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IGF1R cancer

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https://www.readbyqxmd.com/read/28289161/distinct-afatinib-resistance-mechanisms-identified-in-lung-adenocarcinoma-harboring-an-egfr-mutation
#1
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
#2
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/28256105/cis-nerolidol-induces-endoplasmic-reticulum-stress-and-cell-death-in-human-hepatocellular-carcinoma-cells-through-extensive-cyp2c19-and-cyp1a2-oxidation
#3
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
#4
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
#5
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
#6
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/28223541/targeting-growth-hormone-receptor-in-human-melanoma-cells-attenuates-tumor-progression-and-epithelial-mesenchymal-transition-via-suppression-of-multiple-oncogenic-pathways
#7
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
#8
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/28202495/expression-of-grk2-and-igf1r-in-hepatocellular-carcinoma-clinicopathological-and-prognostic-significance
#9
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/28193878/thada-fusion-is-a-mechanism-of-igf2bp3-activation-and-igf1r-signaling-in-thyroid-cancer
#10
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/28173837/insulin-like-growth-factor-1-receptor-activation-promotes-mammary-gland-tumor-development-by-increasing-glycolysis-and-promoting-biomass-production
#11
Bas Ter Braak, Christine L Siezen, Joo S Lee, Pooja Rao, Charlotte Voorhoeve, Eytan Ruppin, Jan Willem van der Laan, Bob van de Water
BACKGROUND: The insulin-like growth factor 1 (IGF1) signaling axis plays a major role in tumorigenesis. In a previous experiment, we chronically treated mice with several agonists of the IGF1 receptor (IGF1R). We found that chronic treatment with insulin analogues with high affinity towards the IGF1R (IGF1 and X10) decreased the mammary gland tumor latency time in a p53(R270H/+)WAPCre mouse model. Frequent injections with insulin analogues that only mildly activated the IGF1R in vivo (glargine and insulin) did not significantly decrease the tumor latency time in this mouse model...
February 7, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28125713/knockdown-of-mediator-complex-subunit-19-suppresses-the-growth-and-invasion-of-prostate-cancer-cells
#12
Shengqiang Yu, Yanwei Wang, Hejia Yuan, Hongwei Zhao, Wei Lv, Jian Chen, Fengchun Wan, Dongfu Liu, Zhenli Gao, Jitao Wu
Prostate cancer (PCa) is one of the most common cancers in elderly men. Mediator Complex Subunit 19 (Med19) is overexpressed and plays promotional roles in many cancers. However, the roles of Med19 in PCa are still obscure. In this study, by using immunohistochemical staining, we found higher expression level of Med19 in PCa tissues than in adjacent benign prostate tissues. We then knocked down the Med19 expression in PCa cell lines LNCaP and PC3 by using lentivirus siRNA. Cell proliferation, anchor-independent growth, migration, and invasion were suppressed in Med19 knockdown PCa cells...
2017: PloS One
https://www.readbyqxmd.com/read/28112398/sumo-modified-insulin-like-growth-factor-1-receptor-igf-1r-increases-cell-cycle-progression-and-cell-proliferation
#13
Yingbo Lin, Hongyu Liu, Ahmed Waraky, Felix Haglund, Prasoon Agarwal, Helena Jernberg-Wiklund, Dudi Warsito, Olle Larsson
Increasing number of studies have shown nuclear localization of the insulin-like growth factor 1 receptor (nIGF-1R) in tumor cells and its links to adverse clinical outcome in various cancers. Any obvious cell physiological roles of nIGF-1R have, however, still not been disclosed. Previously, we reported that IGF-1R translocates to cell nucleus and modulates gene expression by binding to enhancers, provided that the receptor is SUMOylated. In this study, we constructed stable transfectants of wild type IGF1R (WT) and triple-SUMO-site-mutated IGF1R (TSM) using igf1r knockout mouse fibroblasts (R-)...
January 23, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28099935/frequent-amplification-of-receptor-tyrosine-kinase-genes-in-welldifferentiated-dedifferentiated-liposarcoma
#14
Naofumi Asano, Akihiko Yoshida, Sachiyo Mitani, Eisuke Kobayashi, Bunsyo Shiotani, Motokiyo Komiyama, Hiroyuki Fujimoto, Hirokazu Chuman, Hideo Morioka, Morio Matsumoto, Masaya Nakamura, Takashi Kubo, Mamoru Kato, Takashi Kohno, Akira Kawai, Tadashi Kondo, Hitoshi Ichikawa
Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are closely related tumors commonly characterized by MDM2/CDK4 gene amplification, and lack clinically effective treatment options when inoperable. To identify novel therapeutic targets, we performed targeted genomic sequencing analysis of 19 WDLPS and 37 DDLPS tumor samples using a panel of 104 cancer-related genes (NCC oncopanel v3) developed specifically for genomic testing to select suitable molecular targeted therapies. The results of this analysis indicated that these sarcomas had very few gene mutations and a high frequency of amplifications of not only MDM2 and CDK4 but also other genes...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28089377/phase-ii-trial-of-albumin-bound-paclitaxel-and-granulocyte-macrophage-colony-stimulating-factor-as-an-immune-modulator-in-recurrent-platinum-resistant-ovarian-cancer
#15
John B Liao, Ron E Swensen, Kelsie J Ovenell, Katie M Hitchcock-Bernhardt, Jessica L Reichow, Minjun C Apodaca, Leonard D'Amico, Jennifer S Childs, Doreen M Higgins, Barbara J Buening, Barbara A Goff, Mary L Disis
BACKGROUND: Granulocyte macrophage colony-stimulating factor (GM-CSF) stimulates immunity via recruitment of antigen presenting cells and tumor specific T-cell stimulation. Albumin-bound paclitaxel (nab-paclitaxel) followed by GM-CSF may enhance antitumor responses and prolong remissions in ovarian cancer. Immune phenotypes present before treatment may identify responders to chemo-immunotherapy. METHODS: Recurrent platinum-resistant ovarian, peritoneal, or fallopian tube cancer patients received nab-paclitaxel, 100mg/m(2) days 1, 8, 15 followed by GM-CSF 250μg days 16-26 every 28days for 6 planned cycles...
January 12, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28075048/the-sti-and-uba-domains-of-ubqln1-are-critical-determinants-of-substrate-interaction-and-proteostasis
#16
Zimple Kurlawala, Parag P Shah, Charmi Shah, Levi J Beverly
There are 5 Ubiquilin proteins (UBQLN1-4, UBQLN-L), which are evolutionarily conserved and structurally similar. UBQLN proteins have 3 functional domains: N-terminal ubiquitin-like domain (UBL), C-terminal ubiquitin-associated domain (UBA) and STI chaperone-like regions in the middle. Alterations in UBQLN1 gene have been detected in a variety of disorders ranging from Alzheimer's disease to cancer. UBQLN1 has been largely studied in neurodegenerative disorders in the context of protein quality control. Several studies have hypothesized that the UBA domain of UBQLN1 binds to poly-ubiquitin chains of substrate and shuttles it to the proteasome via its UBL domain for degradation...
January 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28067383/the-functional-consequences-and-prognostic-value-of-dosage-sensitivity-in-ovarian-cancer
#17
Zichuang Yan, Yongjing Liu, Yunzhen Wei, Ning Zhao, Qiang Zhang, Cheng Wu, Zhiqiang Chang, Yan Xu
Copy number alteration (CNA) represents an important class of genetic variations that may contribute to tumorigenesis, tumor growth and metastatic spread. CNA can directly affect the expression of genes within the CNA regions; however, genes within the CNA regions exhibit heterogeneity in gene dosage sensitivity. In this study, a computational framework was built to identify 1170 dosage-sensitive genes (DSGs) and 1215 dosage-resistant genes (DRGs) that were related to ovarian serous cystadenocarcinoma (OV) through the association between CNA and gene expression...
January 9, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28064447/up-regulation-of-mir-497-confers-resistance-to-temozolomide-in-human-glioma-cells-by-targeting-mtor-bcl-2
#18
Danhua Zhu, Ming Tu, Bo Zeng, Lin Cai, Weiming Zheng, Zhipeng Su, Zhengquan Yu
The occurrence of an inherent or acquired resistance to temozolomide (TMZ) is a major burden for patients suffering from glioma. Recently, studies have demonstrated that microRNAs play an important role in the regulation of tumor properties in cancers. However, whether miR-497 contributes to glioma resistance to chemotherapy is not fully understood. In this study, we showed that the expression of miR-497 was markedly up-regulated in TMZ-resistant glioma cells; high miR-497 expression level was associated with TMZ-resistant phenotype of glioma cells...
February 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28062706/combinatorial-drug-screening-identifies-ewing-sarcoma-specific-sensitivities
#19
Branka Radic-Sarikas, Kalliopi P Tsafou, Kristina B Emdal, Theodore Papamarkou, Kilian V M Huber, Cornelia Mutz, Jeffrey A Toretsky, Keiryn L Bennett, Jesper V Olsen, Søren Brunak, Heinrich Kovar, Giulio Superti-Furga
Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents including approved drugs...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28043364/inhibition-of-peripubertal-sheep-mammary-gland-development-by-cysteamine-through-reducing-progesterone-and-growth-factor-production
#20
Yong Zhao, Yanni Feng, Hongfu Zhang, Xin Kou, Lan Li, Xinqi Liu, Pengfei Zhang, Liantao Cui, Meiqiang Chu, Wei Shen, Lingjiang Min
Cysteamine has been used for treating cystinosis for many years, and furthermore it has also been used as a therapeutic agent for different diseases including Huntington's disease, Parkinson's disease (PD), nonalcoholic fatty liver disease, malaria, cancer, and others. Although cysteamine has many potential applications, its use may also be problematic. The effects of low doses of cysteamine on the reproductive system, especially the mammary glands are currently unknown. In the current investigation, low dose (10 mg/kg BW/day) of cysteamine did not affect sheep body weight gain or organ index of the liver, spleen, or heart; it did, however, increase the levels of blood lymphocytes, monocytes, and platelets...
February 2017: Theriogenology
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