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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/28703026/placental-transfer-of-tyrosine-kinase-inhibitors-used-for-chronic-myeloid-leukemia-treatment
#16
Ekaterina Chelysheva, Anna Turkina, Evgenia Polushkina, Roman Shmakov, Alexey Zeifman, Sergey Aleshin, Igor Shokhin, Dorel Guranda, Oksana Oksenjuk, Sergey Mordanov, Khamida Kazakbaeva, Ghermes Chilov
Both favorable pregnancy outcomes and fetal abnormalities have been associated with the use of tyrosine kinase inhibitors (TKIs) during pregnancy. The placental transfer of TKIs in humans is poorly understood. We observed women with chronic myeloid leukemia who used imatinib or nilotinib during the late pregnancy stages. The newborns had no birth abnormalities. We evaluated the drug concentrations in maternal blood, umbilical cord blood, and placental samples collected during labor. We found limited placental transfer of the TKIs...
July 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28701512/imatinib-and-nilotinib-off-target-effects-on-human-nk-cells-monocytes-and-m2-macrophages
#17
Francesca Bellora, Alessandra Dondero, Maria Valeria Corrias, Beatrice Casu, Stefano Regis, Fabio Caliendo, Alessandro Moretta, Mario Cazzola, Chiara Elena, Luciana Vinti, Franco Locatelli, Cristina Bottino, Roberta Castriconi
Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas (NB), imatinib showed benefits that might depend on both on-target and immunological off-target effects. We investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of NB cells...
July 12, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28700330/translocation-of-heme-oxygenase-1-contributes-to-imatinib-resistance-in-chronic-myelogenous-leukemia
#18
Bianca Schaefer, Soenke Behrends
Heme oxygenase-1 (HO-1) degrades heme to bilirubin. In addition, it is upregulated in malignant disease and has been described as an important factor for cancer prognosis and therapy. Under physiological conditions HO-1 is anchored to the endoplasmic reticulum (ER). Under stress conditions HO-1 can be cleaved and subsequently translocates to the cytosol and nucleus.In this study we systematically investigated the influence of HO-1's catabolic activity and subcellular localization on resistance against the tyrosine kinase inhibitor imatinib in leukemia cells by confocal laser scanning microscopy, hemoglobin synthesis experiments and cell viability assays...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28698872/proliferation-of-interstitial-cells-in-the-cyclophosphamide-induced-cystitis-and-the-preventive-effect-of-imatinib
#19
Maria Sancho, Domingo Triguero, Aranzazu Lafuente-Sanchis, Angeles Garcia-Pascual
Cyclophosphamide- (CYP-) induced cystitis in the rat is a well-known model of bladder inflammation that leads to an overactive bladder, a process that appears to involve enhanced nitric oxide (NO) production. We investigated the changes in the number and distribution of interstitial cells (ICs) and in the expression of endothelial NO synthase (eNOS) in the bladder and urethra of rats subjected to either intermediate or chronic CYP treatment. Pronounced hyperplasia and hypertrophy of ICs were evident within the lamina propria and in the muscle layer...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28698448/-a-case-of-chronic-myelogenous-leukemia-that-developed-fibrous-pericarditis-owing-to-nilotinib-use
#20
Shogo Miura, Kazuyuki Murase, Akira Sakurada, Kohichi Takada, Satoshi Iyama, Tsutomu Sato, Yasushi Sato, Koji Miyanishi, Masayoshi Kobune, Atsuko Muranaka, Kazutoshi Tachibana, Junji Kato
A 64-year-old man was diagnosed with chronic-phase chronic myelogenous leukemia(CML)in May 2009. He was treated with imatinib and achieved complete cytogenetic response(CCyR)in 2 months. After 4 months of treatment, he developed interstitial pneumonia and became intolerant to imatinib. He was then switched to nilotinib from October of the same year. In June 2013, he was diagnosed with drug-induced pericarditis resulting from nilotinib use, and thus, nilotinib was discontinued. Subsequently, he was followed up without specific treatment for CML...
June 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
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