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https://read.qxmd.com/read/30901734/development-and-validation-of-a-uplc-uv-method-for-the-quantification-of-thiopurine-methyltransferase-enzyme-activity-in-human-erythrocytes
#1
S M Illamola, A K Echaabi, C Mazeron, S Deshayes, M A Loriot, N Pallet
Thiopurines are drugs widely used for the treatment of autoimmune conditions, inflammatory bowel disease or acute lymphoblastic leukemia. Determination of thiopurine methyltransferase activity (TPMT), a major determinant of thiopurines toxicity, has been suggested before implementing thiopurine treatment. An ultraperformance liquid chromatography (UPLC) method was developed and validated for the quantification of TPMT enzyme activity based on the conversion of 6-mercaptopurine (6-MP) to 6-methylmercaptopurine (6-MMP) using S-adenosyl-L-methionine (SAM) as methyl donor in red blood cell lysates (RBC)...
March 14, 2019: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://read.qxmd.com/read/30901283/gold-nanoparticles-for-sustained-antileukemia-drug-release-development-optimization-and-evaluation-by-quality-by-design-approach
#2
Sandeep Kumar Reddy Adena, Mansi Upadhyay, Harsh Vardhan, Brahmeshwar Mishra
AIM: To design, develop, optimize and evaluate sustained-release dasatinib-loaded gold nanoparticles (DSB-GNPs) to treat chronic myeloid leukemia (CML) by using quality by design. MATERIALS & METHODS: In this study, we performed risk assessment, optimization, in vitro characterizations, stability study, drug release studies, cytotoxicity study and in vivo pharmacokinetic evaluation. RESULTS: DSB-GNPs of desired size, entrapment, smooth, spherical, stable and sustained drug release for 48 h were achieved...
March 22, 2019: Nanomedicine
https://read.qxmd.com/read/30900929/employment-status-and-work-ability-in-long-term-young-adult-cancer-survivors
#3
Alv A Dahl, Sophie D Fosså, Hanne C Lie, Jon Håvard Loge, Kristin Valborg Reinertsen, Ellen Ruud, Cecilie Essholt Kiserud
PURPOSE: In young adult cancer survivors (YACSs) to explore the rate of being nonemployed and having low work ability, and to identify factors associated with these two outcomes. METHODS: All Norwegian YACSs (N = 3558) diagnosed at ages 19-39 years and treated between 1985 and 2009 for breast or colorectal cancer, leukemia, non-Hodgkin lymphoma, or melanoma, and alive in 2015, were mailed a questionnaire. The response rate was 42%. For treatment, a minimal surgery-only group (N = 198) was defined as reference group, and 1000 YACSs represented the local, systemic, and systemic plus other treatment groups...
March 22, 2019: Journal of Adolescent and Young Adult Oncology
https://read.qxmd.com/read/30900388/measurable-residual-disease-monitoring-using-wilms-tumor-gene-1-expression-in-childhood-acute-myeloid-leukemia-based-on-child-specific-reference-values
#4
Kristian Løvvik Juul-Dam, Charlotte Guldborg Nyvold, Helen Vålerhaugen, Bernward Zeller, Birgitte Lausen, Henrik Hasle, Hans Beier Ommen
BACKGROUND: Measurable/minimal residual disease (MRD) monitoring can predict imminent hematological relapse in acute myeloid leukemia (AML). The majority of childhood AML patients do not harbor fusion genes or mutations applicable as MRD markers and overexpression of Wilms tumor gene 1 (WT1) may constitute a useful monitoring target. However, age-specific reference values in healthy hematopoiesis and standardization of WT1 assessment are prerequisites for clinical utility. PROCEDURE: We investigated WT1 expression across age in hematologically healthy controls (n = 109), during suspected infection (n = 90) and bone marrow (BM) regeneration (n = 13)...
March 21, 2019: Pediatric Blood & Cancer
https://read.qxmd.com/read/30899476/pulmonary-alveolar-proteinosis-developing-during-steroid-treatment-in-a-patient-with-organizing-pneumonia-in-association-with-atypical-chronic-myeloid-leukemia
#5
Chiaki Hosoda, Keisuke Saito, Shota Fujimoto, Yumie Yamanaka, Naoaki Watanabe, Hanae Miyagawa, Yusuke Kurita, Yoshitaka Seki, Akira Kinoshita, Yasuhiko Endo, Kazuyoshi Kuwano
Organizing pneumonia (OP) and pulmonary alveolar proteinosis (PAP) are rare complications in patients with hematologic disorders. We herein report a case of PAP that developed during steroid treatment for OP in a patient with atypical chronic myeloid leukemia. Physicians should pay close attention to these complications in patients with hematologic malignancies.
March 2019: Clinical Case Reports
https://read.qxmd.com/read/30898889/the-ema-review-of-mylotarg-gemtuzumab-ozogamicin-for-the-treatment-of-acute-myeloid-leukemia
#6
Sahra Ali, Helen-Marie Dunmore, Dominik Karres, Justin L Hay, Tomas Salmonsson, Christian Gisselbrecht, Sinan B Sarac, Ole W Bjerrum, Doris Hovgaard, Yolanda Barbachano, Nithyanandan Nagercoil, Francesco Pignatti
On February 22, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product gemtuzumab ozogamicin (Mylotarg; Pfizer, New York City, NY), intended for the treatment of acute myeloid leukemia. Mylotarg was designated as an orphan medicinal product on October 18, 2000. The applicant for this medicinal product was Pfizer Limited (marketing authorization now held by Pfizer Europe MA EEIG).The demonstrated benefit with Mylotarg is improvement in event-free survival...
March 21, 2019: Oncologist
https://read.qxmd.com/read/30898482/predictive-model-for-infection-risk-in-myelodysplastic-syndromes-acute-myeloid-leukemia-and-chronic-myelomonocytic-leukemia-patients-treated-with-azacitidine-azacitidine-infection-risk-model-the-polish-adult-leukemia-group-study
#7
Krzysztof Mądry, Karol Lis, Przemysław Biecek, Magda Młynarczyk, Jagoda Rytel, Michał Górka, Piotr Kacprzyk, Magdalena Dutka, Marek Rodzaj, Łukasz Bołkun, Dorota Krochmalczyk, Ewa Łątka, Joanna Drozd-Sokołowska, Anna Waszczuk-Gajda, Wanda Knopińska-Posłuszny, Anna Kopińska, Edyta Subocz, Anna Masternak, Renata Guzicka-Kazimierczak, Lidia Gil, Rafał Machowicz, Jarosław Biliński, Sebastian Giebel, Tomasz Czerw, Jadwiga Dwilewicz-Trojaczek
BACKGROUND: Myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) patients, including those treated with azacitidine, are at increased risk for serious infections. The aim of our study was to identify patients with higher infectious risk at the beginning of azacitidine treatment. PATIENTS AND METHODS: We performed a retrospective evaluation of 298 MDS/CMML/AML patients and included in the analysis 232 patients who completed the first 3 cycles of azacitidine therapy or developed Grade III/IV infection before completing the third cycle...
January 23, 2019: Clinical Lymphoma, Myeloma & Leukemia
https://read.qxmd.com/read/30897600/efficacy-and-influencing-factors-of-allogeneic-hematopoietic-stem-cell-transplantation-in-treatment-of-71-children-with-leukemia
#8
Bing-Lei Zhang, Jian Zhou, Tian-Xi Lyu, Rui-Rui Gui, Ying-Ling Zu, Feng-Kuan Yu, Hui-Fang Zhao, Zhen Li, Juan Wang, Yan-Li Zhang, Wen-Lin Zhang, Yue-Wen Fu, Xu-Dong Wei, Bai-Jun Fang, Yu-Fu Li, Ke-Shu Zhou, Yong-Ping Song
No abstract text is available yet for this article.
April 5, 2019: Chinese Medical Journal
https://read.qxmd.com/read/30897165/diagnostic-performance-of-the-molecular-bcr-abl1-monitoring-system-may-impact-on-inclusion-of-cml-patients-in-stopping-trials
#9
Birgit Spiess, Sébastien Rinaldetti, Nicole Naumann, Norbert Galuschek, Ute Kossak-Roth, Patrick Wuchter, Irina Tarnopolscaia, Diana Rose, Astghik Voskanyan, Alice Fabarius, Wolf-Karsten Hofmann, Susanne Saußele, Wolfgang Seifarth
In chronic myeloid leukemia (CML), the duration of deep molecular response (MR) before treatment cessation (MR4 or deeper, corresponding to BCR-ABL1 ≤ 0.01% on the International Scale (IS)) is considered as a prognostic factor for treatment free remission in stopping trials. MR level determination is dependent on the sensitivity of the monitoring technique. Here, we compared a newly established TaqMan (TM) and our so far routinely used LightCycler (LC) quantitative reverse transcription (qRT)-PCR systems for their ability to achieve the best possible sensitivity in BCR-ABL1 monitoring...
2019: PloS One
https://read.qxmd.com/read/30897014/cancer-stem-cells-in-radiation-response-current-views-and-future-perspectives-in-radiation-oncology
#10
Claudia Peitzsch, Ina Kurth, Nadja Ebert, Anna Dubrovska, Michael Baumann
PURPOSE: Despite technological improvement and advances in biology-driven patient stratification, many patients still fail radiotherapy resulting in loco-regional and distant recurrence. Tumor heterogeneity remains a key challenge to effective cancer treatment, and reliable stratification of cancer patients for prediction of outcomes is highly important. Intratumoral heterogeneity is manifested at the different levels, including different tumorigenic properties of cancer cells. Since John Dick and coauthors isolated leukemia initiating cells in 1990th , the populations of tumor initiating or cancer stem cells (CSCs) were identified and characterized also for a broad spectrum of solid tumor types...
March 21, 2019: International Journal of Radiation Biology
https://read.qxmd.com/read/30896824/timosaponin-a%C3%A2-iii-induces-autophagy-of-t%C3%A2-cell-acute-lymphoblastic-leukemia-jurkat-cells-via-inhibition-of-the-pi3k-akt-mtor-pathway
#11
Hong Wang, Rui Dong, Wen-Wen Fan, Xing-Chang Zheng, Ai-Min Li, Wen-Di Wang
Timosaponin A‑III (TAIII) is a saponin isolated from anemarrhena asphodeloides and possesses the inhibitory effect on proliferation of multiple tumor cells. In the present study, the antitumor effect of TAIII and its underlying molecular mechanisms were investigated in vitro in T‑cell acute lymphoblastic leukemia (T‑ALL) Jurkat cells. The results demonstrated that TAIII inhibits the viability of Jurkat cells in a time‑ and dose‑dependent manner, and induces apoptosis of Jurkat cells in a dose‑dependent manner...
March 15, 2019: Oncology Reports
https://read.qxmd.com/read/30896812/role-of-natural-killer-cells-for-immunotherapy-in-chronic-myeloid-leukemia-review
#12
Hye-Rim Lee, Kwang-Hyun Baek
The majority of natural killer (NK) cells serve an important role in eliminating malignant cells. The cytotoxic effects of NK cells were first identified against leukemia cells, and it is now hypothesized that they may have a critical role in leukemia therapy. The cellular functions of NK cells are mediated by their cell surface receptors, which recognize ligands on cancer cells. The role of NK cells is specifically regulated by the activating or inhibitory killer cell immunoglobulin‑like receptors (KIRs) on their surface, which bind to the human leukocyte antigen (HLA) class I ligands present on the target cells...
March 13, 2019: Oncology Reports
https://read.qxmd.com/read/30894378/broad-cytotoxic-targeting-of-acute-myeloid-leukemia-by-polyclonal-delta-one-t-cells
#13
Biagio Di Lorenzo, André E Simões, Francisco Caiado, Paola Tieppo, Daniel V Correia, Tânia Carvalho, Maria Gomes da Silva, Julie Déchanet-Merville, Ton N Schumacher, Immo Prinz, Haakan Norell, Sarina Ravens, David Vermijlen, Bruno Silva-Santos
Acute myeloid leukemia (AML) remains a clinical challenge due to frequent chemotherapy resistance and deadly relapses. We are exploring the immunotherapeutic potential of peripheral blood Vδ1+ T cells, which associate with improved long-term survival of stem-cell transplant recipients but have not yet been applied as adoptive cell therapy. Using our clinical-grade protocol for expansion and differentiation of "Delta One T" (DOT) cells, we found DOT cells to be highly cytotoxic against AML primary samples and cell lines, including cells selected for resistance to standard chemotherapy...
March 20, 2019: Cancer Immunology Research
https://read.qxmd.com/read/30894066/discovery-and-characterization-of-a-novel-highly-potent-and-selective-type-ii-native-and-drug-resistant-v299l-mutant-bcr-abl-inhibitor-chmfl-abl-039-for-chronic-myeloid-leukemia-cml
#14
Jiaxin Wu, Aoli Wang, Xixiang Li, Cheng Chen, Ziping Qi, Chen Hu, Wenliang Wang, Hong Wu, Tao Huang, Ming Zhao, Wenchao Wang, Zhenquan Hu, Qingwang Liu, Beilei Wang, Li Wang, Lili Li, Jian Ge, Tao Ren, Ruixiang Xia, Jing Liu
BCR fused ABL kinase is the critical driving oncogene for chronic myeloid leukemia (CML) and has been extensively studied as the drug discovery target in the past decade. The successful introduction of tyrosine kinase inhibitors (TKI) such as Imatinib, Dasatinib and Bosutinib has greatly improved the CML patient survival rate. However, upon the chronic treatment, a variety of TKI resistant mutants, such as the V299L mutant which has been found in more and more patients with the high-throughput sequencing technology, are observed, although the incidence is still considered rare compared to the more prevalent gatekeeper T315I mutant...
March 20, 2019: Cancer Biology & Therapy
https://read.qxmd.com/read/30893351/differential-expression-of-mirnas-in-acute-myeloid-leukemia-quantified-by-nextgen-sequencing-of-whole-blood-samples
#15
Aakriti Pandita, Poornima Ramadas, Aarati Poudel, Nibal Saad, Ankit Anand, Alina Basnet, Dongliang Wang, Frank Middleton, Diana M Gilligan
New approaches are needed for understanding and treating acute myeloid leukemia (AML). MicroRNAs (miRs) are important regulators of gene expression in all cells and disruption of their normal expression can lead to changes in phenotype of a cell, in particular the emergence of a leukemic clone. We collected peripheral blood samples from 10 adult patients with newly diagnosed AML, prior to induction chemotherapy, and 9 controls. Two and a half ml of whole blood was collected in Paxgene RNA tubes. MiRNA was purified using RNeasy mini column (Qiagen)...
2019: PloS One
https://read.qxmd.com/read/30892988/venetoclax-combined-with-low-dose-cytarabine-for-previously-untreated-patients-with-acute-myeloid-leukemia-results-from-a-phase-ib-ii-study
#16
Andrew H Wei, Stephen A Strickland, Jing-Zhou Hou, Walter Fiedler, Tara L Lin, Roland B Walter, Anoop Enjeti, Ing Soo Tiong, Michael Savona, Sangmin Lee, Brenda Chyla, Relja Popovic, Ahmed Hamed Salem, Suresh Agarwal, Tu Xu, Kaffa M Fakouhi, Rod Humerickhouse, Wan-Jen Hong, John Hayslip, Gail J Roboz
PURPOSE: Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. An international phase Ib/II study evaluated the safety and preliminary efficacy of venetoclax, a selective B-cell leukemia/lymphoma-2 inhibitor, together with low-dose cytarabine (LDAC) in older adults with AML. PATIENTS AND METHODS: Adults 60 years or older with previously untreated AML ineligible for intensive chemotherapy were enrolled...
March 20, 2019: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://read.qxmd.com/read/30891583/anti-leukemic-and-anti-angiogenic-effects-of-d-limonene-on-k562-implanted-c57bl-6-mice-and-the-chick-chorioallantoic-membrane-model
#17
Bhavini B Shah, Ruma Baksi, Kiranj K Chaudagar, Manish Nivsarkar, Anita A Mehta
Background: d-Limonene, a monoterpene from citrus fruit has been found to have chemopreventive and chemotherapeutic activities in various types of cancers. In this study, we evaluated the in vivo effect of d-Limonene on a K562-induced model of chronic myeloid leukemia (CML) in C57BL/6 mice. Method: The tail vein injection model of K562 cells in immunocompromised C57BL/6 mice was developed and evaluated for characteristics of the disease. The mice were treated with d-Limonene and evaluated for haematological parameters...
December 2018: Animal Models and Experimental Medicine
https://read.qxmd.com/read/30891427/chimeric-antigen-receptors-for-t-cell-malignancies
#18
REVIEW
Lauren D Scherer, Malcolm K Brenner, Maksim Mamonkin
Development of chimeric antigen receptor (CAR)-modified T cells for the treatment of T-lineage leukemia and lymphoma has encountered several unique challenges. The most widely expressed tumor antigen targets for malignant T cells are often also expressed on non-malignant T cells. Transducing T cells with CARs targeted to these shared antigens can therefore promote over-activation or fratricide of CAR T cells, reducing their therapeutic potency. If fratricide is resolved, clinical CAR T cell activity may eliminate normal T-cell subsets and cause temporary immunosuppression...
2019: Frontiers in Oncology
https://read.qxmd.com/read/30891424/impact-of-additional-chromosomal-aberrations-on-the-disease-progression-of-chronic-myelogenous-leukemia
#19
Ramachandran Krishna Chandran, Narayanan Geetha, Kunnathur Murugesan Sakthivel, Raveendran Suresh Kumar, Kumarapillai Mohanan Nair Jagathnath Krishna, Hariharan Sreedharan
The emergence of additional chromosomal abnormalities (ACAs) in Philadelphia chromosome/ BCR-ABL1 positive chronic myeloid leukemia (CML), is considered to be a feature of disease evolution. However, their frequency of incidence, impact on prognosis and treatment response effect in CML is not conclusive. In the present study, we performed a chromosome analysis of 489 patients in different clinical stages of CML, using conventional GTG-banding, Fluorescent in situ Hybridization and Spectral Karyotyping. Among the de novo CP cases, ACAs were observed in 30 patients (10...
2019: Frontiers in Oncology
https://read.qxmd.com/read/30890600/high-prognostic-value-of-measurable-residual-disease-detection-by-flow-cytometry-in-chronic-lymphocytic-leukemia-patients-treated-with-front-line-fludarabine-cyclophosphamide-and-rituximab-followed-by-a-three-year-rituximab-maintenance
#20
José A García-Marco, Javier López Jiménez, Valle Recasens, Miguel Fernández Zarzoso, Eva González-Barca, Nieves Somolinos De Marcos, M Jose Ramírez, Francisco Javier Peñalver Parraga, Lucrecia Yañez, Javier De La Serna Torroba, Maria Dolores Garcia Malo, Guillermo Deben Ariznavarreta, Ernesto Perez Persona, M Angeles Ruiz Guinaldo, Raquel De Paz Arias, Elena Bañas Llanos, Isidro Jarque, M Del Carmen Fernandez Valle, Ana Carral Tatay, Jaime Perez De Oteyza, Eva Donato Martin, Inmaculada Perez Fernández, Rafael Martinez Martinez, M Angeles Andreu Costa, Diana Champ, Julio García Suarez, Marcos González Diaz, Secundino Ferrer, Félix Carbonell, José A García-Vela
Monitoring measurable residual disease has been postulated to be a surrogate marker of progression free survival in chronic lymphocytic leukemia patients after treatment with immunochemotherapy regimens. In this study, we have analyzed the outcome of 84 patients at 3 years of follow up after first line treatment with fludarabine, cyclophosphamide and rituximab induction followed by 36 months of rituximab maintenance. Measurable residual disease was assessed by a quantitative four-color flow cytometry panel with a sensitivity level of 10-4...
March 19, 2019: Haematologica
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