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https://www.readbyqxmd.com/read/29778892/structure-based-design-of-novel-quinoxaline-2-carboxylic-acids-and-analogues-as-pim-1-inhibitors
#1
Bruno Oyallon, Marie Brachet-Botineau, Cédric Logé, Pascal Bonnet, Mohamed Souab, Thomas Robert, Sandrine Ruchaud, Stéphane Bach, Pascal Berthelot, Fabrice Gouilleux, Marie-Claude Viaud-Massuard, Caroline Denevault-Sabourin
We identified a new series of quinoxaline-2-carboxylic acid derivatives, targeting the human proviral integration site for Moloney murine leukemia virus-1 (HsPim-1) kinase. Seventeen analogues were synthesized providing useful insight into structure-activity relationships studied. Docking studies realized in the ATP pocket of HsPim-1 are consistent with an unclassical binding mode of these inhibitors. The lead compound 1 was able to block HsPim-1 enzymatic activity at nanomolar concentrations (IC50 of 74 nM), with a good selectivity profile against a panel of mammalian protein kinases...
May 11, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29777449/potential-of-bacillus-subtilis-lipopeptides-in-anti-cancer-i-induction-of-apoptosis-and-paraptosis-and-inhibition-of-autophagy-in-k562-cells
#2
Haobin Zhao, Lu Yan, Xiaoguang Xu, Chunmei Jiang, Junling Shi, Yawen Zhang, Li Liu, Shuzhen Lei, Dongyan Shao, Qingsheng Huang
The lipopeptide iturin from Bacillus subtilis has been found to have a potential inhibitory effect on breast cancer, alveolar adenocarcinoma, renal carcinoma, and colon adenocarcinoma. In this study, the potential of B. subtilis lipopeptides (a mixture of iturin homologues, concentration of 42.75%) to inhibit chronic myelogenous leukemia was evaluated using K562 myelogenous leukemia cells. The results showed that the lipopeptides could completely inhibit the growth of K562 at 100 μM, with an IC50 value of 65...
May 9, 2018: AMB Express
https://www.readbyqxmd.com/read/29775689/biomarkers-for-checkpoint-inhibition-in-hematologic-malignancies
#3
REVIEW
Djordje Atanackovic, Tim Luetkens
In the past few years we have seen remarkable paradigm shifts in the treatment of many solid tumors due to the introduction of inhibitors targeting immune checkpoints such as PD-1/PD-L1 and CTLA-4. Recent results indicate that checkpoint inhibition also represents a very promising approach for certain types of hematologic malignancies. Unfortunately, treatment with checkpoint inhibitors is also associated with substantial toxicities and high costs and only a subset of patients appears to derive clinical benefit from these treatments...
May 15, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29774100/differential-proteomic-profile-of-leukemic-cd34-progenitor-cells-from-chronic-myeloid-leukemia-patients
#4
Maria Rosaria Ricciardi, Valentina Salvestrini, Roberto Licchetta, Simone Mirabilii, Mattia Forcato, Gabriele Gugliotta, Simona Salati, Fausto Castagnetti, Gianantonio Rosti, Massimo Breccia, Giuliana Alimena, Rossella Manfredini, Silvio Bicciato, Roberto Massimo Lemoli, Agostino Tafuri
Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773593/safety-and-efficacy-of-second-line-bosutinib-for-chronic-phase-chronic-myeloid-leukemia-over-a-five-year-period-final-results-of-a-phase-1-2-study
#5
Carlo Gambacorti-Passerini, Jorge E Cortes, Jeff H Lipton, Hagop M Kantarjian, Dong-Wook Kim, Philippe Schafhausen, Rocco Crescenzo, Nathalie Bardy-Bouxin, Mark Shapiro, Kay Noonan, Eric Leip, Liza DeAnnuntis, Tim H Brümmendorf, H Jean Khoury
Bosutinib is a Src/Abl tyrosine kinase inhibitor indicated for adults with newly-diagnosed Ph+ chronic myeloid leukemia or with resistant/intolerant disease. We report the final results of a phase 1/2 study of second-line bosutinib in chronic phase chronic myeloid leukemia patients after imatinib failure (n=284). Median follow-up and treatment durations were 54.8 (range, 0.6-96.3) and 25.6 (0.2&-96.3) months, respectively. At years 2 and 5, 54% and 40% of patients, respectively, remained on bosutinib. Cumulative major cytogenetic response and complete cytogenetic response rates (newly-attained or maintained from baseline) were 58% and 46%, respectively, by year 2 and 60% and 50% by year 5...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773429/real-life-experience-with-ponatinib-in-chronic-myeloid-leukemia-a-multicenter-observational-study
#6
Adi Shacham-Abulafia, Pia Raanani, David Lavie, Yulia Volchek, Ron Ram, Ilana Helman, Liat Shargian, Anna Gourevitch, Evgeni Chubar, Roy Ratzon, Uri Rozovski
BACKGROUND: The strict recruitment criteria of patients for clinical trials often lead to reduced generalizability of the findings. We studied how ponatinib is used outside clinical trials in patients with chronic myeloid leukemia (CML). PATIENTS AND METHODS: The present retrospective study included all patients with a diagnosis of CML who had received ponatinib in 7 medical centers in Israel. RESULTS: From 2011 to 2016, we identified 37 patients with CML who had received ponatinib, 21 in the chronic phase and 16 in the advanced phase...
May 7, 2018: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29772458/phenotyping-and-target-expression-profiling-of-cd34-cd38-and-cd34-cd38-stem-and-progenitor-cells-in-acute-lymphoblastic-leukemia
#7
Katharina Blatt, Ingeborg Menzl, Gregor Eisenwort, Sabine Cerny-Reiterer, Harald Herrmann, Susanne Herndlhofer, Gabriele Stefanzl, Irina Sadovnik, Daniela Berger, Alexandra Keller, Alexander Hauswirth, Gregor Hoermann, Michael Willmann, Thomas Rülicke, Heinz Sill, Wolfgang R Sperr, Christine Mannhalter, Junia V Melo, Ulrich Jäger, Veronika Sexl, Peter Valent
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+ /CD38- LSCs in patients with Ph+ ALL (n = 22) and Ph- ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested...
May 14, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29772439/long-noncoding-rna-meg3-inhibits-proliferation-of-chronic-myeloid-leukemia-cells-by-sponging-microrna21
#8
Ziye Li, Lin Yang, Xiaojun Liu, Ziyuan Nie, Jianmin Luo
The long noncoding RNA (lnc) maternally expressed 3 (MEG3) is downregulated in many types of cancers. However, the relationship between lncRNA MEG3, microRNA-21 (miR-21) and chronic myeloid leukemia (CML) blast crisis is unknown. This study examined bone marrow samples from 40 CML patients and 10 healthy donors. Proliferation and apoptosis assays, real-time polymerase chain reaction (PCR), bisulfite sequencing PCR, Western blotting, luciferase assay, RNA pull-down, RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP) and Chromatin immunoprecipitation (ChIP) were performed...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29771146/nanosized-ethanol-based-malleable-liposomes-of-cytarabine-to-accentuate-transdermal-delivery-formulation-optimization-in-vitro-skin-permeation-and-in-vivo-bioavailability
#9
Rakesh Raj, Pooja Mongia Raj, Alpana Ram
Cytarabine is a pyrimidine nucleoside analog used predominantly for acute myeloid leukemia (AML) and also for other indications, including acute lymphocytic leukemia, chronic myelogenous leukemia, and lymphoma by parenteral route due to its low oral bioavailability. Parenteral administration requires constant plasma level, monitoring for its fluctuation and poor patients compliances. Hence the objective of this work is to construct optimized nanosized malleable liposomes of cytarabine to accentuate transdermal delivery of drug to circumvent previously mentioned drawbacks...
May 17, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29769784/nilotinib-induced-perforating-folliculitis-two-cases
#10
Neerja Saraswat, Ajay Chopra, Debdeep Mitra, Krishna Talukdar
Cutaneous adverse effects of chemotherapy are widely known but underreported. A significant advancement is made in the field of oncology with the advent of new classes of drug being added to the existing classes at a fast pace. Most of these cutaneous adverse effects are self-limiting and subsides on suspending the drug either temporarily or permanently. Some of these effects are merely overlooked by the patients and the treating physician hence goes un-noticed. Nilotinib is a newer second-generation tyrosine-kinase inhibitor approved for the management of chronic myeloid leukemia...
March 2018: International Journal of Trichology
https://www.readbyqxmd.com/read/29769184/explaining-resistance-to-car-t-cells
#11
(no author information available yet)
A new study reveals several attributes of T cells from patients with chronic lymphocytic leukemia who respond to CAR T-cell therapy. The patients' T cells show increased expression of memory-related genes and high activity of STAT3, which promotes memory cell differentiation. The researchers also found that patients who underwent complete remission have certain CD8+ T cells.
May 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29768934/a-safety-profile-of-medications-used-to-treat-waldenstr%C3%A3-m-s-macroglobulinemia
#12
Ramón García-Sanz, Cristina Jiménez, Verónica González de la Calle, María Eugenia Sarasquete
Waldenström's macroglobulinemia (WM) is a B-cell lymphoproliferative disease with serum IgM monoclonal component and bone marrow infiltration by lymphoplasmacytic lymphoma. Traditional therapy was based on that regimens used for closely related entities, such as chronic lymphocytic leukemia or multiple myeloma. This resulted in a lack of drugs specifically approved for WM, until the discovery of the BTK inhibitors. Areas covered. Two main therapeutic attitudes are possible: 1) conventional therapies based on combinations with alkylating agents or proteasome inhibitors with steroids and anti-CD20 monoclonal antibodies, or; 2) new approaches with BTK inhibitors, usually alone...
May 17, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29766234/the-severe-cytokine-release-syndrome-in-phase-i-trials-of-cd19-car-t-cell-therapy-a-systematic-review
#13
REVIEW
Zhen Jin, Rufang Xiang, Kai Qing, Xiaoyang Li, Yunxiang Zhang, Lining Wang, Hongming Zhu, Yuanfei Mao, Zizhen Xu, Junmin Li
CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as the most significant adverse effect in the clinical course of this novel targeting immunotherapy. In this systematic review, we analyzed the incidence of severe CRS in 19 clinical trials selected from studies published between 2010 and 2017...
May 15, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29765537/stat3-activated-cd36-facilitates-fatty-acid-uptake-in-chronic-lymphocytic-leukemia-cells
#14
Uri Rozovski, David M Harris, Ping Li, Zhiming Liu, Preetesh Jain, Alessandra Ferrajoli, Jan Burger, Phillip Thompson, Nitin Jain, William Wierda, Michael J Keating, Zeev Estrov
Although several studies established that unlike normal B cells chronic lymphocytic leukemia (CLL) cells metabolize fatty acids (FA), how CLL cells internalize FA is poorly understood. Because in various cell types CD36 facilitates FA uptake, we wondered whether a similar mechanism is operative CLL. We found that CD36 levels are higher in CLL cells than in normal B cells, and that small interfering RNA, CD36 neutralizing antibodies or sulfosuccinimidyl oleate (SSO) that inhibits CD36 significantly reduced the oxygen consumption of CLL cells incubated with FA...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764573/-clinical-and-laboratory-characteristics-of-juvenile-myelomonocytic-leukemia
#15
Yuan-Yuan Wu, Sheng-Yang Cai, Wei Huang, Si-Si Li, Wei Li, Ao Dong
OBJECTIVE: To study the clinical and laboratory characteristics of juvenile myelomonocytic leukemia (JMML). METHODS: The clinical characteristics and laboratory results were retrospectively analyzed in 10 children with newly diagnosed JMML. They were compared with those of 28 children with myelodysplastic syndrome (MDS) and 44 children with chronic myeloid leukemia (CML). RESULTS: Compared with the children with CML or MDS, the children with JMML had significantly higher rates of skin rashes, ecchymosis, and lymphadenectasis, a significantly lower serum cholinesterase (ChE) level, and a significantly higher fetal hemoglobin level (P<0...
May 2018: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/29764250/immunological-changes-with-kinase-inhibitor-therapy-for-chronic-lymphocytic-leukemia
#16
Christopher Pleyer, Adrian Wiestner, Clare Sun
Ibrutinib and idelalisib are kinase inhibitors that have revolutionized the treatment of chronic lymphocytic leukemia (CLL). Capable of inducing durable remissions, these agents also modulate the immune system. Both ibrutinib and idelalisib abrogate the tumor-supporting microenvironment by disrupting cell-cell interactions, modulating the T-cell compartment, and altering the cytokine milieu. Ibrutinib also partially restores T-cell and myeloid defects associated with CLL. In contrast, immune-related adverse effects, including pneumonitis, colitis, hepatotoxicity, and infections are of particular concern with idelalisib...
May 15, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29763855/identification-of-new-phosphorylation-sites-of-cd23-in-b-cells-of-patients-with-chronic-lymphocytic-leukemia
#17
Martina Maďarová, Rastislav Mucha, Stanislav Hresko, Zuzana Makarová, Zuzana Gdovinová, Jarmila Szilasiová, Marianna Vitková, Tomáš Guman, Natalia Štecová, Tomas Dobransky
B-cell chronic lymphocytic leukemia (B-CLL) is the most common lymphoproliferative disorder in adults. Patients with B-CLL strongly express the CD23 - C type of lectin (low affinity IgE receptor, Fc epsilon RII), which is linked to B cell activation and proliferation. Phosphorylation in lymphocytes is tightly associated with regulation of protein activities, functional regulation and cell signaling, and may thus affect initiation and/or progression of the disease. Here we report changes in the phosphorylation of CD23 on threonine (pThr314) and two serine residues (pSer254, pSer265) in B lymphocytes of B-CLL patients, using a flow cytometry approach...
May 9, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29762880/trim22-knockdown-suppresses-chronic-myeloid-leukemia-via-inhibiting-pi3k-akt-mtor-signaling-pathway
#18
Liyin Li, Yanhua Qi, Xiaobo Ma, Guosheng Xiong, Lijun Wang, Cuixia Bao
Tripartite motif-containing 22 (TRIM22) is reported to participate in numerous cellular activities. Recent studies confirm that TRIM22 is a target gene for P53, and inhibits clonogenic growth of leukemic U-937 cells. The current study aims to discover the effect of TRIM22 in progression of human chronic myeloid leukemia (CML) and explore the related mechanism. TRIM22 was knocked down by siRNA transfection in CML cell K562. We observed that TRIM22 knockdown decreased proliferation and invasion in K562 cells...
May 15, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29762141/pd-1-expression-in-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-cll-sll-and-large-b-cell-richter-transformation-dlbcl-rt-a-characteristic-feature-of-dlbcl-rt-and-potential-surrogate-marker-for-clonal-relatedness
#19
Rong He, Wei Ding, David S Viswanatha, Dong Chen, Min Shi, Daniel Van Dyke, Shulan Tian, Linda N Dao, Sameer A Parikh, Tait D Shanafelt, Timothy G Call, Stephen M Ansell, Jose F Leis, Ming Mai, Curtis A Hanson, Karen L Rech
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT...
May 14, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29761374/the-prognostic-role-of-hbv-infection-in-chronic-lymphocytic-leukemia
#20
Jin-Hua Liang, Rui Gao, Jun-Cheng Dai, Robert Peter Gale, Wang Li, Lei Fan, Zhi-Bin Hu, Wei Xu, Jian-Yong Li
PURPOSE: We attempt to assess the impact of hepatis-B virus (HBV) status on the prognosis of chronic lymphocytic leukemia (CLL) using a Chinese case cohort. METHODS: Five hundred and one consecutive newly diagnosed subjects with CLL were enrolled in this case cohort. HBV infection was defined as hepatitis B surface antigen (HBsAg) positive or hepatitis-B core antibody (HBcAb) positive. Univariate and stepwise multivariate Cox regression analyses were used to screen the prognostic risk factors associated with the end point of time-to-treatment (TTT) or overall survival (OS)...
May 14, 2018: Journal of Cancer Research and Clinical Oncology
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