278 research outputs found
Piet Derksen und seine Medienarbeit: Stein der Weisen oder Stein des Anstoßes?
No full textAm 27.06.1990 wurde im Zentrum der europäischen Hauptstadt Brüssel das \u27Institut deJournalisme- European Media Studies Robert Schuman\u27 (Robert Schuman-Institut) eröffnet und eingeweiht. Die Eröffnungszeremonie bestand aus der Enthüllung einer Tafel zum Andenken an Robert Schuman; sie wurde vollzogen von dem Mitglied des Europaparlaments und ehemaligen belgischen Ministerpräsidenten Leo Tindemans, zusammen mit dem niederländischen Unternehmer (i. R.) Piet Derksen. Msgr. De Hovre, Weihbischof von MechelenBrüssel, führte die Einweihung durch; er ist auch Kuratoriumsmitglied des neuen Brüsseler Instituts und Belgiens \u27Medienbischof. (...) EnglishA Dutch multimillionaire, Piet Derksen, has been endeavouring to missionize world-wide by using all the publishing and electronic media at his disposal. He contributed his fottune to a foundation which has since then supported with !arge sums of money the evangelisation organisation \u27Lumen 2000\u27 which has created a sensation internationally. The radio empire Lumen 2000 wishes to give ]esus Christ a special presentfor his two thousandth birthday: an evangelized world converted by television. Lumen 2000 is also supported by the Pope and the Vatican. Nevertheless the question arises how one has to evaluate this media work controlled by conservative forces; nominally in the light of creation of a Christian community full of life, and of the demand for a credible form of communication. Not only at an international Ievel but also in Holland Piet Derksen has tried to reverse the developments set in motion during the Second Vatican Council among Catholic people. The author explains this obdurate mobilization of the media in the service of conservative thought with the wide-spread uncertainty about standards and values. It offers fertile ground for efforts at regression. The author particularly criticizes as unhelpful Derksen\u27s deliberately encouraged strengtherring of conservative trends in the Dutch Catholic Church and does not expect much good to come from its effect at an international Ievel.
Lobular breast cancer: molecular basis, mouse and cellular models
No full textInfiltrating lobular breast cancer (ILC) is the most common special breast cancer subtype. With mutational or epigenetic inactivation of the cell adhesion molecule E-cadherin (CDH1) being confined almost exclusively to ILC, this tumor entity stands out from all other types of breast cancers. The molecular basis of ILC is linked to loss of E-cadherin, as evidenced by human CDH1 germline mutations and conditional knockout mouse models. A better understanding of ILC beyond the level of descriptive studies depends on physiologically relevant and functional tools. This review provides a detailed overview on ILC models, including well-characterized cell lines, xenograft tumors and genetically engineered mouse models. We consider advantages and limitations of these models and evaluate their representativeness for human ILC. The still incompletely defined mechanisms by which loss of E-cadherin drives malignant transformation are discussed based on recent findings in these models. Moreover, candidate genes and signaling pathways potentially involved in ILC development and progression as well as anticancer drug and endocrine resistance are highlighted
Ken Lum : Works with Photography = Ken Lum : Le travail de l'image
No full textCurator Scott situates Lum’s art (mainly photography) on the Canadian and international scenes, while tracing his evolution from his beginnings, in the 1970s, to the present. Derksen establishes a direct link between Lum’s work and globalization, considering the artist as an observer of the urban territory, where the consequences of this phenomenon are most apparent. The author underlines how the artist reinterprets the notion of “home” – which no longer refers simply to nation and place – in his images of “urban facts”. List of works; texts in English and French. Biographical notes. 25 bibl. ref
Re-inforcing the cell death army in the fight against breast cancer
No full textMetastatic breast cancer is responsible for most breast cancer-related deaths. Disseminated cancer cells have developed an intrinsic ability to resist anchorage-dependent apoptosis (anoikis). Anoikis is caused by the absence of cellular adhesion, a process that underpins lumen formation and maintenance during mammary gland development and homeostasis. In healthy cells, anoikis is mostly governed by B-cell lymphoma-2 (BCL2) protein family members. Metastatic cancer cells, however, have often developed autocrine BCL2-dependent resistance mechanisms to counteract anoikis. In this Review, we discuss how a pro-apoptotic subgroup of the BCL2 protein family, known as the BH3-only proteins, controls apoptosis and anoikis during mammary gland homeostasis and to what extent their inhibition confers tumor suppressive functions in metastatic breast cancer. Specifically, the role of the two pro-apoptotic BH3-only proteins BCL2-modifying factor (BMF) and BCL2-interacting mediator of cell death (BIM) will be discussed here. We assess current developments in treatment that focus on mimicking the function of the BH3-only proteins to induce apoptosis, and consider their applicability to restore normal apoptotic responses in anchorageindependent disseminating tumor cells
LGR6-dependent conditional inactivation of E-cadherin and p53 leads to invasive skin and mammary carcinomas in mice
No full textTissue-specific inactivation of E-cadherin combined with tumor suppressor loss leads to invasive and metastatic cancers in mice. While epidermal E-cadherin loss in mice induces squamous cell carcinomas, inactivation of E-cadherin in the mammary gland leads to invasive lobular carcinoma. To further explore the carcinogenic consequences of cell-cell adhesion loss in these compartments, we developed a new conditional mouse model inactivating E-cadherin (Cdh1) and p53 (Trp53) simultaneously in cells expressing the leucine-rich repeat-containing G-protein coupled receptor 6 (Lgr6), a putative epithelial stem cell marker in the skin and alveolar progenitor marker in the mammary gland.Compound Lgr6-CreERT2;Cdh1F;Trp53F female mice containing either heterozygous or homozygous Cdh1F alleles were bred, and Lgr6-driven Cre expression was activated in pre-puberal mice using tamoxifen. We observed that 41% of the mice (16/39) developed mostly invasive squamous-type skin carcinomas, but also a non-lobular mammary tumor was formed. In contrast to previous K14cre or WAPcre E-cadherin and p53 compound models, no significant differences were detected in the tumor-free survival of Lgr6-CreERT2 heterozygous Cdh1F/WT;Trp53F/F versus homozygous Cdh1F/F;Trp53F/F mice (778 versus 754 days, p=0.5). One Cdh1F homozygous mouse presented with lung metastasis that originated from a non-lobular and ERα negative invasive mammary gland carcinoma with squamous metaplasia. In total, 2/8 (25%) Cdh1F heterozygous and 3/12 (25%) Cdh1F homozygous mice developed metastases to lungs, liver, lymph nodes, or the gastro-intestinal tract.In conclusion, we show that inducible and conditional Lgr6-driven inactivation of E-cadherin and p53 in mice causes squamous cell carcinomas of the skin in approximately 40% of the mice and an occasional ductal-type mammary carcinoma after long latency periods
Not Sheep: New Urban Enclosures and Commons
No full textJamie Hilder on Not Sheep: New Urban Enclosures and Commons, curated by Urban Subjects (US): Sabine Bitter, Jeff Derksen, Helmut Weber, Not Sheep, 2006
Gimme Gimme Gimme. The recent signing behaviour of chimpanzees (Pan troglodytes) in interactions with longterm human companions
No full textContains fulltext :
76506.pdf (Publisher’s version ) (Open Access)This dissertation starts with a critical analysis of the scientific projects with signing chimpanzees, which were set up to see if chimpanzees could learn a human language. These projects consist of the research by the Gardners, the Fouts and the Terrace group. After the results of these projects are presented, the problems of setup, method and interpretation of which this type of research suffered, are discussed. Then a new study is presented in full detail about the recent signing behaviour of these chimpanzees. It was carried out by the author with the famous signing chimpanzees at the Chimpanzee and Human Communication Institute of Central Washington University, among whom the well-known chimpanzee Washoe. Four videotaped corpora from 1992 to 1999 consisting of 3,448 chimpanzee sign utterances were examined. These were analyzed with regard to the individual signs the chimpanzees used, the combinations of signs that they made, and the communicative intentions underlying each chimpanzee sign utterance. The results of this study were as follows. The chimpanzees predominantly used object and action signs. There was no evidence for semantic or syntactic structure in combinations of signs. Longer combinations showed repetition and stringing of object and action signs. The chimpanzees mostly signed with an acquisitive motivation. Requests for objects and actions were the predominant communicative intentions of the sign utterances, though naming and answering also occurred. This recent sign use shows multiple differences with (early) human language. The Discussion of the dissertation presents the implications of this study for the nature of the signing of apes and for ape language research in general. The chimpanzee sign use is also compared with the use of lexigrams by the bonobo Kanzi.KU-Nijmegen, 17 april 2003Promotor : Derksen, A.A. Co-promotor : Cock Buning, T. de603 p
Breast cancer progression cues driven by adherens junction inactivation
No full textInvasive lobular breast cancer (ILC) is a subtype of breast cancer accounting for 10-15% of all invasive breast cancer cases. Unfortunately, early detection of ILC is difficult due to its diffuse growth pattern that hinders detection by palpation or mammography. Also, surgical resection is challenging and most ILC tumors are intrinsically resistant to chemotherapy. Follow-up treatment therefore usually consists of endocrine therapy as most ILCs express ER. Resistance to estrogen antagonists however poses an unmet need for alternative treatment. Interestingly, the majority of ILC cases are marked by early inactivation of the core protein of the adherens junction (AJ) protein E-cadherin, an event that is causal to the development of this disease. As a result, ILC represents a relatively homogeneous group of tumors that are likely to respond to targeted intervention based on the effects of AJ inactivation. In this thesis we have studied these breast cancer progression cues that are driven by the inactivation of the adherens junction. As a consequence of E-cadherin loss, the intracellular component of the AJ p120-catenin (p120) is translocated to the cytosol and the nucleus. To study the contribution of p120 to the development of ILC we made use of genetically engineered mouse models to inactivate p120 in an E-cadherin and p53-driven mouse model of human ILC. In these mice, formation of ILC was mostly prevented pointing towards a critical role for p120 in mouse ILC formation. Loss of E-cadherin also results in the acquisition of anoikis resistance. We have now shown that the ability of E-cadherin negative cells to evade anoikis is based on the prevention of transcriptional upregulation of the BH3-only pro-apoptotic protein BMF. BMF is a direct target of FOXO, an established transcription factor that is inhibited by PI3K-AKT activation upon E-cadherin loss. Interestingly, the BH3-only mimetic ABT199 could re-sensitize E-cadherin negative breast cancer cells to anoikis, advocating for the use of these mimetics in ILC treatment. To provide an overview of the oncogenic signaling pathways affected by loss of E-cadherin we performed a reverse phase protein array. This revealed that E-cadherin inactivation is directly linked to increased AKT activation both in the presence and absence of activating mutations in the PI3K pathway. Inhibition of AKT inhibited cell survival and growth, suggesting that E-cadherin negative breast cancer is likely to respond PI3K pathway targeted therapy. Finally, genome-wide analysis of the p120-catenin binding protein and transcriptional repressor Kaiso has identified a CpG-containing consensus sequence (mKBS) in active promotors. Our data points towards a role for Kaiso in highly expressed target genes functioning in key fundamental cancer-related processes including cell cycle regulation and DNA damage response
Context dependent roles for p120-catenin in breast cancer progression
No full textChapter 1 gives a general overview on epithelial homeostasis and the diverse functions p120 fulfills in adherens junction dynamics, RhoGTPase signaling and transcriptional regulation. Chapter 2 reviews the literature on the contribution of p120 in tumor development of different tissues with a focus on breast cancer. In chapter 3 we report on p120 loss in invasive breast cancer and its correlation to several clinicopathological characteristics. To further investigate the significance of p120 loss, we introduced a conditional p120 allele into a nonmetastatic mouse tumor model based on mammary-specific knockout of p53. Although p120 loss did not affect tumor onset, we observed a marked increase in metastatic dissemination. To determine the causal changes of p120 loss, we generated knockdown cell lines of mouse and human origin, and uncovered that p120 inactivation increased growth factor receptor (GFR) sensitivity, which translated into an increase in anoikis resistance - a hallmark of metastatic capacity. Furthermore, loss of p120 induced secretion of inflammatory cytokines, and as such facilitated formation of a prometastatic microenvironment. Chapter 4 reports on the role for cytosolic p120 in ILC tumor growth and metastasis. Here, p120 confers anoikis resistance through binding of Mrip, a known Rho-Rock antagonist, and subsequent activation of Rock signaling. In this setting, active Rock signaling controls anchorage-independent tumor growth and metastasis. Finally, the potential therapeutic ramifications of Rock inhibition in the treatment of ILC are discussed in chapter 5. Using inducible knock-down systems and pharmacological inhibition in a preclinical setting, we started to investigate the applicability of Rock inhibition for preclinical intervention of metastatic ILC
Lobular breast cancer: Histomorphology and different concepts of a special spectrum of tumors
No full textInvasive lobular breast cancer (ILC) is the most common special histological type of breast cancer (BC). This review recapitulates developments in the histomorphologic assessment of ILC from its beginnings with the seminal work of Foote and Stewart, which was published in 1941, until today. We discuss different concepts of ILC and their implications. These concepts include (i) BC arising from mammary lobules, (ii) BC growing in dissociated cells and single files, and (iii) BC defined as a morpho-molecular spectrum of tumors with distinct histological and molecular characteristics related to impaired cell adhesion. This review also provides a comprehensive overview of ILC variants, their histomorphology, and differential diagnosis. Furthermore, this review highlights recent advances which have contributed to a better understanding of the histomorphology of ILC, such as the role of the basal lamina component laminin, the molecular specificities of triplenegative ILC, and E-cadherin to P-cadherin expression switching as the molecular determinant of tubular elements in CDH1-deficient ILC. Last but not least, we provide a detailed account of the tumor microenvironment in ILC, including tumor infiltrating lymphocyte (TIL) levels, which are comparatively low in ILC compared to other BCs, but correlate with clinical outcome. The distinct histomorphology of ILC clearly reflects a special tumor biology. In the clinic, special treatment strategies have been established for triple-negative, HER2-positive, and ER-positive BC. Treatment specialization for patients diagnosed with ILC is just in its beginnings. Accordingly, ILC deserves greater attention as a special tumor entity in BC diagnostics, patient care, and cancer research
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