Hormone Receptor Status in Breast Cancer and its Relation to Age and Other Prognostic Factors

Background Increasing evidence shows the importance of young age, estrogen receptor (ER), progesterone receptor (PR) status, and HER-2 expression in patients with breast cancers. Patients and methods We organized an analytic cross-sectional study of 105 women diagnosed with breast cancer who have been operated on between 2008 to 2010. We evaluated age, size, hormone receptor status, HER-2 and P53 expression as possible indicator of lymph node involvement. Results There is a direct correlation between positive progesterone receptor status and being younger than 40 ( P < 0.05). Also, compared with older women, young women had tumors that were more likely to be large in size and have higher stages ( P < 0.05). Furthermore patients with negative progesterone receptor status were more likely to have HER-2 overexpression ( P < 0.05). The differences in propensity to lymph node metastasis between hormone receptor statuses were not statically significant. Conclusions Although negative progesterone receptor tumors were more likely to have HER-2 overexpression, it is possible that higher stage and larger size breast cancer in younger women is related to positive progesterone receptor status

Efficient gene silencing by self-assembled complexes of siRNA and symmetrical fatty acid amides of spermine

Gene silencing by siRNA (synthetic dsRNA of 21-25 nucleotides) is a well established biological tool in gene expression studies and has a promising therapeutic potential for difficult-to-treat diseases. Five fatty acids of various chain length and oxidation state (C12:0, C18:0, C18:1, C18:2, C22:1) were conjugated to the naturally occurring polyamine, spermine, and evaluated for siRNA delivery and gene knock-down. siRNA delivery could not be related directly to gene silencing efficiency as N4,N9-dierucoyl spermine resulted in higher siRNA delivery compared to N4,N9-dioleoyl spermine. GFP silencing in HeLa cells showed that the unsaturated fatty acid amides are more efficient than saturated fatty acid amides, with N4,N9-dioleoyl spermine resulting in the most efficient gene silencing in the presence of serum. The alamarBlue cell viability assay showed that fatty acid amides of spermine have good viability (75%–85% compared to control) except N4,N9-dilauroyl spermine which resulted in low cell viability. These results prove that unsaturated fatty acid amides of spermine are efficient, non-toxic, non-viral vectors for siRNA mediated gene silencing

An Optical Thresholding Perceptron

An implementation of an optical perceptron with a soft optical threshold trained with an adapted BP algorithm is described as a precursor to an optical multilayer perceptron (MLP). It has 64 inputs and ten outputs. The soft threshold is implemented by a liquid crystal light valve. Experimental results on perceptron recall are also reported. The effect of a modified grey-scale to weight mapping for weight levels implemented by LCTVs is evaluated based on the results of handwritten digit recognition

Computational Insights on the Competing Effects of Nitric Oxide in Regulating Apoptosis

Despite the establishment of the important role of nitric oxide (NO) on apoptosis, a molecular- level understanding of the origin of its dichotomous pro- and anti-apoptotic effects has been elusive. We propose a new mathematical model for simulating the effects of nitric oxide (NO) on apoptosis. The new model integrates mitochondria-dependent apoptotic pathways with NO-related reactions, to gain insights into the regulatory effect of the reactive NO species N2O3, non-heme iron nitrosyl species (FeLnNO), and peroxynitrite (ONOO−). The biochemical pathways of apoptosis coupled with NO-related reactions are described by ordinary differential equations using mass-action kinetics. In the absence of NO, the model predicts either cell survival or apoptosis (a bistable behavior) with shifts in the onset time of apoptotic response depending on the strength of extracellular stimuli. Computations demonstrate that the relative concentrations of anti- and pro-apoptotic reactive NO species, and their interplay with glutathione, determine the net anti- or pro-apoptotic effects at long time points. Interestingly, transient effects on apoptosis are also observed in these simulations, the duration of which may reach up to hours, despite the eventual convergence to an anti-apoptotic state. Our computations point to the importance of precise timing of NO production and external stimulation in determining the eventual pro- or anti-apoptotic role of NO

Management of high-risk popliteal vascular blunt trauma: clinical experience with 62 cases

Ali Pourzand, Bassir A Fakhri, Ramin Azhough, Mohammad Ali Hassanzadeh, Shahryar Hashemzadeh, Amrollah M BayatDepartment of General Surgery, Tabriz University of Medical Sciences, Tabriz, East Azarbaijan Province, IranPurpose: The purpose of this study is to report the clinical and functional outcomes of patients, treated between 2004 and 2009, with high-risk popliteal vascular injuries due to compound fractures about the knee.Patients and methods: A retrospective analysis was conducted of prospectively collected data from Tabriz Medical Trauma Center. Our aim was to perform surgical revascularization as soon as the arterial injury was recognized. The mechanism of injury was blunt in the entire cohort of patients, and all of them had bone fractures about the knee. The treatment of arterial injury included vein graft interposition in 39 (63%), primary anastomosis in 20 (32.3%), and lateral repair in 3 (4.8%) patients. The patients were divided into 2 study groups: limb salvage group (group 1) and amputation group (group 2). Subgroup analysis consisted of univariate analysis comparing the 2 groups and multivariate analysis examining the factors associated negatively and positively with the primary endpoint, limb salvage.Results: In the entire cohort of patients, 60 patients (97%) were male and 2 were female (3%); the mean age was 34.1 years (16&amp;ndash;49 years). The overall amputation rate in this study was 37.1% (23 amputations). Significant (P &amp;lt; 0.05) independent factors associated negatively with limb salvage were combined tibia and fibula fracture, concomitant artery and vein injury, ligation of venous injury, and lack of backflow after Fogarty catheter thrombectomy, while repair of popliteal artery and vein injury, when present, was associated with improved early limb salvage. For 40 patients, we adopt a liberal attitude toward open 4-compartment fasciotomy through both medially and laterally placed incisions.Conclusion: Expeditious recognition of vascular injury, transport to repair, and repair of associated venous injury when possible are necessary to optimize limb salvage. The importance of a high level of suspicion and low threshold for timely amputation has been emphasized when limb salvage was deemed impossible to prevent life-threatening complication. Delays in surgery, extensive soft tissue defect, compound tibia&amp;ndash;fibula fracture, and other factors are associated with high amputation rate following popliteal artery injury.Keywords: popliteal vascular blunt trauma, knee, fractur

Caged-iron chelators - a novel approach towards protecting skin cells against UVA-induced necrotic cell death

Exposure of human skin cells to solar UVA radiation leads to an immediate dose-dependent increase of labile iron that subsequently promotes oxidative damage and necrotic cell death. Strong iron chelators have been shown to suppress cell damage and necrotic cell death by moderating the amount of labile iron pool (LIP), but chronic use would cause severe side effects owing to systemic iron depletion. Prodrugs that become activated in skin cells at physiologically relevant doses of UVA, such as “caged-iron chelators”, may provide dose- and context-dependent release. Herein, we describe prototypical iron chelator compounds derived from salicylaldehyde isonicotinoyl hydrazone and pyridoxal isonicotinoyl hydrazone and demonstrate that the intracellular LIP and subsequent necrotic cell death of human skin fibroblasts is significantly decreased upon exposure to a combination of the prototypical compounds and physiologically relevant UVA doses. Iron regulatory protein bandshift and calcein fluorescence assays reveal decreased intracellular LIP following irradiation of caged-chelator-treated cells, but not in control samples where either UVA light, or caged-chelator is absent. Furthermore, flow cytometry shows that these compounds have no significant toxicity in the skin fibroblasts. This novel light-activated prodrug strategy may therefore be used to protect skin cells against the deleterious effects of sunlight