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https://www.readbyqxmd.com/read/29226331/a-novel-pathway-activated-by-somatostatin-receptor-type-2-sst2-inhibition-of-pituitary-tumor-cell-migration-and-invasion-through-cytoskeleton-protein-recruitment
#1
E Peverelli, E Giardino, D Treppiedi, R Catalano, F Mangili, M Locatelli, A G Lania, M Arosio, A Spada, G Mantovani
The pharmacological therapy of GH-secreting pituitary tumors is based on somatostatin (SS) analogs that reduce GH secretion and cell proliferation by binding mainly SS receptors type 2 (SST2). Antimigratory effects of SS have been demonstrated in different cell models, but no data on pituitary tumors are available. Aims of this study were to evaluate SST2 effects on migration and invasion of human and rat tumoral somatotrophs, and to elucidate the molecular mechanism involved focusing on the role of cofilin and filamin A (FLNA)...
December 11, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29212901/flnc-filamin-c-a-new-er-player-in-the-field-of-genetic-cardiomyopathies
#2
EDITORIAL
Andreas Brodehl, Anna Gaertner-Rommel, Hendrik Milting
No abstract text is available yet for this article.
December 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29212899/novel-mutation-in-flnc-filamin-c-causes-familial-restrictive-cardiomyopathy
#3
Nathan R Tucker, Micheal A McLellan, Dongjian Hu, Jiangchuan Ye, Victoria A Parsons, Robert W Mills, Sebastian Clauss, Elena Dolmatova, Marisa A Shea, David J Milan, Nandita S Scott, Mark Lindsay, Steven A Lubitz, Ibrahim J Domian, James R Stone, Honghuang Lin, Patrick T Ellinor
BACKGROUND: Restrictive cardiomyopathy (RCM) is a rare cardiomyopathy characterized by impaired diastolic ventricular function resulting in a poor clinical prognosis. Rarely, heritable forms of RCM have been reported, and mutations underlying RCM have been identified in genes that govern the contractile function of the cardiomyocytes. METHODS AND RESULTS: We evaluated 8 family members across 4 generations by history, physical examination, electrocardiography, and echocardiography...
December 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29190677/cortical-actin-nodes-their-dynamics-and-recruitment-of-podosomal-proteins-as-revealed-by-super-resolution-and-single-molecule-microscopy
#4
Yuki M Shirai, Taka A Tsunoyama, Nao Hiramoto-Yamaki, Koichiro M Hirosawa, Akihiro C E Shibata, Kenichi Kondo, Atsushi Tsurumune, Fumiyoshi Ishidate, Akihiro Kusumi, Takahiro K Fujiwara
Electron tomography of the plasma membrane (PM) identified several layers of cortical actin meshwork running parallel to the PM cytoplasmic surface throughout the PM. Here, cortical actin structures and dynamics were examined in living cells, using super-resolution microscopy, with (x,y)- and z-resolutions of ~140 and ~400 nm, respectively, and single-molecule imaging. The super-resolution microscopy identified sub-micron-sized actin clusters that appeared identical by both phalloidin post-fixation staining and Lifeact-mGFP expression followed by fixation, and therefore, these actin clusters were named "actin-pl-clusters"...
2017: PloS One
https://www.readbyqxmd.com/read/29146485/in-frame-variants-in-flna-proximal-rod-1-domain-associate-with-a-predominant-cardiac-valvular-phenotype
#5
Luis Fernández, Jair Tenorio, Coral Polo-Vaquero, Elena Vallespín, María Palomares-Bralo, Sixto García-Miñaúr, Fernando Santos-Simarro, Pedro Arias, Hernán Carnicer, Silvina Giannivelli, Juan Medina, Rosa Pérez-Piaya, Jorge Solís, Mónica Rodríguez, Alexandra Villagrá, Laura Rodríguez, Julián Nevado, Víctor Martínez-Glez, Karen E Heath, Pablo Lapunzina
INTRODUCTION AND OBJECTIVES: X-linked cardiac valvular dysplasia is a rare form of male-specific congenital heart defect mainly characterized by myxomatous degeneration of the atrioventricular valves with variable hemodynamic consequences. It is caused by genetic defects in FLNA-encoded filamin A, a widely expressed actin-binding protein that regulates cytoskeleton organization. Filamin A loss of function has also been associated with often concurring neurologic and connective tissue manifestations, with mutations in the first half of the Rod 1 domain apparently expressing the full cardiac phenotype...
November 13, 2017: Revista Española de Cardiología
https://www.readbyqxmd.com/read/29137275/vinculin-and-filamin-c-are-two-potential-prognostic-biomarkers-and-therapeutic-targets-for-prostate-cancer-cell-migration
#6
Jianzhong Ai, Tao Jin, Lu Yang, Qiang Wei, Yang Yang, Hong Li, Ye Zhu
Prostate cancer (PCa) is one of the most common diseases for male population, and the effective treatment for metastatic castration-resistant PCa is still lacking. To unravel the underlying mechanism of PCa cell migration, we plan to analyze the related crucial proteins and their roles. In our study, we firstly identify the differentially expressed proteins using quantitative proteomics, and confirm their mRNA expression using quantitative polymerase chain reaction (qPCR). The alterations of these proteins at DNA and mRNA levels are obtained from cBioPortal database...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29119312/when-signalling-goes-wrong-pathogenic-variants-in-structural-and-signalling-proteins-causing-cardiomyopathies
#7
Mehroz Ehsan, He Jiang, Kate L Thomson, Katja Gehmlich
Cardiomyopathies are a diverse group of cardiac disorders with distinct phenotypes, depending on the proteins and pathways affected. A substantial proportion of cardiomyopathies are inherited and those will be the focus of this review article. With the wide application of high-throughput sequencing in the practice of clinical genetics, the roles of novel genes in cardiomyopathies are recognised. Here, we focus on a subgroup of cardiomyopathy genes [TTN, FHL1, CSRP3, FLNC and PLN, coding for Titin, Four and a Half LIM domain 1, Muscle LIM Protein, Filamin C and Phospholamban, respectively], which, despite their diverse biological functions, all have important signalling functions in the heart, suggesting that disturbances in signalling networks can contribute to cardiomyopathies...
November 8, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/29100390/flna-is-implicated-in-pulmonary-neuroendocrine-tumors-aggressiveness-and-progression
#8
Eleonora Vitali, Ilena Boemi, Lorenzo Rosso, Valeria Cambiaghi, Pierluigi Novellis, Giovanna Mantovani, Anna Spada, Marco Alloisio, Giulia Veronesi, Stefano Ferrero, Andrea G Lania
Pulmonary neuroendocrine tumors (PNTs) comprise different neoplasms, ranging from low grade carcinoids to the highly malignant small cell lung cancers. Several studies identified the cytoskeleton protein Filamin A (FLNA) as determinant in cancer progression and metastasis, but the role of FLNA in PNT aggressiveness and progression is still unknown. We evaluated FLNA expression in PNTs with different grade of differentiation, the role of FLNA in cell proliferation, colony formation, angiogenesis, cell adhesion and migration in PNT cell line (H727 cells) and primary cultures and the possible interaction between FLNA and Rap1-GTPase...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100323/enhanced-antitumor-effect-of-biodegradable-cationic-heparin-polyethyleneimine-nanogels-delivering-filip1l%C3%AE-c103-gene-combined-with-low-dose-cisplatin-on-ovarian-cancer
#9
Chuan Xie, Maling Gou, Tao Yi, Xiaorong Qi, Ping Liu, Yuquan Wei, Xia Zhao
FILIP1LΔC103 (COOH terminal truncation mutant 1-790 of Filamin A Interacting Protein 1-Like) has been identified to hold therapeutic potential for suppressing tumor growth. Cisplatin (DDP) is commonly used as a first-line drug in the treatment for ovarian cancer. The usage of polymeric nanoparticles to deliver functional genes intraperitoneally holds much promise as an effective therapy for ovarian cancer. In this study, a recombinant plasmid expressing FILIP1LΔC103 (FILIP1LΔC103-p) was constructed, and HPEI nanogels were prepared to deliver FILIP1LΔC103-p into SKOV3 cells...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29095481/biallelic-mutations-in-flnb-cause-a-skeletal-dysplasia-with-46-xy-gonadal-dysgenesis-by-activating-%C3%AE-catenin
#10
K Upadhyay, J Loke, V O, B Taragin, H Ostrer
Filamin B (FLNB) functions as a switch that can affect chrondrocyte development and endochondral bone formation through a series of signaling molecules and transcription factors that also affect Sertoli cell development. Here, we report a subject with a novel skeletal dysplasia and co-existing 46,XY gonadal dysgenesis and biallelic mutations in FLNB. Whole exome sequencing was performed to identify mutations. Quantitative qPCR and flow variant assays were performed to quantify RNA, proteins and phosphorylated proteins...
November 2, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/29065889/injury-induced-expression-of-caveolar-proteins-in-human-kidney-tubules-role-of-megakaryoblastic-leukemia-1
#11
Krzysztof M Krawczyk, Jennifer Hansson, Helén Nilsson, Katarzyna K Krawczyk, Karl Swärd, Martin E Johansson
BACKGROUND: Caveolae are membrane invaginations measuring 50-100 nm. These organelles, composed of caveolin and cavin proteins, are important for cellular signaling and survival. Caveolae play incompletely defined roles in human kidneys. Induction of caveolin-1/CAV1 in diseased tubules has been described previously, but the responsible mechanism remains to be defined. METHODS: Healthy and atrophying human kidneys were stained for caveolar proteins, (caveolin 1-3 and cavin 1-4) and examined by electron microscopy...
October 24, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/29062687/integrity-of-the-corpus-callosum-in-patients-with-periventricular-nodular-heterotopia-related-epilepsy-by-flna-mutation
#12
Wenyu Liu, Dongmei An, Running Niu, Qiyong Gong, Dong Zhou
OBJECTIVE: To investigate the quantitative diffusion properties of the corpus callosum (CC) in a large group of patients with periventricular nodular heterotopia (PNH) related epilepsy and to further investigate the effect of Filamin A (FLNA) mutation on these properties. METHODS: Patients with PNH (n = 34), subdivided into FLNA-mutated (n = 11) and FLNA-nonmutated patients (n = 23) and healthy controls (n = 34), underwent 3.0 T structural MRI and diffusion imaging scan (64 direction)...
2018: NeuroImage: Clinical
https://www.readbyqxmd.com/read/29057305/perk-and-filamin-a-in-actin-cytoskeleton-remodeling-at-er-plasma-membrane-contact-sites
#13
Alexander R van Vliet, Patrizia Agostinis
The endoplasmic reticulum (ER) stress sensor protein kinase RNA-like endoplasmic reticulum kinase (PERK) plays a major role during the unfolded protein response (UPR), mainly through eIF2α phosphorylation. We uncovered that PERK, by interacting with Filamin A, elicits F-actin remodeling required for ER-plasma membrane contact site formation after ER-Ca(2+) depletion, through a UPR-independent mechanism.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/29052574/filamin-a-gene-associated-periventricular-nodular-heterotopia-and-epilepsy-in-a-cohort-of-chinese-patients
#14
Wen-Yu Liu, Dong Zhou
No abstract text is available yet for this article.
October 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29052140/prion-protein-family-contributes-to-tumorigenesis-via-multiple-pathways
#15
Xiaowen Yang, Zhijun Cheng, Lihua Zhang, Guiru Wu, Run Shi, Zhenxing Gao, Chaoyang Li
A wealth of evidence suggests that proteins from prion protein (PrP) family contribute to tumorigenesis in many types of cancers, including pancreatic ductal adenocarcinoma (PDAC), breast cancer, glioblastoma, colorectal cancer, gastric cancer, melanoma, etc. It is well documented that PrP is a biomarker for PDAC, breast cancer, and gastric cancer. However, the underlying mechanisms remain unclear. The major reasons for cancer cell-caused patient death are metastasis and multiple drug resistance, both of which connect to physiological functions of PrP expressing in cancer cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29044292/investigation-of-the-filamin-a-dependent-mechanisms-of-tissue-factor-incorporation-into-microvesicles
#16
Mary Collier, Mary E W Collier, Camille Ettelaie, Benjamin T Goult, Anthony Maraveyas, Alison H Goodall
We have previously shown that phosphorylation of tissue factor (TF) at Ser253 increases the incorporation of TF into microvesicles (MVs) following protease-activated receptor 2 (PAR2) activation through a process involving filamin A, whereas phosphorylation of TF at Ser258 suppresses this process. Here, we examined the contribution of the individual phosphorylation of these serine residues to the interaction between filamin A and TF, and further examined how filamin A regulates the incorporation of TF into MVs...
October 10, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29040517/filamin-a-mitral-valve-disease-prolapse-dystrophy-or-dysplasia
#17
Gaetano Thiene, Cristina Basso
No abstract text is available yet for this article.
October 12, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29030401/a-comparison-of-whole-genome-sequencing-to-multigene-panel-testing-in-hypertrophic-cardiomyopathy-patients
#18
Allison L Cirino, Neal K Lakdawala, Barbara McDonough, Lauren Conner, Dale Adler, Mark Weinfeld, Patrick O'Gara, Heidi L Rehm, Kalotina Machini, Matthew Lebo, Carrie Blout, Robert C Green, Calum A MacRae, Christine E Seidman, Carolyn Y Ho
BACKGROUND: As DNA sequencing costs decline, genetic testing options have expanded. Whole exome sequencing and whole genome sequencing (WGS) are entering clinical use, posing questions about their incremental value compared with disease-specific multigene panels that have been the cornerstone of genetic testing. METHODS AND RESULTS: Forty-one patients with hypertrophic cardiomyopathy who had undergone targeted hypertrophic cardiomyopathy genetic testing (either multigene panel or familial variant test) were recruited into the MedSeq Project, a clinical trial of WGS...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29020406/new-insights-into-mitral-valve-dystrophy-a-filamin-a-genotype-phenotype-and-outcome-study
#19
Thierry Le Tourneau, Solena Le Scouarnec, Caroline Cueff, Daniel Bernstein, Jan J J Aalberts, Simon Lecointe, Jean Mérot, Jonathan A Bernstein, Toon Oomen, Christian Dina, Matilde Karakachoff, Hubert Desal, Ousama Al Habash, Francesca N Delling, Romain Capoulade, Albert J H Suurmeijer, David Milan, Russell A Norris, Roger Markwald, Elena Aikawa, Susan A Slaugenhaupt, Xavier Jeunemaitre, Albert Hagège, Jean-Christian Roussel, Jean-Noël Trochu, Robert A Levine, Florence Kyndt, Vincent Probst, Hervé Le Marec, Jean-Jacques Schott
Aims: Filamin-A (FLNA) was identified as the first gene of non-syndromic mitral valve dystrophy (FLNA-MVD). We aimed to assess the phenotype of FLNA-MVD and its impact on prognosis. Methods and results: We investigated the disease in 246 subjects (72 mutated) from four FLNA-MVD families harbouring three different FLNA mutations. Phenotype was characterized by a comprehensive echocardiography focusing on mitral valve apparatus in comparison with control relatives...
September 6, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28986439/filamin-a-regulates-neutrophil-adhesion-production-of-reactive-oxygen-species-and-neutrophil-extracellular-trap-release
#20
Liisa M Uotila, Carla Guenther, Terhi Savinko, Timo A Lehti, Susanna C Fagerholm
Neutrophils are of fundamental importance in the early immune response and use various mechanisms to neutralize invading pathogens. They kill endocytosed pathogens by releasing reactive oxygen species in the phagosome and release neutrophil extracellular traps (NETs) into their surroundings to immobilize and kill invading micro-organisms. Filamin A (FlnA) is an important actin cross-linking protein that is required for cellular processes involving actin rearrangements, such cell migration. It has also been shown to negatively regulate integrin activation and adhesion...
October 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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