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Department of Experimental Oncology
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Department of Medical Oncology
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Division of Thoracic Surgery
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    ABSTRACT: Background In the clinic, variations in circadian rhythm are evident in patients with cardiovascular disease, and the risk of cardiovascular events increases when rhythms are disrupted. In this study, we focused on the role of the circadian gene period2 (per2) in mobilization and function of endothelial progenitor cells (EPCs) in vitro and in vivo after myocardial infarction (MI) in mice. Methods and Results MI was produced by surgical ligation of the left anterior descending coronary artery in mice with and without per2 deficiency. Trans-thoracic echocardiography was used to evaluate cardiac function in mice. Per2−/− mice with MI showed decreased cardiac function and increased infarct size. The number of CD34+ cells and capillary density were decreased in the myocardium of per2−/− mice on immunohistochemistry. Flow cytometry revealed decreased number of circulating EPCs in per2−/− mice after MI. In vitro, per2−/− EPCs showed decreased migration and tube formation capacity under hypoxia. Western blot analysis revealed inhibited activation of extracellular signal-regulated kinase and Akt signaling in the bone marrow of per2−/− mice and inhibited PI3K/Akt expression in per2−/− EPCs under hypoxia. Conclusions Per2 modulates EPC mobilization and function after MI, which is important to recovery after MI in mice.
    PLoS ONE 09/2014; 9(9):e108806. DOI:10.1371/journal.pone.0108806
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    ABSTRACT: Metronomic therapy (MT) refers to repetitive, low doses of chemotherapy drugs. MT exerts an effect not only on tumour cells, but also on their microenvironment. In particular, the low-dose schedule compromises the repairing process of endothelial cells, leading to an anti-angiogenic effect. In addition to the anti-angiogenic effect, MT could have an immunological action through the restoration of the anticancer effect of the immune system and induction of tumour dormancy. Consequently the association of targeted therapy with anti-angiogenic properties or specific immunologic drugs could enhance the efficacy of MT. During the past 15 years, several studies have been published evaluating the metronomic strategy in breast cancer. We conducted a systematic review of the results of phase I, II and III studies testing MT in breast cancer patients. The analyses included the efficacy and toxicity data of MT, and the future development of this strategy in breast cancer are also discussed. The systematic review presented here suggests that MT is a treatment option for breast cancer patients, has a low toxicity profile, efficacy in most patients and has potentially significant cost-effective advantages for public health.
    Cancer Treatment Reviews 09/2014; 40(8). DOI:10.1016/j.ctrv.2014.06.002
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    ABSTRACT: Chromatin is the macromolecular nucleoprotein complex that governs the organization of genetic material in the nucleus of eukaryotic cells. In chromatin, DNA is packed with histone proteins into nucleosomes. Core histones are prototypes of hyper-modified proteins, being decorated by a large number of site-specific reversible and irreversible post-translational modifications (PTMs), which contribute to the maintenance and modulation of chromatin plasticity, gene activation, and a variety of other biological processes and disease states. The observations of the variety, frequency and co-occurrence of histone modifications in distinct patterns at specific genomic loci have led to the idea that hPTMs can create a molecular barcode, read by effector proteins that translate it into a specific transcriptional state, or process, on the underlying DNA. However, despite the fact that this histone-code hypothesis was proposed more than 10 years ago, the molecular details of its working mechanisms are only partially characterized. In particular, two questions deserve specific investigation: how the different modifications associate and synergize into patterns and how these PTM configurations are read and translated by multi-protein complexes into a specific functional outcome on the genome. Mass spectrometry (MS) has emerged as a versatile tool to investigate chromatin biology, useful for both identifying and validating hPTMs, and to dissect the molecular determinants of histone modification readout systems. We review here the MS techniques and the proteomics methods that have been developed to address these fundamental questions in epigenetics research, emphasizing approaches based on the proteomic dissection of distinct native chromatin regions, with a critical evaluation of their present challenges and future potential. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function.
    Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 08/2014; DOI:10.1016/j.bbagrm.2014.03.008


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    Milano, Italy
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Revista chilena de obstetricia y ginecología 01/1993; 58(2):103-12.
Multimedia Manual of Cardiothoracic Surgery 05/2014; 2014. DOI:10.1093/mmcts/mmu006

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