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IGF-1R

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https://www.readbyqxmd.com/read/28218468/igf-1-receptor-expression-on-circulating-osteoblast-progenitor-cells-predicts-tissue-based-bone-formation-rate-and-response-to-teriparatide-in-premenopausal-women-with-idiopathic-osteoporosis
#1
Adi Cohen, Stavroula Kousteni, Brygida Bisikirska, Jayesh G Shah, J Sanil Manavalan, Robert R Recker, Joan Lappe, David W Dempster, Hua Zhou, Donald J McMahon, Mariana Bucovsky, Mafo Kamanda-Kosseh, Julie Stubby, Elizabeth Shane
We have previously reported that premenopausal women with idiopathic osteoporosis (IOP) have profound microarchitectural deficiencies and heterogeneous bone remodeling. Those with the lowest bone formation rate have higher baseline serum IGF-1 levels and less robust response to teriparatide. Because IGF-1 stimulates bone formation and is critical for teriparatide action on osteoblasts, these findings suggest a state of IGF-1 resistance in some IOP women. To further investigate the hypothesis that osteoblast and IGF-1 related mechanisms mediate differential responsiveness to teriparatide in IOP, we studied circulating osteoblast progenitor (COP) cells and their IGF-1 receptor (IGF-1R) expression...
February 20, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28199951/a-dioxidovanadium-v-complex-of-nno-donor-schiff-base-as-a-selective-inhibitor-of-protein-tyrosine-phosphatase-1b-synthesis-characterization-and-biological-activities
#2
Yuqi Jia, Liping Lu, Miaoli Zhu, Caixia Yuan, Shu Xing, Xueqi Fu
A new dioxidovanadium (V) complex, VO2(HPPCH) (1) (H2PPCH = N'-picolinoylpyridin-1-ium-2-carbohydrazonate) has been synthesized and characterized by elemental analysis, IR, X-ray diffraction analysis and electrospray ionization mass spectra. Complex 1 crystallized in the monoclinic system with space group P21/c. It potently inhibited PTP1B with IC50 of 0.13 μM, about 7, 15 and 125-fold stronger against PTP1B than over TCPTP, SHP-1 and SHP-2, displaying obvious selectivity against PTP1B. Western blotting analysis indicated that complex 1 effectively increased the phosphorylation of PTP1B substrates, especially the phosphorylation of IR/IGF 1R and IRS-1...
February 6, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28188432/correlations-of-igf-1r-and-cox-2-expressions-with-ras-and-braf-genetic-mutations-clinicopathological-features-and-prognosis-of-colorectal-cancer-patients
#3
Mei Jin, Zi-Wen Long, Jing Yang, Xiang Lin
This case-control study aims to investigate the correlations of insulin-like growth factor receptor 1 (IGF-1R) and cyclooxygenase 2 (COX-2) expressions with Ras and BRAF genetic mutations, clinicopathological features and prognosis of colorectal cancer (CRC) patients. A total of 213 CRC patients (case group) and 200 healthy individuals (control group) were selected from our hospital. Ras (K-Ras/N-Ras) and BRAF genetic mutations were detected by direct sequencing. The positive expression rates of IGF-IR and COX-2 in CRC and normal tissues were detected using immunohistochemistry...
February 10, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28153033/klotho-an-anti-aging-gene-acts-as-a-tumor-suppressor-and-inhibitor-of-igf-1r-signaling-in-diffuse-large-b-cell-lymphoma
#4
Xiangxiang Zhou, Xiaosheng Fang, Yujie Jiang, Lingyun Geng, Xinyu Li, Ying Li, Kang Lu, Peipei Li, Xiao Lv, Xin Wang
BACKGROUND: Klotho, is a transmembrane protein, performs as a circulating hormone and upstream modulator of the insulin-like growth factor-1 receptor (IGF-1R), fibroblast growth factor (FGF), and Wnt signaling pathways. These pathways are involved in the development and progression of B cell lymphoma. We aimed to explore the expression pattern and functional mechanism of Klotho in diffuse large B cell lymphoma (DLBCL). METHODS: Immunohistochemistry (IHC) and western blotting were performed to detect the expression level of Klotho in DLBCL patients and cell lines...
February 2, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28138221/immunotherapy-for-the-treatment-of-colorectal-tumors-focus-on-approved-and-in-clinical-trial-monoclonal-antibodies
#5
REVIEW
Alex Françoso, Patricia Ucelli Simioni
Colorectal cancer is considered a disease of the elderly population. Since the number of geriatric patients continues to rise, monoclonal antibody therapy is the most promising therapy in the recent research. Presently, the monoclonal antibodies most frequently used in the treatment of colorectal tumors are bevacizumab, cetuximab, panitumumab, and ramucirumab. Bevacizumab is a monoclonal antibody that acts on VEGF. Cetuximab and panitumumab act on EGFR. Ramucirumab binds directly to the ligand-binding pocket of VEGFR-2 to block the binding of VEGF-A, VEGF-C, and VEGF-D...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28124574/curcumin-regulates-insulin-pathways-and-glucose-metabolism-in-the-brains-of-appswe-ps1de9-mice
#6
Pengwen Wang, Caixin Su, Huili Feng, Xiaopei Chen, Yunfang Dong, Yingxue Rao, Ying Ren, Jinduo Yang, Jing Shi, Jinzhou Tian, Shucui Jiang
Recent studies have shown the therapeutic potential of curcumin in Alzheimer's disease (AD). In 2014, our lab found that curcumin reduced Aβ40, Aβ42 and Aβ-derived diffusible ligands in the mouse hippocampus, and improved learning and memory. However, the mechanisms underlying this biological effect are only partially known. There is considerable evidence in brain metabolism studies indicating that AD might be a brain-specific type of diabetes with progressive impairment of glucose utilisation and insulin signalling...
January 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28123579/mir-143-inhibits-bladder-cancer-cell-proliferation-and-enhances-their-sensitivity-to-gemcitabine-by-repressing-igf-1r-signaling
#7
Hengbing Wang, Qi Li, Xiaobing Niu, Gongcheng Wang, Sinian Zheng, Guangbo Fu, Zengjun Wang
microRNAs (miRNAs) are a class of small RNAs that regulate gene expression. It has been demonstrated that aberrant miRNA expression is associated with cancer development and carcinogenesis. Altered miRNA expression has been suggested to occur in bladder cancer. In other cancer systems, studies have indicated that miR-143, as a tumor suppressor gene, plays essential roles in cancer progression. However, its role in bladder cancer has yet to be elucidated. In the present study, we observed that miR-143 expression was downregulated in human bladder cancer tissues and cells, and that its levels were negatively correlated with bladder cancer clinical stages...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28112398/sumo-modified-insulin-like-growth-factor-1-receptor-igf-1r-increases-cell-cycle-progression-and-cell-proliferation
#8
Yingbo Lin, Hongyu Liu, Ahmed Waraky, Felix Haglund, Prasoon Agarwal, Helena Jernberg-Wiklund, Dudi Warsito, Olle Larsson
Increasing number of studies have shown nuclear localization of the insulin-like growth factor 1 receptor (nIGF-1R) in tumor cells and its links to adverse clinical outcome in various cancers. Any obvious cell physiological roles of nIGF-1R have, however, still not been disclosed. Previously, we reported that IGF-1R translocates to cell nucleus and modulates gene expression by binding to enhancers, provided that the receptor is SUMOylated. In this study, we constructed stable transfectants of wild type IGF1R (WT) and triple-SUMO-site-mutated IGF1R (TSM) using igf1r knockout mouse fibroblasts (R-)...
January 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28109944/synthesis-biological-evaluation-and-molecular-dynamics-md-simulation-studies-of-three-novel-f-18-labeled-and-focal-adhesion-kinase-fak-targeted-5-bromo-pyrimidines-as-radiotracers-for-tumor
#9
Yu Fang, Dawei Wang, Xingyu Xu, Jianping Liu, Aiqin Wu, Xiang Li, Qianqian Xue, Huan Wang, Hang Wang, Huabei Zhang
Focal adhesion kinase (FAK) is considered as an attractive target for oncology. A series of F-18 labeled 5-bromo-N(2)-(4-(2-fluoro-pegylated (FPEG))-3,5-dimethoxyphenyl)-N(4)-(4-methoxyphenyl)pyrimidine-2,4-diamine derivatives were prepared and evaluated as the FAK targeted radiotracers for the early diagnoses of tumor. For the study of the FAK targeted drug molecules, this was the first attempt to develop the tumor diagnostic imaging agents on the radiopharmaceutical level. They inhibited the activity of FAK with IC50 in the range of 91...
January 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28109147/-co-culture-with-umbilical-cord-mesenchymal-stem-cells-promotes-the-synthesis-and-mechnism-of-milk-protein-in-bovine-mammary-epithelial-cells
#10
Yankun Zhao, Wei Shao, Chenglong Luo, Kaile Wu, Xiong Yu
Objective To explore the possible mechanism of umbilical cord mesenchymal stem cells (UCMSCs) regulating milk protein synthesis in bovine mammary gland epithelial cells (BMECs). Methods UCMSCs and BMECs were co-cultured by double-chamber Transwell(TM), and other BMECs were cultured alone as a control group. Insulin like growth factor 1 receptor (IGF-1R) inhibitor AG1024 was used to treat cells. IGF-1, β casein (CSN2) and κ casein (CSN3) content in the supernatants were determined by ELISA; the relative expression abundance of Janus kinase and signal transducer and activator of transcription factor (JAK/STAT) signaling pathway-related genes were detected by quantitative real-time PCR (qRT-PCR); and after the cells were treated with JAK2 signal blocker AG490, qRT-PCR was performed to test the relative expression abundance of CSN2 and CSN3 mRNAs...
February 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28104361/igfbp-a-novel-target-of-lung-cancer
#11
REVIEW
Qiongge Hu, Yong Zhou, Kejing Ying, Wenjing Ruan
The insulin-like growth factor-1 receptor (IGF-1R) is a central component of lung cancer signal transduction pathways. A phase III study failed for carboplatin, paclitaxel, with or without figitumumab in first-line treating metastatic non-small cell lung cancer (NSCLC). There is an urgent need for a better understanding of signaling in IGF system. Insulin-like growth factor-binding proteins (IGFBPs) function as modulators for IGF signaling through sequestration of IGFs in serum and the extracellular fluid. IGFBPs can also act as transporters or modulators for IGF action and insulin action...
January 17, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28101246/detection-of-microrna-200b-may-predict-the-inhibitory-effect-of-gefitinib-on-non-small-cell-lung-cancer-and-its-potential-mechanism
#12
Zhiwu Liu, Liqiong Yao, Bangyun Tan, Li Li, Baojin Chen
The present study aimed to investigate the association and underlying mechanisms between microRNA-200b level and the inhibitory effect of gefitinib on non-small cell lung cancer. In total, 100 patients (43 males and 57 females; median age, 63 years) with advanced non-small cell lung cancer (NSCLC) were selected. All patients were administered with gefitinib orally (250 mg/day) and the effect of gefitinib was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines. Tumor tissue and plasma samples were collected prior to and subsequent to therapy...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28097905/discovery-of-novel-dual-inhibitors-of-receptor-tyrosine-kinases-egfr-and-igf-1r
#13
Cornelius Hempel, Frank Totzke, Christoph Schächtele, Abdulkarim Najjar, Wolfgang Sippl, Christoph Ritter, Andreas Hilgeroth
Novel 4-benzylamino benzo-anellated pyrrolo[2,3-b]pyridines have been synthesized with varied substitution patterns both at the molecular scaffold of the benzo-anellated ring and at the 4-benzylamino residue. With a structural similarity to substituted thieno[2,3-d]pyrimidines as epidermal growth factor receptor (EGFR) inhibitors, we characterized the inhibition of EGFR for our novel compounds. As receptor heterodimerization gained certain interest as mechanism of cancer cells to become resistant against novel protein kinase inhibitors, we additionally measured the inhibition of insulin-like growth factor receptor IGF-1R which is a prominent receptor for such heterodimerizations with EGFR...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28097474/igf-1r-regulates-the-extracellular-level-of-active-mmp-2-pathological-neovascularization-and-functionality-in-retinas-of-oir-mouse-model
#14
Valeria E Lorenc, Paula V Subirada Caldarone, María C Paz, Darío G Ferrer, José D Luna, Gustavo A Chiabrando, María C Sánchez
In ischemic proliferative diseases such as retinopathies, persistent hypoxia leads to the release of numerous neovascular factors that participate in the formation of abnormal vessels and eventually cause blindness. The upregulation and activation of metalloproteinases (MMP-2 and MMP-9) represent a final common pathway in this process. Although many regulators of the neovascular process have been identified, the complete role of the insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) appears to be significantly more complex...
January 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28096479/igf-1-receptor-modulates-foxo1-mediated-tamoxifen-response-in-breast-cancer-cells
#15
Ali Vaziri-Gohar, Yan Zheng, Kevin D Houston
: Tamoxifen is a common adjuvant treatment for ERalpha-positive breast cancer patients, however acquired resistance abrogates the efficacy of this therapeutic approach. We recently demonstrated that G protein-coupled estrogen receptor 1 (GPER1) mediates tamoxifen action in breast cancer cells by inducing insulin-like growth factor binding protein-1 (IGFBP-1) to inhibit IGF-1-dependent signaling. To determine if dysregulation of IGFBP-1 induction is associated with tamoxifen resistance, IGFBP-1 transcription was measured in tamoxifen-resistant MCF-7 cells (TamR) after tamoxifen (Tam) treatment...
January 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28093198/mild-hypothermia-pretreatment-protects-hepatocytes-against-ischemia-reperfusion-injury-via-down-regulating-mir-122-and-igf-1r-akt-pathway
#16
Qi Xiao, Qi-Fa Ye, Wei Wang, Bi-Qi Fu, Zhi-Ping Xia, Zhong-Zhong Liu, Xing-Jian Zhang, Yan-Feng Wang
BACKGROUND: Mild hypothermia has been well known as an effective way to reduce ischemia reperfusion injury (IRI), while the mechanisms are still unclear. More and more evidences have indicated that miRNAs should been involved in the regulation of IRI and expecially some miRNAs have shown temp-responsiveness for temperature variation. Therefore, the role of miR-122 in mild hypothermia pretreatment after IRI was investigated. METHODS: We established a LO2 cell anoxia-reoxygenation injury model to simulate liver IRI...
January 13, 2017: Cryobiology
https://www.readbyqxmd.com/read/28092675/unbalancing-p53-mdm2-igf-1r-axis-by-mdm2-activation-restrains-the-igf-1-dependent-invasive-phenotype-of-skin-melanoma
#17
C Worrall, N Suleymanova, C Crudden, I Trocoli Drakensjö, E Candrea, D Nedelcu, S-I Takahashi, L Girnita, A Girnita
Melanoma tumors usually retain wild-type p53; however, its tumor-suppressor activity is functionally disabled, most commonly through an inactivating interaction with mouse double-minute 2 homolog (Mdm2), indicating p53 release from this complex as a potential therapeutic approach. P53 and the tumor-promoter insulin-like growth factor type 1 receptor (IGF-1R) compete as substrates for the E3 ubiquitin ligase Mdm2, making their relative abundance intricately linked. Hence we investigated the effects of pharmacological Mdm2 release from the Mdm2/p53 complex on the expression and function of the IGF-1R...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28088554/mir-99a-suppresses-proliferation-migration-invasion-and-induces-g1-phase-cell-cycle-arrest-via-targeting-igf-1r-pathway-in-renal-cell-carcinoma-786-0-and-os-rc-2-cells
#18
Bo Hao, Li Cui, Yi Gu, Bo Zhang, Min Wang, Hua Zhou, Renfang Xu, XiaoZhou He
OBJECTIVE: To explore the potential mechanism of microRNA-99a (miR-99a) and IGF-1R (insulin-like growth factor 1 receptor) accounting for RCC. MATERIALS AND METHODS: The RCC 786-O and OS-RC-2 cells were transfected with miR-99a mimics or small interfering RNA (siRNA) that silence the IGF-1R (IGF-1R-siRNA) to upregulate the expression of miR-99a and to downregulate the expression of IGF-1R. Real-time PCR and western-blot were used to detect the expression of proteins...
January 11, 2017: Urology
https://www.readbyqxmd.com/read/28063218/cyclic-glycine-proline-accelerates-mammary-involution-by-promoting-apoptosis-and-inhibiting-igf-1-function
#19
Gagandeep Singh-Mallah, Christopher D McMahon, Jian Guan, Kuljeet Singh
In rodents, post-lactational involution of mammary glands is characterized by the loss of mammary epithelial cells via apoptosis, which is associated with a decline in the expression of insulin-like growth factor-1 (IGF-1). Overexpression of IGF-1 delays involution by inhibiting apoptosis of epithelial cells and preserving the remaining secretory alveoli. Cyclic-glycine-proline (cGP), a metabolite of IGF-1, normalizes IGF-1 function under pathological conditions by regulating the bioavailability of IGF-1. The present study investigated the effect of cGP on the physiological decline in IGF-1 function during post-lactational mammary involution...
January 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28046018/co-targeting-igf-1r-and-autophagy-enhances-the-effects-of-cell-growth-suppression-and-apoptosis-induced-by-the-igf-1r-inhibitor-nvp-aew541-in-triple-negative-breast-cancer-cells
#20
Weibin Wu, Jieyi Ma, Nan Shao, Yawei Shi, Ruiming Liu, Wen Li, Yin Lin, Shenming Wang
BACKGROUND: Triple-negative breast cancer (TNBC) is the most intractable type of breast cancer, and there is a lack of effective targeted therapy. Insulin-like growth factor-1 receptor (IGF-1R) is reportedly a potential target for TNBC treatment. However, satisfying treatment outcomes in breast cancer patients have yet to be achieved with IGF-1R-targeted agents. METHODS: To confirm whether inhibiting IGF-1R could induce autophagy, we detected autophagy-related proteins by western blotting and immunofluorescence staining of LC3-II...
2017: PloS One
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