Cancer stem cell markers in breast cancer: pathological, clinical and prognostic significance

INTRODUCTION: The cancer stem cell (CSC) hypothesis states that tumours consist of a cellular hierarchy with CSCs at the apex driving tumour recurrence and metastasis. Hence, CSCs are potentially of profound clinical importance. We set out to establish the clinical relevance of breast CSC markers by profiling a large cohort of breast tumours in tissue microarrays (TMAs) using immunohistochemistry (IHC). METHODS: We included 4, 125 patients enrolled in the SEARCH population-based study with tumours represented in TMAs and classified into molecular subtype according to a validated IHC-based five-marker scheme. IHC was used to detect CD44/CD24, ALDH1A1, aldehyde dehydrogenase family 1 member A3 (ALDH1A3) and integrin alpha-6 (ITGA6). A 'Total CSC' score representing expression of all four CSC markers was also investigated. Association with breast cancer specific survival (BCSS) at 10 years was assessed using a Cox proportional-hazards model. This study was complied with REMARK criteria. RESULTS: In ER negative cases, multivariate analysis showed that ITGA6 was an independent prognostic factor with a time-dependent effect restricted to the first two years of follow-up (hazard ratio (HR) for 0 to 2 years follow-up, 2.4; 95% confidence interval (95% CI), 1.2 to 4.8; P = 0.009). The composite 'Total CSC' score carried independent prognostic significance in ER negative cases for the first four years of follow-up (HR for 0 to 4 years follow-up, 1.3; 95% CI, 1.1 to 1.6; P = 0.006). CONCLUSIONS: Breast CSC markers do not identify identical subpopulations in primary tumours. Both ITGA6 and a composite Total CSC score show independent prognostic significance in ER negative disease. The use of multiple markers to identify tumours enriched for CSCs has the greatest prognostic value. In the absence of more specific markers, we propose that the effective translation of the CSC hypothesis into patient benefit will necessitate the use of a panel of markers to robustly identify tumours enriched for CSCs

Isolation, Characterization, and Stability of Discretely-Sized Nanolipoprotein Particles Assembled with Apolipophorin-III

Background: Nanolipoprotein particles (NLPs) are discoidal, nanometer-sized particles comprised of self-assembled phospholipid membranes and apolipoproteins. NLPs assembled with human apolipoproteins have been used for myriad biotechnology applications, including membrane protein solubilization, drug delivery, and diagnostic imaging. To expand the repertoire of lipoproteins for these applications, insect apolipophorin-III (apoLp-III) was evaluated for the ability to form discretely-sized, homogeneous, and stable NLPs. Methodology: Four NLP populations distinct with regards to particle diameters (ranging in size from 10 nm to.25 nm) and lipid-to-apoLp-III ratios were readily isolated to high purity by size exclusion chromatography. Remodeling of the purified NLP species over time at 4uC was monitored by native gel electrophoresis, size exclusion chromatography, and atomic force microscopy. Purified 20 nm NLPs displayed no remodeling and remained stable for over 1 year. Purified NLPs with 10 nm and 15 nm diameters ultimately remodeled into 20 nm NLPs over a period of months. Intra-particle chemical cross-linking of apoLp-III stabilized NLPs of all sizes. Conclusions: ApoLp-III-based NLPs can be readily prepared, purified, characterized, and stabilized, suggesting their utilit

Synthesis and characterization of manganese oxide-doped dicalcium silicates obtained from rice hull ash

This work describes the synthesis and hydration behavior of dicalcium silicates doped with manganese. The syntheses were performed using silica obtained from rice hull ash. The solids (SiO2, CaO and MnO) were weighed in stoichiometric proportions to prepare silicates having a ratio (Ca + Mn)/Si = 2. Insertion of manganese varied from I to 10% (mol). Solids were grounded and water was added rendering aqueous suspensions. The suspensions were sonicated for 60 min in an ultrasonic bath. After drying, the resulting solids were grounded and burned at 800 degrees C. The preparation of calcium silicates containing up to 10% of manganese oxide was observed. Hydration degree of a dicalcium silicate and calcium silicate containing 5% of manganese was determined by thermal analysis. Both materials present similar behavior. Hydration degree reaches approximately 70% after 60 days. (c) 2007 Elsevier B.V. All rights reserved.17815

New Strategy for Controlled Release of Nitric Oxide

Nitric oxide (NO) is involved in several physiological processes, such as the control of vascular tone, the inhibition of platelet aggregation, smooth muscle cell replication, immune response and neuronal communication. Several pathologies have been associated to dysfunctions in the endogenous NO production. Thus, there is a great interest in the development of NO-releasing drugs and in matrices which are able to stabilize and release NO locally in different tissues. In this scenario, the preparation of NO-releasing nanomaterials, such as dendrimers, liposomes, metallic, silica, and polymeric nanoparticles, zeolites and metal organic frameworks, is a promising strategy for delivering NO in diverse applications, as discussed in this work.20616

Antibacterial effect of silver nanoparticles produced by fungal process on textile fabrics and their effluent treatment

Microorganisms play an important role in toxic metal remediation through reduction of metal ions. Studies demonstrated that silver ions may be reduced extracellularly using Fusarium oxysporum to generate stable gold or silver nanoparticles in water. These particles can be incorporated in several kinds of materials such as cloths. These cloths with silver nanoparticles are sterile and can be useful in hospitals to prevent or to minimize infection with pathogenic bacteria such as Staphylococcus aureus. In this work, the extracellular production of silver nanoparticles by F oxysporum and its antimicrobial effect when incorporated in cotton fabrics against S. aureus were studied. In addition, all effluent was bioremediated using treatment with C. violaceum. The results showed that cotton fabrics incorporated with silver nanoparticles displayed a significant antibacterial activity against S. aureus. The effluent derived from the process was treated with C. violaceum and exhibited an efficient reduction in the silver nanoparticles concentration. In conclusion, it was demonstrated the application of biological synthesis to silver nanoparticles production and its incorporation in cloths, providing them sterile properties. Moreover, to avoid any damage to the environment the effluent containing silver nanoparticles can be treated with cyanogenic bacterial strains.3220320

DILUTED ACID PRETREATMENT OF PINUS RADIATA FOR BIOETHANOL PRODUCTION USING IMMOBILIZED SACCHAROMYCES CEREVISIAE IR2-9 IN A SIMULTANEOUS SACCHARIFICATION AND FERMENTATION PROCESS

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)The production of bioethanol from pretreated lignocellulosic materials requires the utilization of microorganisms adapted to ferment the materials in conditions were high consistency, temperatures and inhibitors concentrations were commonly found. The yeast immobilization in calcium alginate capsules has been reported to enhance the yeast protection and increase the efficiency in the fermentation process. In this work, it was investigated the use Saccharomyces cerevisiae immobilized in calcium alginate and its performance in simultaneous saccharification and fermentation (SSF) of diluted-acid-pretreated Pinus radiata. Results showed that when immobilized yeast was used, the bioethanol yield from pretreated wood was higher than with free yeast cells during a SSF process. Maximum ethanol yield obtained from the acid pretreated and milled wood chips was 153 L/ton wood, while from the hydrolysate fraction it was 18 L/ton wood. The sum of ethanol produced from dilute acid pretreated P. radiata for both solid and liquid fractions was 171 L ethanol/ton wood from a maximum theoretical of 236 L/ton pretretated wood (or 72% of conversion).564901906Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) [1070492]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)SENACYT-IFARHU, PanamaFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fondo Nacional de Desarrollo Cientifico y Tecnologico (FONDECYT) [1070492

Exploitation of Aspergillus niger for Synthesis of Silver Nanoparticles

Extracellular biosynthesis of silver nanoparticles by Aspergillus niger isolated from soil is being reported in the present paper. The production of silver nanoparticles was evidenced by UV-vis spectrum, showing the absorbance at 420 nm (Perkin Elmer Lambda-25). The nanoparticles characterized by Transmission Electron Microscopy exhibited spherical silver nanoparticles with diameter of around 20 nm. Elemental Spectroscopy imaging showed the presence of fungal protein around the silver nanoparticles thereby increasing their stability in the suspension. The silver nanoparticles (10 mu g/ml) showed remarkable antibacterial activity against gram-positive (Staphylococcus. aureus) and gram-negative (Escherichia coli) bacteria. The reduction of the silver ions might have occurred by a nitrate-dependent reductase enzyme and a shuttle quinone extracellular process. Reduction of silver ions was an extracellular and rapid process; this knowledge may lead to the development of an easy process for biosynthesis of the silver nanoparticles. Potential of fungal-mediated biosynthesis of silver nanoparticles is important for development of effective antibacterial agents showing resistance to drugs available in the market.2324324

Therapeutic potential of biogenic silver nanoparticles in murine cutaneous leishmaniasis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)In the last years, silver nanoparticles have appeared as novel antimicrobial agents. In this work, we evaluated the therapeutic potential of silver nanoparticles prepared by two different processes: 1) chemical synthesis (Chem-AgNP); and 2) biosynthesis from the fungus Fusarium oxysporum (Bio-AgNP), in the treatment of cutaneous leishmaniasis. When tested in vitro against Leishmania amazonensis promastigotes, Bio-AgNP was 4-fold more potent than Chem-AgNP (IC50 = 25 uM and 100 uM, respectively). In vivo studies in mice infected in the ear showed that bi-weekly intralesional injections with only 6.5 ug/Kg of body weight of Bio-AgNP during 4 weeks were equally effective as 300-fold higher doses of the reference drug amphotericin B, and more effective than 3-fold higher doses of Chem-AgNP. Contrary to the hepato- and nephrotoxicity that resulted from amphotericin B treatment, and the slight hepatotoxicity produced by Chem-AgNP, no changes in serum levels of AST, ALT and creatinine were detected with Bio-AgNP. Together, these findings show that the biogenic synthesis resulted in enhanced in vitro and in vivo antileishmanial activities, and safer silver nanoparticles as compared with the chemical synthesis.208997Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

BIOGENIC SILVER NANOPARTICLES AND ITS ANTIFUNGAL ACTIVITY AS A NEW TOPICAL TRANSUNGUAL DRUG

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Silver nanoparticles production was monitored by UV Vis and TEM micrograph and they were obtained as spherical and homogenous nanoparticles with a size of similar to 100 nm by photon correlation spectroscopy (PCS). Silver nanoparticles, in an IC80 range of 1-2 mu g/mL, showed significant antifungal activity against T. rubrum. Cytotoxicity through hemolytic activity against erythrocytes and the viability of V79 fibroblast or HL60 cells showed less toxicity than amphotericin B. The disk diffusion test showed that the silver nanoparticles exerted a similar inhibition zone that amphotericin B by a synergistic effect when added at the same time against T. rubrum culture.2099107Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Brazilian Network of nanocosmeticsFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

New photocatalytic reactor with TiO2 coating on sintered glass cylinders

The antibiotic flumequine was used to evaluate the photocatalytic activity of TiO2 coating on sintered glass cylinders (SGC) tailored on a 0.5-1 annular reactor. The cylinders were prepared with finely powdered silicate glass (150-600 mu m) and then coated with titania Degussa P-25 by thermal treatment. The impregnated SGC were characterized by surface techniques such as EDS, SEM and XRD. The coated cylinders present homogeneous porosity, high mechanical strength, and good light transparency. The photocatalytic activity evaluated against flumequine was found to be comparable to the photocatalytic activity presented by titania in aqueous suspension. After 20 min irradiation, around 55% and 80% of 18 ppm flumequine was degraded by irradiation with black light (360 nm) or germicidal lamp (254 nm), respectively. A high reproducibility of the activity was observed when the reaction was continually repeated using the impregnated cylinders. The antibactericidal activity of irradiated solutions was evaluated in Escherichia coli cultures showing significant inhibition. (C) 2007 Elsevier B.V. All rights reserved.7641671576