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https://www.readbyqxmd.com/read/28329136/chronic-resveratrol-treatment-inhibits-mrc5-fibroblast-sasp-related-protumoral-effects-on-melanoma-cells
#1
Beatrice Menicacci, Anna Laurenzana, Anastasia Chillà, Francesca Margheri, Silvia Peppicelli, Elisabetta Tanganelli, Gabriella Fibbi, Lisa Giovannelli, Mario Del Rosso, Alessandra Mocali
Cellular senescence is related to organismal aging and is observed after DNA damaging cancer therapies, that induce tumor-suppressive modifications, but it is characterized by a strong increase in secreted factors, termed the "senescence-associated secretory phenotype" (SASP). Particularly, SASP from stroma senescent fibroblasts creates a cancer-favoring microenvironment, providing targets for anti-cancer interventions. In the present article, chronic treatment (5 weeks) with 5 µM resveratrol has been used to modulate senescence-related protumoral features of MRC5 fibroblasts, reducing SASP-related interleukins IL1α, IL1β, IL6, and IL8; transforming-growth-factor-β (TGFβ); matrix metallo-proteinases MMP3 and MMP2; urokinase plasminogen activator (uPA); receptor proteins uPAR, IL6R, insulin growth factor receptor-1 (IGF-1R), TGFβ-R2, and CXCR4...
January 20, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28328831/expression-characteristics-of-proteins-of-igf-1r-p-akt-and-survivin-in-papillary-thyroid-carcinoma-patients-with-type-2-diabetes-mellitus
#2
Yuerong Yan, Fengqiu Hu, Weilu Wu, Ruiting Ma, Hui Huang
Type 2 diabetes mellitus (T2DM) is related to increased risk of papillary thyroid carcinoma (PTC). Insulin-like growth factor-1 receptor (IGF-1R) is increased in patients with T2DM. The increased IGF-1R may be responsible for the development of PTC. In this study, we investigated the expression of phosphorylation of Akt (p-Akt)/survivin pathway activated by IGF-1R in PTC subjects with and without diabetes.Clinicopathological data of 20 PTC patients with T2DM were retrospectively analyzed and compared with those of 21 PTC subjects without diabetes...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28324113/microrna-expression-patterns-involved-in-amyloid-beta-induced-retinal-degeneration
#3
Peirong Huang, Junran Sun, Fenghua Wang, Xueting Luo, Jingyang Feng, Qing Gu, Te Liu, Xiaodong Sun
Purpose: Dry age-related macular degeneration (AMD) is characterized by the accumulation of drusen under Bruch's membrane, and amyloid beta (Aβ) is speculated to be one of the key pathologic factors. While the detrimental effects of Aβ on retinas have been widely explored, Aβ-induced epigenetic regulatory changes have yet to be fully investigated. We therefore aimed to identify the microRNA (miRNA) expression profiles in an Aβ-induced mouse model of retinal degeneration. Methods: C57BL/6 mice were intravitreally injected with Aβ1-40 or PBS and the eye tissues were collected for hematoxylin and eosin (H&E) staining, apoptosis immunofluorescence staining, and miRNA profiling...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28320862/differential-involvement-of-the-microtubule-cytoskeleton-in-insulin-receptor-substrate-1-irs-1-and-irs-2-signaling-to-akt-determines-response-to-microtubule-disruption-in-breast-carcinoma-cells
#4
Jose Mercado-Matos, Jennifer L Clark, Andrew J Piper, Jenny Janusis, Leslie M Shaw
The insulin receptor substrate (IRS) proteins serve as essential signaling intermediates for the activation of PI3K by both the insulin-like growth factor-1 receptor (IGF-1R) and its close family member the insulin receptor (IR). Although IRS-1 and IRS-2 share significant homology, they regulate distinct cellular responses downstream of these receptors and play divergent roles in breast cancer. To investigate the mechanism by which signaling through IRS-1 and IRS-2 results in differential outcomes, we assessed the involvement of the microtubule cytoskeleton in IRS-dependent signaling...
March 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28315973/stem-cell-factor-kit-signal-insufficiency-contributes-to-hypoxia-induced-intestinal-motility-dysfunctions-in-neonatal-mice
#5
Hong Ren, Juan Han, Zhifang Li, Zhiyong Xiong
BACKGROUND: Gastrointestinal (GI) motility disorders represent a group of problems that more constantly encountered in preterm infants. However, whether hypoxia exposure contributes to the GI dysfunctions is still unclear. METHODS: Newborn mice were exposed to hypoxia (10%) from P1 to P7. Intestinal motilities were examined by a strain gauge transducer. The proliferation of ICCs was detected by using immunostaining for BrdU, Ki67, Kit, Ano1, and insulin-like growth factor 1 receptor (IGF-1R+)...
March 18, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28315335/microrna-99a-inhibits-insulin-induced-proliferation-migration-dedifferentiation-and-rapamycin-resistance-of-vascular-smooth-muscle-cells-by-inhibiting-insulin-like-growth-factor-1-receptor-and-mammalian-target-of-rapamycin
#6
Zi-Wei Zhang, Rui-Wei Guo, Jin-Lin Lv, Xian-Mei Wang, Jin-Shan Ye, Ni-Hong Lu, Xing Liang, Li-Xia Yang
Patients with type 2 diabetes mellitus (T2DM) are characterized by insulin resistance and are subsequently at high risk for atherosclerosis. Hyperinsulinemia has been associated with proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) during the pathogenesis of atherosclerosis. Moreover, insulin-like growth factor-1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) have been demonstrated to be the underlying signaling pathways. Recently, microRNA-99a (miR-99a) has been suggested to regulate the phenotypic changes of VSMCs in cancer cells...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28302721/involvement-of-notch1-signaling-in-malignant-progression-of-a549-cells-subjected-to-prolonged-cadmium-exposure
#7
Kota Fujiki, Hisako Inamura, Takamitsu Miyayama, Masato Matsuoka
Cadmium exposure is known to increase lung cancer risk, but the underlying molecular mechanisms in cadmium-stimulated progression of malignancy are unclear. Here, we examined the effects of prolonged cadmium exposure on the malignant progression of A549 human lung adenocarcinoma cells and the roles of Notch1, hypoxia-inducible factor 1α (HIF-α), and insulin-like growth factor 1 receptor (IGF-1R)/Akt/extracellular signal-regulated kinase (ERK)/p70 S6 kinase 1 (S6K1) signaling pathways. Exposing A549 cells to 10 or 20 μM cadmium chloride (CdCl2) for 9-15 weeks induced a high proliferative potential, the epithelial-mesenchymal transition (EMT), stress fiber formation, high cell motility, and resistance to anti-tumor drugs...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28296140/inhibitors-of-stat3-%C3%AE-catenin-and-igf-1r-sensitize%C3%A2-mouse-pik3ca%C3%A2-mutant%C3%A2-breast-cancer-to-pi3k-inhibitors
#8
Vanessa F Merino, Soonweng Cho, Xiaohui Liang, Sunju Park, Kideok Jin, Qian Chen, Duojia Pan, Cynthia A Zahnow, Alan R Rein, Saraswati Sukumar
Although mutations in the phosphoinositide 3-kinase-catalytic subunit (PIK3CA) are common in breast cancer, PI3K inhibitors alone have shown modest efficacy. We sought to identify additional pathways altered in PIK3CA mutant tumors that might be targeted in combination with PI3K inhibitors. We generated two transgenic mouse models expressing the human PIK3CA-H1047R and the -E545K hotspot mutant genes in the mammary gland and evaluated their effects on development and tumor formation. Molecular analysis identified pathways altered in these mutant tumors, which were also targeted in multiple cells lines derived from the PIK3CA tumors...
March 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28292957/psma-redirects-cell-survival-signaling-from-the-mapk-to-the-pi3k-akt-pathways-to-promote-the-progression-of-prostate-cancer
#9
Leslie Ann Caromile, Kristina Dortche, M Mamunur Rahman, Christina L Grant, Christopher Stoddard, Fernando A Ferrer, Linda H Shapiro
Increased abundance of the prostate-specific membrane antigen (PSMA) on prostate epithelium is a hallmark of advanced metastatic prostate cancer (PCa) and correlates negatively with prognosis. However, direct evidence that PSMA functionally contributes to PCa progression remains elusive. We generated mice bearing PSMA-positive or PSMA-negative PCa by crossing PSMA-deficient mice with transgenic PCa (TRAMP) models, enabling direct assessment of PCa incidence and progression in the presence or absence of PSMA...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28261624/in-silico-prediction-of-b-cell-epitopes-of-the-extracellular-domain-of-insulin-like-growth-factor-1-receptor
#10
Vahid Bayrami, Mehrnaz Keyhanfar, Hassan Mohabatkar, Manijeh Mahdavi, Violaine Moreau
The insulin-like growth factor-1 receptor (IGF-1R) is a transmembrane receptor with tyrosine kinase activity. The receptor plays a critical role in cancer. Using monoclonal antibodies (MAbs) against the IGF-1R, typically blocks ligand binding and enhances down-regulation of the cell-surface IGF-1R. Some MAbs such as cixutumumab are under clinical trial investigation. Targeting multiple distinct epitopes on IGF-1R, might be an effective strategy to inhibit IGF-1R pathway in cancer. In this study, new linear B cell epitopes for the extracellular domains of IGF-1R were predicted by in silico methods using a combination of linear B cell epitope prediction web servers such as ABCpred, Bepired, BCPREDs, Bcepred and Elliprro...
December 2016: Molecular Biology Research Communications
https://www.readbyqxmd.com/read/28260056/insulin-like-growth-factor-1-receptor-mediated-cell-survival-in-hypoxia-depends-on-the-promotion-of-autophagy-via-suppression-of-the-pi3k-akt-mtor-signaling-pathway
#11
Qi Liu, Jing-Zhi Guan, Yong Sun, Ziyu Le, Ping Zhang, Dong Yu, Yong Liu
Hypoxia is widely accepted as a fundamental biological phenomenon, which is strongly associated with tissue damage and cell viability under stress conditions. Insulin-like growth factor‑1 (IGF‑1) is known to protect tissues from multiple types of damage, and protect cells from apoptosis. Hypoxia is a regulatory factor of the IGF system, however the role of the IGF-1 receptor (IGF‑1R) in hypoxia‑induced apoptosis remains unclear. The present study investigated the potential mechanisms associated with IGF‑1R‑associated apoptosis under hypoxic conditions...
March 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28253329/metformin-inhibits-the-proliferation-of-benign-prostatic-epithelial-cells
#12
Zongwei Wang, Xingyuan Xiao, Rongbin Ge, Jijun Li, Cameron W Johnson, Cyrus Rassoulian, Aria F Olumi
OBJECTIVE: Benign prostatic hyperplasia (BPH) is the most common proliferative abnormality of the prostate affecting elderly men throughout the world. Epidemiologic studies have shown that diabetes significantly increases the risk of developing BPH, although whether anti-diabetic medications preventing the development of BPH remains to be defined. We have previously found that stromally expressed insulin-like growth factor 1 (IGF-1) promotes benign prostatic epithelial cell proliferation through paracrine mechanisms...
2017: PloS One
https://www.readbyqxmd.com/read/28249168/autocrine-igf1-signaling-mediates-pancreatic-tumor-cell-dormancy-in-the-absence-of-oncogenic-drivers
#13
Nirakar Rajbhandari, Wan-Chi Lin, Barbara L Wehde, Aleata A Triplett, Kay-Uwe Wagner
Mutant KRAS and c-MYC are oncogenic drivers and rational therapeutic targets for the treatment of pancreatic cancer. Although tumor growth and homeostasis are largely dependent on these oncogenes, a few residual cancer cells are able to survive the ablation of mutant KRAS and c-MYC. By performing a genome-wide gene expression analysis of in vivo-derived bulk tumor cells and residual cancer cells lacking the expression of mutant KRAS or c-MYC, we have identified an increase in autocrine IGF1/AKT signaling as a common survival mechanism in dormant cancer cells...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28237603/embryonic-only-arsenic-exposure-in-killifish-fundulus-heteroclitus-reduces-growth-and-alters-muscle-igf-levels-one-year-later
#14
Dana B Szymkowicz, Kaleigh C Sims, Noemi M Castro, William C Bridges, Lisa J Bain
Arsenic is a contaminant of drinking water and crops in many parts of the world. Epidemiological studies have shown that arsenic exposure is linked to decreased birth weight, weight gain, and proper skeletal muscle function. The goal of this study was to use killifish (Fundulus heteroclitus) as a model to determine the long-term effects of embryonic-only arsenic exposure on muscle growth and the insulin-like growth factor (IGF) pathway. Killifish embryos were exposed to 0, 50, 200 or 800ppb As(III) from fertilization until hatching...
February 20, 2017: Aquatic Toxicology
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
#15
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 insulin-like growth factor-1 (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
#16
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
#17
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
#18
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
#19
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
#20
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
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