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https://www.readbyqxmd.com/read/28222971/cancer-biology-of-small-gastrointestinal-stromal-tumors-2%C3%A2-cm-what-is-the-risk-of-malignancy
#1
K Søreide
INTRODUCTION: The identification of small (<2 cm) gastrointestinal stromal tumors (GISTs) is increasingly recognized. The malignancy potential is not absent. However, data on risk is scarce. The aim was to review the existing data on perceived risk of small GISTs in population-based studies. METHODS: A combined review of small GISTs (<2 cm) in a population-based dataset compared with a systematic review of available population-based studies. RESULTS: About one in every four (27%) patient has a small GIST, of which 79% were incidental in presentation, and all had a low-risk mitoses index (<5/hpf)...
February 9, 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28212550/plcb4-copy-gain-and-plc%C3%A3-4-overexpression-in-primary-gastrointestinal-stromal-tumors-integrative-characterization-of-a-lipid-catabolizing-enzyme-associated-with-worse-disease-free-survival
#2
Chien-Feng Li, Ting-Ting Liu, I-Chieh Chuang, Yen-Yang Chen, Fu-Min Fang, Ti-Chun Chan, Wan-Shan Li, Hsuan-Ying Huang
To explore the implications of lipid catabolism-associated genes in gastrointestinal stromal tumors, we reappraised transcriptomic and genomic datasets and identified copy-gained and differentially upregulated PLCB4 gene associated with tumor progression. On full sections, PLCB4 mRNA abundance and PLCß4 immunoexpression were validated in 70 cases. On tissue microarrays, PLCB4 gene copies and PLCß4 immunoexpression were both informative in 350 cases with KIT/PDGFRA/BRAF genotypes noted in 213. In GIST48 cell line, we stably silenced PLCB4 and YAP1 to characterize their functional effects and regulatory link...
February 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197361/nkp30-isoforms-and-nkp30-ligands-are-predictive-biomarkers-of-response-to-imatinib-mesylate-in-metastatic-gist-patients
#3
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
#4
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/28191821/crucial-role-of-mesangial-cell-derived-connective-tissue-growth-factor-in-a-mouse-model-of-anti-glomerular-basement-membrane-glomerulonephritis
#5
Naohiro Toda, Kiyoshi Mori, Masato Kasahara, Akira Ishii, Kenichi Koga, Shoko Ohno, Keita P Mori, Yukiko Kato, Keisuke Osaki, Takashige Kuwabara, Katsutoshi Kojima, Daisuke Taura, Masakatsu Sone, Taiji Matsusaka, Kazuwa Nakao, Masashi Mukoyama, Motoko Yanagita, Hideki Yokoi
Connective tissue growth factor (CTGF) coordinates the signaling of growth factors and promotes fibrosis. Neonatal death of systemic CTGF knockout (KO) mice has hampered analysis of CTGF in adult renal diseases. We established 3 types of CTGF conditional KO (cKO) mice to investigate a role and source of CTGF in anti-glomerular basement membrane (GBM) glomerulonephritis. Tamoxifen-inducible systemic CTGF (Rosa-CTGF) cKO mice exhibited reduced proteinuria with ameliorated crescent formation and mesangial expansion in anti-GBM nephritis after induction...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28187274/pdgfra-antibody-for-soft-tissue-sarcoma
#6
Lillian R Klug, Michael C Heinrich
Lartruvo (olaratumab) is a monoclonal antibody against the extracellular domain of PDGFRA. Olaratumab blocks ligand binding and thereby inhibits activation of PDGFRA kinase activity. Pre-clinically, this antibody inhibited PDGFRA-dependent tumor growth. In a randomized Phase II study, adding olaratumab to doxorubicin chemotherapy significantly improved overall survival, leading to FDA approval.
February 9, 2017: Cell
https://www.readbyqxmd.com/read/28186604/-clinical-and-genetic-features-of-a-patient-with-myeloid-neoplasm-in-association-with-pdgfra-and-evi1-gene-rearrangements
#7
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/28183280/whole-genome-scan-reveals-the-genetic-signature-of-african-ankole-cattle-breed-and-potential-for-higher-quality-beef
#8
Mengistie Taye, Jaemin Kim, Sook Hee Yoon, Wonseok Lee, Olivier Hanotte, Tadelle Dessie, Stephen Kemp, Okeyo Ally Mwai, Kelsey Caetano-Anolles, Seoae Cho, Sung Jong Oh, Hak-Kyo Lee, Heebal Kim
BACKGROUND: Africa is home to numerous cattle breeds whose diversity has been shaped by subtle combinations of human and natural selection. African Sanga cattle are an intermediate type of cattle resulting from interbreeding between Bos taurus and Bos indicus subspecies. Recently, research has asserted the potential of Sanga breeds for commercial beef production with better meat quality as compared to Bos indicus breeds. Here, we identified meat quality related gene regions that are positively selected in Ankole (Sanga) cattle breeds as compared to indicus (Boran, Ogaden, and Kenana) breeds using cross-population (XP-EHH and XP-CLR) statistical methods...
February 9, 2017: BMC Genetics
https://www.readbyqxmd.com/read/28167492/disruption-of-pdgfra-alters-endocardial-and-myocardial-fusion-during-zebrafish-cardiac-assembly
#9
Suzan El-Rass, Shahram Eisa-Beygi, Edbert Khong, Koroboshka Brand-Arzamendi, Antonio Mauro, Haibo Zhang, Karl J Clark, Stephen C Ekker, Xiao-Yan Wen
Cardiac development in vertebrates is a finely tuned process regulated by a set of conserved signaling pathways. Perturbations of these processes are often associated with congenital cardiac malformations. Platelet-derived growth factor receptor α (PDGFRα) is a highly conserved tyrosine kinase receptor, which is essential for development and organogenesis. Disruption of Pdgfrα function in murine models are embryonic lethal due to severe cardiovascular defects, suggesting a role in cardiac development, thus necessitating the use of alternative models to explore its precise function...
February 6, 2017: Biology Open
https://www.readbyqxmd.com/read/28163952/unintended-targeting-of-dmp1-cre-reveals-a-critical-role-for-bmpr1a-signaling-in-the-gastrointestinal-mesenchyme-of-adult-mice
#10
Joohyun Lim, Joseph Burclaff, Guangxu He, Jason C Mills, Fanxin Long
Cre/loxP technology has been widely used to study cell type-specific functions of genes. Proper interpretation of such data critically depends on a clear understanding of the tissue specificity of Cre expression. The Dmp1-Cre mouse, expressing Cre from a 14-kb DNA fragment of the mouse Dmp1 gene, has become a common tool for studying gene function in osteocytes, but the presumed cell specificity is yet to be fully established. By using the Ai9 reporter line that expresses a red fluorescent protein upon Cre recombination, we find that in 2-month-old mice, Dmp1-Cre targets not only osteocytes within the bone matrix but also osteoblasts on the bone surface and preosteoblasts at the metaphyseal chondro-osseous junction...
2017: Bone Research
https://www.readbyqxmd.com/read/28159677/clinicopathological-and-molecular-features-of-a-large-cohort-of-gastrointestinal-stromal-tumors-gists-and-review-of-the-literature-braf-mutations-in-kit-pdgfra-wildtype-gists-are-rare-events
#11
Sebastian Huss, Hlen Pasternack, Michaela Angelika Ihle, Sabine Merkelbach-Bruse, Birthe Heitkötter, Wolfgang Hartmann, Marcel Trautmann, Heidrun Gevensleben, Reinhard Büttner, Hans-Ulrich Schildhaus, Eva Wardelmann
In KIT/PDGFRA wild-type gastrointestinal stromal tumors (wt-GISTs), BRAF mutations are regarded as alternative pathogenic event driving tumorigenesis. In our study, we aimed at analyzing a large cohort (n=444) of GISTs for BRAF mutations using molecular and immunohistochemical methods. More than 3000 GIST samples from caucasian patients were available in our GIST and Sarcoma Registry NRW. Of these, we selected 172 wt-GISTs to evaluate the frequency of BRAF mutations. Furthermore, 272 GISTs with a representative KIT and PDGFRA mutational status were selected...
January 31, 2017: Human Pathology
https://www.readbyqxmd.com/read/28133332/-multidisciplinary-treatment-for-high-risk-gist-of-the-stomach
#12
Tomo Ishida, Shigeyuki Tamura, Atsushi Takeno, Kohei Murakami, Yohei Nose, Ryota Mori, Yasuo Oneda, Ryuichi Kuwahara, Takuya Sakamoto, Atsushi Naito, Yoshiteru Katsura, Yoshiaki Ohmura, Yoshinori Kagawa, Yutaka Takeda, Takeshi Kato
A 59-year-old man underwent total gastrectomy(with D2 dissection)and cholecystectomy for gastric cancer and a submucosal tumor of the stomach. The specimen was immunohistochemically positive for c-kit, the Ki-67 label index was 10%, and the mitotic count was 20/HPF. Finally, the patient was diagnosed with high-risk gastrointestinal stromal cancer with normal type gastric cancer. After discharge from hospital, we started administration of TS-1 as adjuvant therapy for the gastric cancer. As multiple recurrences of the GIST in the abdomen developed, the patient underwent 3 radical local resections...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28133162/-a-case-of-a-large-gastric-gastrointestinal-stromal-tumor-with-a-pdgfra-exon-18-mutation
#13
Atsuo Imagawa, Mitsuru Tomizawa, Satoshi Okumura, Sho Toyoda, Hiroshi Kawashima, Kansuke Yamamoto, Aya Ito, Naoto Mizumura, Ken Yoo, Hiromitsu Maehira, Masao Ogawa, Masayasu Kawasaki, Masao Kameyama, Michiko Yoshimura, Seiichi Hirota
A 49-year-old man visited our hospital with a chief complaint of abdominal pain that began 1 day before his visit.An approximately 30 cm tumor that was extensively in contact with the gastric wall in the abdominal cavity was detected on computed tomography(CT).An elevated lesion covered with normal mucosa on the posterior wall of the greater curvature was detected on upper endoscopy.He was diagnosed with a submucosal tumor of the stomach, and he underwent surgery. Surgical findings revealed an elastic soft tumor with a maximal dimension of 38 cm that projected from the posterior wall of the stomach beyond the gastric wall...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28133136/-a-case-of-metastatic-colon-cancer-dramatically-affected-by-anti-egfr-antibody-therapy
#14
Ryoma Yagi, Yoshifumi Shimada, Kohei Miura, Yosuke Tajima, Takuma Okamura, Masato Nakano, Hiroshi Ichikawa, Masayuki Nagahashi, Jun Sakata, Takashi Kobayashi, Hitoshi Kameyama, Toshifumi Wakai, Hitoshi Nogami, Satoshi Maruyama, Yasumasa Takii
RAS mutation is an established predictive biomarker of resistance to anti-epidermal growth factor receptor(EGFR)therapy in metastatic colorectal cancer. In addition, previous studies identified mutations in ERBB2, FGFR1, PDGFRA, BRAF, MAP2K1, PTEN, and PIK3CA as potential mechanisms of resistance to anti-EGFR therapy. Testing for these mutations might be necessary to determine eligibility for anti-EGFR therapy in patients with metastatic colorectal cancer. CancerPlex®is a nextgeneration sequencer for 413 cancer genes...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28130400/genome-wide-analyses-identifies-men1-and-max-mutations-and-a-neuroendocrine-like-molecular-heterogeneity-in-quadruple-wt-gist
#15
Maria A Pantaleo, Milena Urbini, Valentina Indio, Gloria Ravegnini, Margherita Nannini, Matilde De Luca, Giuseppe Tarantino, Sabrina Angelini, Alessandro Gronchi, Bruno Vincenzi, Giovanni Grignani, Chiara Colombo, Elena Fumagalli, Lidia Gatto, Maristella Saponara, Manuela Ianni, Paola Paterini, Donatella Santini, Maria Giulia Pirini, Claudio Ceccarelli, Annalisa Altimari, Elisa Gruppioni, Salvatore L Renne, Paola Collini, Silvia Stacchiotti, Giovanni Brandi, Paolo G Casali, Antonio D Pinna, Annalisa Astolfi, Guido Biasco
: Quadruple wild-type (WT) gastrointestinal stromal tumors (GIST) is a genomic subgroup lacking KIT/PDGFRA/RAS pathways mutations, with an intact succinate dehydrogenase (SDH) complex. The aim of this work is to perform a wide comprehensive genomic study on quadruple WT GIST to improve the characterization of these patients. We selected 14 clinical cases of quadruple WT GIST, of which nine cases showed sufficient DNA quality for Whole Exome Sequencing (WES). NF1 alterations were identified directly by WES...
January 27, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28105789/pdgfra-amplification-in-multiple-skin-lesions-of-undifferentiated-pleomorphic-sarcoma-ups-a-clue-for-intimal-sarcoma-metastases
#16
A Osio, M-D Vignon-Pennamen, F Pedeutour, C Le Maignan, F Koskas, C Lebbé, A Janin, M Battistella
A 62-year-old HIV-positive man was admitted for multiple cutaneous and subcutaneous nodules on his lower limbs, corresponding to an undifferentiated proliferation of spindle and pleomorphic cells, with irregular nuclei and numerous mitoses. The tumor cells were negative for a large panel of immunohistochemical markers, except CD10. MDM2 immunohistochemical staining was also negative, leading to the diagnosis of FNCLCC grade III Undifferentiated Pleomorphic Sarcoma (UPS). aCGH showed a highly complex karyotype, with amplification of the 4q12 region, an area that contains only the PDGFRa gene...
January 20, 2017: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/28102348/ho-1-inhibits-preadipocyte-proliferation-and-differentiation-at-the-onset-of-obesity-via-ros-dependent-activation-of-akt2
#17
Gabriel Wagner, Josefine Lindroos-Christensen, Elisa Einwallner, Julia Husa, Thea-Christin Zapf, Katharina Lipp, Sabine Rauscher, Marion Gröger, Andreas Spittler, Robert Loewe, Florian Gruber, J Catharina Duvigneau, Thomas Mohr, Hedwig Sutterlüty-Fall, Florian Klinglmüller, Gerhard Prager, Berthold Huppertz, Jeanho Yun, Oswald Wagner, Harald Esterbauer, Martin Bilban
Excessive accumulation of white adipose tissue (WAT) is a hallmark of obesity. The expansion of WAT in obesity involves proliferation and differentiation of adipose precursors, however, the underlying molecular mechanisms remain unclear. Here, we used an unbiased transcriptomics approach to identify the earliest molecular underpinnings occuring in adipose precursors following a brief HFD in mice. Our analysis identifies Heme Oxygenase-1 (HO-1) as strongly and selectively being upregulated in the adipose precursor fraction of WAT, upon high-fat diet (HFD) feeding...
January 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28098915/somatic-mutational-spectrum-analysis-in-a-prospective-series-of-104-gastrointestinal-stromal-tumors
#18
David Guenat, Olivier Deroo, Sandrine Magnin, Loïc Chaigneau, Franck Monnien, Christophe Borg, Christiane Mougin, Jean-François Emile, Jean-Luc Prétet
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors distinguished by driver mutations in proto-oncogenes KIT or PDGFRA in 85-90% of cases. These mutations have been linked to the response to imatinib, a multikinase inhibitor, and have independent prognostic impact. Here, we describe the prospective study of the molecular characteristics of 104 GISTs from French adult patients analyzed routinely through the National Hospital Program of Molecular Cancer Diagnosis. All patients with GISTs diagnosed at the University Hospital of Besançon between August 2005 and October 2014 were prospectively included in the present study...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28098558/platelet-derived-growth-factor-pdgf-signaling-directs-cardiomyocyte-movement-toward-the-midline-during-heart-tube-assembly
#19
Joshua Bloomekatz, Reena Singh, Owen Wj Prall, Ariel C Dunn, Megan Vaughan, Chin-San Loo, Richard P Harvey, Deborah Yelon
Communication between neighboring tissues plays a central role in guiding organ morphogenesis. During heart tube assembly, interactions with the adjacent endoderm control the medial movement of cardiomyocytes, a process referred to as cardiac fusion. However, the molecular underpinnings of this endodermal-myocardial relationship remain unclear. Here, we show an essential role for platelet-derived growth factor receptor alpha (Pdgfra) in directing cardiac fusion. Mutation of pdgfra disrupts heart tube assembly in both zebrafish and mouse...
January 18, 2017: ELife
https://www.readbyqxmd.com/read/28092366/malignant-melanoma-of-sun-protected-sites-a-review-of-clinical-histological-and-molecular-features
#20
Emily A Merkel, Pedram Gerami
In most cases of cutaneous melanoma, ultraviolet (UV) radiation is recognized as a prominent risk factor. Less is known regarding the mechanisms of mutagenesis for melanoma arising in sun-protected sites, such as acral and mucosal melanoma. Acral and mucosal melanoma share many common features, including a late age of onset, a broad radial growth phase with prominent lentiginous growth, the presence of field cancerization cells, and, in most cases, lack of a precursor nevus. In addition to early chromosomal instability, many of the same genes are also involved in these two distinct melanoma subtypes...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
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