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https://www.readbyqxmd.com/read/28917668/gut-microbe-mediated-suppression-of-inflammation-associated-colon-carcinogenesis-by-luminal-histamine-production
#1
Chunxu Gao, Bhanu Priya Ganesh, Zhongcheng Shi, Rajesh Rasik Shah, Robert Fultz, Angela Major, Susan Venable, Monica Lugo, Kathleen Hoch, Xiaowei Chen, Anthony Haag, Timothy C Wang, James Versalovic
Microbiome-mediated suppression of carcinogenesis may open new avenues for identification of therapeutic targets and prevention strategies in oncology. Histidine decarboxylase (HDC) deficiency has been shown to promote inflammation-associated colorectal cancer by accumulation of CD11b(+)Gr-1(+) immature myeloid cells, indicating a potential antitumorigenic effect of histamine. Here, we demonstrate that administration of hdc(+)Lactobacillus reuteri in the gut resulted in luminal hdc gene expression and histamine production in the intestines of Hdc(-/-) mice...
September 6, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28804122/shp2-is-required-for-bcr-abl1-induced-hematologic-neoplasia
#2
S Gu, A Sayad, G Chan, W Yang, Z Lu, C Virtanen, R A Van Etten, B G Neel
BCR-ABL1-targeting tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome-positive (Ph(+)) hematologic neoplasms. Nevertheless, acquired TKI resistance remains a major problem in chronic myeloid leukemia (CML), and TKIs are less effective against Ph(+) B-cell acute lymphoblastic leukemia (B-ALL). GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediate leukemogenesis. Using a genetic loss-of-function approach and bone marrow transplantation models for CML and BCR-ABL1(+) B-ALL, we show that SHP2 is required for BCR-ABL1-evoked myeloid and lymphoid neoplasia...
August 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28765154/gemcitabine-induced-timp1-attenuates-therapy-response-and-promotes-tumor-growth-and-liver-metastasis-in-pancreatic-cancer
#3
Zenobia D'Costa, Keaton Jones, Abul Azad, Ruud van Stiphout, Su Y Lim, Ana L Gomes, Paul Kinchesh, Sean C Smart, W Gillies McKenna, Francesca M Buffa, Owen J Sansom, Ruth J Muschel, Eric O'Neill, Emmanouil Fokas
Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC), but patients often respond poorly to this agent. Molecular markers downstream of gemcitabine treatment in pre-clinical models may provide an insight into resistance mechanisms. Using cytokine arrays, we identified potential secretory biomarkers of gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC. We verified the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP1) in primary pancreatic tumors and metastases using both in vitro techniques and animal models...
August 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28725653/calr-positive-myeloproliferative-disorder-in-a-patient-with-ph-positive-chronic-myeloid-leukemia-in-durable-treatment-free-remission-a-case-report
#4
Irene Dogliotti, Carmen Fava, Anna Serra, Enrico Gottardi, Filomena Daraio, Francesca Carnuccio, Emilia Giugliano, Monica Bocchia, Giuseppe Saglio, Giovanna Rege-Cambrin
Current diagnostic criteria for Philadelphia-negative myeloproliferative neoplasia (MPN) have been redefined by the discovery of Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL) and calreticulin (CALR) genetic alterations. Only few cases of coexistence of CALR-mutated MPN and Philadelphia-positive chronic myeloid leukemia (CML) have been described so far. Here we report the case of a patient with CML diagnosed in 2001, treated with imatinib and pegylated interferon (IFN) frontline. She reached complete molecular remission (CMR) and discontinued imatinib, maintaining treatment free remission...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28680586/pulmonary-extra-medullary-hematopoiesis-and-pulmonary-hypertension-from-underlying-polycythemia-vera-a-case-series
#5
Inderjit Singh, Geoffrey Mikita, Daniel Green, Cristobal Risquez, Abraham Sanders
Myeloproliferative neoplasia (MPN)-associated pulmonary hypertension (PH) is included in group five of the most recent clinical classification of PH.(1) The MPNs are a heterogeneous group of disorders that includes disorders with primary expression of a myeloid phenotype and disorders characterized by expression of the Janus Kinase 2 (JAK2) mutation, p.V617F. The latter includes essential thrombocytosis, polycythemia vera, and idiopathic myelofibrosis.(2) Pulmonary extra-medullary hematopoiesis (EMH) refers to the presence of hematopoietic precursor cells in the lung...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28643018/heterogeneity-of-gata2-related-myeloid-neoplasms
#6
REVIEW
Shinsuke Hirabayashi, Marcin W Wlodarski, Emilia Kozyra, Charlotte M Niemeyer
The GATA2 gene codes for a master hematopoietic transcription factor that is essential for the proliferation and maintenance of hematopoietic stem and progenitor cells. Heterozygous germline mutations in GATA2 have been initially associated with several clinical entities that are now collectively defined as GATA2 deficiency. Despite pleiotropic clinical manifestations, the high propensity for the development of myelodysplastic syndromes (MDS) constitutes the most common clinical denominator of this major MDS predisposition syndrome...
August 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28637623/ddx41-related-myeloid-neoplasia
#7
REVIEW
Jaroslaw P Maciejewski, Richard A Padgett, Anna L Brown, Carsten Müller-Tidow
While early presentation of familial leukemia syndromes is typical, long disease anticipation may mask cases of familial traits in seemingly spontaneous disease. Germline mutations in DDX41 gene have been discovered in several leukemia families, as well as in mostly adult patients with seemingly spontaneous disease but having strong family histories of myeloid neoplasia. As with other familial genes, DDX41 mutation carriers can develop neoplasia through acquisition of another somatic mutation, thereby affecting both DDX41 alleles...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637621/gata2-deficiency-and-related-myeloid-neoplasms
#8
Marcin W Wlodarski, Matthew Collin, Marshall S Horwitz
The GATA2 gene codes for a hematopoietic transcription factor that through its two zinc fingers (ZF) can occupy GATA-DNA motifs in a countless number of genes. It is crucial for the proliferation and maintenance of hematopoietic stem cells. During the past 5 years, germline heterozygous mutations in GATA2 were reported in several hundred patients with various phenotypes ranging from mild cytopenia to severe immunodeficiency involving B cells, natural killer cells, CD4(+) cells, monocytes and dendritic cells (MonoMAC/DCML), and myeloid neoplasia...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637618/recognition-of-familial-myeloid-neoplasia-in-adults
#9
REVIEW
Anna L Brown, Jane E Churpek, Luca Malcovati, Hartmut Döhner, Lucy A Godley
Hereditary hematologic malignancy (HM) syndromes are increasingly recognized as causative of adult hematopoietic cancers, and the advent of next-generation sequencing has accelerated the discovery of new syndromes based on dense clustering of these diseases in particular families. Updated classifications schemes for myeloid malignancies will now include recommendations for taking a family history on all patients diagnosed with hematopoietic malignancies and for genetic counseling and testing of appropriate individuals and families...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637617/introduction-genetic-syndromes-predisposing-to-myeloid-neoplasia
#10
EDITORIAL
Marcin W Wlodarski, Charlotte M Niemeyer
No abstract text is available yet for this article.
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28626217/irf8-regulates-the-progression-of-myeloproliferative-neoplasm-mpn-like-syndrome-via-mertk-signaling-in-zebrafish
#11
F Zhao, Y Shi, Y Huang, Y Zhan, L Zhou, Y Li, Y Wan, H Li, H Huang, H Ruan, L Luo, L Li
Interferon regulatory factor (IRF)-8 is a critical transcription factor involved in the pathogenesis of myeloid neoplasia. However, the underlying mechanisms in vivo are not well known. Investigation of irf8 mutant zebrafish in this study indicated that Irf8 is evolutionarily conserved as an essential neoplastic suppressor through tight control of the proliferation and longevity of myeloid cells. Surviving irf8 mutants quickly developed a myeloproliferative neoplasm (MPN)-like disease with enhanced output of the myeloid precursors, which recurred after transplantation...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28576876/targeting-chronic-myeloid-leukemia-stem-cells-with-the-hypoxia-inducible-factor-inhibitor-acriflavine
#12
Giulia Cheloni, Michele Tanturli, Ignazia Tusa, Ngoc Ho DeSouza, Yi Shan, Antonella Gozzini, Fréderic Mazurier, Elisabetta Rovida, Shaoguang Li, Persio Dello Sbarba
Chronic myeloid leukemia (CML) is a hematopoietic stem cell (HSC)-driven neoplasia characterized by expression of the constitutively active tyrosine kinase BCR/Abl. CML therapy based on tyrosine kinase inhibitors (TKIs) is highly effective in inducing remission but not in targeting leukemia stem cells (LSCs), which sustain minimal residual disease and are responsible for CML relapse following discontinuation of treatment. The identification of molecules capable of targeting LSCs appears therefore of primary importance to aim at CML eradication...
August 3, 2017: Blood
https://www.readbyqxmd.com/read/28548080/discovery-of-first-in-class-reversible-dual-small-molecule-inhibitors-against-g9a-and-dnmts-in-hematological-malignancies
#13
Edurne San José-Enériz, Xabier Agirre, Obdulia Rabal, Amaia Vilas-Zornoza, Juan A Sanchez-Arias, Estibaliz Miranda, Ana Ugarte, Sergio Roa, Bruno Paiva, Ander Estella-Hermoso de Mendoza, Rosa María Alvarez, Noelia Casares, Victor Segura, José I Martín-Subero, François-Xavier Ogi, Pierre Soule, Clara M Santiveri, Ramón Campos-Olivas, Giancarlo Castellano, Maite Garcia Fernandez de Barrena, Juan Roberto Rodriguez-Madoz, Maria José García-Barchino, Juan Jose Lasarte, Matias A Avila, Jose Angel Martinez-Climent, Julen Oyarzabal, Felipe Prosper
The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favoured development of epigenetic drugs. In this study, we design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of haematological neoplasia (acute myeloid leukaemia-AML, acute lymphoblastic leukaemia-ALL and diffuse large B-cell lymphoma-DLBCL) with the lead compound CM-272, inhibits cell proliferation and promotes apoptosis, inducing interferon-stimulated genes and immunogenic cell death...
May 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28527473/presence-of-new-mutations-in-the-tp53-gene-in-patients-with-low-risk-myelodysplastic-syndrome-two-case-reports
#14
Fernando Barroso Duarte, Romélia Pinheiro Gonçalves Lemes, Talyta Ellen de Jesus Dos Santos, Maritza Cavalcante Barbosa, João Paulo Leitão de Vasconcelos, Francisco Dário Rocha-Filho, Ilana Zalcberg, Diego Coutinho, Monalisa Feliciano Figueiredo, Luciana Barros Carlos, Paulo Roberto Leitão de Vasconcelos
BACKGROUND: Myelodysplastic syndromes are heterogeneous disorders. Patients with myelodysplastic syndrome disease often have ineffective hematopoiesis, cytopenias, blood cell dysplasia in one or more cell types, and are at high risk for developing acute myeloid leukemia. In myelodysplastic syndrome, mutations of TP53 gene are usually associated with complex karyotype and confer a worse prognosis. In the present study, two mutations in this gene are presented and discussed with the clinical evolution of the patients...
May 21, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28512628/dysplasia-of-granulocytes-in-a-patient-with-hpv-disease-recurrent-infections-and-b-lymphopenia-a-novel-variant-of-whim-syndrome
#15
Giusella M F Moscato, Erica Giacobbi, Lucia Anemona, Silvia Di Cesare, Gigliola Di Matteo, Massimo Andreoni, Alessandro Mauriello, Viviana Moschese
WHIM syndrome is a condition in which affected persons have chronic peripheral neutropenia, lymphopenia, abnormal susceptibility to human papilloma virus infection, and myelokathexis. Myelokathexis refers to the retention of mature neutrophils in the bone marrow (BM), which accounts for degenerative changes and hypersegmentation. Most patients present heterozygous autosomal dominant mutations of the gene encoding CXCR4. Consequently, aberrant CXCL12/CXCR4 signaling impairs the receptor downregulation causing hyperactivation (gain-of-function) that affects BM homing for myelopoiesis and lymphopoiesis and the release of neutrophils in the bloodstream...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28504718/a-tumor-suppressor-role-for-c-ebp%C3%AE-in-solid-tumors-more-than-fat-and-blood
#16
REVIEW
A R Lourenço, P J Coffer
The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) plays a critical role during embryogenesis and is thereafter required for homeostatic glucose metabolism, adipogenesis and myeloid development. Its ability to regulate the expression of lineage-specific genes and induce growth arrest contributes to the terminal differentiation of several cell types, including hepatocytes, adipocytes and granulocytes. CEBPA loss of-function mutations contribute to the development of ~10% of acute myeloid leukemia (AML), stablishing a tumor suppressor role for C/EBPα...
September 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28461756/monosomal-karyotype-in-myeloid-neoplasias-a-literature-review
#17
REVIEW
Luisa Anelli, Crescenza Pasciolla, Antonella Zagaria, Giorgina Specchia, Francesco Albano
In 2008, the concept of the monosomal karyotype (MK) in adult acute myeloid leukemia (AML) patients was introduced, defined by the presence of a chromosomal aberration pattern characterized by the presence of at least two autosomal monosomies or of one monosomy plus one or more structural aberrations (not including loss of a chromosome). We present a systematic review of the literature about the influence of the MK on the outcome of patients affected by myeloid malignancies (AML, myelodysplastic syndromes, and primary myelofibrosis)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28420723/mitochondrial-bax-determines-the-predisposition-to-apoptosis-in-human-aml
#18
Frank Reichenbach, Cornelius Wiedenmann, Enrico Schalk, Diana Becker, Kathrin Funk, Peter Scholz-Kreisel, Franziska Todt, Denise Wolleschak, Konstanze Döhner, Jens U Marquardt, Florian Heidel, Frank Edlich
Purpose: Cell-to-cell variability in apoptosis signaling contributes to heterogenic responses to cytotoxic stress in clinically heterogeneous neoplasia, such as acute myeloid leukemia (AML). The BCL-2 proteins BAX and BAK can commit mammalian cells to apoptosis and are inhibited by retrotranslocation from the mitochondria into the cytosol. The subcellular localization of BAX and BAK could determine the cellular predisposition to apoptotic death.Experimental Design: The relative localization of BAX and BAK was determined by fractionation of AML cell lines and patient samples of a test cohort and a validation cohort...
August 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28415666/azacitidine-or-intensive-chemotherapy-for-older-patients-with-secondary-or-therapy-related-acute-myeloid-leukemia
#19
Pierre-Yves Dumas, Sarah Bertoli, Emilie Bérard, Clémence Médiavilla, Edwige Yon, Suzanne Tavitian, Thibaut Leguay, Françoise Huguet, Edouard Forcade, Noël Milpied, Audrey Sarry, Mathieu Sauvezie, Pierre Bories, Arnaud Pigneux, Christian Récher
The treatment of older patients with acute myeloid leukemia that is secondary to previous myelodysplastic syndrome, myeloproliferative neoplasm, or prior cytotoxic exposure remains unsatisfactory. We compared 92 and 107 patients treated, respectively, with intensive chemotherapy or azacitidine within two centres. Diagnoses were 37.5% post-myelodysplastic syndrome, 17.4% post-myeloproliferative neoplasia, and 45.1% therapy-related acute myeloid leukemia. Patients treated by chemotherapy had less adverse cytogenetics, higher white blood-cell counts, and were younger: the latter two being independent factors entered into the multivariate analyses...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28375825/spontaneous-neoplasms-in-captive-virginia-opossums-didelphis-virginiana-a-retrospective-case-series-1989-2014-and-review-of-the-literature
#20
Jenny P Pope, Robert L Donnell
This retrospective project summarizes the types of neoplasms identified in Virginia opossums ( Didelphis virginiana) presented to the University of Tennessee, College of Veterinary Medicine (UTCVM) postmortem service in 1989-2014 and serves as a review of the literature. Of the 85 Virginia opossums identified from the UTCVM case database, there were 17 diagnoses of neoplasia from 12 cases (14%). These cases included 8 females, 2 males, and 2 neutered males. All opossums with known ages (11 of 12) were >2 y old...
May 2017: Journal of Veterinary Diagnostic Investigation
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