution. Freshly prepared multiple emulsions showed good thermal stability (better using SC) with no creaming. The meat systems had good water and fat binding properties irrespective of formulation. The effect on texture by replacement of pork backfat by W1/O/W2 emulsions generally depends on the type of double emulsion (associated with the hydrophilic emulsifier used in its formulation) and the fat level in the meat system.

Recovery of reusable water from sewage using aerated flat-sheet membranes.

Continuous developments and advances in membrane technology allow recovering to large extent reusable water from untraditional water sources, such as municipal effluents. In this paper, operational results and preliminary cost-analysis of a microfiltration (MF) process used for raw sewage and secondary effluent polishing are given. The research was conducted with a 22 sandwich-type flat-sheet membrane module (0.45 µm and 4.5 m(2)) employing aeration for fouling control. During raw sewage filtration the majority of the organics were retained (effluent COD < 90 mg/L and SS ~ 0 mg/L). However, the fluxes were significantly lower [~7 L/(m(2) h)] compared to those achieved during secondary effluent filtration [~29 L/(m(2) h)] (at TMP 0.14 bar). In the second case, aeration was found to be suitable mean for fouling control. The total costs (capital and operational) for water recovery from raw sewage and secondary effluent were estimated to be in the order of 2 and 0.75 €/m(3) respectively.

Anastomotic pseudoaneurysms: our experience with 49 cases.

We investigated the factors implicated in the pathogenesis of anastomotic aneurysm formation and the postoperative course of patients with such a complication. Forty-five patients with 49 anastomotic aneurysms were diagnosed and treated in two vascular surgery departments in Athens, Greece, during an 8-year period. Emergent complications occurred in 15 cases, rupture in 11, and thromboembolic episodes in another four. Preoperative diagnostic workup in the remaining elective cases (n = 34) included color duplex scan, computed tomographic scan, and angiography. All patients underwent operation, and cultures were obtained during the surgical procedures. Histological examination of the host artery wall adjacent to the aneurysm was also performed. Aortobifemoral bypass was the original operation performed in the majority of cases (71%), and the femoral anastomosis was the most frequent site involved (85.7%). Emergent procedures were associated with increased mortality (46.6%), whereas elective operation resulted in high patency rates and no mortality. In an attempt to isolate predisposing factors that contributed to aneurysm formation, we concluded that the etiology was multifactorial in approximately one-third of the cases and degenerative host artery disease was the main cause (40%). Arterial degeneration is the leading cause of anastomotic aneurysm formation, and emergency arterial reconstruction in cases of aneurysm complication is associated with a poor prognosis.

Our experience with carotid endarterectomy without patch and shunt.

The purpose of the present study was to assess the efficacy of endarterectomy without patch and shunt using a homogeneous group of patients. From January 1987 through December 1994, ninety-eight patients (70 males and 28 females) with mean age 67 years and unilateral atherosclerotic carotid stenosis underwent endarterectomy without the use of a shunt, patch, EEG, stump pressure measurements or other methods. The patients were preoperatively classified into three groups according to clinical symptoms. The overall neurologic morbidity consisted of 2 (2%) permanent and 3 (4%) temporary deficits. Based on our results we concluded that endarterectomy without a shunt is a simple, safe method in cases with no hemodynamically concomitant significant lesions. The neurological complications are probably due to embolization rather than temporary ischemia during operation.

Arterial injuries associated with lower-extremity fractures.

The records of 110 patients with arterial injuries of the lower extremities associated with bone fractures, and managed in the authors' vascular surgery clinic, were reviewed. The majority (72%) were young men; 66 had blunt and 44 penetrating arterial injuries. A total of 92 patients were treated by saphenous vein interposition grafting, 12 with composite grafts and six with polytetrafluoroethylene grafts. The limb salvage rate was 93%. All eight amputations were in neglected cases with arterial injury at the popliteal or infrapopliteal level and associated with muscle loss.