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https://www.readbyqxmd.com/read/27909887/similar-outcome-after-allogeneic-stem-cell-transplantation-with-a-modified-flamsa-conditioning-protocol-substituting-4%C3%A2-gy-tbi-with-treosulfan-in-an-elderly-population-with-high-risk-aml
#1
Udo Holtick, Marco Herling, Natali Pflug, Geothy Chakupurakal, Silke Leitzke, Dominik Wolf, Michael Hallek, Christof Scheid, Jens M Chemnitz
The fludarabine, amsacrine, and cytarabine (FLAMSA)-reduced-intensity conditioning (RIC) protocol has been described to be effective in patients with high-risk and refractory acute myeloic leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (aSCT). To increase safety and tolerability of the conditioning, we previously reported the feasibility to substitute the TBI component by treosulfan in elderly AML patients. We now present long-term follow-up data on patients treated with FLAMSA/treosulfan compared to the original FLAMSA/4Gy TBI protocol...
December 1, 2016: Annals of Hematology
https://www.readbyqxmd.com/read/27906612/stably-transfected-adherent-cancer-cell-models-with-decreased-expression-of-5-nucleotidase-cn-ii
#2
Gabriel Bricard, Emeline Cros-Perrial, Christelle Machon, Charles Dumontet, Lars Petter Jordheim
The 5'-nucleotidase cN-II has been shown to be associated with the sensitivity to nucleoside analogues, the survival of cytarabine treated leukemia patients and to cell proliferation. Due to the lack of relevant cell models for solid tumors, we developed four cell lines with low cN-II expression and characterized them concerning their in vitro sensitivity to cancer drugs and their intracellular nucleotide pools. All four cell models had an important decrease of cN-II expression but did not show modified sensitivity, cell proliferation or nucleotide pools...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27903973/association-of-a-cytarabine-chemosensitivity-related-gene-expression-signature-with-survival-in-cytogenetically-normal-acute-myeloid-leukemia
#3
Han Yan, Lu Wen, Dan Tan, Pan Xie, Feng-Mei Pang, Hong-Hao Zhou, Wei Zhang, Zhao-Qian Liu, Jie Tang, Xi Li, Xiao-Ping Chen
The prognosis of cytogenetically normal acute myeloid leukemia (CN-AML) varies greatly among patients. Achievement of complete remission (CR) after chemotherapy is indispensable for a better prognosis. To develop a gene signature predicting overall survival (OS) in CN-AML, we performed data mining procedure based on whole genome expression data of both blood cancer cell lines and AML patients from open access database. A gene expression signature including 42 probes was derived. These probes were significantly associated with both cytarabine half maximal inhibitory concentration values in blood cancer cell lines and OS in CN-AML patients...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899994/targeting-of-the-leukemia-microenvironment-by-c-rgdfv-overcomes-the-resistance-to-chemotherapy-in-acute-myeloid-leukemia-in-biomimetic-polystyrene-scaffolds
#4
Zhao-Hua Shen, Dong-Feng Zeng, Xiao-Yan Wang, Ying-Ying Ma, Xi Zhang, Pei-Yan Kong
The bone marrow microenvironment provides a relative sanctuary from cytotoxic drugs for leukemia cells. The present niche models concentrate on a two-dimensional (2D) co-culture system in vitro, which does not imitate the in vivo environment, while the 3D scaffolds are more reflective of this. Osteopontin (Opn) secreted by bone marrow osteoblasts, may participate in protecting leukemia cells from apoptosis by binding to its receptor αvβ3, which can be expressed on the surface of the leukemia MV4-11 cell line...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27895780/curcumin-potentiates-the-effect-of-chemotherapy-against-acute-lymphoblastic-leukemia-cells-via-downregulation-of-nf-%C3%AE%C2%BAb
#5
Helia Judith Pimentel-Gutiérrez, Lucina Bobadilla-Morales, César Cenobio Barba-Barba, Citlalli Ortega-De-La-Torre, Fernando Antonio Sánchez-Zubieta, Jorge Román Corona-Rivera, Betsy Annel González-Quezada, Juan S Armendáriz-Borunda, Rocío Silva-Cruz, Alfredo Corona-Rivera
Acute lymphoblastic leukemia (ALL) accounts for 30% of all pediatric cancers. Currently available treatments exhibit toxicity and certain patients may develop resistance. Thus, less toxic and chemoresistance-reversal agents are required. In the present study, the potential effect of curcumin, a component of Curcuma longa, as a pharmacological co-adjuvant of several chemotherapeutic agents against ALL, including prednisone, 6-mercaptopurine, dexamethasone, cyclophosphamide, l-asparaginase, vincristine, daunorubicin, doxorubicin, methotrexate and cytarabine, was investigated in the REH ALL cell line cultures treated in combination with chemotherapeutic agents and curcumin...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27890930/histone-deacetylase-inhibitors-interrupt-hsp90-rasgrp1-and-hsp90-craf-interactions-to-upregulate-bim-and-circumvent-drug-resistance-in-lymphoma-cells
#6
H Ding, K L Peterson, C Correia, B Koh, P A Schneider, G S Nowakowski, S H Kaufmann
Histone deacetylase (HDAC) inhibitors, which are approved for the treatment of cutaneous T cell lymphoma and multiple myeloma, are undergoing evaluation in other lymphoid neoplasms. How they kill susceptible cells is incompletely understood. Here we show that trichostatin A, romidepsin, and panobinostat induce apoptosis across a panel of malignant B cell lines, including lines that are intrinsically resistant to bortezomib, etoposide, cytarabine, and BH3 mimetics. Further analysis traces the pro-apoptotic effects of HDAC inhibitors to increased acetylation of the chaperone heat shock protein 90 (HSP90), causing release and degradation of the HSP90 client proteins RASGRP1 and CRAF, which in turn leads to downregulation of mitogen activated protein kinase pathway signaling and upregulation of the pro-apoptotic BCL2 family member BIM in vitro and in vivo...
November 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27888802/low-dose-triptolide-reverses-chemoresistance-in-adult-acute-lymphoblastic-leukemia-cells-via-reactive-oxygen-species-generation-and-dna-damage-response-disruption
#7
Haijun Zhao, Pengcheng Shi, Manman Deng, Zhiwu Jiang, Yin Li, Vinodh Kannappan, Weiguang Wang, Peng Li, Bing Xu
Chemoresistance represents a major challenge for treatment of acute lymphoblastic leukemia (ALL). Thus, new drugs to overcome chemoresistance in ALL are urgently needed. To this end, we established a cytarabine (araC)-resistant ALL cell line (NALM-6/R), which interestingly displayed cross-resistance towards doxorubicin (ADM). Here we report that low dose of triptolide (TPL), a natural product used for treating inflammatory diseases such as arthritis, could reverse araC and ADM resistance and in NALM-6/R cells as well as primary cells from patients with relapsed or refractory (R/R) ALL, reflected by inhibition of cell proliferation and induction of apoptosis in vitro, and repression of tumor growth in vivo in a mouse xenograft model...
November 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27879990/sequential-chemotherapy-followed-by-reduced-intensity-conditioning-and-allogeneic-haematopoietic-stem-cell-transplantation-in-adult-patients-with-relapse-or-refractory-acute-myeloid-leukaemia-a-survey-from-the-acute-leukaemia-working-party-of-ebmt
#8
Olle Ringdén, Myriam Labopin, Christoph Schmid, Behnam Sadeghi, Emmanuelle Polge, Johanna Tischer, Arnold Ganser, Mauricette Michallet, Lothar Kanz, Rainer Schwerdtfeger, Arnon Nagler, Mohamad Mohty
This study analysed the outcome of 267 patients with relapse/refractory acute myeloid leukaemia (AML) who received sequential chemotherapy including fludarabine, cytarabine and amsacrine followed by reduced-intensity conditioning (RIC) and allogeneic haematopoietic stem cell transplantation (HSCT). The transplants in 77 patients were from matched sibling donors (MSDs) and those in 190 patients were from matched unrelated donors. Most patients (94·3%) were given anti-T-cell antibodies. The incidence of acute graft-versus-host disease (GVHD) of grades II-IV was 32·1% and that of chronic GVHD was 30·2%...
November 23, 2016: British Journal of Haematology
https://www.readbyqxmd.com/read/27863389/nt1721-a-novel-epidithiodiketopiperazine-exhibits-potent-in-vitro-and-in-vivo-efficacy-against-acute-myeloid-leukemia
#9
Claudia M Kowolik, Min Lin, Jun Xie, Larry E Overman, David A Horne
Acute myeloid leukemia (AML) is an aggressive malignancy characterized by heterogeneous genetic and epigenetic changes in hematopoietic progenitors that lead to abnormal self-renewal and proliferation. Despite high initial remission rates, prognosis remains poor for most AML patients, especially for those harboring internal tandem duplication (ITD) mutations in the fms-related tyrosine kinase-3 (FLT3). Here, we report that a novel epidithiodiketopiperazine, NT1721, potently decreased the cell viability of FLT3-ITD+ AML cell lines, displaying IC50 values in the low nanomolar range, while leaving normal CD34+ bone marrow cells largely unaffected...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27859216/cooperation-of-mll-af10-om-lz-with-ptpn11-activating-mutation-induced-monocytic-leukemia-with-a-shorter-latency-in-a-mouse-bone-marrow-transplantation-model
#10
Jen-Fen Fu, Sung-Tzu Liang, Ying-Jung Huang, Kung-Hao Liang, Tzung-Hai Yen, Der-Cherng Liang, Lee-Yung Shih
PTPN11 mutation, a RAS signaling pathway mutation, is associated with MLL translocations in acute leukemia. A girl with MLL/AF10 AML was found to carry PTPN11(G503A) . To study the impact of PTPN11 (G503A) cooperating with MLL/AF10 on leukemogenesis, we established a retroviral transduction/transplantation mouse model. Compared with the MLL/AF10(OM-LZ) leukemia cells harboring PTPN11 (wt) , the cells harboring PTPN11(G503A) were hypersensitive to GM-CSF and IL3, and more resistant to death upon treatment with daunorubicin but sensitive to cytarabine...
November 14, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27835920/-acute-myeloid-leukemia
#11
Jan Braess
Acute myeloid leukemia (AML) has been genetically characterized extensively and can now be subdivided into 9 to 11 pathogenetically different subtypes according to their profile of driver mutations. In clinical practice karyotyping and molecular analysis of NPM1, cEBPa and FLT3-ITD are required for treatment stratification and potentially genotype specific treatment. Some markers such as NPM1 not only offer prognostic information but can also serve as markers of minimal residual disease and thus have the potential to guide therapy in the future...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27833094/enhanced-sensitivity-to-glucocorticoids-in-cytarabine-resistant-aml
#12
D Malani, A Murumägi, B Yadav, M Kontro, S Eldfors, A Kumar, R Karjalainen, M M Majumder, P Ojamies, T Pemovska, K Wennerberg, C Heckman, K Porkka, M Wolf, T Aittokallio, O Kallioniemi
We sought to identify drugs that could counteract cytarabine resistance in acute myeloid leukemia (AML) by generating eight resistant variants from MOLM-13 and SHI-1 AML cell lines by long-term drug treatment. These cells were compared with 66 ex vivo chemorefractory samples from cytarabine-treated AML patients. The models and patient cells were subjected to genomic and transcriptomic profiling and high-throughput testing with 250 emerging and clinical oncology compounds. Genomic profiling uncovered deletion of the deoxycytidine kinase (DCK) gene in both MOLM-13- and SHI-1-derived cytarabine-resistant variants and in an AML patient sample...
December 2, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27821554/assessment-of-drug-sensitivity-in-hematopoietic-stem-and-progenitor-cells-from-acute-myelogenous-leukemia-and-myelodysplastic-syndrome-ex-vivo
#13
Katherine L B Knorr, Laura E Finn, B Douglas Smith, Allan D Hess, James M Foran, Judith E Karp, Scott H Kaufmann
: : Current understanding suggests that malignant stem and progenitor cells must be reduced or eliminated for prolonged remissions in myeloid neoplasms such as acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Multicolor flow cytometry has been widely used to distinguish stem and myeloid progenitor cells from other populations in normal and malignant bone marrow. In this study, we present a method for assessing drug sensitivity in MDS and AML patient hematopoietic stem and myeloid progenitor cell populations ex vivo using the investigational Nedd8-activating enzyme inhibitor MLN4924 and standard-of-care agent cytarabine as examples...
November 7, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27821230/-primary-central-nervous-system-diffuse-large-b-cell-lymphoma-a-clinicopathologic-and-molecular-study
#14
Z P Ma, Babayi Ainiwaer, Z Y Liu, X L Shi, W L Cui, W Zhang, X X Li
Objective: To investigate clinicopathologic characteristics, immunophenotype and EB virus-related molecular genetic alterations in primary central nervous system diffuse large B cell lymphoma (DLBCL) along with correlation with clinical prognosis. Methods: A total of 30 cases of primary central nervous system DLBCL were retrospectively studied by retrieving clinical data, histological evaluation and immunophenotyping by EnVision two steps methods. The expression of EBER mRNA was detected by in situ hybridization and bcl-2, bcl-6 and C-MYC gene abnormalities were analyzed by interphase fluorescence in situ hybridization...
November 8, 2016: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/27807492/novel-brentuximab-vedotin-combination-therapies-show-promising-activity-in-highly-refractory-cd30-non-hodgkin-lymphoma-a-case-series-and-review-of-the-literature
#15
Wilfred Delacruz, Robert Setlik, Arash Hassantoufighi, Shyam Daya, Susannah Cooper, Dale Selby, Alexander Brown
Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of hematologic malignancies which typically respond to standard first-line chemoimmunotherapy regimens. Unfortunately, patients with refractory NHL face a poor prognosis and represent an unmet need for improved therapeutics. We present two cases of refractory CD30+ NHL who responded to novel brentuximab vedotin- (BV-) based regimens. The first is a patient with stage IV anaplastic large cell lymphoma (ALCL) with cranial nerve involvement who failed front-line treatment with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) and second line cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate (MTX), and cytarabine (hyperCVAD) with intrathecal- (IT-) MTX and IT-cytarabine, but responded when BV was substituted for vincristine (hyperCBAD)...
2016: Case Reports in Oncological Medicine
https://www.readbyqxmd.com/read/27806360/fludarabine-and-cytarabine-combination-in-the-induction-of-adult-patients-with-acute-myeloid-leukaemia
#16
Francesco Longu, Claudio Fozza, Laura Dessì, Maurizio Longinotti, Silvana Bonfigli, Maria Grazia Careddu, Lorenzo Coppola, Domenica Barbara Giannico, Rosa Maria Nieddu, Luigi Podda, Simonetta Pardini, Fausto Dore, Simone Dore, Giovanni Sotgiu
No abstract text is available yet for this article.
November 3, 2016: Acta Haematologica
https://www.readbyqxmd.com/read/27804217/acute-myeloid-leukemia-therapy-elicits-durable-complete-response-in-chemoradio-resistant-metastatic-paraganglioma
#17
Sameer Sait, Rachel Kobos, Michael P LaQuaglia, Neeta Pandit-Taskar, Shakeel Modak
Few effective therapeutic options exist for patients with metastatic paraganglioma (PGL). We report the case of a 16-year-old male who developed acute myeloid leukemia (AML) 30 months following the treatment for metastatic PGL. PGL had been refractory to (131) I-meta-iodobenzylguanidine and temozolomide therapy. However, there was a major reduction in primary tumor allowing its gross total resection, and complete resolution of metastatic disease following AML-directed therapy that included daunorubicin, cytarabine, and etoposide...
November 2, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27801323/-analysis-of-the-safety-and-efficacy-of-60-mg%C3%A2-m-2-%C3%A2-d-1-daunorubicin-combined-with-standard-dose-of-cytarabine-as-induction-therapy-in-acute-myeloid-leukemia-patients-under-65-years-old
#18
X X Cao, S J Wang, M H Duan, T N Zhu, W Zhang, B Han, J L Zhuang, H C Cai, M Chen, J Feng, X Han, Y Zhang, C Yang, L Zhang, D B Zhou, J Li
Objective: To evaluate the long- term safety and efficacy of high- dose daunorubicin(DNR)(60 mg·m(-2)·d(-1))combined with standard dose of cytarabine(DA)as induction therapy in patients under 65 years old with newly diagnosed acute myeloid leukemia(AML). Methods: The complete remission(CR)rate, disease free survival(DFS), overall survival(OS)and side effects of therapy were retrospectively assayed in 116 patients with newly diagnosed AML who were younger than 65 years old and received daunorubicin(60 mg · m(-2)·d(-1))combined with cytarabine(Ara- C 200 mg ·m(-2)·d(-1))as induction therapy at Peking Union Medical College Hospital during July 2012 to February 2016...
October 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27797294/targeting-autophagy-to-overcome-chemoresistance-in-acute-myleogenous-leukemia
#19
Sujan Piya, Michael Andreeff, Gautam Borthakur
Therapeutic inhibition of macroautophagy/autophagy is expected to increase chemosensitivity of cancers and alter tumor-stroma interdependence. The hypoxic, metabolically challenged bone marrow microenvironment confers chemoresistance to leukemia cells. The impact of autophagy inhibition in the context of microenvironment-mediated resistance in leukemia is less explored. Our recent studies demonstrated that co-culture of acute myelogenous leukemia (AML) cells with marrow-derived mesenchymal stromal cells (MSC) induces autophagy in AML cells and increases resistance to genotoxic agents (cytarabine and idarubicin)...
October 31, 2016: Autophagy
https://www.readbyqxmd.com/read/27795554/monitoring-therapy-responses-at-the-leukemic-subclone-level-by-ultra-deep-amplicon-resequencing-in-acute-myeloid-leukemia
#20
P N Ojamies, M Kontro, H Edgren, P Ellonen, S Lagström, H Almusa, T Miettinen, S Eldfors, D Tamborero, K Wennerberg, C Heckman, K Porkka, M Wolf, O Kallioniemi
In our individualized systems medicine program, personalized treatment options are identified and administered to chemorefractory AML patients based on exome sequencing and ex-vivo drug sensitivity and resistance testing data. Here, we analyzed how clonal heterogeneity impacts on the responses of 13 AML patients to chemotherapy or targeted treatments using ultra-deep (average 68 000x coverage) amplicon resequencing. Using amplicon resequencing, we identified 16 variants from four patients (frequency 0,54-2%) that were not detected previously by exome sequencing...
October 31, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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