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https://www.readbyqxmd.com/read/29457552/reciprocal-regulation-of-yap-taz-by-the-hippo-pathway-and-the-small-gtpase-pathway
#1
Ju-Won Jang, Min-Kyu Kim, Suk-Chul Bae
Yes-associated protein 1 (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) (YAP/TAZ) are transcriptional coactivators that regulate genes involved in proliferation and transformation by interacting with DNA-binding transcription factors. Remarkably, YAP/TAZ are essential for cancer initiation or growth of most solid tumors. Their activation induces cancer stem cell attributes, proliferation, and metastasis. The oncogenic activity of YAP/TAZ is inhibited by the Hippo cascade, an evolutionarily conserved pathway that is governed by two kinases, mammalian Ste20-like kinases 1/2 (MST1/2) and Large tumor suppressor kinase 1/2 (LATS1/2), corresponding to Drosophila's Hippo (Hpo) and Warts (Wts), respectively...
February 18, 2018: Small GTPases
https://www.readbyqxmd.com/read/29455854/pathophysiology-and-management-of-mild-to-moderate-pediatric-atopic-dermatitis
#2
Kammi Yap Sayaseng, Peggy Vernon
Atopic dermatitis (AD), or eczema, is a chronic inflammatory skin condition characterized by relapsing pruritic and dry, scaly lesions. AD affects 10% to 20% of children in the United States and significantly affects the quality of life of patients and their families. Primary care providers (PCPs) are often the first point of contact for the management of AD symptoms. As many as 70% of patients with mild to moderate disease can be managed by a PCP, underscoring the need for these providers to understand basic AD pathophysiology and current standards of care...
March 2018: Journal of Pediatric Health Care
https://www.readbyqxmd.com/read/29453821/trends-and-predictors-of-cesarean-birth-in-singapore-2005-2014-a-population-based-cohort-study
#3
Claudia Chi, Deanette Pang, Izzuddin M Aris, Wei Ting Teo, Sarah Weiling Li, Arijit Biswas, Eu Leong Yong, Yap Seng Chong, Kelvin Tan, Michael S Kramer
BACKGROUND: Rates of cesarean birth have continued to rise in many high-income countries. We examined the temporal trends and predictors of cesarean birth in Singapore. METHODS: Linked hospitalization and Birth Registry data were used to examine all live births to Singaporean citizens and permanent residents between January 1, 2005 and December 31, 2014 (n = 342 932 births). We calculated cesarean rates and age-adjusted average annual percent change (AAPC) in those rates and used sequential multivariable regression modeling to assess the contribution of changes in predictors to the change in cesarean rates over time...
February 17, 2018: Birth
https://www.readbyqxmd.com/read/29452199/establishment-of-the-nasal-microbiota-in-the-first-18-months-of-life-correlation-with-early-onset-rhinitis-and-wheezing
#4
Le Duc Huy Ta, Gaik Chin Yap, Carina Jing Xuan Tay, Alicia Shi Min Lim, Chiung Hui Huang, Collins Wenhan Chu, Paola Florez De Sessions, Lynette P Shek, Anne Goh, Hugo P S Van Bever, Oon Hoe Teoh, Jian Yi Soh, Biju Thomas, Mahesh Babu Ramamurthy, Daniel Y T Goh, Christophe Lay, Shu-E Soh, Yiong Huak Chan, Seang-Mei Saw, Kenneth Kwek, Yap-Seng Chong, Keith M Godfrey, Martin Lloyd Hibberd, Bee Wah Lee
BACKGROUND: The dynamic establishment of the nasal microbiota in early life influences local mucosal immune responses and the susceptibility to childhood respiratory disorders. OBJECTIVE: The aim of this case-control study was to monitor, evaluate and compare the development of the nasal microbiota of infants who developed rhinitis and wheeze in the first 18 months of life with those of healthy controls. METHODS: Anterior nasal swabs of 122 subjects belonging to the GUSTO birth cohort were collected longitudinally over seven time points in the first 18 months of life...
February 13, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29451005/hiv-infection-and-risk-of-postpartum-infection-complications-and-mortality-in-rural-uganda
#5
Lisa M Bebell, Joseph Ngonzi, Mark J Siedner, Winnie R Muyindike, Bosco M Bwana, Laura E Riley, Yap Boum, David R Bangsberg, Ingrid V Bassett
HIV infection may increase risk of postpartum infection and infection-related mortality. We hypothesized that postpartum infection incidence and attributable mortality in Mbarara, Uganda would be higher in HIV-infected than HIV-uninfected women. We performed a prospective cohort study of 4231 women presenting to a regional referral hospital in 2015 for delivery or postpartum care. All febrile or hypothermic women, and a subset of randomly selected normothermic women were followed during hospitalization and with 6-week postpartum phone interviews...
February 16, 2018: AIDS Care
https://www.readbyqxmd.com/read/29450473/elevated-blood-viscosity-and-micro-recirculation-linked-to-coronary-stent-malapposition
#6
Eric Poon, Vikas Thondapu, Umair Hayat, Peter Barlis, Chooi Yap, Po Kuo, Qisen Wang, Jiawei Ma, Shuang Zhu, Stephen Moore, Andrew Ooi
One particular complexity of coronary artery is the natural tapering of the vessel with proximal segments having larger caliber and distal tapering as the vessel get smaller. The natural tapering of a coronary artery often leads to proximal incomplete stent apposition (ISA). ISA alters coronary hemodynamics and creates pathological path to develop complications such as in-stent restenosis, and more worryingly, stent thrombosis. By employing state-of-the-art computer-aided design software, generic stent hoops were virtually deployed in an idealized tapered coronary artery with decreasing malapposition distance...
February 14, 2018: Journal of Biomechanical Engineering
https://www.readbyqxmd.com/read/29449645/egfr-pi3k-pdk1-pathway-regulates-yap-signaling-in-hepatocellular-carcinoma-the-mechanism-and-its-implications-in-targeted-therapy
#7
Hongwei Xia, Xinyu Dai, Huangfei Yu, Sheng Zhou, Zhenghai Fan, Guoqing Wei, Qiulin Tang, Qiyong Gong, Feng Bi
The epidermal growth factor receptor (EGFR) pathway and Hippo signaling play an important role in the carcinogenesis of hepatocellular carcinoma (HCC). However, the crosstalk between these two pathways and its implications in targeted therapy remains unclear. We found that the activated EGFR signaling could bypass RhoA to promote the expression of YAP(Yes-associated protein), the core effector of the Hippo signaling, and its downstream target Cyr61. Further studies indicated that EGFR signaling mainly acted through the PI3K-PDK1 (Phosphoinositide 3-kinase-Phosphoinositide-dependent kinase-1) pathway to activate YAP, but not the AKT and MAPK pathways...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29449057/prognostic-significance-of-human-papilloma-virus-and-p16-expression-in-patients-with-vulvar-squamous-cell-carcinoma-who-received-radiotherapy
#8
M L Yap, G Allo, J Cuartero, M Pintilie, S Kamel-Reid, J Murphy, H Mackay, B Clarke, A Fyles, M Milosevic
AIMS: Human papilloma virus (HPV) has been identified as an aetiological agent in a subset of patients with vulvar squamous cell carcinoma (VSCC). The prognostic role of HPV status in VSCC patients treated with radiotherapy has not yet been determined. We investigated the associations between HPV, p16 and clinical outcome in these women. MATERIALS AND METHODS: Patients undergoing potentially curative radiation treatment for VSCC at a single institution from 2000 to 2009 were retrospectively identified...
February 12, 2018: Clinical Oncology: a Journal of the Royal College of Radiologists
https://www.readbyqxmd.com/read/29444890/effect-of-gestational-diabetes-and-hypertensive-disorders-of-pregnancy-on-postpartum-cardiometabolic-risk
#9
Ling-Jun Li, Izzuddin M Aris, Lin Lin Su, Yap Seng Chong, Tien Yin Wong, Kok Hian Tan, Jie Jin Wang
AIMS: The cumulative effect of gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP) on postpartum cardio-metabolic diseases is equivocal. We aimed to assess the associations of GDM and HDP's individual and synergic contribution to risks of postpartum cardio-metabolic diseases (metabolic syndrome (MetS), abnormal glucose metabolism and hypertension (HTN)). METHODS: Of participants from a Singapore birth cohort, 276 mothers attending the 5-year postpartum visit were included in this study...
February 14, 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29444550/non-invasive-assessment-of-kidney-allograft-fibrosis-with-shear-wave-elastography-a-radiological-pathological-correlation-analysis
#10
Maggie Km Ma, Helen Kw Law, Kin Sun Tse, Kwok Wah Chan, Gary Cw Chan, Desmond Yh Yap, Maggie My Mok, Lorraine Py Kwan, Sydney Cw Tang, Bo Ying Choy, Tak Mao Chan
OBJECTIVES: To evaluate the use of shear wave elastography in assessment of kidney allograft tubulointerstitial fibrosis. METHODS: Shear wave elastography assessment was carried out by two independent operators in kidney transplant recipients who underwent allograft biopsy for clinical indications (i.e. rising creatinine >15% or proteinuria >1 g/day). Allograft biopsies were interpreted by the same pathologist according to the 2013 Banff Classification. RESULTS: A total of 40 elastography scans were carried out (median creatinine 172...
February 14, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29443401/pediatric-intestinal-failure-associated-liver-disease-challenges-in-identifying-clinically-relevant-biomarkers
#11
Kathleen M Gura, Andrew E Mulberg, Paul D Mitchell, John Yap, Clara Y Kim, Minjun Chen, Alexis Potemkin, Mark Puder
BACKGROUND: Intestinal failure-associated liver disease (IFALD) is complex and diagnosed by concurrent use of parenteral nutrition, clinical presentation, and alterations in hepatic biomarkers exclusive of other causes of liver disease. In comparison with individual measures, composite biomarkers may provide a more effective means for assessing disease progression and response to treatment than single parameters. Since IFALD is considered by some to be a type of drug-induced liver injury (DILI), those diagnostic criteria could potentially be used in this population...
February 2018: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/29441408/macronutrient-composition-and-food-groups-associated-with-gestational-weight-gain-the-gusto-study
#12
Jun S Lai, Shu E Soh, See Ling Loy, Marjorelee Colega, Michael S Kramer, Jerry K Y Chan, Thiam Chye Tan, Lynnette P C Shek, Fabian K P Yap, Kok Hian Tan, Keith M Godfrey, Yap Seng Chong, Mary F F Chong
PURPOSE: To examine the associations of energy, macronutrient and food intakes with GWG on 960 pregnant women from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) mother-offspring cohort. METHODS: Dietary intake was assessed at 26-28 weeks' gestation with a 24-hour recall and 3-day food diary. GWG z-scores were calculated from first (4-13 weeks' gestation) and last (30-40 weeks gestation) measured weights; inadequate and excessive GWG were defined using the Institute of Medicine recommendations based on weights between 15 and 35 weeks' gestation...
February 13, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29440237/tension-dependent-regulation-of-mammalian-hippo-signaling-through-limd1
#13
Consuelo Ibar, Elmira Kirichenko, Benjamin Keepers, Edward Enners, Katelyn Fleisch, Kenneth D Irvine
Hippo signaling is regulated by biochemical and biomechanical cues that influence the cytoskeleton, but the mechanisms that mediate this have remained unclear. We show that all three mammalian Ajuba family proteins - AJUBA, LIMD1, and WTIP - exhibit tension-dependent localization to adherens junctions, and that both Lats family proteins, LATS1 and LATS2, exhibit an overlapping tension-dependent junctional localization. This localization of Ajuba and Lats family proteins is also influenced by cell density, and by Rho activation...
February 13, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29440169/oncogenic-kinase-induced-pkm2-tyrosine-105-phosphorylation-converts-non-oncogenic-pkm2-to-a-tumor-promoter-and-induces-cancer-stem-like-cells
#14
Zhifen Zhou, Min Li, Lin Zhang, Hong Zhao, Özgür Şahin, Jing Chen, Jean J Zhao, Zhou Songyang, Dihua Yu
The role of pyruvate kinase M2 isoform (PKM2) in tumor progression has been controversial. Previous studies showed that PKM2 promoted tumor growth in xenograft models; however, depletion of PKM2 in the Brca1-loss-driven mammary tumor mouse model accelerates tumor formation. Since oncogenic kinases are frequently activated in tumors and PKM2 phosphorylation promotes tumor growth, we hypothesized that phosphorylation of PKM2 by activated kinases in tumor cells confers PKM2 oncogenic function, whereas non-phosphorylated PKM2 is non-oncogenic...
February 12, 2018: Cancer Research
https://www.readbyqxmd.com/read/29440144/spon2-promotes-m1-like-macrophage-recruitment-and-inhibits-hepatocellular-carcinoma-metastasis-by-distinct-integrin-rho-gtpase-hippo-pathways
#15
Yan-Li Zhang, Qing Li, Xiao-Mei Yang, Fang Fang, Jun Li, Ya-Hui Wang, Qin Yang, Lei Zhu, Hui-Zhen Nie, Xue-Li Zhang, Ming-Xuan Feng, Shu-Heng Jiang, Guang-Ang Tian, Li-Peng Hu, Ho-Young Lee, Su-Jae Lee, Qiang Xia, Zhi-Gang Zhang
Tumor-associated macrophages (TAM) represent key regulators of the complex interplay between cancer and the immune microenvironment. Matricellular protein SPON2 is essential for recruiting lymphocytes and initiating immune responses. Recent studies have shown that SPON2 has complicated roles in cell migration and tumor progression. Here we report that, in the tumor microenvironment of hepatocellular carcinoma (HCC), SPON2 not only promotes infiltration of M1-like macrophages but also inhibits tumor metastasis...
February 13, 2018: Cancer Research
https://www.readbyqxmd.com/read/29438698/programming-of-schwann-cells-by-lats1-2-taz-yap-signaling-drives-malignant-peripheral-nerve-sheath-tumorigenesis
#16
Lai Man Natalie Wu, Yaqi Deng, Jincheng Wang, Chuntao Zhao, Jiajia Wang, Rohit Rao, Lingli Xu, Wenhao Zhou, Kwangmin Choi, Tilat A Rizvi, Marc Remke, Joshua B Rubin, Randy L Johnson, Thomas J Carroll, Anat O Stemmer-Rachamimov, Jianqiang Wu, Yi Zheng, Mei Xin, Nancy Ratner, Q Richard Lu
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive Schwann cell (SC)-lineage-derived sarcomas. Molecular events driving SC-to-MPNST transformation are incompletely understood. Here, we show that human MPNSTs exhibit elevated HIPPO-TAZ/YAP expression, and that TAZ/YAP hyperactivity in SCs caused by Lats1/2 loss potently induces high-grade nerve-associated tumors with full penetrance. Lats1/2 deficiency reprograms SCs to a cancerous, progenitor-like phenotype and promotes hyperproliferation...
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29438691/hippo-stampede-in-nerve-sheath-tumors
#17
M Laura Feltri, Yannick Poitelon
Current therapies for malignant peripheral nerve sheath tumors (MPNSTs) are ineffective. The study by Wu et al. in this issue of Cancer Cell provides evidence that the HIPPO pathway is overactive in human MPNSTs and that combined modulation of LATS1/2-YAP/TAZ and PDGFR signaling in Schwann cells reduces MPNST growth.
February 12, 2018: Cancer Cell
https://www.readbyqxmd.com/read/29437787/reg%C3%AE-controls-hippo-signaling-and-reciprocal-nf-%C3%AE%C2%BAb-yap-regulation-to-promote-colon-cancer
#18
Xiaotao Li, Qingwei Wang, Xiao Gao, Tong Yu, Lei Yuan, Jie Dai, Weicang Wang, Geng Chen, Chan Jiao, Wang Zhou, Quan Huang, Long Cui, Pei Zhang, Robb E Moses, Jianhua Yang, Fengyuan Chen, Junjiang Fu, Jianru Xiao, Lei Li, Yongyan Dang
PURPOSE: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers closely associated with inflammation and hyperactive growth. We have previously demonstrated a regulatory circuit between the proteasome activator REGγ and NF-kappaB (NF-κB) during colon inflammation, known to be important in the development of colitis-associated cancer as well as sporadic CRC. How the inflammatory microenvironment affects the Hippo pathway during CRC development is largely unknown. EXPERIMENTAL DESIGN: Here, we used REGγ deficient colon cancer cell lines, REGγ knockout mice and human CRC samples to identify the novel molecular mechanism by which REGγ functions as an oncoprotein in the development of colorectal cancer...
February 6, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29436693/yap-regulates-gastric-cancer-survival-and-migration-via-sirt1-mfn2-mitophagy
#19
Hongzhu Yan, Chengmin Qiu, Weiwei Sun, Minmin Gu, Feng Xiao, Jue Zou, Li Zhang
Gastric cancer is the fifth most common cancer worldwide and Hippo-Yap is the novel signaling pathway which plays an important role in gastric cancer tumor development and progression. However, little insight is available to date regarding the specific role of Yes-associated protein (Yap) in gastric cancer. In the present study, we identified the mechanism through which Yap sustains gastric cancer viability and migration. Yap was greatly upregulated in gastric cancer cells and its expression promoted cellular migration and survival...
February 7, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29435056/furin-inhibitor-d6r-suppresses-epithelial-mesenchymal-transition-in-sw1990-and-patu8988-cells-via-the-hippo-yap-signaling-pathway
#20
Meng Zhou, Youli Zhang, Hong Wei, Junbo He, Dawei Wang, Baoding Chen, Jian Zeng, Aihua Gong, Min Xu
Hexa-D-arginine (D6R), an inhibitor of furin, has potential therapeutic applications in different types of human tumor. However, the function of D6R in targeting pancreatic cancer cells remains to be elucidated. In the present study, the proliferation, invasion and migration abilities of SW1990 and PaTu8988 cells were examined using a Cell Counting Kit-8, and Transwell and wound healing assays. Subsequently, the expression of proteins associated with epithelial-mesenchymal transition (EMT) and the Hippo-yes-associated protein (YAP) pathway were detected using western blot analysis...
March 2018: Oncology Letters
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