Promotion of breast cancer by β-Hexachlorocyclohexane in MCF10AT1 cells and MMTV-neu mice

<p>Abstract</p> <p>Background</p> <p>Exposure to β-Hexachlorocyclohexane (β-HCH), a contaminant of the hexachlorohexane pesticide lindane, has been implicated as a risk factor in the development of breast cancers in epidemiological studies. Previous studies in our laboratory have demonstrated the ability of β-HCH to elicit its actions via a ligand-independent activation of the estrogen receptor through increased c-Neu (= erbB₂or HER-2) expression and kinase activation in both the BG-1 and MCF-7 cell lines. In addition, long term exposure (33 passages) to β-HCH was shown to promote the selection of MCF-7 cells which exhibit a more metastatic phenotype.</p> <p>Methods</p> <p>In this current study, we decided to investigate the long-term effects of β-HCH in both the MCF10AT1 cell line which was derived from a normal epithelial cell line by stably transfecting a mutated c-Ha-ras and a MMTV-Neu mouse model for mammary cancer <it>in vivo</it>. MCF10AT1 cells were exposed for 20 passages with β-HCH, 4-OH-Tamoxifen (Tam), or 17-β-estradiol (E₂) after which cells were analyzed for proliferation rates and mRNA expression by RT-PCR. In our <it>in vivo </it>studies, MMTV-Neu mice were injected with β-HCH and observed for tumor formation over a 70 week period.</p> <p>Results</p> <p>β-HCH and Tam selected MCF10AT1 cells demonstrated increased mRNA expression of MMP-13 (collagenase-3) a marker of increased invasiveness. β-HCH treatment was also seen to increase the expression in a number of proto-oncogenes (c-Neu, Cyclin D1, p27), cell status markers (Met-1, CK19), and the inflammatory marker NFκB. Previous studies, have demonstrated the role of these markers as evidence of malignant transformations, and further illustrate the ability of β-HCH to be carcinogenic. To demonstrate β-HCH's tumorigenic properties in an <it>in vivo </it>system, we used an MMTV-Neu mouse model.</p> <p>MMTV-Neu is a c-Neu overexpressing strain which has been shown to spontaneously develop mammary tumors at later stages of aging. In this experiment, β-HCH exposure was shown to both accelerate the appearance (~8 weeks for median tumor-free period) and incidence (~25% increase at the end of the test period) of tumors when compared to control mice receiving only the corn-oil vehicle.</p> <p>Conclusion</p> <p>Based upon these results, it was concluded that β-HCH does act as a breast cancer promoter which exerts its tumorigenic activity via increased c-Neu expression.</p

A Nested Case-Control Study of Intrauterine Exposure to Persistent Organochlorine Pollutants in Relation to Risk of Type 1 Diabetes

BACKGROUND: The incidence of type 1 diabetes in Europe is increasing at a rate of about 3% per year and there is also an increasing incidence throughout the world. Type 1 diabetes is a complex disease caused by multiple genetic and environmental factors. Persistent organochlorine pollutants (POPs) have been suggested as a triggering factor for developing childhood type 1 diabetes. The aim of this case-control study was to assess possible impacts of in utero exposure to POPs on type 1 diabetes. METHODOLOGY/ PRINCIPAL FINDINGS: The study was performed as a case-control study within a biobank in Malmö, a city located in the Southern part of Sweden. The study included 150 cases (children who had their diagnosis mostly before 18 years of age) and 150 controls, matched for gender and day of birth. 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and the major DDT metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) were used as a biomarkers for POP exposure. When comparing the quartile with the highest maternal serum concentrations of PCB-153 with the other quartiles, an odds ratio (OR) of 0.73 (95% confidence interval [CI] 0.42, 1.27) was obtained. Similar results was obtained for p,p'-DDE (OR 0.56, 95% CI 0.29, 1.08). CONCLUSIONS: The hypothesis that in utero exposure to POPs will trigger the risk for developing type 1 diabetes was not supported by the results. The risk estimates did, although not statistically significant, go in the opposite direction. However, it is not reasonable to believe that exposure to POPs should protect against type 1 diabetes

Liquidation of Corporation

Import 22/07/2015Diplomová práce se zabývá procesem likvidace obchodních společností v České republice. Cílem této práce je popsat postup likvidace obchodních společností a upozornit na některé problémy, které proces likvidace s sebou přináší, poukázat na řešení základních organizačních a ekonomických otázek související s likvidací a propojit právní a daňový pohled na likvidaci. Práce je rozdělena do čtyř kapitol. V první kapitole jsou definovány jednotlivé právní formy obchodních společností a možné způsoby jejich zrušení. Druhá kapitola se zabývá popisem likvidačního procesu, kdy jsou popsány jednotlivé kroky likvidátora v průběhu likvidace. Třetí kapitola je věnována osobě likvidátora, podmínky nutné k výkonu likvidátora, povolání likvidátora do funkce. Čtvrtá kapitola je věnována praktickým problémům spojenými s procesem likvidace.Thesis deals with the process of liquidation of corporations in the Czech Republic. The aim of this thesis is to describe the procedure of liquidation and to point out some possible problems that could occur during liquidation. The legal and tax point view of the topic will also be included. Thesis is divided into 4 main chapters. Different legal forms of the corporations and the ways of dissolution of companies are defined in the first chapter. The second chapter pursues the process of liquidation. One part of this chapter is devoted to activities of the liquidator. The person of the liquidator, including his competences and required skills, is described in the third chapter. The last chapter is focused on practical problems concerning the process of liquidation.119 - Katedra právavelmi dobř

Efficacy of Major Plant Extracts/Molecules on Field Insect Pests

Insect pests are considered the major hurdle in enhancing the production and productivity of any farming system. The use of conventional synthetic pesticides has led to the emergence of pesticide-resistant insects, environmental pollution, and negative effects on natural enemies, which have caused an ecological imbalance of the predator-prey ratio and human health hazards; therefore, eco-friendly alternative strategies are required. The plant kingdom, a rich repertoire of secondary metabolites, can be tapped as an alternative for insect pest management strategies. A number of plants have been documented to have insecticidal properties against various orders of insects in vitro by acting as antifeedants, repellents, sterilant and oviposition deterrents, etc. However, only a few plant compounds are applicable at the field level or presently commercialised. Here, we have provided an overview of the broad-spectrum insecticidal activity of plant compounds from neem, Annona, Pongamia, and Jatropha. Additionally, the impact of medicinal plants, herbs, spices, and essential oils has been reviewed briefl

Sox10 mutation affects enteric neural crest cell migration

Symposium 6: Genetic control of morophogenesis: no. S06-0