The Role of TBX3 In Early Breast Cancer Progression

TBX3 is a transcriptional regulator involved in embryonic development and in tumorigenesis of several cancer types. There are two isoforms of TBX3 (TBX3iso1 and TBX3iso2) with different DNA binding domains. The large-scale functional roles of TBX3iso1 and TBX3iso2 were characterized in a breast cancer context. Both TBX3 isoforms induced invasiveness and an epithelial-to-mesenchymal (EMT) phenotype. Coupling data from genome-wide ChIP-array and RNA-Seq studies provided a novel list of genes regulated by each isoform. Both TBX3 isoforms regulate expression of several EMT-related genes, including SLUG and TWIST1. Importantly, TBX3 is a direct regulator of SLUG, and SLUG expression is required for TBX3-induced migration and invasion. Assessing TBX3 expression in early stage breast cancers by immunohistochemistry (IHC) revealed high expression in low-grade lesions. Within a second non-high-grade cohort, there was an association between TBX3 expression in the pre-invasive ductal carcinoma in situ (DCIS) and size of the invasive focus. Additionally, there was a positive correlation between TBX3/SLUG, and TBX3/TWIST1 expression by IHC in the invasive carcinoma. Pathway analysis of transcriptomics data revealed altered expression of several proteases and their inhibitors, consistent with the ability of tumor cells to degrade basement membrane. These findings strongly suggest the involvement of TBX3 in the promotion of invasiveness and progression of early stage pre-invasive DCIS to invasive carcinoma through the low-grade molecular pathway. Interestingly, only TBX3iso1 overexpressing cells exhibited increased tumorigenic potential in mouse xenograft experiments. Transcriptomics data and functional studies revealed that TBX3iso1 overexpression promotes angiogenesis and secretion of cancer-associated cytokines (including osteopontin) which is able to induce tubule formation by endothelial cells in vitro. Tumorigenic TBX3iso1 overexpressing cells also had elevated hyaluronan synthase 2 (HAS2) levels and high levels of hyaluronan retention. These factors may contribute to the survival of cells and promote angiogenesis, allowing the formation of primary tumors in vivo. In conclusion, I have found evidence for a role of TBX3iso1 and TBX3iso2 in direct modulation of EMT and invasiveness, and a role for TBX3iso1 in inducing angiogenesis. Together these, along with previous work showing anti-senescence and pro-proliferative activities of TBX3, suggest multiple potential activities for promotion of malignancy of breast cancer

Microwave-hydrothermal synthesis of TiO2 and zirconium doped TiO2 adsorbents for removal of As(III) and As(V)

Microwave-hydrothermal method was used for the synthesis of TiO2 and TiO2 doped with zirconium. The method was fast and simple and adsorbents were used for removal of As(III) and As(V) from aqueous solutions. The adsorbents were characterized by BET surface area measurements and powder XRD. Experiments showed that TiO2 doped with 10% of Zr using the microwave-hydrothermal method have greater specific surface area and total pore volume in comparison with TiO2 synthesized using the same method. Better removal with doped adsorbent was obtained for both, As(III) and As(V). Further experiments were carried out with Zr doped TiO2 sorbent in order to examine kinetic of adsorption, influence of pH and effect of common anions present in natural waters. (C) 2014 King Saud University. Production and hosting by Elsevier B.V. All rights reserved

Different levels of humoral immunoreactivity to different wheat cultivars gliadin are present in patients with celiac disease and in patients with multiple myeloma

<p>Abstract</p> <p>Background</p> <p>Immunity to food antigens (gliadin, cow's milk proteins) is in the centre of the attention of modern medicine focused on the prevention of diseases, prevention which is based on the use of appropriate restriction diet. Detection of the enhanced levels of the immune reactions to antigen(s) present in food is from this point of view of great importance because there are reports that some of health disturbances, like celiac disease (CD) and some premalignant conditions, like monoclonal gammopathy of undetermined significance (MGUS), were vanished after the appropriate restriction diets.</p> <p>It is well known that gliadin is toxic to small bowel mucosa of relatively small population of genetically predisposed individuals, who under this toxic action develop celiac disease (CD). As the quantity of immunogenic gliadin could vary between different wheat species, the first aim of this work was to determine the percentage of immunogenic gliadin in ten bread wheat cultivars and in three commercially grown durum wheat cultivars. The second part of the study was initiated by results of previous publication, reporting that sera of some of multiple myeloma (MM) patients showed the presence of elevated levels of anti-gliadin IgA, without the enhanced levels of anti-gliadin IgG antibodies, determined with commercial ELISA test. It was designed to assess is it possible to reveal is there any hidden, especially anti-gliadin IgG immunoreactivity, in serum of mentioned group of patients. For this purpose we tested MM patients sera, as well as celiac disease (CD) patients sera for the immunoreaction with the native gliadin isolated from wheat species used for bread and pasta making in corresponding geographic region.</p> <p>Results</p> <p>Gliadin was isolated from wheat flour by two step 60% ehanolic extraction. Its content was determined by commercial R5 Mendez Elisa using PWG gliadin as the standard. Results obtained showed that immunogenic gliadin content varies between 50.4 and 65.4 mg/g in bread wheat cultivars and between 20 and 25.6 mg/g in durum wheat cultivars.</p> <p>Anti-gliadin IgA and IgG immunoreactivity of patients' sera in (IU/ml) was firstly determined by commercial diagnostic Binding Site ELISA test, and then additionally by non-commercial ELISA tests, using standardized ethanol wheat extracts -gliadin as the antigen.</p> <p>In both patients groups IgA immunoreactivity to gliadin from different cultivars was almost homogenous and in correlation with results from commercial test (except for one patient with IgA(λ) myeloma, they were more then five times higher). But, results for IgG immunoreactivity were more frequently inhomogeneous, and especially for few MM patients, they were more then five times higher and did not correlate with results obtained using Binding Site test.</p> <p>Conclusion</p> <p>Results obtained showed different content of immunogenic gliadin epitopes in various species of wheat.</p> <p>They also point for new effort to elucidate is there a need to develop new standard antigen, the representative mixture of gliadin isolated from local wheat species used for bread production in corresponding geographic region for ELISA diagnostic tests.</p

Fenton-like oxidation of an azo dye using mesoporous Fe/TiO2 catalysts prepared by a microwave-assisted hydrothermal process

Fe-doped TiO2 photocatalysts with different contents of Fe (0.5, 1.6, 3.4 and 6.4 %) were synthesized by a microwave-hydrothermal method and characterized by X-ray diffraction analysis, N-2 physisorption at 77 K and UV-Vis spectrometry. The characterization showed that the Fe ions were highly dispersed in the TiO2 lattice. It was found that all the synthesized catalysts had a mesoporous structure and that Fe-doping increased the BET surface area. The UV-Vis study showed that the absorption spectra were shifted to longer wavelengths (red shift) with increasing dopant concentration. The photocatalytic activity of the samples was evaluated by the decolorization of the textile dye Reactive Blue 52 (RB) in aqueous solutions under sun-like radiation in the presence of H2O2 (a heterogeneous photo-Fenton process). The photocatalyst with 3.4 % Fe was found to be the most efficient in the presence of H2O2. The effect of the initial pH of the dye solution was assessed and dissolution of iron ions was studied as a function of pH value. It was concluded that decolorization was more favorable in acidic pH, and that at pH values gt 4, the release of Fe ions into the solution was negligible. Photocatalytic degradation of 4-chlorophenol (4-CP) was investigated under the optimal conditions and it was shown that the catalyst was capable of degrading colorless pollutants

TBX3 promotes progression of pre-invasive breast cancer cells by inducing EMT and directly up-regulating SLUG

The acquisition of cellular invasiveness by breast epithelial cells and subsequent transition from ductal carcinoma in situ (DCIS) to invasive breast cancer is a critical step in breast cancer progression. Little is known about the molecular dynamics governing this transition. We have previously shown that overexpression of the transcriptional regulator TBX3 in DCIS-like cells increases survival, growth, and invasiveness. To explore this mechanism further and assess direct transcriptional targets of TBX3 in a high-resolution, isoform-specific context, we conducted genome-wide chromatin-immunoprecipitation (ChIP) arrays coupled with transcriptomic analysis. We show that TBX3 regulates several epithelial–mesenchymal transition (EMT)-related genes, including SLUG and TWIST1. Importantly, we demonstrate that TBX3 is a direct regulator of SLUG expression, and SLUG expression is required for TBX3-induced migration and invasion. Assessing TBX3 by immunohistochemistry in early-stage (stage 0 and stage I) breast cancers revealed high expression in low-grade lesions. Within a second independent early-stage non-high-grade cohort, we observed an association between TBX3 level in the DCIS and size of the invasive focus. Additionally, there was a positive correlation between TBX3 and SLUG, and TBX3 and TWIST1 in the invasive carcinoma. Pathway analysis revealed altered expression of several proteases and their inhibitors, consistent with the ability to degrade basement membrane in vivo. These findings strongly suggest the involvement of TBX3 in the promotion of invasiveness and progression of early-stage pre-invasive breast cancer to invasive carcinoma through the low-grade molecular pathway. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland

Life Cycle Analysis as the Corporate Environmental Responsibility Assessment Technique

Lifecycle analysis is one of the techniques for assessing the impact of enterprise on the environment, by monitoring environmental effects of the product along its lifecycle. Since the cycle can be seen in stages (extraction of raw materials, raw materials processing, final product production, product use and end of use of the product), the analysis can be applied to all or only some parts of the aforementioned cycle, hence the different variants of this technique. The analysis itself is defined in phases according to the of ISO 14040 standard series, and involves defining the objectives and scope of analysis, life cycle inventory data analysis, life cycle impact assessment and lifecycle interpretation. Although its use is characterized by certain disadvantages, it can be said that this is still a very valuable management tool without which one cannot imagine the process of effective environmental decision-making in the modern enterprise, and consequently the complete adoption of environmentally responsible way of doing business

Importance of Implementing the Green Economy Concept and its Impact on Financial Performance of an Enterprise

In the modern business environment, sustainable development is largely achieved through the implementation of the concept of the green economy, both at the global and national as well as at the corporate level. The motive for the application of this concept at the level of enterprise can be found in the numerous benefits and positive business experiences of companies that have already decided to take that step. Although there are different opinions regarding the character and direction of the following relation, it is stated that the most important reason for implementation of this concept is possible positive correlation with achieving financial performances and competitive advantage of the enterprise-implementator. One way of understanding this influence is through monitoring the implementation of environmental strategy, or through monitoring the process of environmental performance and social responsibility performance management

Metabolic surgery: A reliable long-term solution? A systematic review

Bakgrunnur: Efnaskiptaaðgerðir eru notaðar til meðferðar við offitu þegar aðrar meðferðir ná ekki tilskildum árangri. Mikil aukning hefur verið á offitu seinustu áratugi sem orsakast m.a. af breyttum lifnaðarháttum. Henni fylgir aukin tíðni fylgisjúkdóma og ótímabærra dauðsfalla. Til eru nokkrar tegundir efnaskiptaaðgerða en þær algengustu eru annars vegar magahjáveita og hins vegar magaermi. Markmið þessara aðgerða er að aðstoða sjúklingana við þyngdartap sem í kjölfar dregur úr alvarleika og algengi fylgisjúkdóma. Efnaskiptaaðgerðir eru framkvæmdar víða í heiminum og eru taldar til viðurkenndra meðferða við sjúklegri offitu. Tilgangur: Markmið þessarar fræðilegu samantektar er að skoða langtímaáhrif efnaskipta-aðgerða á lífsgæði sjúklinga og hvort slíkt úrræði teljist vera vænlegt inngrip fyrir börn og aldraða. Svara verður leitað við því hvort efnaskiptaaðgerðir teljist vera áreiðanleg framtíðarlausn við offitu og hvort ávinningur vegi upp á móti áhættunni og kostnaðinum. Aðferð: Samtals voru 34 greinar notaðar við vinnslu þessarar fræðilegu samantektar. Hjálpartækið PICOT var notað til þróunar á rannsóknarspurningum. Við heimildaleit var aðallega stuðst við rafræna gagnagrunna, þá helst PubMed en einnig Cinahl, Scopus og Web of Science. Viðfangsefni ritgerðarinnar eru langtímaáhrif efnaskiptaaðgerða á lífsgæði einstaklinga sem glíma við offitu og notagildi þess inngrips meðal barna og aldraðra. Niðurstöður: Rannsóknir ná yfir 5 til 15 ára tímabil. Út frá niðurstöðum rannsóknargreinanna sem teknar voru fyrir er hægt að draga þá ályktun að efnaskiptaaðgerðir hafi jákvæð áhrif á lífsgæði þessa sjúklingahóps til langs tíma m.t.t. þyngdartaps og fylgisjúkdóma offitu. Ekki voru jafn góðar bætingar á sviði geðheilsu. Árangur reyndist svipaður milli aldurshópanna sem rannsakaðir voru í verkefninu. Ályktun: Efnaskiptaaðgerð er árangursrík meðferð þegar kemur að langtímaáhrifum á fylgisjúkdóma, þyngdarstjórnun og lífsgæðum. Engu að síður er skortur á langtímarannsóknum sem bera saman lifun einstaklinga með offitu sem gangast undir aðgerð og þeirra sem gera það ekki, og eins rannsóknir sem bera saman niðurstöður milli aldurshópa. Náið eftirlit í umsjá reyndra heilbrigðisstarfsmanna eftir efnaskiptaaðgerð er forsenda þess að viðkomandi nái langtímaárangri og sé fær um að viðhalda þyngd innan æskilegra marka. Lykilorð: Efnaskiptaaðgerð, offituaðgerð, magahjáveituaðgerð, magaermi, offita, lífsgæði, fylgikvillar, langtímaáhrif, aldraðir, ungmenniBackground: Metabolic surgery, also known as bariatric surgery, is often used to treat obesity when other conventional methods have failed. Obesity has been on the rise for the last few decades and was believed to be caused by changes in lifestyle among other things. Increased prevalence of obesity is followed by incidences of morbidity and mortality. There are a few different types of metabolic surgeries – gastric bypass and sleeve gastrectomy being most commonly performed. The goal of these surgeries is to assist patients with desired weight loss that in return reduces the prevalence of life-threatening comorbidities. Metabolic surgeries are performed globally and are considered the standard treatment for morbid obesity. Purpose: The goal of this systematic review was to evaluate the long-term effects of metabolic surgery on quality of life and whether it should be considered a desirable intervention for majority of patients especially regarding adolescents and the elderly. We were looking to answer the question of whether metabolic surgery is a reliable long-term solution to treat obesity and if the gain outweighs the risk. Method: A total of 34 studies were reviewed in this project. PICOT was used as a guideline to develop the research questions. We used online databases to discover the studies for our review – PubMed was mostly implemented, but also databases such as Cinahl, Scopus and Web of Science. The topic of this systematic review included long-term effects of metabolic surgery on quality of life, as well as its usefulness for adolescents and the elderly. Results: The study periods range from 5 to 15 years. Based on the studies investigated we are able to conclude that metabolic surgeries have positive long-term effects on quality of life of the patients, both with regards to substantial weight loss and resolution of common comorbidities. However, the effects on mental health were not as successful. The overall results are similar among the age groups researched in this review. Conclusion: Metabolic surgery is so far a successful treatment when it comes to long-term effects on comorbidities, weight control, and quality of life. Further research in the field of metabolic surgery is needed. Both long-term and comparative studies should be conducted on equal basis, especially with regards to varying age groups. Careful monitoring by medical professionals is the premise of optimal long-term results, while being able to maintain reasonable weight loss after surgery. Keywords: Metabolic surgery, bariatric surgery, gastric bypass, Roux-en-Y, gastric sleeve, obesity, quality of life, comorbities, long-term effects, elderly, adolescent

In vitro and in vivo antifungal properties of cysteine proteinase inhibitor from green kiwifruit

BACKGROUND: Higher plants possess several mechanisms of defense against plant pathogens. Proteins actively synthesized in response to those stresses are called defense-related proteins which, among others, include certain protease inhibitors. It is of particular relevance to investigate plant natural defense mechanisms for pathogen control which include cystatinsspecific inhibitors of cysteine proteases. RESULTS: In this study, a cysteine proteinase inhibitor (CPI), 11 kDa in size, was purified from green kiwifruit to homogeneity. Immuno-tissue print results indicated that CPI is most abundant in the outer layer of pericarp, near the peel, and the inner most part of the pulpsites where it could act as a natural barrier against pathogens entering the fruit. The purified protein (15 mu mol L-1) showed antifungal activity against two phytopathogenic fungi (Alternaria radicina and Botrytis cinerea) by inhibiting fungal spore germination. In vivo, CPI (10 mu mol L-1) was able to prevent artificial infection of apple and carrot with spore suspension of B. cinerea and A. radicina, respectively. It also exerted activity on both intracellular and fermentation fluid proteinases. CONCLUSION: Identification and characterization of plant defense molecules is the first step towards creation of improved methods for pathogen control based on naturally occurring molecules. Copyright (c) 2012 Society of Chemical Industr