Retinyl acetate and all-trans-retinoic acid enhance erythroid colony formation in vitro by circulating human progenitors in an improved serum-free medium

1992 ◽  
Vol 10 (5) ◽  
pp. 286-291 ◽  
Author(s):  
Paulo N. Correa ◽  
Arthur A. Axelrad
Keyword(s):  
Retinoic Acid ◽  
Colony Formation ◽  
Serum Free Medium ◽  
Free Medium ◽  
Retinyl Acetate ◽  
Serum Free ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

All-trans retinoic acid induced differentiation of rat mammary epithelial cells cultured in serum-free medium

1998 ◽  
Vol 21 (3) ◽  
pp. 298-304 ◽  
Author(s):  
Min Hyo Ki ◽  
Kee-Joo Paik ◽  
Ji Hyeon Lee ◽  
Hae Young Chung ◽  
Kyung Hee Lee ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Serum Free Medium ◽  
Free Medium ◽  
Serum Free ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Cells Cultured

Insulin/IGF1 Pathway Inhibition in Combination with All-Trans Retinoic Acid in Acute Promyelocytic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1347-1347
Author(s):  
Tiphanie Durfort ◽  
Luca Mazzarella ◽  
Pier Giuseppe Pelicci
Keyword(s):  
Insulin Receptor ◽  
Drug Target ◽  
Promyelocytic Leukemia ◽  
Serum Free Medium ◽  
Free Medium ◽  
Atra Treatment ◽  
Serum Free ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract Abstract 1347 Chemotherapy-free regimens are now a realistic goal in Acute Promyelocytic Leukemia (APL), as demonstrated by recent studies combining All-Trans Retinoic Acid (ATRA) with Arsenic Trioxide and Gemtuzumab Ozogamicin. Combinations of ATRA with kinase inhibitors, which have shown tremendous efficacy in several malignancies, are interesting alternatives but remain poorly characterized in APL. The Insulin-like growth factor 1 (IGF1) pathway is an attractive drug target because of its pervasive involvement in cell proliferation and metabolism of cancer cells. A variety of strategies to target the Insulin/IGF1 axis have been developed, but trials have struggled to demonstrate real efficacy over standard treatments, probably due to our still incomplete understanding of the intricacies of the downstream signalling cascade. Importantly, recent evidence suggests that inhibition of the sole IGF1 receptor may be inadequate because the structurally similar insulin receptor (IR) or IGF1R/IR heterodimeric receptors may be sufficient to support tumour growth. We dissected the IGF1R/IR pathway in the well established APL cell line NB4. IGF1 and insulin, but not the structurally similar IGF1R ligand IGF2, significantly increased NB4 growth in serum-free medium. ATRA treatment resulted in the downregulation, at both transcript and protein level, of several components of the proximal IR/IGF1R pathway: IGF1R (down by 64,9 ±1,7%), IR (down by 82,5 ±4,9%), the transducer proteins insulin receptor substrate 1 (IRS1) (down by 85,7 %) and IRS2 insulin receptor IRS2) by 98,1% (+/− 0,8). However, the downstream cascade remained ligand-responsive: stimulation of serum-starved cells with IGF1 induced a dose-dependent phosphorylation of AKT, FOXO, the mTOR target ribosomal protein S6 and ERK1-2. In addition, baseline levels of phospho-ERK were elevated after ATRA treatment. This suggested that ATRA-treated cells may increase their dependence on IGF1R for their survival. In agreement with this model, NB4 cell growth was completely inhibited by the anti-IGF1R antibody aIR3, but concomitant treatment with ATRA halved the half-maximal dose (IC50) of aIR3 to 1 ug/ml and promoted apoptosis (as assessed by flow cytometry). To identify IGF1R-targeting compounds with higher efficacy we screened novel small molecule inhibitors and found that the imidazopyrazine-derivative OSI-906 stopped NB4 cell growth with an IC50 of 1.5 μM in IGF1-supplemented serum-free medium. This compound is an orally available dual IR/IGF1R inhibitor, currently on trial for several solid tumours. In conclusion, we show that the Insulin/IGF1 signalling pathway is modulated at different levels by ATRA in APL cell lines and that this pathway represents a suitable and attractive drug target in combination with ATRA treatment. On the basis of data presented here we are currently testing the in vivo efficacy of ATRA/OSI906 combinations in in vivo models of APL. Disclosures: Off Label Use: Linsitinib (OSI-906) is a potent, selective orally active inhibitor of the insulin-like growth factor-1 receptor (IGF-1R).

Development and quality of bovine morulae cultured in serum-free medium with specific retinoid receptor agonists

2008 ◽  
Vol 20 (8) ◽  
pp. 884 ◽  
Author(s):  
Enrique Gómez ◽  
Aida Rodríguez ◽  
Marta Muñoz ◽  
José Néstor Caamaño ◽  
Susana Carrocera ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Receptor Agonist ◽  
Treated Group ◽  
Serum Free Medium ◽  
Free Medium ◽  
Retinoid Receptor ◽  
Serum Free ◽  
Short Term Exposure ◽  
Hatching Rates

Retinoids regulate development and differentiation of the bovine blastocyst in vitro, although the underlying mechanisms remain to be clarified. A challenge in reproductive biotechnology is the identification of pathways that regulate early embryonic development and their influence on blastocyst differentiation, apoptosis and survival to cryopreservation as traits of embryo quality. The present paper analyses the effects of short-term exposure (24 h) to retinoids on in vitro-produced bovine morulae. Immature cumulus oocyte complexes were in vitro matured and fertilised. Presumptive zygotes were subsequently cultured in modified synthetic oviduct fluid up to Day 6, in which morulae were randomly allocated to the different experimental groups. The treatments consisted of 0.1 μm LG100268 (LG; a retinoid X receptor agonist), 0.7 μm all-trans retinoic acid (ATRA; a retinoic acid receptor agonist) or no additives. Day 8 blastocyst development was increased in the ATRA-treated group compared with the LG and untreated embryos. In Day 7 embryos, the number of total cells and cells allocated to the trophectoderm were higher in the ATRA-treated group compared with untreated embryos. Apoptosis in the inner cell mass increased after LG treatment, whereas ATRA had no effect. After vitrification and warming, survival and hatching rates of Day 7 blastocysts did not change with retinoid treatment. Within the LG-treated and untreated blastocyst groups, survival and hatching rates were higher for Day 7 than Day 8 embryos; however, Day 8 blastocysts treated with ATRA showed improved hatching rates. In conclusion, treatment of morulae with ATRA in serum-free medium improves embryo development and quality without increasing the incidence of apoptosis and necrosis.

Enhanced Oral Absorption of All-trans Retinoic Acid upon Encapsulation in Solid Lipid Nanoparticles

2020 ◽  
Vol 8 (6) ◽  
pp. 495-510
Author(s):  
Manoj Kumar ◽  
Garima Sharma ◽  
Dinesh Singla ◽  
Sukhjeet Singh ◽  
Vandita Kakkar ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Side Effects ◽  
Solid Lipid Nanoparticles ◽  
In Vitro Release ◽  
Lipid Nanoparticles ◽  
Solid Lipid ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Vitro Release

Background:: All-trans retinoic acid (ATRA) is widely employed in the treatment of various proliferative and inflammatory diseases. However, its therapeutic efficacy is imperiled due to its poor solubility and stability. Latter was surmounted by its incorporation into a solid matrix of lipidic nanoparticles (SLNs). Methods:: ATRA loaded SLNs (ATRA-SLNs) were prepared using a novel microemulsification technique (USPTO 9907758) and an optimal composition and were characterized in terms of morphology, differential scanning calorimetry (DSC), and powder X-ray diffraction studies (PXRD). In vitro release, oral plasma pharmacokinetics (in rats) and stability studies were also done. Results:: Rod-shaped ATRA-SLNs could successfully incorporate 3.7 mg/mL of ATRA, increasing its solubility (from 4.7 μg/mL) by 787 times, having an average particle size of 131.30 ± 5.0 nm and polydispersibility of 0.283. PXRD, DSC, and FTIR studies confirmed the formation of SLNs. Assay/total drug content and entrapment efficiency of ATRA-SLNs was 92.50 ± 2.10% and 84.60 ± 3.20% (n=6), respectively, which was maintained even on storage for one year under refrigerated conditions as an aqueous dispersion. In vitro release in 0.01 M phosphate buffer (pH 7.4) with 3% tween 80 was extended 12 times from 2h for free ATRA to 24 h for ATRA-SLNs depicting Korsmeyer Peppas release. Oral administration in rats showed 35.03 times enhanced bioavailability for ATRA-SLNs. Conclusion:: Present work reports preparation and evaluation of bioenhanced ATRA-SLNs containing a high concentration of ATRA (>15 times than that reported by others). Latter is attributed to the novel preparation process and intelligent selection of components. Lay Summary: All-trans retinoic acid (ATRA) shows an array of pharmacological activities but its efficacy is limited due to poor solubility, stability and side effects. In present study its solubility and efficacy is improved by 787 and 35.5 times, respectively upon incorporation into solid lipid nanoparticles (ATRA-SLNs). Latter extended its release by 12 times and provided stability for at least a year under refrigeration. A controlled and sustained release will reduce dose related side effects. ATRA-SLNs reported presently can thus be used in treatment /prophylaxis of disorders like cancers, tuberculosis, age related macular degeneration and acne and as an immune-booster.

scholarly journals All-Trans Retinoic Acid Increases DRP1 Levels and Promotes Mitochondrial Fission

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1202
Author(s):  
Bojjibabu Chidipi ◽  
Syed Islamuddin Shah ◽  
Michelle Reiser ◽  
Manasa Kanithi ◽  
Amanda Garces ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Mitochondrial Fission ◽  
Normal Function ◽  
Mitochondrial Network ◽  
Protein Levels ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Area And Perimeter

In the heart, mitochondrial homeostasis is critical for sustaining normal function and optimal responses to metabolic and environmental stressors. Mitochondrial fusion and fission are thought to be necessary for maintaining a robust population of mitochondria, and disruptions in mitochondrial fission and/or fusion can lead to cellular dysfunction. The dynamin-related protein (DRP1) is an important mediator of mitochondrial fission. In this study, we investigated the direct effects of the micronutrient retinoid all-trans retinoic acid (ATRA) on the mitochondrial structure in vivo and in vitro using Western blot, confocal, and transmission electron microscopy, as well as mitochondrial network quantification using stochastic modeling. Our results showed that ATRA increases DRP1 protein levels, increases the localization of DRP1 to mitochondria in isolated mitochondrial preparations. Our results also suggested that ATRA remodels the mitochondrial ultrastructure where the mitochondrial area and perimeter were decreased and the circularity was increased. Microscopically, mitochondrial network remodeling is driven by an increased rate of fission over fusion events in ATRA, as suggested by our numerical modeling. In conclusion, ATRA results in a pharmacologically mediated increase in the DRP1 protein. It also results in the modulation of cardiac mitochondria by promoting fission events, altering the mitochondrial network, and modifying the ultrastructure of mitochondria in the heart.

Differential regulation of GPI‐linked molecules on leukaemic promyelocytes treated in vitro with all‐ trans retinoic acid

1996 ◽  
Vol 93 (2) ◽  
pp. 392-393 ◽  
Author(s):  
R. DI NOTO ◽  
E. M. SCHIAVONE ◽  
C. LO PARDO ◽  
F. FERRARA ◽  
C. MANZO ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Differential Regulation ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals Quantification of Internalized Silica Nanoparticles via STED Microscopy

2015 ◽  
Vol 2015 ◽  
pp. 1-16 ◽  
Author(s):  
Henrike Peuschel ◽  
Thomas Ruckelshausen ◽  
Christian Cavelius ◽  
Annette Kraegeloh
Keyword(s):  
Silica Nanoparticles ◽  
Super Resolution ◽  
Engineered Nanoparticles ◽  
Stimulated Emission ◽  
Alveolar Type ◽  
Serum Free Medium ◽  
Free Medium ◽  
Essential Information ◽  
Serum Free

The development of safe engineered nanoparticles (NPs) requires a detailed understanding of their interaction mechanisms on a cellular level. Therefore, quantification of NP internalization is crucial to predict the potential impact of intracellular NP doses, providing essential information for risk assessment as well as for drug delivery applications. In this study, the internalization of 25 nm and 85 nm silica nanoparticles (SNPs) in alveolar type II cells (A549) was quantified by application of super-resolution STED (stimulated emission depletion) microscopy. Cells were exposed to equal particle number concentrations (9.2×1010particles mL−1) of each particle size and the sedimentation of particles during exposure was taken into account. Microscopy images revealed that particles of both sizes entered the cells after 5 h incubation in serum supplemented and serum-free medium. According to thein vitrosedimentation, diffusion, and dosimetry (ISDD) model 20–27% of the particles sedimented. In comparison, 102-103NPs per cell were detected intracellularly serum-containing medium. Furthermore, in the presence of serum, no cytotoxicity was induced by the SNPs. In serum-free medium, large agglomerates of both particle sizes covered the cells whereas only high concentrations (≥ 3.8 × 1012particles mL−1) of the smaller particles induced cytotoxicity.

Hybridoma antibody production in vitro in type II serum-free medium using Nutridoma-SP supplements Comparisons with in vivo methods

1991 ◽  
Vol 145 (1-2) ◽  
pp. 213-221 ◽  
Author(s):  
Geneviève Federspiel ◽  
Kenneth C. McCullough ◽  
Ulrich Kihm
Keyword(s):  
Antibody Production ◽  
Type Ii ◽  
Serum Free Medium ◽  
Free Medium ◽  
Serum Free
Sign in / Sign up

Export Citation Format

Share Document