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https://www.readbyqxmd.com/read/28727840/dual-inhibition-of-fes-and-flt3-tyrosine-kinases-potently-inhibits-flt3-itd-aml-cell-growth
#1
Mark C Weir, Sabine Hellwig, Li Tan, Yao Liu, Nathanael S Gray, Thomas E Smithgall
Acute myelogenous leukemia (AML) is often associated with activating mutations in the receptor tyrosine kinase, Flt3, including internal tandem duplications (ITDs) within the regulatory juxtamembrane region. Previous studies have linked Flt3-ITD to the activation of the Fes protein tyrosine kinase in AML, and RNAi-knockdown studies suggest that Fes may be required for Flt3 function. In this study, we tested Fes inhibitors from three different chemical classes for their growth-suppressive activity against Flt3-ITD+ myeloid leukemia cell lines (MV4-11, MOLM-13 and MOLM-14) vs...
2017: PloS One
https://www.readbyqxmd.com/read/28727820/active-hexose-correlated-compound-enhances-extrinsic-pathway-mediated-apoptosis-of-acute-myeloid-leukemic-cells
#2
Kavin Fatehchand, Ramasamy Santhanam, Brenda Shen, Ericka L Erickson, Shalini Gautam, Saranya Elavazhagan, Xiaokui Mo, Tesfaye Belay, Susheela Tridandapani, Jonathan P Butchar
Active Hexose Correlated Compound (AHCC) has been shown to have many immunostimulatory and anti-cancer activities in mice and in humans. As a natural product, AHCC has potential to create safer adjuvant therapies in cancer patients. Acute Myeloid Leukemia (AML) is the least curable and second-most common leukemia in adults. AML is especially terminal to those over 60 years old, where median survival is only 5 to 10 months, due to inability to receive intensive chemotherapy. Hence, the purpose of this study was to investigate the effects of AHCC on AML cells both in vitro and in vivo...
2017: PloS One
https://www.readbyqxmd.com/read/28726739/5-aza-2-2-difluroro-deoxycytidine-nuc013-a-novel-nucleoside-dna-methyl-transferase-inhibitor-and-ribonucleotide-reductase-inhibitor-for-the-treatment-of-cancer
#3
Richard Daifuku, Zhenbo Hu, Yogen Saunthararajah
Tumor suppressor genes can be silenced genetically as well as epigenetically. One approach to reversing epigenetic suppression of tumor suppressor genes is to inhibit DNA methyl transferase. 5-aza-2',2'-diflurorodeoxycytidine (NUC013) is a novel DNA methyl transferase and ribonucleotide reductase inhibitor that is a more potent inhibitor of growth than decitabine in the NCI 60 cancer cell line panel. NUC013 is more active than decitabine against p53-null/mutant cancer cell lines (p = 0.027) but is even more so against p53 wild-type (WT) cell lines (p = 0...
July 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28726646/the-prognostic-significance-of-combaind-expression-of-zap-70-and-cd38-in-chronic-lymphocytic-leukemia
#4
T Kirtava, T Vatsadze, E Azrmaiparashili, D Ghirdaladze
Our aim was to assess the inter links of the markers CD38 and ZAP-70 based on our materials, the attitude according to the disease stage, and to document which of them had leading meaning for prognosis and treatmend of the disease. In our study we have used flow cytometry for detection CD38 and ZAP-70+ markers expression. (58 patients to assessments their prognostic value in сhronic lymphocytic leukemia (CLL), Correlation to Rai stages and relationships between this markers and outcome of therapy). We divided all patients in two groups based on level of ZAP-70+ cell and CD38+cells,(I group-patients) ZAP-70+ cells <20% CD38+<30% and ZAP-70+ cells >20% and CD38>30%,(II group) becaus our in investigation shows, that ZAP -70+ is very importance independent prognoctic marker as why in ZAP-70+ cases when its number was <20%, patients had favorable prognosis - the big part of them (13(40...
June 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28726645/chronic-myeloid-leukemia-expected-relapse-s-clinical-laboratory-indexes
#5
T Kirtava, D Ghirdaladze, T Vatsadze
Today Chronic Myeloid Leukemia (CML) relapse's final assessment and monitoring in the whole world is implemented by BCR-ABL gene quantitative detection - during the polymerase chain reaction (by PSR means). Implementation of this monitoring materially and technically is not often available and remission during years is being assessed using monthly clinical-laboratory data. Proceeding from this, the goal of our work was to find the clinical-laboratory features, indicating the expected relapse and require the urgent molecular research carry out...
June 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28726435/-acute-lymphoblastic-leukemia-of-adults-a-case-of-prolonged-hip-pain-diagnostics-with-a-surprising-conclusion-case-report
#6
Štěpán Hrabovský, František Folber, Barbora Jurová, Zdeněk Řehák, Michael Doubek
Though acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood age, it is a rare diagnosis in adults. This disease often manifests with common and nonspecific symptoms, so it can easily escape an early diagnostics without a proper blood count examination. We present a case of an adult ALL patient suffering only from severe hips and thighs pain, without any significant blood count abnormities leading to the diagnostics. In the second part of the article, we summarize current highlights regarding this disease...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/28725969/mastocytosis-from-a-molecular-point-of-view
#7
REVIEW
Daniel Elieh Ali Komi, Todd Rambasek, Stefan Wöhrl
Mast cells (MCs) are physiologically activated by binding of stem cell factor (SCF) to the extracellular domains of the Kit receptor. This binding increases the proliferation and prolongs the survival of normal mature MCs, as well as intensifies the release of mediators. In mastocytosis, somatic mutations of the coding Kit gene cause autocrine dysregulation and lead to constitutive KIT activation even in the absence of its ligand SCF. Clinical symptoms are caused by MC-mediator release and/or infiltration of MCs into tissues...
July 19, 2017: Clinical Reviews in Allergy & Immunology
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
#8
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/28724453/decrease-in-vancomycin-resistant-enterococcus-colonization-after-extensive-renovation-of-a-unit-dedicated-to-the-treatment-of-hematologic-malignancies-and-hematopoietic-stem-cell-transplantation
#9
Clyde D Ford, Michaela A Gazdik Stofer, Jana Coombs, Bert K Lopansri, Brandon J Webb, Gabriela Motyckova, Finn Bo Petersen
OBJECTIVE While a direct relation between hospital construction and concomitant infection rates has been clearly established, few data are available regarding the environmental decontamination effects of renovation in which surfaces are replaced and regarding subsequent infection incidence. DESIGN Retrospective clinical study with vancomycin-resistant Enterococcus (VRE) molecular strain typing and environmental cultures. SETTING A regional referral center for acute leukemia and hematopoietic stem-cell transplantation...
July 20, 2017: Infection Control and Hospital Epidemiology
https://www.readbyqxmd.com/read/28724426/high-expression-of-ets2-predicts-poor-prognosis-in-acute-myeloid-leukemia-and-may-guide-treatment-decisions
#10
Lin Fu, Huaping Fu, Qingyun Wu, Yifan Pang, Keman Xu, Lei Zhou, Jianlin Qiao, Xiaoyan Ke, Kailin Xu, Jinlong Shi
BACKGROUND: ETS2 is a downstream effector of the RAS/RAF/ERK pathway, which plays a critical role in the development of malignant tumor. However, the clinical impact of ETS2 expression in AML remains unknown. METHODS: In this study, we evaluated the prognostic significance of ETS2 expression using two relatively large cohorts of AML patients. RESULTS: In the first cohort, compared to low expression of ETS2 (ETS2 (low)), high expression of ETS2 (ETS2 (high)) showed significant shorter OS, EFS and RFS in the current treatments including the allogeneic HCT group (n = 72) and the chemotherapy group (n = 100)...
July 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28723754/an-economic-analysis-of-high-dose-imatinib-dasatinib-and-nilotinib-for-imatinib-resistant-chronic-phase-chronic-myeloid-leukemia-in-china-a-cheers-compliant-article
#11
Bin Wu, Maobai Liu, Te Li, Houwen Lin, Hua Zhong
BACKGROUND: The aim of the study was to test the cost-effectiveness of dasatinib compared to high-dose imatinib and nilotinib in Chinese patients who were diagnosed with imatinib-resistant chronic myeloid leukemia in the chronic phase (CML-CP). METHODS: A Markov model combined with clinical effectiveness, utility, and cost data was used. The sensitivity analyses were conducted to determine the robustness of the model outcomes. The impact of patient assistance programs (PAPs) was assessed...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28723562/integrative-genomics-identifies-the-molecular-basis-of-resistance-to-azacitidine-therapy-in-myelodysplastic-syndromes
#12
Ashwin Unnikrishnan, Elli Papaemmanuil, Dominik Beck, Nandan P Deshpande, Arjun Verma, Ashu Kumari, Petter S Woll, Laura A Richards, Kathy Knezevic, Vashe Chandrakanthan, Julie A I Thoms, Melinda L Tursky, Yizhou Huang, Zara Ali, Jake Olivier, Sally Galbraith, Austin G Kulasekararaj, Magnus Tobiasson, Mohsen Karimi, Andrea Pellagatti, Susan R Wilson, Robert Lindeman, Boris Young, Raj Ramakrishna, Christopher Arthur, Richard Stark, Philip Crispin, Jennifer Curnow, Pauline Warburton, Fernando Roncolato, Jacqueline Boultwood, Kevin Lynch, Sten Eirik W Jacobsen, Ghulam J Mufti, Eva Hellstrom-Lindberg, Marc R Wilkins, Karen L MacKenzie, Jason W H Wong, Peter J Campbell, John E Pimanda
Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis and progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only ∼50% of patients respond. A response only manifests after many months of treatment and is transient. The reasons underlying AZA resistance are unknown, and few alternatives exist for non-responders. Here, we show that AZA responders have more hematopoietic progenitor cells (HPCs) in the cell cycle...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28722694/early-life-vincristine-exposure-evokes-mechanical-pain-hypersensitivity-in-the-developing-rat
#13
Katie A Schappacher, Lauren Styczynski, Mark L Baccei
Vincristine (VNC) is commonly used to treat pediatric cancers, including the most prevalent childhood malignancy, acute lymphoblastic leukemia. Although clinical evidence suggests that VNC causes peripheral neuropathy in children, the degree to which pediatric chemotherapeutic regimens influence pain sensitivity throughout life remains unclear, in part because of the lack of an established animal model of chemotherapy-induced neuropathic pain during early life. Therefore, this study investigated the effects of VNC exposure between postnatal days (P) 11 and 21 on mechanical and thermal pain sensitivity in the developing rat...
May 30, 2017: Pain
https://www.readbyqxmd.com/read/28722477/advances-toward-lsd1-inhibitors-for-cancer-therapy
#14
Xiaoli Fu, Peng Zhang, Bin Yu
LSD1 has become an important biologically validated epigenetic target for cancer therapy since its identification in 2004. LSD1 mediates many cellular signaling pathways and is involved in the initiation and development of cancers. Aberrant overexpression of LSD1 has been observed in different types of cancers, and inactivation by small molecules suppresses cancer cell differentiation, proliferation, invasion and migration. To date, a large number of LSD1 inhibitors have been reported, RG6016, GSK-2879552, INCB059872, IMG-7289 and CC-90011 are currently undergoing clinical assessment for the treatment of acute myeloid leukemia, small-cell lung cancer, etc...
July 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28721806/l-tetrahydropalmatine-induces-apoptosis-in-eu-4-leukemia-cells-by-down-regulating-x-linked-inhibitor-of-apoptosis-protein-and-increases-the-sensitivity-towards-doxorubicin
#15
S Li, D Chen, Renzhi Pei, Y Lu, P Zhang, J Ma, X Liu, X Du, K Sha, L Chen, J Cao, X Zhuang, J Wu, L Li, Z Fan, P Ye, S Tang, B Zhang, X Shi, K Li
BACKGROUND: L-Tetrahydropalmatine (L-THP) is a tetra-hydro protoberberine isoquinoline alkaloid. The phyto-compounds bearing isoquinoline alkaloids have been reported to show a potential effect against a number of human cancers cell lines including leukemia. We hypothesized that L-THP, being an isoquinoline alkaloid, could be a potential molecule against acute lymphoblastic leukemia (ALL), in this study, we evaluate L-THP against p53 deficient leukemia EU-4 cell lines in vitro. METHODS: For the study, p53 null leukemia EU-4 cells were used and treated with L-THP...
July 18, 2017: Current Molecular Medicine
https://www.readbyqxmd.com/read/28721645/is-cancer-information-exchanged-on-social-media-scientifically-accurate
#16
Elizabeth A Gage-Bouchard, Susan LaValley, Molli Warunek, Lynda Kwon Beaupin, Michelle Mollica
Cancer patients and their caregivers are increasingly using social media as a platform to share cancer experiences, connect with support, and exchange cancer-related information. Yet, little is known about the nature and scientific accuracy of cancer-related information exchanged on social media. We conducted a content analysis of 12 months of data from 18 publically available Facebook Pages hosted by parents of children with acute lymphoblastic leukemia (N = 15,852 posts) and extracted all exchanges of medically-oriented cancer information...
July 19, 2017: Journal of Cancer Education: the Official Journal of the American Association for Cancer Education
https://www.readbyqxmd.com/read/28721499/treg-protected-donor-lymphocyte-infusions-a-new-tool-to-address-the-graft-versus-leukemia-effect-in-the-absence-of-graft-versus-host-disease-in-patients-relapsed-after-hsct
#17
Mauro Di Ianni, Paola Olioso, Raffaella Giancola, Stella Santarone, Annalisa Natale, Gabriele Papalinetti, Ida Villanova, Stefano Baldoni, Ambra Di Tommaso, Tiziana Bonfini, Patrizia Accorsi, Paolo Di Bartolomeo
In high-risk acute leukemia patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), adoptive immunotherapy with T regulatory cells (Tregs) and T conventional cells (Tcons) prevented acute and chronic graft-versus-host disease (GvHD), favored post-transplant immunological reconstitution and was associated with a powerful graft-versus-leukemia (GvL) effect. With a particularly innovative approach, we developed a treatment with a Treg-protected donor lymphocyte infusion (DLI) for patients with early relapse after HSCT and we report here the results obtained in the first patient with APL (M3v) relapsed after a second matched allogeneic HSCT (15% blasts and 75% of donor cells in bone marrow)...
July 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28721449/role-of-regulatory-t-cells-in-acute-myeloid-leukemia-patients-undergoing-relapse-preventive-immunotherapy
#18
Frida Ewald Sander, Malin Nilsson, Anna Rydström, Johan Aurelius, Rebecca E Riise, Charlotta Movitz, Elin Bernson, Roberta Kiffin, Anders Ståhlberg, Mats Brune, Robin Foà, Kristoffer Hellstrand, Fredrik B Thorén, Anna Martner
Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3(+)CD25(high)CD4(+) Tregs during immunotherapy and to determine the potential impact of Tregs on relapse risk and survival...
July 18, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28721069/the-effect-of-circulating-mir-223-on-surveillance-of-different-cancers-a-meta-analysis
#19
Yunfeng Zhang, Jinbo Lin, Wenjie Huang, Yong Cao, Yi Liu, Tieqiang Wang, Weiyi Zhong, Dongli Wang, Rongrong Mao, Xiaoliang Chen
PURPOSE: Abnormal expression of miR-223 in cancerous tissue has confirmed it as an important player in tumorigenesis of cancers, such as hepatocellular carcinoma, colorectal carcinoma, osteosarcoma, gastric cancer, and chronic lymphocytic leukemia. The present meta-analysis aimed to explore the association between circulating miR-223 and prognosis of cancers. METHODS: The studies were accessed by an electronic search of multiple databases. RevMan5.3 and STATA14...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28721056/onset-of-chronic-myeloid-leukemia-with-complex-karyotype-in-a-pregnant-patient-case-report-and-revision-of-literature
#20
Nicola Sgherza, Elisabetta Abruzzese, Gianni Perla, Maria Marta Minervini, Vincenzo Chiello, Natale Sciannamè, Nicola Cascavilla
Approximately 10%-12% of patients in chronic-phase chronic myeloid leukemia (CP-CML) have additional chromosomal aberrations at diagnosis; moreover, CML occurs in up to 10% of pregnancy-associated leukemias, with an annual incidence of 1 per 100,000 pregnancies. In this report we describe the case of a 36-year-old female with CP-CML diagnosed in the 18th week of pregnancy and with a new complex variant translocation t(4;9;22;21)(q24;q34;q11;q22) and an additional chromosomal aberration t(1;20)(p36;p11). In consideration of her pregnancy, the patient strictly monitored her blood cell count without any specific treatment...
2017: Therapeutics and Clinical Risk Management
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