Search results for "leukemia"
showing 10 items of 976 documents
Quantitative Imaging of D-2-Hydroxyglutarate in Selected Histological Tissue Areas by a Novel Bioluminescence Technique
2016
Abstract Patients with malignant gliomas have a poor prognosis with average survival of less than one year. Whereas in other tumor entities the characteristics of tumor metabolism are successfully used for therapeutic approaches, such developments are very rare in brain tumors, notably in gliomas. One metabolic feature characteristic of gliomas, in particular diffuse astrocytomas and oligodendroglial tumors, is the variable content of D-2-hydroxyglutarate (D2HG), a metabolite, which was discovered first in this tumor entity. D2HG is generated in large amounts due to various “gain-of–function” mutations in the isocitrate dehydrogenases IDH-1 and IDH-2. Meanwhile, D2HG has been detected in se…
Persistent immune stimulation exacerbates genetically driven myeloproliferative disorders via stromal remodeling
2017
Abstract Systemic immune stimulation has been associated with increased risk of myeloid malignancies, but the pathogenic link is unknown. We demonstrate in animal models that experimental systemic immune activation alters the bone marrow stromal microenvironment, disarranging extracellular matrix (ECM) microarchitecture, with downregulation of secreted protein acidic and rich in cysteine (SPARC) and collagen-I and induction of complement activation. These changes were accompanied by a decrease in Treg frequency and by an increase in activated effector T cells. Under these conditions, hematopoietic precursors harboring nucleophosmin-1 (NPM1) mutation generated myeloid cells unfit for normal …
Aberrant splicing of the tumor suppressor CYLD promotes the development of chronic lymphocytic leukemia via sustained NF-κB signaling
2017
The pathogenesis of chronic lymphocytic leukemia (CLL) has been linked to constitutive NF-κB activation but the underlying mechanisms are poorly understood. Here we show that alternative splicing of the negative regulator of NF-κB and tumor suppressor gene CYLD regulates the pool of CD5+ B cells through sustained canonical NF-κB signaling. Reinforced canonical NF-κB activity leads to the development of B1 cell-associated tumor formation in aging mice by promoting survival and proliferation of CD5+ B cells, highly reminiscent of human B-CLL. We show that a substantial number of CLL patient samples express sCYLD, strongly implicating a role for it in human B-CLL. We propose that our new CLL-l…
Repurposing of artemisinin-type drugs for the treatment of acute leukemia.
2020
Cancer treatment represents an unmet challenge due to the development of drug resistance and severe side effects of chemotherapy. Artemisinin (ARS)-type compounds exhibit excellent antimalarial effects with few side effects and drug-resistance. ARS and its derivatives were also reported to act against various tumor types in vitro and in vivo, including acute leukemia. Therefore, ARS-type compounds may be exquisitely suitable for repurposing in leukemia treatment. To provide comprehensive clues of ARS and its derivatives for acute leukemia treatment, their molecular mechanisms are discussed in this review. Five monomeric molecules and 72 dimers, trimers and hybrids based on the ARS scaffold …
Mcl-1 targeting could be an intriguing perspective to cure cancer
2018
The Bcl-2 family, which plays important roles in controlling cancer development, is divided into antiapoptotic and proapoptotic members. The change in the balance between these members governs the life and death of the cells. Mcl-1 is an antiapoptotic member of this family and its distribution in normal and cancerous tissues strongly differs from that of Bcl-2. In human cancers, where upregulation of antiapoptotic proteins is common, Mcl-1 expression is regulated independent of Bcl-2 and its inhibition promotes senescence, a major barrier to tumorigenesis. Cancer chemotherapy determines various kinds of responses, such as senescence and autophagy; however, the ideal response to chemotherapy…
Chemopreventive Property of Sencha Tea Extracts towards Sensitive and Multidrug-Resistant Leukemia and Multiple Myeloma Cells
2020
The popular beverage green tea possesses chemopreventive activity against various types of tumors. However, the effects of its chemopreventive effect on hematological malignancies have not been defined. In the present study, we evaluated antitumor efficacies of a specific green tea, sencha tea, on sensitive and multidrug-resistant leukemia and a panel of nine multiple myelomas (MM) cell lines. We found that sencha extracts induced cytotoxicity in leukemic cells and MM cells to different extents, yet its effect on normal cells was limited. Furthermore, sencha extracts caused G2/M and G0/G1 phase arrest during cell cycle progression in CCRF/CEM and KMS-12-BM cells, respectively. Specifically,…
Signalling strength determines proapoptotic functions of STING
2017
Mammalian cells use cytosolic nucleic acid receptors to detect pathogens and other stress signals. In innate immune cells the presence of cytosolic DNA is sensed by the cGAS–STING signalling pathway, which initiates a gene expression programme linked to cellular activation and cytokine production. Whether the outcome of the STING response varies between distinct cell types remains largely unknown. Here we show that T cells exhibit an intensified STING response, which leads to the expression of a distinct set of genes and results in the induction of apoptosis. Of note, this proapoptotic STING response is still functional in cancerous T cells and delivery of small molecule STING agonists prev…
Enniatin B induces expression changes in the electron transport chain pathway related genes in lymphoblastic T-cell line
2018
Abstract Enniatin B is a ionophoric and lipophilic mycotoxin which reaches the bloodstream and has the ability to penetrate into cellular membranes. The purpose of this study was to reveal changes in the gene expression profile caused by enniatin B in human Jurkat lymphoblastic T-cells after 24 h of exposure at 1.5, 3 and 5 μM by next generation sequencing. It was found that up to 27% of human genome expression levels were significantly altered (5750 genes for both down-regulation and up-regulation). In the three enniatin B concentrations studied 245 differentially expressed genes were found to be overlapped, 83 were down and 162 up-regulated. ConsensusPathDB analysis of over-representation…
A rare association of chronic lymphocytic leukemia with c-ANCA-positive Wegener’s granulomatosis: a case report
2016
Background Wegener’s granulomatosis is a systemic vasculitis of the small- and medium-sized vessels, produced by the action of ANCA, which involves the respiratory tract, kidneys, and eyes, with a potential for lethal evolution in the first year after diagnosis. Its association with chronic lymphocytic leukemia is rarely described in the literature, and it may be difficult to diagnose and to treat this association. Case presentation We present the case of a 73-year-old Caucasian patient, a rare case in which Wegener’s granulomatosis is associated in a patient with chronic lymphocytic leukemia, who is admitted in the Infectious Disease Department for fever, diplopia, headache, purulent and h…
Natural Compounds: Molecular Weapons against Leukemia’s
2017
Nowadays cancer is one of the main reasons of death all over the world and it is estimated that deaths caused by cancer will grow dramatically in the next decades. Even if chemotherapy is the election therapy for solid tumors, as well as leukemias and lymphomas, cancer treatments are in continuous evolution trying to solve the problem of resistance mainly due to low accumulation of the drug in tumor cells (MDR). Natural compounds represent a valid alternative to treat several disease and recently the scientific community focus on these natural compounds and plant metabolites with therapeutic activities and low toxicities compared with synthetic ones. A combination therapy, that join convent…