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Yifan Wang
The aim of the current study was to investigate and discuss the function of T-box 3 ( TBX3 ) gene expression in the pathogenesis of renal carcinoma. The carcinoma, adjacent and normal renal tissues of 210 patients with renal carcinoma who presented to The Central Hospital of Wuhan, Tongji Medical College from March, 2006 to March, 2012 were collected to extract total RNAs. The total RNAs were reverse-transcribed into complementary DNA (cDNA), and quantitative polymerase chain reaction (qPCR) was applied to detect the expression of TBX3 gene in these tissues, followed by its association with the prognosis of renal carcinoma as well as clinical features...
April 2018: Oncology Letters
Xiaomeng Li, Xianhui Ruan, Peitao Zhang, Yang Yu, Ming Gao, Shukai Yuan, Zewei Zhao, Jie Yang, Li Zhao
The T-box transcription factor TBX3 has been implicated in the patterning and differentiation of a number of tissues during embryonic development, and is overexpressed in a variety of cancers; however, the precise function of TBX3 in papillary thyroid carcinoma (PTC) development remains to be determined. In the current study, we report downregulation of TBX3 in PTC cells delays the G1/S-phase transition, decreases cell growth in vitro, and inhibits tumor formation in vivo. We identified p57KIP2 as a novel downstream target that serves as the key mediator of TBX3's control over PTC cell proliferation...
March 7, 2018: Oncogene
Lay Teng Ang, Antson Kiat Yee Tan, Matias I Autio, Su Hua Goh, Siew Hua Choo, Kian Leong Lee, Jianmin Tan, Bangfen Pan, Jane Jia Hui Lee, Jen Jen Lum, Christina Ying Yan Lim, Isabelle Kai Xin Yeo, Chloe Jin Yee Wong, Min Liu, Jueween Ling Li Oh, Cheryl Pei Lynn Chia, Chet Hong Loh, Angela Chen, Qingfeng Chen, Irving L Weissman, Kyle M Loh, Bing Lim
How are closely related lineages, including liver, pancreas, and intestines, diversified from a common endodermal origin? Here, we apply principles learned from developmental biology to rapidly reconstitute liver progenitors from human pluripotent stem cells (hPSCs). Mapping the formation of multiple endodermal lineages revealed how alternate endodermal fates (e.g., pancreas and intestines) are restricted during liver commitment. Human liver fate was encoded by combinations of inductive and repressive extracellular signals at different doses...
February 20, 2018: Cell Reports
Kim E M van Kessel, Kirstin A van der Keur, Lars Dyrskjøt, Ferran Algaba, Naeromy Y C Welvaart, Willemien Beukers, Ulrika Segersten, Bastian Keck, Tobias Maurer, Tatjana Simic, Marcus Horstmann, Marc-Oliver Grimm, Gregers G Hermann, Karin Mogensen, Arndt Hartmann, Niels Harving, Astrid C Petersen, Jørgen B Jensen, Kerstin Junker, Joost L Boormans, Francisco X Real, Núria Malats, Per-Uno Malmström, Torben F Ørntoft, Ellen C Zwarthoff
Purpose: The European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathologic parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC. Experimental Design: We prospectively included 1,239 patients in follow-up for NMIBC in six European countries. Fresh-frozen tumor samples were analyzed for GATA2, TBX2, TBX3 , and ZIC4 methylation and FGFR3, TERT, PIK3CA , and RAS mutation status...
January 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Amy E McCart Reed, Jamie R Kutasovic, Katia Nones, Jodi M Saunus, Leonard Da Silva, Felicity Newell, Stephen Kazakoff, Lewis Melville, Janani Jayanthan, Ana Cristina Vargas, Lynne E Reid, Jonathan Beesley, Xiao Qing Chen, Anne Marie Patch, D David Clouston, Alan Porter, Elizabeth Evans, John V Pearson, Georgia Chenevix-Trench, Margaret C Cummings, Nic Waddell, Sunil R Lakhani, Peter T Simpson
Mixed ductal-lobular carcinomas (MDL) display both ductal and lobular morphology, and are an archetypal example of intra-tumour morphological heterogeneity. The mechanisms underlying coexistence of these different morphologic entities are poorly understood, although theories include that these components either represent 'collision' of independent tumours or evolve from a common ancestor. We performed comprehensive clinico-pathological analysis of a cohort of 82 MDLs and found: i) MDLs more frequently co-exist with ductal carcinoma in situ (DCIS) than lobular carcinoma in situ (LCIS); ii) the E-cadherin-catenin complex was normal in the ductal component in 77...
January 18, 2018: Journal of Pathology
Xianguang Feng, Wenhuan Yao, Zengzhen Zhang, Fangshui Yuan, Li Liang, Jingqiang Zhou, Shuang Liu, Jiqing Song
Tbx3, a member of the T-box family of transcription factors, contribute directly to tumor formation, migration and invasion. However, the role of Tbx3 in the metastasis of HCC remains unclear. In the present study, Tbx3 expression was detected in HCC tissues and cells by Western blot, and then the expression of Tbx3 was regulated by siRNAs or lentivirus-mediated vectors. Here, we found that the Tbx3 protein expression increased in HCC tissues and cell lines. Tbx3 expression was positively associated with multiple tumor nodes, venous infiltration and advanced TNM tumor stage...
January 2, 2018: Oncology Research
Ningning He, Xiaoniao Chen, Dan Wang, Ke Xu, Lingling Wu, Yuanyuan Liu, Hongyan Tao, Qinjun Zhao, Xiaocang Cao, Yuhao Li, Na Liu, Xin Qi, Zhongchao Han, Deling Kong, Jun Yang, Zongjin Li
With the abilities of self-renewal and differentiation, embryonic stem (ES) cells provide an unlimited source for stem cell-based therapeutics. However, the maintenance of ES cells with mouse embryonic fibroblasts (MEFs) can limit the clinical translation of ES cells. In the present study, we synthesized a fusion protein of the immunoglobulin G (IgG) fragment crystallizable region and vascular endothelial cadherin (VE-cadherin) extracellular domain (VE-cad-Fc) as a substrate for mouse ES cell culture, and we hypothesized that VE-cadherin could enhance the pluripotency and self-renewal of ES cells...
December 16, 2017: Biomaterials
Zhiheng Li, Xiaolu Li, Lixiao Xu, Yanfang Tao, Chun Yang, Xiaolan Chen, Fang Fang, Yi Wu, Xin Ding, He Zhao, Mei Li, Guanghui Qian, Yunyun Xu, Junli Ren, Weiwei Du, Jian Wang, Jun Lu, Shaoyan Hu, Jian Pan
Neuroblastoma is the most common extracranial solid childhood tumor. Despite the availability of advanced multimodal therapy, high-risk patients still have low survival rates. p21-activated kinase 4 (PAK4) has been shown to regulate many cellular processes in cancer cells, including migration, polarization and proliferation. However, the role of PAK4 in neuroblastoma remains unclear. In the present study, we demonstrated that PAK4 was overexpressed in neuroblastoma tissues and was correlated with tumor malignance and prognosis...
September 22, 2017: Oncology Reports
Patrick A Schweizer, Fabrice F Darche, Nina D Ullrich, Pascal Geschwill, Boris Greber, Rasmus Rivinius, Claudia Seyler, Karin Müller-Decker, Andreas Draguhn, Jochen Utikal, Michael Koenen, Hugo A Katus, Dierk Thomas
BACKGROUND: Human induced pluripotent stem cells (hiPSC) harbor the potential to differentiate into diverse cardiac cell types. Previous experimental efforts were primarily directed at the generation of hiPSC-derived cells with ventricular cardiomyocyte characteristics. Aiming at a straightforward approach for pacemaker cell modeling and replacement, we sought to selectively differentiate cells with nodal-type properties. METHODS: hiPSC were differentiated into spontaneously beating clusters by co-culturing with visceral endoderm-like cells in a serum-free medium...
October 16, 2017: Stem Cell Research & Therapy
Francesca Forzano, Patricia A Foley, Morgan R Keane, Caroline E Brain, Gill D Smith, Robert W Yates, Drew Ellershaw, Alistair D Calder, Richard H Scott
No abstract text is available yet for this article.
January 2018: Clinical Dysmorphology
Rebecca Vicente-Steijn, Tim P Kelder, Leon G Tertoolen, Lambertus J Wisse, Daniël A Pijnappels, Robert E Poelmann, Martin J Schalij, Marco C deRuiter, Adriana C Gittenberger-de Groot, Monique R M Jongbloed
Aims: RHOA-ROCK signalling regulates cell migration, proliferation, differentiation, and transcription. RHOA is expressed in the developing cardiac conduction system in chicken and mice. In early development, the entire sinus venosus myocardium, including both the transient left-sided and the definitive sinoatrial node (SAN), has pacemaker potential. Later, pacemaker potential is restricted to the right-sided SAN. Disruption of RHOA expression in adult mice causes arrhythmias including bradycardia and atrial fibrillation, the mechanism of which is unknown but presumed to affect the SAN...
August 1, 2017: Cardiovascular Research
Ryo Ichijo, Hiroki Kobayashi, Saori Yoneda, Yui Iizuka, Hirokazu Kubo, Shigeru Matsumura, Satsuki Kitano, Hitoshi Miyachi, Tetsuya Honda, Fumiko Toyoshima
The skin surface area varies flexibly in response to body shape changes. Skin homeostasis is maintained by stem cells residing in the basal layer of the interfollicular epidermis. However, how the interfollicular epidermal stem cells response to physiological body shape changes remains elusive. Here, we identify a highly proliferative interfollicular epidermal basal cell population in the rapidly expanding abdominal skin of pregnant mice. These cells express Tbx3 that is necessary for their propagation to drive skin expansion...
September 11, 2017: Nature Communications
Nuria Moreno-Marín, Eva Barrasa, Antonio Morales-Hernández, Beroé Paniagua, Gerardo Blanco-Fernández, Jaime M Merino, Pedro M Fernández-Salguero
The aryl hydrocarbon receptor (AhR) has roles in cell proliferation, differentiation and organ homeostasis, including the liver. AhR depletion induces undifferentiation and pluripotency in normal and transformed cells. Here, AhR-null mice (AhR-/-) were used to explore whether AhR controls liver regeneration and carcinogenesis by restricting the expansion of stem-like cells and the expression of pluripotency genes. Short-term CCl4 liver damage was earlier and more efficiently repaired in AhR-/- than in AhR+/+ mice...
September 5, 2017: Scientific Reports
Qingqing Wei, Liang Zhong, Shaopeng Zhang, Haiyuan Mu, Jinzhu Xiang, Liang Yue, Yunping Dai, Jianyong Han
Preimplantation embryos undergo zygotic genome activation and lineage specification resulting in three distinct cell types in the late blastocyst. The molecular mechanisms underlying this progress are largely unknown in bovines. Here, we sought to analyze an extensive set of regulators at the single-cell level to define the events involved in the development of the bovine blastocyst. Using a quantitative microfluidics approach in single cells, we analyzed mRNA levels of 96 genes known to function in early embryonic development and maintenance of stem cell pluripotency in parallel in 384 individual cells from bovine preimplantation embryos...
July 1, 2017: Biology of Reproduction
Jade Peres, Eliza M Kwesi-Maliepaard, Florian Rambow, Lionel Larue, Sharon Prince
The transcription factor, TBX3, is a key driver of malignant melanoma and any drug that impacts its expression is likely to have an impact on the treatment of this highly aggressive and treatment resistant cancer. Replacement of miRNAs that target oncogenes has gained much attention as a therapy because it is anticipated to be effective with little side-effects since miRNAs are naturally occurring and often target large set of genes in the same oncogenic pathway. Here we show that miR-137 levels correlate inversely with TBX3 mRNA levels in a panel of melanoma cell lines and in a cohort of patients with primary melanoma...
October 1, 2017: Cancer Letters
Bjarke Jensen, Signe Vesterskov, Bastiaan J Boukens, Jan M Nielsen, Antoon F M Moorman, Vincent M Christoffels, Tobias Wang
Mammals evolved from reptile-like ancestors, and while the mammalian heart is driven by a distinct sinus node, a sinus node is not apparent in reptiles. We characterized the myocardial systemic venous pole, the sinus venosus, in reptiles to identify the dominant pacemaker and to assess whether the sinus venosus remodels and adopts an atrium-like phenotype as observed in mammals. Anolis lizards had an extensive sinus venosus of myocardium expressing Tbx18. A small sub-population of cells encircling the sinuatrial junction expressed Isl1, Bmp2, Tbx3, and Hcn4, homologues of genes marking the mammalian sinus node...
July 27, 2017: Scientific Reports
Yun Qiao, Catherine Lipovsky, Stephanie Hicks, Somya Bhatnagar, Gang Li, Aditi Khandekar, Robert Guzy, Kel Vin Woo, Colin G Nichols, Igor R Efimov, Stacey Rentschler
RATIONALE: Notch signaling programs cardiac conduction during development, and in the adult ventricle, injury-induced Notch reactivation initiates global transcriptional and epigenetic changes. OBJECTIVE: To determine whether Notch reactivation may stably alter atrial ion channel gene expression and arrhythmia inducibility. METHODS AND RESULTS: To model an injury response and determine the effects of Notch signaling on atrial electrophysiology, we transiently activate Notch signaling within adult myocardium using a doxycycline-inducible genetic system (inducible Notch intracellular domain [iNICD])...
August 18, 2017: Circulation Research
Tarryn Willmer, Aretha Cooper, Jade Peres, Rehana Omar, Sharon Prince
T-box factors comprise an archaic family of evolutionary conserved transcription factors that regulate patterns of gene expression essential for embryonic development. The T-box transcription factor 3 (TBX3), a member of this family, is expressed in several tissues and plays critical roles in, among other structures, the heart, mammary gland and limbs and haploinsufficiency of the human TBX3 gene is the genetic basis for the autosomal dominant disorder, ulnar-mammary syndrome. Overexpression of TBX3 on the other hand has been linked to several cancers including melanoma, breast, pancreatic, liver, lung, head and neck, ovarian, bladder carcinomas and a number of sarcoma subtypes...
June 4, 2017: Bioscience Trends
Naoya Fujino, Hiroshi Kubo, Rose A Maciewicz
Loss of epithelial barrier integrity is implicated in a number of human lung diseases. However, the molecular pathways underlying this process are poorly understood. In a phenotypic screen, we identified Axl kinase as a negative regulator of epithelial phenotype and function. Furthermore, suppression of Axl activity by a small molecule kinase inhibitor or downregulation of Axl expression by small interfering RNA led to: (1) the increase in epithelial surfactant protein expression; (2) a cell morphology transition from front-rear polarity to cuboidal shape; (3) the cytoskeletal re-organization resulting in decreased cell mobility; and (4) the acquisition of epithelial junctions...
September 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
Yueming Wu, Jiang Feng, Weiwei Hu, Yawei Zhang
T-box 3 (Tbx3), a member of the T-box transcription factor family, serves a crucial role in embryonic development and cancer progression. Previous studies have demonstrated the clinical significance of Tbx3 in numerous types of cancer. However, the expression level and pathological function of Tbx3 in non-small cell lung cancer (NSCLC) are unknown. To the best of our knowledge, the present study provided the first evidence demonstrating the clinicopathological significance of Tbx3 in NSCLC. Tbx3 was revealed to be overexpressed in NSCLC cell lines and tissues obtained from patients with NSCLC by reverse transcription-quantitative polymerase chain reaction and western blot analysis...
May 2017: Oncology Letters
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