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IGF-1R

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https://www.readbyqxmd.com/read/29226348/sevo%C3%AF-urane-induces-liver-injury-by-modulating-the-expression-of-insulin-like-growth-factor-1-via-mir-214
#1
Ligang Ma, Jingjing Zhao, Xiaojuan Xie
This study aimed to detect the effect of sevoflurane anesthesia on liver injury through modulating IGF-1. The expression of IGF-1 and IGF-1R in liver tissues of sevoflurane-exposed rats was examined by qRT-PCR and western blot. The expression levels of miR-214 in liver cells treated with different concentration of sevoflurane at different time points were detected by qRT-PCR. Enzyme-linked immunosorbent (ELISA) assay was used to analyze serum IGF-1 concentration in cell culture media. After pre-treatment with 100 nM miR-214 inhibitor followed by exposure to sevoflurane, the expression level of miR-214 and IGF-1 protein in liver cells was examined...
December 11, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29217770/protein-c-receptor-stimulates-multiple-signaling-pathways-in-breast-cancer-cells
#2
Daisong Wang, Chunye Liu, Jingqiang Wang, Yingying Jia, Xin Hu, Hai Jiang, Zhi-Ming Shao, Yi Arial Zeng
The protein C receptor (PROCR) has emerged as a stem cell marker in several normal tissues and has also been implicated in tumor progression. However, the functional role of PROCR and the signaling mechanisms downstream of PROCR remain poorly understood. Here, we dissected the PROCR signaling pathways in breast cancer cells. Combining protein array, knockdown, and overexpression methods, we found that PROCR concomitantly activates multiple pathways. We also noted that PROCR-dependent ERK and PI3k-Akt-mTOR signaling pathways proceed through Src kinase and trans-activation of insulin-like growth factor 1 receptor (IGF-1R)...
December 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29217764/radiotherapy-activated-cancer-associated-fibroblasts-promote-tumor-progression-through-paracrine-igf-1r-activation
#3
Joke Tommelein, Elly De Vlieghere, Laurine Verset, Elodie Melsens, Justine Leenders, Benedicte Descamps, Annelies Debucquoy, Christian Vanhove, Patrick Pauwels, Christian P Gespach, Anne Vral, Astrid De Boeck, Karin Haustermans, Pascal de Tullio, Wim Ceelen, Pieter Demetter, Tom Boterberg, Marc Bracke, Olivier De Wever
Preoperative radiotherapy (RT) is a mainstay in the management of rectal cancer (RC), a tumor characterized by desmoplastic stroma containing cancer-associated fibroblasts (CAF). Although CAF are abundantly present, the effects of RT to CAF and its impact on cancer cells are unknown. We evaluated the damage responses of CAF to RT and investigated changes in colorectal cancer (CRC) cell growth, transcriptome, metabolome, and kinome in response to paracrine signals emerging from irradiated CAF. RT to CAF induced DNA damage, p53 activation, cell cycle arrest, and secretion of paracrine mediators including insulin-like growth factor-1 (IGF-1)...
December 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/29213282/determination-of-mammalian-target-of-rapamycin-hyperactivation-as-prognostic-factor-in-well-differentiated-neuroendocrine-tumors
#4
G Lamberti, C Ceccarelli, N Brighi, I Maggio, D Santini, C Mosconi, C Ricci, G Biasco, D Campana
Purpose: To evaluate the role of the activation of mTOR (phosphorylated mTOR, p-mTOR) and the expression SSTR2A and IGF-1R as prognostic factor in well-differentiated neuroendocrine tumors. Methods: A retrospective study was conducted on data from patients with diagnosis of neuroendocrine tumor originated from pancreas (pNET) or gastrointestinal tract (stomach, appendix, and ileus; GI-NET) made between January 2003 and December 2004 and followed up at our institution...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/29212962/effects-of-insulin-like-growth-factor-1-on-the-in-vitro-maturation-of-canine-oocytes
#5
Akane Sato, Borjigin Sarentonglaga, Kazuko Ogata, Mio Yamaguchi, Asuka Hara, Khurchabiling Atchalalt, Naoko Sugane, Rika Fukumori, Yoshikazu Nagao
The maturation rate of canine oocytes during in vitro maturation (IVM) needs to be improved. The present study was designed to evaluate the effects of insulin-like growth factor-1 (IGF-1) on the IVM of canine oocytes. Ovaries were obtained by ovariohysterectomy and were sliced to release cumulus-oocyte complexes (COCs). In Experiment 1, the effects of different concentrations of IGF-1 on the nuclear maturation of oocytes was investigated. The COCs were cultured in a modified medium (mTCM199) with IGF-1 (0, 0...
December 7, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/29212236/growth-differentiation-factor-15-mediates-epithelial-mesenchymal-transition-and-invasion-of-breast-cancers-through-igf-1r-foxm1-signaling
#6
Bridgette F Peake, Siobhan M Eze, Lily Yang, Robert C Castellino, Rita Nahta
Expression of the inflammatory cytokine growth differentiation factor 15 (GDF15) is significantly elevated in many tumor types in association with epithelial mesenchymal transition (EMT), drug resistance, and progressive disease. However, few studies have examined GDF15 expression, signaling, or function in breast cancer. In the current study, we demonstrate that GDF15 is associated with high tumor grade, ER-negativity, and HER2 overexpression in patients with breast cancer. Stable overexpression of GDF15 upregulates expression of mesenchymal markers and transcription factors, including FoxM1, and increases cellular invasion...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207154/adipose-derived-stem-cell-conditioned-medium-attenuates-cisplatin-triggered-apoptosis-in-tongue-squamous-cell-carcinoma
#7
Yu-Jen Chiu, Jai-Sing Yang, Han-Shui Hsu, Chi-Han Tsai, Hsu Ma
Autologous fat grafting procedures have noted a markedly increased frequency, not only for cosmetic purposes, but also for deformities after head and neck cancer and breast cancer surgery. Carcinogenesis is always a major concern in cell therapy-related issues. However, there is no literature discussing this issue in head and neck squamous cell carcinoma patients. To evaluate the interaction of tongue cancer cells and adipose-derived stem cells, we performed a series of in vitro experiments. Our results demonstrated that cisplatin significantly reduced the viabilities of SCC‑25 and CAL‑27 cells in a concentration-dependent manner, but it had low cytotoxicity in cisplatin-resistant CAL‑27 (CAR) cells...
December 1, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29206199/a-novel-receptor-tyrosine-kinase-switch-promotes-gastrointestinal-stromal-tumor-drug-resistance
#8
Sergei Boichuk, Aigul Galembikova, Pavel Dunaev, Elena Valeeva, Elena Shagimardanova, Oleg Gusev, Svetlana Khaiboullina
The fact that most gastrointestinal stromal tumors (GISTs) acquire resistance to imatinib (IM)-based targeted therapy remains the main driving force to identify novel molecular targets that are capable to increase GISTs sensitivity to the current therapeutic regimens. Secondary resistance to IM in GISTs typically occurs due to several mechanisms that include hemi- or homo-zygous deletion of the wild-type KIT allele, overexpression of focal adhesion kinase (FAK) and insulin-like growth factor receptor I (IGF-1R) amplification, BRAF mutation, a RTK switch (loss of c-KIT and gain of c-MET/AXL), etc...
December 5, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29200876/effects-of-insulin-analogs-and-glucagon-like-peptide-1-receptor-agonists-on-proliferation-and-cellular-energy-metabolism-in-papillary-thyroid-cancer
#9
Liang He, Siliang Zhang, Xiaowen Zhang, Rui Liu, Haixia Guan, Hao Zhang
Purpose: This study was aimed to investigate the expressions of the insulin receptor (IR), insulin-like growth factor receptor (IGF-1R), and glucagon-like peptide-1 receptor (GLP-1R) in normal thyroid tissue, papillary thyroid cancer (PTC) tissues, and PTC cells, and to examine the possible role of insulin analogs and GLP-1R agonists in cell proliferation and energy metabolism in PTC cells. Methods: The expressions of IR, IGF-1R, and GLP-1R in PTC tissues and PTC cell lines were detected by immunohistochemistry and western blotting, respectively...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29180608/t-darpp-activates-igf-1r-signaling-to-regulate-glucose-metabolism-in-trastuzumab-resistant-breast-cancer-cells
#10
Gal Lenz, Angelica Hamilton, Shuhui Geng, Teresa Hong, Markus Kalkum, Jamil Momand, Susan E Kane, Janice Huss
PURPOSE: Increased glycolysis and glucose dependence is a hallmark of malignancy that enables tumors to maximize cell proliferation. In HER2+ cancers, an increase in glycolytic capacity is associated with trastuzumab resistance. IGF-1R activation and t-Darpp over-expression both confer trastuzumab resistance in breast cancer. We therefore investigated a role for IGF-1R and t-Darpp in regulating glycolytic capacity in HER2+ breast cancers. EXPERIMENTAL DESIGN: We examined the relationship between t-Darpp and IGF-1R expression in breast tumors and their respective relationships with patient survival...
November 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29172484/insulin-like-growth-factor-1-analogs-clicked-in-the-c-domain-chemical-synthesis-and-biological-activities
#11
Katerina Machackova, Michaela Collinsová, Martina Chrudinová, Irena Selicharová, Jan Picha, Miloš Buděšínský, Vaclav Vanek, Lenka Zakova, Andrzej Marek Brzozowski, Jiri Jiracek
Human insulin-like growth factor 1 (IGF-1) is a 70-amino acid protein hormone, with key impact on growth, development and lifespan. The physiological and clinical importance of IGF-1 prompted challenging chemical and biological trials towards the development of its analogs as molecular tools for the IGF-1 receptor (IGF1-R) studies, and as new therapeutics. Here, we report a new method for the total chemical synthesis of IGF-1 analogs, which entails the solid-phase synthesis of two IGF-1 precursor chains that is followed by the CuI-catalyzed azide-alkyne cycloaddition ligation, and by biomimetic formation of a native pattern of disulfides...
November 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29169312/molecular-imaging-of-igf-1r-in-cancer
#12
Yingying Sun, Xilin Sun, Baozhong Shen
The important role of insulin-like growth factor 1 receptor (IGF-1R) in malignant tumors has been well established. Increased IGF-1R activity promotes cancer cell proliferation, migration, and invasion and is associated with tumor metastasis, treatment resistance, poor prognosis, and shortened survival in patients with cancer. However, while IGF-1R has become a promising target for cancer therapy, IGF-1R-targeted therapy is ineffective in unselected patients. It is therefore essential to evaluate IGF-1R expression before treatment in order to identify responsive patients, monitor therapy efficacy, and estimate prognosis...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/29169039/heteromultivalent-targeting-of-integrin-%C3%AE-v%C3%AE-3-and-neuropilin-1-promotes-cell-survival-via-the-activation-of-the-igf-1-insulin-receptors
#13
Tao Jia, Jungyoon Choi, Jéremy Ciccione, Maxime Henry, Ahmad Mehdi, Jean Martinez, Béatrice Eymin, Gilles Subra, Jean-Luc Coll
Angiogenesis strongly depends on the activation of integrins, especially integrin αvβ3, and of neuropilin-1 (NRP-1), a co-receptor of VEGFR2. Dual-targeted molecules that simultaneously block both of them are expected have increased anti-angiogenic and antitumor activity. Toward this goal, we generated bifunctional 40 nm-sized silica nanoparticles (NPs) coated with controlled amounts of cRGD and ATWLPPR peptides and studied their affinity, selectivity and biological activity in HUVECs. Sub-nanomolar concentrations of NPs grafted either with ATWLPPR alone or in combination with cRGD exhibit potent and specific antagonist activity against VEGFR2/AKT signaling...
October 29, 2017: Biomaterials
https://www.readbyqxmd.com/read/29152592/revisiting-the-igf-1r-as-a-breast-cancer-target
#14
Roudy Chiminch Ekyalongo, Douglas Yee
The type I insulin-like growth factor-1 receptor is a well-described target in breast cancer and multiple clinical trials examining insulin-like growth factor-1 receptor have been completed. Unfortunately, monoclonal antibodies and tyrosine kinase inhibitors targeting insulin-like growth factor-1 receptor failed in phase III breast clinical trials for several reasons. First, insulin-like growth factor-1 receptor antibody therapy resulted in hyperglycemia and metabolic syndrome most likely due to disruption of insulin-like growth factor-1 homeostasis and subsequent growth hormone elevation...
2017: NPJ Precision Oncology
https://www.readbyqxmd.com/read/29150385/igf-1r-mrna-expression-is-increased-in-obese-children
#15
Rafaela Cristina Ricco, Rubens Garcia Ricco, Mariangela Carletti Queluz, Mariana Teresa Sarti de Paula, Patricia Volpon Atique, Rodrigo José Custódio, Hugo Tourinho Filho, Raphael Del Roio Liberatori, Carlos Eduardo Martinelli
OBJECTIVES: Obese children are often taller than age-matched subjects. Reports on GH and IGF-I levels in obese individuals are controversial, with normal and reduced GH-IGF-I levels having been reported in this group of patients. Thus, the aim of this study was to analyse insulin-like growth factor type 1 receptor (IGF-IR) mRNA expression in obese children. METHODS: Forty-seven pre-pubertal children were included in this study: 29 were obese and taller than their target height, and 18 were normal eutrophic controls...
November 11, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#16
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29141539/comparative-selectively-targeted-anti-neoplastic-cytotoxicity-of-three-immunopharmaceuticals-with-covalently-bound-fludarabine-gemcitabine-and-dexamethasone-moieties-synthesized-utilizing-organic-chemistry-reactions-in-a-multi-phase-regimen
#17
Cody P Coyne, Lakshmi Narayanan
Background - Unintentional passive diffusion of conventional small molecular weight pharmaceuticals across intact membranes of normal healthy cells in tissues and organ systems induces sequelae that limit therapeutic dosage and duration of administration. Selective "targeted" delivery of pharmaceuticals is a molecular strategy that can potentially provide heightened margins-of-safety with greater potency and improved efficacy. Materials-and-Methods - Monophosphate analogs of fludarabine, gemcitabine, and dexamethasone were combined with a carbodiimide reagent in the presence of imidazole to produce reactive intermediates that were subsequently covalently bound to monoclonal anti-IGF-1R or anti-EGFR IgG-immunoglobulin...
November 14, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29138637/regulation-of-osteogenic-differentiation-of-placental-derived-mesenchymal-stem-cells-by-insulin-like-growth-factors-and-low-oxygen-tension
#18
Amer Youssef, Victor K M Han
Placental mesenchymal stem cells (PMSCs) are multipotent cells that can differentiate in vitro to multiple lineages, including bone. Insulin-like growth factors (IGFs, IGF-1 and IGF-2) participate in maintaining growth, survival, and differentiation of many stem cells, including osteoprogenitors. Low oxygen tension (PO2) can maintain stem cell multipotency and impede osteogenic differentiation. In this study, we investigated whether PMSC osteogenic differentiation is influenced by low PO2 and by IGFs. Our results indicated that low PO2 decreased osteogenic markers RUNX2 and OPN; however, re-exposure to higher oxygen tension (room air) restored differentiation...
2017: Stem Cells International
https://www.readbyqxmd.com/read/29137928/camkii%C3%AE-expression-in-a-mouse-model-of-nmdar-hypofunction-schizophrenia-putative-roles-for-igf-1r-and-tlr4
#19
O M Ogundele, C C Lee
Schizophrenia (SCZ) is a neuropsychiatric disorder that is linked to social behavioral deficits and other negative symptoms associated with hippocampal synaptic dysfunction. Synaptic mechanism of schizophrenia is characterized by loss of hippocampal N-Methyl-d-Aspartate Receptor (NMDAR) activity (NMDAR hypofunction) and dendritic spines. Previous studies show that genetic deletion of hippocampal synaptic regulatory calcium-calmodulin dependent kinase II alpha (CaMKIIα) cause synaptic and behavioral defects associated with schizophrenia in mice...
November 11, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29137261/enhanced-response-of-melanoma-cells-to-mek-inhibitors-following-unbiased-igf-1r-down-regulation
#20
Naida Suleymanova, Caitrin Crudden, Claire Worrall, Anica Dricu, Ada Girnita, Leonard Girnita
Due to its ability to compensate for signals lost following therapeutic MAPK-inhibition, insulin-like growth factor type 1 receptor (IGF-1R) co-targeting is a rational approach for melanoma treatment. However IGF-1R conformational changes associated with its inhibition can preferentially activate MAPK-pathway in a kinase-independent manner, through a process known as biased signaling. We explored the impact of biased IGF-1R signaling, on response to MAPK inhibition in a panel of skin melanoma cell lines with differing MAPK and p53 mutation statuses...
October 10, 2017: Oncotarget
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