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https://www.readbyqxmd.com/read/28632504/what-is-new-in-gastrointestinal-stromal-tumor
#1
Inga-Marie Schaefer, Adrián Mariño-Enríquez, Jonathan A Fletcher
The classification "gastrointestinal stromal tumor" (GIST) became commonplace in the 1990s and since that time various advances have characterized the GIST lineage of origin, tyrosine kinase mutations, and mechanisms of response and resistance to targeted therapies. In addition to tyrosine kinase mutations and their constitutive activation of downstream signaling pathways, GISTs acquire a sequence of chromosomal aberrations. These include deletions of chromosomes 14q, 22q, 1p, and 15q, which harbor putative tumor suppressor genes required for stepwise progression from microscopic, preclinical forms of GIST (microGIST) to clinically relevant tumors with malignant potential...
June 19, 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28627468/a-novel-chalcone-derivative-lqfm064-induces-breast-cancer-cells-death-via-p53-p21-kit-and-pdgfra
#2
Bruna Lannuce Silva Cabral, Artur Christian Garcia da Silva, Renato Ivan de Ávila, Alane Pereira Cortez, Rangel Magalhães Luzin, Luciano Morais Lião, Eric de Souza Gil, Gérman Sanz, Boniek G Vaz, José R Sabino, Ricardo Menegatti, Marize Campos Valadares
This study shows the design, synthesis and antitumoral potential evaluation of a novel chalcone-like compound, (E)-3- (3, 5-di-ter-butyl-4-hydroxyphenyl)-1- (4-hydroxy-3-methoxyphenyl) prop-2-en-1-one [LQFM064) (4)], against human breast adenocarcinoma MCF7 cells. Some toxicological parameters were also investigated. LQFM064) (4) exhibited cytotoxic activity against MCF7 cells (IC50=21μM), in a concentration dependent-manner, and triggered significant changes in cell morphology and biochemical/molecular parameters, which are suggestive of an apoptosis inductor...
June 13, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28619758/co-targeting-of-mek-and-pdgfr-stat3-pathways-to-treat-pancreaticductal-adenocarcinoma
#3
Nisebita Sahu, Emily Chan, Felix Chu, Thinh Pham, Hartmut Koeppen, William Forrest, Mark Merchant, Jeff Settleman
Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal human diseases and remains largely refractory to available drug treatments.  Insufficient targeting of the known oncogenic drivers and activation of compensatory feedback loops and inability to prevent metastatic spread contribute to poor prognosis for this disease. The KRAS-driven MEK pathway is mutationally activated in most pancreatic cancers and is an important target for therapeutics. Using a 2-dimensional monolayer culture system as well as 3-dimensional spheroid culture system, we conducted a screen of a large panel of anti-cancer agents, and found that MEK inhibitors were most effective in targeting PDAC spheroids in comparison to monolayer cultures...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28611108/wnt-%C3%AE-catenin-signaling-contributes-to-tumor-malignancy-and-is-targetable-in-gastrointestinal-stromal-tumor
#4
Shan Zeng, Adrian M Seifert, Jennifer Q Zhang, Michael J Cavnar, Teresa S Kim, Vinod P Balachandran, Juan A Santamaria-Barria, Noah A Cohen, Michael J Beckman, Benjamin Medina, Ferdinand Rossi, Megan H Crawley, Jennifer K Loo, Joanna H Maltbaek, Peter Besmer, Cristina R Antonescu, Ronald P DeMatteo
Gastrointestinal stromal tumor (GIST) is the most common type of sarcoma and usually harbors either a KIT or PDGFRA mutation. However, the molecular basis for tumor malignancy is not well defined. While the Wnt/b-catenin signaling pathway is important in a variety of cancers, its role in GIST is uncertain. Through analysis of nearly 150 human GIST specimens, we found that some human GISTs expressed b-catenin and contained active, dephosphorylated nuclear b-catenin. Furthermore, advanced human GISTs expressed reduced levels of the Wnt antagonist DKK4...
June 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28609680/characterization-and-targeting-of-platelet-derived-growth-factor-receptor-alpha-pdgfra-in-inflammatory-breast-cancer-ibc
#5
Madhura Joglekar-Javadekar, Steven Van Laere, Michael Bourne, Manal Moalwi, Pascal Finetti, Peter B Vermeulen, Daniel Birnbaum, Luc Y Dirix, Naoto Ueno, Monique Carter, Justin Rains, Abhijit Ramachandran, Francois Bertucci, Kenneth L van Golen
PURPOSE: Inflammatory breast cancer (IBC) is arguably the deadliest form of breast cancer due to its rapid onset and highly invasive nature. IBC carries 5- and 10-year disease-free survival rates of ~45% and <20%, respectively. Multiple studies demonstrate that in comparison with conventional breast cancer, IBC has a unique molecular identity. Here, we have identified platelet-derived growth factor receptor alpha (PDGFRA) as being uniquely expressed and active in IBC patient tumor cells...
June 10, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28603561/distinct-dna-methylation-profiles-in-subtypes-of-orofacial-cleft
#6
Gemma C Sharp, Karen Ho, Amy Davies, Evie Stergiakouli, Kerry Humphries, Wendy McArdle, Jonathan Sandy, George Davey Smith, Sarah J Lewis, Caroline L Relton
BACKGROUND: Epigenetic data could help identify risk factors for orofacial clefts, either by revealing a causal role for epigenetic mechanisms in causing clefts or by capturing information about causal genetic or environmental factors. Given the evidence that different subtypes of orofacial cleft have distinct aetiologies, we explored whether children with different cleft subtypes showed distinct epigenetic profiles. METHODS: In whole-blood samples from 150 children from the Cleft Collective cohort study, we measured DNA methylation at over 450,000 sites on the genome...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28596498/somatic-mutations-in-salivary-duct-carcinoma-and-potential-therapeutic-targets
#7
Timothy K Khoo, Bing Yu, Joel A Smith, Angus J Clarke, Peter P Luk, Christina I Selinger, Kate L Mahon, Spiridoula Kraitsek, Carsten Palme, Michael J Boyer, Marcel E Dinger, Mark J Cowley, Sandra A O'Toole, Jonathan R Clark, Ruta Gupta
BACKGROUND: Salivary duct carcinomas (SDCa) are rare highly aggressive malignancies. Most patients die from distant metastatic disease within three years of diagnosis. There are limited therapeutic options for disseminated disease. RESULTS: 11 cases showed androgen receptor expression and 6 cases showed HER2 amplification. 6 Somatic mutations with additional available targeted therapies were identified: EGFR (p.G721A: Gefitinib), PDGFRA (p.H845Y: Imatinib and Crenolanib), PIK3CA (p...
May 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28593047/integration-of-a-bacterial-gene-sequence-into-a-chronic-eosinophilic-leukemia-patient-s-genome-as-part-of-a-fusion-gene-linker
#8
Saveen Sidhoo, Jesusa L Rosales, Ki-Young Lee
Analysis of databases from the human genome project (HGP), the 1000 Genomes Project (1KGP), and The Cancer Genome Atlas (TCGA) revealed bacterial DNA integration into the human somatic genome, particularly in tumor tissues. Fusion genes have also been associated with tumorigenesis and 34 PDGFR fusion genes are linked to hematological malignancies. Here, we determined that a 17-bp homologous sequence in Marinobacter sp. Hb8, Rhodococcus fascians D188, Rhodococcus sp. PBTS2, Micrococcus luteus strain trpE16 and M...
2017: Biomarker Research
https://www.readbyqxmd.com/read/28592523/germline-cdkn2a-p16ink4a-mutations-contribute-to-genetic-determinism-of-sarcoma
#9
Fanélie Jouenne, Isaure Chauvot de Beauchene, Emeline Bollaert, Marie-Françoise Avril, Olivier Caron, Olivier Ingster, Axel Lecesne, Patrick Benusiglio, Philippe Terrier, Vincent Caumette, Daniel Pissaloux, Arnaud de la Fouchardière, Odile Cabaret, Birama N'Diaye, Amélie Velghe, Gaelle Bougeard, Graham J Mann, Serge Koscielny, Jennifer H Barrett, Mark Harland, Julia Newton-Bishop, Nelleke Gruis, Remco Van Doorn, Marion Gauthier-Villars, Gaelle Pierron, Dominique Stoppa-Lyonnet, Isabelle Coupier, Rosine Guimbaud, Capucine Delnatte, Jean-Yves Scoazec, Alexander M Eggermont, Jean Feunteun, Luba Tchertanov, Jean-Baptiste Demoulin, Thierry Frebourg, Brigitte Bressac-de Paillerets
BACKGROUND: Sarcomas are rare mesenchymal malignancies whose pathogenesis is poorly understood; both environmental and genetic risk factors could contribute to their aetiology. METHODS AND RESULTS: We performed whole-exome sequencing (WES) in a familial aggregation of three individuals affected with soft-tissue sarcoma (STS) without TP53 mutation (Li-Fraumeni-like, LFL) and found a shared pathogenic mutation in CDKN2A tumour suppressor gene. We searched for individuals with sarcoma among 474 melanoma-prone families with a CDKN2A-/+ genotype and for CDKN2A mutations in 190 TP53-negative LFL families where the index case was a sarcoma...
June 7, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/28577566/erratum-to-the-progressive-fragmentation-of-the-kit-pdgfra-wild-type-wt-gastrointestinal-stromal-tumors-gist
#10
Margherita Nannini, Milena Urbini, Annalisa Astolf, Guido Biasco, Maria A Pantaleo
No abstract text is available yet for this article.
June 2, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28573215/molecular-histologic-and-radiologic-findings-of-high-grade-invasive-adenocarcinoma-arising-in-oncocytic-subtype-of-intraductal-papillary-mucinous-neoplasm-a-case-report-and-review-of-literature
#11
Jared Shows, Christan Bartsch, Heather Carmichael, Irfan Qureshi, Barish Edil, Hubert Fenton
Background: We present a case of adenocarcinoma arising in the oncocytic subtype of intraductal papillary mucinous neoplasm (O-IPMN), with emphasis on the molecular findings in the adenocarcinoma component. Tissue microdissection and next-generation sequencing were performed using a 26 gene panel (AKT1, ALK, APC, BRAF, CDH1, CTNNB1, EGFR, ERBB2, FBXW7, FGFR2, FOXL2, GNAQ, GNAS, KIT, KRAS, MAP2K1, MET, MSH6, NRAS, PDGFRA, PIK3CA, PTEN, SMAD4, SRC, STK11, TP53) of cancer-related genes. Case Presentation: A 69-year-old Caucasian female presented with chest pain and was found to have findings consistent with acute pancreatitis...
2017: J Pancreat Cancer
https://www.readbyqxmd.com/read/28570130/an-integrative-computational-approach-to-evaluate-genetic-markers-for-chronic-lymphocytic-leukemia
#12
Yu Zheng, Xiaoyang Li, Lydia C Manor, Hongbao Cao, Qiusheng Chen
Recent studies reported hundreds of genes linked to chronic lymphocytic leukemia (CLL). However, many of these candidate genes were lack of replication and results were not always consistent. Here, we proposed a computational workflow to curate and evaluate CLL-related genes. The method integrates large-scale literature knowledge data, gene expression data, and related pathways/network information for quantitative marker evaluation. Pathway Enrichment, Sub-Network Enrichment, and Gene-Gene Interaction analysis were conducted to study the pathogenic profile of the candidate genes, with four metrics proposed and validated for each gene...
June 1, 2017: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/28562323/pdgfra-hsd17b4-and-hmgb2-are-potential-therapeutic-targets-in-polycystic-ovarian-syndrome-and-breast-cancer
#13
Huiyu Xu, Yong Han, Jiaying Lou, Hongxian Zhang, Yue Zhao, Balázs Győrffy, Rong Li
To explore the key genes associated with both PCOS and breast cancer, we overlapped the synchronously differently expressed genes in two obese insulin-resistant GEO datasets in muscle tissue and genes exert essential roles in breast cancer prognosis together base on the following reasons: (1) Androgens excess is believed to contribute to the onset of both PCOS and breast cancer. (2) PCOS is usually complicated with metabolic symptoms, such as obesity and insulin-resistance. (3) Muscle is the main place where energy metabolism and material metabolism take place...
May 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28557709/influence-of-cytochrome-p450-abc-and-slc-gene-polymorphisms-on-imatinib-therapy-outcome-of-patients-with-gastrointestinal-stromal-tumours-gist
#14
K Wasielewski, B Wasag, A Wozniak, J Pikiel, A Kowalik, C Osuch, E Bylina, J A Siedlecki, P Rutkowski, J Limon
The efficacy of imatinib-based therapy depends on the proteins involved in its metabolism and transportation. Therefore, the aim of our study was to investigate the possible correlation of selected P450, ABC and SLC polymorphic variants and the outcome of imatinib therapy. A total of 101 patients with advanced, KIT/PDGFRA(+) GIST treated with imatinib were enrolled to the study. DNA was extracted from peripheral blood samples and genotypes were determined by PCR-RFLP and direct sequencing. Deviation from the Hardy-Weinberg equilibrium was only observed for rs2740574...
2017: Folia Biologica (Praha)
https://www.readbyqxmd.com/read/28548943/intra-tumour-molecular-heterogeneity-of-clear-cell-renal-cell-carcinoma-reveals-the-diversity-of-the-response-to-targeted-therapies-using-patient-derived-xenograft-models
#15
Baoan Hong, Yong Yang, Sheng Guo, Shayiremu Duoerkun, Xiaohu Deng, Dawei Chen, Shijun Yu, Wubin Qian, Qixiang Li, Qing Li, Kan Gong, Ning Zhang
Inter- and intra-tumour molecular heterogeneity is increasingly recognized in clear cell renal cell carcinoma (ccRCC). It may partially explain the diversity of responses to targeted therapies and the various clinical outcomes. In this study, a 56-year-old male ccRCC patient with multiple metastases received radical nephrectomy and resection of the metastatic tumour in chest wall. The surgical specimens were implanted into nude mice to establish patient-derived xenograft (PDX) models with KI2367 model derived from the primary tumour and KI2368 model from the metastastic tumour...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28539323/etv1-positive-cells-give-rise-to-brafv600e-mutant-gastrointestinal-stromal-tumors
#16
Leili Ran, Devan Murphy, Jessica Sher, Zhen Cao, Shangqian Wang, Edward Walczak, Youxin Guan, Yuanyuan Xie, Shipra Shukla, Yu Zhan, Cristina R Antonescu, Yu Chen, Ping Chi
Gastrointestinal Stromal Tumor (GIST) is the most common subtype of sarcoma. Despite clinical advances in the treatment of KIT/PDGFRA-mutant GIST, similar progress against KIT/PDGFRA-wild type GIST, including mutant BRAF-driven tumors, have been limited by a lack of model systems. ETV1 is a master regulator in the intestinal cells of Cajal (ICC), thought to be the cells of origin of GIST. Here we present a model in which the ETV1 promoter is used to specifically and inducibly drive Cre recombinase in ICC as a strategy to study GIST pathogenesis...
May 24, 2017: Cancer Research
https://www.readbyqxmd.com/read/28535771/the-progressive-fragmentation-of-the-kit-pdgfra-wild-type-wt-gastrointestinal-stromal-tumors-gist
#17
Margherita Nannini, Milena Urbini, Annalisa Astolfi, Guido Biasco, Mara A Pantaleo
Recent advances in molecular biology have revolutionized the concept of KIT/PDGFRA wild type (WT) gastrointestinal stromal tumors (GIST) than the past. Indeed, from being defined as GIST without KIT or PDGFRA mutations, we are now faced with the opposite scenario, where KIT/PDGFRA WT GIST are "positively" defined according to their specific molecular alterations. In particular, if until recently KIT/PDGFRA GIST without abnormalities of KIT, PDGFRA, SDH, and the RAS signaling pathway were referred as quadruple WT GIST, today also this small subset of GIST is emerging out as a group of heterogeneous distinct entities with multiple different molecular alterations...
May 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28535583/molecular-testing-of-brain-tumor
#18
REVIEW
Sung-Hye Park, Jaekyung Won, Seong-Ik Kim, Yujin Lee, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi
The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53 , and ATRX , oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC , FUBP1 , and the promoter region of telomerase reverse transcriptase ( TERTp )...
May 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28528977/imatinib-induces-autophagy-via-upregulating-xiap-in-gist882%C3%A2-cells
#19
Qingqing Xie, Qi Lin, Dezhi Li, Jianming Chen
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms originating from the gastrointestinal tract with gain of function mutations in receptor tyrosine kinases KIT or platelet-derived growth factor receptor A (PDGFRA). The main effective treatment for GISTs is tyrosine kinase inhibitors, such as imatinib mesylate. However, GISTs respond to imatinib treatment eventually develop acquired resistance, which is a main obstacle for GISTs therapy. Therefore, it's urgent to have a better understanding of the mechanisms underlying the imatinib resistance in GISTs to develop novel therapeutic strategies...
May 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28521409/evaluation-of-a-novel-approach-to-circulating-tumor-cell-isolation-for-cancer-gene-panel-analysis-in-patients-with-breast-cancer
#20
Soo Jeong Lee, Cham Han Lee, Sung Ho Choi, Sei Hyun Ahn, Byung Ho Son, Jong Won Lee, Jong Han Yu, Nak-Jung Kwon, Woo Chung Lee, Kap-Seok Yang, Dong Hyoung Lee, Du Yeol Han, Mi So Choi, Pyeong-Soo Park, Hyun Kyung Lee, Myoung Shin Kim, Jinseon Lee, Byung Hee Jeon
Liquid biopsy isolation of circulating tumor cells (CTCs) allows the genomic analysis of CTCs, which is useful in the determination of personalized cancer therapy. In the present study, CTCs from patients with breast cancer were enriched and successfully analyzed using cancer gene panel analysis. Blood samples from 11 patients with breast cancer were collected and CTCs enriched for using size-based filtration. The enriched CTCs were analyzed using immunofluorescence staining with antibodies directed against epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 45...
May 2017: Oncology Letters
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