Search results for "leukemia"
showing 10 items of 976 documents
Genetic variation in human leukocyte antigen and susceptibility to acute myeloid leukemia.
2015
In this issue of Acta Haematologica, Authors report the association between the Human Major Histocompatibility complex (MHC) HLA-C3 and Acute Myeloid Leukemia (AML) in Korean population, confirming previous studies on association between HLA-C and AML.
Italian multicentricepidemiological case control strudy on risk factors for childhood leukemia,non hodgkin limphoma and neuroblastoma:study populatio…
2014
Background Aetiology of childhood leukaemia and childhood neoplasm is poorly understood. Information on the prevalence of risk factors in the childhood population is limited. SETIL is a population based case/control study on childhood leukaemia, conducted with two companion studies on non-Hodgkin Lymphoma (NHL) and neuroblastoma. The study relies on questionnaire interviews and 50 Hz magnetic field (ELF-MF) indoor measurements. This paper discusses the SETIL study design and includes descriptive information. Methods The study was carried out in 14 Italian regions (78.3% of Italian population aged 0?10). It included leukaemia, NHL and neuroblastoma cases incident in 0?10 year olds in 1998-20…
TRAIL-induced apoptosis of hepatocellular carcinoma cells is augmented by targeted therapies
2009
AIM: To analyze the effect of chemotherapeutic drugs and specific kinase inhibitors, in combination with the death receptor ligand tumor necrosis factor-related apoptosis inducing ligand (TRAIL), on overcoming TRAIL resistance in hepatocellular carcinoma (HCC) and to study the efficacy of agonistic TRAIL antibodies, as well as the commitment of antiapoptotic BCL-2 proteins, in TRAIL-induced apoptosis. METHODS: Surface expression of TRAIL receptors (TRAIL-R1-4) and expression levels of the antiapoptotic BCL-2 proteins MCL-1 and BCL-xL were analyzed by flow cytometry and Western blotting, respectively. Knock-down of MCL-1 and BCL-xL was performed by transfecting specific small interfering RNA…
Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3-internal tandem duplication mutat…
2020
PURPOSE Despite undergoing allogeneic hematopoietic stem cell transplantation (HCT), patients with acute myeloid leukemia (AML) with internal tandem duplication mutation in the FMS-like tyrosine kinase 3 gene ( FLT3-ITD) have a poor prognosis, frequently relapse, and die as a result of AML. It is currently unknown whether a maintenance therapy using FLT3 inhibitors, such as the multitargeted tyrosine kinase inhibitor sorafenib, improves outcome after HCT. PATIENTS AND METHODS In a randomized, placebo-controlled, double-blind phase II trial (SORMAIN; German Clinical Trials Register: DRKS00000591), 83 adult patients with FLT3-ITD–positive AML in complete hematologic remission after HCT were r…
Cytotoxicity of Artesunic Acid Homo- and Heterodimer Molecules toward Sensitive and Multidrug-Resistant CCRF-CEM Leukemia Cells
2010
A novel approach to circumvent multidrug resistance is hybridization of natural products in dimers. We analyzed homodimers of two artesunic acid molecules and heterohybrids of artesunic acid and betulin in human CCRF-CEM and multidrug-resistant P-glycoprotein-overexpressing CEM/ADR5000 leukemia cells. Multidrug-resistant cells were not cross-resistant to the novel compounds. Collateral sensitivity was observed for artesunic acid homodimer. Artesunic acid and artesunic acid homodimer induced G0/G1 cell cycle arrest, apoptosis, and formation of reactive oxygen species.
Investigating the Molecular Mechanism of H3B-8800: A Splicing Modulator Inducing Preferential Lethality in Spliceosome-Mutant Cancers.
2021
The SF3B1 protein, part of the SF3b complex, recognizes the intron branch point sequence of precursor messenger RNA (pre-mRNA), thus contributing to splicing fidelity. SF3B1 is frequently mutated in cancer and is the target of distinct families of splicing modulators (SMs). Among these, H3B-8800 is of particular interest, as it induces preferential lethality in cancer cells bearing the frequent and highly pathogenic K700E SF3B1 mutation. Despite the potential of H3B-8800 to treat myeloid leukemia and other cancer types hallmarked by SF3B1 mutations, the molecular mechanism underlying its preferential lethality towards spliceosome-mutant cancer cells remains elusive. Here, microsecond-long a…
Stochastic dynamics of leukemic cells under an intermittent targeted therapy
2009
The evolutionary dynamics of cancerous cell populations in a model of Chronic Myeloid Leukemia (CML) is investigated in the presence of an intermittent targeted therapy. Cancer development and progression is modeled by simulating the stochastic evolution of initially healthy cells which can experience genetic mutations and modify their reproductive behavior, becoming leukemic clones. Front line therapy for the treatment of patients affected by CML is based on the administration of tyrosine kinase inhibitors, namely imatinib (Gleevec) or, more recently, dasatinib or nilotinib. Despite the fact that they represent the first example of a successful molecular targeted therapy, the development o…
Tailoring sparse multivariable regression techniques for prognostic single-nucleotide polymorphism signatures.
2011
When seeking prognostic information for patients, modern technologies provide a huge amount of genomic measurements as a starting point. For single-nucleotide polymorphisms (SNPs), there may be more than one million covariates that need to be simultaneously considered with respect to a clinical endpoint. Although the underlying biological problem cannot be solved on the basis of clinical cohorts of only modest size, some important SNPs might still be identified. Sparse multivariable regression techniques have recently become available for automatically identifying prognostic molecular signatures that comprise relatively few covariates and provide reasonable prediction performance. For illus…
Identification of a Terphenyl Derivative that Blocks the Cell Cycle in the G0−G1 Phase and Induces Differentiation in Leukemia Cells
2006
To further explore the SAR of resveratrol-related trans-stilbene derivatives, here we describe the synthesis of (a) a series of 3,5-dimethoxy analogues in which a variety of substituents were introduced at positions 2', 3', 4', and 5' of the stilbene scaffold and (b) a second group of derivatives (2-phenylnaphthalenes and terphenyls) that incorporate a phenyl ring as a bioisosteric replacement of the stilbene alkenyl bridge. We thoroughly characterized all of the new compounds with respect to their apoptosis-inducing activity and their effects on the cell cycle. One of the new derivatives, 13g, behaved differently from the others, as it was able to block the cell cycle in the G(0)-G(1) phas…
Synthesis and in vitro antileukemic activity of new 4-triazenopyrazole derivatives
2003
Several new 4-(3,3-dimethyltriazeno)-5-benzamidopyrazole derivatives were prepared by reacting 4-diazo-5-benzamidopyrazole derivatives with dimethylamine. The compounds were tested at 10 microM for their vitro antileukemic activity against K562 (Human chronic myelogenous leukemia) and Raji (human Burkitt limphoma ) cell lines. Dacarbazine and methotrexate were used for comparative purpose. The 3-methyl-4-(3,3-dimethyltriazeno)-5-(substituted benzamido)pyrazoles, bearing the pyrazole nucleus free at 1 position, resulted more active than the 1-(substituted phenyl)-3-methyl-4-(3,3-dimethyltriazeno)-5-benzamidopyrazoles. Dacarbazine at 10 microM showed no activity in the above tests. The observ…