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https://www.readbyqxmd.com/read/28727765/defining-the-target-and-the-effect-of-imatinib-on-the-filarial-c-abl-homologue
#1
Elise M O'Connell, Olena Kamenyeva, Sara Lustigman, Aaron Bell, Thomas B Nutman
BACKGROUND: Previously we demonstrated the micro- and macrofilaricidal properties of imatinib in vitro. Here we use electron and multiphoton microscopy to define the target of imatinib in the adult and microfilarial stages of Brugia malayi, and assess the effects of pharmacologically relevant levels of imatinib on the adult parasites. METHODS: After fixation of adult B. malayi males and females, sections were stained with polyclonal rabbit anti-c-Abl antibody (or isotype control) and imaged with multiphoton fluorescent microscopy...
July 20, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28726812/a-patient-with-germ-line-gain-of-function-pdgfrb-p-n666h-mutation-and-marked-clinical-response-to-imatinib
#2
Dinel Pond, Florence A Arts, Nancy J Mendelsohn, Jean-Baptiste Demoulin, Gunter Scharer, Yoav Messinger
PurposeHeterozygous germ-line activating mutations in PDGFRB cause Kosaki and Penttinen syndromes and myofibromatosis. We describe a 10-year-old child with a germ-line PDGFRB p.N666H mutation who responded to the tyrosine kinase inhibitor imatinib by inhibition of PDGFRB.MethodsThe impact of p.N666H on PDGFRB function and sensitivity to imatinib was studied in cell culture.ResultsCells expressing the p.N666H mutation showed constitutive PDGFRB tyrosine phosphorylation. PDGF-independent proliferation was abolished by imatinib at 1 μM concentration...
July 20, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28726645/chronic-myeloid-leukemia-expected-relapse-s-clinical-laboratory-indexes
#3
T Kirtava, D Ghirdaladze, T Vatsadze
Today Chronic Myeloid Leukemia (CML) relapse's final assessment and monitoring in the whole world is implemented by BCR-ABL gene quantitative detection - during the polymerase chain reaction (by PSR means). Implementation of this monitoring materially and technically is not often available and remission during years is being assessed using monthly clinical-laboratory data. Proceeding from this, the goal of our work was to find the clinical-laboratory features, indicating the expected relapse and require the urgent molecular research carry out...
June 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28725989/imatinib-in-myeloid-lymphoid-neoplasms-with-eosinophilia-and-rearrangement-of-pdgfrb-in-chronic-or-blast-phase
#4
Mohamad Jawhar, Nicole Naumann, Juliana Schwaab, Herrad Baurmann, Jochen Casper, Tu-Anh Dang, Lutz Dietze, Konstanze Döhner, Annette Hänel, Bernd Lathan, Hartmut Link, Sina Lotfi, Ole Maywald, Stephan Mielke, Lothar Müller, Uwe Platzbecker, Otto Prümmer, Henrike Thomssen, Karin Töpelt, Jens Panse, Tom Vieler, Wolf-Karsten Hofmann, Torsten Haferlach, Claudia Haferlach, Alice Fabarius, Andreas Hochhaus, Nicholas C P Cross, Andreas Reiter, Georgia Metzgeroth
We evaluated clinical characteristics and outcome on imatinib of 22 patients with myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRB. Median age was 49 years (range 20-80), 91% were male. Fifteen different PDGFRB fusion genes were identified. Eosinophilia was absent in 4/19 (21%) cases and only 11/19 (58%) cases had eosinophils ≥1.5×10(9)/L. On imatinib, 17/17 (100%) patients in chronic phase achieved complete hematologic remission after median 2 months (range 0-13)​. Complete cytogenetic remission and/or complete molecular remission by RT-PCR were achieved in 12/13 (92%) and 12/14 patients (86%) after median 10 (range 3-34) and 19 months (range 7-110), respectively...
July 19, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28725653/calr-positive-myeloproliferative-disorder-in-a-patient-with-ph-positive-chronic-myeloid-leukemia-in-durable-treatment-free-remission-a-case-report
#5
Irene Dogliotti, Carmen Fava, Anna Serra, Enrico Gottardi, Filomena Daraio, Francesca Carnuccio, Emilia Giugliano, Monica Bocchia, Giuseppe Saglio, Giovanna Rege-Cambrin
Current diagnostic criteria for Philadelphia-negative myeloproliferative neoplasia (MPN) have been redefined by the discovery of Janus kinase 2 (JAK2), myeloproliferative leukemia (MPL) and calreticulin (CALR) genetic alterations. Only few cases of coexistence of CALR-mutated MPN and Philadelphia-positive chronic myeloid leukemia (CML) have been described so far. Here we report the case of a patient with CML diagnosed in 2001, treated with imatinib and pegylated interferon (IFN) frontline. She reached complete molecular remission (CMR) and discontinued imatinib, maintaining treatment free remission...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28723770/initial-application-of-transanal-endoscopic-microsurgery-for-high-risk-lower-rectal-gastrointestinal-stromal-tumor-after-imatinib-mesylate-neoadjuvant-chemotherapy-a-case-report
#6
Qiaofei Liu, Guangxi Zhong, Weixun Zhou, Guole Lin
RATIONALE: The lower rectal gastrointestinal stromal tumor (GIST) is a rare entity and warrants special attentions because of the considerations of preserving of anal and urinal functions. Neoadjuvant therapy with imatinib mesylate (IM) has achieved great success in GIST, which potentially extends the applications of function-preserving minimally invasive surgical procedures. Transanal endoscopic microsurgery (TEM) is a well-developed minimally invasive technique for benign tumors in lower rectum...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28723754/an-economic-analysis-of-high-dose-imatinib-dasatinib-and-nilotinib-for-imatinib-resistant-chronic-phase-chronic-myeloid-leukemia-in-china-a-cheers-compliant-article
#7
Bin Wu, Maobai Liu, Te Li, Houwen Lin, Hua Zhong
BACKGROUND: The aim of the study was to test the cost-effectiveness of dasatinib compared to high-dose imatinib and nilotinib in Chinese patients who were diagnosed with imatinib-resistant chronic myeloid leukemia in the chronic phase (CML-CP). METHODS: A Markov model combined with clinical effectiveness, utility, and cost data was used. The sensitivity analyses were conducted to determine the robustness of the model outcomes. The impact of patient assistance programs (PAPs) was assessed...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28723416/unravelling-the-pharmacologic-opportunities-and-future-directions-for-targeted-therapies-in-gastro-intestinal-cancers-part-2-neuroendocrine-tumours-hepatocellular-carcinoma-and-gastro-intestinal-stromal-tumours
#8
REVIEW
Cindy Neuzillet, Louis de Mestier, Benoît Rousseau, Olivier Mir, Mohamed Hebbar, Hemant M Kocher, Philippe Ruszniewski, Christophe Tournigand
Until the 1990s, cytotoxic chemotherapy has been the cornerstone of medical therapy for gastrointestinal (GI) cancers. Better understanding of the cancer cell molecular biology has led to the therapeutic revolution of targeted therapies, i.e. monoclonal antibodies or small molecule inhibitors directed against proteins that are specifically overexpressed or mutated in cancer cells. These agents, being more specific to cancer cells, were expected to be less toxic than conventional cytotoxic agents. However, their effects have sometimes been disappointing, due to intrinsic or acquired resistance mechanisms, or to an activity restricted to some tumour settings, illustrating the importance of patient selection and early identification of predictive biomarkers of response to these therapies...
July 16, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28722363/-erdheim-chester-disease-a-differential-diagnosis-of-retroperitoneal-fibrosis
#9
Raphaël André, Jörg D Seebach
Erdheim-Chester disease is a rare multisystemic non-Langerhans histiocytosis with about 500 reported cases. Typical features include retroperitoneal and perirenal fibrosis (hairy kidney), periaortitis with a coated aorta, osteosclerosis of the lower limbs, and sometimes exophthalmia or diabetes insipidus. Histology is the cornerstone for diagnosis showing an infiltrate with foamy histiocytes and occasional multinucleated giant cells (Touton cells). There is no standard treatment regimen, current options include corticosteroids, interferon alpha, systemic chemotherapy, and radiation therapy ; however, a better understanding of the pathophysiological mechanisms has allowed the emergence of novel targeted treatments such as vemurafenib, imatinib, and anakinra...
April 5, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28719608/cholesterol-esterification-inhibition-and-imatinib-treatment-synergistically-inhibit-growth-of-bcr-abl-mutation-independent-resistant-chronic-myelogenous-leukemia
#10
Shovik Bandyopadhyay, Junjie Li, Elie Traer, Jeffrey W Tyner, Amy Zhou, Stephen T Oh, Ji-Xin Cheng
Since the advent of tyrosine kinase inhibitors (TKIs) such as imatinib, nilotinib, and dasatinib, chronic myelogenous leukemia (CML) prognosis has improved greatly. However, ~30-40% of patients develop resistance to imatinib therapy. Although most resistance is caused by mutations in the BCR-ABL kinase domain, 50-85% of these patients develop resistance in the absence of new mutations. In these cases, targeting other pathways may be needed to regain clinical response. Using label-free Raman spectromicroscopy, we evaluated a number of leukemia cell lines and discovered an aberrant accumulation of cholesteryl ester (CE) in CML, which was found to be a result of BCR-ABL kinase activity...
2017: PloS One
https://www.readbyqxmd.com/read/28717743/chronic-myeloid-leukemia-in-india
#11
REVIEW
Prasanth Ganesan, Lalit Kumar
BACKGROUND: In the last decade, the use of imatinib has brought a paradigm shift in the management of chronic myeloid leukemia (CML). In India, imatinib has been available for more than a decade and has been made accessible to all segments of the population because of patient assistance programs and cheaper generic versions. Despite improvements in survival, there are unique challenges in the Indian context. METHODS: We reviewed published data pertaining to CML in India for the period of 1990 to 2016, using PubMed advanced search with the terms chronic myeloid leukemia and India, and included studies that reported on epidemiology, monitoring for therapy, treatment outcomes, and resistance...
February 2017: Journal of Global Oncology
https://www.readbyqxmd.com/read/28716746/controlled-release-and-anti-proliferative-effect-of-imatinib-mesylate-loaded-sporopollenin-microcapsules-extracted-from-pollens-of-betula-pendula
#12
Idris Sargin, Lalehan Akyuz, Murat Kaya, Gamze Tan, Talip Ceter, Kevser Yildirim, Seymanur Ertosun, Gozde Hatun Aydin, Muge Topal
Sporopollenin is a promising material for drug encapsulation due to its excellent properties; uniformity in size, non-toxicity, chemically and thermally resilient nature. Herein, morphologically intact sporopollenin microcapsules were extracted from Betula pendula pollens. Cancer therapeutic agent (imatinib mesylate) was loaded into the microcapsules. The encapsulation efficiency by passive loading technique was found to be 21.46%. Release behaviour of the drug from microcapsules was found to be biphasic, with an initial fast release followed by a slower rate of release...
July 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28715941/moderate-anemia-at-diagnosis-is-an-independent-prognostic-marker-of-the-eutos-sokal-and-hasford-scores-for-survival-and-treatment-response-in-chronic-phase-chronic-myeloid-leukemia-patients-with-frontline-imatinib
#13
Po-Shen Ko, Yuan-Bin Yu, Yao-Chung Liu, Yi-Tsui Wu, Man-Hsin Hung, Jyh-Pyng Gau, Chia-Jen Liu, Liang-Tsai Hsiao, Po-Min Chen, Tzeon-Jye Chiou, Chun-Yu Liu, Jin-Hwang Liu
OBJECTIVES: We aimed to examine the prognostic value of anemia for the diagnosis of chronic myeloid leukemia in the chronic phase (CML-CP) receiving imatinib. METHODS: One hundred fifty-four CML-CP patients were enrolled. The influences of moderate anemia with hemoglobin (Hb) < 10 g/dl, four scoring systems and the early molecular response at three months (BCR-ABL ≤ 10%; 3M-EMR) on the achievement of a deep molecular response (DMR, MR4.5), progression-free survival (PFS), event-free survival (EFS) and overall survival (OS) were compared...
July 18, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28714357/pharmaceutical-assistance-programs-for-cancer-patients-in-the-era-of-orally-administered-chemotherapeutics
#14
Aaron Mitchell, Benyam Muluneh, Rachana Patel, Ethan Basch
Introduction The rising cost of cancer drugs may make treatment unaffordable for some patients. Patients often rely on drug manufacturer-administered Pharmaceutical Assistance Programs (PAPs) to obtain drugs and reduced or no cost. The overall usage of PAPs within cancer care delivery is unknown. Methods We included all cancer patients across an academically affiliated, integrated health system in North Carolina during 2014 ( N = 8591). We identified the subset of patients receiving PAP assistance to afford one or more cancer drugs, in order to calculate the proportion of patients receiving PAP assistance, and the retail value of the assistance...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/28712742/analyses-of-treatment-outcome-according-to-age-in-patients-with-chronic-myeloid-leukemia-receiving-front-line-imatinib-therapy
#15
Irena Ćojbašić, Lana Mačukanović-Golubović, Miodrag Vučić, Ivan Tijanić
BACKGROUND: Previous studies have indicated that the effect of age at the diagnosis of chronic myeloid leukemia (CML) is minimized in patients treated with imatinib. The treatment response and survival rates were similar for younger and elderly patients. The aim of the present study was to evaluate the effect of age on the treatment outcomes in patients with CML receiving front-line imatinib therapy. PATIENTS AND METHODS: Using age, 101 patients were divided into 3 groups: young (age, 18-44 years; YP), middle-age (age, 45-64 years; MP), and elderly (age, ≥ 65 years; EP)...
June 24, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28711648/alteration-of-pdgfr%C3%AE-akt-mtor-pathway-signaling-in-fibrosarcomatous-transformation-of-dermatofibrosarcoma-protuberans
#16
Yuka Hiraki-Hotokebuchi, Yuichi Yamada, Kenichi Kohashi, Hidetaka Yamamoto, Makoto Endo, Nokitaka Setsu, Kuma Yuki, Takamichi Ito, Yukihide Iwamoto, Masutaka Furue, Yoshinao Oda
Dermatofibrosarcoma protuberans (DFSP) is a cutaneous mesenchymal tumor of intermediate malignancy and fibroblastic/myofibroblastic differentiation. Fibrosarcomatous (FS) component is a high-grade component of DFSP. The detailed oncogenic difference between DFSP and FS components is not clear. We thus investigated the Akt-mTOR pathway in both components. We used 65 tumor samples obtained from 65 patients. The phosphorylation of Akt-mTOR pathway proteins (Akt, mTOR, 4EBP1, and S6RP) and PDGFRα/β was assessed by immunohistochemical staining, the results of which were confirmed by western blotting...
July 12, 2017: Human Pathology
https://www.readbyqxmd.com/read/28710991/the-impact-assessment-of-anticancer-drug-imatinib-on-the-feeding-behavior-of-rotifers-with-an-integrated-perspective-exposure-post-exposure-and-re-exposure
#17
Zhengyu Yan, Kun Yan, Xingliang He, Yanhua Liu, Jie Zhang, Oscar Lopez Torres, Ruixin Guo, Jianqiu Chen
The anticancer drugs are getting increasing attention as an emerging contaminant in the aquatic environments. In the present study, feeding behavior of the rotifer Brachionus calyciflorus under the impact of anticancer drug imatinib was evaluated. Traditional toxicological studies usually focus on dose-effect relationship at a given exposure time, while ignore the possible impact after the exposure. Thus, how the impact varied in the post-exposure and re-exposure was also considered in the present study. The feeding depression of the rotifers was attributed to the increased concentration of imatinib...
July 12, 2017: Chemosphere
https://www.readbyqxmd.com/read/28710566/remarkable-effects-of-imatinib-in-a-family-with-young-onset-gastrointestinal-stromal-tumors-and-cutaneous-hyperpigmentation-associated-with-a-germline-kit-trp557arg-mutation-case-report-and-literature-overview
#18
S Farag, L E van der Kolk, H H van Boven, A C J van Akkooi, G L Beets, J W Wilmink, N Steeghs
Gastrointestinal stromal tumors (GISTs) occur mostly sporadically. GISTs associated with a familial syndrome are very rare and are mostly wild type for KIT and platelet-derived growth factor alpha (PDGFRA). To date 35 kindreds and 8 individuals have been described with GISTs associated with germline KIT mutations. This is the third family described with a germline p.Trp557Arg mutation in exon 11 of the KIT gene. The effect of imatinib in patients harboring a germline KIT mutation has been rarely described. Moreover, in some studies imatinib treatment was withheld considering the lack of evidence for efficacy of this treatment in GIST patients harboring a germline KIT mutation...
July 14, 2017: Familial Cancer
https://www.readbyqxmd.com/read/28706179/nilotinib-induced-recurrent-gastric-polyps-case-report-and-review-of-literature
#19
Nancy Kassem, Omar M Ismail, Halima Elomri, Mohamad A Yassin
BACKGROUND Tyrosine kinase inhibitors (TKIs) are currently an important targeted drug class in the treatment of chronic myeloid leukemia (CML). Imatinib was the first approved TKI for CML in 2001. Nilotinib is a second-generation TKI, approved in 2007; it inhibits BCR-ABL, PDGFR, and c-KIT, and is 30 times more potent than imatinib. Tyrosine kinase enzymes are expressed in multiple tissues and are involved in several signaling pathways; they have been shown to have several off-target side effects. CASE REPORT We report a case of an elderly male with CML and no history of gastrointestinal diseases, treated with nilotinib, and developed recurrent gastric polyps after three years of treatment...
July 14, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28704552/ptch1-is-a-reliable-marker-for-predicting-imatinib-response-in-chronic-myeloid-leukemia-patients-in-chronic-phase
#20
Juan M Alonso-Dominguez, Luis Felipe Casado, Eduardo Anguita, Maria Teresa Gomez-Casares, Ismael Buño, Francisca Ferrer-Marín, Alicia Arenas, Rafael Del Orbe, Rosa Ayala, Pilar Llamas, Rocio N Salgado, Santiago Osorio, Pedro Sanchez-Godoy, Carmen Burgaleta, Ignacio Mahíllo-Fernández, Valentin Garcia-Gutierrez, Juan Luis Steegmann, Joaquín Martinez-Lopez
Patched homolog 1 gene (PTCH1) expression and the ratio of PTCH1 to Smoothened (SMO) expression have been proposed as prognostic markers of the response of chronic myeloid leukemia (CML) patients to imatinib. We compared these measurements in a realistic cohort of 101 patients with CML in chronic phase (CP) using a simplified qPCR method, and confirmed the prognostic power of each in a competing risk analysis. Gene expression levels were measured in peripheral blood samples at diagnosis. The PTCH1/SMO ratio did not improve PTCH1 prognostic power (area under the receiver operating characteristic curve 0...
2017: PloS One
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