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https://www.readbyqxmd.com/read/28766011/rnai-screen-identifies-essential-regulators-of-human-brain-metastasis-initiating-cells
#1
Mohini Singh, Chitra Venugopal, Tomas Tokar, Kevin R Brown, Nicole McFarlane, David Bakhshinyan, Thusyanth Vijayakumar, Branavan Manoranjan, Sujeivan Mahendram, Parvez Vora, Maleeha Qazi, Manvir Dhillon, Amy Tong, Kathrin Durrer, Naresh Murty, Robin Hallet, John A Hassell, David R Kaplan, Jean-Claude Cutz, Igor Jurisica, Jason Moffat, Sheila K Singh
Brain metastases (BM) are the most common brain tumor in adults and are a leading cause of cancer mortality. Metastatic lesions contain subclones derived from their primary lesion, yet their functional characterization is limited by a paucity of preclinical models accurately recapitulating the metastatic cascade, emphasizing the need for a novel approach to BM and their treatment. We identified a unique subset of stem-like cells from primary human patient brain metastases, termed brain metastasis-initiating cells (BMICs)...
August 1, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28718375/emp3-is-induced-by-twist1-2-and-regulates-epithelial-to-mesenchymal-transition-of-gastric-cancer-cells
#2
Ming Han, Wanpeng Xu
In this study, we aimed to explore new downstream effectors of TWIST1/2 in inducing epithelial-to-mesenchymal transition in gastric cancer. Bioinformatic data mining was performed using data in The Cancer Genome Atlas Stomach Adenocarcinoma. Survival curves were generated using Kaplan-Meier plotter. Gastric cancer cell lines (AGS and SGC-7901) were used as in vitro cell model to investigate the regulative effect of TWIST1/2 on epithelial membrane protein 3 expression and the progression of epithelial-to-mesenchymal transition...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28690482/barber-say-syndrome-and-ablepharon-macrostomia-syndrome-a-patient-s-view
#3
Beatrice De Maria, Tresia de Jager, Caitlin Sarubbi, Oliver Bartsch, Alberto Bianchi, Francesco Brancati, Hon-Yin B Chung, Albert David, Ariana Kariminejad, Maura Foresti, Marina Gallottini, Bertrand Isidor, Shannon Marchegiani, Fabiana Martins, Laura Mazzanti, Nathalie Roche, Ankur Singh, Cathy Stevens, Kenichi Suga, Martin Zenker, Raoul C Hennekam
Barber-Say syndrome (BSS) and ablepharon-macrostomia syndrome (AMS) are infrequently reported congenital malformation disorders caused by mutations in the TWIST2 gene. Both are characterized by abnormalities in ectoderm-derived structures and cause a very unusual morphology of mainly the face in individuals with otherwise normal cognition and normal physical functioning. We studied the impact that the presence of BSS and AMS has on psychosocial functioning of affected individuals and their families, using their point of view to start with...
June 2017: Molecular Syndromology
https://www.readbyqxmd.com/read/28680619/barber-say-syndrome-a-confirmed-case-of-twist2-gene-mutation
#4
Mulakkan David Yohannan, Jennifer Hilgeman, Katlin Allsbrook
Barber-Say syndrome is a rare disorder characterized by hypertrichosis, redundant skin, and facial dysmorphism. TWIST2 gene mutation previously described in this syndrome was identified in our patient. Genetic testing is recommended in patients presenting with these phenotypic abnormalities, along with their parents, to establish de novo or inherited mutations.
July 2017: Clinical Case Reports
https://www.readbyqxmd.com/read/28664156/ltrs-of-endogenous-retroviruses-as-a-source-of-tbx6-binding-sites
#5
Yukuto Yasuhiko, Yoko Hirabayashi, Ryuichi Ono
Retrotransposons are abundant in mammalian genomes and can modulate the gene expression of surrounding genes by disrupting endogenous binding sites for transcription factors (TFs) or providing novel TFs binding sites within retrotransposon sequences. Here, we show that a (C/T)CACACCT sequence motif in ORR1A, ORR1B, ORR1C, and ORR1D, Long Terminal Repeats (LTRs) of MaLR endogenous retrovirus (ERV), is the direct target of Tbx6, an evolutionary conserved family of T-box TFs. Moreover, by comparing gene expression between control mice (Tbx6 +/-) and Tbx6-deficient mice (Tbx6 -/-), we demonstrate that at least four genes, Twist2, Pitx2, Oscp1, and Nfxl1, are down-regulated with Tbx6 deficiency...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/28658273/a-structural-variant-in-the-5-flanking-region-of-the-twist2-gene-affects-melanocyte-development-in-belted-cattle
#6
Nivedita Awasthi Mishra, Cord Drögemüller, Vidhya Jagannathan, Irene Keller, Daniel Wüthrich, Rémy Bruggmann, Julia Beck, Ekkehard Schütz, Bertram Brenig, Steffi Demmel, Simon Moser, Heidi Signer-Hasler, Aldona Pieńkowska-Schelling, Claude Schelling, Marcos Sande, Ronald Rongen, Stefan Rieder, Robert N Kelsh, Nadia Mercader, Tosso Leeb
Belted cattle have a circular belt of unpigmented hair and skin around their midsection. The belt is inherited as a monogenic autosomal dominant trait. We mapped the causative variant to a 37 kb segment on bovine chromosome 3. Whole genome sequence data of 2 belted and 130 control cattle yielded only one private genetic variant in the critical interval in the two belted animals. The belt-associated variant was a copy number variant (CNV) involving the quadruplication of a 6 kb non-coding sequence located approximately 16 kb upstream of the TWIST2 gene...
2017: PloS One
https://www.readbyqxmd.com/read/28644763/methyltransferase-g9a-regulates-osteogenesis-via-twist-gene-repression
#7
N Higashihori, B Lehnertz, A Sampaio, T M Underhill, F Rossi, J M Richman
Here we investigate the role of epigenetic factors in controlling the timing of cranial neural crest cell differentiation. The gene coding for histone H3 lysine 9 methyltransferase G9A was conditionally deleted in neural crest cells with Wnt1-Cre. The majority of homozygous-null animals survived to birth but thereafter failed to thrive. Phenotypic analysis of postnatal animals revealed that the mutants displayed incomplete ossification and 20% shorter jaws as compared to their wild-type littermates. At E13...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28599281/hif-2%C3%AE-promotes-the-formation-of-vasculogenic-mimicry-in-pancreatic-cancer-by-regulating-the-binding-of-twist1-to-the-ve-cadherin-promoter
#8
Jian Yang, Dong-Ming Zhu, Xiao-Gang Zhou, Ni Yin, Yi Zhang, Zi-Xiang Zhang, De-Chun Li, Jian Zhou
Vasculogenic mimicry (VM) is a blood supply modality that occurs independently of endothelial cell angiogenesis. Hypoxia and the epithelial-mesenchymal transition (EMT) induce VM formation by remodeling the extracellular matrix. Our previous study demonstrated that hypoxia-inducible factor-2 alpha (HIF-2α) promotes the progress of EMT in pancreatic cancer; however, whether HIF-2α promotes VM formation in pancreatic cancer remains unknown. In this study, we investigated HIF-2α expression and VM by immunohistochemistry in 70 pancreatic cancer patients as well as the role of Twist1and Twist2 in HIF-2α-induced VM in vitro and in vivo...
July 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28549095/klf4-plays-an-essential-role-in-corneal-epithelial-homeostasis-by-promoting-epithelial-cell-fate-and-suppressing-epithelial-mesenchymal-transition
#9
Anil Tiwari, Chelsea L Loughner, Sudha Swamynathan, Shivalingappa K Swamynathan
Purpose: The purpose of this study was to test the hypothesis that KLF4 promotes corneal epithelial (CE) cell fate by suppressing the epithelial-mesenchymal transition (EMT), using spatiotemporally regulated CE-specific ablation of Klf4 in Klf4Δ/ΔCE (Klf4LoxP/LoxP/Krt12rtTA/rtTA/Tet-O-Cre) mice. Methods: CE-specific ablation of Klf4 was achieved by feeding Klf4Δ/ΔCE mice with doxycycline chow. The wild-type (WT; normal chow-fed littermates) and the Klf4Δ/ΔCE histology was compared by hematoxylin and eosin-stained sections; EMT marker expression was quantified by quantitative PCR, immunoblots, and immunofluorescent staining; and wound healing rate was measured by CE debridement using Algerbrush...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28397045/celastrol-protects-tgf-%C3%AE-1-induced-endothelial-mesenchymal-transition
#10
Fei Gong, Fang Zhao, Xue-Dong Gan
The endothelial-to-mesenchymal transition (EndMT) in endothelial cells contributes to the development of cardiac fibrosis, ultimately leading to cardiac remodeling. In this study, the effects and molecular mechanisms of celastrol (CEL) on transforming growth factor-β1 (TGF-β1)-induced EndMT in human umbilical vein endothelial (HUVEC-12) cells were investigated. The presented data demonstrated that CEL significantly blocked the morphology change of HUVEC-12 cells induced by TGF-β1 without cell cytotoxicity...
April 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28369379/localized-twist1-and-twist2-basic-domain-substitutions-cause-four-distinct-human-diseases-that-can-be-modeled-in-caenorhabditis-elegans
#11
Sharon Kim, Stephen R F Twigg, Victoria A Scanlon, Aditi Chandra, Tyler J Hansen, Arwa Alsubait, Aimee L Fenwick, Simon J McGowan, Helen Lord, Tracy Lester, Elizabeth Sweeney, Astrid Weber, Helen Cox, Andrew O M Wilkie, Andy Golden, Ann K Corsi
Twist transcription factors, members of the basic helix-loop-helix family, play crucial roles in mesoderm development in all animals. Humans have two paralogous genes, TWIST1 and TWIST2, and mutations in each gene have been identified in specific craniofacial disorders. Here, we describe a new clinical entity, Sweeney-Cox syndrome, associated with distinct de novo amino acid substitutions (p.Glu117Val and p.Glu117Gly) at a highly conserved glutamic acid residue located in the basic DNA binding domain of TWIST1, in two subjects with frontonasal dysplasia and additional malformations...
June 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28350298/oncogenic-braf-disrupts-thyroid-morphogenesis-and-function-via-twist-expression
#12
Viviana Anelli, Jacques A Villefranc, Sagar Chhangawala, Raul Martinez-McFaline, Eleonora Riva, Anvy Nguyen, Akanksha Verma, Rohan Bareja, Zhengming Chen, Theresa Scognamiglio, Olivier Elemento, Yariv Houvras
Thyroid cancer is common, yet the sequence of alterations that promote tumor formation are incompletely understood. Here, we describe a novel model of thyroid carcinoma in zebrafish that reveals temporal changes due to BRAF(V600E). Through the use of real-time in vivo imaging, we observe disruption in thyroid follicle structure that occurs early in thyroid development. Combinatorial treatment using BRAF and MEK inhibitors reversed the developmental effects induced by BRAF(V600E). Adult zebrafish expressing BRAF(V600E) in thyrocytes developed invasive carcinoma...
March 28, 2017: ELife
https://www.readbyqxmd.com/read/28270406/akr1b1-promotes-basal-like-breast-cancer-progression-by-a-positive-feedback-loop-that-activates-the-emt-program
#13
Xuebiao Wu, Xiaoli Li, Qiang Fu, Qianhua Cao, Xingyu Chen, Mengjie Wang, Jie Yu, Jingpei Long, Jun Yao, Huixin Liu, Danping Wang, Ruocen Liao, Chenfang Dong
Basal-like breast cancer (BLBC) is associated with high-grade, distant metastasis and poor prognosis. Elucidating the determinants of aggressiveness in BLBC may facilitate the development of novel interventions for this challenging disease. In this study, we show that aldo-keto reductase 1 member B1 (AKR1B1) overexpression highly correlates with BLBC and predicts poor prognosis in breast cancer patients. Mechanistically, Twist2 transcriptionally induces AKR1B1 expression, leading to nuclear factor κB (NF-κB) activation...
April 3, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28248307/twist-of-fate-for-skeletal-muscle-mesenchymal-cells
#14
Natalya A Goloviznina, Michael Kyba
Skeletal muscles are composed of different types of fibres. Can these be thought of as distinct lineages with specific lineage-restricted progenitors? A provocative study now proposes that mesenchymal cells expressing the transcription factor Twist2 act as myogenic progenitors with selective type IIb fibre-differentiation potential.
March 1, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28218909/a-twist2-dependent-progenitor-cell-contributes-to-adult-skeletal-muscle
#15
Ning Liu, Glynnis A Garry, Stephen Li, Svetlana Bezprozvannaya, Efrain Sanchez-Ortiz, Beibei Chen, John M Shelton, Priscilla Jaichander, Rhonda Bassel-Duby, Eric N Olson
Skeletal muscle possesses remarkable regenerative potential due to satellite cells, an injury-responsive stem cell population located beneath the muscle basal lamina that expresses Pax7. By lineage tracing of progenitor cells expressing the Twist2 (Tw2) transcription factor in mice, we discovered a myogenic lineage that resides outside the basal lamina of adult skeletal muscle. Tw2(+) progenitors are molecularly and anatomically distinct from satellite cells, are highly myogenic in vitro, and can fuse with themselves and with satellite cells...
March 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28208580/twist2-is-upregulated-in-early-stages-of-repair-following-acute-kidney-injury
#16
Elizabeth A Grunz-Borgmann, LaNita A Nichols, Xinhui Wang, Alan R Parrish
The aging kidney is a marked by a number of structural and functional changes, including an increased susceptibility to acute kidney injury (AKI). Previous studies from our laboratory have shown that aging male Fischer 344 rats (24 month) are more susceptible to apoptosis-mediated injury than young counterparts. In the current studies, we examined the initial injury and early recovery phases of mercuric chloride-induced AKI. Interestingly, the aging kidney had decreased serum creatinine compared to young controls 1 day following mercuric chloride injury, but by day 4, serum creatinine was significantly elevated, suggesting that the aging kidney did not recover from injury...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27829009/the-morphogenesis-of-cranial-sutures-in-zebrafish
#17
Jolanta M Topczewska, Ramy A Shoela, Joanna P Tomaszewski, Rupa B Mirmira, Arun K Gosain
Using morphological, histological, and TEM analyses of the cranium, we provide a detailed description of bone and suture growth in zebrafish. Based on expression patterns and localization, we identified osteoblasts at different degrees of maturation. Our data confirm that, unlike in humans, zebrafish cranial sutures maintain lifelong patency to sustain skull growth. The cranial vault develops in a coordinated manner resulting in a structure that protects the brain. The zebrafish cranial roof parallels that of higher vertebrates and contains five major bones: one pair of frontal bones, one pair of parietal bones, and the supraoccipital bone...
2016: PloS One
https://www.readbyqxmd.com/read/27750268/the-twist2-mutation-causes-setleis-syndrome-a-rare-clinical-case-report
#18
Akif Ayaz, Sinem Yalcintepe, Ozge Ozalp Yuregir, Yavuz Sahin, Ahmet Ozer, Metin Eser, Umit Celik
No abstract text is available yet for this article.
April 2017: Clinical Dysmorphology
https://www.readbyqxmd.com/read/27750041/paracrine-il-6-signaling-mediates-the-effects-of-pancreatic-stellate-cells-on-epithelial-mesenchymal-transition-via-stat3-nrf2-pathway-in-pancreatic-cancer-cells
#19
Yuan Seng Wu, Ivy Chung, Won Fen Wong, Atsushi Masamune, Maw Shin Sim, Chung Yeng Looi
BACKGROUND: We previously showed that pancreatic stellate cells (PSC) secreted interleukin (IL)-6 and promoted pancreatic ductal adenocarcinoma (PDAC) cell proliferation via nuclear factor erythroid 2 (Nrf2)-mediated metabolic reprogramming. Epithelial-mesenchymal transition (EMT) is a key process for the metastatic cascade. To study the mechanism of PDAC progression to metastasis, we investigated the role of PSC-secreted IL-6 in activating EMT and the involvement of Nrf2 in this process...
February 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27583933/an-enzyme-and-serum-free-neural-stem-cell-culture-model-for-emt-investigation-suited-for-drug-discovery
#20
Martin H M Sailer, Durga Sarvepalli, Catherine Brégère, Urs Fisch, Marin Guentchev, Michael Weller, Raphael Guzman, Bernhard Bettler, Arkasubhra Ghosh, Gregor Hutter
Epithelial to mesenchymal transition (EMT) describes the process of epithelium transdifferentiating into mesenchyme. EMT is a fundamental process during embryonic development that also commonly occurs in glioblastoma, the most frequent malignant brain tumor. EMT has also been observed in multiple carcinomas outside the brain including breast cancer, lung cancer, colon cancer, gastric cancer. EMT is centrally linked to malignancy by promoting migration, invasion and metastasis formation. The mechanisms of EMT induction are not fully understood...
August 23, 2016: Journal of Visualized Experiments: JoVE
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