The rhino mouse model: the effects of topically applied all-trans retinoic acid and CD271 on the fine structure of the epidermis and utricle wall of pseudocomedones

1991 ◽  
Vol 283 (2) ◽  
pp. 100-107 ◽  
Author(s):  
F. Bernerd ◽  
J. -P. Ortonne ◽  
M. Bouclier ◽  
A. Chatelus ◽  
C. Hensby
PLoS ONE ◽  
2017 ◽  
Vol 12 (11) ◽  
pp. e0188887 ◽  
Author(s):  
Jamie M. Ahrens ◽  
James D. Jones ◽  
Nirca J. Nieves ◽  
Ann M. Mitzey ◽  
Hector F. DeLuca ◽  
...  

1997 ◽  
Vol 10 (3) ◽  
pp. 135-143 ◽  
Author(s):  
Salvador González ◽  
María Victoría Alcaraz ◽  
Florentina Díaz ◽  
Thomas J. Flotte ◽  
Ignacio Pérez de Vargas ◽  
...  

Blood ◽  
2010 ◽  
Vol 115 (3) ◽  
pp. 653-656 ◽  
Author(s):  
Kouichi Furugaki ◽  
Katerina Pokorna ◽  
Carole Le Pogam ◽  
Masayuki Aoki ◽  
Murielle Reboul ◽  
...  

Abstract DNA vaccination and all-trans retinoic acid (ATRA) result in a survival advantage in a mouse model of acute promyelocytic leukemia (APL). Depletion of CD4+ or CD8+ cells abolished this effect. CD4+ depletions of long-term survivors resulted in relapse and death within 3 months, thus demonstrating the need of both CD4+ and CD8+ subsets for the generation of DNA-driven antileukemic immune responses and underscoring a crucial role of CD4+ cells in the maintenance of durable remissions. Degranulation and cytotoxic carboxyfluorescein diacetate succinimidyl ester–based assays showed major histocompatibility complex–restricted APL-specific T cell–mediated immune responses. Sorted APL-specific CD8+CD107a+ T cells showed an increase of antileukemic activity. Effectors from ATRA + DNA–treated mice were shown to secrete interferon-γ when stimulated with either APL cells or peptides from the promyelocytic leukemia-RARα vaccine-derived sequences as detected by ELISpot assays. Our results demonstrate that DNA vaccination with ATRA confers the effective boosting of interferon-γ–producing and cytotoxic T cells in the leukemic mice.


PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0118176 ◽  
Author(s):  
Xiaofeng Liao ◽  
Jingjing Ren ◽  
Cheng-Hsin Wei ◽  
A. Catharine Ross ◽  
Thomas E. Cecere ◽  
...  

2021 ◽  
Author(s):  
Eisuke Suganuma ◽  
Satoshi Sato ◽  
Satoko Honda ◽  
Atsuko Nakazawa

Abstract Coronary artery (CA) stenosis is a detrimental and often life-threatening sequela in Kawasaki disease (KD) patients with coronary artery aneurysm (CAA). Therapeutic strategies for these patients have not yet been established. All-trans-retinoic acid (atRA) is a modulator of smooth muscle cell functions. The purpose of this study was to investigate the effect of atRA on CA stenosis in a mouse model of KD. Lactobacillus casei cell wall extract (LCWE) was intraperitoneally injected into 5-week-old male C57BL/6J mice to induce CA stenosis. Two weeks later, the mice were orally administered atRA (30 mg/kg) 5 days per week for 14 weeks (LCWE+atRA group, n=7). Mice in the untreated group (LCWE group, n=6) received corn oil alone. Control mice were injected with phosphate-buffered saline (PBS, n=5). Treatment with atRA significantly suppressed CA inflammation (19.3±2.8 vs 4.4±2.8, p<0.0001) and reduced the incidence of CA stenosis (100% vs 18.5%, p<0.05). In addition, atRA suppressed the migration of human coronary artery smooth muscle cells (HCASMCs) induced by platelet-derived growth factor subunit B homodimer (PDGF-BB). In conclusion, atRA dramatically alleviated CA stenosis by suppressing SMC migration. Therefore, it is expected to have clinical applications preventing CA stenosis in KD patients with CAA.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2938-2938
Author(s):  
Carole Le Pogam ◽  
Patricia Krief ◽  
Stéphanie Beurlet ◽  
Murielle Reboul ◽  
Robert West ◽  
...  

Abstract Abstract 2938 Background: Myelodysplastic syndromes (MDS) are clonal stem cell hematological disorders characterized by ineffective hematopoiesis leading to cytopenia, which evolve to acute myeloid leukemia (AML). The ability of the DNA vaccination to induce effective immune responses has been demonstrated in different preclinical models of diseases. Having previously shown that DNA vaccination with a PMLRARaFrC plasmid in combination with all-trans retinoic acid (ATRA) induced long term remissions with appropriate immune responses in a mouse model of acute promyelocytic leukemia (APL), our aim was to use this strategy in a mouse model of MDS we have created using transgenic mice bearing a mutant NRAS and overexpression of human BCL-2. Methods: We used our MDS-like triple transgenic mice bearing NRASD12/MMTVLTRtTA/TetoBCL-2 (Omidvar et al Cancer Res 67:11657-67, 2007). We cloned part of the kanamycin resistance gene and adjacent pVax1 plasmid sequences flipped so the antisense sequences were inserted into the pVax1 vector (named Flipper). These sequences code for 5 polypeptides. We treated the MDS mice with either DNA alone, ATRA alone (10mg daily release for 21 days) or a combination of ATRA+DNA or as add-on therapy with 5-azacytidine (5-aza). 5-aza (5mg/kg) was administered 3 times a week and continued until death. Treatment with ATRA and/or DNA was initiated after 12 courses of 5-aza injections. Results and Conclusions: Sequencing of the Flipper insert predicted 5 peptides, which were synthesized and shown not to affect growth in vitro of myeloid leukemic NB4, K562 and p39 cell lines. In vivo injections of healthy mice with these peptides had no effect on mortality. The inserted sequences did not appear to have detrimental effects. The studies on our MDS mouse model show that DNA vaccination, alone or in combination with ATRA induces a long-term survival of the treated mice compared to untreated controls (p<0,0001). DNA vaccination results in an increase of interferon-gamma secretion as measured by ELISPOT, increased CD4+/CD44hi/CD62-Llo memory T cells in the peripheral blood and maintains stable disease as determined by the persistence of low peripheral blood platelet counts and the of the Mac-1hi/GR-1lo populations, which mark the primitive cells and the ERK phosphorylation signatures measured by the NanoPro (Cell Biosciences). Memory T-cell levels increased 3-fold (at 6% compared to 2% in healthy controls) and remained high. The DNA vaccine stabilized the disease and its protective effect may persist for up to 10 months with increased expression of MYD88, which is downstream of toll-like receptors, in long-term survivors, suggesting the activation of this DNA pathway. ATRA alone also had efficacy in this model. As there was no evidence of differentiation as the Mac-1hi/Gr-1lo blast cell population remained unchanged after treatment compared to the levels before treatment, it is possible that in this setting where the leukemic stem cells are pro-apoptotic, that ATRA is acting as an immuno-adjuvant and the antigen shedding that occurs allows cross presentation and induces immune responses potentiated by ATRA. However, the disease in this group progresses and the mice die earlier than the other treatment groups (mean survival of 4.5 months compared with the untreated group of 1 month, p=0.0016). Vaccination with an adjuvant DNA alone or in combination with ATRA, results in a significant extension of lifespan in MDS mice. As add-on therapy to 5-aza the response rate increases from 20% with 5-aza alone to 50% with either ATRA or DNA and 100% with the 5-aza, ATRA and DNA combination. These studies suggest that adjuvant therapy with ATRA+DNA may have a role in addition to conventional therapy in prolonging remissions and may be promising for clinical trials. Disclosures: Fenaux: Novartis, Janssen, Cilag, Roche, Amgem, GSK, Merck and Cephalon: Honoraria, Research Funding. Chomienne:Vivavacs SAS: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Padua:Vivavacs SAS: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.


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