Search results for "Myelogenous"

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…

Type-I interferons are potent inhibitors of interleukin-8 production in hematopoietic and bone marrow stromal cells

1993

Abstract nterleukin-8 (IL-8) is produced by many cell types upon stimulation with bacterial products or inflammation-associated cytokines such as tumor necrosis factor-alpha and IL-1. Interferons (IFNs) represent another group of cytokines that are induced by similar stimuli in inflammatory reactions. We show now that type-I IFNs are potent inhibitors of IL-8 expression in vitro and in vivo. A significant reduction of both secretion of IL-8 protein and accumulation of IL-8 mRNA in vitro was observed in several cell types comprising peripheral blood mononuclear cells (PBMNC) from healthy donors and from patients with chronic myelogenous leukemia (CML), the myelomonocytic cell line THP-1, and…

Chronic myeloid leukemia-derived exosomes promote tumor growth through an autocrine mechanism.

2014

Background Chronic myeloid leukemia (CML) is a clonal hematopoietic stem cell disorder in which leukemic cells display a reciprocal t(9:22) chromosomal translocation that results in the formation of the chimeric BCR-ABL oncoprotein, with a constitutive tyrosine kinase activity. Consequently, BCR-ABL causes increased proliferation, inhibition of apoptosis, and altered adhesion of leukemic blasts to the bone marrow (BM) microenvironment. It has been well documented that cancer cells can generate their own signals in order to sustain their growth and survival, and recent studies have revealed the role of cancer-derived exosomes in activating signal transduction pathways involved in cancer cell…

Mechanisms of Autocrine and Paracrine Growth Control in Acute Myelogenous Leukemia

1990

Blast cells of a high proportion of patients with acute myelogenous leukemia (AML) proliferate in response to exogenous hematopoetic growth factors, both in vitro [9, 14, 26, 36, 48, 65] and in vivo [20]. Whereas leukemic colony-forming cells (L-CFCs) from most patients share their growth factor dependence with normal committed myeloid progenitor cells (CFU-GMs), some AML samples autonomously form colonies in agar and are therefore believed to bypass growth factor requirements [17, 42, 72]. Autocrine growth factor production has been identified as one mechanism used by AML blasts to supply various growth-promoting molecules. Moreover nontransformed accessory bone marrow cells have been show…

Overcoming Imatinib resistance using CAI, a calcium-mediated signal transduction inhibitor: A new therapeutic strategy for chronic myelogenous leucem…

2008

Molecular profiling of chronic myelogenous leukemia cell lines: identification of new molecular markers for the characterization of leukemia phenotype

2009

CarboxyAmido-Triazole Orotate inhibits the growth of Imatinib-resistant chronic myeloid leukaemia cells and modulates exosomes-stimulated angiogenesis

2012

Chronic myelogenous leukemia is a myeloproliferative disorder characterized by the t(9:22) (q34:q11) reciprocal chromosomal translocation, resulting in the expression of the chimeric Bcr–Abl oncoprotein with constitutive tyrosine kinase activity. Deregulated Bcr–Abl induces the hyperactivation of various signalling pathways that promote cell growth, suppress apoptosis and alter cell adhesion. Bcr-Abl has also been involved in VEGF-mediated angiogenesis in CML and evidence indicates that the formation of new vessels plays an important role in the development and progression of CML. Imatinib mesylate (IM) is a selective well tolerated inhibitor of the Bcr–Abl tyrosine kinase that has signific…

V gamma 9V delta 2 T lymphocytes efficiently recognize and kill zoledronate-sensitized, imatinib-sensitive, and imatinib-resistant chronic myelogenou…

2010

Abstract Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective against chronic myelogenous leukemia (CML) cells. However, because 20–30% of patients affected by CML display either primary or secondary resistance to imatinib, intentional activation of Vγ9Vδ2 T cells by phosphoantigens or by agents that cause their accumulation within cells, such as zoledronate, may represent a promising strategy for the design of a novel and highly innovative immunotherapy capable to overcome imatinib resistance. In this study, we show that Vγ9Vδ2 T lymphocytes recognize, trogocytose, and efficiently kill imatinib-sensitive and -resistant CML cell lines pre…

A minireview on NHE1 inhibitors. A rediscovered hope in oncohematology.

2015

Background: Na+/H+ exchanger-1 (NHE-1) is involved in pH regulation and is up-regulated in different malignancies. Activation of NHE-1 is one way for allowing cells to avoid intracellular acidification and protect them against apoptosis. Inhibitors of NHE-1 are able to decrease intracellular pH and induce apoptosis. Some statins can also act by partial inhibition of NHE-1. This review presents progress in understanding the mechanisms of action of these inhibitors, connections with certain genetic mutations and acquired treatment resistance, as well as new patents on them. Methods: A MEDLINE search for original and review articles using key terms, Na+/H+ exchanger, leukemia, cariporide, and …

Combination Treatment with Imatinib and Mitoxantrone/Etoposide Is a Suitable Preparative Regimen before Allogeneic Transplantation in Patients with M…

2005

Abstract In advanced BCR-ABL-positive leukemia, combination of chemotherapy with imatinib is expected to result in better reduction of leukemia cell load and may delay or offset clonal selection of resistant leukemia cells, thus improving the survival. We carried out a prospective phase I/II combination trial for patients (pts) with myeloid blast crisis of chronic myelogenous leukemia (CML). Pts were treated with imatinib+mitoxantrone/etoposide in four cohorts starting from mitoxantrone 10mg/m2/d and etoposide 100 mg/m2/d for 2 or 3 consecutive days and start of imatinib 600mg/d from day 15 (coh. 1 and 2) or from day 1 (coh. 3 and 4, respectively). After hematologic reconstitution following…