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Masaru Katoh
β‑catenin/CTNNB1 is an intracellular scaffold protein that interacts with adhesion molecules (E‑cadherin/CDH1, N‑cadherin/CDH2, VE‑cadherin/CDH5 and α‑catenins), transmembrane‑type mucins (MUC1/CD227 and MUC16/CA125), signaling regulators (APC, AXIN1, AXIN2 and NHERF1/EBP50) and epigenetic or transcriptional regulators (BCL9, BCL9L, CREBBP/CBP, EP300/p300, FOXM1, MED12, SMARCA4/BRG1 and TCF/LEF). Gain‑of‑function CTTNB1 mutations are detected in bladder cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, pancreatic cancer, prostate cancer and uterine cancer, whereas loss‑of‑function CTNNB1 mutations are also detected in human cancer...
May 17, 2018: International Journal of Molecular Medicine
Xiao Hu, Kinga Majchrzak, Xikui Liu, Megan M Wyatt, Chauncey Spooner, Jacques Moisan, Weiping Zou, Laura L Carter, Chrystal M Paulos
Adoptive T cell transfer therapy is an FDA-approved treatment for leukemia that relies on the ex vivo expansion and re-infusion of a patient's immune cells, which can be engineered with a chimeric antigen receptor (CAR) for more efficient tumor recognition. Type 17 T cells, controlled transcriptionally by RORγ, have been reported to mediate potent anti-tumor effects superior to those observed with conventionally expanded T cells. Here we demonstrate that addition of a synthetic, small molecule RORγ agonist during ex vivo expansion potentiates the anti-tumor activity of human Th17 and Tc17 cells redirected with a CAR...
May 16, 2018: Cancer Research
Masafumi Seki, Junko Takita
The outcome of treatment-refractory and/or relapsed pediatric T-cell acute lymphoblastic leukemia (T-ALL) is extremely poor, and the genetic basis of these cases remains poorly understood. Here, we report comprehensive profiling of 121 cases of pediatric T-ALL using RNA sequencing and/or targeted capture sequencing through which we identified new recurrent gene fusions involving SPI1 (STMN1-SPI1 and TCF7-SPI1). Cases positive for fusions involving SPI1 (encoding PU.1), which accounted for 3.9% (7/181) of the total examined pediatric T-ALL cases, had uniformly poor overall survival...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Hua Ma, Wenyi Li, Pinduan Bi, Qiang Wang, Jian Li, Bin Yang
BACKGROUND: Mucin plays an essential role in the intrahepatic stone formation, but the mechanism of mucin regulation is unclear. OBJECTIVE: To investigate the potential implication of miR-93 and WNT pathway in the regulation of intrahepatic bile duct mucin expression. METHODS: Thirty patients with or without intrahepatic bile duct stones are involved; Reverse-transcription polymerase chain reaction was performed to evaluate the expression of MUC3, MUC4, MUC5B, MUC5AC mRNA and miR-93 levels...
April 25, 2018: Clinics and Research in Hepatology and Gastroenterology
Thomas J Lynch, Preston J Anderson, Pavana G Rotti, Scott R Tyler, Adrianne K Crooke, Soon H Choi, Daniel T Montoro, Carolyn L Silverman, Weam Shahin, Rui Zhao, Chandler W Jensen-Cody, Andrea Adamcakova-Dodd, T Idil Apak Evans, Weiliang Xie, Yulong Zhang, Hongmei Mou, B Paul Herring, Peter S Thorne, Jayaraj Rajagopal, Charles Yeaman, Kalpaj R Parekh, John F Engelhardt
The mouse trachea is thought to contain two distinct stem cell compartments that contribute to airway repair-basal cells in the surface airway epithelium (SAE) and an unknown submucosal gland (SMG) cell type. Whether a lineage relationship exists between these two stem cell compartments remains unclear. Using lineage tracing of glandular myoepithelial cells (MECs), we demonstrate that MECs can give rise to seven cell types of the SAE and SMGs following severe airway injury. MECs progressively adopted a basal cell phenotype on the SAE and established lasting progenitors capable of further regeneration following reinjury...
May 3, 2018: Cell Stem Cell
Carlos Eduardo Barros Jucá, Leandro Machado Colli, Clarissa Silva Martins, Marina Lanciotti Campanini, Beatriz Paixão, Renata Viana Jucá, Fabiano Pinto Saggioro, Ricardo Santos de Oliveira, Ayrton Custódio Moreira, Hélio Rubens Machado, Luciano Neder, Sonir Rauber Antonini, Margaret de Castro
CTNNB1 mutations and abnormal β-catenin distribution are associated with the pathogenesis of adamantinomatous craniopharyngioma (aCP). We evaluated the expression of the canonical Wnt pathway components in aCPs and its association with CTNNB1 mutations and tumor progression. Tumor samples from 14 aCP patients and normal anterior pituitary samples from eight individuals without pituitary disease were studied. Gene expression of Wnt pathway activator ( WNT4 ), inhibitors ( SFRP1 , DKK3 , AXIN1 , and APC ), transcriptional activator ( TCF7 ), target genes ( MYC , WISP2 , and, CDH1 ), and Wnt modulator ( TP53 ) was evaluated by qPCR...
April 6, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
Daniel T Utzschneider, Arnaud Delpoux, Dominik Wieland, Xin Huang, Chen-Yen Lai, Maike Hofmann, Robert Thimme, Stephen M Hedrick
Immunity following an acutely resolved infection or the long-term equipoise of chronic viral infections often depends on the maintenance of antigen-specific CD8+ T cells, yet the ongoing transcriptional requirements of these cells remain unclear. We show that active and continuous programming by FOXO1 is required for the functional maintenance of a memory population. Upon Foxo1 deletion following resolution of an infection, memory cells rapidly lost their characteristic gene expression, gradually declined in number, and were impaired in self-renewal...
March 27, 2018: Cell Reports
Izumi Oda-Ishii, Tetsuya Abe, Yutaka Satou
In animal embryos, transcription is repressed for a definite period of time after fertilization. In the embryo of the ascidian, Ciona intestinalis (type A; or Ciona robusta), transcription of regulatory genes is repressed before the 8- or 16-cell stages. This initial transcriptional quiescence is important to enable the establishment of initial differential gene expression patterns along the animal-vegetal axis by maternal factors, because the third cell division separates the animal and vegetal hemispheres into distinct blastomeres...
May 1, 2018: Developmental Biology
Fu-Shu Jin, Hong-Mei Wang, Xiao-Yan Song
Long non-coding RNA (lnc)TCF7 has been reported to promote the self‑renewal of human cancer stem cells, and enhance the aggressiveness of human non‑small cell lung cancer and hepatocellular carcinoma cells. However, the effect of lncTCF7 on colorectal cancer (CRC) tumorigenesis and progression is currently unclear. In the present study, reverse transcription‑quantitative polymerase chain reaction results demonstrated that lncTCF7 expression was higher in CRC tissues compared with adjacent normal tissues and was significantly associated with tumor size, differentiation degree, tumor‑node‑metastasis grade, lymph node metastasis and invasion depth...
May 2018: Molecular Medicine Reports
Maxime Danilo, Vijaykumar Chennupati, Joana Gomes Silva, Stefanie Siegert, Werner Held
The formation of central CD8 T cell memory in response to infection depends on the transcription factor Tcf1 (Tcf7). Tcf1 is expressed at high levels in naive CD8 T cells but downregulated in most CD8 T cells during effector differentiation. The relevance of Tcf1 downregulation for effector differentiation and the signals controlling Tcf1 expression have not been elucidated. Here, we show that systemic inflammatory signals downregulated Tcf1 in CD8 T cells during dendritic cell vaccination and bacterial infections...
February 20, 2018: Cell Reports
Lufang Wang, Yanyan Zhao, Qiong Wu, Yifu Guan, Xin Wu
Concurrent radio chemotherapy treatment prolongs the survival rate of patients with advanced cervical cancer; however, it has adverse side‑effects. β‑elemene, an active component of the traditional Chinese medicinal herb Curcuma zedoaria, is a promising alternative therapeutic drug for the treatment of advanced cervical cancer. The aim of the present study was to investigate the antitumor effects of β‑elemene in human cervical cancer SiHa cells and to determine its underlying therapeutic molecular mechanisms...
March 2018: Molecular Medicine Reports
Ricardo Raúl Cevallos, Griselda Rodríguez-Martínez, Karlen Gazarian
Somatic cell reprogramming is a biphasic phenomenon that goes through a mesenchymal-to-epithelial transition, called initiation phase, followed by a maturation phase wherein reprogramming cells acquire pluripotency. Here, we show that these phases display a differential response to Wnt signaling activation. Wnt signaling increases colony formation by promoting cellular epithelialization during the initiation phase in a TCF7-dependent manner. However, during maturation phase, it is also responsible for inducing mesendodermal differentiation, which is negatively regulated by TCF7L1...
January 23, 2018: Stem Cells
Qian Li, Yue Hua, Yilin Yang, Xinyu He, Wei Zhu, Jiyong Wang, Xiaoqing Gan
Osteocalcin has recently been shown to regulate energy homeostasis through multiple pathways. Adipose tissue is a main organ of energy metabolism, and administration of recombinant osteocalcin in mice promoted energy consumption, thus counteracting obesity and glucose intolerance. The regulation of osteocalcin in islet β cells has been well documented; however, it is unknown whether osteocalcin can also act on adipocytes, and if does, how it functions. Here, we provided evidence to demonstrate a specific role for osteocalcin in brown adipocyte thermogenesis...
January 22, 2018: Molecular and Cellular Biology
Tengyu Li, Jing Zhu, Xin Wang, Guowei Chen, Lie Sun, Shuai Zuo, Junling Zhang, Shanwen Chen, Ju Ma, Zihao Yao, Youwen Zheng, Zeyang Chen, Yucun Liu, Pengyuan Wang
Long non-coding RNA (Lnc)TCF7 is a novel lncRNA that is involved in tumorigenesis. Previous studies have revealed that lncTCF7 serves an essential role in maintaining cancer stem cell self-renewal; however, the functions of lncTCF7 in colorectal cancer (CRC) remain unknown. Therefore, the present study aimed to investigate the role of lncTCF7 in CRC. LncTCF7 was upregulated in 52/58 CRC tissues, and its expression correlated with tumor size, lymph metastasis and tumor-node-metastasis stage in CRC. Knocking down lncTCF7 in colon cancer cell lines decreased cell proliferation, migration and invasion, while lncTCF7 overexpression showed opposite changes...
December 2017: Oncology Letters
Thaís Dos Santos Fontes Pereira, Marina Gonçalves Diniz, Josiane Alves França, Rennan Garcias Moreira, Grazielle Helena Ferreira de Menezes, Sílvia Ferreira de Sousa, Wagner Henriques de Castro, Carolina Cavaliéri Gomes, Ricardo Santiago Gomez
OBJECTIVE: The molecular pathogenesis of cemento ossifying fibroma (COF) is unclear. The purpose of this study was to investigate mutations in 50 oncogenes and tumor suppressor genes, including APC and CTNNB1, in which mutations in COF have been previously reported. In addition, we assessed the transcriptional levels of the Wnt/β-catenin pathway genes in COF. STUDY DESIGN: We used a quantitative polymerase chain reaction array to evaluate the transcriptional levels of 44 Wnt/β-catenin pathway genes in 6 COF samples, in comparison with 6 samples of healthy jaws...
February 2018: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Joshua N Farr, Megan M Weivoda, Kristy M Nicks, Daniel G Fraser, Brittany A Negley, Jennifer L Onken, Brianne S Thicke, Ming Ruan, Hong Liu, Douglas Forrest, John R Hawse, Sundeep Khosla, David G Monroe
There is a clinical need to identify new molecular targets for the treatment of osteoporosis, particularly those that simultaneously inhibit bone resorption while stimulating bone formation. We have previously shown in overexpression studies that retinoic acid receptor-related orphan receptor β (Rorβ) suppresses in vitro osteoblast differentiation. In addition, the expression of Rorβ is markedly increased in bone marrow-derived mesenchymal stromal cells with aging in both mice and humans. Here we establish a critical role for Rorβ in regulating bone metabolism using a combination of in vitro and in vivo studies...
December 5, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Hongbo Zhang, Rui Ren, Juan Du, Tingli Sun, Ping Wang, Ping Kang
BACKGROUND/AIMS: Injury of podocytes plays an important role in decline of glomerular filtration and proteinuria. It is well-known that proteinuria is associated with numerous chronic kidney diseases (CKD). However, the underlying mechanism of podocyte injury remains unclear. METHODS: We used reverse transcription-quantitative PCR (RT-qPCR) to compare the expression level of the ALL1-fused from the chromosome 1q (AF1q) gene in mice and mouse podocytes (MPC5) with or without Adriamycin (ADR) treatment...
2017: Kidney & Blood Pressure Research
Jacob S Bowers, Kinga Majchrzak, Michelle H Nelson, Bulent Arman Aksoy, Megan M Wyatt, Aubrey S Smith, Stefanie R Bailey, Lillian R Neal, Jeffrey E Hammerbacher, Chrystal M Paulos
Phosphatidylinositol-3-kinase p110δ (PI3Kδ) inhibition by Idelalisib (CAL-101) in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells. Yet, little is known about the direct impact of PI3Kδ blockade on effector T cells from CAL-101 therapy. Herein, we demonstrate a direct effect of p110δ inactivation via CAL-101 on murine and human CD8+ T cells that promotes a strong undifferentiated phenotype (elevated CD62L/CCR7, CD127, and Tcf7)...
2017: Frontiers in Immunology
Arnaud Delpoux, Chen-Yen Lai, Stephen M Hedrick, Andrew L Doedens
The factors and steps controlling postinfection CD8(+) T cell terminal effector versus memory differentiation are incompletely understood. Whereas we found that naive TCF7 (alias "Tcf-1") expression is FOXO1 independent, early postinfection we report bimodal, FOXO1-dependent expression of the memory-essential transcription factor TCF7 in pathogen-specific CD8(+) T cells. We determined the early postinfection TCF7(high) population is marked by low TIM3 expression and bears memory signature hallmarks before the appearance of established memory precursor marker CD127 (IL-7R)...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
Lifan Xu, Qizhao Huang, Haoqiang Wang, Yaxing Hao, Qiang Bai, Jianjun Hu, Yiding Li, Pengcheng Wang, Xiangyu Chen, Ran He, Bingshou Li, Xia Yang, Tingting Zhao, Yanyan Zhang, Yifei Wang, Juanjuan Ou, Houjie Liang, Yuzhang Wu, Xinyuan Zhou, Lilin Ye
Follicular regulatory T (Tfr) cells differentiate from conventional regulatory T (Treg) cells and suppress excessive germinal center (GC) responses by acting on both GC B cells and T follicular helper (Tfh) cells. Here, we examined the impact of mTOR, a serine/threonine protein kinase that senses and integrates diverse environmental cues, on the differentiation and functional competency of Tfr cells in response to protein immunization or viral infection. By genetically deleting Rptor or Rictor, essential components for mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), respectively, we found that mTORC1 but not mTORC2 is essential for Tfr differentiation...
September 19, 2017: Immunity
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