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https://www.readbyqxmd.com/read/28209946/pdgfr%C3%A1%C2%B5-rearranged-myeloid-neoplasm-with-marked-eosinophilia-in-a-37-year-old-man-and-a-literature-review
#1
Mirela Andrei, Andrei Bandarchuk, Cherif Abdelmalek, Ajay Kundra, Vladimir Gotlieb, Jen Chin Wang
BACKGROUND PDGFRᵝ-positive myeloid neoplasms are rare. Marked leukocytosis (over 100×10⁹/L) with marked eosinophilia (over 10%) has been rarely described in myeloid neoplasms associated with PDGFRᵝ rearrangement. CASE REPORT We report a case of 37-year-old man with myeloid neoplasm associated with PDGFRᵝ rearrangement who presented with marked eosinophilia of 13.3% and leukocytosis with WBC count of 189×10⁹/L. He was found to have PDGFRᵝ locus rearrangement at 5q32-33 by fluorescent in situ hybridization (FISH)...
February 17, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28203166/gastrointestinal-stromal-tumour-with-synchronous-bone-metastases-a-case-report-and-literature-review
#2
Philippe Rochigneux, Lénaig Mescam-Mancini, Delphine Perrot, Erwan Bories, Laurence Moureau-Zabotto, Anthony Sarran, Jérôme Guiramand, François Bertucci
Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours of the digestive tract, derived from Cajal interstitial cells. Bone metastases are very rare, and there is no consensus regarding their treatment. Here, we present the unusual case of a 66-year-old man with a gastric GIST with synchronous bone and liver metastases, fully documented at the pathological and molecular levels with a KIT exon 11 mutation. After 9 months of imatinib, the scanner showed a 33% partial response of target lesions. We also review the literature and describe the characteristics, treatment, and outcome of all cases previously reported...
January 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28198176/what-is-changing-in-the-surgical-treatment-of-gastrointestinal-stromal-tumors-after-multidisciplinary-approach-a-comprehensive-literature-s-review
#3
Belinda De Simone, Luca Ansaloni, Massimo Sartelli, Federico Coccolini, Salomone Di Saverio, Maria A Pantaleo, Maristella Saponara, Margherita Nannini, Harishine K Abongwa, Josephine A Napoli, Fausto Catena
INTRODUCTION: GIST represent the most common mesenchymal neoplasms of the gastrointestinal tract Surgery is the only curative treatment for GIST. The aim of our review is to highlight the changes in the surgical treatment of GIST after the introduction of TKI therapy in a multimodality management ( neo-adiuvant or adiuvant setting). EVIDENCE ACQUISITION: We carried out a review of the recent literature about surgical treatment of GIST according to its anatomical location and size according to PRISMA STATEMENT to systematic review...
February 14, 2017: Minerva Chirurgica
https://www.readbyqxmd.com/read/28197361/nkp30-isoforms-and-nkp30-ligands-are-predictive-biomarkers-of-response-to-imatinib-mesylate-in-metastatic-gist-patients
#4
Sylvie Rusakiewicz, Aurélie Perier, Michaela Semeraro, Jonathan M Pitt, Elke Pogge von Strandmann, Katrin S Reiners, Sandrine Aspeslagh, Christelle Pipéroglou, Frédéric Vély, Alexandre Ivagnes, Sarah Jegou, Niels Halama, Loic Chaigneau, Pierre Validire, Christos Christidis, Thierry Perniceni, Bruno Landi, Anne Berger, Nicolas Isambert, Julien Domont, Sylvie Bonvalot, Philippe Terrier, Julien Adam, Jean-Michel Coindre, Jean-François Emile, Vichnou Poirier-Colame, Kariman Chaba, Benedita Rocha, Anne Caignard, Antoine Toubert, David Enot, Joachim Koch, Aurélien Marabelle, Marion Lambert, Sophie Caillat-Zucman, Serge Leyvraz, Christian Auclair, Eric Vivier, Alexander Eggermont, Christophe Borg, Jean-Yves Blay, Axel Le Cesne, Olivier Mir, Laurence Zitvogel
Despite effective targeted therapy acting on KIT and PDGFRA tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions of NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196207/correlation-of-long-term-results-of-imatinib-in-advanced-gastrointestinal-stromal-tumors-with-next-generation-sequencing-results-analysis-of-phase-3-swog-intergroup-trial-s0033
#5
Michael Heinrich, Cathryn Rankin, Charles D Blanke, George D Demetri, Ernest C Borden, Christopher W Ryan, Margaret von Mehren, Martin E Blackstein, Dennis A Priebat, William D Tap, Robert G Maki, Christopher L Corless, Jonathan A Fletcher, Kouros Owzar, John J Crowley, Robert S Benjamin, Laurence H Baker
Importance: After identification of activating mutations of the KIT gene in gastrointestinal stromal tumor (GIST)-the most common sarcomaof the gastrointestinal tract-a phase 2 study demonstrated efficacy of imatinib mesylate in patients with metastatic GIST harboring a KIT exon 11 mutation. Initial results of long-term follow-up have found a survival benefit in this subgroup of patients. Obective: To assess the long-term survival of patients with GIST who were treated in SWOG study S0033 and to present new molecular data regarding treatment outcomes...
February 9, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28195260/everything-you-always-wanted-to-know-about-gist-but-were-afraid-to-ask-an-update-on-gist-pathology
#6
R Ricci, L Saragoni
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The discovery of the occurrence of activating KIT mutations and KIT expression in GISTs opened the way to the unequivocal diagnosis of these tumors and to their successful treatment with imatinib, a tyrosin kinase inhibitor. Since then, research progress revealed molecular GIST triggers alternative to KIT, implying heterogeneous analytic approaches and prognostic expectations. Several targeted therapies, variably specific for each GIST trigger, have been developed or are being investigated...
September 2016: Pathologica
https://www.readbyqxmd.com/read/28194061/performance-of-sokal-and-eutos-scores-for-predicting-cytogenetic-and-molecular-response-in-newly-diagnosed-chronic-myeloid-leukemia-chronic-phase-patients-on-imatinib
#7
Sandip Ganguly, K C Lakshmaiah, Linu Abraham Jacob, Suresh Babu, Lokanatha Dasappa, K S Govind Babu
Sokal index was developed in the pre-imatinib era to predict and prognosticate the outcome of Chronic myeloid leukemia (CML) patients. In the Imatinib era, a new scoring system called EUTOS scoring system has been validated as a predictive marker in CML. The scores have shown variable correlation with complete cytogenetic response (CCyR) and major molecular response (MMR). To assess the performance of Sokal score and EUTOS score as a predictive marker for CCyR and MMR for newly diagnosed CML-CP patients treated with TKIs...
March 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/28192400/oncogenic-signaling-by-kit-tyrosine-kinase-occurs-selectively-on-the-golgi-apparatus-in-gastrointestinal-stromal-tumors
#8
Y Obata, K Horikawa, T Takahashi, Y Akieda, M Tsujimoto, J A Fletcher, H Esumi, T Nishida, R Abe
Gastrointestinal stromal tumors (GISTs) are caused by gain-of-function mutations in the Kit receptor tyrosine kinase. Most primary GIST patients respond to the Kit inhibitor imatinib, but this drug often becomes ineffective because of secondary mutations in the Kit kinase domain. The characteristic intracellular accumulation of imatinib-sensitive and -resistant Kit protein is well documented, but its relationship to oncogenic signaling remains unknown. Here, we show that in cancer tissue from primary GIST patients as well as in cell lines, mutant Kit accumulates on the Golgi apparatus, whereas normal Kit localizes to the plasma membrane (PM)...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28191810/gist-institutional-experience-at-srms-ims-india
#9
Shubhanshu Gupta, Keshri Amit, Ashish Gupta, Tanu Argawal
Gastro-Intestinal Stromal Tumors (GIST) is a malignant, non-epithelial, mesenchymal tumor of the digestive tract that is not uncommon in clinical practice nowadays; diagnosis being based upon immuno-histo-chemical analysis of the resected or biopsied (FNAC) specimen. Abdominal lump with or without intra-luminal bleed is a common mode of presentation. Early diagnosis and appropriate management with surgery and/or Imatinib therapy improves recurrence free survival and may impact overall survival. We present here our institutional experience of four patients, admitted in Onco-Surgery Dept...
September 2016: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28191803/population-pharmacokinetics-of-imatinib-and-its-application-to-the-therapeutic-drug-monitoring-middle-east-cml-population
#10
Mehdi Ansari, Behjat Kalantary-Khandani, Abbas Pardakhty, Moein Safavi, Nabi Mosavi, Ehsan Mohajeri
INTRODUCTION: Despite the outstanding results generally obtained with Imatinib in the treatment of chronic myeloid leukemia, some patients show sub-optimal or no response. To evaluate the relationship between steady-state through plasma concentration and clinical response in CML patients. The objectives of this study were to assess the variability in Imatinib pharmacokinetics and to explore the effects of several demographic and biological covariates on the disposition of Imatinib. METHODS: A population pharmacokinetic analysis was performed on 170 plasma samples from 74 adult Iranian chronic myeloid leukemia patients...
September 2016: Gulf Journal of Oncology
https://www.readbyqxmd.com/read/28190859/renal-artery-stenosis-following-nilotinib-administration-in-a-patient-with-chronic-myelogenous-leukemia
#11
Mayumi Hatsuse, Yuka Daikoku, Yuta Tamoto, Masahiro Uehara, Takashi Kitani, Keiichi Tamagaki, Shin-Ichi Fuchida, Akira Okano, Satoshi Murakami, Chihiro Shimazaki
A 63-year-old male was diagnosed as having chronic phase CML in 2001. He obtained a major molecular response with imatinib (IM). In 2012, amulodipin was started for hypertension. In January 2013, IM was switched to nilotinib (NIL) in a clinical trial, and in February 2015, NIL was discontinued because MR(4.5) had been maintained for two years. One month later, he was admitted to our hospital because of headache and high blood pressure (194/108 mmHg). His urine test showed protein 3+ and occult blood 2+. His eGFR rapidly deteriorated from 45...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28186604/-clinical-and-genetic-features-of-a-patient-with-myeloid-neoplasm-in-association-with-pdgfra-and-evi1-gene-rearrangements
#12
Wenmin Han, Hongying Chao, Min Zhou, Ling Cen, Suning Chen, Xuefeng He, Xuzhang Lu
OBJECTIVE: Todelineate the clinical and genetic features of a patient with myeloproliferative neoplasm (MPN) in association with PDGFRA and EVI1 genes rearrangements. METHODS: Clinical data of the patient was collected. Conventional cytogenetics, fluorescence in situ hybridization (FISH) and nested PCR were carried out for the patient. RESULTS: The patient has featured recurrent rash, joint pain, and intermittent fever. Laboratory tests showed hyperleukocytosis and marked eosinophilia...
February 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28186602/-analysis-of-isodicentric-ph-chromosomes-in-chronic-myeloid-leukemia-blast-crisis
#13
Qian Li, Xiaoji Lin, Ying Lin, Rongxin Yao, Wu Huang, Handong Mei, Jian Gong, Hui Chen, Ningyan Teng
OBJECTIVE: To explore the genetic and clinical characteristics of isodicentric Ph chromosomes [idic(Ph)] in lymphoid blast crisis of chronic myeloid leukemia (CML-BLC). METHODS: Bone marrow aspirates of 2 patients with CML-BLC were analyzed by R banding after 24 hours of culturing. Genomic copy number variations (CNV) were analyzed by single nucleotide polymorphism array (SNP array) in case 1. The results were confirmed with fluorescence in situ hybridization (FISH)...
February 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28183263/aryl-butenes-active-against-k562-cells-and-lacking-tyrosinase-inhibitory-activity-as-new-leads-in-the-treatment-of-leukemia
#14
Mehdi El Arbi, Emna Ketata, Aref Neifar, Wafa Mihoubi, Girish K Gupta, Pascal Pigeon, Siden Top, Ali Gargouri, Gérard Jaouen
The inhibitory effects of four series of aryl butene derivatives, active against breast cancer, on the monophenolase activity of tyrosinase, in melanin-free ink from Sepia officinalis, have been studied. Hydroxytamoxifen 1, ferrociphenol 17 and several aryl butene analogs have shown strong antiproliferative activity on hormone-dependent and hormone-independent breast cancer cells and were evaluated in leukemia K562 cell proliferation. Their potential to induce skin depigmentation by evaluating their anti-tyrosinase activity was also estimated...
February 8, 2017: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/28178968/imatinib-relaxes-the-pulmonary-venous-bed-of-guinea-pigs
#15
Nina A Maihöfer, Said Suleiman, Daniela Dreymüller, Paul W Manley, Rolf Rossaint, Stefan Uhlig, Christian Martin, Annette D Rieg
BACKGROUND: Recently, the IMPRES study revealed that systemic imatinib improves exercise capacity in patients with advanced pulmonary arterial hypertension. Imatinib blocks the tyrosine kinase activity of the platelet-derived growth factor (PDGF)-receptor (PDGFR), acts antiproliferative and relaxes pulmonary arteries. However so far, the relaxant effects of imatinib on pulmonary veins (PVs) and on the postcapillary resistance are unknown, although pulmonary hypertension (PH) due to left heart disease (LHD) is most common and primarily affects PVs...
February 8, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28166823/giant-gastric-gastrointestinal-stromal-tumor-with-severe-peritoneal-dissemination-controlled-by-imatinib-therapy-following-debulking-surgery-a-case-report
#16
Shuichi Fukuda, Yoshinori Fujiwara, Tomoko Wakasa, Kotaro Kitani, Masanori Tsujie, Masao Yukawa, Yoshio Ohta, Masatoshi Inoue
BACKGROUND: At the time of diagnosis, giant gastric gastrointestinal stromal tumors are sometimes associated with severe peritoneal dissemination. Unresectable gastrointestinal stromal tumors are considered a systemic disease; therefore, imatinib therapy is currently the primary treatment option in these cases. CASE PRESENTATION: A 49-year-old Japanese woman was referred to our hospital with symptoms of anorexia, abdominal discomfort, and a palpable abdominal mass...
February 7, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/28156651/oams-at-the-end-the-end-of-the-beginning-or-the-beginning-of-the-end
#17
Barbara Marie Galligan, Chintan Shah, Iris Chen Zhao, Brian Paciotti, Nathan Fairman, Quy Tran
: 229 Background: In 2001, after three months of review, the FDA approved the oral anticancer agent imatinib, making it the fastest approval in FDA history. Since then, the FDA has approved over 40 oral anti-cancer medications (OAMs) and the number continues to rise, transforming cancer care, improving survival in specific cancers and providing new hope. However, the rapid development of OAMs has produced uncertainty over the best use of these new medications, particularly at the end of life...
October 9, 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28154092/increased-peroxisome-proliferator-activated-receptor-gamma-activity-reduces-imatinib-uptake-and-efficacy-in-chronic-myeloid-leukemia-mononuclear-cells
#18
Jueqiong Wang, Liu Lu, Chung H Kok, Verity A Saunders, Jarrad M Goyne, Phuong Dang, Tamara M Leclercq, Timothy P Hughes, Deborah L White
Imatinib is actively transported by OCT-1 influx transporter, and low OCT-1 activity in diagnostic chronic myeloid leukemia blood mononuclear cells is significantly associated with poor molecular response to imatinib. Here we report that, in diagnostic chronic myeloid leukemia mononuclear cells and BCR-ABL1+ cell lines, peroxisome proliferator-activated receptor gamma agonists (GW1929, rosiglitazone, pioglitazone) significantly decrease OCT-1 activity; conversely, peroxisome proliferator-activated receptor gamma antagonists (GW9662, T0070907) increase OCT-1 activity...
February 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28141797/a-combination-of-low-dose-bevacizumab-and-imatinib-enhances-vascular-normalisation-without-inducing-extracellular-matrix-deposition
#19
L M Schiffmann, M Brunold, M Liwschitz, V Goede, S Loges, M Wroblewski, A Quaas, H Alakus, D Stippel, C J Bruns, M Hallek, H Kashkar, U T Hacker, O Coutelle
BACKGROUND: Vascular endothelial growth factor (VEGF)-targeting drugs normalise the tumour vasculature and improve access for chemotherapy. However, excessive VEGF inhibition fails to improve clinical outcome, and successive treatment cycles lead to incremental extracellular matrix (ECM) deposition, which limits perfusion and drug delivery. We show here, that low-dose VEGF inhibition augmented with PDGF-R inhibition leads to superior vascular normalisation without incremental ECM deposition thus maintaining access for therapy...
January 31, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28139720/inhibition-of-pdgfr-signaling-prevents-muscular-fatty-infiltration-after-rotator-cuff-tear-in-mice
#20
Hideyuki Shirasawa, Noboru Matsumura, Masayuki Shimoda, Satoshi Oki, Masaki Yoda, Takahide Tohmonda, Yae Kanai, Morio Matsumoto, Masaya Nakamura, Keisuke Horiuchi
Fatty infiltration in muscle is often observed in patients with sizable rotator cuff tear (RCT) and is thought to be an irreversible event that significantly compromises muscle plasticity and contraction strength. These changes in the mechanical properties of the affected muscle render surgical repair of RCT highly formidable. Therefore, it is important to learn more about the pathology of fatty infiltration to prevent this undesired condition. In the present study, we aimed to generate a mouse model that can reliably recapitulate some of the important characteristics of muscular fatty infiltration after RCT in humans...
January 31, 2017: Scientific Reports
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