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https://www.readbyqxmd.com/read/27891760/muscle-ras-oncogene-homolog-mras-recurrent-mutation-in-borrmann-type-iv-gastric-cancer
#1
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...
November 28, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27879396/integrating-network-reconstruction-with-mechanistic-modeling-to-predict-cancer-therapies
#2
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
https://www.readbyqxmd.com/read/27862334/tgf%C3%AE-signaling-confers-sorafenib-resistance-via-induction-of-multiple-rtks-in-hepatocellular-carcinoma-cells
#3
Nathan Ungerleider, Chang Han, Jinqiang Zhang, Lu Yao, Tong Wu
Transforming growth factor β (TGFβ) is a multifunctional cytokine which is importantly implicated in hepatocarcinogenesis. The current study provides novel evidence that TGFβ upregulates the expression of multiple receptor tyrosine kinases (RTKs), including IGF1R, EGFR, PDGFβR, and FGFR1 in human hepatocellular carcinoma (HCC) cells. This, in turn, sensitized HCC cells to individual cognate RTK ligands, leading to cell survival. Our data showed that the TGFβ-mediated increase in growth factor sensitivity led to evasion of apoptosis induced by the mutikinase inhibitor, sorafenib...
November 15, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27861515/involvement-of-igf1r-in-bronchiolar-epithelial-regeneration-role-during-repair-kinetics-after-selective-club-cell-ablation
#4
Icíar P López, Sergio Piñeiro-Hermida, Rosete S Pais, Raquel Torrens, Andreas Hoeflich, José G Pichel
Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny...
2016: PloS One
https://www.readbyqxmd.com/read/27858328/adverse-events-and-efficacy-of-cixutumumab-in-phase-ii-clinical-trials-a-systematic-review-and-meta-analysis
#5
REVIEW
Hongxin Cao, Lixuan Cui, Wei Ma, Linhai Zhu, Kai Wang, Yang Ni, Yibing Wang, Jiajun Du
BACKGROUND AND OBJECTIVES: Cixutumumab is a monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF1R). We sought to evaluate the efficacy of cixutumumab in the treatment of cancer, and to comprehensively assess the associated adverse events in phase II clinical trials. METHODS: Data were collected from PubMed, Embase, and Clinicaltrials.gov. The improvement on progression-free survival (PFS) was evaluated by hazard ratio (HR) and 95% confidence intervals (95% CIs)...
November 17, 2016: Clinical Drug Investigation
https://www.readbyqxmd.com/read/27856640/g-protein-coupled-receptors-gpcrs-that-signal-via-protein-kinase-a-pka-cross-talk-at-insulin-receptor-substrate-1-irs1-to-activate-the-pi3k-akt-pathway
#6
Nathan C Law, Morris F White, Mary E Hunzicker-Dunn
GPCRs (G protein-coupled receptors)2 activate PI3K/AKT (phosphatidylinositol-3 kinase/v-AKT thymoma viral oncoprotein) to regulate many cellular functions that promote cell survival, proliferation, and growth. However, the mechanism by which GPCRs activate PI3K/AKT remains poorly understood. We used ovarian preantral granulosa cells (GCs) to elucidate the mechanism by which the GPCR agonist FSH (follicle-stimulating hormone) via PKA (protein kinase A) activates the PI3K/AKT cascade. IGF1 (insulin-like growth factor 1) is secreted in an autocrine/paracrine manner by GCs and activates the IGF1R (IGF1 receptor), but in the absence of FSH fails to stimulate YXXM phosphorylation of IRS1 (insulin receptor substrate 1) required for PI3K/AKT activation...
November 17, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27836546/apbb1-reinforces-cancer-stem-cell-and-epithelial-to-mesenchymal-transition-by-regulating-the-igf1r-signaling-pathway-in-non-small-cell-lung-cancer-cells
#7
Jei Ha Lee, Jung Yul Kim, Seo Yeon Kim, Soo Im Choi, Kuk Chan Kim, Eun Wie Cho, In Gyu Kim
Amyloid β precursor protein binding family B member 1(APBB1) was first identified as a binding partner of amyloid precursor protein during brain development, but its function in the context of cancer remain unclear. Here we show for the first time that APBB1 is partly associated with intensifying cancer stem cell(CSC) and epithelial-to-mesenchymal transition (EMT) and enhancing radiation-resistant properties of lung cancer cells. We found that APBB1 was highly expressed in ALDH1(high) CSC-like cells sorted from A549 lung cancer cells...
November 9, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27813496/the-cea-lo-colorectal-cancer-cell-population-harbors-cancer-stem-cells-and-metastatic-cells
#8
Chang Yan, Yibing Hu, Bo Zhang, Lei Mu, Kaiyu Huang, Hui Zhao, Chensen Ma, Xiaolan Li, Deding Tao, Jianping Gong, Jichao Qin
Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA-/lo) levels of CEA...
November 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27808166/lpa-receptor-activity-is-basal-specific-and-coincident-with-early-pregnancy-and-involution-during-mammary-gland-postnatal-development
#9
Deanna Acosta, Susmita Bagchi, Pilib Ó Broin, Daniel Hollern, Silvia E Racedo, Bernice Morrow, Rani S Sellers, John M Greally, Aaron Golden, Eran Andrechek, Teresa Wood, Cristina Montagna
During pregnancy, luminal and basal epithelial cells of the adult mammary gland proliferate and differentiate resulting in remodeling of the adult gland. While pathways that control this process have been characterized in the gland as a whole, the contribution of specific cell subtypes, in particular the basal compartment, remains largely unknown. Basal cells provide structural and contractile support, however they also orchestrate the communication between the stroma and the luminal compartment at all developmental stages...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27765041/lack-of-interaction-between-erbb2-and-insulin-receptor-substrate-signaling-in-breast-cancer
#10
Susan M Farabaugh, Bonita T Chan, Xiaojiang Cui, Robert K Dearth, Adrian V Lee
BACKGROUND: ErbB2 Receptor Tyrosine Kinase 2 (ErbB2, HER2/Neu) is amplified in breast cancer and associated with poor prognosis. Growing evidence suggests interplay between ErbB2 and insulin-like growth factor (IGF) signaling. For example, ErbB2 inhibitors can block IGF-induced signaling while, conversely, IGF1R inhibitors can inhibit ErbB2 action. ErbB receptors can bind and phosphorylate insulin receptor substrates (IRS) and this may be critical for ErbB-mediated anti-estrogen resistance in breast cancer...
October 21, 2016: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/27742686/chemoresistance-in-pancreatic-cancer-is-driven-by-stroma-derived-insulin-like-growth-factors
#11
Lucy Ireland, Almudena Santos, Muhammad S Ahmed, Carolyn Rainer, Sebastian R Nielsen, Valeria Quaranta, Ulrike Weyer-Czernilofsky, Danielle D Engle, Pedro A Perez-Mancera, Sarah E Coupland, Azzam Taktak, Thomas Bogenrieder, David A Tuveson, Fiona Campbell, Michael C Schmid, Ainhoa Mielgo
Tumor-associated macrophages (TAM) and myofibroblasts are key drivers in cancer that are associated with drug resistance in many cancers, including pancreatic ductal adenocarcinoma (PDAC). However, our understanding of the molecular mechanisms by which TAM and fibroblasts contribute to chemoresistance is unclear. In this study, we found that TAM and myofibroblasts directly support chemoresistance of pancreatic cancer cells by secreting insulin-like growth factors (IGF) 1 and 2, which activate insulin/IGF receptors on pancreatic cancer cells...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27736013/igfbp3-and-mapk-erk-signaling-mediates-melatonin-induced-antitumor-activity-in-prostate-cancer
#12
Juan C Mayo, David Hevia, Isabel Quiros-Gonzalez, Aida Rodriguez-Garcia, Pedro Gonzalez-Menendez, Vanesa Cepas, Iván Gonzalez-Pola, Rosa M Sainz
Treatment of prostate cancer (PCa), a leading cause of cancer among males, lacks successful strategies especially in advanced, hormone-refractory stages. Some clinical studies have shown an increase in neuroendocrine-like cells parallel to the tumor progression but their exact role is a matter of debate. The prostate is a well-known target for melatonin, which reduces PCa cells proliferation and induces neuroendocrine differentiation. To evaluate the mechanisms underlying the indole effects on neuroendocrine differentiation and its impact on PCa progression, we used a cell culture model (LNCaP) and a murine model (TRAMP)...
October 13, 2016: Journal of Pineal Research
https://www.readbyqxmd.com/read/27735036/mir-494-inhibits-invasion-and-proliferation-of-gastric-cancer-by-targeting-igf-1r
#13
X-Q Zhao, T-J Liang, J-W Fu
OBJECTIVE: The aim of this study was to investigate the target gene of miR-494 and its roles in tumor growth of gastric cancer (GC). PATIENTS AND METHODS: Expression of miR-494 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) in gastric cancer tissues and cell lines. Then, luciferase reporter assay was used to elucidate whether insulin-like growth factor 1 receptor (IGF1R) is a target gene of miR-494. Finally, the roles and mechanism of miR-494 in the regulation of tumor invasion were further investigated...
September 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27733416/combination-therapy-approaches-to-target-insulin-like-growth-factor-receptor-signaling-in-breast-cancer
#14
Aleksandra M Ochnik, Robert C Baxter
Insulin-like growth factor receptor (IGF1R) signaling as a therapeutic target has been widely studied and clinically tested. Despite the vast amount of literature supporting the biological role of IGF1R in breast cancer, effective clinical translation in targeting its activity as a cancer therapy has not been successful. The intrinsic complexity of cancer cell signaling mediated by many tyrosine kinase growth factor receptors that work together to modulate each other and intracellular downstream mediators in the cell highlights that studying IGF1R expression and activity as a prognostic factor and therapeutic target in isolation is certainly associated with problems...
November 2016: Endocrine-related Cancer
https://www.readbyqxmd.com/read/27705911/targeting-sall4-by-entinostat-in-lung-cancer
#15
Kol Jia Yong, Ailing Li, Wen-Bin Ou, Clarice Kit Yee Hong, Wenxiu Zhao, Fei Wang, Hiro Tatetsu, Benedict Yan, Lihua Qi, Jonathan A Fletcher, Henry Yang, Ross Soo, Daniel G Tenen, Li Chai
The overall survival of lung cancer patients remains dismal despite the availability of targeted therapies. Oncofetal protein SALL4 is a novel cancer target. We herein report that SALL4 was aberrantly expressed in a subset of lung cancer patients with poor survival. SALL4 silencing by RNA interference or SALL4 peptide inhibitor treatment led to impaired lung cancer cell growth. Expression profiling of SALL4-knockdown cells demonstrated that both the EGFR and IGF1R signaling pathways were affected. Connectivity Map analysis revealed the HDAC inhibitor entinostat as a potential drug in treating SALL4-expressing cancers, and this was confirmed in 17 lung cancer cell lines...
September 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27683110/polarization-of-macrophages-in-the-tumor-microenvironment-is-influenced-by-egfr-signaling-within-colon-cancer-cells
#16
Weina Zhang, Lechuang Chen, Kai Ma, Yahui Zhao, Xianghe Liu, Yu Wang, Mei Liu, Shufang Liang, Hongxia Zhu, Ningzhi Xu
Epidermal growth factor receptor (EGFR) is a target of colon cancer therapy, but the effects of this therapy on the tumor microenvironment remain poorly understood. Our in vivo studies showed that cetuximab, an anti-EGFR monoclonal antibody, effectively inhibited AOM/DSS-induced, colitis-associated tumorigenesis, downregulated M2-related markers, and decreased F4/80+/CD206+ macrophage populations. Treatment with conditioned medium of colon cancer cells increased macrophage expression of the M2-related markers arginase-1 (Arg1), CCL17, CCL22, IL-10 and IL-4...
September 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27662660/genomic-characterization-of-liver-metastases-from-colorectal-cancer-patients
#17
José María Sayagués, Luís Antonio Corchete, María Laura Gutiérrez, Maria Eugenia Sarasquete, María Del Mar Abad, Oscar Bengoechea, Encarna Fermiñán, María Fernanda Anduaga, Sofia Del Carmen, Manuel Iglesias, Carmen Esteban, María Angoso, Jose Antonio Alcazar, Jacinto García, Alberto Orfao, Luís Muñoz-Bellvis
Metastatic dissemination is the most frequent cause of death of sporadic colorectal cancer (sCRC) patients. Genomic abnormalities which are potentially characteristic of such advanced stages of the disease are complex and so far, they have been poorly described and only partially understood. We evaluated the molecular heterogeneity of sCRC tumors based on simultaneous assessment of the overall GEP of both coding mRNA and non-coding RNA genes in primary sCRC tumor samples from 23 consecutive patients and their paired liver metastases...
September 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27661454/improved-decision-making-for-prioritizing-tumor-targeting-antibodies-in-human-xenografts-utility-of-fluorescence-imaging-to-verify-tumor-target-expression-antibody-binding-and-optimization-of-dosage-and-application-schedule
#18
Michael Dobosz, Ute Haupt, Werner Scheuer
Preclinical efficacy studies of antibodies targeting a tumor-associated antigen are only justified when the expression of the relevant antigen has been demonstrated. Conventionally, antigen expression level is examined by immunohistochemistry of formalin-fixed paraffin-embedded tumor tissue section. This method represents the diagnostic "gold standard" for tumor target evaluation, but is affected by a number of factors, such as epitope masking and insufficient antigen retrieval. As a consequence, variances and discrepancies in histological staining results can occur, which may influence decision-making and therapeutic outcome...
September 23, 2016: MAbs
https://www.readbyqxmd.com/read/27659519/profiles-of-mirnas-matched-to-biology-in-aromatase-inhibitor-resistant-breast-cancer
#19
Reiner Hoppe, Ping Fan, Florian Büttner, Stefan Winter, Amit K Tyagi, Heather Cunliffe, V Craig Jordan, Hiltrud Brauch
Aromatase inhibitor (AI) resistance during breast cancer treatment is mimicked by MCF-7:5C (5C) and MCF-7:2A (2A) cell lines that grow spontaneously. Survival signaling is reconfigured but cells are vulnerable to estradiol (E2)-inducible apoptosis. These model systems have alterations of stress related pathways including the accumulation of endoplasmic reticulum, oxidative, and inflammatory stress that occur prior to E2-induced apoptosis. We investigated miRNA expression profiles of 5C and 2A to characterize their AI resistance phenotypes...
September 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27648145/anti-proliferative-role-and-prognostic-implication-of-mir-141-in-gastric-cancer
#20
Mingwei Huang, Liucheng Wu, Yuzhou Qin, Zhao Li, Shanshan Luo, Haiquan Qin, Yang Yang, Jiansi Chen
Gastric cancer is a prevalent disease causing a high annual death rate worldwide. Recent studies suggest the pivotal regulatory role of microRNAs in gastric cancer and the aberrant expression of microRNA-141 (miR-141) in gastric cancer cells. This study aims to explore the role and possible mechanism of miR-141 in gastric cancer prognosis and cell proliferation. A total of 30 gastric cancer patients were recruited for miR-141 level detection and a follow up of 115 weeks. Human adenocarcinoma cell line AGS was transfected with miR-141 mimic or inhibitor for cell viability, colony formation and cell cycle assays...
2016: American Journal of Translational Research
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