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https://www.readbyqxmd.com/read/29342447/design-synthesis-and-anticancer-studies-of-novel-aminobenzazolyl-pyrimidines-as-tyrosine-kinase-inhibitors
#1
Rupesh Chikhale, Sonali Thorat, Rajan Kumar Choudhary, Nikhil Gadewal, Pramod Khedekar
Abnormal signalling from the Protein tyrosine kinases (PTKs) like receptor tyrosine kinases and intracellular tyrosine kinases can lead to diseases such as cancer especially non-small cell lung cancer, chronic myeloid leukaemia and gastrointestinal stromal tumours. Various Protein tyrosine kinase inhibitors are available but face poor bioavailability, severe toxicities and recent cases of drug-resistant cancers prompts for development of better drug molecules. In this study we report the design and development of a novel Protein Tyrosine Kinase (PTK) inhibitor on the basis of pharmacophore modelling...
January 4, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29342136/clonal-evolution-mechanisms-in-nt5c2-mutant-relapsed-acute-lymphoblastic-leukaemia
#2
Gannie Tzoneva, Chelsea L Dieck, Koichi Oshima, Alberto Ambesi-Impiombato, Marta Sánchez-Martín, Chioma J Madubata, Hossein Khiabanian, Jiangyan Yu, Esme Waanders, Ilaria Iacobucci, Maria Luisa Sulis, Motohiro Kato, Katsuyoshi Koh, Maddalena Paganin, Giuseppe Basso, Julie M Gastier-Foster, Mignon L Loh, Renate Kirschner-Schwabe, Charles G Mullighan, Raul Rabadan, Adolfo A Ferrando
Relapsed acute lymphoblastic leukaemia (ALL) is associated with resistance to chemotherapy and poor prognosis. Gain-of-function mutations in the 5'-nucleotidase, cytosolic II (NT5C2) gene induce resistance to 6-mercaptopurine and are selectively present in relapsed ALL. Yet, the mechanisms involved in NT5C2 mutation-driven clonal evolution during the initiation of leukaemia, disease progression and relapse remain unknown. Here we use a conditional-and-inducible leukaemia model to demonstrate that expression of NT5C2(R367Q), a highly prevalent relapsed-ALL NT5C2 mutation, induces resistance to chemotherapy with 6-mercaptopurine at the cost of impaired leukaemia cell growth and leukaemia-initiating cell activity...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29342133/a-myc-enhancer-cluster-regulates-normal-and-leukaemic-haematopoietic-stem-cell-hierarchies
#3
Carsten Bahr, Lisa von Paleske, Veli V Uslu, Silvia Remeseiro, Naoya Takayama, Stanley W Ng, Alex Murison, Katja Langenfeld, Massimo Petretich, Roberta Scognamiglio, Petra Zeisberger, Amelie S Benk, Ido Amit, Peter W Zandstra, Mathieu Lupien, John E Dick, Andreas Trumpp, François Spitz
The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies. Here we show that an evolutionarily conserved region located 1.7 megabases downstream of the Myc gene that has previously been labelled as a 'super-enhancer' is essential for the regulation of Myc expression levels in both normal haematopoietic and leukaemic stem cell hierarchies in mice and humans. Deletion of this region in mice leads to a complete loss of Myc expression in haematopoietic stem cells and progenitors...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29341317/apoptosis-induction-in-k562-human-myelogenous-leukaemia-cells-is-connected-to-the-modulation-of-wnt-%C3%AE-catenin-signalling-by-bhx-a-novel-pyrazoline-derivative
#4
Hanmei Bao, Qing Zhang, Yibo Du, Cai Zhang, Hui Xu, Zhongling Zhu, Zhao Yan
OBJECTIVES: The goal of this study was to explore the effects of BHX on human chronic myeloid leukaemia (CML) cells and to elucidate the underlying molecular mechanism. MATERIALS AND METHODS: CML cell line K562 cells were treated with BHX. The effects of BHX on cell proliferation, apoptosis and cell cycle were detected. Subsequently, the caspase, ATP activity, Ca2+ , ROS and mitochondrial membrane potential (MMP) levels treated with various concentrations of BHX were analysed...
January 16, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29341283/mogamulizumab-induced-phosensitivity-in-patients-with-mycosis-fungoides-and-other-t-cell-neoplasms
#5
Y Masuda, K Tatsuno, S Kitano, H Miyazawa, J Ishibe, M Aoshima, T Shimauchi, T Fujiyama, T Ito, Y Tokura
BACKGROUND: Mogamulizumab (Mog) is a defucosylated, therapeutic monoclonal antibody, targeting CCR4, and was first approved in Japan for the treatment of adult T cell leukaemia/lymphoma (ATLL), followed by cutaneous T cell lymphoma and peripheral T cell lymphoma. OBJECTIVE: To retrospectively investigate development of photosensitivity in patients with mycosis fungoides and other T cell neoplasms after treatment with Mog. METHODS: We treated 7 cutaneous lymphoma patients with Mog...
January 16, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29340396/synthesis-and-antiproliferative-activity-of-a-series-of-new-platinum-and-palladium-diphosphane-complexes
#6
Carleen Cullinane, Glen B Deacon, Penny R Drago, Anja P Erven, Peter C Junk, Jenny Luu, Gerd Meyer, Simon Schmitz, Ingo Ott, Julia Schur, Lorraine K Webster, Axel Klein
New organometallic complexes [M(dppe)(R)2] {where M = Pt or Pd, dppe = 1,2-bis(diphenylphosphano)ethane, and R = C6F4H-x (x = 6,5,4), C6F3H2-3,5, C6F3H2-5,6, C6F3H2-3,6, C6F4(OMe)-4, and C6F4(cyclo-C5H10N)-4, the numbers x refer to the positions of the protons in the polyfluoroaryl ligands} were synthesised either through transmetalation from the dichlorido complexes [M(dppe)Cl2] or through ligand exchange using [M(diene)Cl2] precursor complexes with diene = 1,5-cyclooctadiene (cod) or 1,5-hexadiene (hex). Alternatively, [M(dppX)Cl(R)] complexes with dppX = dppm (1,1-bis(diphenylphosphano)methane), dppe, dppp (1,3-bis(diphenylphosphano)propane), and dppb (1,4-bis(diphenylphosphano)butane) were prepared in decarboxylation reactions from thallium(i) carboxylates Tl(O2CR)...
January 17, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29340085/6-methylsulfonyl-hexyl-isothiocyanate-as-potential-chemopreventive-agent-molecular-and-cellular-profile-in-leukaemia-cell-lines
#7
Monia Lenzi, Veronica Cocchi, Marco Malaguti, Maria Cristina Barbalace, Silvia Marchionni, Silvana Hrelia, Patrizia Hrelia
Numerous laboratory and epidemiological studies show that the risk of developing several types of cancer can be reduced with the employment of natural substances that act with multiple mechanisms. In this context, an important role is played by the isothiocyanates. Recently, 6-(methylsulfonyl)hexyl isothiocyanate (6-MITC), present in the root of Wasabia Japonica, has stimulated the interest of researchers as a chemopreventive agent. In this particular study we have focused on evaluating 6-MITC's in vitro cytotoxic, cytostatic and cytodifferentiating activities, as well as its pro-apoptotic potential...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340063/a-molecular-signature-of-dormancy-in-cd34-cd38-acute-myeloid-leukaemia-cells
#8
Mazin Gh Al-Asadi, Grace Brindle, Marcos Castellanos, Sean T May, Ken I Mills, Nigel H Russell, Claire H Seedhouse, Monica Pallis
Dormant leukaemia initiating cells in the bone marrow niche are a crucial therapeutic target for total eradication of acute myeloid leukaemia. To study this cellular subset we created and validated an in vitro model employing the cell line TF-1a, treated with Transforming Growth Factor β1 (TGFβ1) and a mammalian target of rapamycin inhibitor. The treated cells showed decreases in total RNA, Ki-67 and CD71, increased aldehyde dehydrogenase activity, forkhead box 03A (FOX03A) nuclear translocation and growth inhibition, with no evidence of apoptosis or differentiation...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339097/safety-and-preliminary-efficacy-of-venetoclax-with-decitabine-or-azacitidine-in-elderly-patients-with-previously-untreated-acute-myeloid-leukaemia-a-non-randomised-open-label-phase-1b-study
#9
Courtney D DiNardo, Keith W Pratz, Anthony Letai, Brian A Jonas, Andrew H Wei, Michael Thirman, Martha Arellano, Mark G Frattini, Hagop Kantarjian, Relja Popovic, Brenda Chyla, Tu Xu, Martin Dunbar, Suresh K Agarwal, Rod Humerickhouse, Mack Mabry, Jalaja Potluri, Marina Konopleva, Daniel A Pollyea
BACKGROUND: Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating agents such as azacitidine and decitabine is common, but responses are modest and typically short-lived. The oral anti-apoptotic B-cell lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent activity in patients with relapsed or refractory acute myeloid leukaemia and preclinical data suggested synergy between hypomethylating agents and venetoclax, which led to this combination phase 1b study...
January 12, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29339096/a-new-option-for-remission-induction-in-acute-myeloid-leukaemia
#10
Carsten Müller-Tidow, Richard F Schlenk
No abstract text is available yet for this article.
January 12, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29339045/deficiency-of-dietary-pyridoxine-disturbed-the-intestinal-physical-barrier-function-of-young-grass-carp-ctenopharyngodon-idella
#11
Pei Wu, Xin Zheng, Xiao-Qiu Zhou, Wei-Dan Jiang, Yang Liu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Yong-An Zhang, Lin Feng
The aim of this study was to assess the effects of dietary pyridoxine (PN) deficiency on intestinal antioxidant capacity, cell apoptosis and intercellular tight junction in young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (231.85 ± 0.63 g) were fed six diets containing graded levels of PN (0.12-7.48 mg/kg diet) for 10 weeks. At the end of the feeding trial, the fish were challenged with Aeromonas hydrophila for 2 weeks. The results showed that compared with the optimal PN level, PN deficiency (1) increased the contents of reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl (PC), decreased the activities and mRNA levels of antioxidant enzymes such as copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) (P < ...
January 12, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29338345/effect-of-anacardium-occidentale-leaf-extract-on-human-acute-lymphoblastic-leukaemia-cell-lines
#12
Janaína M Santos, Nathalia M Cury, José A Yunes, Jorge A López, Maria L Hernández-Macedo
Anacardium occidentale leaves are used in folk medicine due its therapeutic properties attributed to phenolic compounds. Therefore, this study was undertaken on its hydroethanolic leaf extract (AoHE) to evaluate cytotoxicity and apoptosis induction on acute lymphoblastic leukaemia cells. Results indicated that AoHE interfered in the cell cycle progression, inducing apoptosis by activation of casp3 at lower concentrations, thence, a promising candidate for the development of new cancer drugs.
January 16, 2018: Natural Product Research
https://www.readbyqxmd.com/read/29337707/induction-chemotherapy-in-acute-myeloid-leukaemia-origins-and-emerging-directions
#13
Vivek A Upadhyay, Amir T Fathi
PURPOSE OF REVIEW: This review summarizes the hallmark developments in induction chemotherapy for acute myeloid leukaemia and further describes future directions in its evolution. RECENT FINDINGS: We describe the origin of induction chemotherapy. We also describe notable modifications and adjustments to 7+3 induction chemotherapy since its development. Finally, we describe new efforts to modify and add new agents to induction therapy, including '7+3 Plus' combinations...
January 13, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29337382/frailty-in-patients-with-acute-myeloid-leukaemia-conceptual-misapprehension-of-chronological-age
#14
E G Umit, M Baysal, A M Demir
In haematology practice, patients with acute myeloid leukaemia (AML) are generally assessed for frailty only if they are older and not able to tolerate intensive and remission targeted treatments. We aimed to focus on frailty in patients with AML, in all ages and aimed to evaluate its role and practicality in daily routine. Data of patients diagnosed and treated for AML between 2006 and 2016 are recorded and assessed for their survival predictivity. One hundred and ninety-seven patients were <65 years of age and 175 were ≥65...
January 16, 2018: European Journal of Cancer Care
https://www.readbyqxmd.com/read/29336301/-acute-promyelocytic-leukaemia
#15
Michael Tøstesen, Lene S G Østergård, Eigil Kjeldsen, Jesper Stentoft, Jan M Nørgaard
Acute promyelocytic leukaemia has changed from being a highly fatal to a highly curable disease. Over time, key discoveries have identified the genetic and molecular abnormalities, which cause the disease. First choice of treatment has now changed from all-trans retinoic acid (ATRA) and chemotherapy to a chemo-free combination of arsenic trixoide and ATRA. This new regimen has shown equal responses and overall cure rates compared with the previous standard of care containing conventional chemotherapy, but with much lower toxicity...
January 15, 2018: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/29336300/-successful-treatment-of-acute-promyelocytic-leukaemia-without-chemotherapy-and-blood-transfusion
#16
Michael Tøstesen, Lene S G Østgård, Eigil Kjeldsen, Jesper Stentoft, Jan M Nørgaard
Untreated acute promyelocytic leukaemia (APL) is a rapidly lethal blood cancer. Conventional treatment consists of all-trans retinoic acid and chemotherapy. Standard chemo-therapy-containing treatments necessitate the use of blood products. This is a case report of typical APL in a 32-year-old female patient, who due to religious conviction refused supportive therapy with blood products. A treatment regimen consisting of all-trans retinoic acid and arsenic trioxide was successful without the use of blood transfusions...
January 15, 2018: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/29335431/synaptic-localisation-of-srf-coactivators-mkl1-and-mkl2-and-their-role-in-dendritic-spine-morphology
#17
Marisa Kaneda, Hiroyuki Sakagami, Yamato Hida, Toshihisa Ohtsuka, Natsumi Satou, Yuta Ishibashi, Mamoru Fukuchi, Anna Krysiak, Mitsuru Ishikawa, Daisuke Ihara, Katarzyna Kalita, Akiko Tabuchi
The megakaryoblastic leukaemia (MKL) family are serum response factor (SRF) coactivators, which are highly expressed in the brain. Accordingly, MKL plays important roles in dendritic morphology, neuronal migration, and brain development. Further, nucleotide substitutions in the MKL1 and MKL2 genes are found in patients with schizophrenia and autism spectrum disorder, respectively. Thus, studies on the precise synaptic localisation and function of MKL in neurons are warranted. In this study, we generated and tested new antibodies that specifically recognise endogenously expressed MKL1 and MKL2 proteins in neurons...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29333125/association-between-slc19a1-gene-polymorphism-and-high-dose-methotrexate-toxicity-in-childhood-acute-lymphoblastic-leukaemia-and-non-hodgkin-malignant-lymphoma-introducing-a-haplotype-based-approach
#18
Barbara Faganel Kotnik, Janez Jazbec, Petra Bohanec Grabar, Cristina Rodriguez-Antona, Vita Dolzan
Background: We investigated the clinical relevance of SLC 19A1 genetic variability for high dose methotrexate (HD-MTX) related toxicities in children and adolescents with acute lymphoblastic leukaemia (ALL) and non Hodgkin malignant lymphoma (NHML). Patients and methods: Eighty-eight children and adolescents with ALL/NHML were investigated for the influence of SLC 19A1 single nucleotide polymorphisms (SNPs) and haplotypes on HD-MTX induced toxicities. Results: Patients with rs2838958 TT genotype had higher probability for mucositis development as compared to carriers of at least one rs2838958 C allele (OR 0...
December 2017: Radiology and Oncology
https://www.readbyqxmd.com/read/29330371/transcriptional-inaccuracy-threshold-attenuates-differences-in-rna-dependent-dna-synthesis-fidelity-between-retroviral-reverse-transcriptases
#19
Alba Sebastián-Martín, Verónica Barrioluengo, Luis Menéndez-Arias
In M13mp2 lacZα forward mutation assays measuring intrinsic fidelity of DNA-dependent DNA synthesis, wild-type human immunodeficiency virus type 1 (HIV-1) RTs of group M/subtype B previously showed >10-fold higher error rates than murine leukaemia virus (MLV) and avian myeloblastosis virus (AMV) RTs. An adapted version of the assay was used to obtain error rates of RNA-dependent DNA synthesis for several RTs, including wild-type HIV-1BH10, HIV-1ESP49, AMV and MLV RTs, and the high-fidelity mutants of HIV-1ESP49 RT K65R and K65R/V75I...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330269/central-nervous-system-graft-versus-host-disease-cns-gvhd-after-allogeneic-haematopoietic-stem-cell-transplantation
#20
Karolina Polchlopek Blasiak, Federico Simonetta, Maria-Isabel Vargas, Yves Chalandon
A 60-year-old man presented with impaired consciousness and psychomotor agitation after a second allogeneic haematopoietic stem cell transplantation (HSCT) from a matched unrelated donor for acute myeloid leukaemia. Clinical, biological and radiological evidence suggested a diagnosis of central nervous system graft-versus-host disease (CNS-GvHD). After intrathecal infusion of methylprednisolone, the clinical symptoms as well as the radiological abnormalities disappeared. The present report illustrates the difficulties in the diagnosis and the management of CNS-GvHD, a very rare and still challenging neurological complication that can occur after allogeneic HSCT...
January 12, 2018: BMJ Case Reports
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