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https://www.readbyqxmd.com/read/28442505/overexpressed-fatty-acid-synthase-in-gastrointestinal-stromal-tumors-targeting-a-progression-associated-metabolic-driver-enhances-the-antitumor-effect-of-imatinib
#1
Chien-Feng Li, Fu-Min Fang, Yeng-Yang Chen, Ting-Ting Liu, Ti-Chun Chan, Shih-Chen Yu, Li-Tzong Chen, Hsuan-Ying Huang
Purpose: In gastrointestinal stromal tumors (GISTs), lipid-metabolizing enzymes remain underexplored, including fatty acid synthase (FASN). <p>Experimental Design: Forty GISTs were quantitated for FASN mRNA abundance. FASN immunoexpression was informative in 350 GISTs, including 213 with known KIT/PDGFRA/BRAF genotypes. In imatinib-resistant FASN-overexpressing GIST cells, the roles of overexpressed FASN and FASN-targeting C75 in tumor phenotypes, apoptosis and autophagy, KIT transcription, PI3K/AKT/mTOR activation, and imatinib resistance were analyzed by RNA interference or myristoylated-AKT transfection...
April 25, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28440714/hypereosinophilic-syndrome-endomyocardial-biopsy-versus-echocardiography-to-diagnose-cardiac-involvement
#2
Joseph H Butterfield, Garvan C Kane, Catherine R Weiler
OBJECTIVE: To compare echocardiograms and endomyocardial biopsies to diagnose cardiac involvement in hypereosinophilic syndrome. METHODS: We examined the agreement between echocardiography and endomyocardial biopsies to detect cardiac involvement in hypereosinophilic syndrome by reviewing cases identified as hypereosinophilia or hypereosinophilic syndrome in Mayo Clinic databases from January 1978 through June 2009. Single-organ cases of eosinophilia such as eosinophilic fasciitis and eosinophilic gastroenteritis were excluded...
April 25, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28423517/next-generation-sequencing-of-extraskeletal-myxoid-chondrosarcoma
#3
Elizabeth J Davis, Yi-Mi Wu, Dan Robinson, Scott M Schuetze, Laurence H Baker, Jyoti Athanikar, Xuhong Cao, Lakshmi P Kunju, Arul M Chinnaiyan, Rashmi Chugh
Extraskeletal myxoid chondrosarcoma (EMC) is an indolent translocation-associated soft tissue sarcoma with a high propensity for metastases. Using a clinical sequencing approach, we genomically profiled patients with metastatic EMC to elucidate the molecular biology and identify potentially actionable mutations. We also evaluated potential predictive factors of benefit to sunitinib, a multi-targeted tyrosine kinase inhibitor with reported activity in a subset of EMC patients. Between January 31, 2012 and April 15, 2016, six patients with EMC participated in the clinical sequencing research study...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415678/genetic-progression-in-gastrointestinal-stromal-tumors-mechanisms-and-molecular-interventions
#4
REVIEW
Ke Li, Haibo Cheng, Zhang Li, Yuzhi Pang, Xiaona Jia, Feifei Xie, Guohong Hu, Qingping Cai, Yuexiang Wang
Gastrointestinal stromal tumors (GISTs) are the most common sarcomas in humans. Constitutively activating mutations in the KIT or PDGFRA receptor tyrosine kinases are the initiating oncogenic events. Most metastatic GISTs respond dramatically to therapies with KIT/PDGFRA inhibitors. Asymptomatic and mitotically-inactive KIT/PDGFRA-mutant "microGISTs" are found in one third of adults, but most of these small tumors never progress to malignancy, underscoring that a progression of oncogenic mutations is required...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415643/new-transcriptional-based-insights-into-the-pathogenesis-of-desmoplastic-small-round-cell-tumors-dsrcts
#5
Tiziana Negri, Silvia Brich, Fabio Bozzi, Chiara V Volpi, Ambra V Gualeni, Silvia Stacchiotti, Loris De Cecco, Silvana Canevari, Annunziata Gloghini, Silvana Pilotti
To gain new insights into desmoplastic small round cell tumors (DSRCTs) by means of gene expression profiling (GEP). Formalin-fixed, paraffin-embedded surgical specimens obtained from seven pretreated DSRCT patients were interrogated using GEP complemented by immunohistochemistry, a cancer stem cell array, and miRNA in situ hybridisation, including the combined chimera modules miRNA-200/ZEB1 and miRNA-34/SLUG. The chimera modules divided the cases into three classes that respectively recapitulated the traits of mesenchymal epithelial reverse transition (MErT), epithelial mesenchymal transition (EMT), and hybrid/partial EMT...
March 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415580/the-n-terminal-polypeptide-derived-from-viral-macrophage-inflammatory-protein-ii-reverses-breast-cancer-epithelial-tomesenchymal-transition-via-a-pdgfra-dependent-mechanism
#6
Qing-Ling Yang, Ling-Yu Zhang, Hai-Feng Wang, Yu Li, Yue-Yue Wang, Tian-Tian Chen, Meng-Fen Dai, Hai-Hua Wu, Su-Lian Chen, Wen-Rui Wang, Qiong Wu, Chang-Jie Chen, Cong-Zhao Zhou
NT21MP, a 21-residue peptide derived from the viral macrophage inflammatory protein II, competed effectively with the natural ligand of CXC chemokine receptor 4 (CXCR4), stromal cell-derived factor 1-alpha, to induce apoptosis and inhibit growth in breast cancer. Its role in tumor epithelial-to-mesenchymal transition (EMT) regulation remains unknown. In this study, we evaluated the reversal of EMT upon NT21MP treatment and examined its role in the inhibition of EMT in breast cancer. The parental cells of breast cancer (SKBR-3 and MCF-7) and paclitaxel-resistant (SKBR-3 PR and MCF-7 PR) cells were studied in vitro and in combined immunodeficient mice...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410244/platelet-derived-growth-factor-receptor-alpha-positive-cardiac-progenitor-cells-derived-from-multipotent-germline-stem-cells-are-capable-of-cardiomyogenesis-in-vitro-and-in-vivo
#7
Bang-Jin Kim, Yong-Hee Kim, Yong-An Lee, Sang-Eun Jung, Yeong Ho Hong, Eun-Ju Lee, Byung-Gak Kim, Seongsoo Hwang, Jeong Tae Do, Myung-Geol Pang, Buom-Yong Ryu
Cardiac cell therapy has the potential to revolutionize treatment of heart diseases, but its success hinders on the development of a stem cell therapy capable of efficiently producing functionally differentiated cardiomyocytes. A key to unlocking the therapeutic application of stem cells lies in understanding the molecular mechanisms that govern the differentiation process. Here we report that a population of platelet-derived growth factor receptor alpha (PDGFRA) cells derived from mouse multipotent germline stem cells (mGSCs) were capable of undergoing cardiomyogenesis in vitro...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408374/expression-of-biglycan-in-first-trimester-chorionic-villous-sampling-placental-samples-and-altered-function-in-telomerase-immortalized-microvascular-endothelial-cells
#8
Amy Chui, Tilini Gunatillake, Shaun P Brennecke, Vera Ignjatovic, Paul T Monagle, John M Whitelock, Dagmar E van Zanten, Jasper Eijsink, Yao Wang, James Deane, Anthony J Borg, Janet Stevenson, Jan Jaap Erwich, Joanne M Said, Padma Murthi
OBJECTIVE: Biglycan (BGN) has reduced expression in placentae from pregnancies complicated by fetal growth restriction (FGR). We used first trimester placental samples from pregnancies with later small for gestational age (SGA) infants as a surrogate for FGR. The functional consequences of reduced BGN and the downstream targets of BGN were determined. Furthermore, the expression of targets was validated in primary placental endothelial cells isolated from FGR or control pregnancies. APPROACH AND RESULTS: BGN expression was determined using real-time polymerase chain reaction in placental tissues collected during chorionic villous sampling performed at 10 to 12 weeks' gestation from pregnancies that had known clinical outcomes, including SGA...
April 13, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28402935/mirna-profiling-of-gastrointestinal-stromal-tumors-by-next-generation-sequencing
#9
Ugne Gyvyte, Simonas Juzenas, Violeta Salteniene, Juozas Kupcinskas, Lina Poskiene, Laimutis Kucinskas, Sonata Jarmalaite, Kristina Stuopelyte, Ruta Steponaitiene, Georg Hemmrich-Stanisak, Matthias Hübenthal, Alexander Link, Sabine Franke, Andre Franke, Dalia Pangonyte, Vaiva Lesauskaite, Limas Kupcinskas, Jurgita Skieceviciene
Deregulation of miRNAs has been observed virtually in all major types of cancer, whereas the miRNA signature in GIST is not well characterized yet. In this study the first high-throughput miRNA profiling of 15 paired GIST and adjacent normal tissue samples was performed using small RNA-seq approach and differentially expressed miRNAs as well as isomiRNAs were defined. Highly significantly deregulated miRNAs were selected for validation by Taq-Man low-density array in replication group of 40 paired samples. Validated miRNAs were further subjected to enrichment analysis, which revealed significantly enriched KEGG pathways in the main GIST associated pathways...
March 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401334/h3-idh-wild-type-pediatric-glioblastoma-is-comprised-of-molecularly-and-prognostically-distinct-subtypes-with-associated-oncogenic-drivers
#10
Andrey Korshunov, Daniel Schrimpf, Marina Ryzhova, Dominik Sturm, Lukas Chavez, Volker Hovestadt, Tanvi Sharma, Antje Habel, Anna Burford, Chris Jones, Olga Zheludkova, Ella Kumirova, Christof M Kramm, Andrey Golanov, David Capper, Andreas von Deimling, Stefan M Pfister, David T W Jones
Pediatric glioblastoma (pedGBM) is an extremely aggressive pediatric brain tumor, accounting for ~6% of all central nervous system neoplasms in children. Approximately half of pedGBM harbor recurrent somatic mutations in histone 3 variants or, infrequently, IDH1/2. The remaining subset of pedGBM is highly heterogeneous, and displays a variety of genomic and epigenetic features. In the current study, we aimed to further stratify an H3-/IDH-wild type (wt) pedGBM cohort assessed through genome-wide molecular profiling...
April 11, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28401062/genomic-insights-into-diffuse-intrinsic-pontine-glioma
#11
REVIEW
Danielle H Lapin, Maria Tsoli, David S Ziegler
Diffuse intrinsic pontine glioma (DIPG) is a highly aggressive pediatric brainstem tumor with a peak incidence in middle childhood and a median survival of less than 1 year. The dismal prognosis associated with DIPG has been exacerbated by the failure of over 250 clinical trials to meaningfully improve survival compared with radiotherapy, the current standard of care. The traditional practice to not biopsy DIPG led to a scarcity in available tissue samples for laboratory analysis that till recently hindered therapeutic advances...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28398518/epigenetic-regulation-of-cd133-in-gastrointestinal-stromal-tumors
#12
Helene Geddert, Alexander Braun, Claudia Kayser, Arno Dimmler, Gerhard Faller, Abbas Agaimy, Florian Haller, Evgeny A Moskalev
Objectives: This study ascertained the regulation of the stem cell marker CD133 and its potential applicability for prognostication of gastrointestinal stromal tumors (GISTs). Methods: A total of 95 resected GISTs were included in the study. CD133 protein expression was assessed immunohistochemically on tissue microarrays. Methylation percentage was quantified by pyrosequencing. Gene expression in cell lines GIST48b and GIST882 upon treatment with DNA demethylation agent 5-aza-2'-deoxycytidine was analyzed by quantitative polymerase chain reaction...
April 7, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28386563/the-effect-of-phototherapy-on-cancer-predisposition-genes-of-diabetic-and-normal-human-skin-fibroblasts
#13
Pongsathorn Chotikasemsri, Boonsin Tangtrakulwanich, Surasak Sangkhathat
The purpose of this study was to investigate whether LED light at different wavelengths affects the expression profile of 143 cancer predisposition genes in both diabetic and normal human fibroblasts. In this study, both diabetic and normal fibroblast cell lines were cultured and irradiated with red (635 nm), green (520 nm), and blue (465 nm) LED light for 10 minutes at 0.67 J/cm(2) each. After that, mRNA from all cell lines was extracted for microarray analysis. We found that green light activates EPHB2, KIT, ANTXR2, ESCO2, MSR1, EXT1, TSC1, KIT, NF1, BUB1B, FANCD2, EPCAM, FANCD2, NF, DIS3L2, and RET in normal fibroblast cells, while blue and red light can upregulate RUNX1, PDGFRA, EHBP1, GPC3, AXIN2, KDR, GLMN, MSMB, EPHB2, MSR1, KIT, FANCD2, BMPR1A, BUB1B, PDE11A, and RET...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28379539/foxa3-is-expressed-in-multiple-cell-lineages-in-the-mouse-testis-and-regulates-pdgfra-expression-in-leydig-cells
#14
Gabriel Garon, Francis Bergeron, Catherine Brousseau, Nicholas M Robert, Jacques J Tremblay
The three FOXA transcription factors are mainly known for their roles in the liver. However, Foxa3-deficient mice become progressively sub/infertile due to germ cell. Since no data was available regarding the localization of the FOXA3 protein in the testis, immunohistochemistry was performed on mouse testis sections. In the fetal testis, a weak but consistent staining for FOXA3 is detected in the nucleus of Sertoli cells. In prepubertal and adult life, FOXA3 remains present in Sertoli cells of some but not all seminiferous tubules...
April 3, 2017: Endocrinology
https://www.readbyqxmd.com/read/28379477/strong-fgfr3-staining-is-a-marker-for-fgfr3-fusions-in-diffuse-gliomas
#15
Kirsi J Granberg, Matti Annala, Birgitta Lehtinen, Juha Kesseli, Joonas Haapasalo, Pekka Ruusuvuori, Olli Yli-Harja, Tapio Visakorpi, Hannu Haapasalo, Matti Nykter, Wei Zhang
Background.: Inhibitors of fibroblast growth factor receptors (FGFRs) have recently arisen as a promising treatment option for patients with FGFR alterations. Gene fusions involving FGFR3 and transforming acidic coiled-coil protein 3 (TACC3) have been detected in diffuse gliomas and other malignancies, and fusion-positive cases have responded well to FGFR inhibition. As high FGFR3 expression has been detected in fusion-positive tumors, we sought to determine the clinical significance of FGFR3 protein expression level as well as its potential for indicating FGFR3 fusions...
April 1, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28376187/a-novel-diagnostic-tool-for-selecting-patients-with-mesenchymal-type-colon-cancer-reveals-intratumor-subtype-heterogeneity
#16
Inge Ubink, Sjoerd G Elias, Cathy B Moelans, Miangela M Laclé, Wilhelmina M U van Grevenstein, Paul J van Diest, Inne H M Borel Rinkes, Onno Kranenburg
Background: Consensus molecular subtype 4 (CMS4) is a recently identified aggressive colon cancer subtype for which platelet-derived growth factor receptors (PDGFRs) and KIT are potential therapeutic targets. We aimed to develop a clinically applicable CMS4 reverse transcription polymerase chain reaction (RT-qPCR) test to select patients for PDGFR/KIT-targeted therapy. Methods: We used logistic regression to develop a CMS4 prediction rule based on microarray expression values of PDGFRA , PDGFRB , PDGFC , and KIT (566 training and 1259 test samples, using the 273-gene random forest classifier as CMS4 reference standard)...
August 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28374041/imatinib-treatment-of-lymphomatoid-papulosis-associated-with-myeloproliferative-hypereosino-philic-syndrome-presenting-the-fip1l1-pdgfra-fusion-gene
#17
Pablo García-Martínez, Dolors Sitjas, Enric Llistosella, Blanca Espinet, María Rodríguez-Rivera, Maria Hernandez-Muñoz, Fernando Gallardo, Ramon M Pujol
is missing (Short communication).
April 4, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28359267/aberrant-expression-of-alk-and-ezh2-in-merkel-cell-carcinoma
#18
Tuukka Veija, Virve Koljonen, Tom Bohling, Mia Kero, Sakari Knuutila, Virinder Kaur Sarhadi
BACKGROUND: Distinct characteristic features categorize Merkel cell carcinoma (MCC) into two subgroups according to the Merkel cell polyomavirus infection. Many mutational studies on MCC have been carried out in recent years without identifying a prominent driver mutation. However, there is paucity reporting the expression of cancer genes at the RNA level in MCC tumors. In this study, we studied the RNA expression profiles of 26 MCC tumors, with a goal to identify prospective molecular targets that could improve the treatment strategies of MCC...
March 31, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28356974/gastrointestinal-stromal-tumor-with-a-pdgfra-mutation-masquerading-as-gastric-plexiform-fibromyxoma-a-comparative-clinicopathological-study-of-two-cases
#19
Jun Zhou, Jingjing Xu, Guozhong Jiang, Yihui Ma, Jingwen Qi, Wencai Li, Dandan Zhang
Gastric plexiform fibromyxoma (PF) is a rare mesenchymal tumor with a histologically distinctive multinodular pattern, dissimilar to conventional gastrointestinal stromal tumor (GIST). The current study presents one case of gastric PF, and one case of GIST with a platelet-derived growth factor receptor α (PDGFRA) mutation mimicking PF, and discusses their differential diagnoses. The two patients were a 51-year-old male with PF and a 47-year-old female with GIST, each of whom presented with an occupying lesion in the gastric antrum...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28351781/geis-guidelines-for-gastrointestinal-sarcomas-gist
#20
REVIEW
Andrés Poveda, Xavier García Del Muro, Jose Antonio López-Guerrero, Ricardo Cubedo, Virginia Martínez, Ignacio Romero, César Serrano, Claudia Valverde, Javier Martín-Broto
Gastrointestinal stromal sarcomas (GISTs) are the most common mesenchymal tumours originating in the digestive tract. They have a characteristic morphology, are generally positive for CD117 (c-kit) and are primarily caused by activating mutations in the KIT or PDGFRA genes(1). On rare occasions, they occur in extravisceral locations such as the omentum, mesentery, pelvis and retroperitoneum. GISTs have become a model of multidisciplinary work in oncology: the participation of several specialties (oncologists, pathologists, surgeons, molecular biologists, radiologists…) has forested advances in the understanding of this tumour and the consolidation of a targeted therapy, imatinib, as the first effective molecular treatment in solid tumours...
March 2, 2017: Cancer Treatment Reviews
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