gleevec

PURPOSE: The study aimed to assess the effectiveness of Imatinib in chronic myeloid leukaemia (CML) in our hospital population. In addition to identify which brand of imatinib (Gleevec/Veenat) is cost effective for CML patients and to assess the possible adverse drug reactions during the treatment for chronic myeloid leukaemia. METHODS: A non-interventional (observational), both retrospective and prospective study was carried out in the department of Medical Oncology and Haematology of our hospital...

Schistosomiasis, caused by schistosome parasites, is a neglected tropical disease affecting humans and animals. There is no vaccine available yet, and fear of upcoming resistance against the only widely used drug, praziquantel, is omnipresent. Previously, we showed that imatinib (Gleevec), an anticancer drug, affected schistosome physiology and caused the death of adult Schistosoma mansoni in vitro. Here, we present the first known evidence that one effect of imatinib is the induction of autophagy in S. mansoni...

Taxanes are widely used cancer chemotherapeutics. However, intrinsic resistance limits their efficacy without any actionable resistance mechanism. We have discovered a microtubule (MT) plus-end-binding CLIP-170 protein variant, hereafter CLIP-170S, which we found enriched in taxane-resistant cell lines and patient samples. CLIP-170S lacks the first Cap-Gly motif, forms longer comets, and impairs taxane access to its MT luminal binding site. CLIP-170S knockdown reversed taxane resistance in cells and xenografts, whereas its re-expression led to resistance, suggesting causation...

Since the introduction of imatinib, the management of chronic myeloid leukemia (CML) has changed considerably. Tyrosine kinase inhibitors (TKIs) are the mainstay of CML treatment; however, the high financial burden of TKIs can be problematic for both the patients and health care systems. After the emergence of generics, reimbursement policies of many countries have changed, and generics offered an alternative treatment option for CML patients. There are many papers published on the use of generics in CML patients with conflicting results regarding both efficacy and safety...

Targeted strategies against specific driver molecules of cancer have brought about many advances in cancer treatment since the early success of the first small molecule inhibitor Gleevec. Today, there are a multitude of targeted therapies approved by the Food and Drug Administration for the treatment of cancer. However, the initial efficacy of virtually every targeted treatment is often reversed by tumor resistance to the inhibitor through acquisition of new mutations in the target molecule, or reprogramming of the epigenome, transcriptome, or kinome of the tumor cells...

OBJECTIVE: This study investigates the synergistic effects of Gleevec (imatinib) and rapamycin on the proliferative and angiogenic properties of mouse bone marrow-derived endothelial progenitor cells (EPCs). MATERIALS AND METHODS: EPCs were isolated from mouse bone marrow and treated with different concentrations of Gleevec or rapamycin individually or in combination. The cell viability and proliferation were examined using the MTT assay. An analysis of cell cycle and apoptosis was performed using flow cytometry...

BACKGROUND: Type 1 diabetes results from autoimmune-mediated destruction of β cells. The tyrosine kinase inhibitor imatinib might affect relevant immunological and metabolic pathways, and preclinical studies show that it reverses and prevents diabetes. Our aim was to evaluate the safety and efficacy of imatinib in preserving β-cell function in patients with recent-onset type 1 diabetes. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial...

A group of clinically approved cancer therapeutic tyrosine kinase inhibitors was screened to test their effects on the expression of angiotensin-converting enzyme 2 (ACE2), the cell surface receptor for SARS-CoV-2. Here, we show that the receptor tyrosine kinase inhibitor imatinib (also known as STI571, Gleevec) can inhibit the expression of the endogenous ACE2 gene at both the transcript and protein levels. Treatment with imatinib resulted in inhibition of cell entry of the viral pseudoparticles (Vpps) in cell culture...

Imatinib is transported extracellularly by ABCB1 and ABCG2 efflux transporters and bound to alpha-1-acid glycoprotein (AGP) in the bloodstream. However, the clinical and pharmacokinetic effects of ABCB1 and ABCG2 on imatinib were inconsistent in the previous literature and have not been confirmed. Therefore, in the present study, we explored the effects of the ABCG2 and ABCB1 genetic polymorphisms on imatinib pharmacokinetics in association with plasma AGP levels in healthy subjects. Twenty-seven healthy individuals were recruited, genotyped for ABCG2 and ABCB1 , and given a single oral dose of 400 mg imatinib...

Gleevec (a.k.a., imatinib) is an important anticancer (e.g., chronic myeloid leukemia) chemotherapeutic drug due to its inhibitory interaction with the Abl kinase. Here, we use atomically detailed simulations within the Milestoning framework to study the molecular dissociation mechanism of Gleevec from Abl kinase. We compute the dissociation free energy profile, the mean first passage time for unbinding, and explore the transition state ensemble of conformations. The milestones form a multidimensional network with average connectivity of about 2...

No abstract text is available yet for this article.

Histiocytic sarcoma is a rare malignant histiocytic neoplasm composed of cells with morphologic and immunophenotypic features of mature tissue histiocytes. It occurs anywhere in the body and behaves aggressively. However, its etiology is unknown. Here, we report a 68-year-old female who developed histiocytic sarcoma following chemotherapy with imatinib (Gleevec) for gastrointestinal stromal tumor. Possible mechanisms of transdifferentiation from gastrointestinal stromal tumor to histiocytic sarcoma are discussed based on the features of our case and other two similar cases in the literature...

Rapid identification of inhibitors for a family of proteins and prediction of ligand specificity are highly desirable for structure-based drug design. However, sequentially docking ligands into each protein target with conventional single-target docking methods is too computationally expensive to achieve these two goals, especially when the number of the targets is large. In this work, we use an efficient ensemble docking algorithm for simultaneous docking of ligands against multiple protein targets. We use protein kinases, a family of proteins that are highly important for many cellular processes and for rational drug design, as an example to demonstrate the feasibility of investigating ligand selectivity with this algorithm...

No abstract text is available yet for this article.

Researchers have developed several three-dimensional (3D) culture systems, including spheroids, organoids, and tumoroids with increased properties of cancer stem cells (CSCs), also called cancer-initiating cells (CICs). Drug resistance is a crucial issue involving recurrence in cancer patients. Many studies on anti-cancer drugs have been reported using 2D culture systems, whereas 3D cultured tumoroids have many advantages for assessing drug sensitivity and resistance. Here, we aimed to investigate whether Cisplatin (a DNA crosslinker), Imatinib (a multiple tyrosine kinase inhibitor), and 5-Fluorouracil (5-FU: an antimetabolite) alter the tumoroid growth of metastatic colorectal cancer (mCRC)...

BACKGROUND: Duodenal gastrointestinal stromal tumors (GISTs) are uncommon, making up only 3-5% of all GISTs. [1,2] Historically, the treatment of choice for duodenal GIST tumors was pancreaticoduodenectomy. [3]Currently, newer surgical intervention methods including local resection via laparotomy, endoscopic resection, and robotic resection are feasible. When doing a local resection, the defect can be closed either primarily or via a Roux-en-Y duodenojejunostomy. [3] Case presentation: Our patient is a 64-year- old female who presented initially with shortness of breath and was found to have a pulmonary embolism...

The approval of the first kinase inhibitor, Gleevec, ushered in a paradigm shift for oncological treatment-the use of genomic data for targeted, efficacious therapies. Since then, over 48 additional small-molecule kinase inhibitors have been approved, solidifying the case for kinases as a highly druggable and attractive target class. Despite the role deregulated kinase activity plays in cancer, only 8% of the kinome has been effectively "drugged." Moreover, 24% of the 634 human kinases are understudied...

BACKGROUND: Cancer is spreading all over the world and it is becoming leading cause of major deaths. Today's most difficult task for every researcher is to invent a new drug that can treat cancer with minimal side effects. Many factors including pollution, modern lifestyle and food habits, exposure to oncogenic agents or radiations, enhanced industrialization etc. are causing cancer. Treatment of cancer is done by various methods that include chemotherapy, radiotherapy, surgery and immunotherapy in combination or singly along with kinase inhibitors...

Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal neoplasm of the gastrointestinal tract but consist of only 1% of all primary gastrointestinal neoplasms. Differentiated from other spindle cell tumors, GISTs are uniquely positive for CD117 expression which allows for molecular targeting therapy with imatinib mesylate (Gleevec). Clinical presentations are variable, ranging from asymptomatic to vague symptoms of abdominal pain, early satiety, abdominal distention or gastrointestinal bleeding...

Intracerebral hemorrhage (ICH) remains one of the most debilitating types of stroke and is characterized by a sudden bleeding from a ruptured blood vessel. ICH often results in high mortality and in survivors, permanent disability. Most studies have focused on neuroprotective strategies designed to minimize secondary consequences and prevent further pathology. Lacking is an understanding of how ICH acutely affects cerebrovascular components and their response to therapeutic interventions. We hypothesized that ICH alters cortical vessel complexity in the parenchyma adjacent to site of the initial vascular disruption and that vascular abnormalities would be mitigated by administration of the PDGFR inhibitor, Imatinib mesylate (Gleevec)...