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https://www.readbyqxmd.com/read/28424219/down-regulation-of-rbo-pi4kiii%C3%AE-facilitates-a%C3%AE-42-secretion-and-ameliorates-neural-deficits-in-a%C3%AE-42-expressing-drosophila
#1
Xiao Zhang, Wen-An Wang, Li-Xiang Jiang, Hai-Yan Liu, Bao-Zhu Zhang, Nastasia Lim, Qing-Yi Li, Fu-De Huang
Phosphoinositides and their metabolizing enzymes are involved in Aβ42 metabolism and Alzheimer's disease (AD) pathogenesis. In yeast and mammals, Eighty-five requiring 3 (EFR3), whose Drosophila homolog is Rolling Blackout (RBO), forms a plasma membrane-localized protein complex with phosphatidylinositol-4-kinase type IIIα(PI4KIIIα) and a scaffold protein to tightly control the level of plasmalemmal phosphatidylinositol-4-phosphate (PI4P). Here, we report that RBO binds to Drosophila PI4KIIIα, and that in an Aβ42-expressing Drosophila model, separate genetic reduction of PI4KIIIα and RBO, or pharmacological inhibition of PI4KIIIα ameliorated synaptic transmission deficit, climbing ability decline, and premature death, and reduced neuronal accumulation of Aβ42 Moreover, we found that RBO-PI4KIIIa downregulation increased neuronal Aβ42 release, and that PI4P facilitated the assembly or oligomerization of Aβ42 in/on liposomes...
April 19, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28419723/characteristics-and-outcomes-of-alk-non-small-cell-lung-cancer-patients-in-korea
#2
Sung Hee Lim, Kyung Ah Yoh, Jong Seok Lee, Myung-Ju Ahn, Yu Jung Kim, Se Hyun Kim, Jie Zhang, Dony Patel, Elyse Swallow, Andrew Kageleiry, Philip Galebach, Dongyeol Lee, Karen Stein, Ravi Degun, Keunchil Park
AIM: This study aimed to describe characteristics, treatment patterns and survival among Korean patients diagnosed with locally advanced or metastatic anaplastic lymphoma kinase (ALK)+ non-small cell lung cancer (NSCLC). METHODS: A retrospective patient chart review was conducted in major cancer centers in Korea in 2014-2015. Participating physicians reviewed patient charts and reported characteristics, treatment patterns, clinician-defined progression-free survival (PFS) and overall survival (OS) of ALK+ locally advanced or metastatic NSCLC patients...
April 16, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28418920/complementary-utility-of-targeted-next-generation-sequencing-and-immunohistochemistry-panels-as-a-screening-platform-to-select-targeted-therapy-for-advanced-gastric-cancer
#3
Hyo Song Kim, Hanna Lee, Su-Jin Shin, Seung-Hoon Beom, Minkyu Jung, Sujin Bae, Eun Young Lee, Kyu Hyun Park, Yoon Young Choi, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Jun Chul Park, Sung Kwan Shin, Sang Kil Lee, Yong Chan Lee, Woong Sub Koom, Joon Seok Lim, Hyun Cheol Chung, Sung Hoon Noh, Sun Young Rha, Hyunki Kim, Soonmyung Paik
We tested the clinical utility of combined profiling of Ion Torrent PGM based next-generation sequencing (NGS) and immunohistochemistry (IHC) for assignment to molecularly targeted therapies. A consecutive cohort of 93 patients with advanced/metastatic GC who underwent palliative chemotherapy between March and December 2015 were prospectively enrolled. Formalin fixed paraffin embedded tumor biopsy specimens were subjected to a 10 GC panels [Epstein Barr virus encoding RNA in-situ hybridization, IHC for mismatch repair proteins (MMR; MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (HER2, EGFR, and MET), PTEN, and p53 protein], and a commercial targeted NGS panel of 52 genes (Oncomine Focus Assay)...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415597/phosphorylation-of-androgen-receptors-at-serine-515-is-a-potential-prognostic-marker-for-triple-negative-breast-cancer
#4
Antonia K Roseweir, Pamela McCall, Alison Scott, Benjamin Liew, Zhi Lim, Elizabeth A Mallon, Joanne Edwards
1.7 million cases of breast cancer are diagnosed every year with 522,000 deaths. Molecular classifications of breast cancer have resulted in improved treatments. However, treatments for triple negative breast cancer (TNBC) are lacking. Analysis of molecular targets for TNBC is a priority. One potential candidate is androgen receptor (AR) phosphorylation. This study assessed the role of AR phosphorylation at ser81/ser515 and their two upstream effectors, cyclin-dependent kinase 1 (pCDK1) and extracellular-regulated kinase 1/2 (pERK1/2) in 332 ductal breast cancer patients by immunohistochemistry...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414323/pyrimidine-tract-binding-protein-1-mediates-pyruvate-kinase-m2-dependent-phosphorylation-of-signal-transducer-and-activator-of-transcription-3-and-oncogenesis-in-anaplastic-large-cell-lymphoma
#5
Steven R Hwang, Carlos Murga-Zamalloa, Noah Brown, Johnvesly Basappa, Scott Rp McDonnell, Veronica Mendoza-Reinoso, Venkatesha Basrur, Ryan Wilcox, Kojo Elenitoba-Johnson, Megan S Lim
PKM2 (pyruvate kinase M2), a critical regulator of glycolysis, is phosphorylated by numerous growth factor receptors and oncogenic tyrosine kinases including NPM-ALK which is expressed in a subset of aggressive T-cell non-Hodgkin lymphomas known as anaplastic large cell lymphoma, ALK-positive. Our previous work demonstrated that phosphorylation of Y105-PKM2 by NPM-ALK regulates a major metabolic shift to promote lymphomagenesis. In addition to its role in metabolism, recent studies have shown that PKM2 promotes oncogenesis by phosphorylating nuclear STAT3 (signal transducer and activator of transcription 3) and regulating transcription of genes involved in cell survival and proliferation...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28414311/a-self-sustained-loop-of-inflammation-driven-inhibition-of-beige-adipogenesis-in-obesity
#6
Kyoung-Jin Chung, Antonios Chatzigeorgiou, Matina Economopoulou, Ruben Garcia-Martin, Vasileia I Alexaki, Ioannis Mitroulis, Marina Nati, Janine Gebler, Tjalf Ziemssen, Susan E Goelz, Julia Phieler, Jong-Hyung Lim, Katia P Karalis, Thalia Papayannopoulou, Matthias Blüher, George Hajishengallis, Triantafyllos Chavakis
In obesity, inflammation of white adipose tissue (AT) is associated with diminished generation of beige adipocytes ('beige adipogenesis'), a thermogenic and energy-dissipating function mediated by beige adipocytes that express the uncoupling protein UCP1. Here we delineated an inflammation-driven inhibitory mechanism of beige adipogenesis in obesity that required direct adhesive interactions between macrophages and adipocytes mediated by the integrin α4 and its counter-receptor VCAM-1, respectively; expression of the latter was upregulated in obesity...
April 17, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28413329/protective-effect-of-ginsenoside-rh3-against-anticancer-drug-induced-apoptosis-in-llc-pk1-kidney-cells
#7
Hye Lim Lee, Ki Sung Kang
BACKGROUND: Ginsenosides are active components of Panax ginseng that exert various health benefits including kidney protection effect. The medicinal activity of ginsenosides can be enhanced by modulating their stereospecificity by heat processing. Ginsenosides Rk2 and Rh3 represent positional isomers of the double bond at C-20(21) or C-20(22). METHODS: The present study investigated the kidney-protective effects of ginsenosides Rk2 and Rh3 against cisplatin, a platinum based anticancer drug, induced apoptotic damage in renal proximal LLC-PK1 cells...
April 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28412249/the-t-lak-cell-originated-protein-kinase-signal-pathway-promotes-colorectal-cancer-metastasis
#8
Tatyana A Zykova, Feng Zhu, Lei Wang, Haitao Li, Ruihua Bai, Do Young Lim, Ke Yao, Ann M Bode, Zigang Dong
Approximately 90% of all cancer deaths arise from the metastatic dissemination of primary tumors. Metastasis is the most lethal attribute of colorectal cancer. New data regarding the molecules contributing to the metastatic phenotype, the pathways they control and the genes they regulate are very important for understanding the processes of metastasis prognosis and prevention in the clinic. The purpose of this study was to investigate the role of T-LAK cell-originated protein kinase (TOPK) in the promotion of colorectal cancer metastasis...
April 6, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28395342/stimulatory-effects-of-fibroblast-growth-factor-2-on-proliferation-and-migration-of-uterine-luminal-epithelial-cells-during-early-pregnancy%C3%A2-%C3%A2
#9
Whasun Lim, Hyocheol Bae, Fuller W Bazer, Gwonhwa Song
Fibroblast growth factor 2 (FGF2) is a mitogen that induces proliferation, differentiation, and migration of cells, as well as angiogenesis and carcinogenesis via autocrine or paracrine actions. Fibroblast growth factor 2 expression is abundant in porcine conceptuses and endometrium during the estrous cycle and peri-implantation period of pregnancy. However, its intracellular actions in uterine epithelial cells have not been reported. The results of this study indicated abundant expression of FGFR1 and FGFR2 predominantly in uterine luminal and glandular epithelia during early pregnancy and that their expression decreased with increasing parity of the sows...
January 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28391780/clinical-significance-linked-to-functional-defects-in-bone-morphogenetic-protein-type-2-receptor-bmpr2
#10
Myung-Jin Kim, Seon Young Park, Hae Ryung Chang, Eun Young Jung, Anudari Munkhjargal, Jong-Seok Lim, Myeong-Sok Lee, Yonghwan Kim
Bone morphogenetic protein type 2 receptor (BMPR2) is one of the transforming growth factor-β (TGF-β) superfamily receptors, playing diverse roles during embryonic development, vasculogenesis, and osteogenesis. Human BMPR2 consists of 1,038 amino acids and contains functionally conserved extracellular, transmembrane, kinase, and C-terminal cytoplasmic domains. Bone morphogenetic proteins (BMPs) engage the tetrameric complex, composed of BMPR2 and its corresponding type 1 receptors, which initiates SMAD family of proteins-mediated signal transduction leading to expression of target genes implicated in development or differentiation of the embryo, organs and bones...
April 10, 2017: BMB Reports
https://www.readbyqxmd.com/read/28386357/fasudil-inhibits-proliferation-and-collagen-synthesis-and-induces-apoptosis-of-human-fibroblasts-derived-from-urethral-scar-via-the-rho-rock-signaling-pathway
#11
Ning Xu, Shao-Hao Chen, Gen-Yi Qu, Xiao-Dong Li, Wen Lin, Xue-Yi Xue, Yun-Zhi Lin, Qing-Shui Zheng, Yong Wei
Fasudil has shown antifibrotic effects in various fibrotic diseases. However, its effects on human urethral fibroblasts are unknown. This study evaluated the effects of fasudil on cellular proliferation, migration, apoptosis, and collagen synthesis in human fibroblasts derived from urethral scar tissues. Human urethral scar fibroblasts were cultured by explant and incubated for 24 h or 48 h with fasudil (12.5, 25, 50 µmol/L) with or without transforming growth factor β1 (TGF-β1, 10 ng/mL), or left untreated (control)...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28385009/inhibitory-effects-of-resveratrol-on-hepatitis-b-virus-x-protein-hbx-induced-hepatocellular-carcinoma-hcc
#12
Seungmo Park, Jihae Lim, Jong Rhan Kim, Seongbeom Cho
Liver cancer occurs very frequently worldwide and hepatocellular carcinoma (HCC) accounts for more than 80% of total primary liver cancer cases. Here, the anticarcinogenic effects of resveratrol against hepatitis B virus (HBV)-induced HCC were investigated using HBV X-protein-overexpressing Huh7 (Huh7-HBx) human hepatoma cells. MTT assay showed that resveratrol decreased cell viability. Fluorescence-activated cell sorter analysis showed that it induced G1 cell cycle arrest without increasing the sub-G1 phase cell population...
April 6, 2017: Journal of Veterinary Science
https://www.readbyqxmd.com/read/28382076/multicenter-single-arm-phase-iv-study-of-combined-aspirin-and-high-dose-ivig-sn-therapy-for-pediatric-patients-with-kawasaki-disease
#13
Kyung Lim Yoon, Hae Yong Lee, Jeong Jin Yu, Jae Young Lee, Mi Young Han, Ki Yong Kim, June Huh
BACKGROUND AND OBJECTIVES: Intravenous immunoglobulin-SN (IVIG-SN) is a new human immunoglobulin product. Its safety is ensured by pathogen-elimination steps comprising solvent/detergent treatment and a nanofiltration process. This multicenter clinical study was designed to evaluate the efficacy and safety of combined aspirin and high-dose IVIG-SN therapy in pediatric patients with Kawasaki disease (KD). SUBJECTS AND METHODS: We evaluated coronary artery lesions (CALs) at 2 and 7 weeks after administering IVIG-SN; total fever duration; and variations in erythrocyte sedimentation rate, N-terminal pro B-type natriuretic peptide or B-type natriuretic peptide, and creatine kinase-myocardial band level before and after treatment with IVIG-SN (2 g/kg)...
March 2017: Korean Circulation Journal
https://www.readbyqxmd.com/read/28381571/discovery-of-novel-small-molecule-inhibitors-of-lim-domain-kinase-for-inhibiting-hiv-1
#14
Fei Yi, Jia Guo, Deemah Dabbagh, Mark Spear, Sijia He, Kylene Kehn-Hall, Jacque Fontenot, Yan Yin, Mathieu Bibian, Chul Min Park, Ke Zheng, HaJeung Park, Veronica Soloveva, Dima Gharaibeh, Cary Retterer, Rouzbeh Zamani, Margaret L Pitt, John Naughton, Yongjun Jiang, Hong Shang, Ramin M Hakami, Binhua Ling, John A T Young, Sina Bavari, Xuehua Xu, Yangbo Feng, Yuntao Wu
A dynamic actin cytoskeleton is necessary for viral entry, intracellular migration, and virion release. For HIV-1 infection, during entry, the virus triggers early actin activity through hijacking chemokine coreceptor signaling which activates a host dependency factor cofilin and its kinase, the LIM domain kinase (LIMK). Although knockdown of human LIMK1 with shRNA inhibits HIV infection, no specific small molecule inhibitor of LIMK was available. Here we describe the design and discovery of novel classes of small molecule inhibitors of LIMK for inhibiting HIV infection...
April 5, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28374824/crosstalk-between-signals-initiated-from-tlr4-and-cell-surface-baff-results-in-synergistic-induction-of-proinflammatory-mediators-in-thp-1-cells
#15
Su-Geun Lim, Jae-Kwan Kim, Kyoungho Suk, Won-Ha Lee
Cellular response to stimulation is mediated by meshwork of signaling pathways that may share common signaling adaptors. Here, we present data demonstrating that signaling pathways initiated from the membrane-bound form of B-cell activating factor (BAFF) can crosstalk with lipopolysaccharide (LPS)-induced signaling for synergistic expression of proinflammatory mediators in the human macrophage-like cell line THP-1. Co-treatment of the cells with BAFF-specific monoclonal antibody and LPS resulted in enhanced mitogen-activated protein kinase (MAPK)/mitogen- and stress-activated protein kinase (MSK)-mediated phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 subunit (Ser276), which then interacts with CREB binding protein (CBP) for subsequent acetylation...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28373445/pi3k-catalytic-isoform-alteration-promotes-the-limk1-related-metastasis-through-the-pak1-or-rock1-2-activation-in-cigarette-smoke-exposed-ovarian-cancer-cells
#16
Ga Bin Park, Daejin Kim
AIM: To investigate the molecular mechanisms by which long-term exposure to cigarette smoke extract (CSE) contributes to ovarian cancer metastasis. MATERIALS AND METHODS: Western blot analysis for diverse p110 isoforms of phosphoinositide 3-kinase (PI3K)-related signaling pathway and epithelial-mesenchymal transition (EMT) markers was performed to analyze the underlying mechanisms. Migratory activity of CSE-exposed ovarian cancer cells was determined by transendothelial migration and invasion assay...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28369848/end-stage-renal-disease-induced-hypercalcemia-may-promote-aortic-valve-calcification-via-annexin-vi-enrichment-of-valve-interstitial-cell-derived-matrix-vesicles
#17
Lin Cui, Nabil A Rashdan, Dongxing Zhu, Elspeth Milne, Paul Ajuh, Gillian Milne, Miep Helfrich, Kelvin Lim, Sai Prasad, Daniel Lerman, Alex Vesey, Marc Dweck, W S Jenkins, David Newby, Colin Farquharson, Vicky E Macrae
Patients with end-stage renal disease (ESRD) have elevated circulating calcium (Ca) and phosphate (Pi), and exhibit accelerated progression of calcific aortic valve disease (CAVD). We hypothesised that matrix vesicles (MVs) initiate the calcification process in CAVD. Ca induced rat valve interstitial cells (VICs) calcification at 4.5 mM (16.4 fold; P < 0.05) whereas Pi treatment alone had no effect. Ca (2.7 mM) and Pi (2.5 mM) synergistically induced calcium deposition (10.8 fold; P < 0...
March 30, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28359791/plumbagin-reduces-osteopontin-induced-invasion-through-inhibiting-the-rho-associated-kinase-signaling-pathway-in-a549-cells-and-suppresses-osteopontin-induced-lung-metastasis-in-balb-c-mice
#18
Chi Gu Kang, Eunji Im, Hyo-Jeong Lee, Eun-Ok Lee
Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer deaths in both men and women in the United States. It has been recently demonstrated that osteopontin (OPN) effectively inhibits cofilin activity through the focal adhesion kinase (FAK)/AKT/Rho-associated kinase (ROCK) pathway to induce the invasion of human non-small cell lung cancer (NSCLC) cells. Plumbagin was isolated from the roots of the medicinal plant Plumbago zeylanica L. and has been reported to possess anticancer activities...
May 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28358928/regulation-of-white-and-brown-adipocyte-differentiation-by-rhogap-dlc1
#19
Choon Kiat Sim, Sun-Yee Kim, Reinhard Brunmeir, Qiongyi Zhang, Hongyu Li, Dharmini Dharmasegaran, Carol Leong, Ying Yan Lim, Weiping Han, Feng Xu
Adipose tissues constitute an important component of metabolism, the dysfunction of which can cause obesity and type II diabetes. Here we show that differentiation of white and brown adipocytes requires Deleted in Liver Cancer 1 (DLC1), a Rho GTPase Activating Protein (RhoGAP) previously studied for its function in liver cancer. We identified Dlc1 as a super-enhancer associated gene in both white and brown adipocytes through analyzing the genome-wide binding profiles of PPARγ, the master regulator of adipogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28358024/downregulation-of-limk1-adf-cofilin-by-dads-inhibits-the-migration-and-invasion-of-colon-cancer
#20
Jian Su, Yujuan Zhou, Zhibing Pan, Ling Shi, Jing Yang, Aijun Liao, Qianjin Liao, Qi Su
This study aimed to explore whether the downregulation of LIM kinase 1 (LIMK1)-actin depolymerization factor (ADF, also known as destrin)/cofilin by diallyl disulfide (DADS) inhibited the migration and invasion of colon cancer. Previous studies have shown that silencing LIMK1 could significantly enhance the inhibitory effect of DADS on colon cancer cell migration and invasion, suggesting that LIMK1 was a target molecule of DADS, which needed further confirmation. This study reported that LIMK1 and destrin were highly expressed in colon cancer and associated with poor prognosis of patients with colon cancer...
March 30, 2017: Scientific Reports
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