Search results for "Bone Marrow"
showing 10 items of 538 documents
Selective targeting of IRF4 by synthetic microRNA-125b-5p mimics induces anti-multiple myeloma activity in vitro and in vivo
2015
Interferon regulatory factor 4 (IRF4) is an attractive therapeutic target in multiple myeloma (MM). We here report that expression of IRF4 mRNA inversely correlates with microRNA (miR)-125b in MM patients. Moreover, we provide evidence that miR-125b is downregulated in TC2/3 molecular MM subgroups and in established cell lines. Importantly, constitutive expression of miR-125b-5p by lentiviral vectors or transfection with synthetic mimics impaired growth and survival of MM cells and overcame the protective role of bone marrow stromal cells in vitro. Apoptotic and autophagy-associated cell death were triggered in MM cells on miR-125b-5p ectopic expression. Importantly, we found that the anti-…
Oncogene-driven intrinsic inflammation induces leukocyte production of tumor necrosis factor that critically contributes to mammary carcinogenesis.
2010
Abstract Oncogene activation promotes an intrinsic inflammatory pathway that is crucial for cancer development. Here, we have investigated the actual effect of the inflammatory cytokine tumor necrosis factor (TNF) on the natural history of spontaneous mammary cancer in the HER2/neuT (NeuT) transgenic mouse model. Bone marrow transplantation from TNF knockout mice into NeuT recipients significantly impaired tumor growth, indicating that the source of TNF fostering tumor development was of bone marrow origin. We show that the absence of leukocyte-derived TNF disarranged the tumor vasculature, which lacked pericyte coverage and structural integrity, leading to diffuse vascular hemorrhage and s…
Erythropoietin for the treatment of anemia of malignancy associated with neoplastic bone marrow infiltration.
1990
This clinical trial was performed to study the effects of intravenously (IV) administered recombinant human (rh) erythropoietin (EPO) at escalating doses (150, 300, and 450 U/kg, administered as an IV bolus injection, twice weekly, for 6, 4, and 4 weeks, respectively) in five patients with low-grade non-Hodgkin's lymphoma (Ig NHL) and bone marrow involvement and one patient with multiple myeloma (MM). All patients were anemic due to underlying disease. None of the patients had a history of bleeding, hemolysis, renal insufficiency, or other disorders causing anemia in addition to bone marrow infiltrating malignancy. Endogenous EPO serum levels were significantly increased in all patients (7…
“Masked” Philadelphia chromosome resulting from a t(X;22) in chronic myeloid leukemia
1988
Abstract A rare cytogenetic finding in chronic myeloid leukemia is reported. It consisted in a “masked” Philadelphia chromosome, resulting from an unusual translocation between chromosomes #22 and X. The t(X;22) was present in 100% of direct and cultured bone marrow cell preparations. Chromosome #9 did not seem to be involved in the formation of the Ph marker. Involvement of the X chromosome in karyotypic changes of hematologic diseases, with particular respect to chronic myeloid leukemia, is discussed.
Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profil…
2011
Purpose Abnormal cytokine expression accompanies myelofibrosis and might be a therapeutic target for Janus-associated kinase (JAK) inhibitor drugs. This study describes the spectrum of plasma cytokine abnormalities in primary myelofibrosis (PMF) and examines their phenotypic correlates and prognostic significance. Patients and Methods Patients included in this study were required to have archived plasma, bone marrow biopsy, and cytogenetic information available at the time of first referral to the Mayo Clinic. Multiplex biometric sandwich immunoassay was used to measure plasma levels of 30 cytokines. Results In total, 127 PMF patients were studied; comparison with normal controls (n = 35) r…
p38 MAP kinase drives the expression of mast cell-derived IL-9 via activation of the transcription factor GATA-1.
2007
Mast cells are able to produce a huge panel of mediators including the Th2-type cytokine IL-9, which is considered to be a key mediator for the pathogenesis of allergic asthma, but detailed information on the regulation of IL-9 transcription in mast cells has been scarce. Herein we provide evidence that the erythroid/myeloid transcription factor GATA-1, which is not expressed in Th2 cells, is a potent activator of IL-9 expression in murine bone marrow-derived mast cells (BMMC). Furthermore, in mast cells, but not in Th2 cells, production of IL-9 is sensitive to inhibition of p38 MAP kinase. As transactivation mediated by GATA-1 is also sensitive to inhibition of p38 MAP kinase, and GATA-1 i…
The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia.
2011
AbstractIdentification of patients at risk of early disease progression is the mainstay of tailored management in chronic lymphocytic leukemia (CLL). Although application of established biomarkers is limited by intrinsic detection/readout complexities, abnormality of κ and λ serum-free light chain ratio [sFLC (κ/λ)] was proposed as a straightforward prognosticator in CLL. By analyzing 449 therapy-naive patients, we show that an abnormal sFLC(κ/λ), along with CD38, ZAP-70, IGHV mutations, cytogenetics and stage, independently predicts treatment-free survival (TFS) but becomes prognostically irrelevant if the cumulative amount of clonal and nonclonal FLCs [sFLC(κ + λ)], a variable associated …
Fjord-region diol-epoxides of benzo[c]chrysene are potent inducers of micronuclei in murine bone marrow
1994
Abstract Vicinal diol-epoxides are the best established carcinogenic metabolites of polycyclic aromatic hydrocarbons. Numerous studies have demonstrated their high genotoxic activity in various in vitro test systems. However, in vivo mutagenicity data are not available. The fjor-region diol-epoxides of benzo[ c ]chrysene combine high mutagenic activity in vitro with hydrolytic stability. They were tested for the induction of micronuclei in the bone marrow following intraperitoneal administration to NMRI mice. The anti diasteromer of the diol-epixode enhanced the frequency of micronucleated polycrhomatic erythrocytes strongly (7–19-fold above the value in untreated controls) over a very wide…
Protective Effects of Fruits and Vegetables against In Vivo Clastogenicity of Cyclophosphamide or Benzo[a]pyrene in Mice
1998
Seven fruits and 10 vegetables commonly consumed in Germany were investigated for their anticlastogenic potencies against cyclophosphamide (CP) and benzo[a]pyrene (BaP) in the in vivo mouse bone marrow micronucleus assay. We detected protective effects in 76.5% and 70.6% of the samples, respectively, and more or less distinct quantitative differences between the various plant materials and the two clastogens investigated. With respect to CP, moderate activities were exerted by sweet cherries, strawberries, cucumber, radish and tomatoes, average activities by bananas, oranges, peaches, asparagus and red beets and strong activities by yellow red peppers and especially spinach. Apples (cultiva…
Bone marrow cell transcripts from Fanconi anaemia patients revealin vivoalterations in mitochondrial, redox and DNA repair pathways
2013
Fanconi anaemia (FA) is a genetic cancer predisposition disorder associated with cytogenetic instability, bone marrow failure and a pleiotropic cellular phenotype, including low thresholds of responses to oxidative stress, cross-linking agents and selected cytokines. This study was aimed at defining the scope of abnormalities in gene expression using the publicly available FA Transcriptome Consortium (FTC) database (Gene Expression Omnibus, 2009 and publicly available as GSE16334). We evaluated the data set that included transcriptomal analyses on RNA obtained from low-density bone marrow cells (BMC) from 20 patients with FA and 11 healthy volunteers, by seeking to identify changes in expre…