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IGF1R cancer

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
Lucy Ireland, Almudena Santos, Muhammad S Ahmed, Carolyn Rainer, Sebastian R Nielsen, Valeria Quaranta, Ulrike Weyer-Czernilofsky, Danielle D Engle, Pedro Perez-Mancera, Sarah E Coupland, Azzam F 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 1 and 2 (IGF), which activate Insulin/IGF receptors on pancreatic cancer cells...
October 14, 2016: Cancer Research
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
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
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
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
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
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
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
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
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
Patricia Jaaks, Valentina D'Alessandro, Nicole Grob, Sina Büel, Katarina Hajdin, Beat W Schäfer, Michele Bernasconi
The proprotein convertase (PC) furin cleaves precursor proteins, an important step in the activation of many cancer-associated proteins. Substrates of furin and furin-like PCs play a role in proliferation, metastasis and invasion. Some of them are involved in the progression of the pediatric soft tissue sarcoma rhabdomyosarcoma (RMS). In this study, we show that PCs, and in particular furin, are expressed in RMS cell lines. To investigate the functional role of furin, we generated RMS cell lines with modulated furin activity...
2016: PloS One
K Tominaga, T Shimamura, N Kimura, T Murayama, D Matsubara, H Kanauchi, A Niida, S Shimizu, K Nishioka, E-I Tsuji, M Yano, S Sugano, Y Shimono, H Ishii, H Saya, M Mori, K Akashi, K-I Tada, T Ogawa, A Tojo, S Miyano, N Gotoh
The transcription factor nuclear factor-κB (NF-κB) has important roles for tumorigenesis, but how it regulates cancer stem cells (CSCs) remains largely unclear. We identified insulin-like growth factor 2 (IGF2) is a key target of NF-κB activated by HER2/HER3 signaling to form tumor spheres in breast cancer cells. The IGF2 receptor, IGF1 R, was expressed at high levels in CSC-enriched populations in primary breast cancer cells. Moreover, IGF2-PI3K (IGF2-phosphatidyl inositol 3 kinase) signaling induced expression of a stemness transcription factor, inhibitor of DNA-binding 1 (ID1), and IGF2 itself...
August 22, 2016: Oncogene
Samuel Gusscott, Catherine E Jenkins, Sonya H Lam, Vincenzo Giambra, Michael Pollak, Andrew P Weng
Insulin-like growth factor 1 receptor (IGF1R) is a prevalent signaling pathway in human cancer that supports cell growth/survival and thus contributes to aggressive biological behavior. Much work has gone into development of IGF1R inhibitors; however, candidate agents including small molecule tyrosine kinase inhibitors and blocking antibodies have yet to fulfill their promise clinically. Understanding cellular features that define sensitivity versus resistance are important for effective patient selection and anticipation of outgrowth of a resistant clone...
2016: PloS One
Bai Li, Liang Ge, Minghe Li, Lei Wang, Zhihong Li
Accumulating evidence has demonstrated that miR-448 expression was downregulated, and exerted tumor suppressor roles in several types of cancer. However, the biological function and underlying mechanism of miR-448 in colorectal cancer (CRC) have not been elucidated. In this study, we detected the miR-448 expression in CRC tumor tissues and adjacent normal tissues (ANT) and five colorectal cancer cell lines by real time quantitative RT-PCR (qRT-PCR). Cell proliferation, colony formation, migration and invasion were investigated in CRC cells transfected miR-448 mimic or negative control mimic by MTT, colony forming, wound healing and transwell invasion assays, respectively...
2016: American Journal of Translational Research
Michaela C Huber, Rebecca Mall, Herbert Braselmann, Annette Feuchtinger, Sara Molatore, Katrin Lindner, Axel Walch, Eva Gross, Manfred Schmitt, Natalie Falkenberg, Michaela Aubele
BACKGROUND: Due to lack of a targeted therapy for the triple-negative breast cancer (TNBC) patients, it is important to explore this aggressive breast cancer type in more detail and to establish novel therapeutic approaches. TNBC is defined negative for the protein expression of oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). One prominent feature of this cancer type is the frequent overexpression of major components of the urokinase-type plasminogen activator system (uPAS) including uPA, its receptor uPAR and the inhibitor PAI-1, which may be valuable as therapeutic targets...
2016: BMC Cancer
Tarik Ghadban, André Jessen, Matthias Reeh, Judith L Dibbern, Sven Mahner, Volkmar Mueller, Ulrich F Wellner, Cenap Güngör, Jakob R Izbicki, Yogesh K Vashist
Heat shock protein (HSP)90 has emerged as an important target in cancer therapeutics. Diverse HSP90 inhibitors are under evaluation. The aim of the present study was to investigate the growth inhibitory effects of the newly developed water-soluble HSP90 inhibitors, 17-[2-(Pyrrolidin-1-yl)ethyl]amino-17-demethoxygeldanamycin (17-AEPGA) and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), compared to that of the non-water-soluble HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG)...
October 2016: International Journal of Molecular Medicine
Qian Liu, Xu Gao, Shengshun Que, Xi Yang, Hongxia Fan, Min Liu, Xin Li, Hua Tang
Long non-coding RNAs (lncRNAs) can regulate gene expression at different levels and are widely participate in various physiological and pathological processes. Emerging evidences suggests that a number of differentially expressed lncRNAs are involved in tumorigenesis. However, the function and expression regulation of a vast majority of these unique RNAs is little known. Here, we found that the lncRNA Ras suppressor protein 1 pseudogene 2 (RSU1P2) is upregulateded in cervical cancer tissues and has a tumour-promoting role...
July 26, 2016: Oncotarget
Toshiki Hirakawa, Masakazu Yashiro, Yosuke Doi, Haruhito Kinoshita, Tamami Morisaki, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Kenjiro Kimura, Ryosuke Amano, Kosei Hirakawa
Pancreatic ductal adenocarcinoma (PDAC) is characterized by its hypovascularity, with an extremely poor prognosis because of its highly invasive nature. PDAC proliferates with abundant stromal cells, suggesting that its invasive activity might be controlled by intercellular interactions between cancer cells and fibroblasts. Using four PDAC cell lines and two pancreas cancer-associated fibroblasts (CAFs), the expression of insulin-like growth factor-1 (IGF1) and IGF1 receptor (IGF1R) was evaluated by RT-PCR, FACScan, western blot, or ELISA...
2016: PloS One
Hajar Shali, Majid Ahmadi, Hossein Samadi Kafil, Abbasali Dorosti, Mehdi Yousefi
The type 1 IGF receptor (IGF1R) and mesenchymal-epithelial transition (MET) are hetrodimeric and transmembrane receptor tyrosine kinases, which are frequently overexpressed by several tumor types, including colorectal cancer (CRC). These receptors bind to their specific ligands, insulin growth factors (IGFs) and hepatocyte growth factor (HGF), respectively, and promote signaling cascades which mediates many functions such as proliferation and protection against apoptosis, cell scattering, tumor cell motility, invasion and metastasis...
August 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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