Recent evidence suggests that breast cancer and other solid tumors possess a rare population of cells capable of extensive self-renewal that contribute to metastasis and treatment resistance. We ...report here the development of a strategy to target these breast cancer stem cells (CSCs) through blockade of the IL-8 receptor CXCR1. CXCR1 blockade using either a CXCR1-specific blocking antibody or repertaxin, a small-molecule CXCR1 inhibitor, selectively depleted the CSC population in 2 human breast cancer cell lines in vitro. Furthermore, this was followed by the induction of massive apoptosis in the bulk tumor population via FASL/FAS signaling. The effects of CXCR1 blockade on CSC viability and on FASL production were mediated by the FAK/AKT/FOXO3A pathway. In addition, repertaxin was able to specifically target the CSC population in human breast cancer xenografts, retarding tumor growth and reducing metastasis. Our data therefore suggest that CXCR1 blockade may provide a novel means of targeting and eliminating breast CSCs.
Afadin/AF6, an F-actin-binding protein, is ubiquitously expressed in epithelia and has a key role during development, through its regulatory role in cell-cell junction organization. Afadin loss of ...expression in 15% of breast carcinoma is associated with adverse prognosis and increased risk of metastatic relapse. To determine the role of afadin in breast cancer, we studied the functional consequences of afadin protein extinction using in vitro and in vivo models. Three different breast cancer cell lines representative of the major molecular subtypes were stably repressed for afadin expression (knockdown of afadin (afadin KD)) using RNA interference. Collective and individual migrations as well as Matrigel invasion were markedly increased in afadin KD cells. Heregulin-β1 (HRG-β1)-induced migration and invasion were increased by twofold in afadin KD cells. Conversely, ectopic expression of afadin in the afadin-negative T47D cell line inhibited spontaneous and HRG-β1-induced migrations. RAS/MAPK and SRC kinase pathways were activated in afadin KD cells. Activation levels positively correlated with migration and invasion strength. Use of MEK1/2 (U0126) and SRC kinases (SU6656) inhibitors reduced afadin-dependent migration and invasion. Afadin extinction in the SK-BR-3 cell line markedly accelerated tumor growth development in mouse mammary gland and lung metastasis formation. These results may explain why the loss of afadin expression in tumors correlates with high tumor size and poor metastasis-free survival in patients.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ethical issues in transfusion medicine Tissot, J-D; Danic, B; Cabaud, J-J ...
Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine
23, Issue:
3
Journal Article
Peer reviewed
Ethics is on the cross road of off values that are present along the ways of transfusion medicine. This is an important tool to afford opinions as well as debates that always emerge when discussing ...transfusion medicine. The wording is particularly important; this was one among several others that characterized the soul of Jean-Jacques Lefrère when he opened the doors of the ethical issues of transfusion medicine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
List of abbreviations CMS consensus molecular subtype CRC color rectal cancer EMS epithelium/mesenchyme switches EMT epithelial-to-mesenchymal transition GO Gene Ontology GSEA Gene Set Enrichment ...Analysis MET mesenchymal-to-epithelial transition RFS recurrence-free survival TGF-β transforming growth factor-beta Dear Editor, To metastasize, epithelial cancer cells undergo an epithelial-to-mesenchymal transition (EMT) during migration, whereupon they activate a mesenchymal-to-epithelial transition (MET) when colonizing the new niche 1. Induction of EMS program in HT29 cells grown as spheroid regulates the cholesterol pathway and influences disease-free survival in colon cancer patients. Cholesterol is involved in multiple biological homeostatic metabolic processes (bile acids, steroid hormones and vitamin D precursors, membrane stability and rigidity, lipid raft organization). The “Cholesterol homeostasis” and the “Bile acid metabolism” pathways can be targeted by statins (β-hydroxy β-methylglutaryl-CoA HMG-CoA reductase inhibitors).
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
6.
Ethics and blood transfusion Tissot, J-D; Garraud, O; Danic, B ...
Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine,
09/2013, Volume:
20, Issue:
4
Journal Article
Peer reviewed
Blood donation is an act of solidarity. Most often, this act is done on a volunteer basis and, depending on countries and circumstances, is not remunerated. The increase in need, the always-greater ...number of deferral criteria, the safety issues and the changes in the structures of our societies are among the many subjects for ethical debates. Taking these into account, the actors of the transfusion must analyze certain parameters: the value of a donation, the meaning of volunteering, the appropriateness of remunerating the act of giving a part of one's self, no longer as a donation or an expression of altruism and solidarity, but as a commercial act regimented by economic laws.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
In the developing area of personalized medicine, targeted therapies are mainly based on genomic characterization of each tumor, and is currently proposed as promising strategies for advanced ...breast cancer (ABC). Despite the promises of advanced genome sequencing, many patients still fail therapy, resulting in disease progression, recurrence, and metastases. Cancer stem cells (CSCs) concept illustrates the non-genetic intrinsic resistance, recapitulates tumor heterogeneity that creates hierarchically organized tumor tissues where a subpopulation of self-renewing cancer stem cells (CSCs) sustains the long- term clonal maintenance of the neoplasm. Evidences indicate that CSCs survive many commonly employed cancer therapeutics. Patient-derived tumor xenograft (PDXs) models recapitulate tumor complexity and heterogeneity at cellular and molecular level.
We aimed to specifically address the therapeutic sensitivity in ABC, by using an ex vivo assay based on PDX prospective collection, fully characterized for genomic alterations.
In this work, we aim at defining for each tumor the best therapy to target breast cancer intratumor heterogeneity, the CSC component. For that, we defined a panel of 44 FDA-approved compounds used for cancer treatment, including breast and other types of cancer, cancer stem cell drugs, chemo or targeted therapies. For each drug, we screened the differential sensitivity of the bulk tumor cells and the CSC components for 12 PDX models using an ex vivo screening approach on short term culture. To assess intra tumor heterogeneity, we set up an original dual strategy: for the bulk cells, an ex vivo assay based on IC50, and for breast CSC component a miniaturized Aldefluor assay. First, we demonstrate that bulk cells and CSCs sensitivity may be dissociated for the same drug in the same PDX models. Then, we observed that whereas bulk cell sensitivity may be correlated to tumor genomic abnormalities, CSC drug sensitivity seems not to follow the rule.CSC are selectively sensitive to specific compounds. We are exploring the pathways that sustain this selective sensitivity in the CSCs components. We are currently identifying targets using mass spectrometry in CSCs and bulk cells.Then, we validated the hits predicted from ex vivo screening assays by in vivo treatment of using PDX models for the selected drugs, and in a patient with ABC.
In that work, we demonstrated that CSCs display different sensitivity profiles than bulk cells to the same agents, irrespective to their genomic background and are identifying the CSC specific targets. Here, we propose a new model of precision medicine based on ex vivo CSC assays for personalized testing of drug susceptibility in advanced breast cancer.
Citation Format: Charafe-Jauffret E, Wicinski J, Cabaud O, Lopez M, Audebert S, Adelaide J, Chaffanet M, Guille A, Goncalves A, Bertucci F, Birnbaum D, Ginestier C. Ex vivo CSC assays for personalized testing of drug susceptibility in advanced breast cancer abstract. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-06-02.
Blood products transport, pedagogy and application Cabaud, J-J; Bourguignat, L
Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine
19, Issue:
4-5
Journal Article
Peer reviewed
Transport products blood and samples of human blood is one of the keys of transfusional safety forcing all actors to update their know how and to comply with rigorous rules and high level ...capabilities requirements. This must lead blood transfusion institutes and medical and biologic laboratories to implement specific process insuring safe transport, preservation and avaibility of the items in accordance with patients' therapic needs. Training and regular valuation of involved actors make necessary to update tools and training methods. E-learning allows a fast and homogeneous learning.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
9.
Ethics and transfusion--seminar report Hervé, C; Tissot, J-D; Bouësseau, M-C ...
Transfusion clinique et biologique : journal de la Societe francaise de transfusion sanguine
21, Issue:
2
Journal Article
Peer reviewed
This paper brings together the abstracts and proceedings of a seminar held on the topic of "ethics and transfusion", October 15, 2013 at the National Institute of Blood Transfusion, Paris.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In front of increasing organizational difficulties, health institutions opted for a transfusion safety e-learning training. Hindsight of two years, an initial assessment highlights success factors ...and desirable improvements.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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