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IGF-1R

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https://www.readbyqxmd.com/read/28645676/a-journey-through-growth-plates-tracking-differences-in-morphology-and-regulation-between-the-spine-and-long-bones-in-a-pig-model
#1
Adalbert Raimann, Alireza Javanmardi, Monika Egerbacher, Gabriele Haeusler
BACKGROUND CONTEXT: The process of linear growth is driven by axial elongation of both long bones and vertebral bodies and accomplished by enchondral ossification. Differences in regulation between the two skeletal sites are mirrored clinically by the age course in body proportions. Whereas growth plates in long bones can easily be discriminated, vertebral growth plates are part of the cartilaginous endplate, which typically shows important species differences. PURPOSE: To describe and compare histological, histomorphometric and regulatory characteristics in the growth plates of the spine and long bones in a porcine model...
June 20, 2017: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/28644734/high-throughput-phenotypic-screening-of-kinase-inhibitors-to-identify-drug-targets-for-polycystic-kidney-disease
#2
Tijmen H Booij, Hester Bange, Wouter N Leonhard, Kuan Yan, Michiel Fokkelman, Steven J Kunnen, Johannes G Dauwerse, Yu Qin, Bob van de Water, Gerard J P van Westen, Dorien J M Peters, Leo S Price
Polycystic kidney disease (PKD) is a prevalent disorder characterized by renal cysts that lead to kidney failure. Various signaling pathways have been targeted to stop disease progression, but most interventions still focus on alleviating PKD-associated symptoms. The mechanistic complexity of the disease, as well as the lack of functional in vitro assays for compound testing, has made drug discovery for PKD challenging. To identify modulators of PKD, Pkd1(-/-) kidney tubule epithelial cells were applied to a scalable and automated 3D cyst culture model for compound screening, followed by phenotypic profiling to determine compound efficacy...
June 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28638122/synergistic-effects-of-various-her-inhibitors-in-combination-with-igf-1r-c-met-and-src-targeting-agents-in-breast-cancer-cell-lines
#3
Aryan Stanley, G Hossein Ashrafi, Alan M Seddon, Helmout Modjtahedi
Overexpression of HER2 has been reported in around 25% of human breast cancers. Despite recent advances in HER2 targeted therapy, many patients still experience primary and secondary resistance to such treatments, the mechanisms for which are poorly understood. Here, we investigated the sensitivity of a panel of breast cancer cell lines to treatment with various types of HER-family inhibitors alone or in combination with other tyrosine kinase inhibitors or chemotherapeutic agents. We found that treatment with the second-generation irreversible HER-family inhibitors, particularly afatinib and neratinib, were more effective than treatment with the first-generation reversible inhibitors in inhibiting growth, migration and downstream cell signalling in breast cancer cells...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28628857/identification-of-b-and-t-cell-epitope-based-peptide-vaccine-from-igf-1-receptor-in-breast-cancer
#4
Manijeh Mahdavi, Violaine Moreau, Majid Kheirollahi
The insulin-like growth factor-1 receptor (IGF-1R) plays a key role in proliferation, growth, differentiation, and development of several human malignancies including breast and pancreatic adenocarcinoma. IGF-1R targeted immunotherapeutic approaches are particularly attractive, as they may potentially elicit even stronger antitumor responses than traditional targeted approaches. Cancer peptide vaccines can produce immunologic responses against cancer cells by triggering helper T cell (Th) or cytotoxic T cells (CTL) in association with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells...
June 8, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28627639/microrna-187-inhibits-tumor-growth-and-metastasis-via-targeting-of-igf-1r-in-hepatocellular-carcinoma
#5
Xinqiang Han, Xuemin Wang, Baolei Zhao, Gang Chen, Yuguo Sheng, Wenming Wang, Mujian Teng
Hepatocellular carcinoma (HCC) is the primary and most frequently occurring type of malignant liver cancer, accounting for 70-85% of total liver cancer cases worldwide. It has previously been demonstrated that the aberrant expression of microRNAs (miR) contributes to carcinogenesis and progression of various human malignancies, including HCC. However, mechanisms underlying the differential expression and specific roles of miR‑187 in HCC remain to be elucidated, particularly regarding how the modulation of malignant phenotypes in HCC cells occurs...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28625631/cd52-cd22-cd26-eg5-and-igf-1r-expression-in-thymic-malignancies
#6
J Remon, N Abedallaa, E Taranchon-Clermont, V Bluthgen, C R Lindsay, B Besse, V Thomas de Montpréville
BACKGROUND: Thymic epithelial tumours are rare cancers for which new treatment options are required. Identification of putative predictive markers is important for developing clinical trials. We studied the expression of five putative predictive biomarkers, potentially actionable by approved experimental drugs. METHODS: CD52, CD22, CD26, EG5, and IGF-1R expression were investigated by immunohistochemistry in formalin-fixed surgical samples of thymic epithelial tumour patients...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28624391/efficacy-of-melatonin-il-25-and-siil-17b-in-tumorigenesis-associated-properties-of-breast-cancer-cell-lines
#7
Gabriela Bottaro Gelaleti, Thaiz Ferraz Borin, Larissa Bazela Maschio-Signorini, Marina Gobbe Moschetta, Bruna Victorasso Jardim-Perassi, Guilherme Berto Calvinho, Mariana Castilho Facchini, Alicia M Viloria-Petit, Debora Aparecida Pires de Campos Zuccari
Mammary tumorigenesis can be modulated by melatonin, which has oncostatic action mediated by multiple mechanisms, including the inhibition of the activity of transcription factors such as NF-κB and modulation of interleukins (ILs) expression. IL-25 is an active cytokine that induces apoptosis in tumor cells due to differential expression of its receptor (IL-17RB). IL-17B competes with IL-25 for binding to IL-17RB in tumor cells, promoting tumorigenesis. This study purpose is to address the possibility of engaging IL-25/IL-17RB signaling to enhance the effect of melatonin on breast cancer cells...
June 14, 2017: Life Sciences
https://www.readbyqxmd.com/read/28619711/igfbp7-deletion-promotes-hepatocellular-carcinoma
#8
Maaged Akiel, Chunqing Guo, Xia Li, Devaraja Rajasekaran, Rachel G Mendoza, Chadia L Robertson, Nidhi Jariwala, Fang Yuan, Mark A Subler, Jolene Windle, Dawn K Garcia, Zhao Lai, Hung-I Harry Chen, Yidong Chen, Shah Giashuddin, Paul B Fisher, Xiang-Yang Wang, Devanand Sarkar
Activation of IGF signaling is a major oncogenic event in diverse cancers, including hepatocellular carcinoma (HCC). In this setting, the insulin-like growth factor binding protein IGFBP7 inhibits IGF signaling by binding the IGF-1 receptor (IGF-1R), functioning as a candidate tumor suppressor. IGFBP7 abrogates tumors by inhibiting angiogenesis and inducing cancer-specific senescence and apoptosis. Here we report that Igfbp7-deficient mice exhibit constitutively active IGF signaling, presenting with pro-inflammatory and immunosuppressive microenvironments and spontaneous liver and lung tumors occurring with increased incidence in carcinogen-treated subjects...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28608366/complement-component-1-q-subcomponent-binding-protein-c1qbp-in-lipid-rafts-mediates-hepatic-metastasis-of-pancreatic-cancer-by-regulating-igf-1-igf-1r-signaling
#9
Haojun Shi, Winston Fang, Minda Liu, Deliang Fu
Pancreatic cancer shows a remarkable predilection for hepatic metastasis. Complement component 1, q subcomponent binding protein (C1QBP) can mediate growth factor-induced cancer cell chemotaxis and distant metastasis by activation of receptor tyrosine kinases. Coincidentally, insulin-like growth factor-1 (IGF-1) derived from the liver and cancer cells itself has been recognized as a critical inducer of hepatic metastasis. However, the mechanism underlying IGF-1-dependent hepatic metastasis of pancreatic cancer, in which C1QBP may be involved, remains unknown...
June 12, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28599502/microrna-10b-inhibits-proliferation-migration-and-invasion-in-cervical-cancer-cells-via-direct-targeting-of-insulin-like-growth-factor-1-receptor
#10
Ren Hou, Daixian Wang, Jian Lu
MicroRNAs are deregulated in numerous types of human cancers and have crucial roles in the carcinogenesis and progression of human cancers. MicroRNA-10b (miR-10b) has been studied in several types of human cancer. However, the expression and roles of miR-10b in cervical cancer remain unknown. In the present study, the expression, functions and molecular mechanisms of miR-10b were explored in cervical cancer. The present data revealed that miR-10b was significantly downregulated in cervical cancer tissues and cell lines...
June 2017: Oncology Letters
https://www.readbyqxmd.com/read/28591197/efficacy-of-targeted-drugs-in-germ-cell-cancer-cell-lines-with-differential-cisplatin-sensitivity
#11
Judith Schaffrath, Hans-Joachim Schmoll, Wieland Voigt, Lutz P Müller, Carsten Müller-Tidow, Thomas Mueller
METHODS: The in vitro activity of kinase inhibitors targeting mTOR (RAD001), EGFR, HER2/neu, VEGFR (AEE788) and IGF-1R (AEW541) alone or in combination with cisplatin was tested in the cisplatin sensitive TGCT cell lines H12.1 and GCT72 as well as in the resistant cell lines H12.1RA, H12.1D, 1411HP and 1777NRpmet using the sulforhodamin-B-(SRB)-cytotoxicity-assay. To evaluate the activity of the kinase inhibitors, western blot analysis of the targeted receptors and their phosphorylated state was performed before and after exposure to each substance...
2017: PloS One
https://www.readbyqxmd.com/read/28583713/igf-1r-signalling-contributes-to-il-6-production-and-t-cell-dependent-inflammation-in-rheumatoid-arthritis
#12
Malin C Erlandsson, Sofia Töyrä Silfverswärd, Mitra Nadali, Minna Turkkila, Mattias N D Svensson, Ing-Marie Jonsson, Karin M E Andersson, Maria I Bokarewa
BACKGROUND: Signalling through insulin-like growth factor 1 receptor (IGF-1R) is essential for cell survival, but may turn pathogenic in uncontrolled tissue growth in tumours. In rheumatoid arthritis (RA), the IGF-1R signalling is activated and supports expansion of the inflamed synovia. AIM: In the present study, we assess if disruption of IGF-1R signalling resolves arthritis. MATERIAL AND METHODS: Clinical associations of IGF-1R expression in leukocytes of the peripheral blood were studied in 84 RA patients...
June 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28581517/functional-antagonism-of-%C3%AE-arrestin-isoforms-balance-igf-1r-expression-and-signalling-with-distinct-cancer-related-biological-outcomes
#13
N Suleymanova, C Crudden, T Shibano, C Worrall, I Oprea, A Tica, G A Calin, A Girnita, L Girnita
With very similar 3D structures, the widely expressed β-arrestin isoforms 1 and 2 play at times identical, distinct or even opposing roles in regulating various aspects of G protein-coupled receptors (GPCR) expression and signalling. Recent evidence recognizes the β-arrestin system as a key regulator of not only GPCRs, but also receptor tyrosine kinases, including the highly cancer relevant insulin-like growth factor type 1 receptor (IGF-1R). Binding of β-arrestin1 to IGF-1R leads to ligand-dependent degradation of the receptor and generates additional MAPK/ERK signalling, protecting cancer cells against anti-IGF-1R therapy...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28576774/aff-1-fusogen-can-rejuvenate-the-regenerative-potential-of-adult-dendritic-trees-via-self-fusion
#14
Veronika Kravtsov, Meital Oren-Suissa, Benjamin Podbilewicz
The aging brain undergoes structural changes, affecting brain homeostasis, neuronal function and consequently cognition. The complex architecture of dendritic arbors poses a challenge to understanding age-dependent morphological alterations, behavioral plasticity and remodeling following brain injury. Here, we use the PVD polymodal neurons of C. elegans as a model to study how aging affects neuronal plasticity. Using confocal live imaging of C. elegans PVD neurons, we demonstrate age-related progressive morphological alterations of intricate dendritic arbors...
June 2, 2017: Development
https://www.readbyqxmd.com/read/28560388/inhibition-of-igf-1-receptor-kinase-blocks-the-differentiation-into-cardiomyocyte-like-cells-of-bmscs-induced-by-igf-1
#15
Haibin Gong, Xiuli Wang, Lei Wang, Ying Liu, Jie Wang, Qian Lv, Hui Pang, Qinglin Zhang, Zhenquan Wang
Bone marrow mesenchymal stem cells (BMSCs) have the potential to transdifferentiate into cardiomyocyte‑like cells (CLCs) if an appropriate cardiac environment is provided. Insulin‑like growth factor‑1 (IGF‑1) plays an important role in the cell migration, survival and differentiation of BMSCs. However, the effect of IGF‑1 on the cellular differentiation remains unclear. In the present study, BMSCs were isolated from rat femurs and tibias and the cells were purified at passage 6 (P6). IGF‑1 and IGF‑1 receptor (IGF‑1R) kinase inhibitor I‑OMe AG538 were added to detect if IGF‑1 could induce BMSCs to transdifferentiate into CLCs and if I‑OMe AG538 could inhibit IGF‑1‑mediated receptor activation and downstream signaling...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28557430/identification-of-a-water-soluble-indirubin-derivative-as-potent-inhibitor-of-insulin-like-growth-factor-1-receptor-through-structural-modification-of-the-parent-natural-molecule
#16
Xinlai Cheng, Karl-Heinz Merz, Sandra Vatter, Jochen Zeller, Stephan Muehlbeyer, Andrea Thommet, Jochen Christ, Stefan Wölfl, Gerhard Eisenbrand
Indirubins have been identified as potent ATP-competitive protein kinase inhibitors. Structural modifications in the 5- and 3'-position have been extensively investigated, but the impact of substituents in 5'-position is not equally well-studied. Here, we report the synthesis of new indirubin 3'- and 5'-derivatives in the search of water-soluble indirubins by introducing basic centers. Antiproliferative activity of all compounds in tumor cells was evaluated along with kinase inhibition of selected compounds...
June 6, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28545426/insulin-like-growth-factor-1-receptor-affects-the-survival-of-primary-prostate-cancer-patients-depending-on-tmprss2-erg-status
#17
Caterina Mancarella, Irene Casanova-Salas, Ana Calatrava, Maria García-Flores, Cecilia Garofalo, Andrea Grilli, José Rubio-Briones, Katia Scotlandi, José Antonio López-Guerrero
BACKGROUND: Prostate cancer (PCa) is characterized by clinical and biological heterogeneity and has differential outcomes and mortality rates. Therefore, it is necessary to identify molecular alterations to define new therapeutic strategies based on the risk of progression. In this study, the prognostic relevance of the insulin-like growth factor (IGF) system was examined in molecular subtypes defined by TMPRSS2-ERG (T2E) gene fusion within a series of patients with primary localized PCa...
May 25, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28544544/insulin-like-growth-factor-1-signaling-is-responsible-for-cathepsin-g-induced-aggregation-of-breast-cancer-mcf-7-cells
#18
Riyo Morimoto-Kamata, Satoru Yui
Cathepsin G (CG), a neutrophil serine protease, induces cell migration and multicellular aggregation of human breast cancer MCF-7 cells in a process that is dependent on E-cadherin and CG enzymatic activity. While these tumor cell aggregates can cause tumor emboli that could represent intravascular growth and extravasation into the surrounding tissues, resulting in metastasis, the molecular mechanism underlying this process remains poorly characterized. In this study, we aimed to identify the signaling pathway that is triggered during CG-mediated stimulation of cell aggregation...
May 24, 2017: Cancer Science
https://www.readbyqxmd.com/read/28529580/microrna-592-targets-igf-1r-to-suppress-cellular-proliferation-migration-and-invasion-in-hepatocellular-carcinoma
#19
Wenyao Wang, Hongfei Zhang, Mao Tang, Longlong Liu, Zhengfang Zhou, Shaojun Zhang, Lichao Wang
MicroRNAs (miRs) can function as tumor suppressors or oncogenes in different types of human malignancy, and may provide an effective therapy for cancer. The expression and functions of miR-592 have previously been studied in relation to cancer. However, the expression and potential functions of miR-592 in hepatocellular carcinoma (HCC) are still unknown. Using quantitative polymerase chain reaction, MTT assays, cellular migration and invasion assays, bioinformatics software, western blot analysis and dual-luciferase report assays, the present study explored the expression and roles of miR-592 in HCC...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28528692/insulin-like-growth-factor-igf-axis-in-cancerogenesis
#20
REVIEW
Aldona Kasprzak, Wojciech Kwasniewski, Agnieszka Adamek, Anna Gozdzicka-Jozefiak
Determination of the role of insulin-like growth factor (IGF) family components in carcinogenesis of several human tumors is based on numerous epidemiological and pre-clinical studies, experiments in vivo and in vitro and on attempts at application of drugs affecting the IGF axis. Investigative hypotheses in original studies were based on biological functions manifested by the entire family of IGF (ligands, receptors, linking proteins, adaptor molecules). In the context of carcinogenesis the most important functions of IGF family involve intensification of proliferation and inhibition of cell apoptosis and effect on cell transformation through synthesis of several regulatory proteins...
April 2017: Mutation Research
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