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https://www.readbyqxmd.com/read/28810322/-comparison-of-generic-and-original-imatinib-in-the-treatment-of-newly-diagnosed-patients-with-chronic-myelogenous-leukemia-in-chronic-phase-a-multicenter-retrospective-clinical-study
#1
H Jiang, L T Zhi, M Hou, J X Wang, D P Wu, X J Huang
Objective: To evaluate the efficacy and safety of generic imatinib (Genike, Chiatai Tianqing Pharmaceutical Group Co., Ltd.) and imatinib (Glevic, Novartis, Switzerland) in newly diagnosed patients with chronic myeloid leukemia in chronic phase (CML-CP) . Methods: A retrospective study of 323 CML-CP patients (205 in Glivec treatment group and 118 in Genike group) who were ≥ 18 years old receiving imatinib monotherapy over the period of June 2013 to March 2016 was done to compare the differences of cytogenetics, molecular curative effect, survival, and adverse reactions between the two groups...
July 14, 2017: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/28712399/-expressions-of-stem-cell-factor-and-hypoxia-inducible-factor-1-alpha-in-pancreatic-cancer-cells-and-related-mechanism
#2
Min Zhang, Yunjian Wang, Qiong Li, Qingjun Li, Nanmu Yang, Guohua You, Li Wang
Objective To study the correlation between the expressions of stem cell factor (SCF) and hypoxia inducible factor 1 alpha (HIF-1α) in pancreatic cancer, and investigate the mechanism by which SCF regulates the expression of HIF-1α. Methods Immunohistochemistry was used to detect the expressions of SCF and HIF-1α in pancreatic cancer specimens and to analyze the correlation between SCF and HIF-1α expressions. Pancreatic cancer PANC-1 cells were treated with different doses of SCF (0, 1, 10, 100 ng/mL) alone or combined with c-KIT inhibitor Gleevec (5 μmol/L)...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28559151/generic-imatinib-in-chronic-myeloid-leukemia-survival-of-the-cheapest
#3
Madhav Danthala, Sadashivudu Gundeti, Siva Prasad Kuruva, Krishna Chaitanya Puligundla, Praveen Adusumilli, Ashok Pillai Karnam, Stalin Bala, Meher Lakshmi Konatam, Lakshmi Srinivas Maddali, Raghunadha Rao Digumarti
INTRODUCTION: The patent expiration of imatinib mesylate (Gleevec; Novartis) on February 1, 2016, has brought the focus back on generic versions of the drug, and an opportunity to provide a safe and cost-effective alternative. The objective of our study was to determine the molecular and cytogenetic responses, survival endpoints (event-free survival, failure-free survival, transformation-free survival, overall survival), and safety of innovator and generic brands of imatinib. MATERIALS AND METHODS: In this retrospective analysis, data from 1812 patients with chronic myeloid leukemia treated with frontline imatinib mesylate (innovator/generic) at a single institution between 2008 and 2014 is included...
May 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28418852/structural-homologies-between-phenformin-lipitor-and-gleevec-aim-the-same-metabolic-oncotarget-in-leukemia-and-melanoma
#4
REVIEW
Gábor Somlyai, T Que Collins, Emmanuelle J Meuillet, Patel Hitendra, Dominic P D'Agostino, László G Boros
Phenformin's recently demonstrated efficacy in melanoma and Gleevec's demonstrated anti-proliferative action in chronic myeloid leukemia may lie within these drugs' significant pharmacokinetics, pharmacodynamics and structural homologies, which are reviewed herein. Gleevec's success in turning a fatal leukemia into a manageable chronic disease has been trumpeted in medical, economic, political and social circles because it is considered the first successful targeted therapy. Investments have been immense in omics analyses and while in some cases they greatly helped the management of patients, in others targeted therapies failed to achieve clinically stable recurrence-free disease course or to substantially extend survival...
July 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28115709/gleevec-shifts-app-processing-from-a-%C3%AE-cleavage-to-a-nonamyloidogenic-cleavage
#5
William J Netzer, Karima Bettayeb, Subhash C Sinha, Marc Flajolet, Paul Greengard, Victor Bustos
Neurotoxic amyloid-β peptides (Aβ) are major drivers of Alzheimer's disease (AD) and are formed by sequential cleavage of the amyloid precursor protein (APP) by β-secretase (BACE) and γ-secretase. Our previous study showed that the anticancer drug Gleevec lowers Aβ levels through indirect inhibition of γ-secretase activity. Here we report that Gleevec also achieves its Aβ-lowering effects through an additional cellular mechanism. It renders APP less susceptible to proteolysis by BACE without inhibiting BACE enzymatic activity or the processing of other BACE substrates...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27983799/on-chip-peptide-mass-spectrometry-imaging-for-protein-kinase-inhibitor-screening
#6
Young-Lai Cho, Young-Pil Kim, Jin Gyeong Son, Miyoung Son, Tae Geol Lee
Protein kinases are enzymes that are important targets for drug discovery because of their involvement in regulating the essential cellular processes. For this reason, the changes in protein kinase activity induced by each drug candidate (the inhibitor in this case) need to be accurately determined. Here, an on-chip secondary ion mass spectrometry (SIMS) imaging technique of the peptides was developed for determining protein kinase activity and inhibitor screening without a matrix. In our method, cysteine-tethered peptides adsorbed onto a gold surface produced changes in the relative peak intensities of the phosphorylated and unphosphorylated substrate peptides, which were quantitatively dependent on protein kinase activity...
December 16, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27909636/imatinib-induced-ototoxicity-in-a-patient-with-gastrointestinal-stromal-tumor-gist
#7
Komal Wasif, Nawal Wasif, Muhammad W Saif
Imatinib (Gleevec) is a biological agent that is approved for the treatment of chronic myeloid leukemia (CML) as well as gastrointestinal stromal tumor (GIST). The most frequently seen adverse effects in patients treated with imatinib include superficial edema, muscle cramps, musculoskeletal pain, rash, fatigue, headache, abdominal pain, and joint pain. Ototoxicity has rarely been reported except in two cases. We report a case of bilateral irreversible sensorineural hearing loss (SNHL) caused by imatinib in a patient receiving this agent in the adjuvant setting...
October 26, 2016: Curēus
https://www.readbyqxmd.com/read/27865145/rectal-gastrointestinal-stromal-tumor-with-metastasis-to-the-penis-case-report-and-review-of-literature
#8
Jacob Carlson, Wilson Alobuia, Jason Mizell
We report the case of a 51-year-old gentleman with previously diagnosed gastrointestinal stromal tumor (GIST) of the rectum with metastasis to the penis. The patient underwent abdominoperineal resection of the primary tumor with negative margins and completed a three-year course of imatinib mesylate (Gleevec). Forty months after resection of his rectal tumor, the patient presented to his urologist with worsening testicular pain, mild lower urinary tract obstructive symptoms, and nocturia. A pelvic MRI revealed the presence of an ill-defined mass in the right perineum extending from the base of the penis to the penoscrotal junction...
2016: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/27801778/antiviral-screening-of-multiple-compounds-against-ebola-virus
#9
Stuart D Dowall, Kevin Bewley, Robert J Watson, Seshadri S Vasan, Chandradhish Ghosh, Mohini M Konai, Gro Gausdal, James B Lorens, Jason Long, Wendy Barclay, Isabel Garcia-Dorival, Julian Hiscox, Andrew Bosworth, Irene Taylor, Linda Easterbrook, James Pitman, Sian Summers, Jenny Chan-Pensley, Simon Funnell, Julia Vipond, Sue Charlton, Jayanta Haldar, Roger Hewson, Miles W Carroll
In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests...
October 27, 2016: Viruses
https://www.readbyqxmd.com/read/27550925/original-research-featured-article-imatinib-mesylate-gleevec-inhibits-notch-and-c-myc-signaling-five-day-treatment-permanently-rescues-mammary-development
#10
Robert Callahan, Barry A Chestnut, Ahmed Raafat
Wap-Int3 transgenic females expressing the Notch4 intracellular domain (designated Int3) from the whey acidic protein promoter exhibit two phenotypes in the mammary gland: blockage of lobuloalveolar development and lactation, and tumor development with 100% penetrance. Previously, we have shown that treatment of Wap-Int3 tumor bearing mice with Imatinib mesylate (Gleevec) is associated with complete regression of the tumor. In the present study, we show that treatment of Wap-Int3 mice during day 1 through day 6 of pregnancy with Gleevec leads to the restoration of their lobuloalveolar development and ability to lactate in subsequent pregnancies in absence of Gleevec treatment...
January 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27540313/optical-coherence-tomography-findings-of-bilateral-foveal-leukemic-infiltration
#11
John Q Le, Puneet S Braich, Vikram S Brar
We report a case of a 59-year-old man with a history of atypical chronic myelogenous leukemia who presented with a several-week history of decreased vision in both eyes. His clinical examination revealed bilateral foveal infiltration, which was also demonstrated on optical coherence tomography. After a failed induction with imatinib (Gleevec(®)), he was treated with omacetaxine (Synribo(®)) with an appropriate hematologic response. As his leukemia improved with chemotherapy, his retinal lesions regressed as demonstrated by serial optical coherence tomography and fundus photographs, with near complete restoration of foveal architecture...
2016: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/27511868/palladium-catalyzed-defluorinative-coupling-of-1-aryl-2-2-difluoroalkenes-and-boronic-acids-stereoselective-synthesis-of-monofluorostilbenes
#12
Richard T Thornbury, F Dean Toste
The palladium-catalyzed defluorinative coupling of 1-aryl-2,2-difluoroalkenes with boronic acids is described. Broad functional-group tolerance arises from a redox-neutral process by a palladium(II) active species which is proposed to undergo a β-fluoride elimination to afford the products. The monofluorostilbene products were formed with excellent diastereoselectivity (≥50:1) in all cases, and it is critical, as traditional chromatographic techniques often fail to separate monofluoroalkene isomers. As a demonstration of this method's unique combination of reactivity and functional-group tolerance, a Gleevec® analogue, using a monofluorostilbene as an amide isostere, was synthesized...
September 12, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27489753/perforation-of-the-colon-during-imatinib-mesylate-gleevec-treatment-in-a-patient-with-chronic-myeloid-leukemia-cml
#13
Najla El Jurdi, Mark Bankoff, Andreas Klein, Muhammad W Saif
Imatinib (Gleevec; STI-571) is a tyrosine-kinase inhibitor (TKI) used in the treatment of multiple cancers, most notably Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) as well as gastrointestinal stromal tumor (GIST). The most common adverse effects with imatinib include superficial edema, muscle cramps, musculoskeletal pain, rash, fatigue, headache, and gastrointestinal side effects. Less frequent side effects include pancytopenia, febrile neutropenia, flushing, and liver function test abnormalities...
2016: Curēus
https://www.readbyqxmd.com/read/27382024/caga-phosphorylation-in-helicobacter-pylori-infected-b-cells-is-mediated-by-the-nonreceptor-tyrosine-kinases-of-the-src-and-abl-families
#14
Linda M Krisch, Gernot Posselt, Peter Hammerl, Silja Wessler
CagA is one of the most important virulence factors of the human pathogen Helicobacter pylori CagA expression can be associated with the induction of severe gastric disorders such as gastritis, ulceration, gastric cancer, or mucosa-associated lymphoid tissue (MALT) lymphoma. After translocation through a type IV secretion system into epithelial cells, CagA is tyrosine phosphorylated by kinases of the Src and Abl families, leading to drastic cell elongation and motility. While the functional role of CagA in epithelial cells is well investigated, knowledge about CagA phosphorylation and its associated signal transduction pathways in B cells is only marginal...
September 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27303656/a-novel-four-way-complex-variant-translocation-involving-chromosome-46-xy-t-4-9-19-22-q25-q34-p13-3-q11-2-in-a-chronic-myeloid-leukemia-patient
#15
Muhammad Asif, Mohammad Sarwar Jamal, Abdul Rehman Khan, Muhammad Imran Naseer, Abrar Hussain, Hani Choudhry, Arif Malik, Shahida Aziz Khan, Maged Mostafa Mahmoud, Ashraf Ali, Saima Iram, Kashif Kamran, Asim Iqbal, Zainularifeen Abduljaleel, Peter Natesan Pushparaj, Mahmood Rasool
Philadelphia (Ph) chromosome (9;22)(q34;q11) is well established in more than 90% of chronic myeloid leukemia (CML) patients, and the remaining 5-8% of CML patients show variant and complex translocations, with the involvement of third, fourth, or fifth chromosome other than 9;22. However, in very rare cases, the fourth chromosome is involved. Here, we found a novel case of four-way Ph+ chromosome translocation involving 46,XY,t(4;9;19;22)(q25:q34;p13.3;q11.2) with CML in the chronic phase. Complete blood cell count of the CML patient was carried out to obtain total leukocytes count, hemoglobin, and platelets...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27302678/role-of-pdgf-d-and-pdgfr-%C3%AE-in-neuroinflammation-in-experimental-ich-mice-model
#16
Peng Yang, Anatol Manaenko, Feng Xu, Liyan Miao, Gaiqing Wang, Xuezhen Hu, Zhen-Ni Guo, Qin Hu, Richard E Hartman, William J Pearce, Andre Obenaus, John H Zhang, Gang Chen, Jiping Tang
OBJECTIVE: Inflammation plays a key role in the pathophysiological processes after intracerebral hemorrhage (ICH). Post-ICH macrophages infiltrate the brain and release pro-inflammatory factors (tumor necrosis factor-α), amplifying microglial activation and neutrophil infiltration. Platelet-derived growth factor receptor-β (PDGFR-β) is expressed on macrophages and it's activation induces the recruitment of macrophages. Platelet-derived growth factor-D (PDGF-D) is an agonist with a significantly higher affinity to the PDGFR-β compared to another isoform of the receptor...
September 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27030078/immunological-off-target-effects-of-imatinib
#17
REVIEW
Laurence Zitvogel, Sylvie Rusakiewicz, Bertrand Routy, Maha Ayyoub, Guido Kroemer
Around 15 years ago, imatinib mesylate (Gleevec(®) or Glivec(®), Novartis, Switzerland) became the very first 'targeted' anticancer drug to be clinically approved. This drug constitutes the quintessential example of a successful precision medicine that has truly changed the fate of patients with Philadelphia-chromosome-positive chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours by targeting the oncogenic drivers of these diseases, BCR-ABL1 and KIT and/or PDGFR, mutations in which lead to gain of function of tyrosine kinase activities...
July 2016: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/26875198/a-multi-centric-bioequivalence-trial-in-ph-chronic-myeloid-leukemia-patients-to-assess-bioequivalence-and-safety-evaluation-of-generic-imatinib-mesylate-400-mg-tablets
#18
Rachna Arora, Manju Sharma, Tausif Monif, Sunil Iyer
PURPOSE: This study was designed to characterize the pharmacokinetic profile and to assess bioequivalence of the sponsor's test formulation (imatinib mesylate 400 mg tablets) with an innovator product (Gleevec 400 mg tablets, Novartis Pharmaceuticals) under fed conditions, in adult patients of Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) stabilized on imatinib mesylate 400 mg. In addition, the aim of this study was to monitor the safety profile of investigational medicinal products (IMPs)...
July 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/26646459/platelet-derived-growth-factor-receptor-%C3%AE-regulates-vascular-smooth-muscle-cell-phenotypic-transformation-and-neuroinflammation-after-intracerebral-hemorrhage-in-mice
#19
Peng Yang, Jiang Wu, Liyan Miao, Anatol Manaenko, Nathanael Matei, Yang Zhang, Liang Xu, William J Pearce, Richard E Hartman, Andre Obenaus, John H Zhang, Feng Xu, Jiping Tang
OBJECTIVE: Platelet-derived growth factor-BB activates platelet-derived growth factor receptor-β and promotes vascular smooth muscle cell phenotypic transformation. Elevated levels of non-muscle myosin IIB (SMemb) are found in secretory smooth muscle cells along with inflammatory mediators, such as intercellular adhesion molecule-1, which can amplify neutrophil infiltration into the brain. In the present study, we investigated the role of platelet-derived growth factor-BB/platelet-derived growth factor receptor-β following intracerebral hemorrhage-induced brain injury in mice, with emphasis on its ability to promote vascular smooth muscle cell phenotypic transformation followed by increased intercellular adhesion molecule-1 expression and elevated neutrophil infiltration in the vicinity of the hematoma...
June 2016: Critical Care Medicine
https://www.readbyqxmd.com/read/26580599/vitamin-d-analogs-potentiate-the-antitumor-effect-of-imatinib-mesylate-in-a-human-a549-lung-tumor-model
#20
Ewa Maj, Beata Filip-Psurska, Marta Świtalska, Andrzej Kutner, Joanna Wietrzyk
In previous papers, we presented data on studies on the anticancer activity of the vitamin D₃ analogs, named PRI-2191 and PRI-2205, in different cancer models. In this study, we showed the improved antiproliferative activity of a combination of imatinib mesylate (Gleevec, GV) and cytostatic agents in in vitro studies, when used with a third compound, namely PRI-2191, in an A549 human lung cancer model. Furthermore, we analyzed the influence of both PRI-2191, as well as PRI-2205 on the anticancer activity of GV in mice bearing A549 tumors...
2015: International Journal of Molecular Sciences
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