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https://www.readbyqxmd.com/read/28104295/systematic-drug-sensitivity-testing-reveals-synergistic-growth-inhibition-by-dasatinib-or-mtor-inhibitors-with-paclitaxel-in-ovarian-granulosa-cell-tumor-cells
#1
Ulla-Maija Haltia, Noora Andersson, Bhagwan Yadav, Anniina Färkkilä, Evgeny Kulesskiy, Matti Kankainen, Jing Tang, Ralf Bützow, Annika Riska, Arto Leminen, Markku Heikinheimo, Olli Kallioniemi, Leila Unkila-Kallio, Krister Wennerberg, Tero Aittokallio, Mikko Anttonen
OBJECTIVE: Resistance to standard chemotherapy poses a major clinical problem in the treatment of ovarian cancer patients. Adult-type granulosa cell tumor (AGCT) is a unique ovarian cancer subtype for which efficient treatment options are lacking in advanced disease. To this end, systematic drug response and transcriptomics profiling were performed to uncover new therapy options for AGCTs. METHODS: The responses of three primary and four recurrent AGCTs to 230 anticancer compounds were screened in vitro using a systematic drug sensitivity and resistance testing (DSRT) platform, coupled with mRNA sequencing...
January 16, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28102731/microfluidic-whole-blood-testing-of-platelet-response-to-pharmacological-agents
#2
Ruizhi Li, Tilo Grosser, Scott L Diamond
Platelets present a number of intracellular and transmembrane targets subject to pharmacological modulation, either for cardiovascular disease reduction or as an unintended drug response. Microfluidic devices allow human blood to clot on a defined surface under controlled hemodynamic and pharmacological conditions. The potencies of a number of antiplatelet and anticancer drugs have been tested with respect to platelet deposition on collagen under flow. Inhibitors of cyclooxygenase-1 (COX-1) reduce platelet deposition, either when added ex vivo to blood or ingested orally by patients prior to testing...
January 19, 2017: Platelets
https://www.readbyqxmd.com/read/28098949/identification-of-cellular-targets-involved-in-cardiac-failure-caused-by-pki-in-oncology-an-approach-combining-pharmacovigilance-and-pharmacodynamics
#3
E Patras de Campaigno, E Bondon-Guitton, G Laurent, F Montastruc, J L Montastruc, M Lapeyre-Mestre, F Despas
AIMS: To evaluate the risk of cardiac failure (CF) of 15 anticancer protein kinase inhibitors (PKIs) through a case/non-case analysis and to identify which PK(s) and pathways are involved in PKI-induced CF. METHODS: To evaluate the risk of CF, adjusted reporting odds ratios (aRORs) were calculated for the 15 anticancer PKIs in the WHO safety report database (VigiBase®). We realised a literature review to identify 21 PK possibly involved in CF caused by PKIs. Pearson's correlation coefficients (r) between aROR and affinity data of the 15 PKIs for the 21 PKs were calculated to identify the cellular target most likely involved in PKI-induced CF...
January 18, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28093990/insight-to-pharmacokinetics-of-tkis-optimizing-practical-guidelines-for-individualized-therapy
#4
Ruiqing Wang, Chaoqin Zhong, Chen Zhang, Mingqiang Hua, Daoxin Ma
Tyrosine kinase inhibitors (TKIs) are widely used drugs which have high availability in reducing the activity of BCR-ABL1 tyrosine kinase, therefore they play an indispensable role in the treatment of Chronic myeloid leukemia (CML). Imatinib, dasatinib and nilotinib have been proved to have absolute bioavailability and stable blood concentration in humans. TKIs pharmacokinetics has close relationships with the clinical response and clinical treatment of CML. We conducted a systematic PubMed search to look for studies relating to TKIs pharmacokinetics with proper inclusion/exclusion criteria...
January 16, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28090053/a-suspected-case-of-an-alveolar-haemorrhage-caused-by-dasatinib
#5
Yoritake Sakoda, Yojiro Arimori, Masakatsu Ueno, Takafumi Matsumoto
A 39-year-old man treated with dasatinib for chronic myelogenous leukaemia presented to our hospital with haemoptysis, coughing, and dyspnoea. Chest radiography and computed tomography revealed ground-glass opacities and a crazy-paving pattern. Bronchoalveolar lavage was not performed due to serious hypoxemia and bleeding. Significant bleeding from the peripheral bronchi led to a diagnosis of an alveolar haemorrhage. Dasatinib-induced alveolar haemorrhaging was suspected based on the clinical findings. His condition improved immediately after dasatinib withdrawal and initiation of steroid therapy...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28074043/correction-dasatinib-a-src-inhibitor-sensitizes-liver-metastatic-colorectal-carcinoma-to-oxaliplatin-in-tumors-with-high-levels-of-phospho-src
#6
Marco Perez, Antonio Lucena-Cacace, Luis Miguel Marín-Gómez, Javier Padillo-Ruiz, Maria Jose Robles-Frias, Carmen Saez, Rocio Garcia-Carbonero, Amancio Carnero
No abstract text is available yet for this article.
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28073814/donor-derived-mycosis-fungoides-following-reduced-intensity-haematopoietic-stem-cell-transplantation-from-a-matched-unrelated-donor
#7
Francesca A M Kinsella, Mohammad Rasoul Amel Kashipaz, Julia Scarisbrick, Ram Malladi
A 46-year-old woman with a history of dasatinib-resistant chronic myeloid leukaemia, clonal evolution and monosomy 7 underwent reduced intensity conditioned in vivo T-cell-depleted allogeneic haematopoietic stem cell transplantation (HSCT) from a matched unrelated donor. Following the transplantation, she developed recurrent cutaneous graft versus host disease (GvHD), which required treatment with systemic immunosuppression and electrocorporeal photophoresis. Concurrently, she developed a lichenoid rash with granulomatous features suggestive of cutaneous sarcoidosis...
January 10, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28073775/dasatinib-changes-immune-cell-profiles-concomitant-with-reduced-tumor-growth-in-several-murine-solid-tumor-models
#8
Can Hekim, Mette Ilander, Jun Yan, Erin Michaud, Richard Smykla, Markus Vähä-Koskela, Paula Savola, Siri Tähtinen, Leena Saikko, Akseli Hemminki, Panu E Kovanen, Kimmo Porkka, Francis Yf Lee, Satu Mustjoki
Dasatinib, a broad range tyrosine kinase inhibitor (TKI), induces rapid mobilization of lymphocytes and clonal expansion of cytotoxic cells in leukemia patients. Here, we investigated whether dasatinib could induce beneficial immunomodulatory effects in solid tumor models. The effects on tumor growth and on the immune system were studied in four different syngeneic mouse models (B16.OVA melanoma, 1956 sarcoma, MC38 colon, and 4T1 breast carcinoma). Both peripheral blood (PB) and tumor samples were immunophenotyped during treatment...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28070919/clinical-utility-of-the-basophil-activation-test-for-analysis-of-allergic-transfusion-reactions-a-pilot-study
#9
I Okamura, N Matsuyama, K Yasui, F Hirayama, T Ikeda
BACKGROUND AND OBJECTIVES: In previous studies, we demonstrated that the basophil-activating effects of supernatants found in residual-transfused platelet concentrates (PC-SNs) on whole blood basophils in cases of allergic transfusion reactions (ATRs) could be assessed by the basophil activation test (BAT) in terms of allergen/IgE dependency. However, in these studies, the basophils were derived from third-party healthy volunteers. In this study, we performed BAT using patients' own blood basophils to analyse ATRs...
January 10, 2017: Vox Sanguinis
https://www.readbyqxmd.com/read/28057740/dasatinib-and-allogeneic-stem-cell-transplantation-enable-sustained-response-in-an-elderly-patient-with-rcsd1-abl1-positive-acute-lymphoblastic-leukemia
#10
Miriam Frech, Lutz B Jehn, Kathleen Stabla, Stephan Mielke, Björn Steffen, Hermann Einsele, Stephan K Metzelder, Andreas Neubauer
No abstract text is available yet for this article.
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28052354/evaluation-of-long-term-chronic-myeloid-leukemia-treatment-practices-with-tyrosine-kinase-inhibitors-in-a-national-cohort-of-veterans
#11
Eugene D Kreys, Christopher R Frei, Sarah M Villarreal, Mary J Bollinger, Xavier Jones, Jim M Koeller
STUDY OBJECTIVE: To evaluate nationwide chronic myeloid leukemia treatment practices over an extended period and across multiple lines of tyrosine kinase inhibitor (TKI) therapy with imatinib, dasatinib, and nilotinib. DESIGN: Retrospective cohort study. DATA SOURCE: Veterans Health Administration (VHA) national database. PATIENTS: A total of 2,873 VHA beneficiaries aged 18-89 years who had at least one encounter at any of the approximately 150 VHA hospitals and 800 VHA clinics, had a diagnosis code for chronic myeloid leukemia, and filled at least one prescription for imatinib, nilotinib, or dasatinib between October 1, 2001, and September 30, 2010...
January 4, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28051857/broad-spectrum-kinase-profiling-in-live-cells-with-lysine-targeted-sulfonyl-fluoride-probes
#12
Qian Zhao, Xiaohu Ouyang, Xiaobo Wan, Ketan S Gajiwala, John C Kath, Lyn H Jones, Alma L Burlingame, Jack Taunton
Protein kinases comprise a large family of structurally related enzymes. A major goal in kinase-inhibitor development is to selectively engage the desired kinase while avoiding myriad off-target kinases. However, quantifying inhibitor interactions with multiple endogenous kinases in live cells remains an unmet challenge. Here, we report the design of sulfonyl fluoride probes that covalently label a broad swath of the intracellular kinome with high efficiency. Protein crystallography and mass spectrometry confirmed a chemoselective reaction between the sulfonyl fluoride and a conserved lysine in the ATP binding site...
January 18, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28050024/principal-component-analysis-uncovers-cytomegalovirus-associated-nk-cell-activation-in-ph-leukemia-patients-treated-with-dasatinib
#13
K Ishiyama, T Kitawaki, N Sugimoto, T Sozu, N Anzai, M Okada, M Nohgawa, K Hatanaka, N Arima, T Ishikawa, S Tabata, T Onaka, S Oka, Y Nakabo, R Amakawa, M Matsui, T Moriguchi, A Takaori-Kondo, N Kadowaki
No abstract text is available yet for this article.
January 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28049640/cml-patients-with-deep-molecular-responses-to-tki-have-restored-immune-effectors-decreased-pd-1-and-immune-suppressors
#14
Amy Hughes, Jade Clarson, Carine Tang, Ljiljana Vidovic, Deborah L White, Timothy P Hughes, Agnes S M Yong
Immunological control may contribute to achievement of deep molecular response in chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment free remission (TFR). We investigated effector and suppressor immune responses in CML patients at diagnosis (n=21), on TKI (imatinib, nilotinib, dasatinib) prior to achieving major molecular response (pre-MMR, BCR-ABL1 >0.1%, n=8), MMR (BCR-ABL1 ≤0.1%, n=20), molecular response(4.5) (MR(4.5), BCR-ABL1 ≤0.0032%, n=16) and sustained TFR (BCR-ABL1 undetectable following cessation of TKI therapy, n=13)...
January 3, 2017: Blood
https://www.readbyqxmd.com/read/28045960/modelling-predictors-of-molecular-response-to-frontline-imatinib-for-patients-with-chronic-myeloid-leukaemia
#15
Haneen Banjar, Damith Ranasinghe, Fred Brown, David Adelson, Trent Kroger, Tamara Leclercq, Deborah White, Timothy Hughes, Naeem Chaudhri
BACKGROUND: Treatment of patients with chronic myeloid leukaemia (CML) has become increasingly difficult in recent years due to the variety of treatment options available and challenge deciding on the most appropriate treatment strategy for an individual patient. To facilitate the treatment strategy decision, disease assessment should involve molecular response to initial treatment for an individual patient. Patients predicted not to achieve major molecular response (MMR) at 24 months to frontline imatinib may be better treated with alternative frontline therapies, such as nilotinib or dasatinib...
2017: PloS One
https://www.readbyqxmd.com/read/28044939/inhibition-of-tgf-%C3%AE-signaling-in-tumor-cells-by-small-molecule-src-family-kinase-inhibitors
#16
Tobias Bartscht, Benjamin Rosien, Dirk Rades, Roland Kaufmann, Harald Biersack, Hendrik Lehnerta, Hendrik Ungefroren
In a series of studies carried out over the last couple of years in various cell types, it was observed that the experimentally used Src family kinase inhibitors PP1 and PP2 and the clinically used Src/Abl inhibitors AZM475271 and dasatinib are potent inhibitors of TGF-β mediated cellular responses such as Smad and p38 mitogen-activated protein kinase phosphorylation, Smad-dependent transcriptional activation, growth inhibition, epithelial-mesenchymal transition (EMT), and cell motility. While for PP1/PP2 it was demonstrated shown that these agents directly inhibit the kinase activity of the TGF-β type I receptor activin receptor-like kinase 5, the mechanism of the anti-TGF-β effect of AZM475271 and dasatinib is less clear...
January 2, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28032244/dasatinib-a-review-in-chronic-myeloid-leukaemia-and-ph-acute-lymphoblastic-leukaemia
#17
Gillian M Keating
Dasatinib (Sprycel(®)) is an orally administered, small molecule inhibitor of multiple tyrosine kinases. In the phase 3 DASISION trial, dasatinib 100 mg once daily resulted in deeper and faster cytogenetic and molecular responses than imatinib 400 mg once daily in patients with newly diagnosed, chronic-phase chronic myeloid leukaemia (CML), although there was no significant between-group difference in progression-free survival (PFS) or overall survival (OS) in the longer term. In the phase 3 CA180-034 trial, a regimen of dasatinib 100 mg once daily provided the most favourable benefit-risk profile in patients with imatinib-resistant or -intolerant chronic-phase CML...
January 2017: Drugs
https://www.readbyqxmd.com/read/28032081/philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-8-years-experience-from-a-tertiary-care-center-in-india
#18
Madhav Danthala, Sadashivudu Gundeti, Laxmi Srinivas Maddali, Ashok Pillai, Krishna Chaitanya Puligundla, Raja Praveen Adusumilli
INTRODUCTION: The Philadelphia chromosome (Ph) is the most common cytogenetic abnormality associated with adult acute lymphoblastic leukemia (ALL) occurring in 20% to 40% of patients. It is also detected in 2% to 5% of children with ALL. Historically, patients with Ph-positive ALL carried a dismal prognosis, with poor response to most chemotherapy combinations, short remission durations, and long-term disease-free survival rates of 10% to 20%. The advent of tyrosine kinase inhibitors (TKIs) has revolutionized therapy of Ph-positive ALL...
October 2016: South Asian Journal of Cancer
https://www.readbyqxmd.com/read/28007774/combined-kit-and-ctla-4-blockade-in-patients-with-refractory-gist-and-other-advanced-sarcomas-a-phase-ib-study-of-dasatinib-plus-ipilimumab
#19
Sandra P D'Angelo, Alexander N Shoushtari, Mary Louise Keohan, Mark A Dickson, Mrinal M Gounder, Ping Chi, Jennifer K Loo, Leigh Gaffney, Lee Schneider, Zarine Patel, Joseph P Erinjeri, Mark Bluth, Ana Sjoberg, Howard Streicher, Naoko Takebe, Li-Xuan Qin, Cristina R Antonescu, Ronald P DeMatteo, Richard D Carvajal, William D Tap
PURPOSE: A phase Ib study of dasatinib plus ipilimumab in GIST and other sarcomas was performed based on pre-clinical data demonstrating that combined KIT and CTLA-4 blockade is synergistic. EXPERIMENTAL DESIGN: A standard 3+3 design was used evaluate the safety, efficacy and immune correlates of treatment. Dose escalation cohorts received ipilimumab 10 or 3 mg/kg every 3 weeks followed by maintenance every 12 weeks with escalating doses of dasatinib (70mg daily, 100 mg daily or 70 mg twice daily)...
December 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28006851/poor-outcomes-associated-with-der-22-t-9-22-and-9-9p-in-patients-with-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-receiving-chemotherapy-plus-a-tyrosine-kinase-inhibitor
#20
Nicholas J Short, Hagop M Kantarjian, Koji Sasaki, Farhad Ravandi, Heidi Ko, C Cameron Yin, Guillermo Garcia-Manero, Jorge E Cortes, Rebecca Garris, Susan M O'Brien, Keyur Patel, Maria Khouri, Deborah Thomas, Nitin Jain, Tapan M Kadia, Naval Daver, Christopher B Benton, Ghayas C Issa, Marina Konopleva, Elias Jabbour
In patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with chemotherapy plus a tyrosine kinase inhibitor (TKI), the prognostic impact of additional chromosomal abnormalities (ACAs) is not well-established. We evaluated the prognostic impact of individual ACAs in 152 patients with Ph+ ALL receiving first-line intensive chemotherapy plus either imatinib (n=36), dasatinib (n=74) or ponatinib (n=42). ACAs were identified in 118 patients (78%). Compared to outcomes of patients without ACAs, ACAs were not associated with differences in either relapse-free survival (RFS; P=0...
December 22, 2016: American Journal of Hematology
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