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https://www.readbyqxmd.com/read/29220734/high-throughput-routine-determination-of-17-tyrosine-kinase-inhibitors-by-lc-ms-ms
#1
Camille Merienne, Marine Rousset, Dominique Ducint, Nadège Castaing, Karine Titier, Mathieu Molimard, Stéphane Bouchet
Several studies have shown that therapeutic drug monitoring of tyrosine kinase inhibitors (TKI) can improve their benefit in cancer. An analytical tool has been developed in order to quantify 17 tyrosine kinase inhibitors and 2 metabolites in human plasma (afatinib, axitinib, bosutinib, crizotinib, dabrafenib, dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, ponatinib, regorafenib, regorafenib M2, regorafenib M5, ruxolitinib, sorafenib, sunitinib, vandetanib). Drugs were arranged in four groups, according to their plasma concentration range: 0...
November 28, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29217540/cancer-stem-cell-suppressing-activity-of-chrysotoxine-a-bibenzyl-from-dendrobium-pulchellum
#2
Narumol Bhummaphan, Varisa Pongrakhananon, Boonchoo Sritularak, Pithi Chanvorachote
Cancer stem cells (CSCs) have been recognized as rare populations driving cancer progression, metastasis, and drug resistance in leading cancers. Attempts have been paid toward identifying compound that specifically targets these CSCs. Therefore, the investigations of the novel therapeutic strategies for CSCs targeting is required. The cytotoxic effects of Chrysotoxine on human NSCLC-derived H460 and H23 cells were tested by MTT assay. The Effect of Chrysotoxine suppresses CSC-like phenotypes was determined in CSC-rich populations and primary CSCs in 3D culture and Extreme limiting dilution assay...
December 7, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29212971/-chronic-myeloid-leukemia-complicated-by-pulmonary-hypertension-during-dasatinib-therapy-a-single-center-retrospective-study
#3
Yoko Edahiro, Tomoiku Takaku, Hakuoh Konishi, Yutaka Tsukune, Isao Fujioka, Kiyoshi Takasu, Akihiko Gotoh, Hiroyuki Daida, Norio Komatsu
Pulmonary artery hypertension (PAH) has been reported to be a severe adverse event associated with dasatinib therapy. Among the 76 chronic myeloid patients who were treated with dasatinib at our hospital, six patients showed high estimated pulmonary arterial systolic pressure, as observed by echocardiography. PAH was confirmed using right heart catheterization in three (3.9%) patients with increased mean pulmonary artery pressure (mPAP). In one patient, although mPAP was higher than the normal range, it did not fulfill the criteria of pulmonary hypertension...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/29207935/cardiac-birth-defects-in-a-twin-infant-born-to-a-woman-with-chronic-myeloid-leukemia-on-dasatinib
#4
David J Hermel, Victor Chiu, Melody H Hermel, Anil Tulpule, Mojtaba Akhtari
Preclinical animal studies have demonstrated an association between maternal use of tyrosine kinase inhibitors and embryofetal toxicity; yet, multiple clinical case series have reported normal pregnancy outcomes and healthy infants in women on these medications during the course of their pregnancy. We describe a case of a woman with chronic myeloid leukemia who had taken the second-generation tyrosine kinase inhibitor dasatinib during the first 12 weeks of her dichorionic diamniotic twin pregnancy and subsequently delivered two low-birth weight infants, one with severe cardiac malformations and the other without apparent birth abnormalities...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29202231/identification-of-novel-aurora-kinase-a-aurka-inhibitors-via-hierarchical-ligand-based-virtual-screening
#5
Yue Kong, Andreas Bender, Aixia Yan
Aurora kinases are essential for cell mitosis, amplified and overexpressed in various human malignancies. Therefore, Aurora kinases have been promising targets for anticancer therapies, which has prompted an intensive search for their small-molecule inhibitors. In this work, we performed a hierarchical and time-efficient virtual screening cascade for scaffold hopping, aiming to obtain structurally novel and highly potent hit compounds targeting Aurora kinases. The cascade consisted of a shape- and an electrostatic-based protocol, combined with a QSAR-based selection protocol...
December 4, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29200684/the-role-of-mutation-testing-in-patients-with-chronic-myeloid-leukemia-in-chronic-phase-after-imatinib-failure-and-their-outcomes-after-treatment-modification-single-institutional-experience-over-13-years
#6
Puligundla Krishna Chaitanya, Karnam Ashok Kumar, Bala Stalin, Gundeti Sadashivudu, Maddali Lakshmi Srinivas
Introduction: BCR-ABL1 kinase domain mutations represent the most frequent mechanism of resistance to tyrosine kinase inhibitor (TKI) therapy, being detected in 40%-50% of imatinib-resistant patients with chronic myeloid leukemia in chronic phase (CML-CP). Over 100 BCR-ABL1 single-point mutations have been reported in patients with imatinib-resistant CML. There were few studies reported from India on BCR-ABL kinase mutations in imatinib failure patients. We present our data on imatinib resistance mutation analysis (IRMA) and use of imatinib dose hike and 2nd-generation TKI at our institute...
July 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/29199677/effect-of-tyrosine-kinase-inhibitors-on-the-glucose-levels-in-diabetic-and-nondiabetic-patients
#7
E Y Romero-Ventosa, L Otero-Millán, S González-Costas, P Vilasoa-Boo, A Silva-López, C Arroyo-Conde, G Piñeiro-Corrales
CONTEXT: Tyrosine kinase inhibitors (TKIs) are used in different types of cancers due to their good profile of adverse reactions and their convenience in the oral administration. Some studies describe that certain TKIs are associated with changes in the glycemic profile of the patients. AIMS: This study aims to determine if treatment with ITK affects to serum glucose levels in clinical practice. SETTINGS AND DESIGN: A retrospective study was carried out in 136 episodes (112 patients treated with sorafenib, sunitinib, imatinib, dasatinib, or nilotinib)...
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29191803/dasatinib-approved-for-pediatric-cml
#8
(no author information available yet)
The FDA approved dasatinib to treat pediatric chronic myeloid leukemia. This drug is the second tyrosine kinase inhibitor, alongside imatinib, approved for this indication and represents an important new option for first- and second-line treatment.
November 30, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29190494/fus-chop-promotes-invasion-in-myxoid-liposarcoma-through-a-src-fak-rho-rock-dependent-pathway
#9
Juan Tornin, Francisco Hermida-Prado, Ranjit Singh Padda, M Victoria Gonzalez, Carlos Alvarez-Fernandez, Veronica Rey, Lucia Martinez-Cruzado, Oscar Estupiñan, Sofia T Menendez, Lucia Fernandez-Nevado, Aurora Astudillo, Juan P Rodrigo, Fabrice Lucien, Yohan Kim, Hon S Leong, Juana Maria Garcia-Pedrero, Rene Rodriguez
Deregulated SRC/FAK signaling leads to enhanced migration and invasion in many types of tumors. In myxoid and round cell liposarcoma (MRCLS), an adipocytic tumor characterized by the expression of the fusion oncogene FUS-CHOP, SRC have been found as one of the most activated kinases. Here we used a cell-of-origin model of MRCLS and an MRCLS cell line to thoroughly characterize the mechanisms of cell invasion induced by FUS-CHOP using in vitro (3D spheroid invasion assays) and in vivo (chicken chorioallantoic membrane model) approaches...
November 27, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29188580/10-year-complete-remission-in-a-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-patient-using-imatinib-without-high-intensity-chemotherapy-or-allogeneic-stem-cell-transplantation
#10
Katsumichi Fujimaki, Yukako Hattori, Hideaki Nakajima
The outcome of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL) has improved with the use of tyrosine kinase inhibitors, such as imatinib and dasatinib. We report a 63-year-old woman with Ph-ALL who maintained complete remission for 10 years using imatinib without high-intensity chemotherapy or allogeneic stem cell transplantation. She underwent induction therapy with imatinib plus prednisolone and achieved complete remission by day 53. Imatinib was continued until 103 months, when it was stopped in response to renal dysfunction; however, the patient continued to exhibit molecular remission at 120 months...
November 29, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29187020/a-rare-case-of-pediatric-chronic-myelogenous-leukemia-presenting-with-severe-thrombocytosis-without-leukocytosis
#11
Albert N Huho, Niveen Issaq, Ionela Iacobas, Tarek M Elghetany, Dolores López-Terrada, Kevin E Fisher, Jyotinder N Punia
Pediatric chronic myelogenous leukemia is uncommon. We report a pediatric patient with chronic myelogenous leukemia presenting with a normal white blood cell count and no circulating immature myeloid cells. The patient presented with extreme thrombocytosis (platelet count range: 2175-3064 × 109/L) noted incidentally. No splenomegaly was found. Examination of the bone marrow aspirate revealed normal cellularity and normal myeloid: erythroid ratio with marked megakaryocytic hyperplasia. Molecular studies on the bone marrow aspirate detected both the major BCR/ABL1 p210 fusion transcript (9280 copies; p210/ ABL1 ratio: 38...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/29185155/successful-treatment-of-follicular-lymphoma-with-second-generation-tyrosine-kinase-inhibitors-administered-for-coexisting-chronic-myeloid-leukemia
#12
Shin-Ichiro Fujiwara, Yuya Shirato, Takashi Ikeda, Shin-Ichiro Kawaguchi, Yumiko Toda, Shoko Ito, Shin-Ichi Ochi, Takashi Nagayama, Kiyomi Mashima, Kento Umino, Daisuke Minakata, Hirofumi Nakano, Kaoru Morita, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Masahiro Ashizawa, Chihiro Yamamoto, Kaoru Hatano, Kazuya Sato, Iekuni Oh, Ken Ohmine, Kazuo Muroi, Yoshinobu Kanda
Tyrosine kinase inhibitors (TKIs) are standard therapy for chronic myeloid leukemia (CML). However, the effects of these agents on mature B cell lymphoma are not well known. We describe a 50-year-old man who was diagnosed with CML in the chronic phase and treated with imatinib. After 3 years of imatinib therapy that achieved a complete cytogenetic response of CML, he developed Philadelphia-negative follicular lymphoma (FL). Rituximab monotherapy induced a partial response of FL, and he subsequently achieved a major molecular response (MMR) of CML...
November 28, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29177615/etv6-abl1-fusion-combined-with-monosomy-7-in-childhood-b-precursor-acute-lymphoblastic-leukemia
#13
Suguru Uemura, Noriyuki Nishimura, Daiichiro Hasegawa, Akemi Shono, Kimiyoshi Sakaguchi, Hisayuki Matsumoto, Yuji Nakamachi, Jun Saegusa, Takehito Yokoi, Teppei Tahara, Akihiro Tamura, Nobuyuki Yamamoto, Atsuro Saito, Aiko Kozaki, Kenji Kishimoto, Toshiaki Ishida, Nanako Nino, Satoru Takafuji, Takeshi Mori, Kazumoto Iijima, Yoshiyuki Kosaka
ETV6-ABL1 fusion is a rare but recurrent oncogenic lesion found in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), without an established chromosomal abnormality, and is associated with poor outcome. In ETV6-ABL1-positive cases, an in-frame fusion produced by a complex rearrangement results in constitutive chimeric tyrosine kinase activity. Monosomy 7 is also a rare and unfavorable chromosomal abnormality in childhood BCP-ALL. Here, we report a 14-year-old female BCP-ALL patient with ETV6-ABL1 fusion combined with monosomy 7...
November 24, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/29168352/patient-satisfaction-with-information-on-oral-anticancer-agent-use
#14
Christel C L M Boons, Lonneke Timmers, Natasja M van Schoor, Eleonora L Swart, N Harry Hendrikse, Jeroen J W M Janssen, Jacqueline G Hugtenburg
Adequate information on oral anticancer agent (OACA) use is an essential element of optimal cancer care. The present study aimed to get insight into the experiences of patients with information on OACA treatment and their characteristics regarding information dissatisfaction. Patients of four Dutch university hospitals using OACA participated in this observational study and completed the Satisfaction with Information about Medicines Scale (SIMS), EORTC Quality of Life Questionnaire-C30, Brief Illness Perception Questionnaire, and Beliefs about Medicines Questionnaire-Specific...
November 23, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29165716/targeting-bcr-abl-independent-tki-resistance-in-chronic-myeloid-leukemia-by-mtor-and-autophagy-inhibition
#15
Rebecca Mitchell, Lisa E M Hopcroft, Pablo Baquero, Elaine K Allan, Kay Hewit, Daniel James, Graham Hamilton, Arunima Mukhopadhyay, Jim O'Prey, Alan Hair, Junia V Melo, Edmond Chan, Kevin M Ryan, Véronique Maguer-Satta, Brian J Druker, Richard E Clark, Subir Mitra, Pawel Herzyk, Franck E Nicolini, Paolo Salomoni, G Vignir Helgason
Background: Imatinib and second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib have statistically significantly improved the life expectancy of chronic myeloid leukemia (CML) patients; however, resistance to TKIs remains a major clinical challenge. Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment...
November 20, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29165288/treatment-related-noncontiguous-radiologic-changes-in-children-with-diffuse-intrinsic-pontine-glioma-treated-with-expanded-irradiation-fields-and-antiangiogenic-therapy
#16
Zoltan Patay, Thomas E Merchant, Rosa Nguyen, Christopher R Pierson, Arzu Onar-Thomas, Alberto Broniscer
PURPOSE: We previously reported the cases of 3 children with diffuse intrinsic pontine glioma (DIPG) in whom noncontiguous treatment-related abnormalities (NCTRAs) developed in the brain after expanded-field radiation therapy (RT). To investigate the occurrence and putative mechanism of NCTRAs, we reviewed brain magnetic resonance imaging studies of patients with DIPG treated in 2 consecutive phase I clinical trials (trials 1 and 2). METHODS AND MATERIALS: The 55 children included in these trials received small-molecule inhibitors: vandetanib in trial 1 (n=32; mean age 6...
December 1, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29161920/development-optimization-and-in-vitro-characterization-of-dasatinib-loaded-peg-functionalized-chitosan-capped-gold-nanoparticles-using-box-behnken-experimental-design
#17
Sandeep Kumar Reddy Adena, Mansi Upadhyay, Harsh Vardhan, Brahmeshwar Mishra
OBJECTIVE: The purpose of this research study was to develop, optimize, and characterize dasatinib loaded polyethylene glycol (PEG) stabilized chitosan capped gold nanoparticles (DSB-PEG-Ch-GNPs). METHODS: Gold (III) chloride hydrate was reduced with chitosan and the resulting nanoparticles were coated with thiol-terminated PEG and loaded with dasatinib (DSB). Plackett-Burman design (PBD) followed by Box-Behnken experimental design (BBD) were employed to optimize the process parameters...
November 21, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/29151104/clinical-efficacy-and-safety-of-first-line-dasatinib-therapy-and-the-relevance-of-velocity-of-bcr-abl1-transcript-decline-for-achievement-of-molecular-responses-in-newly-diagnosed-chronic-phase-chronic-myeloid-leukemia-report-from-the-juntendo-yamanashi-cooperative
#18
Tomoiku Takaku, Noriyoshi Iriyama, Toru Mitsumori, Eriko Sato, Akihiko Gotoh, Keita Kirito, Masaaki Noguchi, Michiaki Koike, Junichi Sakamoto, Koji Oba, Norio Komatsu
OBJECTIVE: The use of tyrosine kinase inhibitors led to an improvement in the prognoses of patients with chronic myeloid leukemia (CML). The aims of this study were to investigate the efficacy and safety of dasatinib in Japanese patients and to explore the factors that affect the achievement of molecular responses. METHODS: The primary endpoint was a major molecular response (MMR) by 12 months. The halving time for BCR-ABL1 transcripts was calculated using transcript levels...
November 18, 2017: Oncology
https://www.readbyqxmd.com/read/29150111/primary-imatinib-failure-rescued-by-dasatinib-and-maintained-by-reintroduction-of-imatinib
#19
Rajiv Kumar, Rajan Kapoor
No abstract text is available yet for this article.
October 2017: Revista Brasileira de Hematologia e Hemoterapia
https://www.readbyqxmd.com/read/29138996/ichthyosiform-pityriasis-rubra-pilaris-like-eruption-secondary-to-ponatinib-therapy-case-report-and-literature-review
#20
Ariel E Eber, Alyx Rosen, Kate E Oberlin, Alessio Giubellino, Paolo Romanelli
Tyrosine kinase inhibitors have revolutionized the chemotherapy arena as targeted therapies for a multitude of malignancies. They are more selective than conventional chemotherapy, and often elicit fewer systemic adverse events, however toxicities still exist. Cutaneous toxicities are common and their management presents a novel challenge to physicians and patients. Ponatinib is a third-generation tyrosine kinase inhibitor increasingly reported to cause cutaneous eruption. A 50-year-old woman with a history of chronic myelogenous leukemia presented with a 4-month history of worsening atrophic and ichthyosiform pink plaques involving the axillae, thighs and abdomen; red patches were also observed on the cheeks and forehead...
November 14, 2017: Drug Safety—Case Reports
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