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IGF1R cancer

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https://www.readbyqxmd.com/read/28202495/expression-of-grk2-and-igf1r-in-hepatocellular-carcinoma-clinicopathological-and-prognostic-significance
#1
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
#2
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 13, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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...
January 8, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28062706/combinatorial-drug-screening-identifies-ewing-sarcoma-specific-sensitivities
#11
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
#12
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
https://www.readbyqxmd.com/read/28032929/downregulation-of-mir-100-mir-125b-is-associated-with-lymph-node-metastasis-in-early-colorectal-cancer-with-submucosal-invasion
#13
Yasuteru Fujino, Shunsaku Takeishi, Kensei Nishida, Koichi Okamoto, Naoki Muguruma, Tetsuo Kimura, Shinji Kitamura, Hiroshi Miyamoto, Akiko Fujimoto, Jun Higashijima, Mitsuo Shimada, Kazuhito Rokutan, Tetsuji Takayama
A majority of early colorectal cancers (CRCs) with submucosal invasion undergo surgical operation despite very low incidence of lymph node metastasis. Our study aimed to identify microRNAs (miRNAs) specifically responsible for lymph node metastasis in submucosal CRCs. MicroRNA microarray analysis revealed that miR-100 and miR-125b expression levels were significantly lower in CRC tissues with lymph node metastases than in those without metastases. These results were validated by quantitative real-time PCR in a larger set of clinical samples...
December 29, 2016: Cancer Science
https://www.readbyqxmd.com/read/28030849/combined-and-individual-tumor-specific-expression-of-insulin-like-growth-factor-i-receptor-insulin-receptor-and-phospho-insulin-like-growth-factor-i-receptor-insulin-receptor-in-primary-breast-cancer-implications-for-prognosis-in-different-treatment-groups
#14
Sofie Björner, Ann H Rosendahl, Maria Simonsson, Andrea Markkula, Karin Jirström, Signe Borgquist, Carsten Rose, Christian Ingvar, Helena Jernström
Clinical trials examining insulin-like growth factor-I receptor (IGF1R)-targeting strategies have emphasized that better predictive biomarkers are required to improve patient selection.Immunohistochemical tumor-specific protein expression of IGF1R, insulin receptor (InsR), and phosphorylated IGF1R/InsR (pIGF1R/InsR) individually and combined in relation to breast cancer prognosis was evaluated in a population-based cohort of 1,026 primary invasive breast cancer patients without preoperative treatment diagnosed in Sweden...
December 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/28017727/silencing-hs6st3-inhibits-growth-and-progression-of-breast-cancer-cells-through-suppressing-igf1r-and-inducing-xaf1
#15
Omid Iravani, Boon-Huat Bay, George Wai-Cheong Yip
Heparan sulfate 6-O-sulfation is biologically edited by 6-O-sulfotransferases (HS6STs) within heparan sulfate chains. Three isoforms of HS6ST have been identified. These enzymes are found to be differentially expressed in a variety of tissues. Recently, several studies have shown that dysregulation of 6-O-sulfotransferases could be involved in tumorigenesis of several cancers. This study aimed to analyze the expression and function of HS6ST3 in breast cancer. HS6ST3 was found up-regulated in T47D, MCF7 and MDA-MB231 breast cancer cell lines...
December 23, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27989801/molecular-checkpoint-decisions-made-by-subverted-vascular-niche-transform-indolent-tumor-cells-into-chemoresistant-cancer-stem-cells
#16
Zhongwei Cao, Joseph M Scandura, Giorgio G Inghirami, Koji Shido, Bi-Sen Ding, Shahin Rafii
Tumor-associated endothelial cells (TECs) regulate tumor cell aggressiveness. However, the core mechanism by which TECs confer stem cell-like activity to indolent tumors is unknown. Here, we used in vivo murine and human tumor models to identify the tumor-suppressive checkpoint role of TEC-expressed insulin growth factor (IGF) binding protein-7 (IGFBP7/angiomodulin). During tumorigenesis, IGFBP7 blocks IGF1 and inhibits expansion and aggresiveness of tumor stem-like cells (TSCs) expressing IGF1 receptor (IGF1R)...
January 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/27964748/non-coding-single-nucleotide-variants-affecting-estrogen-receptor-binding-and-activity
#17
Amir Bahreini, Kevin Levine, Lucas Santana-Santos, Panayiotis V Benos, Peilu Wang, Courtney Andersen, Steffi Oesterreich, Adrian V Lee
BACKGROUND: Estrogen receptor (ER) activity is critical for the development and progression of the majority of breast cancers. It is known that ER is differentially bound to DNA leading to transcriptomic and phenotypic changes in different breast cancer models. We investigated whether single nucleotide variants (SNVs) in ER binding sites (regSNVs) contribute to ER action through changes in the ER cistrome, thereby affecting disease progression. Here we developed a computational pipeline to identify SNVs in ER binding sites using chromatin immunoprecipitation sequencing (ChIP-seq) data from ER+ breast cancer models...
December 13, 2016: Genome Medicine
https://www.readbyqxmd.com/read/27956702/snail-modulated-mir-493-forms-a-negative-feedback-loop-with-igf1r-pathway-and-blocks-tumorigenesis
#18
Arathy S Kumar, Sankar Jagadeeshan, Ravi Shankar Pitani, Vijayalakshmi Ravishankar, Kesavan Venkitasamy, Ganesh Venkatraman, Suresh K Rayala
In this study, we have identified one microRNA - miR-493, which could simultaneously and directly regulate multiple genes downstream of IGF1R pathway including IGF1R, by binding with complementary sequences in the 3' UTR of mRNAs of IGF1R, IRS1 and MAPK1, thereby potentiating their inhibitory function at multiple levels in development and progression of cancers. This binding was further confirmed by pull down of miR with AGO-2 antibody. Further, results from head and neck samples showed that miR-493 levels were significantly downregulated in tumors with a concomitant increase in the expression of IGF1R and key downstream effectors...
December 12, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27891760/muscle-ras-oncogene-homolog-mras-recurrent-mutation-in-borrmann-type-iv-gastric-cancer
#19
Makiko Yasumoto, Etsuko Sakamoto, Sachiko Ogasawara, Taro Isobe, Junya Kizaki, Akiko Sumi, Hironori Kusano, Jun Akiba, Takuji Torimura, Yoshito Akagi, Hiraku Itadani, Tsutomu Kobayashi, Shinichi Hasako, Masafumi Kumazaki, Shinji Mizuarai, Shinji Oie, Hirohisa Yano
The prognosis of patients with Borrmann type IV gastric cancer (Type IV) is extremely poor. Thus, there is an urgent need to elucidate the molecular mechanisms underlying the oncogenesis of Type IV and to identify new therapeutic targets. Although previous studies using whole-exome and whole-genome sequencing have elucidated genomic alterations in gastric cancer, none has focused on comprehensive genetic analysis of Type IV. To discover cancer-relevant genes in Type IV, we performed whole-exome sequencing and genome-wide copy number analysis on 13 patients with Type IV...
January 2017: Cancer Medicine
https://www.readbyqxmd.com/read/27879396/integrating-network-reconstruction-with-mechanistic-modeling-to-predict-cancer-therapies
#20
Melinda Halasz, Boris N Kholodenko, Walter Kolch, Tapesh Santra
Signal transduction networks are often rewired in cancer cells. Identifying these alterations will enable more effective cancer treatment. We developed a computational framework that can identify, reconstruct, and mechanistically model these rewired networks from noisy and incomplete perturbation response data and then predict potential targets for intervention. As a proof of principle, we analyzed a perturbation data set targeting epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) pathways in a panel of colorectal cancer cells...
November 22, 2016: Science Signaling
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