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  • 1
    Publication Date: 2018-02-14
    Description: Autosomal dominant tubulointerstitial kidney disease associated to the MUC1 gene (ADTKD-MUC1; formerly MCKD1) belongs to a heterogenous group of rare hereditary kidney diseases that is prototypically caused by frameshift mutations in the MUC1 repeat domain. The mutant MUC1(insC) lacks the transmembrane domaine, exhibits aberant cellular topology and hence might gain a function during the pathological process. To get insight into potential pathomechanisms we performed differential proteomics of extracellular vesicles shed by renal epithelia into the urine of patients. The study was based on three ADTKD patients and individual controls applying iTRAQ/LC-MS/MS. A total of 796 proteins were identified across all biological and technical replicates, and 298 proteins were quantified. A proportion of 47 proteins were fold-changed species. GO Term Enrichment analysis revealed proteins with significantly changed expression in ADTKD-associated extracellular vesicles as vesicular transport-associated proteins. Among these VTA1 is involved in the endosomal multivesicular body (MVB) pathway associated with transport to lysosomes or export via exosomes. VTA1 is also claimed to play roles as a cofactor of the AAA ATPases VPS4A and VPS4B in the disassembly of ESCRT III. Protein interaction databases list VPS4B, CHMP2A and IST1 as VTA1 binding partners. (Data are available via ProteomeXchange with identifier PXD008389.) This article is protected by copyright. All rights reserved
    Print ISSN: 1615-9853
    Electronic ISSN: 1615-9861
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 2
    Publication Date: 2011-10-11
    Description: The mammary epithelium is composed of several cell lineages including luminal, alveolar and myoepithelial cells. Transplantation studies have suggested that the mammary epithelium is maintained by the presence of multipotent mammary stem cells. To define the cellular hierarchy of the mammary gland during physiological conditions, we performed genetic lineage-tracing experiments and clonal analysis of the mouse mammary gland during development, adulthood and pregnancy. We found that in postnatal unperturbed mammary gland, both luminal and myoepithelial lineages contain long-lived unipotent stem cells that display extensive renewing capacities, as demonstrated by their ability to clonally expand during morphogenesis and adult life as well as undergo massive expansion during several cycles of pregnancy. The demonstration that the mammary gland contains different types of long-lived stem cells has profound implications for our understanding of mammary gland physiology and will be instrumental in unravelling the cells at the origin of breast cancers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Keymeulen, Alexandra -- Rocha, Ana Sofia -- Ousset, Marielle -- Beck, Benjamin -- Bouvencourt, Gaelle -- Rock, Jason -- Sharma, Neha -- Dekoninck, Sophie -- Blanpain, Cedric -- England -- Nature. 2011 Oct 9;479(7372):189-93. doi: 10.1038/nature10573.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Universite Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21983963" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Cell Differentiation ; *Cell Lineage ; Cell Transplantation ; Epithelium ; Female ; Homeostasis ; Lactation/physiology ; Mammary Glands, Animal/*cytology/*growth & development/physiology/transplantation ; Mice ; Multipotent Stem Cells/cytology ; Pregnancy ; Stem Cells/*cytology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2011-10-21
    Description: Angiogenesis is critical during tumour initiation and malignant progression. Different strategies aimed at blocking vascular endothelial growth factor (VEGF) and its receptors have been developed to inhibit angiogenesis in cancer patients. It has become increasingly clear that in addition to its effect on angiogenesis, other mechanisms including a direct effect of VEGF on tumour cells may account for the efficiency of VEGF-blockade therapies. Cancer stem cells (CSCs) have been described in various cancers including squamous tumours of the skin. Here we use a mouse model of skin tumours to investigate the impact of the vascular niche and VEGF signalling on controlling the stemness (the ability to self renew and differentiate) of squamous skin tumours during the early stages of tumour progression. We show that CSCs of skin papillomas are localized in a perivascular niche, in the immediate vicinity of endothelial cells. Furthermore, blocking VEGFR2 caused tumour regression not only by decreasing the microvascular density, but also by reducing CSC pool size and impairing CSC renewal properties. Conditional deletion of Vegfa in tumour epithelial cells caused tumours to regress, whereas VEGF overexpression by tumour epithelial cells accelerated tumour growth. In addition to its well-known effect on angiogenesis, VEGF affected skin tumour growth by promoting cancer stemness and symmetric CSC division, leading to CSC expansion. Moreover, deletion of neuropilin-1 (Nrp1), a VEGF co-receptor expressed in cutaneous CSCs, blocked VEGF's ability to promote cancer stemness and renewal. Our results identify a dual role for tumour-cell-derived VEGF in promoting cancer stemness: by stimulating angiogenesis in a paracrine manner, VEGF creates a perivascular niche for CSCs, and by directly affecting CSCs through Nrp1 in an autocrine loop, VEGF stimulates cancer stemness and renewal. Finally, deletion of Nrp1 in normal epidermis prevents skin tumour initiation. These results may have important implications for the prevention and treatment of skin cancers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Beck, Benjamin -- Driessens, Gregory -- Goossens, Steven -- Youssef, Khalil Kass -- Kuchnio, Anna -- Caauwe, Amelie -- Sotiropoulou, Panagiota A -- Loges, Sonja -- Lapouge, Gaelle -- Candi, Aurelie -- Mascre, Guilhem -- Drogat, Benjamin -- Dekoninck, Sophie -- Haigh, Jody J -- Carmeliet, Peter -- Blanpain, Cedric -- England -- Nature. 2011 Oct 19;478(7369):399-403. doi: 10.1038/nature10525.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IRIBHM, Universite Libre de Bruxelles, 808 route de Lennik, 1070 Brussels, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22012397" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinoma, Squamous Cell/*blood supply/*pathology ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Disease Models, Animal ; Epithelial Cells/cytology ; Gene Deletion ; Gene Expression Regulation, Neoplastic ; Mice ; Neoplastic Stem Cells ; Neuropilin-1/genetics/*metabolism ; *Signal Transduction ; Skin Neoplasms/*blood supply/*pathology ; Vascular Endothelial Growth Factor A/genetics/*metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2014-06-10
    Description: Cancer stem cells (CSCs) have been reported in various cancers, including in skin squamous-cell carcinoma (SCC). The molecular mechanisms regulating tumour initiation and stemness are still poorly characterized. Here we find that Sox2, a transcription factor expressed in various types of embryonic and adult stem cells, was the most upregulated transcription factor in the CSCs of squamous skin tumours in mice. SOX2 is absent in normal epidermis but begins to be expressed in the vast majority of mouse and human pre-neoplastic skin tumours, and continues to be expressed in a heterogeneous manner in invasive mouse and human SCCs. In contrast to other SCCs, in which SOX2 is frequently genetically amplified, the expression of SOX2 in mouse and human skin SCCs is transcriptionally regulated. Conditional deletion of Sox2 in the mouse epidermis markedly decreases skin tumour formation after chemical-induced carcinogenesis. Using green fluorescent protein (GFP) as a reporter of Sox2 transcriptional expression (SOX2-GFP knock-in mice), we showed that SOX2-expressing cells in invasive SCC are greatly enriched in tumour-propagating cells, which further increase upon serial transplantations. Lineage ablation of SOX2-expressing cells within primary benign and malignant SCCs leads to tumour regression, consistent with the critical role of SOX2-expressing cells in tumour maintenance. Conditional Sox2 deletion in pre-existing skin papilloma and SCC leads to tumour regression and decreases the ability of cancer cells to be propagated upon transplantation into immunodeficient mice, supporting the essential role of SOX2 in regulating CSC functions. Transcriptional profiling of SOX2-GFP-expressing CSCs and of tumour epithelial cells upon Sox2 deletion uncovered a gene network regulated by SOX2 in primary tumour cells in vivo. Chromatin immunoprecipitation identified several direct SOX2 target genes controlling tumour stemness, survival, proliferation, adhesion, invasion and paraneoplastic syndrome. We demonstrate that SOX2, by marking and regulating the functions of skin tumour-initiating cells and CSCs, establishes a continuum between tumour initiation and progression in primary skin tumours.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boumahdi, Soufiane -- Driessens, Gregory -- Lapouge, Gaelle -- Rorive, Sandrine -- Nassar, Dany -- Le Mercier, Marie -- Delatte, Benjamin -- Caauwe, Amelie -- Lenglez, Sandrine -- Nkusi, Erwin -- Brohee, Sylvain -- Salmon, Isabelle -- Dubois, Christine -- del Marmol, Veronique -- Fuks, Francois -- Beck, Benjamin -- Blanpain, Cedric -- England -- Nature. 2014 Jul 10;511(7508):246-50. doi: 10.1038/nature13305. Epub 2014 Jun 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Universite Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium. ; 1] Universite Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium [2]. ; 1] Department of Pathology, Erasme Hospital, Universite Libre de Bruxelles, Brussels B-1070, Belgium [2] DIAPATH-Center for Microscopy and Molecular Imaging (CMMI), Gosselies B-6041, Belgium. ; Department of Pathology, Erasme Hospital, Universite Libre de Bruxelles, Brussels B-1070, Belgium. ; Laboratory of Cancer Epigenetics, Universite Libre de Bruxelles, Brussels B-1070, Belgium. ; Machine Learning Group, Computer Science Department, Faculte des Sciences, Universite Libre de Bruxelles, Brussels B-1050, Belgium. ; Department of Dermatology, Erasme Hospital, Universite Libre de Bruxelles, Brussels B-1070, Belgium. ; 1] Universite Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium [2] WELBIO, Universite Libre de Bruxelles, Brussels B-1070, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24909994" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Carcinoma, Squamous Cell/genetics/pathology ; Cell Adhesion/genetics ; Cell Proliferation ; Cell Transformation, Neoplastic/*genetics/metabolism ; Disease Models, Animal ; Gene Deletion ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Gene Regulatory Networks/genetics ; Mice ; Mice, Inbred Strains ; Neoplastic Stem Cells/*metabolism ; SOXB1 Transcription Factors/genetics/*metabolism ; *Skin Neoplasms/genetics/pathology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2012-08-03
    Description: Recent studies using the isolation of a subpopulation of tumour cells followed by their transplantation into immunodeficient mice provide evidence that certain tumours, including squamous skin tumours, contain cells with high clonogenic potential that have been referred to as cancer stem cells (CSCs). Until now, CSC properties have only been investigated by transplantation assays, and their existence in unperturbed tumour growth is unproven. Here we make use of clonal analysis of squamous skin tumours using genetic lineage tracing to unravel the mode of tumour growth in vivo in its native environment. To this end, we used a genetic labelling strategy that allows individual tumour cells to be marked and traced over time at different stages of tumour progression. Surprisingly, we found that the majority of labelled tumour cells in benign papilloma have only limited proliferative potential, whereas a fraction has the capacity to persist long term, giving rise to progeny that occupy a significant part of the tumour. As well as confirming the presence of two distinct proliferative cell compartments within the papilloma, mirroring the composition, hierarchy and fate behaviour of normal tissue, quantitative analysis of clonal fate data indicates that the more persistent population has stem-cell-like characteristics and cycles twice per day, whereas the second represents a slower cycling transient population that gives rise to terminally differentiated tumour cells. Such behaviour is shown to be consistent with double-labelling experiments and detailed clonal fate characteristics. By contrast, measurements of clone size and proliferative potential in invasive squamous cell carcinoma show a different pattern of behaviour, consistent with geometric expansion of a single CSC population with limited potential for terminal differentiation. This study presents the first experimental evidence for the existence of CSCs during unperturbed solid tumour growth.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Driessens, Gregory -- Beck, Benjamin -- Caauwe, Amelie -- Simons, Benjamin D -- Blanpain, Cedric -- 079249/Wellcome Trust/United Kingdom -- 092096/Wellcome Trust/United Kingdom -- England -- Nature. 2012 Aug 23;488(7412):527-30. doi: 10.1038/nature11344.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Universite Libre de Bruxelles, IRIBHM, Brussels B-1070, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22854777" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carcinoma, Squamous Cell/genetics/pathology ; Cell Count ; Cell Differentiation ; *Cell Lineage ; Cell Proliferation ; *Cell Tracking ; Clone Cells/metabolism/pathology ; Disease Models, Animal ; Humans ; Mice ; Models, Biological ; Neoplastic Stem Cells/metabolism/pathology ; Skin Neoplasms/genetics/*pathology ; Stochastic Processes ; Tumor Microenvironment
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 6
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    German Medical Science; Düsseldorf, Köln
    In:  German Medical Science; VOL: 1; DOC06 /20031015/
    Publication Date: 2003-10-16
    Description: Cognitive processes related to client motivation are important mediators of alcoholism treatment outcome. The present study aimed to expand previous research on client motivation and treatment outcome by establishing the predictive utility of self-efficacy, alcohol expectancies, and readiness to change in a sample of alcohol-dependent inpatients (N = 83). Treatment outcome was assessed three months following discharge. According to self-reported alcohol use, 22 clients were classified as abstainers and 41 clients as relapsers. Twenty participants were lost to follow-up. Readiness to change and anticipated reinforcement from alcohol predicted abstinence at follow-up. Client motivation was unrelated to both frequency and quantity of alcohol use. In accordance with social learning theory, self-efficacy was inversely correlated with alcohol expectancies. The results of the present study suggest that once abstinence has been violated factors other than pretreatment motivation determine drinking behavior.
    Description: Zuversicht ist eine wesentliche Voraussetzung der erfolgreichen Behandlung von Alkoholabhängigkeit und -missbrauch. Darüber hinaus lassen die Ergebnisse zahlreicher Untersuchungen einen Zusammenhang zwischen Alkoholwirkungserwartungen und Veränderungsbereitschaft einerseits und Abstinenz andererseits vermuten. Bislang wurde jedoch nicht untersucht, inwiefern zum Beispiel Alkoholwirkungserwartungen einen stärkeren Beitrag zur Vorhersage des Behandlungserfolgs leisten als Abstinenzzuversicht und Veränderungsbereitschaft. Daher wurde die relative prognostische Relevanz dieser Faktoren an einer Stichprobe von 83 alkoholabhängigen Patienten überprüft. Veränderungsbereitschaft und Alkoholwirkungserwartungen erlaubten eine Vorhersage der Abstinenz drei Monate nach Entlassung aus stationärer Behandlung. Häufigkeit und Ausmaß des Alkoholkonsums konnten jedoch nicht vorhergesagt werden. Positive Alkoholwirkungserwartungen gingen mit geringer Zuversicht einher.
    Keywords: ALCOHOLISM/* ; ALCOHOLISM/psychology ; PATIENT ACCEPTANCE OF HEALTH CARE/psychology ; MOTIVATION/* ; FEMALE ; MALE ; HUMAN ; TREATMENT OUTCOME/* ; ALKOHOLISMUS/* ; ALKOHOLISMUS/Psychologie ; AKZEPTANZ DER GESUNDHEITSVERSORGUNG DURCH DEN PATIENTEN/Psychologie ; MOTIVATION/* ; WEIBLICH ; MÄNNLICH ; MENSCH ; BEHANDLUNGSERGEBNIS/* ; ddc: 610
    Language: English
    Type: article
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  • 7
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN); 20120912-20120915; Erlangen; DOC12dgnnPP5.10 /20120911/
    Publication Date: 2012-09-12
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 8
    ISSN: 0196-9781
    Keywords: Caloric intake ; GIP ; Gastrin ; Test meal ; VIP
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2307
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-5233
    Keywords: Lower-extremity amputation ; Diabetes mellitus ; Age at amputation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To assess whether diabetic patients undergo lower-extremity amputations (LEA) at an earlier age than non-diabetic patients, and whether there is a relationship between duration of diabetes mellitus and the age at which such amputations occur, we performed a retrospective analysis of data on 289 consecutive diabetic and 484 consecutive non-diabetic patients who underwent LEA for macrovascular disease. The mean age of diabetic patients who had LEA (69.1±0.6 years) was not different from that of non-diabetic patients (69.6±0.6 years, 0.4〉P〉0.5), with no significant differences in age distribution. Age at diagnosis of diabetes mellitus and duration of diabetes mellitus until LEA were inversely related. Patients who were diagnosed as diabetics at a young age had the longest time lag until LEA (r=0.73,P〈0.0001). In addition, age at amputation was not significantly different between subgroups of patients with varying duration of diabetes. In conclusion, mean age and age distribution in diabetics and non-diabetics who underwent LEA were not different, and age at LEA was comparable for groups with varying duration of diabetes. These data on a large group of diabetic and non-diabetic patients are not compatible with the view that duration of diabetes mellitus is related to early LEA.
    Type of Medium: Electronic Resource
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