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https://www.readbyqxmd.com/read/28933312/characterization-of-imatinib-resistant-cml-leukemic-stem-initiating-cells-and-their-sensitivity-to-cbp-catenin-antagonists
#1
Yi Zhao, Kaijin Wu, Yongfeng Wu, Elizabeth Melendez, Goar Smbatyan, David Massiello, Michael Kahn
The development of the tyrosine kinase inhibitor Imatinib (IM) represents a milestone breakthrough in CML (Chronic Myeloid Leukemia) treatment. However, it is not curative and patients develop IM resistance. IM resistance has been previously correlated with the emergence of drug-resistant LIC/LSC (Leukemia Initiating Cell/Leukemia Stem Cell) and increased nuclear catenin levels and enhanced Wnt signaling. It has been demonstrated previously that drug resistant CML LIC/LSC can be safely eliminated both in vitro and in vivo via disruption of the CBP/catenin interaction, utilizing the highly biochemically selective small molecule CBP/catenin antagonist ICG-001...
September 19, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28932084/characterizing-gastrointestinal-stromal-tumors-and-evaluating-neoadjuvant-imatinib-by-sequencing-of-endoscopic-ultrasound-biopsies
#2
Per Hedenström, Bengt Nilsson, Akif Demir, Carola Andersson, Fredrik Enlund, Ola Nilsson, Riadh Sadik
AIM: To evaluate endoscopic ultrasound (EUS)-guided biopsies for the pretreatment characterization of gastrointestinal stromal tumors (GIST) to personalize the management of patients. METHODS: All patients with lesions suspected to be GIST who were referred for EUS-sampling at a tertiary Swedish center were eligible for inclusion 2006-2015. During the observational study phase (2006-2011), routine fine-needle-aspiration (EUS-FNA) was performed. In 2012-2015, we converted to an interventional, randomized protocol with dual sampling EUS-FNA and fine-needle-biopsy-sampling (EUS-FNB) for all lesions...
August 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28929332/deeper-molecular-response-is-a-predictive-factor-for-treatment-free-remission-after-imatinib-discontinuation-in-patients-with-chronic-phase-chronic-myeloid-leukemia-the-jalsg-stim213-study
#3
Naoto Takahashi, Tetsuzo Tauchi, Kunio Kitamura, Koichi Miyamura, Yoshio Saburi, Yoshihiro Hatta, Yasuhiko Miyata, Shinichi Kobayashi, Kensuke Usuki, Itaru Matsumura, Yosuke Minami, Noriko Usui, Tetsuya Fukuda, Satoru Takada, Maho Ishikawa, Katsumichi Fujimaki, Hiroshi Gomyo, Osamu Sasaki, Kohshi Ohishi, Takaaki Miyake, Kiyotoshi Imai, Hitoshi Suzushima, Hideki Mitsui, Kazuto Togitani, Toru Kiguchi, Yoshiko Atsuta, Shigeki Ohtake, Kazunori Ohnishi, Yukio Kobayashi, Hitoshi Kiyoi, Yasushi Miyazaki, Tomoki Naoe
The objective of this prospective clinical trial (JALSG-STIM213, UMIN000011971) was to evaluate treatment-free remission (TFR) rates after discontinuation of imatinib in chronic myeloid leukemia (CML). CML patients who received imatinib treatment for at least 3 years and sustained deep molecular response for at least 2 years were eligible. Molecular recurrence was defined as loss of major molecular response (MMR). Of the 68 eligible patients, 38.2% were women, the median age was 55.0 years, and the median duration of imatinib treatment was 97...
September 19, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28929180/-treatment-of-chronic-myeloid-leukemia-with-imatinib-iris-study
#4
S Saußele, S Nitschmann
No abstract text is available yet for this article.
September 19, 2017: Der Internist
https://www.readbyqxmd.com/read/28928163/high-bcr-abl-gusis-levels-at-diagnosis-of-chronic-phase-cml-are-associated-with-unfavorable-responses-to-standard-dose-imatinib
#5
Paolo Vigneri, Fabio Stagno, Stefania Stella, Alessandra Cupri, Stefano Forte, Michele Massimino, Agostino Antolino, Sergio Siragusa, Donato Mannina, Stefana S Impera, Caterina Musolino, Alessandra Malato, Giuseppe Mineo, Carmela Tomaselli, Pamela Murgano, Maurizio Musso, Fortunato Morabito, Stefano Molica, Bruno Martino, Livia Manzella, Martin C Müller, Andreas Hochhaus, Francesco Di Raimondo
PURPOSE: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate Imatinib responses. EXPERIMENTAL DESIGN: We correlated BCR-ABL/GUSIS and BCR-ABL/ABLIS transcripts at diagnosis with the outcome - defined by the 2013 European LeukemiaNet recommendations - of 272 newly diagnosed CML patients receiving Imatinib 400 mg/daily...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28927158/regulation-of-htra2-on-wt1-gene-expression-under-imatinib-stimulation-and-its-effects-on-the-cell-biology-of-k562-cells
#6
Lixia Zhang, Yan Li, Xiaoyan Li, Qing Zhang, Shaowei Qiu, Qi Zhang, Min Wang, Haiyan Xing, Qing Rao, Zheng Tian, Kejing Tang, Jianxiang Wang, Yingchang Mi
The aim of the present study was to investigate the regulation of Wilms Tumor 1 (WT1) by serine protease high-temperature requirement protein A2 (HtrA2), a member of the Htr family, in K562 cells. In addition, the study aimed to observe the effect of this regulation on cell biological functions and its associated mechanisms. Expression of WT1 and HtrA2 mRNA, and proteins following imatinib and the HtrA2 inhibitor 5-[5-(2-nitrophenyl) furfuryl iodine]-1, 3-diphenyl-2-thiobarbituric acid (UCF-101) treatment was detected with reverse transcription-quantitative polymerase chain reaction and western blot analysis...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28923937/direct-engagement-of-the-pi3k-pathway-by-mutant-kit-dominates-oncogenic-signaling-in-gastrointestinal-stromal-tumor
#7
Benedikt Bosbach, Ferdinand Rossi, Yasemin Yozgat, Jennifer Loo, Jennifer Q Zhang, Georgina Berrozpe, Katherine Warpinski, Imke Ehlers, Darren Veach, Andrew Kwok, Katia Manova, Cristina R Antonescu, Ronald P DeMatteo, Peter Besmer
Gastrointestinal stromal tumors (GISTs) predominantly harbor activating mutations in the receptor tyrosine kinase KIT. To genetically dissect in vivo the requirement of different signal transduction pathways emanating from KIT for tumorigenesis, the oncogenic Kit(V558Δ) mutation was combined with point mutations abrogating specific phosphorylation sites on KIT. Compared with single-mutant Kit(V558Δ/+) mice, double-mutant Kit(V558Δ;Y567F/Y567F) knock-in mice lacking the SRC family kinase-binding site on KIT (pY567) exhibited attenuated MAPK signaling and tumor growth...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28920959/targeting-mitochondrial-oxidative-phosphorylation-eradicates-therapy-resistant-chronic-myeloid-leukemia-stem-cells
#8
Elodie M Kuntz, Pablo Baquero, Alison M Michie, Karen Dunn, Saverio Tardito, Tessa L Holyoake, G Vignir Helgason, Eyal Gottlieb
Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second- and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically. Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner, we searched for such vulnerabilities in CML LSCs...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28919770/swollen-lymph-nodes-may-not-be-clinical-manifestations-of-chronic-myeloid-leukemia-case-report-and-revision-of-literature
#9
Zhihe Liu, Siyun Li, Ou Bai
We present here the case of a 33-year-old Chinese female patient with synchronous double primary malignant tumors (chronic myeloid leukemia [CML] and classic Hodgkin lymphoma). This patient was admitted to our hospital because of bilateral cervical lymph node enlargement and recurrent fever for 2 weeks. The complete blood cell count revealed white blood cell counts of 18.2×10(9)/L, hemoglobin of 9.6 g/dL, and platelet counts of 1,547×10(9)/L. Chromosome karyotype analysis demonstrated that t(9;22)(q34;q11) was positive in all 20 cells examined...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28918995/cutaneous-adverse-events-of-targeted-therapies-for-hematolymphoid-malignancies
#10
REVIEW
Julia D Ransohoff, Bernice Y Kwong
The identification of oncogenic drivers of liquid tumors has led to the rapid development of targeted agents with distinct cutaneous adverse event (AE) profiles. The diagnosis and management of these skin toxicities has motivated a novel partnership between dermatologists and oncologists in developing supportive oncodermatology clinics. In this article we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common and significant cutaneous AEs observed during treatment with targeted therapies for hematologic and lymphoid malignancies...
July 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28916158/pyrrolizines-design-synthesis-anticancer-evaluation-and-investigation-of-the-potential-mechanism-of-action
#11
Ahmed M Gouda, Ahmed H Abdelazeem, Hany A Omar, Ashraf N Abdalla, Mohammed A S Abourehab, Hamed I Ali
A novel set of pyrrolizine-5-carboxamides has been synthesized and evaluated for their anticancer potential against human breast MCF-7, lung carcinoma A549 and hepatoma Hep3B cancer cell lines. Compound 10c was the most active against MCF-7 with IC50 value of 4.72µM, while compound 12b was the most active against A549 and Hep3B cell lines. Moreover, kinases/COXs inhibition and apoptosis induction were suggested as potential molecular mechanisms for the anticancer activity of the novel pyrrolizines based on their structural features...
August 24, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28915580/molecular-and-functional-characterization-of-a-new-3-end-kit-juxtamembrane-deletion-in-a-duodenal-gist-treated-with-neoadjuvant-imatinib
#12
Vittorio Perfetti, Erik Laurini, Suzana Aulić, Maurizio Fermeglia, Roberta Riboni, Marco Lucioni, Elena Dallera, Sara Delfanti, Luigi Pugliese, Francesco Saverio Latteri, Andrea Pietrabissa, Sabrina Pricl
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs express the receptor tyrosine kinase KIT, and the majority of GISTs present KIT gain-of-function mutations that cluster in the 5' end of the receptor juxtamembrane domain. On the other hand, little information is known about GISTs carrying mutations in the 3' end of the KIT juxtamembrane domain. Here we report and discuss a clinical case of localized duodenal GIST whose molecular characterization revealed the presence of a new 21 nucleotide/7 amino acid deletion in the 3' end of KIT juxtamembrane domain (Δ574-580)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914399/surgery-for-duodenal-gastrointestinal-stromal-tumors-a-single-center-experience
#13
Ping Chen, Tianqiang Song, Xin Wang, Hongyuan Zhou, Ti Zhang, Qiang Wu, Dalu Kong, Yunlong Cui, Huikai Li, Qiang Li
BACKGROUND: The duodenal gastrointestinal stromal tumors (GISTs) are an extremely rare subset of GISTs. The optimal surgical procedure remains not well defined. AIMS: We assessed the surgical approach and long-term outcomes of patients with duodenal GISTs who underwent limited resection (LR) versus pancreaticoduodenectomy (PD). METHODS: From November 2005 to January 2016, 64 consecutive patients with duodenal GISTs in a single center were retrospectively analyzed...
September 15, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28905092/drug-induced-oral-lichenoid-reactions-a-real-clinical-entity-a-systematic-review
#14
REVIEW
Giulio Fortuna, Massimo Aria, Julie H Schiavo
PURPOSE: Drug-induced oral lichenoid reactions (DIOLRs) have been extensively reported in the literature, but the validity of the causality relationship between any drug and the oral lichenoid lesions (OLLs) still remains questionable. We sought to determine whether this causality relationship really exists, whether a resolution of the oral lesions upon withdrawal occurs, and what the most common alleged offending medications are. METHODS: Nine electronic databases from January 1966 to December 2016 were systematically searched to identify all relevant studies selected with specific inclusion criteria (a clinical and histopathological diagnosis of DIOLRs, and clearly statement on the systemic offending medication)...
September 13, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28902634/antiproliferative-activity-of-synthesized-some-new-benzimidazole-carboxamidines-against-mcf-7-breast-carcinoma-cells
#15
Cigdem Karaaslan, Filiz Bakar, Hakan Goker
Breast cancer is the most endemic cause of cancer among women in both developed and developing countries. Benzimidazole derivatives exemplify one of the chemical classes that show strong cytotoxic activity especially against breast cancer cells (MCF-7). Aromatic amidine derivatives are known as a group of DNA interactive compounds that bind minor groove of the genome, especially A-T base pairs, and show significant in vitro and in vivo toxicity toward cancer cells. In light of these studies, some new mono/dicationic amidino benzimidazole derivatives were synthesized and evaluated for cytotoxic activity on cultured MCF-7 breast cancer cells...
September 13, 2017: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
https://www.readbyqxmd.com/read/28901467/aberrantly-expressed-transcription-factors-c-ebp-and-sox4-have-positive-effects-in-the-development-of-chronic-myeloid-leukemia
#16
Fei Dong, Guili Zhang, Xia Zhang, Xuena Liu, Na Wang, Chengming Sun
The aim of the present study was to examine the expression and significance of CCAAT/enhancer binding protein α (C/EBPα) and SRY‑related high mobility group box containing transcription factor 4 (SOX4) in chronic myeloid leukemia (CML). Bone marrow samples were collected from patients with CML, and peripheral blood mononuclear cells were collected from healthy controls. Protein and mRNA were extracted from the collected samples, and analyzed using western blotting and reverse transcription‑quantitative polymerase chain reaction analyses, respectively...
September 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28900995/-association-between-genetic-polymorphisms-and-variation-of-imatinib-pharmacokinetics-in-gastrointestinal-stromal-tumors
#17
Haibo Qiu, Wei Zhuang, Xueding Wang, Min Huang, Zhiwei Zhou
OBJECTIVE: To investigate the influence of metabolic enzymes polymorphisms on variations of imatinib (IM) pharmacokinetics in gastrointestinal stromal tumors (GIST) patients. METHODS: Clinical data of 118 Chinese GIST patients receiving 400 mg/d IM at Sun Yat-sen University Cancer Center between 2014 and 2016 were retrospectively analyzed. The plasma concentration of imatinib mesylate(IM) and its main metabolic N-demethyl imatinib (NDI) were determined by LC-MS/MS...
September 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28900994/-analysis-of-gastric-gastrointestinal-stromal-tumors-in-shandong-province-a-midterm-report-of-multicenter-gissg1201-study
#18
Qingsheng Hou, Wenqiang Luo, Leping Li, Yong Dai, Lixin Jiang, Ailiang Wang, Xianqun Chu, Yuming Li, Daogui Yang, Chunlei Lu, Linguo Yao, Gang Cui, Huizhong Lin, Gang Chen, Qing Cui, Huanhu Zhang, Zengjun Lun, Lijian Xia, Yingfeng Su, Guoxin Han, Xizeng Hui, Zhixin Wei, Zuocheng Sun, Hongliang Guo, Yanbing Zhou
OBJECTIVE: To summarize the treatment status of gastric gastrointestinal stromal tumor (GIST) in Shandong province,by analyzing the clinicopathological features and prognostic factors. METHODS: Clinicopathological and follow-up data of 1 165 patients with gastric GIST between January 2000 and December 2013 from 23 tertiary referral hospitals in Shandong Province were collected to establish a database. The risk stratification of all cases was performed according to the National Institutes of Health(NIH) criteria proposed in 2008...
September 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28900984/-targeted-therapy-combined-with-immunotherapy-in-gastrointestinal-stromal-tumor-a-new-era-of-hope-and-challenges
#19
Wenyi Zhao, Hui Cao
New immunotherapy represented by immune checkpoint inhibitor therapy and chimeric antigen receptor T-Cell immunotherapy (CAR-T) has already become hot trend in the treatment of malignant tumors. In gastrointestinal stromal tumor (GIST), with notable tumor-infiltrating immune cells existing in GIST tissues and immunological effects reported in imatinib mesylate (IM) treatment, the clinicians and researchers started to realize the possibilities of immunotherapy in GIST. Recent studies reported that PD-1/PD-L1 or CTLA-4 blockade may enhance the T-cell activity and anti-tumor effect of targeted therapy, which can be applied in advanced GIST, and anti-KIT CAR T-cells indicated a new immunotherapeutic targeted strategy for GIST patients with TKI resistance...
September 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28900983/-updates-on-adjuvant-therapy-in-gastrointestinal-stromal-tumor
#20
Haibo Qiu, Xiaowei Sun, Zhiwei Zhou
Surgery remains the primary treatment for patients with localized gastrointestinal stromal tumor (GIST), however, even after complete resection of the tumor, there is still a part of patients with tumor recurrence and metastasis. Imatinib, as adjuvant therapy in GIST patients with intermediate and high risk of recurrence, can significantly improve the disease-free survival, but whether it can prolong the overall survival is still unknown. It has reached a consensus that the intermediate and high risk patients should receive adjuvant therapy, but the duration for adjuvant therapy is still under investigation, especially for high-risk patients...
September 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
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