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https://www.readbyqxmd.com/read/30242244/lmtk3-is-essential-for-oncogenic-kit-expression-in-kit-mutant-gist-and-melanoma
#1
Lillian R Klug, Amber E Bannon, Nathalie Javidi-Sharifi, Ajia Town, William H Fleming, Judy K VanSlyke, Linda S Musil, Jonathan A Fletcher, Jeffrey W Tyner, Michael C Heinrich
Certain cancers, including gastrointestinal stromal tumor (GIST) and subsets of melanoma, are caused by somatic KIT mutations that result in KIT receptor tyrosine kinase constitutive activity, which drives proliferation. The treatment of KIT-mutant GIST has been revolutionized with the advent of KIT-directed cancer therapies. KIT tyrosine kinase inhibitors (TKI) are superior to conventional chemotherapy in their ability to control advanced KIT-mutant disease. However, these therapies have a limited duration of activity due to drug-resistant secondary KIT mutations that arise (or that are selected for) during KIT TKI treatment...
September 21, 2018: Oncogene
https://www.readbyqxmd.com/read/30237583/an-exploratory-study-by-dmet-array-identifies-a-germline-signature-associated-with-imatinib-response-in-gastrointestinal-stromal-tumor
#2
Gloria Ravegnini, Milena Urbini, Vittorio Simeon, Chiara Genovese, Annalisa Astolfi, Margherita Nannini, Lidia Gatto, Maristella Saponara, Manuela Ianni, Valentina Indio, Giovanni Brandi, Stefania Trino, Patrizia Hrelia, Guido Biasco, Sabrina Angelini, Maria A Pantaleo
Imatinib represents the standard therapy for gastrointestinal stromal tumor (GIST) patients with metastatic/unresectable disease. Despite  the excellent results achieved with its introduction, the majority of patients quite invariably experience disease progression. The aim of this study was to understand the contribution of germline DNA polymorphisms in discriminating between imatinib clinical response [evaluated as progression free survival (PFS)] and toxicity. In particular, a discovery cohort (34 GIST with a KIT exon 11 primary mutation, and no toxicity) was analyzed through DMET array that interrogates 1936 variants in 231 genes of the ADME process...
September 20, 2018: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/30237572/the-impact-of-fluid-balance-on-outcomes-in-critically-ill-near-term-term-neonates-a-report-from-the-awaken-study-group
#3
David T Selewski, Ayse Akcan-Arikan, Elizabeth M Bonachea, Katja M Gist, Stuart L Goldstein, Mina Hanna, Catherine Joseph, John D Mahan, Arwa Nada, Amy T Nathan, Kimberly Reidy, Amy Staples, Pia Wintermark, Louis J Boohaker, Russell Griffin, David J Askenazi, Ronnie Guillet
BACKGROUND: In sick neonates admitted to the NICU, improper fluid balance can lead to fluid overload. We report the impact of fluid balance in the first postnatal week on outcomes in critically ill near-term/term neonates. METHODS: This analysis includes infants ≥36 weeks gestational age from the Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) study (N = 645). Fluid balance: percent weight change from birthweight. PRIMARY OUTCOME: mechanical ventilation (MV) on postnatal day 7...
September 20, 2018: Pediatric Research
https://www.readbyqxmd.com/read/30232470/the-extraction-of-natural-scene-gist-in-visual-crowding
#4
Mingliang Gong, Yuming Xuan, L James Smart, Lynn A Olzak
The gist of natural scenes can be extracted very rapidly and even without focal attention. However, it is unclear whether and to what extent the gist of natural scenes can break through the bottleneck of crowding, a phenomenon in which object recognition will be immensely impaired. In the first two experiments, a target scene, either presented alone or surrounded by four flankers, was categorized at basic (Experiment 1) or global levels (Experiment 2). It was showed that the elimination of high-level semantic information of flankers greatly alleviated the crowding effect, demonstrating that high-level information played an important role in crowding of scene gist...
September 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30230048/endoscopic-selective-muscular-dissection-for-gastric-submucosal-tumor
#5
Mitsuru Esaki, Sho Suzuki, Takuji Gotoda
Gastric submucosal tumors (G-SMTs), such as gastrointestinal stromal tumors (GISTs), often arise from the muscularis propria, which consists of at least two layers (inner circle and outer longitudinal muscle). Laparoscopic and endoscopic cooperative surgery or endoscopic resection has been performed for G-SMTs1-5 However, these procedures require closure of the gastric-wall. Here, we present a case of successful endoscopic selective muscular dissection for a G-SMT without closure. This article is protected by copyright...
September 19, 2018: Digestive Endoscopy: Official Journal of the Japan Gastroenterological Endoscopy Society
https://www.readbyqxmd.com/read/30226855/epigist-an-observational-real-life-study-on-patients-with-metastatic-gastrointestinal-stromal-tumors-receiving-imatinib
#6
Olivier Bouché, Axel Le Cesne, Maria Rios, Loic Chaigneau, Antoine Italiano, Florence Duffaud, Thierry Lecomte, Dominique Arsène, Sylvain Manfredi, Thomas Aparicio, Stéphane Remy, Nicolas Isambert, Olivier Collard, Frank Priou, François Bertucci, Roland Sambuc, Ségolene Bisot-Locard, Olivier Bourges, Sylvie Chabaud, Jean-Yves Blay
BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare, but represent the most common mesenchymal neoplasms of the gastrointestinal tract. EPIdemiology GIST, is an observational multicenter longitudinal follow-up cohort study reporting the prescribing patterns of imatinib in patients with GIST and the impact of the treatment in a real-world (standard clinical) setting. METHODS: Eligible patients had a confirmed diagnosis of unresectable or metastatic KIT-positive GIST and started treatment with imatinib for the first time between May 24, 2002, and June 30, 2010...
2018: PloS One
https://www.readbyqxmd.com/read/30225388/pediatric-gastrointestinal-stromal-tumors-a-review-of-diagnostic-modalities
#7
REVIEW
Hallie J Quiroz, Brent A Willobee, Matthew S Sussman, Bradley R Fox, Chad M Thorson, Juan E Sola, Eduardo A Perez
Gastrointestinal stromal tumors are exceedingly rare tumors in the pediatric population, as a result many clinicians either may never see this diagnosis or will encounter it only a few times throughout their careers. It is imperative in the pediatric population to follow appropriate steps to ensure a swift diagnosis and referral to specialized centers that are equipped with the multidisciplinary teams accustomed to treating rare diseases. This review aims to discuss the most recent data available on the diagnostic modalities utilized in cases of suspected Pediatric GIST...
2018: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/30225387/current-treatment-strategies-in-pediatric-gastrointestinal-stromal-cell-tumor
#8
REVIEW
Brent A Willobee, Hallie J Quiroz, Matthew S Sussman, Chad M Thorson, Juan E Sola, Eduardo A Perez
Gastrointestinal stromal tumors (GIST) are exceedingly rare tumors in the pediatric population. As a result, many clinicians either may never see this diagnosis or will encounter it only a few times throughout their careers. Additionally, the more we discover about this disease, it becomes evident that it represents a distinct clinical entity from adult GIST. Many of the treatments and strategies used to combat the adult tumor are either ineffective or may be harmful to the pediatric population with this disease...
2018: Translational Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/30224936/genomic-subtypes-of-gists-for-stratifying-patient-response-to-sunitinib-following-imatinib-resistance-a-pooled-analysis-and-systematic-review
#9
REVIEW
Siyuan Tan, Ping Chen, Jiafu Ji, Shanshan Guo, Dapeng Yu, Tetsuya Asakawa, Yu Zhou, Masanobu Abe, Liang Zong
Objectives: Sunitinib (a second-line chemotherapeutic agent that inhibits multiple kinases, including KIT and PDGFR) is widely used in imatinib-resistant patients with gastrointestinal stromal tumors (GISTs). However, diverse responses to sunitinib have been observed in the clinic. We aimed to evaluate whether the different GIST genotypes could be used to stratify patient response to sunitinib. Methods: We searched the PubMed, Embase, and Cochrane databases and included English-language literature published up to August 31, 2017...
2018: Disease Markers
https://www.readbyqxmd.com/read/30221743/identification-of-key-genes-and-associated-pathways-in-kit-pdgfra-wild%C3%A2-type-gastrointestinal-stromal-tumors-through-bioinformatics-analysis
#10
Wen-Jie Wang, Hong-Tao Li, Jian-Ping Yu, Yu-Min Li, Xiao-Peng Han, Peng Chen, Wen-Wen Yu, Wei-Kai Chen, Zuo-Yi Jiao, Hong-Bin Liu
Gastrointestinal stromal tumors (GISTs) are the most common type of mesenchymal tumor in the gastrointestinal tract. The present study aimed to identify the potential candidate biomarkers that may be involved in the pathogenesis and progression of v‑kit Hardy‑Zuckerman 4 feline sarcoma viral oncogene homolog (KIT)/platelet‑derived growth factor receptor α (PDGFRA) wild‑type GISTs. A joint bioinformatics analysis was performed to identify the differentially expressed genes (DEGs) in wild‑type GIST samples compared with KIT/PDGFRA mutant GIST samples...
September 5, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/30218977/notch-pathway-inhibition-with-ly3039478-in-soft-tissue-sarcoma-and-gastrointestinal-stromal-tumours
#11
Olivier Mir, Analia Azaro, Jaime Merchan, Rashmi Chugh, Jonathan Trent, Jordi Rodon, Ute Ohnmacht, J T Diener, Claire Smith, Eunice Yuen, Gerard Joseph Oakley, Axel Le Cesne, Jean-Charles Soria, Karim A Benhadji, Christophe Massard
BACKGROUND: LY3039478 is an orally bioavailable selective Notch inhibitor. This phase 1a/b trial evaluated the safety, pharmacokinetics and antitumour activity of LY3039478 in patients with soft tissue sarcoma (STS) and gastrointestinal stromal tumour (GIST). METHODS: This multipart, phase 1 trial enrolled patients with refractory advanced/metastatic STS and GIST, measurable disease, Eastern Cooperative Oncology Group ≤1 and baseline tumour tissue. Eligible patients received LY3039478 50mg/75 mg three times per week, for 28-day cycle until disease progression...
September 12, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/30218589/differential-diagnosis-of-mesenchymal-neoplasms-of-the-digestive-tract-by-cell-block-and-immunohistochemistry
#12
César Vivian Lopes, Péttala Rigon, Cláudio Galleano Zettler, Antônio Atalíbio Hartmann
OBJECTIVES: To evaluate the diagnostic yield of the cell block (CB) technique with immunohistochemistry in patients with mesenchymal neoplasms of the gastrointestinal tract collected by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). METHODS: Tissue samples from consecutive patients with subepithelial lesions collected by EUS-FNA, without analysis by on-site cytopathology, were evaluated by the same pathologist only using CBs in AAF fixative. Sections were stained with haematoxylin-eosin and underwent complementary immunohistochemical staining for SMA, CD117, DOG-1 and S100 in the presence of mesenchymal neoplasms...
September 15, 2018: Cytopathology: Official Journal of the British Society for Clinical Cytology
https://www.readbyqxmd.com/read/30214792/-gistoscopy
#13
Vincent Zimmer, Frank Lammert
Gastrointestinal stromal tumors (GIST) tumors are a rare, though typical cause for upper GI bleeding. Excavated ulcerated lesions are common; however, a clear-cut visualization of the tumor surface (" GISToscopy ") itself has not yet been reported. In line, careful biopsy taking streamlines the diagnostic work-up by providing pathologic diagnosis.
September 2018: Clinical Case Reports
https://www.readbyqxmd.com/read/30214331/role-of-normal-sleep-and-sleep-apnea-in-human-memory-processing
#14
REVIEW
Shilpi Ahuja, Rebecca K Chen, Korey Kam, Ward D Pettibone, Ricardo S Osorio, Andrew W Varga
A fundamental problem in the field of obstructive sleep apnea (OSA) and memory is that it has historically minimized the basic neurobiology of sleep's role in memory. Memory formation has been classically divided into phases of encoding, processing/consolidation, and retrieval. An abundance of evidence suggests that sleep plays a critical role specifically in the processing/consolidation phase, but may do so differentially for memories that were encoded using particular brain circuits. In this review, we discuss some of the more established evidence for sleep's function in the processing of declarative, spatial navigational, emotional, and motor/procedural memories and more emerging evidence highlighting sleep's importance in higher order functions such as probabilistic learning, transitive inference, and category/gist learning...
2018: Nature and Science of Sleep
https://www.readbyqxmd.com/read/30210112/endoscopic-submucosal-dissection-for-gastric-phenotype-adenoma-on-the-surface-of-gastric-gastrointestinal-stromal-tumor
#15
Shumpei Yamamoto, Naoyuki Nishimura, Motowo Mizuno, Yuichi Shimodate, Akira Doi, Hirokazu Mouri, Kazuhiro Matsueda, Hiroshi Yamamoto
We herein report a rare case of a gastric adenoma overlying a gastrointestinal stromal tumor (GIST) that was removed by endoscopic submucosal dissection (ESD). A 78-year-old woman was referred to our hospital. Esophagogastroduodenoscopy revealed an elevated lesion of 15 mm in diameter overlying a submucosal mass in the gastric cardia. ESD was performed for the epithelial neoplasm, and biopsy specimens were obtained directly from the exposed surface of the submucosal tumor. The epithelial tumor was a tubular adenoma with focal severe atypia and a gastric phenotype...
September 12, 2018: Internal Medicine
https://www.readbyqxmd.com/read/30209248/clinicopathological-and-prognostic-significance-of-expression-of-b-cell-specific-moloney-murine-leukemia-virus-insertion-site-1-bmi-1-gene-and-protein-in-gastrointestinal-stromal-tumors
#16
Kun Zhu, Kang Li, Da-Wei Yuan, Gang Xu, Li Kang, Cheng-Xue Dang, Yong Zhang
BACKGROUND Gastrointestinal stromal tumor (GIST) is an uncommon visceral sarcoma that arises predominantly in the gastrointestinal tract. Since GISTs are encountered infrequently and inflexible to traditional therapy, the aim of the present study was to explore the correlation of B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI-1) mRNA and BMI-1 protein levels with the clinicopathological characteristics and prognosis significance of GISTs. MATERIAL AND METHODS GIST tissues and normal tissues were collected from 156 patients who had undergone surgical treatment...
September 13, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/30208433/eccentricity-scale-independence-for-scene-perception-in-the-first-tens-of-milliseconds
#17
Anna C Geuzebroek, Albert V van den Berg
Visual processing of scenes in the first tens of milliseconds relies on global image summary statistics rather than localized processing. Although natural scenes typically involve our entire visual field, scenes are usually presented experimentally at limited eccentricity. Receptive-field size increases with foveal eccentricity while increasingly pooling activity from local receptive fields. Here, we asked to what extent an observer's performance on a scene-gist perception task depends on the contents of the scene as well as on the eccentricity of the scene...
September 4, 2018: Journal of Vision
https://www.readbyqxmd.com/read/30204441/discovery-of-n-4-6-7-dimethoxyquinazolin-4-yl-oxy-phenyl-2-4-propan-2-yl-1h-1-2-3-triazol-1-yl-acetamide-azd3229-a-potent-pan-kit-mutant-inhibitor-for-the-treatment-of-gastrointestinal-stromal-tumors
#18
Jason Grant Kettle, Rana Anjum, Evan Barry, Deepa Bhavsar, Crystal Brown, Scott Boyd, Andrew Campbell, Kristin Goldberg, Michael Grondine, Sylvie Guichard, Christopher Hardy, Tom Hunt, Rhys Jones, Xiuwei Li, Olga Moleva, Derek Ogg, Ross Overman, Martin J Packer, Stuart Pearson, Marianne Schimpl, Wenlin Shao, Aaron Smith, James Smith, Darren Stead, Stephen Stokes, Michael Tucker, Yang Ye
While the treatment of Gastrointestinal Stromal Tumors (GIST) has been revolutionised by the application of targeted tyrosine kinase inhibitors capable of inhibiting KIT-driven proliferation, diverse mutations to this kinase drive resistance to established therapies. Here we describe the identification of potent pan-KIT mutant kinase inhibitors that can be dosed without being limited by the tolerability issues seen with multi-targeted agents. This effort focussed on identification and optimisation of an existing kinase scaffold through the use of structure-based design...
September 11, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30201342/it-s-a-gist-right
#19
Robert Summey, Mohamad Mouchli, Douglas J Grider
No abstract text is available yet for this article.
September 7, 2018: Gastroenterology
https://www.readbyqxmd.com/read/30199578/successful-treatment-of-metastatic-mucosal-melanoma-with-a-del579-c-kit-mutation-by-imatinib-after-treatment-of-anti-pd-1-antibody
#20
Chisato Yamashita, Atsushi Otsuka, Motoo Nomura, Tetsuya Honda, Kenji Kabashima
C-KIT mutations and amplifications are seen in approximately 15 to 30% of acral and mucosal melanomas. As c-KIT is a validated therapeutic target in other cancers, such as gastrointestinal stromal tumor (GIST) and chronic myelogenous leukemia (CML), there are several reports of melanoma patients with c-KIT mutation achieving good response to the off-label use of multi-tyrosine kinase inhibitors such as imatinib. The improved efficacy of sequential treatment with immunotherapies including programmed cell death1 (PD-1) blockade is currently being investigated...
September 10, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
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