L’antivaccinisme est-il de droite ou de gauche ?

National audienc

ANTIVAX. La résistance aux vaccins du XVIIIe siècle à nos jours

International audienc

Sprechen Sie Deutsch ? Un savoir en construction : les cahiers de traduction de Louis Pasteur à Arbois

National audienc

L’antivaccinisme est-il de droite ou de gauche ?

Depuis l’entrée en vigueur en janvier 2018 de la loi portant à onze le nombre de vaccins obligatoires, les anti-vaccin sont ressortis du bois pour clamer haut et fort leur opposition. En réalité, dans ses différentes variantes et formes militantes, cette opinion n’a jamais cessé d’accompagner les vaccins depuis leur invention par Edward Jenner à la fin du XVIIIe siècle, et même depuis l’introduction en Europe vers 1720 du procédé apparenté de l’inoculation variolique. L’OMS vient de désigner ..

Peroxisome proliferator-activated receptor alpha deficiency impairs regulatory T cell functions: Possible application in the inhibition of melanoma tumor growth in mice.

International audienceRegulatory T (Treg) cells are important to induce and maintain immunological self-tolerance. Although the progress accomplished in understanding the functional mechanism of Treg cells, intracellular molecules that control the mechanisms of their suppressive capacity are still on investigation. The present study showed that peroxisome proliferator-activated receptor-alpha deficiency impaired the suppressive activity of Treg cells on CD4(+)CD25(-) and CD8(+) T cell proliferation. In Treg cells, PPARα gene deletion also induced a decrease of migratory abilities, and downregulated the expression of chemokine receptors (CCR-4, CCR-8 and CXCR-4) and p27(KIP1) mRNA. Treg cells from PPARα(-/-) mice also lost their anergic property. Since low Treg activity, as observed in PPARα(-/-) mice, is known to be associated with the inhibition of tumor growth, we inoculated these mice with B16 melanoma cells and assessed tumor proliferation. In PPARα(-/-) mice, cancer growth was significantly curtailed, and it was correlated with high expression of granzyme B and perforin mRNA in tumor bed. Degranulation of cytolytic molecules by CD8(+) T cells, assessed by a perforin-release marker CD107a expression, was higher in PPARα(-/-) mice than that in wild-type mice. Tumor-infiltrating lymphocytes (TIL) in melanoma tumors in PPARα(-/-) mice exhibited high pro-inflammatory Th1 phenotype. Consistently, adoptive transfer into lymphopenic RAG2(-/-) mice of total PPARα(-/-)splenic T cells inhibited more the growth rate of B16 tumor than the wild type splenic T cells. Our findings suggest that PPARα deficiency, by diminishing Treg cell functions and upregulating pro-inflammatory T cell phenotype, exerts an in vivo anti-cancer properties

Impact de la production de monoxyde d'azote par la tumeur sur l'expression de VEGFA et la croissance tumorale dans un modèle de xénogreffe de gliome de rat chez le poisson zèbre

International audienceTo investigate the effect of nitric oxide on tumor development, we established a rat tumor xenograft model in zebrafish embryos. The injected tumor cells formed masses in which nitric oxide production could be detected by the use of the cell-permeant DAF-FM-DA (diaminofluorophore 4-amino-5-methylamino-2'-7'-difluorofluorescein diacetate) and DAR-4M-AM (diaminorhodamine-4M). This method revealed that nitric oxide production could be co-localized with the tumor xenograft in 46% of the embryos. In 85% of these embryos, tumors were vascularized and blood vessels were observed on day 4 post injection. Furthermore, we demonstrated by qRT-PCR that the transplanted glioma cells highly expressed Nos2, Vegfa and Cyclin D1 mRNA. In the xenografted embryos we also found increased zebrafish vegfa expression. Glioma and zebrafish derived Vegfa and tumor Cyclin D1 expression could be down regulated by the nitric oxide scavenger 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide or CPTIO. We conclude that even if there is a heterogeneous nitric oxide production by the xenografted glioma cells that impacts Vegfa and Cyclin D1 expression levels, our results suggest that reduction of nitric oxide levels by nitric oxide scavenging could be an efficient approach to treat glioma

Impact de la production de monoxyde d'azote par la tumeur sur l'expression de VEGFA et la croissance tumorale dans un modèle de xénogreffe de gliome de rat chez le poisson zèbre

International audienceTo investigate the effect of nitric oxide on tumor development, we established a rat tumor xenograft model in zebrafish embryos. The injected tumor cells formed masses in which nitric oxide production could be detected by the use of the cell-permeant DAF-FM-DA (diaminofluorophore 4-amino-5-methylamino-2'-7'-difluorofluorescein diacetate) and DAR-4M-AM (diaminorhodamine-4M). This method revealed that nitric oxide production could be co-localized with the tumor xenograft in 46% of the embryos. In 85% of these embryos, tumors were vascularized and blood vessels were observed on day 4 post injection. Furthermore, we demonstrated by qRT-PCR that the transplanted glioma cells highly expressed Nos2, Vegfa and Cyclin D1 mRNA. In the xenografted embryos we also found increased zebrafish vegfa expression. Glioma and zebrafish derived Vegfa and tumor Cyclin D1 expression could be down regulated by the nitric oxide scavenger 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide or CPTIO. We conclude that even if there is a heterogeneous nitric oxide production by the xenografted glioma cells that impacts Vegfa and Cyclin D1 expression levels, our results suggest that reduction of nitric oxide levels by nitric oxide scavenging could be an efficient approach to treat glioma

The Impact of Tumor Nitric Oxide Production on VEGFA Expression and Tumor Growth in a Zebrafish Rat Glioma Xenograft Model

<div><p>To investigate the effect of nitric oxide on tumor development, we established a rat tumor xenograft model in zebrafish embryos. The injected tumor cells formed masses in which nitric oxide production could be detected by the use of the cell-permeant DAF-FM-DA (diaminofluorophore 4-amino-5-methylamino-2’-7’-difluorofluorescein diacetate) and DAR-4M-AM (diaminorhodamine-4M). This method revealed that nitric oxide production could be co-localized with the tumor xenograft in 46% of the embryos. In 85% of these embryos, tumors were vascularized and blood vessels were observed on day 4 post injection. Furthermore, we demonstrated by qRT-PCR that the transplanted glioma cells highly expressed <i>Nos2</i>, <i>Vegfa</i> and <i>Cyclin D1</i> mRNA. In the xenografted embryos we also found increased zebrafish <i>vegfa</i> expression. Glioma and zebrafish derived <i>Vegfa</i> and tumor <i>Cyclin D1</i> expression could be down regulated by the nitric oxide scavenger 2-(4-Carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide or CPTIO. We conclude that even if there is a heterogeneous nitric oxide production by the xenografted glioma cells that impacts <i>Vegfa</i> and <i>Cyclin D1</i> expression levels, our results suggest that reduction of nitric oxide levels by nitric oxide scavenging could be an efficient approach to treat glioma.</p></div

Alkaline phosphatase assay of xenografted DAF-FM-DA treated embryos.

<p>Embryos were injected with red CM-Dil labeled tumor cells, incubated at 4 dpi in DAF (5μM) and fixed at 4dpi before detection of alkaline phosphatase activity. (A) Bright field image of the embryos before treatments. (B) Neovascularisation was observed in 12 of 14 (85.5%) embryos presenting NO production in tumor environment. (D) Fluorescence detection of glioma cells, (C) DAF signal, (E) merge. The white arrows indicate the part of the tumor mass that co-localizes with DAF fluorescence signal. (F) A control embryo with absence of vessels in this region of the yolk.</p

QRT-PCR analysis of <i>nos</i> gene expression in control and xenografted embryos.

<p>(A) In xenografted embryos, rat <i>Nos2</i> is highly expressed in comparison to <i>Nos1</i> and <i>Nos</i>3. (B) Zebrafish <i>nos1</i> gene is strongly expressed in transplanted and control embryos. A significant difference is only observed for <i>nos2a</i>. Error bars represent SE, * p≤ 0, 05, **<0,01 (one way ANOVA).</p