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Membrane lipids in invadopodia and podosomes: Key structures for cancer invasion and metastasis

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Membrane lipids in invadopodia and podosomes: Key structures for cancer invasion and metastasis Invadopodia are extracellular matrix (ECM)-degrading protrusions formed by invasive cancer cells. Podosomes are structures functionally similar to invadopodia that are found in oncogene-transformed fibroblasts and monocyte-derived cells, including macrophages and osteoclasts. These structures are thought to play important roles in the pericellular remodeling of ECM during cancer invasion and metastasis. Much effort has been directed toward identification of the molecular components and regulators of invadopodia/podosomes, which could be therapeutic targets in the treatment of malignant cancers. However, it remains largely unknown how these components are assembled into invadopodia/podosomes and how the assembly process is spatially and temporally regulated. This review will summarize recent progress on the molecular mechanisms of invadopodia/podosome formation, with strong emphasis on the ro
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Neoplastic cells are a rare component in human glioblastoma microvasculature

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Neoplastic cells are a rare component in human glioblastoma microvasculature ABSTRACT Microvascular proliferation is a key biological and diagnostic hallmark of human glioblastoma, one of the most aggressive forms of human cancer. It has recently been suggested that stem-like glioblastoma cells have the capacity to differentiate into functional endothelial cells, and that a significant proportion of the vascular lining in tumors has a neoplastic origin. In principle, this finding could significantly impact the efficacy and development of antiangiogenic therapies targeting the vasculature. While the potential of stem-like cancer cells to form endothelium in culture seems clear, in our clinical experience using a variety of molecular markers, neoplastic cells do not contribute significantly to the endothelial-lined vasculature of primary human glioblastoma. We sought to confirm this impression by analyzing vessels in glioblastoma previously examined using chromogenic in situ hybridizatio
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Cardiac progenitors cellsfor vascular repair

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Cardiac progenitors cellsfor vascular repair   The heart is the first functional organ to develop, and cardiomyocytes (cardiac muscle cells) are the essentialand specific-cell type that supports its function during the entire lifespan, being highly resistant to cell damage and aging. Cardiomyocytes occupy ≈ 80% of the volume of mammalian heart, however, they are relatively few in total number compared with non-myocyte cells (endothelial cells, smooth muscle cells, fibroblasts; ≈ 70% of total cardiac cells) [1]. Both myocytes and non-myocytes respond to physiological and pathological insults and their maladaptive responses are linked with the pathogenesis of the cardiac tissue. During the last decade, various studies have identified cardiac progenitor-like cells, including immature cardiomyocytes, that contribute to the low cardiomyocyte turnover (< 2% per year), decreasing their contribution in an age-dependent manner. While cardiac regenerative response is effective in embryo and n
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Age-related changes in human sperm DNA integrity

Age-related changes in human sperm DNA integrity Abstract Abnormal standard semen characteristics and reduced sperm chromatin maturity can appear with increasing male age. However, the influence of paternal age on semen parameters is still controversial. Therefore, this study was designed to estimate the influence of paternal age not only on conventional semen characteristics but also on sperm DNA integrity. This research was carried out on ejaculated sperm cells obtained from men (n = 1124) aged ≥40 y and <40 y. Our data revealed a decreased semen volume and an increased percentage of DFI (sperm DNA fragmentation index) in older men compared to younger men in the entire study cohort, in men with normozoospermia and in men with abnormal semen parameters. Moreover, there was a higher incidence of sperm DNA damage (>10% DFI, low fertility potential) in the groups of men aged ≥40 y than in the groups of men aged <40 y. Older men had over twice the odds ratio for high sperm DNA da
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Accumulation of hypoxia-inducible factor-1α is limited by transcription-dependent depletion

Accumulation of hypoxia-inducible factor-1α is limited by transcription-dependent depletion http://vivo.med.cornell.edu/display/person484997 abstract In the presence of oxygen and iron, hypoxia-inducible factor (HIF-1alpha) is rapidly degraded via the prolyl hydroxylases (PHD)/VHL pathways. Given striking similarities between p53 and HIF-1alpha regulation, we previously suggested that HIF-1 transcriptionally initiates its own degradation and therefore inhibitors of transcription must induce HIF-1alpha. Under normoxia, while inducing p53, inhibitors of transcription did not induce HIF-1alpha. Under hypoxia or low iron (DFX), inhibitors of transcription dramatically super-induced HIF-1alpha. Removal of inhibitors resulted in outburst of the HIF-1-dependent transcription followed by depletion of HIF-1alpha. Although hypoxia/DFX induced PHD3, we excluded the PHD/VHL pathway in the regulation of HIF-1alpha under hypoxia/DFX. The transcription-dependent degradation of HIF-1alpha under hypoxi
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GSK-3 as potential target for therapeutic intervention in cancer

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GSK-3 as potential target for therapeutic intervention in cancer ABSTRACT The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified and studied in the regulation of glycogen synthesis. GSK-3 functions in a wide range of cellular processes. Aberrant activity of GSK-3 has been implicated in many human pathologies including: bipolar depression, Alzheimer’s disease, Parkinson’s disease, cancer, non-insulin-dependent diabetes mellitus (NIDDM) and others. In some cases, suppression of GSK-3 activity by phosphorylation by Akt and other kinases has been associated with cancer progression. In these cases, GSK-3 has tumor suppressor functions. In other cases, GSK-3 has been associated with tumor progression by stabilizing components of the beta-catenin complex. In these situations, GSK-3 has oncogenic properties. While many inhibitors to GSK-3 have been developed, their use remains controversial because of the ambiguous role of GSK-3 in cancer development. In this r
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Polyphenols from green tea inhibit the growth of melanoma cells through inhibition of class I histone deacetylases and induction of DNA damage

Polyphenols from green tea inhibit the growth of melanoma cells through inhibition of class I histone deacetylases and induction of DNA damage ABSTRACT Melanoma is the leading cause of skin cancer-related deaths. We have examined the effect of green tea polyphenols (GTPs), a natural mixture of epicatechin monomers, on melanoma cancer cell growth and the molecular mechanism underlying these effects using different human melanoma cell lines as an  in vitro  model. Treatment of melanoma cell lines (A375, Hs294t, SK-Mel28 and SK-Mel119) with GTPs significantly inhibited the cell viability as well as colony formation ability of melanoma cells in a dose-dependent manner. These effects of GTPs were associated with a significant inhibition of histone deacetylase (HDAC) activity, reduction in the levels of class I HDAC proteins, enhancement of histone acetyltransferase (HAT) activity and induction of DNA damage, as detected by Comet assay, in melanoma cells. GTPs-induced decrease in the levels
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