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Geneviève Dom, Sandra Frank, Sebastien Floor, Pashalina Kehagias, Frederick Libert, Catherine Hoang, Guy Andry, Alex Spinette, Ligia Craciun, Nicolas de Saint Aubin, Christophe Tresallet, Frederique Tissier, Frederique Savagner, Samira Majjaj, Ilse Gutierrez-Roelens, Etienne Marbaix, Jacques E Dumont, Carine Maenhaut
Non-autonomous thyroid nodules are common in the general population with a proportion found to be cancerous. A current challenge in the field is to be able to distinguish benign adenoma (FA) from preoperatively malignant thyroid follicular carcinoma (FTC), which are very similar both histologically and genetically. One controversial issue, which is currently not understood, is whether both tumor types represent different molecular entities or rather a biological continuum. To gain a better insight into FA and FTC tumorigenesis, we defined their molecular profiles by mRNA and miRNA microarray...
February 13, 2018: Oncotarget
Ni Kou, Sha Liu, Xiaojie Li, Wuwei Li, Weijian Zhong, Lin Gui, Songling Chai, Xiang Ren, Risu Na, Tao Zeng, Huiying Liu
The long noncoding RNA (lncRNA) H19 has been described to participate in various tumors metastasis. Nevertheless, whether H19 promotes or impedestongue squamous cell carcinoma (TSCC) cells migration and invasion remains controversial. Here, we found that the expression of H19 was elevated in TSCC tissues compared with adjacent normal tissues. Moreover, we demonstrated that the expression of H19 was higher in metastasized tumors compared with un-metastasized tumors. Consistently, TSCC cells express higher levels of H19 than human squanous cells...
March 9, 2018: Oncology Research
Riccardo Sgarra, Silvia Pegoraro, Gloria Ros, Carlotta Penzo, Eusebio Chiefari, Daniela Foti, Antonio Brunetti, Guidalberto Manfioletti
Cancer heterogeneity is one of the factors that constitute an obstacle towards an efficient targeting of this multifaceted disease. Molecular information can help in classifying cancer subtypes and in providing clinicians with novel targeted therapeutic opportunities. In this regard, classification of breast cancer into intrinsic subtypes based on molecular profiling represents a valuable prototype. The High Mobility Group A (HMGA) chromatin architectural factors (HMGA1a, HMGA1b, and HMGA2) have a relevant and causal role in breast cancer onset and development, by influencing virtually all cancer hallmarks...
March 5, 2018: Biochimica et Biophysica Acta
Xi Xu, Yunfeng Wang, Hong Deng, Chungang Liu, Jingjing Wu, Maode Lai
Drug resistance is one of the main hurdles to overcome for the improvement of cancer patient survival. However, the underlying mechanisms remain largely unknown, and therapeutic options are limited. Here, we demonstrate a strong correlation between HMGA2 expression and chemosensitivity to 5-fluorouracil (5-FU), a widely used first-line systemic chemotherapy regimen for colorectal cancer (CRC) patients. Overexpression of HMGA2 enhances chemoresistance to 5-FU of CRC both in vitro and in vivo . Further experiments indicate that HMGA2 directly binds to the promoter of Dvl2 and induces its transcription, which leads to increased activation of the Wnt/β-catenin pathway...
February 9, 2018: Oncotarget
Bo Hou, Hajime Ishinaga, Kaoru Midorikawa, Satoshi Nakamura, Yusuke Hiraku, Shinji Oikawa, Ning Ma, Kazuhiko Takeuchi, Mariko Murata
To elucidate the molecular mechanisms underlying the progression of head and neck squamous cell carcinoma (HNSCC), we investigated the function of let-7c as a tumor suppressor. Let-7c expression was significantly down-regulated in HNSCC tumor tissues and cell lines. In vitro and in vivo studies revealed that let-7c negatively regulated HNSCC proliferation, migration and epithelial-mesenchymal transition (EMT). To explore the underlying mechanisms that affect these molecular events achieved by let-7c, we predicted its target genes...
February 6, 2018: Oncotarget
Frederik Heldt, Hannah Wallaschek, Tim Ripperger, Susanne Morlot, Thomas Illig, Thomas Eggermann, Brigitte Schlegelberger, Caroline Scholz, Doris Steinemann
We report here on the first family with short stature and Silver-Russell-like phenotype due to a microdeletion in 12q14.3. The Netchine-Harbison clinical scoring system was used for the clinical diagnosis of Silver-Russell syndrome (SRS). The three affected first-degree relatives (index patient, mother and brother) presented with prenatal and postnatal growth retardation, feeding difficulties, a prominent forehead and a failure to thrive but did not show relative macrocephaly. In addition, our index patient showed dysmorphic facial features, periodically increased sweating, and scoliosis...
March 1, 2018: European Journal of Medical Genetics
Liming Wang, Hui Shen, Da Zhu, Bei Feng, Lan Yu, Xun Tian, Ci Ren, Chun Gao, Xiaomin Li, Ding Ma, Zheng Hu, Hui Wang
Integration of the high risk human papillomavirus (HR-HPV) genome into host chromatin is an important step in cervical carcinogenesis. We identified HR-HPV integration sites within the human genome through detection of integrated papillomavirus sequences-PCR and assessed the role of high mobility group A 2 (HMGA2) in cervical carcinogenesis in clinical samples and cell lines. HPV integration sites were analyzed in 40 cervical cancer samples, while copy number variation and protein expression were assessed in 19 normal cervixes, 49 cervical intraepithelial neoplasia (CIN), and 52 cervical cancer samples...
January 30, 2018: Oncotarget
Wenyan Zhao, Donghua Geng, Shuqiang Li, Zhaofu Chen, Ming Sun
To study the regulatory effect of lncRNA HOTAIR/miR-20a-5p/HMGA2 axis on breast cancer (BC) cell growth, cell mobility, invasiveness, and apoptosis. The microarray data of lncRNAs and mRNAs with differential expression in BC tissues were analyzed in the Cancer Genome Atlas (TCGA) database. LncRNA HOX transcript antisense RNA (lncRNA HOTAIR) expression in BC was assessed by qRT-PCR. Cell viability was confirmed using MTT and colony formation assay. Cell apoptosis was analyzed by TdT-mediated dUTP nick-end labeling (TUNEL) assay...
February 23, 2018: Cancer Medicine
Gregory Costain, Rebekah Jobling, Susan Walker, Miriam S Reuter, Meaghan Snell, Sarah Bowdin, Ronald D Cohn, Lucie Dupuis, Stacy Hewson, Saadet Mercimek-Andrews, Cheryl Shuman, Neal Sondheimer, Rosanna Weksberg, Grace Yoon, M Stephen Meyn, Dimitri J Stavropoulos, Stephen W Scherer, Roberto Mendoza-Londono, Christian R Marshall
Whole-genome sequencing (WGS) as a first-tier diagnostic test could transform medical genetic assessments, but there are limited data regarding its clinical use. We previously showed that WGS could feasibly be deployed as a single molecular test capable of a higher diagnostic rate than current practices, in a prospectively recruited cohort of 100 children meeting criteria for chromosomal microarray analysis. In this study, we report on the added diagnostic yield with re-annotation and reanalysis of these WGS data ~2 years later...
February 16, 2018: European Journal of Human Genetics: EJHG
Yukihiro Shiga, Masato Akiyama, Koji M Nishiguchi, Kota Sato, Nobuhiro Shimozawa, Atsushi Takahashi, Yukihide Momozawa, Makoto Hirata, Matsuda Koichi, Taiki Yamaji, Motoki Iwasaki, Shoichiro Tsugane, Isao Oze, Haruo Mikami, Mariko Naito, Kenji Wakai, Munemitsu Yoshikawa, Masahiro Miyake, Kenji Yamashiro, Kenji Kashiwagi, Takeshi Iwata, Fumihiko Mabuchi, Mitsuko Takamoto, Mineo Ozaki, Kazuhide Kawase, Makoto Aihara, Makoto Araie, Tetsuya Yamamoto, Yoshiaki Kiuchi, Makoto Nakamura, Yasuhiro Ikeda, Koh-Hei Sonoda, Tatsuro Ishibashi, Koji Nitta, Aiko Iwase, Shiroaki Shirato, Yoshitaka Oka, Mamoru Satoh, Makoto Sasaki, Nobuo Fuse, Yoichi Suzuki, Ching-Yu Cheng, Chiea Chuen Khor, Mani Baskaran, Shamira Perera, Tin Aung, Eranga N Vithana, Jessica N Cooke Bailey, Jae H Kang, Louis R Pasquale, Jonathan L Haines, Janey L Wiggs, Kathryn P Burdon, Puya Gharahkhani, Alex W Hewitt, David A Mackey, Stuart MacGregor, Jamie E Craig, R Rand Allingham, Micheal Hauser, Adeyinka Ashaye, Donald L Budenz, Stephan Akafo, Susan E I Williams, Yoichiro Kamatani, Toru Nakazawa, Michiaki Kubo
Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7,378 POAG cases and 36,385 controls from a Japanese population. After combining the GWAS and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (p < 5...
February 14, 2018: Human Molecular Genetics
Tobias Hofving, Yvonne Arvidsson, Bilal Almobarak, Linda Inge, Roswitha Pfragner, Marta Persson, Göran Stenman, Erik Kristiansson, Viktor Johanson, Ola Nilsson
Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not...
March 2018: Endocrine-related Cancer
Simon Andreasen, Sarah L von Holstein, Preben Homøe, Steffen Heegaard
PURPOSE: Lacrimal gland tumours constitute a wide spectrum of neoplastic lesions that are histologically similar to tumours of the salivary gland. In the salivary gland, pleomorphic adenoma (PA) is frequently characterized by recurrent chromosomal rearrangements of the PLAG1 and HMGA2 genes, a genetic feature retained in carcinoma ex pleomorphic adenoma (ca-ex-PA) that makes it possible to distinguish ca-ex-PA from de novo carcinomas. However, whether PLAG1 and HMGA2 gene rearrangements are found in lacrimal gland PA and ca-ex-PA is not known...
February 13, 2018: Acta Ophthalmologica
Zhi-Hua Ye, Ding-Wen Gui
Renal cell carcinoma (RCC) is one of the most common urinary malignancies with a high rate of morbidity. MicroRNAs (miRNAs) have been shown to be critical post‑transcriptional regulators in tumorigenesis. The present study aimed to investigate the effect of miRNA (miR)‑539 on the proliferation and apoptosis of RCC. The expression of miR‑539 and high mobility group AT‑hook 2(HMGA2) were examined in clinical RCC specimens. The 786‑O RCC cell line was also used and was transfected with miR‑539 mimics or inhibitors...
February 8, 2018: Molecular Medicine Reports
Xiaohai Liu, Ming Feng, Ye Zhang, Congxin Dai, Bowen Sun, Xinjie Bao, Kan Deng, Yong Yao, Renzhi Wang
OBJECTIVE: MMP-9, PTTG, and HMGA2 play important roles in the tumorigenesis of adrenocorticotrophic hormone (ACTH)-secreting pituitary tumors, but their associations with tumor recurrence after transsphenoidal adenomectomy remain unclear. The aim of the study was to investigate the immunohistochemical expression profiles of MMP-9, PTTG, HMGA2, and Ki-67 in recurrent and non-recurrent ACTH-secreting pituitary tumors and to identify their associations with tumor behavior and recurrence status...
February 9, 2018: World Neurosurgery
Dan Nie, Lingping Zhang, Qian Guo, Xiguang Mao
Overexpression of the high mobility group protein A2 (HMGA2), an architectural transcription factor, has been linked to poor prognosis in many malignancies, although this remains controversial. Herein, we conducted a meta-analysis to investigate whether HMGA2 has prognostic value, and evaluated the association between HMGA2 and clinicopathologic factors in malignancies. A total of 29 studies involving 4114 patients were included in this meta-analysis. The pooled results demonstrated that elevated HMGA2 predicted a poor overall survival (OS) (hazard ratio [HR] = 1...
January 2, 2018: Oncotarget
Ivan Šamija, Neven Mateša, Sanja Kožaj, Ivana Majstorović, Ante Bolanča, Zvonko Kusić
There is a great interest in molecular markers that would help in the preoperative diagnosis of malignant thyroid nodules in cases of indeterminate fine-needle aspiration cytology. The aim of this study was to determine the diagnostic accuracy of HMGA2 gene expression in discriminating benign from malignant thyroid nodules. In this study, 237 preoperative thyroid fine-needle aspiration samples were analyzed prospectively for the expression of the HMGA2 gene by real-time reverse transcription polymerase chain reaction...
February 5, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Jian Ma, Da Li, Fan-Fei Kong, Di Yang, Hui Yang, Xiao-Xin Ma
BACKGROUND: Metastasis is one of the main reasons for treatment failure in endometrial cancer. Notably, high mobility group AT-hook 2 (HMGA2) has been recognized as a driving factor of tumour metastasis. microRNAs (miRNAs) are powerful posttranscriptional regulators of HMGA2. METHODS: The binding sites of miR-302a-5p and miR-367-3p on HMGA2 mRNA were identified using bioinformatics prediction software and were validated via luciferase assay. The expression levels of miR-302a-5p and miR-367-3p were detected using quantitative real-time PCR and in situ hybridization...
February 1, 2018: Journal of Experimental & Clinical Cancer Research: CR
Li Tan, Hongfa Xu, Guoshu Chen, Xiaoping Wei, Baodan Yu, Jingmei Ye, Lihua Xu, Huo Tan
BACKGROUND: High-mobility group AT-hook 2 (HMGA2) may serve as an architectural transcription factor, and it can regulate a range of normal biological processes including proliferation and differentiation. Upregulation of HMGA2 expression is correlated to the undifferentiated phenotype of immature leukaemic cells. However, the underlying mechanism of HMGA2-dependent myeloid differentiation blockage in leukaemia is unknown. METHODS: To reveal the role and mechanism of HMGA2 in differentiation arrest of myeloid leukaemia cells, the quantitative expression of HMGA2 and homeobox A9 (HOXA9) was analysed by real-time PCR (qRT-PCR)...
January 2, 2018: British Journal of Cancer
Lourdes Hontecillas-Prieto, Daniel J García-Domínguez, Rosa García-Mejías, Gema L Ramírez-Villar, Carmen Sáez, Enrique de Álava
Wilms tumor (WT) is an embryonal malignant neoplasm of the kidney that accounts for 6-7% of all childhood cancers. WT seems to derive from multipotent embryonic renal stem cells that have failed to differentiate properly. Since mechanisms underlying WT tumorigenesis remain largely unknown, the aim of this study was to explore the expression of embryonic stem cell (ESC) markers in samples of WT patients after chemotherapy treatment SIOP protocol, as the gene expression patterns of ESC are like those of most cancer cells...
December 29, 2017: Oncotarget
Robin N Beaumont, Nicole M Warrington, Alana Cavadino, Jessica Tyrrell, Michael Nodzenski, Momoko Horikoshi, Frank Geller, Ronny Myhre, Rebecca C Richmond, Lavinia Paternoster, Jonathan P Bradfield, Eskil Kreiner-Møller, Ville Huikari, Sarah Metrustry, Kathryn L Lunetta, Jodie N Painter, Jouke-Jan Hottenga, Catherine Allard, Sheila J Barton, Ana Espinosa, Julie A Marsh, Catherine Potter, Ge Zhang, Wei Ang, Diane J Berry, Luigi Bouchard, Shikta Das, Hakon Hakonarson, Jani Heikkinen, Øyvind Helgeland, Berthold Hocher, Albert Hofman, Hazel M Inskip, Samuel E Jones, Manolis Kogevinas, Penelope A Lind, Letizia Marullo, Sarah E Medland, Anna Murray, Jeffrey C Murray, Pål R Njølstad, Ellen A Nohr, Christoph Reichetzeder, Susan M Ring, Katherine S Ruth, Loreto Santa-Marina, Denise M Scholtens, Sylvain Sebert, Verena Sengpiel, Marcus A Tuke, Marc Vaudel, Michael N Weedon, Gonneke Willemsen, Andrew R Wood, Hanieh Yaghootkar, Louis J Muglia, Meike Bartels, Caroline L Relton, Craig E Pennell, Leda Chatzi, Xavier Estivill, John W Holloway, Dorret I Boomsma, Grant W Montgomery, Joanne M Murabito, Tim D Spector, Christine Power, Marjo-Ritta Järvelin, Hans Bisgaard, Struan Fa Grant, Thorkild Ia Sørensen, Vincent W Jaddoe, Bo Jacobsson, Mads Melbye, Mark I McCarthy, Andrew T Hattersley, M Geoffrey Hayes, Timothy M Frayling, Marie-France Hivert, Janine F Felix, Elina Hyppönen, William L Lowe, David M Evans, Debbie A Lawlor, Bjarke Feenstra, Rachel M Freathy
Genome-wide association studies (GWAS) of birth weight have focused on fetal genetics, while relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86,577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother-child pairs to quantify the separate maternal and fetal genetic effects...
January 3, 2018: Human Molecular Genetics
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