117 research outputs found

    Necrosis related HIF-1α expression predicts prognosis in patients with endometrioid endometrial carcinoma

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    <p>Abstract</p> <p>Background</p> <p>Hypoxia inducible factor 1α (HIF-1α) plays an essential role in the adaptive response of cells to hypoxia and is associated with aggressive tumour behaviour. We have shown p27<sup>kip1</sup>, which is generally reduced in endometrial cancer, to be re-expressed in hypoxic regions. This possibly contributes to survival of cancer cells. The aim of this study was to evaluate the prognostic value of HIF-1α and p27<sup>kip </sup>expression in patients with endometrioid endometrial cancer.</p> <p>Methods</p> <p>Expression levels of HIF-1α, CAIX, Glut-1, and p27<sup>kip1 </sup>were analyzed by immunohistochemistry. Percentage of positive cells, staining pattern (perinecrotic, diffuse, or mixed) and presence of necrosis were noted.</p> <p>Results</p> <p>Necrosis was correlated with shortened disease free survival (DFS) (p <it>= </it>0.008) and overall survival (OS) (p <it>= </it>0.045). For DFS, perinecrotic HIF-1α expression was also prognostic (p <it>= </it>0.044). Moreover, high p27<sup>kip1 </sup>expression was an additional prognostic factor for these patients with perinecrotic HIF-1α expression. In multivariate Cox regression, perinecrotic HIF-expression emerged as an independent prognostic factor. Perinecrotic HIF-1α expression was significantly associated with CAIX and Glut-1 expression, pointing towards functional HIF-1.</p> <p>Conclusions</p> <p>In patients with endometrioid endometrial cancer, necrosis and necrosis-related expression of HIF-1α are important prognostic factors. More aggressive adjuvant treatment might be necessary to improve the outcome of patients with these characteristics.</p

    Investigations into, and development of, a lyophilized and formulated recombinant human factor IX produced from CHO cells

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    Objectives: To develop a recombinant human factor IX (rFIX) formulation equivalent to commercially available products in terms of cake appearance, residual moisture, proportion of soluble aggregates and activity maintenance for 3 months at 4–8 °C. Results: NaCl and low bulking agent/cryoprotectant mass ratio had a negative impact on cake quality upon lyophilisation for a wide range of formulations tested. Particular devised formulations maintained rFIX activity after lyophilization with a similar performance when compared with the rFIX formulated using the excipients reported for a commercially available FIX formulation (Benefix). rFIX remained active after 3 months when stored at 4 °C, though this was not the case with samples stored at 40 °C. Interestingly, particular formulations had an increase in residual moisture after 3 months storage, but not above a 3% threshold. All four formulations tested were equivalent to the Benefix formulation in terms of particle size distribution and cake appearance. Conclusions: Three specific formulations, consisting of surfactant polysorbate-80, sucrose or trehalose as cryoprotectant, mannitol or glycine as bulking agent, l-histidine as buffering agent, and NaCl added in the reconstitution liquid at 0.234% (w/v) were suitable for use with a CHO cell-derived recombinant FIX

    Nanotechnology advances towards development of targeted-treatment for obesity

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    Obesity through its association with type 2 diabetes (T2D), cancer and cardiovascular diseases (CVDs), poses a serious health threat, as these diseases contribute to high mortality rates. Pharmacotherapy alone or in combination with either lifestyle modifcation or surgery, is reliable in maintaining a healthy body weight, and preventing progression to obesity-induced diseases. However, the anti-obesity drugs are limited by non-specifcity and unsustainable weight loss efects. As such, novel and improved approaches for treatment of obesity are urgently needed. Nanotechnology-based therapies are investigated as an alternative strategy that can treat obesity and be able to overcome the drawbacks associated with conventional therapies. The review presents three nanotechnology-based anti-obesity strategies that target the white adipose tissues (WATs) and its vasculature for the reversal of obesity. These include inhibition of angiogenesis in the WATs, transformation of WATs to brown adipose tissues (BATs), and photothermal lipolysis of WATs. Compared to conventional therapy, the targeted-nanosystems have high tolerability, reduced side efects, and enhanced efcacy. These efects are reproducible using various nanocarriers (liposomes, polymeric and gold nanoparticles), thus providing a proof of concept that targeted nanotherapy can be a feasible strategy that can combat obesity and prevent its comorbiditie

    Tailored clays for acid and effluent treatment

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    Natural clay minerals have been used as adsorbent for heavy metal removal, dyestuff and effluent treatment for several decades. The performance of Tailored Clays (TCL) on acid and effluents from pharmaceutical and textile industries are investigated in the present study. Suspended solid (SS) removal from acid could be achieved by Ashaphos. Solid removal mechanism has been studied in detail and optimized process could remove nearly all the SS and improve the optical density. The COD reduction studies for pharmaceutical and chemical industrial effluents were carried out by varying dose modified clays and accordingly products Oxylock and Metsorb products are being developed. Metsorb could show the Zn reduction in the effluent upto 90%

    Identification of methylnaphthalenes by PMR: some useful rules

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    Quenched hexacene optoacoustic nanoparticles.

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    Optoacoustic (photoacoustic) imaging enables high-resolution optical imaging at depths well beyond optical microscopy, revolutionizing optical interrogation of tissues. Operation in the near-infrared (NIR) is nevertheless necessary to capitalize on the technology potential and reach depths of several centimeters. Using Flash NanoPrecipitation for highly-scalable single-step encapsulation of hydrophobic hexacene at self-quenching concentrations, we propose quenched fluorescence-dye nanoparticles as a potent alternative to NIR metal nanoparticles for strong optoacoustic signal generation. Comprehensive hexacene-based nanoparticle characterization was based on a 5-step approach that examined the physicochemical features (Step 1), optoacoustic signal generation (Step 2), stability (Step 3), biocompatibility (Step 4) and spectral sensitivity (Step 5). Using this characterization framework we showcase the discovery of two nanoparticle formulations, QH2-50 nm and QH2-100 nm that attain superior stability characteristics and optimal optoacoustic properties compared to gold standards commonly employed for near-infrared optoacoustics. We discuss encapsulation and self-quenching (ESQ) of organic dyes as a promising strategy to generate optimal optoacoustic particles
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