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https://www.readbyqxmd.com/read/28643781/recurrent-mutation-of-igf-signalling-genes-and-distinct-patterns-of-genomic-rearrangement-in-osteosarcoma
#1
Sam Behjati, Patrick S Tarpey, Kerstin Haase, Hongtao Ye, Matthew D Young, Ludmil B Alexandrov, Sarah J Farndon, Grace Collord, David C Wedge, Inigo Martincorena, Susanna L Cooke, Helen Davies, William Mifsud, Mathias Lidgren, Sancha Martin, Calli Latimer, Mark Maddison, Adam P Butler, Jon W Teague, Nischalan Pillay, Adam Shlien, Ultan McDermott, P Andrew Futreal, Daniel Baumhoer, Olga Zaikova, Bodil Bjerkehagen, Ola Myklebost, M Fernanda Amary, Roberto Tirabosco, Peter Van Loo, Michael R Stratton, Adrienne M Flanagan, Peter J Campbell
Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours...
June 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28633944/gene-expression-analysis-identify-a-metabolic-and-cell-function-alterations-as-a-hallmark-of-obesity-without-metabolic-syndrome-in-peripheral-blood-a-pilot-study
#2
Daniel Antonio de Luis, Raquel Almansa, Rocío Aller, Olatz Izaola, E Romero
BACKGROUND: Understanding molecular basis involved in overweight is an important first step in developing therapeutic pathways against excess in body weight gain. OBJECTIVE: The purpose of our pilot study was to evaluate the gene expression profiles in the peripheral blood of obese patients without other metabolic complications. DESIGN: A sample of 17 obese patients without metabolic syndrome and 15 non obese control subjects was evaluated in a prospective way...
June 10, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28630090/t-cell-transcriptomes-from-paroxysmal-nocturnal-hemoglobinuria-patients-reveal-novel-signaling-pathways
#3
Kohei Hosokawa, Sachiko Kajigaya, Keyvan Keyvanfar, Wangmin Qiao, Yanling Xie, Danielle M Townsley, Xingmin Feng, Neal S Young
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder originating from hematopoietic stem cells and is a life-threating disease characterized by intravascular hemolysis, bone marrow (BM) failure, and venous thrombosis. The etiology of PNH is a somatic mutation in the phosphatidylinositol glycan class A gene (PIG-A) on the X chromosome, which blocks synthesis of the glycolipid moiety and causes deficiency in GPI-anchored proteins. PNH is closely related to aplastic anemia, in which T cells mediate destruction of BM...
June 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28627468/a-novel-chalcone-derivative-lqfm064-induces-breast-cancer-cells-death-via-p53-p21-kit-and-pdgfra
#4
Bruna Lannuce Silva Cabral, Artur Christian Garcia da Silva, Renato Ivan de Ávila, Alane Pereira Cortez, Rangel Magalhães Luzin, Luciano Morais Lião, Eric de Souza Gil, Gérman Sanz, Boniek G Vaz, José R Sabino, Ricardo Menegatti, Marize Campos Valadares
This study shows the design, synthesis and antitumoral potential evaluation of a novel chalcone-like compound, (E)-3- (3, 5-di-ter-butyl-4-hydroxyphenyl)-1- (4-hydroxy-3-methoxyphenyl) prop-2-en-1-one [LQFM064) (4)], against human breast adenocarcinoma MCF7 cells. Some toxicological parameters were also investigated. LQFM064) (4) exhibited cytotoxic activity against MCF7 cells (IC50=21μM), in a concentration dependent-manner, and triggered significant changes in cell morphology and biochemical/molecular parameters, which are suggestive of an apoptosis inductor...
June 13, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28626787/5-ht2a-receptor-deficiency-alters-the-metabolic-and-transcriptional-but-not-the-behavioral-consequences-of-chronic-unpredictable-stress
#5
Minal Jaggar, Noelia Weisstaub, Jay A Gingrich, Vidita A Vaidya
Chronic stress enhances risk for psychiatric disorders, and in animal models is known to evoke depression-like behavior accompanied by perturbed neurohormonal, metabolic, neuroarchitectural and transcriptional changes. Serotonergic neurotransmission, including serotonin2A (5-HT2A) receptors, have been implicated in mediating specific aspects of stress-induced responses. Here we investigated the influence of chronic unpredictable stress (CUS) on depression-like behavior, serum metabolic measures, and gene expression in stress-associated neurocircuitry of the prefrontal cortex (PFC) and hippocampus in 5-HT2A receptor knockout (5-[Formula: see text]) and wild-type mice of both sexes...
December 2017: Neurobiology of Stress
https://www.readbyqxmd.com/read/28624790/co-targeting-of-igf1r-mtor-pathway-by-mir-497-and-mir-99a-impairs-hepatocellular-carcinoma-development
#6
Henghui Cheng, Jin Xue, Shouhua Yang, Yaobin Chen, Yu Wang, Yuanli Zhu, Xiaoyan Wang, Dong Kuang, Qiurong Ruan, Yaqi Duan, Guoping Wang
Persistent activation of IGF1R/mTOR signaling pathway plays crucial role in the development of hepatocellular carcinoma (HCC). Therefore, our goal was to elucidate microRNAs (miRNAs) targeting IGF1R/mTOR and the therapeutic potential of single or dual miRNA on HCC development. In this study, we found that miR-497 and miR-99a that target the 3'-UTR of both IGF1R and mTOR were down-regulated in HCC human tissues and cell lines. Functional assay revealed that ectopic expression of miR-497 or miR-99a in HCC cells resulted in a significant inhibition on tumor growth and invasiveness in vitro and tumor development in vivo via repressing the expression of IGF1R and mTOR...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623308/improved-growth-patterns-in-cystic-fibrosis-mice-after-loss-of-histone-deacetylase-6
#7
Sharon M Rymut, Deborah A Corey, Dana M Valerio, Bernadette O Erokwu, Chris A Flask, Thomas J Kelley, Craig A Hodges
Growth failure in cystic fibrosis (CF) patients has been well-documented and shown to correlate with poorer disease outcomes. This observation is also true in CF animal models, including mouse, pig, rat, and ferret. The etiology underlying growth deficits is unknown, and our previous work demonstrated reduced tubulin acetylation in CF cell models and tissue that is correctable by inhibition of histone deacetylase-6 (HDAC6). Here, we hypothesize that loss of HDAC6 will improve growth phenotype in a CF mouse model...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28622965/tumour-derived-human-growth-hormone-as-a-therapeutic-target-in-oncology
#8
REVIEW
Jo K Perry, Zheng-Sheng Wu, Hichem C Mertani, Tao Zhu, Peter E Lobie
The growth hormone (GH) and insulin-like growth factor-1 (IGF1) axis is the key regulator of longitudinal growth, promoting postnatal bone and muscle growth. The available data suggest that GH expression by tumour cells is associated with the aetiology and progression of various cancers such as endometrial, breast, liver, prostate, and colon cancer. Accordingly there has been increased interest in targeting GH-mediated signal transduction in a therapeutic setting. Because GH has endocrine, autocrine, and paracrine actions, therapeutic strategies will need to take into account systemic and local functions...
June 13, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28620819/cellular-growth-and-tube-formation-of-htr8-svneo-trophoblast-effects-of-exogenously-added-fatty-acid-binding-protein-4-and-its-inhibitor
#9
Sanjay Basak, Arnab Sarkar, Santosh Mathapati, Asim K Duttaroy
Adequate placental angiogenesis is critical for the establishment of the placental circulation and thus for normal feto-placental growth and development. Fatty acid-binding protein-4 (FABP4) plays a pro-angiogenic role in endothelial cells; however, very little information is available in placental first trimester trophoblast cells. Here we report that exogenously added FABP4 (exo-FABP4) stimulated tube formation (as a measure of in vitro angiogenesis) in HTR8/SVneo trophoblastic cells. HTR-8/SVneo cells were incubated in the presence of exogenously added FABP4 at different concentrations and time points...
June 15, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28620496/growth-hormone-and-insulin-like-growth-factor-1-affect-the-severity-of-graves-disease
#10
Alfredo Di Cerbo, Federica Pezzuto, Alessandro Di Cerbo
Graves' disease, the most common form of hyperthyroidism in iodine-replete countries, is associated with the presence of immunoglobulins G (IgGs) that are responsible for thyroid growth and hyperfunction. In this article, we report the unusual case of a patient with acromegaly and a severe form of Graves' disease. Here, we address the issue concerning the role of growth hormone (GH) and insulin-like growth factor 1 (IGF1) in influencing thyroid function. Severity of Graves' disease is exacerbated by coexistent acromegaly and both activity indexes and symptoms and signs of Graves' disease improve after the surgical remission of acromegaly...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28617135/influence-of-personalized-exercise-recommendations-during-rehabilitation-on-the-sustainability-of-objectively-measured-physical-activity-levels-fatigue-and-fatigue-related-biomarkers-in-patients-with-breast-cancer
#11
Philipp Zimmer, Freerk T Baumann, Max Oberste, Joachim Schmitt, Niklas Joisten, Philipp Hartig, Alexander Schenk, Rafaela Kuhn, Wilhelm Bloch, Monika Reuss-Borst
PURPOSE: Only one-third of patients with breast cancer reach the recommended activity level of 15 to 25 MET h/wk. The aim of this study was to determine the influence of personalized exercise recommendations during rehabilitation on patients' physical activity level, fatigue, and self-perceived cognitive function as well as on side effect-associated biomarkers. METHODS: Total metabolic rate, physical activity level, mean MET and steps, fatigue, self-perceived cognitive functioning , and biomarkers (C-reactive protein [CRP], interleukin 6, macrophage migration inhibiting factor [MIF], tumor necrosis factor [TNF]-α, brain-derived neurotrophic factor [BDNF], insulin-like growth factor 1 [IGF1]) were assessed in 60 patients with breast cancer in the aftercare phase before ( t0) and 8 months after ( t1) the intervention...
June 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28613101/targeting-igf1r-pathway-in-cancer-with-micrornas-how-close-are-we
#12
Arathy S Kumar, Suresh K Rayala, Ganesh Venkatraman
Cancer of the head and neck are the most common cancers in India and account for 30% of all cancers. At molecular level, it could be attributed to the over-expression of growth factors like IGF1-R, EGFR, VEGF-R and deregulation of cell cycle regulators and tumor suppressors. IGF1-R is an emerging target in head and neck cancer treatment, because of its reported role in tumor development, progression and metastasis. IGF1R targeted agents are in advanced stages of clinical development. Nevertheless, these agents suffer from several disadvantages including acquired resistance and toxic side effects...
June 14, 2017: RNA Biology
https://www.readbyqxmd.com/read/28611056/igf1-potentiates-the-pro-inflammatory-response-in-human-peripheral-blood-mononuclear-cells-via-mapk
#13
Thalijn Liliana Catharina Wolters, Mihai Gheorghe Netea, Ad R Hermus, Jan Wa Smit, Romana T Netea-Maier
Introduction: Acromegaly is characterized by growth hormone (GH) and Insulin-like Growth Factor 1 (IGF1) excess and is accompanied by an increased cardiovascular diseases (CVD) risk. As innate immune responses are crucial in CVD development, and IGF1 is linked to subclinical inflammation, we hypothesized that GH/IGF1 excess contributes to CVD development via potentiating systemic inflammation. We aimed to assess the effects of GH/IGF1 on inflammatory cytokine production. Methods: Whole blood from acromegaly patients and healthy volunteers, and peripheral blood mononuclear cells (PBMC) from healthy volunteers were stimulated with Toll-like receptor (TLR) ligands, with or without adding GH or IGF1 (in PBMC)...
June 13, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28607354/igf-1-mediated-neurogenesis-involves-a-novel-rit1-akt-sox2-cascade
#14
Sajad Mir, Weikang Cai, Shaun W Carlson, Kathryn E Saatman, Douglas A Andres
Insulin-like growth factor 1 (IGF-1) is known to have diverse effects on brain structure and function, including the promotion of stem cell proliferation and neurogenesis in the adult dentate gyrus. However, the intracellular pathways downstream of the IGF-1 receptor that contribute to these diverse physiological actions remain relatively uncharacterized. Here, we demonstrate that the Ras-related GTPase, RIT1, plays a critical role in IGF-1-dependent neurogenesis. Studies in hippocampal neuronal precursor cells (HNPCs) demonstrate that IGF-1 stimulates a RIT1-dependent increase in Sox2 levels, resulting in pro-neural gene expression and increased cellular proliferation...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28602743/apple-cider-vinegar-boosted-immunomodulatory-and-health-promoting-effects-of-lactobacillus-casei-in-common-carp-cyprinus-carpio
#15
Roghieh Safari, Seyed Hossein Hoseinifar, Shabnam Nejadmoghadam, Mohsen Khalili
The present study was performed to investigate the immunomodulatory and health promoting effects of combined or singular administration of apple cider vinegar (ACV) and Lactobacillus casei in common carp (Cyprinus carpio) diet. An 8-week feeding trial was designed with following treatments: Control (basal diet), Pro (contains 10(7) CFU g(-1)L. casei), LACV (contains 1% ACV), HACV (contains 2% ACV), Pro + LACV (contains 10(7) CFU g(-1)L. casei plus 1% ACV) and Pro + HACV (contains 10(7) CFU g(-1)L...
June 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28596684/insulin-like-growth-factor-1-igf-binding-protein-3-and-the-risk-of-esophageal-cancer-in-a-nested-case-control-study
#16
Yasushi Adachi, Masanori Nojima, Mitsuru Mori, Kentaro Yamashita, Hiro-O Yamano, Hiroshi Nakase, Takao Endo, Kenji Wakai, Kiyomi Sakata, Akiko Tamakoshi
AIM: To assess the relationship between serum levels of insulin-like growth factor-1 (IGF1)/IGF-binding protein-3 (IGFBP3) and the risk of esophageal carcinoma. METHODS: We assessed the relationship between the serum levels of these molecules and the risk of esophageal cancer in a prospective, nested case-control study of participants from the Japan Collaborative Cohort Study. A baseline survey was conducted from 1988 to 1990. Of the 110585 enrolled participants, 35% donated blood samples...
May 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28596451/serum-insulin-like-growth-factor-1-and-the-risk-of-ischemic-stroke-the-framingham-study
#17
Hamidreza Saber, Jayandra J Himali, Alexa S Beiser, Ashkan Shoamanesh, Aleksandra Pikula, Ronenn Roubenoff, Jose R Romero, Carlos S Kase, Ramachandran S Vasan, Sudha Seshadri
BACKGROUND AND PURPOSE: Low insulinlike growth factor 1 (IGF1) has been associated with increased risk of atherosclerosis and atrial fibrillation in crosssectional studies. Yet, prospective data linking IGF1 levels to the development of ischemic stroke remain inconclusive. We examined prospectively the association between serum IGF-1 levels and incident ischemic stroke. METHODS: We measured serum IGF-1 levels in 757 elderly individuals (mean age 79±5, 62% women), free of prevalent stroke, from the Framingham original cohort participants at the 22nd examination cycle (1990-1994) and were followed up for the development of ischemic stroke...
June 8, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28589682/expansion-of-adipose-tissue-derived-stromal-cells-at-physiologic-hypoxia-attenuates-replicative-senescence
#18
Andrey Ratushnyy, Margarita Lobanova, Ludmila B Buravkova
Multipotent mesenchymal stromal cells are considered as a perspective tool in cell therapy and regenerative medicine. Unfortunately, autologous cell therapy does not always provide positive outcomes in elder donors, perhaps as a result of the alterations of stem cell compartments. The mechanisms of stem and progenitor cell senescence and the factors engaged are investigated intensively. In present paper, we elucidated the effects of tissue-related O2 on morphology, functions, and transcriptomic profile of adipose tissue-derived stromal cells (ASCs) in replicative senescence in vitro model...
June 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/28587396/identification-of-the-mirna-target-gene-regulatory-network-in-intracranial-aneurysm-based-on-microarray-expression-data
#19
Kezhen Wang, Xinmin Wang, Hongzhu Lv, Chengzhi Cui, Jiyong Leng, Kai Xu, Guosong Yu, Jianwei Chen, Peiyu Cong
Intracranial aneurysm (IA) remains one of the most devastating neurological conditions. However, the pathophysiology of IA formation and rupture still remains unclear. The purpose of the present study was to identify the crucial microRNA (miRNA/miR) and genes involved in IAs and elucidate the mechanisms underlying the development of IAs. In the present study, novel miRNA regulation activities in IAs were investigated through the integration of public gene expression data of miRNA and mRNA using the Gene Expression Omnibus database, combined with bioinformatics prediction...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28586424/role-of-er%C3%AE-in-mediating-female-uterine-transcriptional-responses-to-igf1
#20
Sylvia C Hewitt, Wipawee Winuthayanon, Sydney L Lierz, Katherine J Hamilton, Lauren J Donoghue, J Tyler Ramsey, Sara A Grimm, Yukitomo Arao, Kenneth S Korach
Estrogen (E2) signaling through its nuclear receptor, estrogen receptor α (ERα) increases insulin-like growth factor 1 (IGF1) in the rodent uterus, which then initiates further signals via the IGF1 receptor (IGF1R). Directly administering IGF1 results in similar biological and transcriptional uterine responses. Our studies using global ERα-null mice demonstrated a loss of uterine biological responses of the uterus to E2 or IGF1 treatment, while maintaining transcriptional responses to IGF1. To address this discrepancy in the need for uterine ERα in mediating the IGF1 transcriptional vs...
June 6, 2017: Endocrinology
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