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https://www.readbyqxmd.com/read/29435021/long-lasting-memory-of-cellular-immunity-in-a-chronic-myeloid-leukemia-patient-maintains-molecular-response-5-after-cessation-of-dasatinib
#1
Tatsuro Jo, Kazuhiro Noguchi, Shizuka Hayashi, Sadaharu Irie, Risa Hayase, Haruna Shioya, Youhei Kaneko, Kensuke Horio, Jun Taguchi
Tyrosine kinase inhibitors (TKIs), including imatinib, dasatinib and nilotinib are primarily used in the initial treatment of chronic phase (CP)-chronic myeloid leukemia (CML), as CMLs harbor the BCR-ABL fusion product. An increased number of lymphocytes and large granular lymphocytes (LGLs) have been observed in patients treated with dasatinib, but not other TKIs. The LGLs have been reported to be primarily natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). In the present study, a CP-CML patient who has maintained molecular response 5 for >2...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434033/pdgfrb-mutation-and-tyrosine-kinase-inhibitor-resistance-in-ph-like-acute-lymphoblastic-leukemia
#2
Yingchi Zhang, Yufeng Gao, Hui Zhang, Jingliao Zhang, Fuhong He, Aleš Hnízda, Maoxiang Qian, Xiaoming Liu, Yoshihiro Gocho, Ching-Hon Pui, Tao Cheng, Qianfei Wang, Jun J Yang, Xiaofan Zhu, Xin Liu
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) comprises of approximately 10-15% of childhood ALL cases, many of whom respond exquisitely to tyrosine kinase inhibitors (TKIs), e.g., imatinib in PDGFRB-rearranged ALL. However, some cases developed drug resistance to TKIs with mechanisms poorly understood. In this study, we identified a novel PDGFRB fusion gene, namely AGGF1-PDGFRB, and functionally characterized its oncogenic potential in vitro. Further genomic profiling of longitudinally collected samples during treatment revealed the emergence of a mutation PDGFRBC843G , which directly conferred resistance to all generations of ABL TKIs, including imatinib, dasatinib, nilotinib, and ponatinib...
February 6, 2018: Blood
https://www.readbyqxmd.com/read/29431866/monocyte-subsets-and-their-phenotypes-during-treatment-with-bcr-abl1-tyrosine-kinase-inhibitors-for-philadelphia-chromosome-positive-leukemia
#3
Takaaki Konuma, Chisato Kohara, Eri Watanabe, Motoko Mizukami, Etsuko Nagai, Susumu Tanoue, Masamichi Isobe, Koji Jimbo, Seiko Kato, Nobuhiro Ohno, Satoshi Takahashi, Arinobu Tojo
BCR-ABL1 tyrosine kinase inhibitors (TKIs) are effective agents in the treatment of Philadelphia chromosome-positive leukemia. However, vascular events have developed in some patients receiving each TKI. The perturbation of circulating monocyte subsets and their expressions of chemokine and scavenger receptors are associated with the development of cardiovascular events. Here, we examined the subsets of circulating monocytes and their phenotypes in 51 patients treated with imatinib, nilotinib, and dasatinib, and 11 healthy subjects in our institute...
February 12, 2018: Hematological Oncology
https://www.readbyqxmd.com/read/29427149/phase-i-trial-of-dasatinib-lenalidomide-and-temozolomide-in-children-with-relapsed-or-refractory-central-nervous-system-tumors
#4
Nathan J Robison, Kee Kiat Yeo, Adrian P Berliner, Jemily Malvar, Michael A Sheard, Ashley S Margol, Robert C Seeger, Teresa Rushing, Jonathan L Finlay, Richard Sposto, Girish Dhall
Single agent studies targeting the tumor microenvironment in central nervous system (CNS) tumors have largely been disappointing. Combination therapies targeting various pathways and cell types may be a more effective strategy. In this phase I study, we evaluated the combination of dasatinib, lenalidomide, and temozolomide in children with relapsed or refractory primary CNS tumors. Patients 1-21 years old with relapsed or refractory CNS tumors were eligible. Starting doses of dasatinib and lenalidomide were 65 mg/m2/dose twice daily and 55 mg/m2 once daily, respectively, while temozolomide was constant at 75 mg/m2 daily...
February 9, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29416938/complete-response-in-advanced-breast-cancer-patient-treated-with-a-combination-of-capecitabine-oral-vinorelbine-and-dasatinib
#5
V Sgroi, M Bassanelli, M Roberto, E Iannicelli, R Porrini, P Pellegrini, A Tafuri, P Marchetti
Background: Currently, there are no data available on the best choice of treatment in heavily pretreated patients with advanced breast cancer. However, the combination of oral vinorelbine and capecitabine has been demonstrated to be effective and safe in patients with advanced breast cancer pretreated with anthracycline. Furthermore, some studies assessed the activity of dasatinib, an oral tyrosine kinase inhibitor that inhibits five oncogenic tyrosine kinase families, alone or in combination with different chemotherapy in patients affected with advanced breast cancer...
2018: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/29416058/divergent-roles-for-antigenic-drive-in-the-aetiology-of-primary-versus-dasatinib-associated-cd8-tcr-v%C3%AE-expansions
#6
Anna Lissina, James E McLaren, Mette Ilander, Emma I Andersson, Catherine S Lewis, Mathew Clement, Andrew Herman, Kristin Ladell, Sian Llewellyn-Lacey, Kelly L Miners, Emma Gostick, J Joseph Melenhorst, A John Barrett, David A Price, Satu Mustjoki, Linda Wooldridge
CD8+ T-cell expansions are the primary manifestation of T-cell large granular lymphocytic leukemia (T-LGLL), which is frequently accompanied by neutropenia and rheumatoid arthritis, and also occur as a secondary phenomenon in leukemia patients treated with dasatinib, notably in association with various drug-induced side-effects. However, the mechanisms that underlie the genesis and maintenance of expanded CD8+ T-cell receptor (TCR)-Vβ+ populations in these patient groups have yet to be fully defined. In this study, we performed a comprehensive phenotypic and clonotypic assessment of expanded (TCR-Vβ+) and residual (TCR-Vβ-) CD8+ T-cell populations in T-LGLL and dasatinib-treated chronic myelogenous leukemia (CML) patients...
February 7, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29415932/-management-of-cardiovascular-complications-in-cml-patients-treated-with-tyrosine-kinase-inhibitors
#7
Itaru Matsumura
Tyrosine kinase inhibitors (TKIs) have significantly improved the clinical outcomes of patients with chronic myeloid leukemia (CML). However, patients with CML need to receive TKI therapy for several years. Hence, the safety of long-term TKI treatment warrants utmost attention. Among various adverse events caused by TKI therapy, cardiovascular events (CVEs), such as acute myocardial infarction, cerebral infarction, and pulmonary hypertension, are the most serious with high mortality. TKIs inhibit various off-target molecules involved in the occurrence of CVEs such as c-Kit, platelet-derived growth factor receptor (PDGFR), vascular endothelial growth factor receptor (VEGFR), and Tie-2/Tec...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29414500/priapism-as-the-initial-sign-in-hematologic-disease-case-report-and-literature-review
#8
Luis Cuitláhuac Becerra-Pedraza, Luis Enrique Jiménez-Martínez, Iran Peña-Morfin, Rogelio Nava-Esquivel, Juan Alfredo Villegas-Martínez
INTRODUCTION: Priapism is an uncommon sign and sometimes considered a diagnosis challenge into systemic disease; this is defined as ≥4 h continuous penile erection, without sexual stimulation. We state that this work has been reported in line with the SCARE criteria PRESENTATION OF CASE: A Mexican 52-year-old man was brought to the emergency room with priapism of six days of evolution. His medical history reported fatigue and waxy pallor had begun a month ago, the rest of interrogation was unremarked...
January 12, 2018: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29411417/chronic-myeloid-leukemia-2018-update-on-diagnosis-therapy-and-monitoring
#9
Elias Jabbour, Hagop Kantarjian
DISEASE OVERVIEW: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an incidence of 1-2 cases per 100 000 adults. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults. DIAGNOSIS: CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome...
March 2018: American Journal of Hematology
https://www.readbyqxmd.com/read/29407585/regulatory-t-cell-inhibition-by-dasatinib-is-associated-with-natural-killer-cell-differentiation-and-a-favorable-molecular-response-the-final-results-of-the-d-first-study
#10
Yuho Najima, Chikashi Yoshida, Noriyoshi Iriyama, Shin Fujisawa, Hisashi Wakita, Shigeru Chiba, Shinichiro Okamoto, Kimihiro Kawakami, Naoki Takezako, Takashi Kumagai, Kazuma Ohyashiki, Jun Taguchi, Shingo Yano, Tadahiko Igarashi, Yasuji Kouzai, Satoshi Morita, Junichi Sakamoto, Hisashi Sakamaki, Koiti Inokuchi
We evaluated the effects of regulatory T cell (Treg) inhibition during dasatinib treatment on the anticancer immune response, particularly on natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Fifty-two newly diagnosed Japanese patients with chronic myeloid leukemia (CML) in the chronic phase were enrolled in the D-first study; all received 100 mg of dasatinib once daily and were followed for at least 36 months. The cumulative deep molecular response (DMR, MR4) rate was 65% by 36 months; the 3-year overall survival was 96%...
February 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29406237/a-68-year-old-man-with-chronic-myelogenous-leukemia-and-a-large-unilateral-pleural-effusion
#11
Adam Alter, Neal Chaisson, Sudipto Mukherjee, Thomas Gildea
A 68-year-old man with chronic myelogenous leukemia presents for evaluation of 2 months of dyspnea with exertion. He denies cough, fever, chest pain, weight gain, orthopnea, and edema. Since diagnosis of chronic myelogenous leukemia 5 years ago, he has been treated with dasatinib, with recent BCR-ABL1 assay showing no detectable disease in the peripheral blood. Medical history also includes hyperlipidemia, prostate enlargement, and hypothyroidism, but no prior heart or lung disease. Born in the Middle East, he immigrated to the United States 30 years ago and is working as a physician...
February 2018: Chest
https://www.readbyqxmd.com/read/29405196/haematological-cancer-dasatinib-regulates-immune-cell-function
#12
Diana Romero
No abstract text is available yet for this article.
February 6, 2018: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/29404062/a-validated-uplc-ms-ms-method-for-simultaneous-determination-of-imatinib-dasatinib-and-nilotinib-in-human-plasma
#13
Jing Zeng, Hua Lin Cai, Zhi Ping Jiang, Qing Wang, Yan Zhu, Ping Xu, Xie Lan Zhao
A sensitive, rapid, simple and economical ultra-performance liquid chromatography-tandem mass spectrometric method (UPLC-MS/MS) was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard (IS). Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A (aqueous phase: 0.15% formic acid and 0...
December 2017: Journal of Pharmaceutical Analysis
https://www.readbyqxmd.com/read/29395973/design-and-synthesis-of-novel-dasatinib-derivatives-as-inhibitors-of-leukemia-stem-cells
#14
Hui-Ying Li, Ding-Di He, Xiu-Juan Zhao, Tong-Yan Sun, Quan Zhang, Cui-Gai Bai, Yue Chen
We used the concept of bioisosteres to design and synthesize a novel series of dasatinib derivatives for the treatment of leukemia. Unfortunately, most of the dasatinib derivatives did not show appreciable inhibition against leukemia cell lines K562 and HL60. However, acrylamide compound 2c had comparable inhibitory activity with dasatinib against K562 cells (IC50 = 0.039 nM vs. 0.069 nM). And amide compound 2a and acrylamide compound 2c also had comparable inhibitory activity with dasatinib against the leukemia cell line HL60 (IC50 = 0...
January 12, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29386436/-analysis-of-time-to-onset-of-interstitial-lung-disease-after-the-administration-of-small-molecule-molecularly-targeted-drugs
#15
Fusao Komada
 The aim of this study was to investigate the time-to-onset of drug-induced interstitial lung disease (DILD) following the administration of small molecule molecularly-targeted drugs via the use of the spontaneous adverse reaction reporting system of the Japanese Adverse Drug Event Report database. DILD datasets for afatinib, alectinib, bortezomib, crizotinib, dasatinib, erlotinib, everolimus, gefitinib, imatinib, lapatinib, nilotinib, osimertinib, sorafenib, sunitinib, temsirolimus, and tofacitinib were used to calculate the median onset times of DILD and the Weibull distribution parameters, and to perform the hierarchical cluster analysis...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/29385210/abcc6-plays-a-significant-role-in-the-transport-of-nilotinib-and-dasatinib-and-contributes-to-tki-resistance-in-vitro-in-both-cell-lines-and-primary-patient-mononuclear-cells
#16
Laura N Eadie, Phuong Dang, Jarrad M Goyne, Timothy P Hughes, Deborah L White
ATP Binding Cassette family efflux proteins ABCB1 and ABCG2 have previously been demonstrated to interact with Tyrosine Kinase Inhibitors (TKIs); however, evidence for the interaction of other potentially relevant drug transporters with TKIs is lacking. Through Taqman transporter array technology we assessed the impact of nilotinib on mRNA expression of ABC transporters, with ABCC6 identified as a transporter of interest. Additionally, increased expression of ABCC6 mRNA was observed during in vitro development of nilotinib resistance in BCR-ABL1-expressing cell lines...
2018: PloS One
https://www.readbyqxmd.com/read/29384978/efficacy-and-safety-of-autologous-peripheral-blood-stem-cell-transplantation-for-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-a-study-protocol-for-a-multicenter-exploratory-prospective-study-auto-ph17-study
#17
Satoshi Nishiwaki, Isamu Sugiura, Yasuhiko Miyata, Shigeki Saito, Masashi Sawa, Tetsuya Nishida, Koichi Miyamura, Yachiyo Kuwatsuka, Akio Kohno, Masaaki Yuge, Masanobu Kasai, Hiroatsu Iida, Shingo Kurahashi, Masahide Osaki, Tatsunori Goto, Seitaro Terakura, Makoto Murata, Hiroyoshi Nishikawa, Hitoshi Kiyoi
INTRODUCTION: The prognosis of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL) has been dramatically improved since the introduction of tyrosine kinase inhibitors (TKIs). Although allogeneic hematopoietic cell transplantation (allo-HCT) is a major treatment option, the role of autologous peripheral blood stem cell transplantation (auto-PBSCT) has been reconsidered, especially in patients who achieved early molecular remission. METHODS AND ANALYSIS: This is a multicenter exploratory study for Ph + ALL patients aged between 55 and 70 years who achieved complete molecular remission within 3 cycles of chemotherapy...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29370463/dasatinib-dose-management-for-the-treatment-of-chronic-myeloid-leukemia
#18
REVIEW
Moshe Talpaz, Giuseppe Saglio, Ehab Atallah, Philippe Rousselot
Chronic myeloid leukemia (CML) has evolved into a chronic disease that is managed with tyrosine kinase inhibitor therapy. Now that long-term survival has been achieved in patients with CML, the focus of treatment has shifted to dose optimization, with the goal of maintaining response while improving quality of life. In this review, the authors discuss optimizing the dose of the second-generation tyrosine kinase inhibitor dasatinib. Once-daily dosing regimens for dasatinib in the first and later lines of treatment were established through long-term (5-year and 7-year) trials...
January 25, 2018: Cancer
https://www.readbyqxmd.com/read/29348177/dasatinib-increases-endothelial-permeability-leading-to-pleural-effusion
#19
Carole Phan, Etienne-Marie Jutant, Ly Tu, Raphaël Thuillet, Andrei Seferian, David Montani, Alice Huertas, Jan van Bezu, Fabian Breijer, Anton Vonk Noordegraaf, Marc Humbert, Jurjan Aman, Christophe Guignabert
Pleural effusion is a frequent side-effect of dasatinib, a second-generation tyrosine kinase inhibitor used in the treatment of chronic myelogenous leukaemia. However, the underlying mechanisms remain unknown. We hypothesised that dasatinib alters endothelial integrity, resulting in increased pulmonary vascular endothelial permeability and pleural effusion.To test this, we established the first animal model of dasatinib-related pleural effusion, by treating rats with a daily regimen of high doses of dasatinib (10 mg·kg-1·day-1 for 8 weeks)...
January 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29345355/effects-of-antioxidants-on-apoptosis-induced-by-dasatinib-and-nilotinib-in-k562-cells
#20
Sara Damiano, Serena Montagnaro, Maria Valeria Puzio, Lorella Severino, Ugo Pagnini, Marcella Barbarino, Daniele Cesari, Antonio Giordano, Salvatore Florio, Roberto Ciarcia
In clinical practice for the treatment of chronic myeloid leukemia, second generation of tyrosine kinase inhibitors such as Nilotinib (NIL) specific and potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS) a inhibitor of BCR/ABL and Src family kinase were developed to clinically overcome imatinib resistance. In this study we wanted to test the ability of some antioxidants such Resveratrol (RES) or a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) or δ-tocotrienol (δ-TOCO) to interact with DAS and NIL on viability, reactive oxygen species (ROS) production, lipid peroxidation and apoptosis...
January 18, 2018: Journal of Cellular Biochemistry
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