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https://www.readbyqxmd.com/read/28324020/paracrine-pathways-in-uterine-leiomyoma-stem-cells-involve-insulin-like-growth-factor-2-and-insulin-receptor-a
#1
Molly B Moravek, Ping Yin, John S Coon V, Masanori Ono, Stacy A Druschitz, Saurabh S Malpani, Matthew T Dyson, Alfred W Rademaker, Jared C Robins, Jian-Jun Wei, J Julie Kim, Serdar E Bulun
Context: Uterine leiomyoma (fibroids) are the most common benign tumor in women. Recently, three populations of leiomyoma cells were discovered based on CD34 and CD49b expression, but the molecular differences between these populations remain unknown. Objective: Define differential gene expression and signaling pathways in leiomyoma cell populations. Design: Cells from human leiomyoma were sorted by flow cytometry into three populations: CD34+/CD49b+, CD34+/CD49b-, and CD34-/CD49b-...
January 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28296881/transcriptomic-responses-to-environmental-temperature-by-turtles-with-temperature-dependent-and-genotypic-sex-determination-assessed-by-rnaseq-inform-the-genetic-architecture-of-embryonic-gonadal-development
#2
Srihari Radhakrishnan, Robert Literman, Jennifer Neuwald, Andrew Severin, Nicole Valenzuela
Vertebrate sexual fate is decided primarily by the individual's genotype (GSD), by the environmental temperature during development (TSD), or both. Turtles exhibit TSD and GSD, making them ideal to study the evolution of sex determination. Here we analyze temperature-specific gonadal transcriptomes (RNA-sequencing validated by qPCR) of painted turtles (Chrysemys picta TSD) before and during the thermosensitive period, and at equivalent stages in soft-shell turtles (Apalone spinifera-GSD), to test whether TSD's and GSD's transcriptional circuitry is identical but deployed differently between mechanisms...
2017: PloS One
https://www.readbyqxmd.com/read/28290552/overexpression-of-decorin-promoted-angiogenesis-in-diabetic-cardiomyopathy-via-igf1r-akt-vegf-signaling
#3
Jinsheng Lai, Fuqiong Chen, Jing Chen, Guoran Ruan, Mengying He, Chen Chen, Jiarong Tang, Dao Wen Wang
Microcirculatory dysfunction is believed to play an important role in diabetic cardiomyopathy. The small leucine-rich proteoglycan decorin is generally considered a pro-angiogenic factor. Here, we investigate whether overexpression of decorin ameliorates diabetic cardiomyopathy and its effects on angiogenesis in vivo and in vitro. Diabetes was induced through intraperitoneal injection with streptozotocin combined with a high-fat diet, and decorin was overexpressed via recombinant adeno-associated virus in Wistar rats...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289161/distinct-afatinib-resistance-mechanisms-identified-in-lung-adenocarcinoma-harboring-an-egfr-mutation
#4
Toshimitsu Yamaoka, Tohru Ohmori, Motoi Ohba, Satoru Arata, Yasunori Murata, Sojiro Kusumoto, Koichi Ando, Hiroo Ishida, Tsukasa Ohnishi, Yasutsuna Sasaki
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are associated with significant responses in non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations. However, acquired resistance to reversible EGFR-TKIs remains a major obstacle. In particular, while the second-generation irreversible EGFR-TKI afatinib is currently used for treating NSCLC patients, the mechanisms underlying acquired afatinib resistance remain poorly understood. Here, heterogeneous mechanisms of acquired resistance were identified following long-term exposure to increasing doses of afatinib in EGFR mutant lung adenocarcinoma PC9 cells...
March 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28286973/curcumin-inhibits-urothelial-tumor-development-by-suppressing-igf2-and-igf2-mediated-pi3k-akt-mtor-signaling-pathway
#5
Binqiang Tian, Yingmei Zhao, Tao Liang, Xuxiao Ye, Zuowei Li, Dongliang Yan, Qiang Fu, Yonghui Li
We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells and N-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin...
March 11, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28282122/discovery-of-r-1-3-4-amino-3-3-chloro-4-pyridin-2-ylmethoxy-phenyl-1h-pyrazolo-3-4-d-pyrimidin-1-yl-piperidin-1-yl-prop-2-en-1-one-chmfl-egfr-202-as-a-novel-irreversible-egfr-mutants-kinase-inhibitor-with-a-distinct-binding-mode
#6
Aoli Wang, Xixiang Li, Hong Wu, Fengming Zou, Xiao-E Yan, Cheng Chen, Chen Hu, Kailin Yu, Wenchao Wang, Peng Zhao, Jiaxin Wu, Ziping Qi, Wei Wang, Beilei Wang, Li Wang, Tao Ren, Shanchun Zhang, Cai-Hong Yun, Jing Liu, Qingsong Liu
Based on Ibrutinib's core pharmacophore, which was moderately active to EGFR T790M mutant, we discovered a novel EGFR inhibitor compound 19 (CHMFL-EGFR-202), which potently inhibited EGFR primary mutants (L858R, del19) and drug resistant mutant L858R/T790M. Compound 19 displayed a good selectivity profile among 468 kinases/mutants tested in the KINOMEscan assay (S score (1) = 0.02), especially it did not exhibit apparent activities against INSR and IGF1R kinases. The X-ray crystal structure revealed that this class of inhibitors formed a covalent bond with Cys797 in a distinct "DFG-in-C-Helix-out" inactive EGFR conformation...
March 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28277190/mir-422a-inhibits-glioma-proliferation-and-invasion-by-targeting-igf1-and-igf1r
#7
Haiyang Wang, Chongyang Tang, Meng Na, Wei Ma, Zhenfeng Jiang, Yifei Gu, Guizhen Ma, Haitao Ge, Hong Shen, Zhiguo Lin
Glioma is a common type of malignant brain tumor characterized by aggressive metastasis capability. Recent evidence has suggested that noncoding RNAs, including microRNAs, have important functions in the pathophysiology of glioma development. In this study, we investigated the biological function of miR-422a in human glioma. We found that miR-422a was downregulated in glioma tissues. We also demonstrated that expression of miR-422a in glioma cells markedly suppressed cell proliferation, migration, and invasion...
January 26, 2017: Oncology Research
https://www.readbyqxmd.com/read/28256105/cis-nerolidol-induces-endoplasmic-reticulum-stress-and-cell-death-in-human-hepatocellular-carcinoma-cells-through-extensive-cyp2c19-and-cyp1a2-oxidation
#8
Bruna Isabela Biazi, Thalita Alves Zanetti, Adrivanio Baranoski, Amanda Cristina Corveloni, Mário Sérgio Mantovani
Of late, many studies are attempting to find new molecules with anti-cancer properties, especially those with the capability to inhibit cell growth. The aim of this work was to evaluate nerolidol, a plant-based compound, as its cytotoxicity, genotoxicity, antiproliferative and apoptotic induction, cell cycle, mitochondrial membrane potential, and RT-qPCR of transcripts related to those pathways in the human hepatocellular carcinoma cell line (HepG2/C3A). Only cis-nerolidol (C-NER) demonstrated cytotoxicity (100 to 250 μM) activity and was selected to conduct the following experiments...
March 2, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28243682/an-allometric-pharmacokinetic-pharmacodynamics-model-for-bi-893923-a-novel-igf-1-receptor-inhibitor
#9
Melanie I Titze, Otmar Schaaf, Marco H Hofmann, Michael P Sanderson, Stephan K Zahn, Jens Quant, Thorsten Lehr
PURPOSE: BI 893923 is a novel IGF1R/INSR inhibitor with promising anti-tumor efficacy. Dose-limiting hyperglycemia has been observed for other IGF1R/INSR inhibitors in clinical trials. To counterbalance anti-tumor efficacy with the risk of hyperglycemia and to determine the therapeutic window, we aimed to develop a translational pharmacokinetic/pharmacodynamics model for BI 893923. This aimed to translate pharmacokinetics and pharmacodynamics from animals to humans by an allometrically scaled semi-mechanistic model...
February 27, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28236033/co-targeting-the-her-and-igf-insulin-receptor-axis-in-breast-cancer-with-triple-targeting-with-endocrine-therapy-for-hormone-sensitive-disease
#10
Ashok Chakraborty, Christos Hatzis, Michael P DiGiovanna
PURPOSE: Interactions between HER2, estrogen receptor (ER), and insulin-like growth factor I receptor (IGF1R) are implicated in resistance to monotherapies targeting these receptors. We have previously shown in pre-clinical studies synergistic anti-tumor effects for co-targeting each pairwise combination of HER2, IGF1R, and ER. Strikingly, synergy for HER2/IGF1R targeting occurred not only in a HER2+ model, but also in a HER2-normal model. The purpose of the current study was therefore to determine the generalizability of synergistic anti-tumor effects of co-targeting HER2/IGF1R, the anti-tumor activity of triple-targeting HER2/IGF1R/ER in hormone-dependent cell lines, and the effect of using the multi-targeting drugs neratinib (pan-HER) and BMS-754807 (dual IGF1R/insulin receptor)...
February 24, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28235715/down-regulation-of-anti-apoptotic-genes-in-tumor-cell-lines-is-facilitated-by-suppression-of-oct4b1
#11
Mohammad Reza Mirzaei, Mehdi Mahmoodi, Gholamhossein Hassanshahi, Zahra Ahmadi
PURPOSE: The OCT4B1 as a variant of OCT4 is expressed in both cancer cells and tissues. The anti-apoptotic property of this variant aid cancer cells to escape from apoptosis. Therefore, the aim of the present study was to determine the effects of OCT4B1 suppression on regulation of 25 genes involved in anti-apoptotic pathway in tumor cell lines. MATERIAL AND METHODS: AGS (gastric adenocarcinoma), 5637 (bladder tumor) and U-87MG (brain tumor) cells were transfected with specific OCT4B1 siRNA and a scramble siRNA by siRNA silencing gene technology, using Lipofectamine 2000 commercial kit...
May 10, 2016: Advances in Medical Sciences
https://www.readbyqxmd.com/read/28223742/insulin-like-growth-factor-1-increases-the-expression-of-inflammatory-biomarkers-and-sebum-production-in-cultured-sebocytes
#12
Hyojin Kim, Sun Young Moon, Mi Yeung Sohn, Weon Ju Lee
BACKGROUND: Acne vulgaris has been linked to the Western diet. Hyperglycemic diet increases insulin and insulin-like growth factor (IGF)-1. Deeper insights into IGF-1-mediated signal pathway are critical importance to understand the impact of Western diet. OBJECTIVE: We investigated the effect of IGF-1 on the expression of inflammatory biomarkers and sebum production in cultured sebocytes. METHODS: Polymerase chain reaction and enzyme-linked immunosorbent assay were performed to measure changes in the expression of inflammatory biomarkers including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), IGF1R, IGFBP2, sterol response element-binding protein (SREBP), and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3KCA) after the treatment of cultured sebocytes with 10(-7) M or 10(-5) M IGF-1...
February 2017: Annals of Dermatology
https://www.readbyqxmd.com/read/28223541/targeting-growth-hormone-receptor-in-human-melanoma-cells-attenuates-tumor-progression-and-epithelial-mesenchymal-transition-via-suppression-of-multiple-oncogenic-pathways
#13
Reetobrata Basu, Shiyong Wu, John J Kopchick
Recent reports have confirmed highest levels of growth hormone (GH) receptor (GHR) transcripts in melanoma, one of the most aggressive forms of human cancer. Yet the mechanism of GH action in melanoma remains mostly unknown. Here, using human malignant melanoma cells, we examined the effects of GH excess or siRNA mediated GHR knock-down (GHRKD) on tumor proliferation, migration and invasion. GH promoted melanoma progression while GHRKD attenuated the same. Western blot analysis revealed drastic modulation of multiple oncogenic signaling pathways (JAK2, STAT1, STAT3, STAT5, AKT, mTOR, SRC and ERK1/2) following addition of GH or GHRKD...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223169/igf1-igf1r-stat3-signaling-inducible-ifitm2-promotes-gastric-cancer-growth-and-metastasis
#14
Li Xu, Rui Zhou, Lezhong Yuan, Shiqing Wang, Xiaoyin Li, Huanrong Ma, Minyu Zhou, Changqie Pan, Jingwen Zhang, Na Huang, Min Shi, Jianping Bin, Yulin Liao, Wangjun Liao
Interferon-induced transmembrane proteins (IFITMs) are expressed in some types of cancer. However, their precise roles in tumor progression remain unclear. The present study investigated the function of IFITM2 in gastric cancer (GC) progression. A retrospective analysis of a public database and 167 GC patients revealed that IFITM2 expression was upregulated in gastric tumor samples, which was positively correlated with disease progression, more frequent postoperative recurrence, and higher mortality rate. IFITM2 knockdown decreased GC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition in vitro...
February 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28213921/maternal-igf1-and-igf1r-polymorphisms-and-the-risk-of-spontaneous-preterm-birth
#15
Jian-Rong He, Yu-Mian Lai, Hui-Hui Liu, Guang-Jian Liu, Wei-Dong Li, Xue-Jiao Fan, Xue-Ling Wei, Xiao-Yan Xia, Ya-Shu Kuang, Xiao-Dan Liu, Nian-Nian Chen, Jin-Hua Lu, Qiao-Zhu Chen, Wei-Bi Mai, Hui-Min Xia, Xiu Qiu
BACKGROUND: The insulin-like growth factor (IGF) pathway was involved in the occurrence of spontaneous preterm birth (SPTB), but little is known regarding the relationship between genetic variations in IGF pathway and the risk of SPTB. We aimed to investigate the associations of IGF1 rs972936 and IGF1 receptor (IGF1R) rs2229765 polymorphisms with SPTB risk in a Chinese population. METHOD: A total of 114 cases of SPTB and 250 controls of term delivery were included from Guangzhou Women and Children's Medical Center, China...
February 18, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28207927/attenuated-airway-hyperresponsiveness-and-mucus-secretion-in-hdm-exposed-igf1r-deficient-mice
#16
S Piñeiro-Hermida, J A Gregory, I P López, R Torrens, C Ruíz-Martínez, M Adner, J G Pichel
BACKGROUND: Asthma is a common chronic lung disease characterized by airflow obstruction, airway hyperresponsiveness (AHR) and inflammation. IGFs have been reported to play a role in asthma but little is known about how the Insulin-like Growth Factor 1 Receptor (IGF1R) affects asthma pathobiology. METHODS: Female Igf1r-deficient and control mice were intranasally challenged with house dust mite (HDM) extract or PBS five days per week for four weeks. Lung function measurements, and bronchioalveolar lavage fluid (BALF), serum and lungs were collected on day 28 for further cellular, histological and molecular analysis...
February 16, 2017: Allergy
https://www.readbyqxmd.com/read/28202495/expression-of-grk2-and-igf1r-in-hepatocellular-carcinoma-clinicopathological-and-prognostic-significance
#17
Song-Bai Lin, Li Zhou, Zhi-Yong Liang, Wei-Xun Zhou, Ye Jin
AIM: It has been shown that G-protein-coupled receptor kinase 2 (GRK2) negatively regulates the insulin-like growth factor 1 receptor (IGF1R) signalling pathway in hepatocellular carcinoma (HCC). The aim of this study was to evaluate the clinicopathological and prognostic significance of GRK2 and IGF1R in HCC. METHODS: Expression of GRK2 and IGF1R was first detected by tissue microarray-based immunohistochemistry in 156 patients with HCC. Staining results, termed the H-score, were then correlated with clinicopathological variables and patient survival...
February 15, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28196816/bone-marrow-derived-microrna-223-works-as-an-endocrine-genetic-signal-in-vascular-endothelial-cells-and-participates-in-vascular-injury-from-kawasaki-disease
#18
Maoping Chu, Rongzhou Wu, Shanshan Qin, Wenfeng Hua, Zhen Shan, Xing Rong, Jingjing Zeng, Lanlan Hong, Yeying Sun, Ying Liu, Wen Li, Shenming Wang, Chunxiang Zhang
BACKGROUND: Kawasaki disease (KD) is now the most common cause of acquired cardiac disease in children due to permanent coronary artery damage with unknown etiology. The study sought to determine the role of blood microRNA miR-223 in KD and KD-induced injuries in vascular endothelial cells (ECs) as well as the mechanisms involved. METHODS AND RESULTS: MicroRNA profiles in serum from patients with KD and from healthy controls were assessed by microarray analysis...
February 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28193878/thada-fusion-is-a-mechanism-of-igf2bp3-activation-and-igf1r-signaling-in-thyroid-cancer
#19
Federica Panebianco, Lindsey M Kelly, Pengyuan Liu, Shan Zhong, Sanja Dacic, Xiaosong Wang, Aatur D Singhi, Rajiv Dhir, Simion I Chiosea, Shih-Fan Kuan, Rohit Bhargava, David Dabbs, Sumita Trivedi, Manoj Gandhi, Rachel Diaz, Abigail I Wald, Sally E Carty, Robert L Ferris, Adrian V Lee, Marina N Nikiforova, Yuri E Nikiforov
Thyroid cancer development is driven by known point mutations or gene fusions found in ∼90% of cases, whereas driver mutations in the remaining tumors are unknown. The insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) plays an important role in cancer, yet the mechanisms of its activation in cancer cells remain poorly understood. Using whole-transcriptome and whole-genome analyses, we identified a recurrent fusion between the thyroid adenoma-associated (THADA) gene on chromosome 2 and the LOC389473 gene on chromosome 7 located 12 kb upstream of the IGF2BP3 gene...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28190785/crosstalk-between-insulin-like-growth-factor-igf-receptor-and-integrins-through-direct-integrin-binding-to-igf1
#20
Yoshikazu Takada, Yoko K Takada, Masaaki Fujita
It has been generally accepted that integrin cell adhesion receptors are involved in growth factor signaling (integrin-growth factor crosstalk), since antagonists to integrins often suppress growth factor signaling. Partly because integrins have been originally identified as cell adhesion receptors to extracellular matrix (ECM) proteins, current models of the crosstalk between IGF1 and integrins propose that ECM ligands (e.g., vitronectin) bind to integrins and IGF1 binds to IGF receptor type 1 (IGF1R), and two separate signals merge inside the cells...
February 3, 2017: Cytokine & Growth Factor Reviews
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