Search results for "Lymphatic"
showing 10 items of 1179 documents
Persistence of Human Bocavirus 1 in Tonsillar Germinal Centers and Antibody-Dependent Enhancement of Infection
2021
Human bocavirus 1 (HBoV1), a common pediatric respiratory pathogen, can persist in airway secretions for months hampering diagnosis. It also persists in tonsils, providing potential reservoirs for airway shedding, with the exact location, host cell types, and virus activity unknown.
Combined Targeting of the Menin-MLL1 Chromatin Complex and FLT3 As a Novel Therapeutic Concept Against NPM1 Mutant or MLL-Rearranged AML with Mutated…
2019
NPM1mutant (NPM1mut) and MLL1-rearranged (MLL-r) acute myeloid leukemias (AMLs) exhibit aberrant expression of HOX and MEIS1 transcription factors and commonly harbor an activating mutation in the receptor tyrosine kinase FLT3. Pharmacologic inhibition of the menin-MLL1 complex reverses leukemogenic gene expression including MEIS1 and FLT3 and represents a therapeutic opportunity for the treatment of these leukemias. Here, we investigate the contribution of the menin-MLL1 complex to leukemic FLT3 signaling and assess the therapeutic potential of dual menin-MLL1 and FLT3 targeting. First, we performed RNA sequencing to delineate transcriptional changes associated with menin-MLL1 inhibition (…
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…
High frequency of subclonal ALK mutations in high risk neuroblastoma patients. A SIOPEN study
2015
Introduction: In neuroblastoma (NB), activating ALK receptor tyrosine kinase point mutations are detected in 8–10% at diagnosis using conventional sequencing. To determine the potential occurrence and the prognostic impact of ALK mutations in a series of high risk NB patients we studied ALK variation frequencies using targeted deep sequencing in samples of patients enrolled in the SIOPEN HR-NBL01 study
ChemInform Abstract: Synthesis and Antineoplastic Activity of New 4-Diazopyrazole Derivatives.
2010
Several new 4-diazopyrazole derivatives were synthesized by reaction of 1-(R-substituted)phenyl-3-methyl-5-benzamidopyrazoles with a sevenfold excess of nitrous acid in acetic media. The compounds were tested at 20 microM concentration for their antineoplastic activity in vitro against Raji (human Burkitt lymphoma), K562 (human chronic myelogenous leukemia) and U937 (human histiocytic lymphoma) cell lines. They showed a percent of growth inhibition in the range 23.4-100%.
Proteomic Profile Study of Chronic Lymphocytic Leukemia-B Patients with IGVH and BCL6 Mutated or Unmutated Genes.
2004
Abstract Introduction: Chronic lymphocytic leukemia B (CLL-B) is the most frequent chronic lymphoproliferative disorder in western countries. The majority of patients are diagnosed in incipient Binet stage A. Some prognostic factors have been identified, as mutations in the genes coding for immunoglobulin variable regions (IgVH). Complementary somatic mutations in the BCL6 gene have been observed in 25% of CLL-B patients, although its clinical relevance remains unclear. Objective: To identify molecular markers of different patient groups of lymphoproliferative disorder through analysis of their proteomic profiles. Material and Methods: 15 samples of peripheral blood lymphocytes B from Binet…
Seawater carbonate chemistry and carbon sources of mussel shell carbonate
2018
Ocean acidification and warming is widely reported to affect the ability of marine bivalves to calcify, but little is known about the underlying mechanisms. In particular, the response of their calcifying fluid carbonate chemistry to changing seawater carbonate chemistry remains poorly understood. The present study deciphers sources of the dissolved inorganic carbon (DIC) in the calcifying fluid of the blue mussel (Mytilus edulis) reared at two pH (8.1 and 7.7) and temperature (16 and 22 °C) levels for five weeks. Stable carbon isotopic ratios of seawater DIC, mussel soft tissues and shells were measured to determine the relative contribution of seawater DIC and metabolically generated carb…
Prognostic Impact of Mutant to Wild-Type Ratio and Insertion Site in Acute Myeloid Leukemia with FLT3 Internal Tandem Duplication
2012
Abstract Abstract 785 Background: FLT3 internal tandem duplications (FLT3-ITD) occur in about 25% of acute myeloid leukemia (AML), are associated with cooperating gene mutations (NPM1, DNMT3A), and confer an adverse prognosis. Several studies have indicated that the unfavorable impact of FLT3-ITD is influenced by a number of factors, such as the mutant to wild-type ratio (allelic ratio), insertion site of FLT3-ITD in the beta1 sheet of the tyrosine kinase domain 1, and the molecular background of cooperating mutations. Aims: To evaluate the relative impact of FLT3-ITD allelic ratio and insertion site, as well as cooperating genetic lesions on prognosis and treatment decision making in a lar…
Deep MRD profiling defines outcome and unveils different modes of treatment resistance in standard- and high-risk myeloma
2021
PETHEMA/GEM Cooperative Group.
Assessing the impact of CMF-like/Anthracycline-based/Anthracycline-Taxane-based/dose-dense chemotherapy in dependency of positive axillary lymph node…
2014
Abstract Aim Adjuvant chemotherapy has changed dramatically in the last decades. Anthracycline-/Taxane-based and dose-dense chemotherapy regimens improved survival in node positive breast cancer. This study tries to answer the following questions: (1)Are there differences in survival dependent on chemotherapy regimens in stratified by number of positive lymph nodes/grading (G)/hormone receptor-status (HR)/T-stage? (2)Is it possible to attribute these effects to chemotherapy by only investigating patients who received 100% guideline-conform surgery, radiotherapy and endocrine therapy? Methods This is a German multi-centre (17 participating hospitals all certified as breast cancer centres) re…