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IGF-1R

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https://www.readbyqxmd.com/read/28726241/investigating-the-role-of-the-igf-axis-as-a-predictor-of-biochemical-recurrence-in-prostate-cancer-patients-post-surgery
#1
Kieran J Breen, Amanda O'Neill, Lisa Murphy, Yue Fan, Susie Boyce, Noel Fitzgerald, Emma Dorris, Lauren Brady, Stephen P Finn, Brian D Hayes, Ann Treacy, Ciara Barrett, Mardiana Abdul Aziz, Elaine W Kay, John M Fitzpatrick, R William G Watson
BACKGROUND: Between 20% and 35% of prostate cancer (PCa) patients who undergo treatment with curative intent (ie, surgery or radiation therapy) for localized disease will experience biochemical recurrence (BCR). Alterations in the insulin-like growth factor (IGF) axis and PTEN expression have been implicated in the development and progression of several human tumors including PCa. We examined the expression of the insulin receptor (INSR), IGF-1 receptor (IGF-1R), PTEN, and AKT in radical prostatectomy tissue of patients who developed BCR post-surgery...
July 20, 2017: Prostate
https://www.readbyqxmd.com/read/28724578/induction-of-regulatory-t-cells-and-its-regulation-with-insulin-like-growth-factor-insulin-like-growth-factor-binding-protein-4-by-human-mesenchymal-stem-cells
#2
Ippei Miyagawa, Shingo Nakayamada, Kazuhisa Nakano, Kaoru Yamagata, Kei Sakata, Kunihiro Yamaoka, Yoshiya Tanaka
Human mesenchymal stem cells (MSCs) are multipotent and exert anti-inflammatory effects, but the underlying mechanism remains to be elucidated. In the current study, we investigated the regulatory mechanism of regulatory T cell (Treg) induction through the growth factors released by human MSCs. Human naive CD4(+) T cells were stimulated with anti-CD3/28 Abs and cocultured with human MSC culture supernatant for 48 h. The proliferation and cytokine production of CD4(+) T cells and surface molecule expression on CD4(+) T cells were evaluated...
July 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28722660/glypican-3-induces-oncogenicity-by-preventing-igf-1r-degradation-a-process-that-can-be-blocked-by-grb10
#3
Wei Cheng, Po-Chun Huang, Hsiao-Mei Chao, Yung-Ming Jeng, Hey-Chi Hsu, Hung-Wei Pan, Wuh-Liang Hwu, Yu-May Lee
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a major cause of cancer-related death worldwide. Previously, we demonstrated that glypican-3 (GPC3) is highly expressed in HCC, and that GPC3 induces oncogenicity and promotes the growth of cancer cells through IGF-1 receptor (IGF-1R). In the present study, we investigated the mechanisms of GPC3-mediated enhancement of IGF-1R signaling. We demonstrated that GPC3 decreased IGF-1-induced IGF-1R ubiquitination and degradation and increased c-Myc protein levels...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28716107/biomarkers-of-resistance-to-radiation-therapy-a-prospective-study-in-cervical-carcinoma
#4
P Moreno-Acosta, A Vallard, S Carrillo, O Gamboa, A Romero-Rojas, M Molano, J Acosta, D Mayorga, C Rancoule, M A Garcia, M Cotes Mestre, N Magné
BACKGROUND: Clinical parameters and proteins have recently been suggested as possible causes of radiotherapy (RT) resistance in cervical carcinoma (CC). The objective of the present study was to validate prognostic biomarkers of radiation resistance. METHODS: The present prospective study included patients undergoing RT with curative intent for histologically proven locally advanced squamous cell CC. Tissues and blood samples were systematically collected before RT initiation...
July 17, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28714005/microrna%C3%A2-455-is-downregulated-in-gastric-cancer-and-inhibits-cell-proliferation-migration-and-invasion-via-targeting-insulin%C3%A2-like-growth-factor-1-receptor
#5
Shan Zhang, Wan-Ling Yin, Xin Zhang, Xiao-Yu Zhang
Gastric cancer is the fourth most common and the second leading cause of cancer mortality worldwide. The dysregulation of microRNAs has been demonstrated to be significant in gastric cancer carcinogenesis and progression due to changes in expression of their target genes. In the current study, microRNA‑455 (miR‑455) was identified to be significantly downregulated in gastric cancer tissue samples and cell lines. A low expression level of miR‑455 was correlated with the clinical stage, lymph node metastasis and tumor invasion in gastric cancer...
July 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28711909/h2o2-attenuates-igf-1r-tyrosine-phosphorylation-and-its-survival-signaling-properties-in-neuronal-cells-via-nr2b-containing-nmda-receptor
#6
Zhiwen Zeng, Dejun Wang, Uma Gaur, Liao Rifang, Haitao Wang, Wenhua Zheng
Impairment of insulin-like growth factor I (IGF-I) signaling plays an important role in the development of neurodegeneration. In the present study, we investigated the effect of H2O2 on the survival signaling of IGF-1 and its underlying mechanisms in human neuronal cells SH-SY5Y. Our results showed that IGF-1 promoted cell survival and stimulated phosphorylation of IGF-1R as well as its downstream targets like AKT and ERK1/2 in these cells. Meanwhile, these effects of IGF-1 were abolished by H2O2 at 200μM concentration which did not cause any significant toxicity to cells itself in our experiments...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28709872/s-nitrosylation-of-the-igf-1-receptor-disrupts-the-cell-proliferative-action-of-igf-1
#7
Kazushi Okada, Bao-Ting Zhu
The insulin-like growth factor 1 receptor (IGF-1R) is a disulfide-linked heterotetramer containing two α-subunits and two β-subunits. Earlier studies demonstrate that nitric oxide (NO) can adversely affect IGF-1 action in the central nervous system. It is known that NO can induce S-nitrosylation of the cysteine residues in proteins, thereby partly contributing to the regulation of protein function. In the present study, we sought to determine whether S-nitrosylation of the cysteine residues in IGF-1R is an important post-translational modification that regulates its response to IGF-1...
July 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28708941/regulation-of-the-insulin-akt-signaling-pathway-and-glycolysis-during-dehydration-stress-in-the-african-clawed-frog-xenopus-laevis
#8
Cheng-Wei Wu, Shannon N Tessier, Kenneth B Storey
Estivation is an adaptive stress response utilized by some amphibians during periods of drought in the summer season. In this study, we examine the regulation of the insulin signaling cascade and glycolysis pathway in the African clawed frog Xenopus laevis during dehydration stress induced state of estivation. We show that in the brain and heart of X. laevis, dehydration reduces the phosphorylation of the insulin growth factor-1 receptor (IGF-1R), and this is followed by similar reductions in the phosphorylation of the Akt and mechanistic target of rapamycin (mTOR) kinase...
July 14, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28706275/novel-function-of-pregnancy-associated-plasma-protein-a-promotes-endometrium-receptivity-by-up-regulating-n-fucosylation
#9
Ming Yu, Jiao Wang, Shuai Liu, Xiaoqi Wang, Qiu Yan
Glycosylation of uterine endometrial cells plays important roles to determine their receptive function to blastocysts. Trophoblast-derived pregnancy-associated plasma protein A (PAPPA) is specifically elevated in pregnant women serum, and is known to promote trophoblast cell proliferation and adhesion. However, the relationship between PAPPA and endometrium receptivity, as well as the regulation of N-fucosylation remains unclear. We found that rhPAPPA and PAPPA in the serum samples from pregnant women or conditioned medium of trophoblast cells promoted endometrium receptivity in vitro...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696156/the-igf-1r-akt-pathway-has-opposing-effects-on-nutlin-3a-induced-apoptosis
#10
Batzaya Davaadelger, Ricardo E Perez, Yalu Zhou, Lei Duan, Steven Gitelis, Carl G Maki
Nutlin-3a is a small molecule MDM2 antagonist and potent activator of wild-type p53. Nutlin-3a disrupts MDM2 binding to p53, thus increasing p53 levels and allowing p53 to inhibit proliferation or induce cell death. Factors that control sensitivity to Nutlin-3a-induced apoptosis are incompletely understood. In this study we isolated cisplatin-resistant clones from MHM cells, an MDM2-amplified and p53 wild-type osteosarcoma cell line. Cisplatin resistance in these clones resulted in part from heightened activation of the IGF-1R/AKT pathway...
July 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28687332/systemic-analysis-of-different-colorectal-cancer-cell-lines-and-tcga-datasets-identified-igf-1r-egfr-ppar-caspase-axis-as-important-indicator-for-radiotherapy-sensitivity
#11
Lin Chen, Zhe Zhu, Wei Gao, Qixin Jiang, Jiangming Yu, Chuangang Fu
Insulin-like growth factor 1 receptor (IGF-1R) is proved to contribute the development of many types of cancers. But, little is known about its roles in radio-resistance of colorectal cancer (CRC). Here, we demonstrated that low IGF-1R expression value was associated with the better radiotherapy sensitivity of CRC. Besides, through Quantitative Real-time PCR (qRT-PCR), the elevated expression value of epidermal growth factor receptor (EGFR) was observed in CRC cell lines (HT29, RKO) with high radio-sensitivity compared with those with low sensitivity (SW480, LOVO)...
July 4, 2017: Gene
https://www.readbyqxmd.com/read/28685689/arylurea-derivatives-a-class-of-potential-cancer-targeting-agents
#12
Jia-Nian Chen, De-Wen Wu, Ting Li, Kang-Jian Yang, Li Cheng, Zu-Ping Zhou, Shi-Ming Pu, Wan-Hua Lin
Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), platelet-derived growth factor receptors (PDGFRs), epidermal growth factor receptors (EGFRs), insulin-like growth factor 1 receptor (IGF-1R), Fms-like tyrosine kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include checkpoint kinases (Chks), cyclin-dependent kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include matrix metalloproteinases (MMPs), LIM kinase (Limk), nicotinamide phosphoribosyltransferase (Nampt), and histone deacetylase (HDAC); (6) arylureas from the rational modification of natural products...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28682648/kinase-inhibitors-of-the-igf-1r-as-a-potential-therapeutic-agent-for-rheumatoid-arthritis
#13
Hiroshi Tsushima, Shinji Morimoto, Maki Fujishiro, Yuko Yoshida, Kunihiro Hayakawa, Takuya Hirai, Tomoko Miyashita, Keigo Ikeda, Ken Yamaji, Kenji Takamori, Yoshinari Takasaki, Iwao Sekigawa, Naoto Tamura
We have previously shown that the inhibition of connective tissue growth factor (CTGF) is a potential therapeutic strategy against rheumatoid arthritis (RA). CTGF consists of four distinct modules, including the insulin-like growth factor binding protein (IGFBP). In serum, insulin-like growth factors (IGFs) bind IGFBPs, interact with the IGF-1 receptor (IGF-1 R), and regulate anabolic effects and bone metabolism. We investigated the correlation between IGF-1 and the pathogenesis of RA, and the inhibitory effect on osteoclastogenesis and angiogenesis of the small molecular weight kinase inhibitor of the IGF-1 R, NVP-AEW541, against pathogenesis of RA in vitro...
July 6, 2017: Autoimmunity
https://www.readbyqxmd.com/read/28681171/a-randomized-phase-ii-trial-of-ridaforolimus-dalotuzumab-and-exemestane-compared-with-ridaforolimus-and-exemestane-in-patients-with-advanced-breast-cancer
#14
Hope S Rugo, Olivier Trédan, Jungsil Ro, Serafin M Morales, Mario Campone, Antonino Musolino, Noémia Afonso, Marta Ferreira, Kyong Hwa Park, Javier Cortes, Antoinette R Tan, Joanne L Blum, Lamar Eaton, Christine K Gause, Zhen Wang, Ellie Im, David J Mauro, Mary Beth Jones, Andrew Denker, José Baselga
PURPOSE: To evaluate whether adding humanized monoclonal insulin growth factor-1 receptor (IGF-1R) antibody (dalotuzumab) to mammalian target of rapamycin (mTOR) inhibitor (ridaforolimus) plus aromatase inhibitor (exemestane) improves outcomes in patients with estrogen receptor (ER)-positive advanced/metastatic breast cancer. METHODS: This randomized, open-label, phase II trial enrolled 80 postmenopausal women with high-proliferation (Ki67 index staining ≥15%), ER-positive breast cancer that progressed after a non-steroidal aromatase inhibitor (NCT01605396)...
July 5, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28677770/the-function-of-androgen-androgen-receptor-and-insulin-growth-factor%C3%A2-1-insulin-growth-factor%C3%A2-1-receptor-on-the-effects-of-tribulus%C3%A2-terrestris-extracts-in-rats-undergoing-high-intensity-exercise
#15
Yin Wu, Hongfang Yang, Xiaohui Wang
Our previous study demonstrated that treatment with Tribulus terrestris (TT) extracts (120 mg/kg) promoted the muscle weight gain and performance of rats undergoing high intensity exercise. The present study was designed to explore the mechanisms underlying the effect of treatment with TT extracts and the involvement of androgens, the androgen receptor (AR), insulin growth factor‑1 (IGF‑1) and the IGF‑1 receptor (IGF‑1R). A total of 32 Sprague‑Dawley rats were randomly divided into groups as follows: Control; TT, treated with TT extracts, E, high intensity exercise; E+TT, high intensity exercise plus TT treatment...
June 30, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28674429/citrate-suppresses-tumor-growth-in-multiple-models-through-inhibition-of-glycolysis-the-tricarboxylic-acid-cycle-and-the-igf-1r-pathway
#16
Jian-Guo Ren, Pankaj Seth, Huihui Ye, Kun Guo, Jun-Ichi Hanai, Zaheed Husain, Vikas P Sukhatme
In this study we have tested the efficacy of citrate therapy in various cancer models. We found that citrate administration inhibited A549 lung cancer growth and additional benefit accrued in combination with cisplatin. Interestingly, citrate regressed Ras-driven lung tumors. Further studies indicated that citrate induced tumor cell differentiation. Additionally, citrate treated tumor samples showed significantly higher infiltrating T-cells and increased blood levels of numerous cytokines. Moreover, we found that citrate inhibited IGF-1R phosphorylation...
July 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28673204/abnormality-of-klotho-signaling-is-involved-in-polycystic-ovary-syndrome
#17
Zenghui Mao, Liqing Fan, Qiao Yu, Shuwei Luo, Xianling Wu, Jun Tang, Gehua Kang, Le Tang
This study investigated the involvement of the klotho-associated signaling in the apoptosis of granulosa cells (GCs) from the ovaries of patients with polycystic ovary syndrome (PCOS) and PCOS animals. Primary GCs were obtained from 26 healthy women and 43 women with PCOS. The PCOS animal model was established by the injection of dehydroepiandrosterone (DHEA). Klotho protein and associated microRNA expression in human primary GCs and rats' ovarian tissues were measured by Western blot and real-time polymerase chain reaction, respectively...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28672911/microrna-30a-5p-inhibits-the-proliferation-and-invasion-of-gastric-cancer-cells-by-targeting-insulin-like-growth-factor-1-receptor
#18
Yang Liu, Yu Zhou, Xun Gong, Changjie Zhang
MicroRNAs (miRs) are a class of small non-coding RNAs of 18-25 nucleotides in length that serve as key regulators in the development and progression of human cancers. Recently, miR-30b-5p, as a member of the miR-30 family, has been reported to act as a tumor suppressor in gastric cancer. However, the expression and function of miR-30a-5p in gastric cancer, as well as the corresponding underlying mechanism, remain unknown. In the present study, it was demonstrated that the expression of miR-30a-5p was significantly reduced in gastric cancer tissues (n=43) compared with normal gastric tissues (n=10; P<0...
July 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28669167/the-prognostic-value-of-pre-treatment-leukocytosis-in-patients-with-previously-treated-stage-iiib-iv-non-small-cell-lung-cancer-treated-with-the-igf-1r-pathway-modulator-axl1717-or-docetaxel-a-retrospective-analysis-of-a-phase-ii-trial
#19
Georg Holgersson, Michael Bergqvist, Jonas Nilsson, Marcus Thureson, Johan Harmenberg, Stefan Bergstrom
Background: The aim of the present study was to investigate any prognostic value of pre-treatment anemia, leukocytosis and thrombocytosis in patients with advanced pretreated NSCLC. Methods: A randomized, multicenter phase II study comparing the IGF-1R modulator AXL with standard docetaxel in the treatment of previously treated stage IIIB or IV NSCLC patients was conducted in 2011-2013. Clinical and laboratory data were collected, including serum values for hemoglobin (Hgb), white blood cells (WBC) and platelets (Plt) at baseline...
June 25, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28668953/iga-enhances-igf-1-mitogenic-activity-via-receptor-modulation-in-glomerular-mesangial-cells-implications-for-iga-induced-nephropathy
#20
Amal Al-Eisa, Gursev S Dhaunsi
BACKGROUND/AIM: Glomerulonephritis due to mesangial proliferation is responsible for renal dysfunction in IgA nephropathy (IgAN), however molecular mechanisms of pathogenesis are not well known. We examined the effect of IgA on Insulin-like Growth Factor-1 (IGF-1) activity, a potent mitogen with vital role in growth and development of children, and IGF-1 receptor (IGF-1R) in cultures of glomerular mesangial cells (GMC). METHODS: GMC were isolated from rat kidneys using sieving and enzymatic digestion of tissue homogenates, and cultured in RPMI 1640 medium...
June 27, 2017: Kidney & Blood Pressure Research
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