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https://www.readbyqxmd.com/read/28938595/multiple-receptor-tyrosine-kinase-activation-related-to-alk-inhibitor-resistance-in-lung-cancer-cells-with-alk-rearrangement
#1
Se Hoon Choi, Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Woo Sung Kim, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
The activation of alternative receptor tyrosine kinases (RTKs) is known to mediate resistance to ALK inhibitors. However, the role of multiple RTK activation in resistance has yet to be determined. Two crizotinib-resistant (H3122/CR-1 and H3122/CR-2) and one TAE684-resistant (H2228/TR) cell lines were established. Multi-RTK arrays and Western blots were performed to detect the activation of bypass signals. There were no secondary mutations in the sequencing. EGFR and MET were activated in H3122/CR-1 cells whereas EGFR and IGF1R were activated in H3122/CR-2 cells...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28936199/bone-status-in-a-patient-with-insulin-like-growth-factor-1-receptor-deletion-syndrome-bone-quality-and-structure-evaluation-using-dual-energy-x-ray-absorptiometry-peripheral-quantitative-computed-tomography-and-quantitative-ultrasonography
#2
Paola Pelosi, Elisabetta Lapi, Loredana Cavalli, Alberto Verrotti, Marilena Pantaleo, Maurizio de Martino, Stefano Stagi
Haploinsufficiency of the insulin-like growth factor (IGF)-1 receptor (IGF1R) gene is a rare, probably under-diagnosed, cause of short stature. However, the effects of IGF1R haploinsufficiency on glucose metabolism, bone status, and metabolism have rarely been investigated. We report the case of a patient referred to our center at the age of 18 months for short stature, failure to thrive, and Silver-Russell-like phenotype. Genetic analysis did not show hypomethylation of the 11p15.5 region or uniparental disomy of chromosome 7...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28935632/cargo-selective-snx-bar-proteins-mediate-retromer-trimer-independent-retrograde-transport
#3
Arunas Kvainickas, Ana Jimenez-Orgaz, Heike Nägele, Zehan Hu, Jörn Dengjel, Florian Steinberg
The retromer complex, which recycles the cation-independent mannose 6-phosphate receptor (CI-MPR) from endosomes to the trans-Golgi network (TGN), is thought to consist of a cargo-selective VPS26-VPS29-VPS35 trimer and a membrane-deforming subunit of sorting nexin (SNX)-Bin, Amphyphysin, and Rvs (BAR; SNX-BAR) proteins. In this study, we demonstrate that heterodimers of the SNX-BAR proteins, SNX1, SNX2, SNX5, and SNX6, are the cargo-selective elements that mediate the retrograde transport of CI-MPR from endosomes to the TGN independently of the core retromer trimer...
September 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28932920/microrna-30a-inhibits-colorectal-cancer-metastasis-through-down-regulation-of-type-i-insulin-like-growth-factor-receptor
#4
Y C Liu, Y R Park, S L Kim, S T Lee, S W Kim
BACKGROUND: miR-30a expression is down-regulated and regulates tumor suppressors in various cancers. AIM: We investigated the mechanisms underlying the biological role of miR-30a in CRC. METHODS: MicroRNA, mRNA, and protein expression were analyzed by quantitative real-time PCR and Western blot. The migration and invasion abilities of CRC were determined by wound healing assay, and trans-well migration and invasion. A luciferase reporter assay was used to confirm the targets of miR-30a...
September 20, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28924044/nuclear-insulin-like-growth-factor-1-receptor-phosphorylates-proliferating-cell-nuclear-antigen-and-rescues-stalled-replication-forks-after-dna-damage
#5
Ahmed Waraky, Yingbo Lin, Dudi Warsito, Felix Haglund, Eiman Aleem, Olle Larsson
We have previously shown that the insulin like growth factor 1 receptor (IGF1R) translocates to the cell nucleus, where it binds to enhancer like regions and increases gene transcription. Further studies have demonstrated that nuclear IGF1R (nIGF1R) physically and functionally interacts with some nuclear proteins, i.e. the lymphoid enhancer binding factor 1 (Lef1), histone H3, and Brahma related gene 1 proteins. In the present study, we identified the proliferating cell nuclear antigen (PCNA) as a nIGF1R binding partner...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28900330/role-of-insulin-like-growth-factor-insulin-like-growth-factor-receptors-and-insulin-like-growth-factor-binding-proteins-in-ovarian-cancer
#6
REVIEW
Periyasamy Amutha, Thangarajan Rajkumar
Insulin and IGFs play an important role in cancer initiation and progression, including ovarian cancer (OC). Epithelial ovarian cancer (EOC) is the most frequent type of OC in women and it is the most lethal gynecological malignancy worldwide. Generally, insulin is associated with metabolism, whereas Insulin like growth factors (IGFs) are involved in cell proliferation. Hence, Insulin-like growth factor binding proteins (IGFBPs) determines the bioavailability of IGFs in circulation. The interplay between these molecules such as insulin, IGFs, IGFBPs and insulin-like growth factor receptor 1 (IGF1R) may be crucial for ovarian cancer cell biology and cancer progression...
April 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/28899882/chromosome-15-structural-abnormalities-effect-on-igf1r-gene-expression-and-function
#7
Rossella Cannarella, Teresa Mattina, Rosita A Condorelli, Laura M Mongioì, Giuseppe Pandini, Sandro La Vignera, Aldo E Calogero
Insulin-like growth factor 1 receptor (IGF1R), mapping on the 15q26.3 chromosome, is required for normal embryonic and postnatal growth. The aim of the present study was to evaluate the IGF1R gene expression and function in three unrelated patients with chromosome 15 structural abnormalities. We report two male patients with the smallest 15q26.3 chromosome duplication described so far, and a female patient with ring chromosome 15 syndrome. Patient one, with a 568 kb pure duplication, had overgrowth, developmental delay, mental and psychomotor retardation, obesity, cryptorchidism, borderline low testis volume, severe oligoasthenoteratozoospermia and gynecomastia...
October 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28898232/crosstalk-between-tems-and-endothelial-cells-modulates-angiogenesis-and-metastasis-via-igf1-igf1r-signalling-in-epithelial-ovarian-cancer
#8
Xinjing Wang, Qinyi Zhu, Yingying Lin, Li Wu, Xiaoli Wu, Kai Wang, Qizhi He, Congjian Xu, Xiaoping Wan, Xipeng Wang
BACKGROUND: Epithelial ovarian cancer (EOC) is the leading cause of death from gynaecologic malignancies and has a poor prognosis due to metastasis. Drugs targeting the angiogenesis pathway significantly improve patient outcome. However, the key factors linking angiogenesis and metastasis have not been elucidated. In this study, we found Tie2 expressing monocytes (CD14(+)Tie2(+), TEMs) as key contributors to angiogenesis and metastasis of EOC. METHODS: Tissue slides were evaluated by immunofluorescence for the presence of total tissue macrophages and TEMs...
September 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28882129/igf1r-activation-and-the-in-vitro-antiproliferative-efficacy-of-igf1r-inhibitor-are-inversely-correlated-with-igfbp5-expression-in-bladder-cancer
#9
Yann Neuzillet, Elodie Chapeaublanc, Clémentine Krucker, Leanne De Koning, Thierry Lebret, François Radvanyi, Isabelle Bernard-Pierrot
BACKGROUND: The insulin growth factor (IGF) pathway has been proposed as a potential therapeutic target in bladder cancer. We characterized the expression of components of the IGF pathway - insulin growth factor receptors (INSR, IGF1R, IGF2R), ligands (INS, IGF1, IGF2), and binding proteins (IGFBP1-7, IGF2BP1-3) - in bladder cancer and its correlation with IGF1R activation, and the anti-proliferative efficacy of an IGF1R kinase inhibitor in this setting. METHODS: We analyzed transcriptomic data from two independent bladder cancer datasets, corresponding to 200 tumoral and five normal urothelium samples...
September 7, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28873464/direct-integrin-binding-to-insulin-like-growth-factor-2-through-the-c-domain-is-required-for-insulin-like-growth-factor-receptor-type-1-igf1r-signaling
#10
Dora Maria Cedano Prieto, Yushen Cheng, Chih-Chieh Chang, Jessica Yu, Yoko K Takada, Yoshikazu Takada
We have reported that integrins crosstalk with growth factors through direct binding to growth factors (e.g., fibroblast growth factor-1, insulin-like growth factor 1 (IGF1), neuregulin-1, fractalkine) and subsequent ternary complex formation with cognate receptor [e.g., integrin/IGF1/IGF1 receptor (IGF1R)]. IGF1 and IGF2 are overexpressed in cancer and major therapeutic targets. We previously reported that IGF1 binds to integrins ανβ3 and α6β4, and the R36E/R37E mutant in the C-domain of IGF1 is defective integrin binding and signaling functions of IGF1, and acts as an antagonist of IGF1R...
2017: PloS One
https://www.readbyqxmd.com/read/28873240/gastric-poorly-cohesive-carcinoma-a-correlative-study-of-mutational-signatures-and-prognostic-significance-based-on-histopathologic-subtypes
#11
Chae Hwa Kwon, Young Keum Kim, Sojeong Lee, Ahrong Kim, Hye Ji Park, Yuri Choi, Yeo Jin Won, Do Youn Park, Gregory Y Lauwers
AIMS: Genome-wide next-generation sequencing has revealed several driver mutations and allows establishing a molecular taxonomy of gastric cancer. However, correlation between the broad mutational spectrum of gastric cancer and its various clinicopathological characteristics has yet to be fully elucidated. METHODS AND RESULTS: Herein, we analyzed the mutational pattern of 77 genes in a cohort of 91 patients with poorly cohesive carcinoma using targeted sequencing and evaluated the clinicopathological significance of the various mutations based its histologic pattern, either signet ring cell (SRC) or other types of poorly cohesive carcinoma (not otherwise specified) (PCC-NOS)...
September 5, 2017: Histopathology
https://www.readbyqxmd.com/read/28856781/cellular-apoptosis-and-cardiac-dysfunction-in-stz-induced-diabetic-rats-attenuated-by-anthocyanins-via-activation-of-igfi-r-pi3k-akt-survival-signaling
#12
Yin-Tso Liu, Pei-Chen Huang, Guei-Jane Wang, Ming-Jen Fan, Marthandam Asokan Shibu, Vijaya Padma Viswanadha, Yi-Lin Lin, Chao-Hung Lai, Yu-Feng Chen, Hung-En Liao, Chih-Yang Huang
Anthocyanins are known cyto-protective agents against various stress conditions. In this study cardio-protective effect of anthocyanins from black rice against diabetic mellitus (DM) was evaluated using a streptozotocin (STZ)-induced DM rat model. Five-week-old male Wistar rats were administered with STZ (55 mg kg(-1) , IP) to induce DM; rats in the treatment group received 250 mg oral anthocyanin/kg/day during the 4-week treatment period. DM and the control rats received normal saline through oral gavage...
August 30, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28834114/galangin-suppresses-h2-o2-induced-aging-in-human-dermal-fibroblasts
#13
Su-Ying Wen, Jia-Yi Chen, Yueh-Shan Weng, Ritu Aneja, Chih-Jung Chen, Chih-Yang Huang, Wei-Wen Kuo
Human skin aging is a progressive process that includes intrinsic aging and extrinsic photodamage, both of which can cause an accumulation of reactive oxygen species (ROS), resulting in dermal fibrosis dysfunction and wrinkle formation. Galangin is a flavonoid that exhibits anti-inflammatory and antioxidative potential. Previous studies have reported that galangin has antioxidative activity against ROS-mediated stress. The aim of the present study is to determine the antiaging effects of galangin on dermal fibroblasts exposed to H2 O2 ...
August 18, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28830678/expression-and-purification-of-functional-insulin-and-insulin-like-growth-factor-1-holoreceptors-from-mammalian-cells
#14
Richard J Delle Bovi, W Todd Miller
The insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) are receptor tyrosine kinases (RTKs) involved in the regulation of many important cellular processes. The current proposed models of activation are derived from structural studies using soluble extracellular domains and cytoplasmic tyrosine kinase domains. Preparations of full length IR and IGF1R have been hampered by the need for unconventional affinity chromatography resins and/or harsh eluting conditions. Here, we present a purification protocol to obtain full-length, detergent solubilized IR and IGF1R at quantities suitable for biochemical and structural characterization...
August 19, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28822459/oral-propylene-glycol-modifies-follicular-fluid-and-gene-expression-profiles-in-cumulus-oocyte-complexes-and-embryos-in-feed-restricted-heifers
#15
G Gamarra, C Ponsart, S Lacaze, F Nuttinck, A Cordova, P Mermillod, B Marquant-Le Guienne, D Monniaux, P Humblot, A A Ponter
Dietary supplementation with propylene glycol (PG) increases in vitro production of high-quality embryos in feed-restricted heifers. The aim of the present study was to evaluate the effects of PG in feed-restricted heifers on follicular fluid insulin and insulin-like growth factor (IGF) 1 concentrations, expression of IGF system genes in oocytes and cumulus cells and the expression of selected genes in blastocysts. Feed-restricted (R) heifers were drenched with water or PG during induced oestrous cycles (400mL of PG or water/drench, daily drenching at 1600 hours for the first 9 days of the oestrous cycle)...
August 21, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28822014/functional-igf1r-variant-predicts-breast-cancer-risk-in-women-with-preeclampsia-in-california-teachers-study
#16
Mark J Powell, Julie Von Behren, Susan Neuhausen, Peggy Reynolds, Christopher C Benz
PURPOSE: Hypertension in pregnancy has been associated with decreased future risk of breast cancer in many but not all studies. In the Marin Women's Study, pregnancy-induced hypertension was shown to interact with the T allele of a functional IGF1R gene variant, rs2016347, to result in lower breast density, as well as decreased breast cancer risk. Our objective was to explore these findings in a larger sample of women from the California Teachers Study (CTS). METHODS: The CTS cohort consists of over 130,000 female educators...
August 18, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28821223/maternal-nutrient-restriction-in-mid-to-late-gestation-influences-fetal-mrna-expression-in-muscle-tissues-in-beef-cattle
#17
Francois Paradis, Katie M Wood, Kendall C Swanson, Stephen P Miller, Brian W McBride, Carolyn Fitzsimmons
BACKGROUND: Manipulating maternal nutrition during specific periods of gestation can result in re-programming of fetal and post-natal development. In this experiment we investigated how a feed restriction of 85% compared with 140% of total metabolizable energy requirements, fed to cows during mid-to-late gestation, influences phenotypic development of fetuses and mRNA expression of growth (Insulin-Like Growth Factor family and Insulin Receptor (INSR)), myogenic (Myogenic Differentiation 1 (MYOD1), Myogenin (MYOG), Myocyte Enhancer Factor 2A (MEF2A), Serum Response Factor (SRF)) and adipogenic (Peroxisome Proliferator Activated Receptor Gamma (PPARG)) genes in fetal longissimus dorsi (LD) and semitendinosus (ST) muscle...
August 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28816378/correlation-of-the-expressions-of-igf1r-rack1-stat3-and-bcl-xl-in-nasopharyngeal-carcinoma-with-the-clinicopathological-features-and-prognosis-of-nasopharyngeal-carcinoma
#18
Shan Wang, Min Shen, Xin Wen, Xin-Rui Han, Yong-Jian Wang, Shao-Hua Fan, Juan Zhuang, Zi-Feng Zhang, Qun Shan, Meng-Qiu Li, Bin Hu, Chun-Hui Sun, Xia Ge, Qiu-Mei Lei, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
The aim of this study was to investigate the correlation of expression of IGF1R-RACK1-STAT3 and Bcl-xl in nasopharyngeal carcinoma (NPC) with the clinicopathological features and the prognosis of NPC. Our study selected 215 NPC tissues and 178 chronic nasopharyngitis tissues (control group). Positive expression rates of IGF1R, RACK1, STAT3 and Bcl-xl were tested by immunohistochemical method, and expression of IGF1R, RACK1, STAT3, Bcl-xl, Bcl-2 and Bax by western blotting. Correlation of IGF1R, RACK1, STAT3 and Bcl-xl with the clinicopathological features of NPC was analyzed...
August 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28814964/milk-disrupts-p53-and-dnmt1-the-guardians-of-the-genome-implications-for-acne-vulgaris-and-prostate-cancer
#19
Bodo C Melnik
There is accumulating evidence that milk shapes the postnatal metabolic environment of the newborn infant. Based on translational research, this perspective article provides a novel mechanistic link between milk intake and milk miRNA-regulated gene expression of the transcription factor p53 and DNA methyltransferase 1 (DNMT1), two guardians of the human genome, that control transcriptional activity, cell survival, and apoptosis. Major miRNAs of milk, especially miRNA-125b, directly target TP53 and complex p53-dependent gene regulatory networks...
2017: Nutrition & Metabolism
https://www.readbyqxmd.com/read/28800359/the-selective-pi3k%C3%AE-inhibitor-byl719-as-a-novel-therapeutic-option-for-neuroendocrine-tumors-results-from-multiple-cell-line-models
#20
Svenja Nölting, Jakob Rentsch, Helma Freitag, Katharina Detjen, Franziska Briest, Markus Möbs, Victoria Weissmann, Britta Siegmund, Christoph J Auernhammer, Elke Tatjana Aristizabal Prada, Michael Lauseker, Ashley Grossman, Samantha Exner, Christian Fischer, Carsten Grötzinger, Jörg Schrader, Patricia Grabowski
BACKGROUND/AIMS: The therapeutic options for metastatic neuroendocrine tumors (NETs) are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1) and pulmonary (H727) NET cell lines. METHODS: Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA...
2017: PloS One
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