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https://www.readbyqxmd.com/read/29327917/peptide-based-photoelectrochemical-cytosensor-using-a-hollow-tio2-eg-znin2s4-co-sensitized-structure-for-ultrasensitive-detection-of-early-apoptotic-cells-and-drug-evaluation
#1
Rong Wu, Gao-Chao Fan, Li-Ping Jiang, Jun-Jie Zhu
The ability to rapidly detect apoptotic cells and accurately evaluate therapeutic effects is significant in cancer research. To address this target, a biocompatible, ultrasensitive photoelectrochemical (PEC) cytosensing platform was developed based on electrochemically reduced graphene (EG)/ZnIn2S4 co-sensitized TiO2 coupled with specific recognition between apoptotic cells and phosphatidylserine (PS)-binding peptide (PSBP). In this strategy, HL-60 cells were selected as a model, and C005, nilotinib and imatinib were selected as apoptosis inducers to show cytosensing performance...
January 12, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29324374/ileal-gist-presenting-with-bacteremia-and-liver-abscess-a-case-report-and-review-of-literature
#2
Marina Gorelik, Braulio Sabates, Adel Elkbuli, Tony Dunne
INTRODUCTION: Small intestine gastrointestinal stromal tumors can infrequently present with intra-abdominal abscess, perforation, obstruction or fistula. Tumor-small intestine fistula is a rare phenomenon and occurs as a result of GISTs' propensity to cause mucosal ulceration. This allows bacteria from the gut to gain access to the systemic circulation and predisposes the patient to bacteremia and pyogenic liver abscess. PRESENTATION OF CASE: We present a case of a 63-year-old female whose initial symptoms included fever, nausea, vomiting and right upper quadrant pain...
December 27, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29321163/antitumor-effects-of-blocking-protein-neddylation-in-t315i-bcr-abl-leukemia-cells-and-leukemia-stem-cells
#3
Chang Liu, Danian Nie, Juan Li, Xin Du, Yuhong Lu, Yangqiu Li, Jingfeng Zhou, Yanli Jin, Jingxuan Pan
Imatinib (IM) revolutionized the treatment of chronic myeloid leukemia (CML) but drug resistance and disease recurrence remain a challenge. In this study, we suggest a novel strategy based on blocking protein neddylation to address BCR-ABL point mutations and leukemia stem cells (LSCs) that lie at the root of IM-resistant recurrences. Based on the finding that the NEDD8-activating enzyme subunit NAE1 is overexpressed in CML cells, we hypothesized that the function of certain neddylation-dependent protein substrates might be targeted to therapeutic ends in IM-resistant CML cells and LSCs...
January 10, 2018: Cancer Research
https://www.readbyqxmd.com/read/29316665/towards-comprehension-of-the-abcb1-p-glycoprotein-role-in-chronic-myeloid-leukemia
#4
REVIEW
Raquel C Maia, Flavia C Vasconcelos, Paloma S Souza, Vivian M Rumjanek
Abstract: The introduction of imatinib (IM), a BCR-ABL1 tyrosine kinase inhibitor (TKI), has represented a significant advance in the first-line treatment of chronic myeloid leukemia (CML). However, approximately 30% of patients need to discontinue IM due to resistance or intolerance to this drug. Both resistance and intolerance have also been observed in treatment with the second-generation TKIs-dasatinib, nilotinib, and bosutinib-and the third-generation TKI-ponatinib. The mechanisms of resistance to TKIs may be BCR-ABL1-dependent and/or BCR-ABL1-independent...
January 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29316372/can-therapeutic-drug-monitoring-increase-the-safety-of-imatinib-in-gist-patients
#5
Wei Zhuang, Jing-Dun Xie, Shan Zhou, Zhi-Wei Zhou, Yi Zhou, Xiao-Wei Sun, Xiu-Hong Yuan, Min Huang, Si Liu, Shuang Xin, Qi-Biao Su, Hai-Bo Qiu, Xue-Ding Wang
Imatinib at 400 mg daily is the standard treatment for patients affected with CML and GIST. The intervariability in plasma concentration is very significant. In many reports, a good therapeutic effect is attributed to an adequate concentration of Imatinib. However, few studies have been conducted to investigate the association between plasma concentration and side effects. Besides, no upper concentration limit of Imatinib plasma concentration detection has been established. The correlation of Imatinib trough concentrations (Cmin ) with adverse effects (AEs) was described here...
January 7, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29315500/long-term-outcome-of-dasatinib-first-line-treatment-in-gastrointestinal-stromal-tumor-a-multicenter-2-stage-phase-2-trial-swiss-group-for-clinical-cancer-research-56-07
#6
Michael Montemurro, Angela Cioffi, Julien Dômont, Piotr Rutkowski, Arnaud D Roth, Roger von Moos, Roman Inauen, Maud Toulmonde, Roger O Burkhard, Claudio Knuesli, Sebastian Bauer, Philippe Cassier, Heike Schwarb, Axel Le Cesne, Dieter Koeberle, Daniela Bärtschi, Daniel Dietrich, Christine Biaggi, John Prior, Serge Leyvraz
BACKGROUND: Tyrosine kinase inhibitors (TKIs) have improved the outcome of patients with gastrointestinal stromal tumors (GISTs), but most patients eventually develop resistance and progress. Dasatinib is a potent inhibitor of BCR-ABL, KIT, and SRC family kinases as well as imatinib-resistant cells. In GISTs, response evaluation is routinely done using computed tomography (CT) and 18 F-fluorodeoxyglucose positron emission tomography coupled to CT (FDG-PET/CT) for early response assessment and outcome prediction...
January 9, 2018: Cancer
https://www.readbyqxmd.com/read/29312652/tyrosine-kinase-inhibitor-sensitive-pdgfr%C3%AE-mutations-in-gist-two-cases-and-review-of-the-literature
#7
Pieter A Boonstra, Jourik A Gietema, Albert J H Suurmeijer, Matthew R Groves, Fernando de Assis Batista, Ed Schuuring, Anna K L Reyners
Gastrointestinal stromal tumors (GISTs) are rare mesenchymal malignancies of the gastrointestinal tract. Most GISTs harbor a c-KIT (80%) or a PDGFRα (10%) mutation that leads to constitutive activation of the tyrosine kinase receptor. Response to treatment with tyrosine kinase inhibitors (TKIs) is dependent on mutational status of the tumor. The most common mutation in PDGFRα, D842V, is known to be imatinib resistant. Almost all other PDGFRα mutations are imatinib sensitive. We describe two patients with a PDGFRα exon 18 mutated GIST responding to treatment with TKIs...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29310833/myeloid-neoplasm-with-eosinophilia-associated-with-isolated-extramedullary-fip1l1-pdgfra-rearrangement
#8
Talal Hilal, Veena Fauble, Rhett P Ketterling, Katalin Kelemen
Myeloid neoplasms with eosinophilia associated with PDGFRA rearrangement are very responsive to tyrosine kinase inhibitors (TKIs). Herein, we report a case of a 53-year-old man with eosinophilia and a well-differentiated extramedullary myeloid tumor with evidence of FIP1L1/PDGFRA rearrangement by fluorescent in situ hybridization in the extramedullary tissue. His bone marrow evaluation revealed a hypercellular marrow with eosinophilia but without evidence of a FIP1L1/PDGFRA rearrangement. The patient was treated with imatinib at a dose of 100 mg daily and responded with normalization of his peripheral eosinophil count...
January 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29310342/efficacy-and-safety-of-regorafenib-for-advanced-gastrointestinal-stromal-tumor-after-failure-with-imatinib-and-sunitinib-treatment-a-meta-analysis
#9
Zhenan Zhang, Tao Jiang, Wensheng Wang, Daxun Piao
AIMS: This meta-analysis aimed to evaluate the safety and efficacy of regorafenib as a treatment for patients with advanced (metastatic and/or unresectable) gastrointestinal stromal tumor (AGIST) after developing resistance to imatinib and sunitinib. METHODS: A literature search of databases such as PubMed, Embase, and Cochrane library was conducted up to February 2017. The pooled percentages and the corresponding 95% confidence intervals (CIs) were calculated using the Stata 11...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29305721/paragangliomas-arise-through-an-autonomous-vasculo-angio-neurogenic-program-inhibited-by-imatinib
#10
Fabio Verginelli, Silvia Perconti, Simone Vespa, Francesca Schiavi, Sampath Chandra Prasat, Paola Lanuti, Alessandro Cama, Lorenzo Tramontana, Diana Liberata Esposito, Simone Guarnieri, Artenca Sheu, Mattia Russel Pantalone, Rosalba Florio, Annalisa Morgano, Cosmo Rossi, Giuseppina Bologna, Marco Marchisio, Andrea D'Argenio, Elisa Taschin, Rosa Visone, Giuseppe Opocher, Angelo Veronese, Carlo T Paties, Vinalogu K Rajasekhar, Cecilia Söderberg-Nauclér, Mario Sanna, Lavinia Vittoria Lotti, Renato Mariani-Costantini
Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas, prototypical organoid tumours constituted by dysmorphic variants of the vascular and neural tissues found in normal paraganglia, provide a model to test this hypothesis. To understand the origin of paragangliomas, we built a biobank comprising 77 cases, 18 primary cultures, 4 derived cell lines, 80 patient-derived xenografts and 11 cell-derived xenografts...
January 5, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29305630/chronic-myeloid-leukemia-patients-in-tunisia-epidemiology-and-outcome-in-the-imatinib-era-a-multicentric-experience
#11
Raihane Ben Lakhal, Hela Ghedira, Hatem Bellaaj, Yosra Ben Youssef, Samia Menif, Zeineb Manai, Manel Bedoui, Amel Lakhal, Fehmi M'Sadek, Moez Elloumi, Abderrahmane Khélif, Neila Ben Romdhane, Mohamed Adnène Laatiri, Tarek Ben Othmen, Balkis Meddeb
Data are limited in developing countries regarding the clinicopathologic features and response to therapy of chronic myeloid leukemia (CML) in the era of imatinib (IM). The objective of this study is to report on the clinicoepidemiologic features of CML in Tunisia, to evaluate the long-term outcome of patients in chronic (CP) or accelerated phase (AP) treated with IM 400 mg daily as frontline therapy, and to determine imatinib's efficacy and safety. From October 2002 to December 2014, 410 CML patients were treated with IM in six Tunisian departments of hematology...
January 6, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29304783/desmoid-tumours-of-the-extremity-and-trunk-a-retrospective-study-of-44-patients
#12
Laura Wirth, Alexander Klein, Andrea Baur-Melnyk, Thomas Knösel, Lars H Lindner, Falk Roeder, Volkmar Jansson, Hans Roland Dürr
BACKGROUND: Desmoid-type fibromatosis (DF) is a aggressive (myo)fibroblastic neoplasm with an infiltrative growth and a tendency to local recurrence. Resection of the tumour and/or radiation were proposed as principal treatment. The aim of this retrospective study was to analyze the local control rates focusing on the effect of surgical margins and radiotherapy. METHODS: From 1981 to 2014, 44 patients had been treated. Fifty four therapies had been applied, in 50 cases surgery +/- radiation therapy, NSAIDs or chemotherapy...
January 5, 2018: BMC Musculoskeletal Disorders
https://www.readbyqxmd.com/read/29303368/imatinib-for-the-treatment-of-hypereosinophilic-syndromes
#13
Grzegorz Helbig
Hypereosinophilic syndromes (HES) encompass a group of disorders defined by sustained peripheral blood hypereosinophilia >1500/mm3 and evidence of eosinophilia-associated organ impairment. Approximately 10% of HES patients may harbor a cryptic deletion on chromosome 4 leading to formation of the FIP1L1-PDGFRA (F/P) fusion gene; these patients are diagnosed as F/P-mutated myeloid/lymphoid neoplasms with eosinophilia (MLN-eo). The results of numerous studies on the efficacy of tyrosine kinase inhibitor, imatinib mesylate (IM), in patients with HES have been published in the literature...
January 5, 2018: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/29299155/neuroprotection-by-aripiprazole-against-%C3%AE-amyloid-induced-toxicity-by-p-ck2%C3%AE-activation-via-inhibition-of-gsk-3%C3%AE
#14
So Youn Park, Hwa Kyoung Shin, Won Suk Lee, Sun Sik Bae, Koanhoi Kim, Ki Whan Hong, Chi Dae Kim
Psychosis is reported over 30% of patients with Alzheimer's disease (AD) in clinics. Aripiprazole is an atypical antipsychotic drug with partial agonist activity at the D2 dopamine and 5-HT1A receptors with low side-effect profile. We identified aripiprazole is able to overcome the amyloid-β (Aβ)-evoked neurotoxicity and then increase the cell viability. This study elucidated the mechanism(s) by which aripiprazole ameliorates Aβ1-42-induced decreased neurite outgrowth and viability in neuronal cells. Pretreatment with aripiprazole increased Brain-derived neurotrophic factor (BDNF) mRNA and protein expressions in N2a cells...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29298654/determination-of-the-apoptotic-effect-and-molecular-docking-of-benzamide-derivative-xt5-in-k562-cells
#15
Tulin Ozkan, Yalda Hekmatshoar, Tugba Ertan-Bolelli, Andry Nur Hidayat, Meral Beksac, Esin Aki-Yalcin, Ismail Yalcin, Asuman Sunguroglu
BACKGROUND: The tyrosine kinase inhibitor imatinib used as a first line treatment in chronic myeloid leukemia (CML) patients, may lead to resistance and failure to therapy. Novel combinations of imatinib with other drugs is a strategy to improve treatment efficiency. OBJECTIVE: In this study, the antileukemic and apoptotic effects of a benzamide derivative XT5 and benzoxazole derivative XT2B and their combination with imatinib were investigated in imatinib-sensitive (K562S) and imatinib-resistant (K562R) CML cells...
December 29, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29297244/how-is-the-relationship-between-twist-1-and-bcr-abl1-gene-expressions-in-chronic-myeloid-leukemia-patients
#16
Nazanin Heidari, Tina Vosoughi, Javad Mohammadi Asl, Amal Saki Malehi, Najmaldin Saki
BACKGROUND: The activation and increased expression of BCR-ABL1 lead to malignant chronic myelogenous leukemia (CML) cells, as well as the resistance to antitumor agents and apoptosis inducers. Moreover, TWIST-1 protein is a prognostic factor of leukemogenesis, and its level is raised in CML patients with cytogenetic resistance to imatinib. So, there is a likely relationship between BCR-ABL1 and TWIST-1 genes. OBJECTIVE: The aim of the study was to assess the relationship between TWIST-1 and BCR-ABL1 expressions...
January 3, 2018: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/29296778/asxl1-and-bim-germ-line-variants-predict-response-and-identify-cml-patients-with-the-greatest-risk-of-imatinib-failure
#17
Justine E Marum, David T Yeung, Leanne Purins, John Reynolds, Wendy T Parker, Doris Stangl, Paul P S Wang, David J Price, Jonathan Tuke, Andreas W Schreiber, Hamish S Scott, Timothy P Hughes, Susan Branford
Scoring systems used at diagnosis of chronic myeloid leukemia (CML), such as Sokal risk, provide important response prediction for patients treated with imatinib. However, the sensitivity and specificity of scoring systems could be enhanced for improved identification of patients with the highest risk. We aimed to identify genomic predictive biomarkers of imatinib response at diagnosis to aid selection of first-line therapy. Targeted amplicon sequencing was performed to determine the germ line variant profile in 517 and 79 patients treated with first-line imatinib and nilotinib, respectively...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296724/the-incidence-and-natural-history-of-dasatinib-complications-in-the-treatment-of-chronic-myeloid-leukemia
#18
Lucy C Fox, Katherine D Cummins, Ben Costello, David Yeung, Rebecca Cleary, Cecily Forsyth, Maciek Tatarczuch, Kate Burbury, Olga Motorna, Jake Shortt, Shaun Fleming, Andrew McQuillan, Anthony Schwarer, Rosemary Harrup, Amy Holmes, Sumita Ratnasingam, Kah-Lok Chan, Wei-Hsun Hsu, Asma Ashraf, Faye Putt, Andrew Grigg
Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions...
May 23, 2017: Blood Advances
https://www.readbyqxmd.com/read/29291008/upfront-treatment-with-the-first-and-second-generation-tyrosine-kinase-inhibitors-in-ph-positive-acute-lymphoblastic-leukemia
#19
Guopan Yu, Fang Chen, Changxin Yin, Qifa Liu, Jing Sun, Li Xuan, Zhiping Fan, Qiang Wang, Xiaoli Liu, Qianli Jiang, Dan Xu
The treatment of Ph-positive acute lymphoblastic leukemia (Ph+ ALL) has entranced tyrosine kinase inhibitors (TKIs) era. Currently both imatinib and dasatinib are registered as the front-line treatment for Ph+ ALL, and the other 2nd-generation TKIs are suggested as an alternative for those who failed the first-line treatment. However, it remains unclear who could benefit from the 2nd-generation TKIs as the first-line treatment for Ph+ ALL. In this study we compared the efficacy and safety of the 1st and 2nd-generation TKIs in the front-line treatment of Ph+ ALL and found a trend toward better disease-free survival (DFS) in the 2nd-generation TKIs group, though no significant difference in early response and long-term survival between the two groups...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29289364/imatinib-is-protective-against-ischemia-reperfusion-injury-in-an-ex%C3%A2-vivo-rabbit-model-of-lung-injury
#20
J Trent Magruder, Joshua C Grimm, Todd C Crawford, Laura Johnston, Lakshmi Santhanam, R Scott Stephens, Dan E Berkowitz, Ashish S Shah, Errol L Bush, Mahendra Damarla, Rachel L Damico, Paul M Hassoun, Bo S Kim
BACKGROUND: Ischemia-reperfusion injury is characterized by an increase in oxidative stress and leads to significant morbidity and death. The tyrosine kinase c-Abl is activated by oxidative stress and mediates processes that affect endothelial barrier function. We hypothesized treatment with the c-Abl inhibitor imatinib would be protective against ischemia-reperfusion injury in our ex vivo rabbit model. METHODS: Heart-lung blocs were harvested from rabbits and stored in cold in Perfadex (Vitrolife, Englewood, CO) for 18 hours...
December 27, 2017: Annals of Thoracic Surgery
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