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IGF-1 and cancer

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https://www.readbyqxmd.com/read/28344885/pappalysin-1-t-cell-receptor-transgenic-allo-restricted-t-cells-kill-ewing-sarcoma-in-vitro-and-in-vivo
#1
Andreas Kirschner, Melanie Thiede, Thomas G P Grünewald, Rebeca Alba Rubio, Günther H S Richter, Thomas Kirchner, Dirk H Busch, Stefan Burdach, Uwe Thiel
Pregnancy-associated plasma protein-A (PAPPA), also known as pappalysin, is a member of the insulin-like growth factor (IGF) family. PAPPA acts as a protease, cleaving IGF inhibitors, i.e., IGF binding proteins (IGFBPs), thereby setting free IGFs. The insulin/IGF-axis is involved in cancer in general and in Ewing sarcoma (ES) in particular. ES is a highly malignant bone tumor characterized by early metastatic spread. PAPPA is associated with various cancers. It is overexpressed and required for proliferation in ES...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28335515/dehydroepiandrosterone-dhea-feeding-protects-liver-steatosis-in-obese-breast-cancer-rat-model
#2
Reza Hakkak, Andrea Bell, Soheila Korourian
Obesity is a major health problem in the US and globally. Obesity is associated with the risk of cardiovascular disease, type 2 diabetes, cancers, hyperlipidemia, and liver steatosis development. Dehydroepiandrosterone (DHEA) is a dietary supplement used as an anti-obesity supplement. Previously, we reported that DHEA feeding protects 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors. The objectives of this study were to investigate the effects of obesity and DHEA feeding on liver steatosis, body weight gain, and serum DHEA, DHEA sulfate (DHEA-S), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) levels...
March 20, 2017: Scientia Pharmaceutica
https://www.readbyqxmd.com/read/28329136/chronic-resveratrol-treatment-inhibits-mrc5-fibroblast-sasp-related-protumoral-effects-on-melanoma-cells
#3
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/28325826/a-phase-ii-randomized-double-blind-presurgical-trial-of-polyphenon-e-in-bladder-cancer-patients-to-evaluate-pharmacodynamics-and-bladder-tissue-biomarkers
#4
Jason R Gee, Daniel R Saltzstein, KyungMann Kim, Jill M Kolesar, Wei Huang, Thomas C Havighurst, Barbara W Wollmer, Jeanne Stublaski, Tracy Downs, Hasan Mukhtar, Margaret House, Howard L Parnes, Howard H Bailey
We performed a phase 2 pharmacodynamic, prevention trial of Polyphenon E® (a green tea polyphenol formulation primarily consisting of epigallocatechin gallate (EGCG)) in patients prior to bladder cancer surgery. Patients with a bladder tumor were randomized to receive Polyphenon E® containing either 800 or 1200 mg of EGCG or placebo for 14 to 28 days prior to TURBT or cystectomy. The primary objective was to compare the post-intervention EGCG tissue levels in patients receiving Polyphenon E® as compared to placebo...
March 21, 2017: Cancer Prevention Research
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
#5
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/28316059/prevention-of-tumour-cell-apoptosis-associated-with-sustained-protein-kinase-b-phosphorylation-is-more-sensitive-to-regulation-by-insulin-signalling-than-stimulation-of-proliferation-and-extracellular-signal-regulated-kinase
#6
Christoph Schmid, Claudia Ghirlanda, Markus Niessen
Insulin controls blood glucose while insulin-like growth factor (IGF) 1 is an important growth factor. Interestingly, both hormones have overlapping bioactivities and can activate the same intracellular signal transduction cascades. Growth control (mainly by IGF1) and metabolic function (predominantly by insulin) are believed to depend on activation of extracellular signal-regulated kinases (ERKs) 1/2 and protein kinase B (Akt/PKB), respectively. Therefore, insulin analogues that are used to normalize blood glucose are tested for their ability to preferentially activate Akt/PKB but not ERK1/2 and mitogenesis...
March 18, 2017: Molecular and Cellular Biochemistry
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
#7
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/28315227/insulin-like-growth-factor-1-gene-polymorphism-in-women-with-breast-cancer
#8
Danylo Rafhael Costa-Silva, Maria da Conceição Barros-Oliveira, Rafael Soares Borges, Larysse Maira Campos-Verdes, João Paulo da Silva-Sampaio, Carla Solange Escorcio-Dourado, Luana Mota Martins, Airlane Pereira Alencar, Edmund Chada Baracat, Vladimir Costa Silva, Benedito Borges da Silva
Breast cancer is a disease of unknown etiology; however, the major risk factors are genetic alterations. Studies have demonstrated an association between insulin-like growth factor 1 (IGF-1) gene polymorphism and cell proliferation and reduced apoptosis, in addition to its role in breast cancer growth and aggressiveness. Two polymorphic variants of the IGF-1 gene are highlighted in association with breast cancer, rs6220 and rs7136446, although controversy exists as to this relationship. The current study included 137 women (68 breast cancer cases and 69 controls without breast cancer) who had 3 ml of peripheral blood drawn for the study of genomic DNA extracted from leukocytes using the genotyping technique by real-time polymerase chain reaction...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28302721/involvement-of-notch1-signaling-in-malignant-progression-of-a549-cells-subjected-to-prolonged-cadmium-exposure
#9
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
#10
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
#11
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/28291214/-modern-diagnosis-and-postoperative-monitoring-of-acromegaly-patients-at-a-neurosurgical-clinic
#12
L I Astaf'eva, P L Kalinin, B A Kadashev
Acromegaly is a severe disease associated with chronic overproduction of the growth hormone (GH) and insulin-like growth factor-1 (IGF-1), which is caused in most cases by pituitary adenoma. The main causes of mortality in acromegaly are cardiovascular diseases, respiratory diseases, and cancers. At present, the most effective treatment for acromegaly is surgical pituitary adenomectomy. Complete resection of pituitary tumors leads to the normalization of GH and IGF-1 levels, regression of symptoms, and a reduction in the risk of death...
2017: Zhurnal Voprosy Neĭrokhirurgii Imeni N. N. Burdenko
https://www.readbyqxmd.com/read/28275156/the-importance-of-staying-small
#13
Christopher Hine
Long-lived and cancer-resistant adult dwarf rodents have enhanced DNA repair capacity due to decreased GH/IGF-1 signaling during peripubertal development.
March 8, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28272775/cryptotanshinone-inhibition-of-mammalian-target-of-rapamycin-pathway-is-dependent-on-oestrogen-receptor-alpha-in-breast-cancer
#14
Yanhong Pan, Junfeng Shi, Wenting Ni, Yuping Liu, Siliang Wang, Xu Wang, Zhonghong Wei, Aiyun Wang, Wenxing Chen, Yin Lu
Cryptotanshinone (CPT) has been demonstrated to inhibit proliferation and mammalian target of rapamycin (mTOR) pathway in MCF-7 breast cancer cells. However, the same results are unable to be repeated in MDA-MB-231 cells. Given the main difference of oestrogen receptor α (ERα) between two types of breast cancer cells, It is possibly suggested that CPT inhibits mTOR pathway dependent on ERα in breast cancer. CPT could significantly inhibit cell proliferation of ERα-positive cancer cells, whereas ERα-negative cancer cells are insensitive to CPT...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28271457/insulin-growth-factor-1-correlates-with-higher-bone-mineral-density-and-lower-inflammation-status-in-obese-adult-subjects
#15
Rachele Fornari, Chiara Marocco, Davide Francomano, Simona Fittipaldi, Carla Lubrano, Viviana M Bimonte, Lorenzo M Donini, Emanuele Nicolai, Antonio Aversa, Andrea Lenzi, Emanuela A Greco, Silvia Migliaccio
PURPOSE: Obesity is a severe public health problem worldwide, leading to an insulin-resistant state in liver, adipose, and muscle tissue, representing a risk factor for type 2 diabetes mellitus, cardiovascular diseases, and cancer. We have shown that abdominal obesity is associated with homeostasis derangement, linked to several hormonal and paracrine factors. Data regarding potential link between GH/IGF1 axis, bone mineral density, and inflammation in obesity are lacking. Thus, aim of this study was to evaluate correlation among IGF-1, BMD, and inflammation in obese individuals...
March 7, 2017: Eating and Weight Disorders: EWD
https://www.readbyqxmd.com/read/28261624/in-silico-prediction-of-b-cell-epitopes-of-the-extracellular-domain-of-insulin-like-growth-factor-1-receptor
#16
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/28258988/serum-igf-1-igfbp-3-levels-and-circulating-tumor-cells-ctcs-in-early-breast-cancer-patients
#17
Georgios Z Papadakis, Dimitrios Mavroudis, Vasilios Georgoulias, John Souglakos, Athanasios K Alegakis, George Samonis, Ulas Bagci, Antonis Makrigiannakis, Odysseas Zoras
OBJECTIVE: Insulin-like growth factor (IGF)-axis is involved in human oncogenesis and metastasis development for various solid tumors including breast cancer. Aim of this study was to assess the association between IGF-1, IGF-binding protein-3 (IGFBP-3) serum levels and the presence of circulating tumor cells (CTCs) in the peripheral blood of women diagnosed with early breast cancer (EBC), before and after adjuvant chemotherapy. DESIGN: 171 patients with early-stage breast adenocarcinomas were retrospectively evaluated...
February 16, 2017: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/28253833/emerging-antibodies-for-the-treatment-of-pancreatic-cancer
#18
Kalliopi Andrikou, Chiara Peterle, Stefania Pipitone, Massimiliano Salati, Stefano Cascinu
Pancreatic ductal adenocarcinoma cancer (PDAC) is the fourth leading cause of cancer death worldwide. Recently, two chemotherapy regimens have proven to improve median overall survival in comparison with gemcitabine. Based on better understanding of tumor molecular biology and of the role of tumor microenvironment, monoclonal antibodies (mAbs) could be an interesting and new type of targeted treatment of PDAC. Areas covered: Preclinical and clinical trials have evaluated the efficacy of several mAbs in pancreatic cancer treatment...
March 2017: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/28252552/effects-of-resistance-training-and-protein-supplementation-in-breast-cancer-survivors
#19
Takudzwa A Madzima, Michael J Ormsbee, Erica A Schleicher, Robert J Moffatt, Lynn B Panton
INTRODUCTION: To evaluate 12 wk of resistance training (RT; n=16) and protein supplementation (RT+protein; n=17) on muscular strength, body composition and blood biomarkers of muscle (insulin-like growth factor-1 (IGF-1)), fat (adiponectin), and inflammation [human C-reactive protein (CRP)] in breast cancer survivors (BCS). METHODS: Thirty-three BCS (59±8yr) were measured pre and post training for one-repetition maximum (1-RM) muscular strength (chest press: leg extension); body composition (lean mass (LM); fat mass (FM)) via DXA and serum concentrations of IGF-1, adiponectin, and CRP...
March 1, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28246150/changes-in-the-management-and-comorbidities-of-acromegaly-over-three-decades-the-french-acromegaly-registry
#20
Luigi Maione, Thierry Brue, Albert Beckers, Brigitte Delemer, Patrick Petrossians, Francoise Borson-Chazot, Olivier Chabre, Patrick Francois, Jerome Bertherat, Christine Cortet, Philippe Chanson
CONTEXT: Acromegaly is a rare disease associated with chronic multisystem complications. National registries have been created in several countries. DESIGN: The French registry contains data on acromegaly epidemiology, management and comorbidities recorded over more than three decades, retrospectively until 1999 and prospectively from 1999 until 2012. RESULTS: Data could be analyzed for 999 of the 1034 patients included in the registry (46% males)...
February 28, 2017: European Journal of Endocrinology
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