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IGF-1R

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https://www.readbyqxmd.com/read/27903254/mir-96-mir-145-and-mir-9-expression-increases-and-igf-1r-and-foxo1-expression-decreases-in-peripheral-blood-mononuclear-cells-of-aging-humans
#1
Monika Budzinska, Magdalena Owczarz, Eliza Pawlik-Pachucka, Malgorzata Roszkowska-Gancarz, Przemyslaw Slusarczyk, Monika Puzianowska-Kuznicka
BACKGROUND: In mammals, the IGF-1 pathway affects the phenotype of aging. Since the function of the immune system is modulated by IGF-1, it is plausible that immunosenescence might in part result from altered control by this pathway. We therefore examined whether the expression of IGF-1R, FOXO1, and FOXO3a in peripheral blood mononuclear cells (PBMC) changes with age and if this might be due to changes in the expression of select miRNAs. METHODS: The expression of IGF-1R, FOXO1, FOXO3a, as well as of miR-9, miR-96, miR-99a, miR-132, miR-145, and miR-182 was examined in PBMC of young (27...
November 30, 2016: BMC Geriatrics
https://www.readbyqxmd.com/read/27895663/mir-30a-5p-overexpression-may-overcome-egfr-inhibitor-resistance-through-regulating-pi3k-akt-signaling-pathway-in-non-small-cell-lung-cancer-cell-lines
#2
Fei Meng, Fengfeng Wang, Lili Wang, S C Cesar Wong, William C S Cho, Lawrence W C Chan
Lung cancer is one of the most common deadly diseases worldwide, most of which is non-small cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) mutant NSCLCs frequently respond to the EGFR tyrosine kinase inhibitors (EGFR-TKIs) treatment, such as Gefitinib and Erlotinib, but the development of acquired resistance limits the utility. Multiple resistance mechanisms have been explored, e.g., the activation of alternative tyrosine kinase receptors (TKRs) sharing similar downstream pathways to EGFR...
2016: Frontiers in Genetics
https://www.readbyqxmd.com/read/27893850/a-convenient-in-vivo-model-using-small-interfering-rna-silencing-to-rapidly-assess-skeletal-gene-function
#3
Wen Zhang, Can Liu, Bao Hai, Guohong Du, Hong Wang, Huijie Leng, Yingsheng Xu, Chunli Song
It is difficult to study bone in vitro because it contains various cell types that engage in cross-talk. Bone biologically links various organs, and it has thus become increasingly evident that skeletal physiology must be studied in an integrative manner in an intact animal. We developed a model using local intraosseous small interfering RNA (siRNA) injection to rapidly assess the effects of a target gene on the local skeletal environment. In this model, 160-g male Sprague-Dawley rats were treated for 1-2 weeks...
2016: PloS One
https://www.readbyqxmd.com/read/27893412/molecular-mechanism-and-therapeutic-implications-of-selinexor-kpt-330-in-liposarcoma
#4
Manoj Garg, Deepika Kanojia, Anand Mayakonda, Jonathan W Said, Ngan B Doan, Wenwen Chien, Trivadi S Ganesan, Linda Shyue Huey Chuang, Nachiyappan Venkatachalam, Erkan Baloglu, Sharon Shacham, Michael Kauffman, H Phillip Koeffler
Exportin-1 mediates nuclear export of multiple tumor suppressor and growth regulatory proteins. Aberrant expression of exportin-1 is noted in human malignancies, resulting in cytoplasmic mislocalization of its target proteins. We investigated the efficacy of selinexor against liposarcoma cells both in vitro and in vivo. Exportin-1 was highly expressed in liposarcoma samples and cell lines as determined by immunohistochemistry, western blot, and immunofluorescence assay. Knockdown of endogenous exportin-1 inhibited proliferation of liposarcoma cells...
November 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27886437/the-microrna-99-family-modulates-hepatitis-b-virus-replication-by-promoting-igf-1r-pi3k-akt-mtor-ulk1-signaling-induced-autophagy
#5
Yong Lin, Wanyu Deng, Jinke Pang, Thekla Kemper, Jing Hu, Jian Yin, Jiming Zhang, Mengji Lu
MicroRNAs (miRNAs) are small highly conserved noncoding RNAs that are widely expressed in multicellular organisms and participate in the regulation of various cellular processes including autophagy and viral replication. Evidently, miRNAs are able to modulate host gene expression and thereby inhibit or enhance hepatitis B virus (HBV) replication. The miR-99 family members are highly expressed in the liver. Interestingly, the plasma levels of miR-99 family in the peripheral blood correspond with HBV DNA loads...
November 25, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27886192/phytanic-acid-attenuates-insulin-like-growth-factor-1-activity-via-nitric-oxide-mediated-%C3%AE-secretase-activation-in-rat-aortic-smooth-muscle-cells-possible-implications-for-pathogenesis-of-infantile-refsum-disease
#6
Gursev S Dhaunsi, Mayra Alsaeid, Saghir Akhtar
BACKGROUND: Infantile Refsum disease (IRD), a peroxisomal disease with defective phytanic acid oxidation, causes neurological impairment and development delay. Insulin-like growth factor-1 (IGF-1) regulates child development and to understand molecular mechanism(s) of IRD, we examined the effect of PA on IGF-1 activity. METHODS: BrdU incorporation was measured in rat aortic smooth muscle cell (SMC) cultures following treatment with fetal bovine serum (FBS), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) or IGF-1 in the absence or presence of PA...
November 25, 2016: Pediatric Research
https://www.readbyqxmd.com/read/27884723/ir-and-igf-1r-expression-affects-insulin-induced-proliferation-and-dna-damage
#7
Eman Maher Othman, Tahanee Altabaa, Henning Hintzsche, Helga Stopper
Diabetes mellitus type 2 is in its prediagnostic and early phase characterized by hyperinsulinemia. Previously, we pointed out hyperinsulinemia as a potential link between diabetes mellitus and the increased cancer risk that is associated with this disease through its induction of oxidative stress and DNA damage. In the present study, we address the relationship between the induction of proliferation and genomic damage in vitro in cell lines with different expression of the insulin and the IGF-1 receptors after treating the cells with insulin and the insulin analog glargine...
November 21, 2016: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/27882820/phase-ii-randomized-study-of-the-igf-1r-pathway-modulator-axl1717-compared-to-docetaxel-in-patients-with-previously-treated-locally-advanced-or-metastatic-non-small-cell-lung-cancer
#8
Michael Bergqvist, Georg Holgersson, Igor Bondarenko, Elena Grechanaya, Alexey Maximovich, György Andor, Maria Klockare, Marcus Thureson, Markus Jerling, Johan Harmenberg
BACKGROUND: The primary objective of this study was to compare the progression-free survival (PFS) at 12 weeks between patients treated with IGF-1R pathway modulator AXL1717 (AXL) and patients treated with docetaxel (DCT). MATERIAL AND METHODS: The study was conducted at 19 study centers in five countries. A total of 99 patients with previously treated, locally advanced or metastatic non-small cell lung cancer (NSCLC) of the squamous cell carcinoma (SCC) or adenocarcinoma (AC) subtypes in need of additional treatment were randomized and treated with either 300 or 400 mg of AXL as daily BID treatment (58 patients) or DCT given as 75 mg/m(2) in three-week cycles (41 patients) as monotherapy in a 3:2 ratio for each NSCLC subtype...
November 24, 2016: Acta Oncologica
https://www.readbyqxmd.com/read/27881235/elucidating-the-role-of-the-foxo3a-transcription-factor-in-the-igf-1-induced-migration-and-invasion-of-uveal-melanoma-cancer-cells
#9
Fengxia Yan, Rifang Liao, Mohd Farhan, Tinghuai Wang, Jiashu Chen, Zhong Wang, Peter J Little, Wenhua Zheng
Uveal melanoma (UM) is the most common primary intraocular malignant tumor of adults. It has high mortality rate due to liver metastasis. However, the epidemiology and pathogenesis of liver metastasis in UM are not elucidated and there is no effective therapy available for preventing the development of this disease. IGF-1 is a growth factor involved in cell proliferation, malignant transformation and inhibition of apoptosis. In previous report, IGF-1 receptor was found to be highly expressed in UM and this was related to tumor prognosis...
November 20, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27877053/synergistic-activity-of-vorinostat-combined-with-gefitinib-but-not-with-sorafenib-in-mutant-kras-human-non-small-cell-lung-cancers-and-hepatocarcinoma
#10
Victor Jeannot, Benoit Busser, Laetitia Vanwonterghem, Sophie Michallet, Sana Ferroudj, Murat Cokol, Jean-Luc Coll, Mehmet Ozturk, Amandine Hurbin
Development of drug resistance limits the efficacy of targeted therapies. Alternative approaches using different combinations of therapeutic agents to inhibit several pathways could be a more effective strategy for treating cancer. The effects of the approved epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (gefitinib) or a multi-targeted kinase inhibitor (sorafenib) in combination with a histone deacetylase inhibitor (vorinostat) on cell proliferation, cell cycle distribution, apoptosis, and signaling pathway activation in human lung adenocarcinoma and hepatocarcinoma cells with wild-type EGFR and mutant KRAS were investigated...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27875952/in-vitro-sensitivity-profiling-of-neuroblastoma-cells-against-a-comprehensive-small-molecule-kinase-inhibitor-library-to-identify-agents-for-future-therapeutic-studies
#11
Anjali Singh, Vanessa Meier-Stephenson, Aarthi Jayanthan, Aru Narendran
Solid tumors represent one of the most widespread causes of death in children across the world. Neuroblastoma (NB) constitutes about 8% of all childhood tumors, yet accounts for more than 15% of death, with an unacceptable overall survival rate. Despite the current multimodal therapeutic approaches involving surgery, radiation, chemotherapy with myeloablative therapy and hematopoietic stem cell rescue, there is growing realization of the limitations of conventional agents to improve the outcome in high risk metastatic disease...
November 22, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27874961/letter-to-the-editor-mir-494-inhibits-invasion-and-proliferation-of-gastric-cancer-by-targeting-igf-1r
#12
C Cavaliere, C D'Aniello, I Cerillo, G Facchini
No abstract text is available yet for this article.
November 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27857021/effects-and-mechanisms-of-metformin-on-the-proliferation-of-esophageal-cancer-cells-in-vitro-and-in-vivo
#13
Jian-Cai Tang, Rui An, Yi-Qing Jiang, Jian Yang
Purpose: To observe the effects of metformin on human esophageal cancer cell, and to investigate its possible mechanisms. Materials and Methods: Cell viability was detected by using a cell counting kit-8(CCK-8), while cell cycle and apoptosis were assessed by flow cytometry and western blot was used to measure the expression of the related proteins. RNAi was used to knockout pyruvate kinase muscle isozyme 2 (PKM2). An Eca109 tumor model was established to evaluate the antitumor effect in vivo...
November 11, 2016: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/27849005/insulin-igf-signaling-affects-cell-transformation-in-the-balb-c-3t3-cell-model
#14
Doerte Poburski, Christiane Leovsky, Josefine Barbara Boerner, Luisa Szimmtenings, Michael Ristow, Michael Glei, René Thierbach
The increased cancer mortality of diabetes type 2 patients is most likely an evidence of the tight connection between tumor development and energy metabolism. A major focus of today's research is still the identification of key proteins of both diseases and the development of corresponding inhibitors. In this study we combined the two-stage BALB/c-3T3 cell transformation assay (BALB-CTA) with the IR/IGF-1R inhibitor OSI-906 (linsitinib) and analyzed alterations in protein activity and energy parameters in non-transformed as well as transformed cells...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27843613/mechanisms-of-resistance-to-egfr-targeted-drugs-lung-cancer
#15
REVIEW
Floriana Morgillo, Carminia Maria Della Corte, Morena Fasano, Fortunato Ciardiello
Despite the improvement in clinical outcomes derived by the introduction of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) in the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumours harbour EGFR-activating mutations, prognosis remains unfavourable because of the occurrence of either intrinsic or acquired resistance. We reviewed the published literature and abstracts of oral and poster presentations from international conferences addressing EGFR-TKIs resistance mechanisms discovered in preclinical models and in patients with NSCLC...
2016: ESMO Open
https://www.readbyqxmd.com/read/27835791/the-role-of-pdgfr-%C3%AE-activation-in-acquired-resistance-to-igf-1r-blockade-in-preclinical-models-of-rhabdomyosarcoma
#16
Christine M Heske, Choh Yeung, Arnulfo Mendoza, Joshua T Baumgart, Leah D Edessa, Xiaolin Wan, Lee J Helman
To determine what alternative pathways may act as mechanisms of bypass resistance to type 1 insulin-like growth factor receptor (IGF-1R) blockade in rhabdomyosarcoma (RMS), we compared expression of receptor tyrosine kinase activity in a number of IGF-1R antibody-resistant and -sensitive RMS cell lines. We found that platelet-derived growth factor receptor β (PDGFR-β) activity was upregulated in three xenograft-derived IGF-1R antibody-resistant cell lines that arose from a highly sensitive fusion-positive RMS cell line (Rh41)...
November 8, 2016: Translational Oncology
https://www.readbyqxmd.com/read/27835596/cd99-triggering-induces-methuosis-of-ewing-sarcoma-cells-through-igf-1r-ras-rac1-signaling
#17
Maria Cristina Manara, Mario Terracciano, Caterina Mancarella, Marika Sciandra, Clara Guerzoni, Michela Pasello, Andrea Grilli, Nicoletta Zini, Piero Picci, Mario P Colombo, Andrea Morrione, Katia Scotlandi
CD99 is a cell surface molecule that has emerged as a novel target for Ewing sarcoma (EWS), an aggressive pediatric bone cancer. This report provides the first evidence of methuosis in EWS, a non-apoptotic form of cell death induced by an antibody directed against the CD99 molecule. Upon mAb triggering, CD99 induces an IGF-1R/RAS/Rac1 complex, which is internalized into RAB5-positive endocytic vacuoles. This complex is then dissociated, with the IGF-1R recycling to the cell membrane while CD99 and RAS/Rac1 are sorted into immature LAMP-1-positive vacuoles, whose excessive accumulation provokes methuosis...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27833148/igf-1-igf-1r-hsa-let-7c-axis-regulates-the-committed-differentiation-of-stem-cells-from-apical-papilla
#18
Shu Ma, Genxia Liu, Lin Jin, Xiyao Pang, Yanqiu Wang, Zilu Wang, Yan Yu, Jinhua Yu
Insulin-like growth factor-1 (IGF-1) and its receptor IGF-1R play a paramount role in tooth/bone formation while hsa-let-7c actively participates in the osteogenic differentiation of mesenchymal stem cells. However, the interaction between IGF-1/IGF-1R and hsa-let-7c on the committed differentiation of stem cells from apical papilla (SCAPs) remains unclear. In this study, human SCAPs were isolated and treated with IGF-1 and hsa-let-7c over/low-expression viruses. The odonto/osteogenic differentiation of these stem cells and the involvement of mitogen-activated protein kinase (MAPK) pathway were subsequently investigated...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27831000/targeted-therapies-for-the-treatment-of-non-small-cell-lung-cancer-monoclonal-antibodies-and-biological-inhibitors
#19
Ana P S Silva, Priscila V Coelho, Maristella Anazetti, Patricia U Simioni
The usual treatments for patients with non-small-cell lung cancer (NSCLC), such as advanced lung adenocarcinoma, are unspecific and aggressive, and include lung resection, radiotherapy and chemotherapy. Recently, treatment with monoclonal antibodies and biological inhibitors has emerged as an effective alternative, generating effective results with few side effects. In recent years, several clinical trials using monoclonal antibodies presented potential benefits to NSCLC, and four of them are already approved for the treatment of NSCLC, such as cetuximab, bevacizumab, nivolumab and pembrolizumab...
November 10, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27821486/heterogeneous-stromal-signaling-within-the-tumor-microenvironment-controls-the-metastasis-of-pancreatic-cancer
#20
Agnieszka A Rucki, Kelly Foley, Pingbo Zhang, Qian Xiao, Jennifer Kleponis, Annie Wu, Rajni Sharma, Guanglan Mo, Angen Liu, Jennifer Van Eyk, Elizabeth M Jaffee, Lei Zheng
Understanding how stromal signals regulate the development of pancreatic ductal adenocarcinoma (PDAC) may suggest novel therapeutic interventions in this disease. In this study, we assessed the metastatic role of stromal signals suggested to be important in the PDAC microenvironment. Src and IGF-1R phosphorylated the pro-metastatic molecule Annexin A2 (AnxA2) at Y23 and Y333 in response to stromal signals HGF and IGF-1, respectively, and IGF-1 expression was regulated by the Sonic Hedgehog (Shh) pathway. Both Shh and HGF were heterogeneously expressed in PDAC stroma, and only dual inhibition of these pathways could significantly suppress AnxA2 phosphorylation, PDAC growth and metastasis...
November 7, 2016: Cancer Research
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