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IGF-1 cancer

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https://www.readbyqxmd.com/read/28815409/insulin-like-growth-factor-igf-pathway-targeting-in-cancer-role-of-the-igf-axis-and-opportunities-for-future-combination-studies
#1
Aaron Simpson, Wilfride Petnga, Valentine M Macaulay, Ulrike Weyer-Czernilofsky, Thomas Bogenrieder
Despite a strong preclinical rationale for targeting the insulin-like growth factor (IGF) axis in cancer, clinical studies of IGF-1 receptor (IGF-1R)-targeted monotherapies have been largely disappointing, and any potential success has been limited by the lack of validated predictive biomarkers for patient enrichment. A large body of preclinical evidence suggests that the key role of the IGF axis in cancer is in driving treatment resistance, via general proliferative/survival mechanisms, interactions with other mitogenic signaling networks, and class-specific mechanisms such as DNA damage repair...
August 16, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28810619/microrna-503-suppresses-cell-proliferation-and-invasion-in-osteosarcoma-via-targeting-insulin-like-growth-factor-1-receptor
#2
Zili Wang, Chenhuang Zheng, Kunqi Jiang, Jinshen He, Xu Cao, Song Wu
MicroRNAs (miRs) are a class of small non-coding RNAs and have key roles in various cancer types. Recently, miR-503 has been reported to act as a tumor suppressor in osteosarcoma. However, the detailed mechanism of the regulatory role of miR-503 in osteosarcoma cell proliferation and invasion has largely remained elusive. The present study found that miR-503 was significantly downregulated in osteosarcoma tissues compared to that in matched adjacent non-tumorous tissues. In addition, the expression of miR-503 in osteosarcoma of T3-T4 stage was significantly lower when compared with that in T1-T2 stage samples...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28803443/solasodine-inhibits-human-colorectal-cancer-cells-via-suppression-of-akt-gsk-3%C3%AE-%C3%AE-catenin-pathway
#3
Yu-Wen Zhuang, Cun-En Wu, Jin-Yong Zhou, Xu Chen, Jian Wu, Shan Jiang, Hai-Yan Peng, Xi Zou, Jia-Yun Liu, Da-Peng Wu, Tao Gong, Ming-Hao Qi, Tian Xue, Shen-Lin Liu, Hui Cai
Solasodine is a main active component isolated from Solanum incanum L, who performs a wide range of functions containing anti-oxidant, anti-infection and neurogenesis promotion. In this study, we explored the influence of solasodine on three types of human colorectal cancer (CRC) cell lines. The consequences displayed that solasodine apparently prohibited CRC cell proliferation dose- and time-dependently and impeded CRC cell motility by downregulating Matrix metalloprotease (MMPs). Besides, solasodine was investigated to fuel caspase-cascade reaction and increase the ratio between Bax and Bcl-2 so as to induce CRC cell apoptosis...
August 13, 2017: Cancer Science
https://www.readbyqxmd.com/read/28768896/the-effects-of-graded-levels-of-calorie-restriction-xi-evaluation-of-the-main-hypotheses-underpinning-the-life-extension-effects-of-cr-using-the-hepatic-transcriptome
#4
Davina Derous, Sharon E Mitchell, Lu Wang, Cara L Green, Yingchun Wang, Luonan Chen, Jing-Dong J Han, Daniel E L Promislow, David Lusseau, Alex Douglas, John R Speakman
Calorie restriction (CR) may extend longevity by modulating the mechanisms involved in aging. Different hypotheses have been proposed for its main mode of action. We quantified hepatic transcripts of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months, and evaluated the responses relative to these various hypotheses. Of the four main signaling pathways implied to be linked to the impact of CR on lifespan (insulin/insulin like growth factor 1 (IGF-1), nuclear factor-kappa beta (NF-ĸB), mechanistic target of rapamycin (mTOR) and sirtuins (SIRTs)), all the pathways except SIRT were altered in a manner consistent with increased lifespan...
July 31, 2017: Aging
https://www.readbyqxmd.com/read/28758175/next-generation-sequencing-of-progressive-colorectal-liver-metastases-after-portal-vein-embolization
#5
Eve Simoneau, Jarred Chicoine, Sarita Negi, Ayat Salman, Anthoula Lazaris, Mazen Hassanain, Nicole Beauchemin, Stephanie Petrillo, David Valenti, Ramila Amre, Peter Metrakos
Portal vein embolization (PVE) can be required to stimulate liver regeneration before hepatectomy for colorectal liver metastasis (CRCLM), however PVE may also trigger CRCLM progression in patients initially exhibiting chemotherapy response. Using RNA-seq, we aimed to determine the molecular networks involved in metastatic progression in this context. A prospective study including all CRCLM patients undergoing PVE prior to hepatectomy was conducted. Paired biopsies of metastatic lesions were obtained prior to and after PVE and total RNA was isolated and used to prepare Illumina rRNA-depleted TruSeq stranded cDNA libraries for HiSeq 100 bp paired-end sequencing...
July 31, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28742836/the-impact-of-met-igf-1-igf1r-expression-and-egfr-mutations-on-survival-of-patients-with-non-small-cell-lung-cancer
#6
Samer Al-Saad, Elin Richardsen, Thomas K Kilvaer, Tom Donnem, Sigve Andersen, Mehrdad Khanehkenari, Roy M Bremnes, Lill-Tove Busund
INTRODUCTION: To compare the efficacy of silver in situ hybridization (SISH) and immunohistochemistry (IHC) in detecting MET and IGF1R alterations and to investigate their prevalence and prognostic significance. A possible correlation between MET receptor expression, MET gene alterations and the two most frequent occurring EGFR gene mutations was also investigated. MATERIALS AND METHODS: Stage I to IIIA tumors from 326 patients with NSCLC were immunohistochemically tested for protein expression of MET and IGF-1...
2017: PloS One
https://www.readbyqxmd.com/read/28740570/quercetin-reverses-rat-liver-preneoplastic-lesions-induced-by-chemical-carcinogenesis
#7
Gabriela Carrasco-Torres, Hugo Christian Monroy-Ramírez, Arturo Axayacatl Martínez-Guerra, Rafael Baltiérrez-Hoyos, María de Los Ángeles Romero-Tlalolini, Saúl Villa-Treviño, Xariss Sánchez-Chino, Verónica Rocío Vásquez-Garzón
Quercetin is a flavonoid widely studied as a chemopreventive agent in different types of cancer. Previously, we reported that quercetin has a chemopreventive effect on the liver-induced preneoplastic lesions in rats. Here, we evaluated if quercetin was able not only to prevent but also to reverse rat liver preneoplastic lesions. We used the modified resistant hepatocyte model (MRHM) to evaluate this possibility. Treatment with quercetin was used 15 days after the induction of preneoplastic lesions. We found that quercetin reverses the number of preneoplastic lesions and their areas...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28732480/metformin-and-longevity-metal-a-window-of-opportunity-study-investigating-the-biological-effects-of-metformin-in-localised-prostate-cancer
#8
Danielle Crawley, Ashish Chandra, Massimo Loda, Cheryl Gillett, Paul Cathcart, Ben Challacombe, Gary Cook, Declan Cahill, Aida Santa Olalla, Fidelma Cahill, Gincy George, Sarah Rudman, Mieke Van Hemelrijck
BACKGROUND: Metformin is a biguanide oral hypoglycaemic agent commonly used for the treatment of type 2 diabetes mellitus. In addition to its anti-diabetic effect, metformin has also been associated with a reduced risk of cancer incidence of a number of solid tumours, including prostate cancer (PCa). However, the underlying biological mechanisms for these observations have not been fully characterised in PCa. One hypothesis is that the indirect insulin lowering effect may have an anti-neoplastic action as elevated insulin and insulin like growth factor - 1 (IGF-1) levels play a role in PCa development and progression...
July 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28731223/neferine-modulates-igf-1r-nrf2-signaling-in-doxorubicin-treated-h9c2-cardiomyoblasts
#9
Lohanathan Bharathi Priya, Rathinasamy Baskaran, Chih-Yang Huang, Viswanadha Vijaya Padma
Doxorubicin (DOX) induced cardiotoxicity is a major problem during chemotherapy of cancers. DOX-mediated suppression of type 1 IGF receptor (IGF-1R) signaling leads to cardiac dysfunction. Neferine, a bisbezylisoquinoline alkaloid from the seed embryos of Nelumbo nucifera Gaertn possesses a distinct range of pharmacological properties. Herewith, the present study attempts to elucidate the protective role of neferine against DOX induced toxicity in H9c2 rat cardiomyoblast cell line model. DOX-treated H9c2 cells significantly increased mitochondrial superoxide generation, depleted cellular antioxidant status, suppressed the activation of IGF-1R signaling via PI3K/Akt/mTOR and induced autophagy by the activation of ULK1, Beclin1, Atg7 and LC3B...
July 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28731178/microrna-379-acts-as-a-tumor-suppressor-in-non-small-cell-lung-cancer-by-targeting-the-igf%C3%A2-1r-mediated-akt-and-erk-pathways
#10
Fangzheng Zhou, Long Nie, Dali Feng, Siyan Guo, Ren'na Luo
Lung cancer is one of the most common types of malignancy in humans and is a leading cause of cancer-related deaths among men and women worldwide. Aberrantly expressed microRNAs in non-small cell lung cancer (NSCLC) contribute to tumor occurrence and development as either tumor suppressors or promoters. MicroRNA-379 (miR‑379) is dysregulated in several types of human cancer. However, its expression pattern, role and underlying mechanism in NSCLC progression and metastasis are poorly understood. In this study, assay of reverse transcription-quantitative polymerase chain reaction showed that miR‑379 was downregulated in both NSCLC tissue and cell lines...
September 2017: Oncology Reports
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
#11
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/28722660/glypican-3-induces-oncogenicity-by-preventing-igf-1r-degradation-a-process-that-can-be-blocked-by-grb10
#12
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/28715819/effect-of-microrna-135a-on-cell-proliferation-migration-invasion-apoptosis-and-tumor-angiogenesis-through-the-igf-1-pi3k-akt-signaling-pathway-in-non-small-cell-lung-cancer
#13
Yufei Zhou, Shaoxia Li, Jiangtao Li, Dongfeng Wang, Quanxing Li
OBJECTIVE: This study explored the ability of microRNA-135a (miR-135a) to influence cell proliferation, migration, invasion, apoptosis and tumor angiogenesis through the IGF-1/PI3K/Akt signaling pathway in non-small cell lung cancer (NSCLC). METHODS: NSCLC tissues and adjacent normal tissues were collected from 138 NSCLC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-135a and IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 mRNA; western blotting was used to determine the expression levels of IGF-1, PI3K and Akt protein; and enzyme-linked immunosorbent assay (ELISA) was used to analyze the expression levels of VEGF, bFGF and IL-8 protein...
July 17, 2017: Cellular Physiology and Biochemistry
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
#14
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...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28710407/role-of-insulin-receptor-substrates-in-the-progression-of-hepatocellular-carcinoma
#15
Yoshitaka Sakurai, Naoto Kubota, Iseki Takamoto, Atsushi Obata, Masahiko Iwamoto, Takanori Hayashi, Masakazu Aihara, Tetsuya Kubota, Hiroshi Nishihara, Takashi Kadowaki
Several cellular signaling pathways, including insulin/IGF signaling, are known to be activated in hepatocellular carcinoma (HCC). Here, we investigated the roles of insulin receptor substrate (Irs) 1 and Irs2, both of which are the major molecules to be responsible for transducing insulin/IGF signaling in the liver, in the development of HCC by inducing chemical carcinogenesis using diethylnitrosamine (DEN) in mice. The Irs1 mRNA and protein expressions were upregulated in the tumors, along with enhanced insulin signaling...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698593/differential-adiponectin-signalling-couples-er-stress-with-lipid-metabolism-to-modulate-ageing-in-c-elegans
#16
Emmanouil Kyriakakis, Nikolaos Charmpilas, Nektarios Tavernarakis
The metabolic and endocrine functions of adipose tissue and the ability of organisms to cope with cellular stress have a direct impact on physiological ageing and the aetiology of various diseases such as obesity-related pathologies and cancer. The endocrine effects of adipose tissue are mediated by secreted adipokines, which modulate metabolic processes and influence related maladies. Although a plethora of molecules and signaling pathways associate ageing with proteotoxic stress and cellular metabolism, our understanding of how these pathways interconnect to coordinate organismal physiology remains limited...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28695747/novel-strategies-for-anti-aging-drug-discovery
#17
Komal Saraswat, Syed Ibrahim Rizvi
Scientific achievements in the last few decades, leading to effective therapeutic interventions, have dramatically improved human life expectancy. Consequently, aging has become a significant problem and represents the major risk factor for most human pathologies including diabetes, cardiovascular diseases, neurological disorders, and cancer. Scientific discoveries over the past two decades have been instrumental in dissecting molecular mechanism(s) which play important roles in determining longevity. The same understanding has also led to the acknowledgement of the plurality of 'causes' which act either alone or in combination to create the condition which can be defined as 'aging'...
September 2017: Expert Opinion on Drug Discovery
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
#18
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
#19
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/28681171/a-randomized-phase-ii-trial-of-ridaforolimus-dalotuzumab-and-exemestane-compared-with-ridaforolimus-and-exemestane-in-patients-with-advanced-breast-cancer
#20
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
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