Search results for "2A"
showing 10 items of 282 documents
Synergistic targeting of FLT3 mutations in AML via combined menin-MLL and FLT3 inhibition
2020
Abstract The interaction of menin (MEN1) and MLL (MLL1, KMT2A) is a dependency and provides a potential opportunity for treatment of NPM1-mutant (NPM1mut) and MLL-rearranged (MLL-r) leukemias. Concomitant activating driver mutations in the gene encoding the tyrosine kinase FLT3 occur in both leukemias and are particularly common in the NPM1mut subtype. In this study, transcriptional profiling after pharmacological inhibition of the menin-MLL complex revealed specific changes in gene expression, with downregulation of the MEIS1 transcription factor and its transcriptional target gene FLT3 being the most pronounced. Combining menin-MLL inhibition with specific small-molecule kinase inhibitors…
Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma
2013
Background Tumor models are critical for our understanding of cancer and the development of cancer therapeutics. Here, we present an integrated map of the genome, transcriptome and immunome of an epithelial mouse tumor, the CT26 colon carcinoma cell line. Results We found that Kras is homozygously mutated at p.G12D, Apc and Tp53 are not mutated, and Cdkn2a is homozygously deleted. Proliferation and stem-cell markers, including Top2a, Birc5 (Survivin), Cldn6 and Mki67, are highly expressed while differentiation and top-crypt markers Muc2, Ms4a8a (MS4A8B) and Epcam are not. Myc, Trp53 (tp53), Mdm2, Hif1a, and Nras are highly expressed while Egfr and Flt1 are not. MHC class I but not MHC class…
Two-step nilpotent Leibniz algebras
2022
In this paper we give a complete classification of two-step nilpotent Leibniz algebras in terms of Kronecker modules associated with pairs of bilinear forms. In particular, we describe the complex and the real case of the indecomposable Heisenberg Leibniz algebras as a generalization of the classical $(2n+1)-$dimensional Heisenberg Lie algebra $\mathfrak{h}_{2n+1}$. Then we use the Leibniz algebras - Lie local racks correspondence proposed by S. Covez to show that nilpotent real Leibniz algebras have always a global integration. As an application, we integrate the indecomposable nilpotent real Leibniz algebras with one-dimensional commutator ideal. We also show that every Lie quandle integr…
Modulation of biotransformation and elimination systems by BM-21, an aqueous ethanolic extract from Thalassia testudinum, and thalassiolin B on human…
2012
Abstract BM-21 is an extract obtained from Thalassia testudinum marine plant with pharmacological properties. The effects of BM-21 and thalassiolin B (TB), its main component, on enzyme and transport proteins involved in drug metabolism and excretion in human cultured hepatocytes were evaluated. Cells were exposed for 48 h to sub-cytotoxic concentrations of BM-21 or TB. Effects on P450 isoforms revealed significant reductions of CYP1A2, 3A4 and 2D6 activities (up to 56%, 66% and 44% inhibition, respectively) after exposition to BM-21, no changes on CYP2A6 and 2C9 activities. TB produced a concentration-dependent reduction of all P450 activities. In addition, a decrease in total UGT and UGT2…
Vinblastine and interferon-alpha-2a regimen in the treatment of metastatic renal cell carcinoma.
1990
Thirteen patients with histologically proven advanced and/or metastatic renal cell carcinoma (RCC) were treated with vinblastine (Velbe, Eli Lilly, Sesto Fiorentino, Italy) and interferon-alpha-2a (Roferon-A, Roche, Milan). Eleven out of 13 patients were evaluable. Eighteen percent of patients had partial response, 46 % stable disease (SD), and 36 % progressive disease (PD). The mean survival of responders was 228+ days, whereas the patients showing SD and PD had a mean survival of 154+ and 107+ days respectively. Toxicity, including influenza-like syndrome, fever, neurological and gastrointestinal side effects, was generally mild. However, medication with paracetamol was required in 82 % …
PDCT-08. SUPERIOR OUTCOME FOR BRAF V600E PEDIATRIC GLIOMAS TREATED WITH TARGETED BRAF INHIBITION
2019
Abstract BACKGROUND Children with pediatric low grade glioma’s (PLGG) harboring BRAF V600E mutation have poor outcome due to relative resistance to chemo-radiation and higher risk of malignant transformation. However, the role of targeted BRAF inhibition in these tumors is poorly defined. METHODS We assembled an international cohort of children with BRAF V600E mutant gliomas treated with BRAF inhibition, from 29 centers participating in the PLGG taskforce, and collected response, survival and molecular parameters. RESULTS Sixty-seven patients were treated with BRAFi (56 PLGG and 11 high grade gliomas) for a median time of 17.4 months (6 – 61 months), with 13 PLGG treated upfront. Objective …
285 DOWNREGULATION OF ORGANIC CATION TRANSPORTERS OCT1 (SLC22A1) AND OCT3 (SLC22A3) IN HUMAN HEPATOCELLULAR CARCINOMA AND THEIR PROGNOSTIC SIGNIFICAN…
2012
Background Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).
Evapotranspiration simulations in ISIMIP2a-Evaluation of spatio-temporal characteristics with a comprehensive ensemble of independent datasets
2018
Actual land evapotranspiration (ET) is a key component of the global hydrological cycle and anessential variable determining the evolution of hydrological extreme events under different climate change scenarios. However, recently available ET products show persistent uncertainties thatare impeding a precise attribution of human-induced climate change. Here, we aim at comparing arange of independent global monthly land ET estimates with historical model simulations from theglobal water, agriculture, and biomes sectors participating in the second phase of the Inter-SectoralImpact Model Intercomparison Project (ISIMIP2a). Among the independent estimates, we use theEartH2Observe Tier-1 dataset …
Gadd45α modulates aversive learning through post‐transcriptional regulation of memory‐related mRNA s
2018
Abstract Learning is essential for survival and is controlled by complex molecular mechanisms including regulation of newly synthesized mRNAs that are required to modify synaptic functions. Despite the well‐known role of RNA‐binding proteins (RBPs) in mRNA functionality, their detailed regulation during memory consolidation is poorly understood. This study focuses on the brain function of the RBP Gadd45α (growth arrest and DNA damage‐inducible protein 45 alpha, encoded by the Gadd45a gene). Here, we find that hippocampal memory and long‐term potentiation are strongly impaired in Gadd45a‐deficient mice, a phenotype accompanied by reduced levels of memory‐related mRNAs. The majority of the Ga…
First Case Report of Primary Carnitine Deficiency Manifested as Intellectual Disability and Autism Spectrum Disorder
2019
Systemic primary carnitine deficiency (PCD) is a genetic disorder caused by decreased or absent organic cation transporter type 2 (OCTN2) carnitine transporter activity, resulting in low serum carnitine levels and decreased carnitine accumulation inside cells. In early life, PCD is usually diagnosed as a metabolic decompensation, presenting as hypoketotic hypoglycemia, Reye syndrome, or sudden infant death; in childhood, PCD presents with skeletal or cardiac myopathy. However, the clinical presentation of PCD characterized by autism spectrum disorder (ASD) with intellectual disability (ID) has seldom been reported in the literature. In this report, we describe the clinical features of a sev…