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  • 1
    Abstract: Melanoma originates in the epidermis and becomes metastatic after invasion into the dermis. Prior interactions between melanoma cells and dermis are poorly studied. Here, we show that melanoma cells directly affect the formation of the dermal tumour niche by microRNA trafficking before invasion. Melanocytes, cells of melanoma origin, are specialized in releasing pigment vesicles, termed melanosomes. In melanoma in situ, we found melanosome markers in distal fibroblasts before melanoma invasion. The melanosomes carry microRNAs into primary fibroblasts triggering changes, including increased proliferation, migration and pro-inflammatory gene expression, all known features of cancer-associated fibroblasts (CAFs). Specifically, melanosomal microRNA-211 directly targets IGF2R and leads to MAPK signalling activation, which reciprocally encourages melanoma growth. Melanosome release inhibitor prevented CAF formation. Since the first interaction of melanoma cells with blood vessels occurs in the dermis, our data suggest an opportunity to block melanoma invasion by preventing the formation of the dermal tumour niche.
    Type of Publication: Journal article published
    PubMed ID: 27548915
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 52 (1997), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In a limited number of severe chronic idiopathic urticaria (CIU) patients, low-dose cyclosporin A (CsA) treatment was found to be effective. This open study aimed to extend this clinical observation and determine the safety of treatment with CsA. In addition, it aimed to determine the prevalence and characteristics of the autologous serum skin test (AST) in such patients, and whether this test is affected by CsA treatment. Thirty-five patients who suffered from severe CIU (score 3), and who were followed for 6 months (using a clinical urticaria-severity score [range 0–3]) were divided into three groups: 19/35 were treated for 3 months with low-dose CsA, and thereafter followed for an additional 3 months; 6/35 dropped out of protocol treatment; and 10/35 untreated patients (followed for the same period) served as a disease controls. In the treated group, no side-effects were observed, and by the end of treatment, 13/19 (68%) patients were in full remission (score 0) and the remainder scored 1. In contrast, the 10 CsA-untreated patients scored 3 for the whole follow-up period of 6 months. Positive AST was found in 14/35 (40%) of patients, whereas none were detected in 20 healthy control subjects. AST neither correlated with disease activity nor predicted response to treatment. This uncontrolled study shows that low-dose CsA is effective in treating CIU patients, and can be given safely for 3 months. However, CIU patients requiring initially high doses of glucocorticosteroids and with a long clinical history are less amenable to CsA treatment.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 52 (1997), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Oecologia 85 (1990), S. 122-127 
    ISSN: 1432-1939
    Keywords: Porcupine diggins ; Ecological disturbance ; Desert annual plants, pioneers and remnants ; Succession of annual plants
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The influence of porcupine diggings upon annual vegetation on a north-facing hillslope in the Negev Desert, Israel, has been observed for some 10 years. It was found that within the porcupine diggins there are changes over time in terms of species richness, plant density and plant biomass, and that such changes take place in three stages. During the initial growing season (stage 1), species richness, plant density and plant biomass are lower than in the surrounding non-disturbed area, followed by progressive plant succession. Subsequently, a maximum level is attained when a dig becomes 50–60% filled in (stage 2). As the extent of filling exceeds 60%, a decrease in species richness, plant density and plant biomass is observed (stage 3). This process concurs with models derived in other ecosystems with animals that create surface disturbances. The role of porcupine diggings as a model of disturbance and recovery is discussed.
    Type of Medium: Electronic Resource
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  • 5
    Publication Date: 2016-03-17
    Description: Diploidy is a fundamental genetic feature in mammals, in which haploid cells normally arise only as post-meiotic germ cells that serve to ensure a diploid genome upon fertilization. Gamete manipulation has yielded haploid embryonic stem (ES) cells from several mammalian species, but haploid human ES cells have yet to be reported. Here we generated and analysed a collection of human parthenogenetic ES cell lines originating from haploid oocytes, leading to the successful isolation and maintenance of human ES cell lines with a normal haploid karyotype. Haploid human ES cells exhibited typical pluripotent stem cell characteristics, such as self-renewal capacity and a pluripotency-specific molecular signature. Moreover, we demonstrated the utility of these cells as a platform for loss-of-function genetic screening. Although haploid human ES cells resembled their diploid counterparts, they also displayed distinct properties including differential regulation of X chromosome inactivation and of genes involved in oxidative phosphorylation, alongside reduction in absolute gene expression levels and cell size. Surprisingly, we found that a haploid human genome is compatible not only with the undifferentiated pluripotent state, but also with differentiated somatic fates representing all three embryonic germ layers both in vitro and in vivo, despite a persistent dosage imbalance between the autosomes and X chromosome. We expect that haploid human ES cells will provide novel means for studying human functional genomics and development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sagi, Ido -- Chia, Gloryn -- Golan-Lev, Tamar -- Peretz, Mordecai -- Weissbein, Uri -- Sui, Lina -- Sauer, Mark V -- Yanuka, Ofra -- Egli, Dieter -- Benvenisty, Nissim -- England -- Nature. 2016 Apr 7;532(7597):107-11. doi: 10.1038/nature17408. Epub 2016 Mar 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Silberman Institute of Life Sciences, The Hebrew University, Jerusalem 91904, Israel. ; Department of Pediatrics, Columbia University, New York, New York 10032, USA. ; Center for Women's Reproductive Care, College of Physicians and Surgeons, Columbia University, New York, New York 10019, USA. ; The New York Stem Cell Foundation Research Institute, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982723" target="_blank"〉PubMed〈/a〉
    Keywords: *Cell Differentiation ; Cell Self Renewal ; Cell Separation ; Cell Size ; Chromosomes, Human, X/genetics ; Diploidy ; Down-Regulation/genetics ; Gene Deletion ; Genetic Association Studies/*methods ; Germ Layers/cytology ; *Haploidy ; Human Embryonic Stem Cells/*cytology/*metabolism ; Humans ; Karyotyping ; Oocytes/metabolism ; Oxidative Phosphorylation ; Parthenogenesis ; Pluripotent Stem Cells/cytology/metabolism ; X Chromosome Inactivation/genetics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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