Search results for "Eloi"

Evolutionary dynamics of imatinib-treated leukemic cells by stochastic approach

2008

The evolutionary dynamics of a system of cancerous cells in a model of chronic myeloid leukemia (CML) is investigated by a statistical approach. Cancer progression is explored by applying a Monte Carlo method to simulate the stochastic behavior of cell reproduction and death in a population of blood cells which can experience genetic mutations. In CML front line therapy is represented by the tyrosine kinase inhibitor imatinib which strongly affects the reproduction of leukemic cells only. In this work, we analyze the effects of a targeted therapy on the evolutionary dynamics of normal, first-mutant and cancerous cell populations. Several scenarios of the evolutionary dynamics of imatinib-tr…

2019

Here we explore the carbon and oxygen isotope compositions of the co-existing carbonate and phosphate fractions of fish tooth enameloid as a tool to reconstruct past aquatic fish environments and harvesting grounds. The enameloid oxygen isotope compositions of the phosphate fraction (δ18OPO4) vary by as much as ~4‰ for migratory marine fish such as gilthead seabream (Sparus aurata), predominantly reflecting the different saline habitats it occupies during its life cycle. The offset in enameloid Δ18OCO3-PO4 values of modern marine Sparidae and freshwater Cyprinidae from the Southeast Mediterranean region vary between 8.1 and 11.0‰, similar to values reported for modern sharks. The mean δ13C …

Cancer growth dynamics: stochastic models and noise induced effects

2009

In the framework of the Michaelis‐Menten (MM) reaction kinetics, we analyze the cancer growth dynamics in the presence of the immune response. We found the coexistence of noise enhanced stability (NES) and resonant activation (RA) phenomena which act in an opposite way with respect to the extinction of the tumor. The role of the stochastic resonance (SR) in the case of weak cancer therapy has been analyzed. The evolutionary dynamics of a system of cancerous cells in a model of chronic myeloid leukemia (CML) is investigated by a Monte Carlo approach. We analyzed the effects of a targeted therapy on the evolutionary dynamics of normal, first‐mutant and cancerous cell populations. We show how …

Identification of a novel type of ITD mutations located in nonjuxtamembrane domains of the FLT3 tyrosine kinase receptor

2009

Abstract In acute myeloid leukemia (AML), internal tandem duplications (ITDs) of the juxtamembrane (JM) of FLT3 have been shown to play a crucial role in driving proliferation and survival of the leukemic clone. Here, we report the identification of FLT3_ITD mutations located in non-JM domains of the FLT3-receptor. This novel type of FLT3_ITD mutation was found in 216 of 753 (28.7%) of unselected FLT3_ITD-positive AML cases. An FLT3 receptor harbouring a prototypic non-JM ITD (FLT3_ITD627E) mediated constitutive phosphorylation of FLT3 and of STAT5, suggesting that non-JM ITDs confer constitutive activation of the receptor. FLT3_ITD627E induced transformation of hematopoietic 32D cells and …

DNMT3A mutations Predict for Inferior Outcome in NPM1-Wildtype and Molecular Unfavorable Cytogenetically-Normal Acute Myeloid Leukemia: A Study of th…

2011

Abstract Abstract 415 Background: Alteration of DNA methylation, a hallmark of epigenetic modification, is currently discussed as one important pathomechanism in leukemogenesis. Using a next-generation sequencing approach, a frameshift mutation of the gene encoding the DNA methyltransferase (DNMT3A) in an acute myeloid leukemia (AML) case was identified. DNMT3A catalyses the addition of a methyl group to the cytosine residue of CpG dinucleotides, thereby affecting promoter methylation status and gene expression. Subsequent sequencing analysis in an independent cohort of 288 AML patients (pts) revealed DNMT3A mutations (DNMT3Amut) in 22% of the pts; mutations were associated with intermediat…

Antiproliferative Effects of St. John’s Wort, Its Derivatives, and Other Hypericum Species in Hematologic Malignancies

2021

Hypericumis a widely present plant, and extracts of its leaves, flowers, and aerial elements have been employed for many years as therapeutic cures for depression, skin wounds, and respiratory and inflammatory disorders. Hypericum also displays an ample variety of other biological actions, such as hypotensive, analgesic, anti-infective, anti-oxidant, and spasmolytic abilities. However, recent investigations highlighted that this species could be advantageous for the cure of other pathological situations, such as trigeminal neuralgia, as well as in the treatment of cancer. This review focuses on the in vitro and in vivo antitumor effects of St. John’s Wort (Hypericum perforatum), its derivat…

The suppressive effects of recombinant human tumor necrosis factor‐alpha on normal and malignant myelopoiesis: Synergism with interferon‐gamma

1988

The modulation of growth of normal and leukemic myeloid progenitor cells in soft agar cultures by recombinant human tumor necrosis factor-alpha (TNF alpha) and recombinant human interferon-gamma (IFN gamma) was investigated. TNF alpha inhibited colony formation of all colony types representing different maturational stages of normal progenitor cells committed to the myeloid lineage with different orders of sensitivity. Blast-type colonies derived from patients with acute myelogenous leukemia were more sensitive to TNF alpha inhibition than progenitor cells purified from normal bone marrow or bone marrow from patients with stable-phase chronic myelogenous leukemia. The response of most colon…

Bcr-Abl kinase promotes cell cycle entry of primary myeloid CML cells in the absence of growth factors

1998

Cell cycle control of both immature and differentiated primary myeloid normal and chronic-phase chronic myeloid leukaemia (CML) cells to growth factor deprivation was studied. CD34+ cells were cultured in liquid culture. After removal of growth factors for 48 h normal cells were very efficiently arrested with the fraction of cells in S phase reduced by 70.8 +/- 6.5% in CD34+ and 50.5 +/- 4.2% in CD34- cells. In contrast, a significantly higher proportion of leukaemic cells remained in S phase. The fraction of S-phase cells was reduced by only 29.3 +/- 5.7% in CD34+ CML cells and 21.2 +/- 3.8% in CD34- cells. This abnormal negative cell cycle control in leukaemic cells was specific for growt…

A novel neural stem cell-derived immunocompetent mouse model of glioblastoma for preclinical studies

2020

AbstractGlioblastomas are the most lethal tumors affecting the central nervous system in adults. Simple and inexpensive syngeneicin vivomodels that closely mirror human glioblastoma, including interactions between tumor and immune cells, are urgently needed for deciphering glioma biology and developing more effective treatments. Here, we generated glioblastoma cell lines by repeatedin-vivopassaging of cells isolated from a neural stem cell-specific Pten/p53 double-knockout genetic mouse brain tumor model. Transcriptome and genome analyses of the cell lines revealed molecular heterogeneity comparable to that observed in human glioblastoma. Upon orthotopic transplantation into syngeneic hosts…

Signalling through TLR2/MyD88 induces differentiation of murine bone marrow stem and progenitor cells to functional phagocytes in response to Candida…

2009

Summary We have previously demonstrated that inactivated yeasts and hyphae of Candida albicans induce in vitro the proliferation of murine haematopoietic stem and progenitor cells (HSPCs, sorted as LKS cells: Lin - c-Kit + Sca-1 + ) as well as their differentia- tion to lineage-positive cells, through a MyD88- dependent pathway. In this work, we have found that this process is mainly mediated by TLR2, and that expanding cells express myeloid and not lym- phoid markers. Incubation of long-term repopulat- ing HSCs (Lin - CD105 + and Sca-1 + ) with C. albicans yeasts resulted in their proliferation and up regu- lation of the common myeloid progenitors (CMPs) markers, CD34 and FcgRII/III, by a …