33 research outputs found

    Carbon Nanohorns as Effective Nanotherapeutics in Cancer Therapy

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    Different carbon nanostructures have been explored as functional materials for the development of effective nanomaterials in cancer treatment applications. This review mainly aims to discuss the features, either strength or weakness, of carbon nanohorn (CNH), carbon conical horn-shaped nanostructures of sp2 carbon atoms. The interest for these materials arises from their ability to couple the clinically relevant properties of carbon nanomaterials as drug carriers with the negligible toxicity described in vivo. Here, we offer a comprehensive overview of the recent advances in the use of CNH in cancer treatments, underlining the benefits of each functionalization route and approach, as well as the biological performances of either loaded and unloaded materials, while discussing the importance of delivery devices

    Proteome characterization of a human urothelial cell line resistant to the bladder carcinogen 4-aminobiphenyl

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    <p>Abstract</p> <p>Background</p> <p>The aromatic amine 4-aminobiphenyl (4-ABP) is an environmental and occupational contaminant known to be a major etiological agent of human bladder cancer. 4-ABP metabolites are able to form DNA adducts that may induce mutations and initiate bladder carcinogenesis. Cells exposed to 4-ABP may develop resistance to the carcinogen. The aim of the present study was to detect and identify proteins whose expression is altered in the bladder carcinoma RT112 sub-lines selected for acquired resistance to 4-ABP, in order to disentangle the mechanisms.</p> <p>Results</p> <p>Differential proteome analysis of cell lysates showed an overall perturbation in cell metabolism and energy pathways in the 4-ABP-resistant human urothelial clones, with over-expression of membrane trafficking proteins such as annexin 2. The resistant clones had altered expression of many proteins linked directly (<it>i.e</it>. lamin A/C, programmed cell death 6 interacting protein) or indirectly (<it>i.e</it>. 94 kDa glucose-regulated protein, fatty acid-binding protein) to decreased apoptosis, suggesting that resistance to 4-ABP might be associated with low apoptotic activity.</p> <p>Conclusion</p> <p>Our data provide evidence that deregulation of apoptosis and membrane trafficking proteins might be strongly implicated in the selection of carcinogen resistant cells. Some of these proteins might have potential as biomarkers of resistance and cancer risk.</p

    Iron chelator-mediated alterations in gene expression: identification of novel iron-regulated molecules that are molecular targets of hypoxia-inducible factor-1α and p53

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    ABSTRACT Iron deficiency affects 500 million people, yet the molecular role of iron in gene expression remains poorly characterized. In addition, the alterations in global gene expression after iron chelation remain unclear and are important to assess for understanding the molecular pathology of iron deficiency and the biological effects of chelators. Considering this, we assessed the effect on whole genome gene expression of two iron chelators (desferrioxamine and 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone) that have markedly different permeability properties. Sixteen genes were significantly regulated by both ligands, whereas a further 50 genes were significantly regulated by either compound. Apart from ironmediated regulation of expression via hypoxia inducible factor-1␣, it was noteworthy that the transcription factor p53 was also involved in iron-regulated gene expression. Examining 16 genes regulated by both chelators in normal and neoplastic cells, five genes (APP, GDF15, CITED2, EGR1, and PNRC1) were significantly differentially expressed between the cell types. In view of their functions in tumor suppression, proliferation, and apoptosis, these findings are important for understanding the selective antiproliferative effects of chelators against neoplastic cells. Most of the genes identified have not been described previously to be iron-regulated and are important for understanding the molecular and cellular effects of iron depletion. Iron deficiency affects approximately 500 million people. However, despite the enormity of this problem, very little is understood concerning the precise molecular roles played by iron in growth, cell-cycle progression, and apoptosis. Iron plays essential roles in cells, including DNA synthesis and cell cycle control CIP1/WAF1 , GADD45, p53, cyclin D1, etc.) Iron chelators are well known therapeutics for the treatment of iron-overload disease and some of these agents show potential for cancer therap

    Exploration of CTNNB1 ctDNA as a putative biomarker for hepatoblastoma

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    Driver mutations in the CTNNB1 gene (encoding β-catenin) are a hallmark of sporadic hepatoblastoma (HBL). Our results show that CTNNB1 circulating tumour DNA (ctDNA) is readily detected in patients diagnosed with localised HBL, with serial sampling along the course of therapy and follow up providing a sensitive mechanism to monitor tumour dynamics and response to treatment. This exciting potential for CTNNB1 ctDNA to serve as a biomarker for treatment response in HBL holds clinical value, and requires assessment in a larger cohort of mixed tumour stages and recurrent disease
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