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https://www.readbyqxmd.com/read/29160922/igf1r-signalling-in-testicular-germ-cell-tumour-cells-impacts-on-cell-survival-and-acquired-cisplatin-resistance
#1
Joanna Selfe, Neil C Goddard, Alan McIntyre, Kathryn R Taylor, Jane Renshaw, Sergey D Popov, Khin Thway, Brenda Summersgill, Robert A Huddart, Duncan C Gilbert, Janet M Shipley
Testicular germ cell tumours (TGCT) are the most frequent malignancy and cause of death from solid tumours in the 20-40 year age group. Although most cases show sensitivity to cis-platinum-based chemotherapy, this is associated with long-term toxicities and chemo-resistance. Roles for receptor tyrosine kinases other than KIT are largely unknown in TGCT. We therefore conducted a phosphoproteomic screen and identified the insulin growth factor receptor-1 (IGF1R) as both highly expressed and activated in TGCT cell lines representing the non-seminomatous subtype...
November 21, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29160127/the-fetal-programming-effect-of-prenatal-smoking-on-igf1r-and-igf1-methylation-is-organ-and-sex-specific
#2
Karolin F Meyer, Rikst Nynke Verkaik-Schakel, Wim Timens, Lester Kobzik, Torsten Plösch, Machteld N Hylkema
The impact of prenatal smoke exposure (PSE) on DNA methylation has been demonstrated in blood samples from children of smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. As the identified differentially methylated genes can be associated with developmental processes, and insulin-like growth factors (IGFs) play a critical role in prenatal tissue growth, we hypothesized that PSE induces fetal programming of Igf1r and Igf1. Using a mouse model of smoking during pregnancy, we show that PSE alters promoter methylation of Igf1r and Igf1 and deregulates their gene expression in lung and liver of fetal (E17...
November 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29156819/mir-29a-3p-suppresses-cell-proliferation-and-migration-by-downregulating-igf1r-in-hepatocellular-carcinoma
#3
Xiao Wang, Shasha Liu, Ling Cao, Tengfei Zhang, Dongli Yue, Liping Wang, Yu Ping, Qianyi He, Chaoqi Zhang, Meng Wang, Xinfeng Chen, Qun Gao, Dan Wang, Zhen Zhang, Fei Wang, Li Yang, Jieyao Li, Lan Huang, Bin Zhang, Yi Zhang
Hepatocellular carcinoma (HCC), the most common primary tumor of the liver, has a poor prognosis and rapid progression. MicroRNAs (miRNAs) play important roles in carcinogenesis and tumor progression. Insulin-like growth factor 1 receptor (IGF1R) is a transmembrane heterotetrameric protein that has been reported to promote transformation to malignancy and cancer cell proliferation and survival. In this study, we found that the expression of miR-29a-3p was downregulated in HCC patients, resulting in poor survival rates...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29147569/growth-hormone-insensitivity-mexican-case-report
#4
I Castilla-Cortazar, J R De Ita, G A Aguirre, M García-Magariño, I Martín-Estal, V J Lara-Diaz, M I Elizondo
Herein, we present a 14-year-old patient with short stature (134 cm) referred from Paediatrics to our department for complementary evaluation since growth hormone (GH) treatment failed to show any improvement. He was born premature and small for gestational age. Genital examination classified the patient as Tanner I-II with small penis and testicular size for his age. Biochemical analyses revealed normal GH levels with low serum insulin-like growth factor-1 (IGF-1). Molecular diagnosis confirmed several mutations in IGF1R and IGFALS, and so he was diagnosed with Laron Syndrome or GH insensibility and treated with IGF-1 substitutive therapy...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/29142763/array-characterization-of-prenatally-diagnosed-15q26-microdeletion-and-2q37-1-duplication-report-of-a-new-case-with-multicystic-kidneys-and-review-of-the-literature
#5
Molka Kammoun, Wafa Slimani, Hanene Hannachi, Mohamed Bibi, Ali Saad, Soumaya Mougou-Zerelli
We report on a molecular cytogenetic characterization of 15q26 deletion and 2q37.1 duplication in a fetus presenting with intrauterine growth restriction (IUGR), diaphragmatic hernia, multicystic kidneys, left kidney pyelectasis, and clubfeet. A terminal 15q26 deletion and a terminal 2q duplication of at least 10 and 9 Mb, respectively, derived from a maternal translocation, were found. The 15q26 deletion represents a contiguous gene deletion syndrome mainly characterized by IUGR, congenital diaphragmatic hernia, and less frequently kidney defects...
December 2017: Journal of Pediatric Genetics
https://www.readbyqxmd.com/read/29139225/oolong-tea-prevents-cardiomyocyte-loss-against-hypoxia-by-attenuating-p-jnk-mediated-hypertrophy-and-enhancing-p-igf1r-p-akt-and-p-bad-ser136-activity-and-by-fortifying-nrf2-antioxidation-system
#6
Marthandam Asokan Shibu, Chia-Hua Kuo, Bih-Cheng Chen, Da-Tong Ju, Ray-Jade Chen, Chao-Hung Lai, Pei-Jane Huang, Vijaya Padma Viswanadha, Wei-Wen Kuo, Chih-Yang Huang
Tea, the most widely consumed natural beverage has been associated with reduced mortality risk from cardiovascular disease. Oolong tea is a partially fermented tea containing high levels of catechins, their degree of oxidation varies between 20%-80% causing differences in their active metabolites. In this study we examined the effect of oolong tea extract (OTE) obtained by oxidation at low-temperature for short-time against hypoxic injury and found that oolong tea provides cyto-protective effects by suppressing the JNK mediated hypertrophic effects and by enhancing the innate antioxidant mechanisms in neonatal cardiomyocytes and in H9c2 cells...
November 15, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29137348/reverse-phase-protein-array-rppa-combined-with-computational-analysis-to-unravel-relevant-prognostic-factors-in-non-small-cell-lung-cancer-nsclc-a-pilot-study
#7
Vienna Ludovini, Rita Chiari, Lorenzo Tomassoni, Chiara Antonini, Elisa Baldelli, Sara Baglivo, Annamaria Siggillino, Francesca Romana Tofanetti, Guido Bellezza, K Alex Hodge, Emanuel Petricoin, Mariaelena Pierobon, Lucio Crinò, Fortunato Bianconi
In this work high throughput technology and computational analysis were used to study two stage IV lung adenocarcinoma patients treated with standard chemotherapy with markedly different survival (128 months vs 6 months, respectively) and whose tumor samples exhibit a dissimilar protein activation pattern of the signal transduction. Tumor samples of the two patients were subjected to Reverse Phase Protein Microarray (RPPA) analysis to explore the expression/activation levels of 51 signaling proteins. We selected the most divergent proteins based on the ratio of their RPPA values in the two patients with short (s-OS) and long (l-OS) overall survival (OS) and tested them against a EGFR-IGF1R mathematical model...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29133622/ceritinib-enhances-the-efficacy-of-trametinib-in-braf-nras-wild-type-melanoma-cell-lines
#8
Daniel Verduzco, Brent M Kuenzi, Fumi Kinose, Vernon K Sondak, Zeynep Eroglu, Uwe Rix, Keiran S M Smalley
Targeted therapy options are currently lacking for the heterogeneous population of patients whose melanomas lack BRAF or NRAS mutations (~35% of cases). We undertook a chemical biology screen to identify potential novel drug targets for this understudied group of tumors. Screening a panel of 8 BRAF/NRAS-WT melanoma cell lines against 240 targeted drugs identified ceritinib and trametinib as potential hits with single agent activity. Ceritinib enhanced the efficacy of trametinib across the majority of the BRAF/NRAS-WT cell lines, and the combination showed increased cytotoxicity in both 3D spheroid culture and long-term colony formation experiments...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29130665/-effects-and-its-mechanism-of-igf-1r-on-the-synthesis-of-hyaluronic-acid-in-orbital-fibroblasts-of-thyroid-associated-ophthalmopathy
#9
Xiao-Ling Chen, Wei-Min He, Wei Li
OBJECTIVE: To explore the effects of insulin-like growth factor1 (IGF1) receptor (IGF1R) on the synthesis of hyaluronic acid (HA) in orbital fibroblasts of thyroid associated ophthalmopathy (TAO) and its signal pathway. METHODS: Orbital fibroblasts were harvested from TAO ( n=19) and normal control ( n=5),then were primary cultured and treated with recombinant human IGF1 in different concentrations. Before the treatment of IGF1,the cells were pretreated respectively with 1H7,LY294002 or AKT inhibitor Ⅳ for 24 h...
September 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29119846/carbonate-apatite-nanoparticles-carry-sirna-s-targeting-growth-factor-receptor-genes-egfr1-and-erbb2-to-regress-mouse-breast-tumor
#10
Snigdha Tiash, Nur Izyani Binti Kamaruzman, Ezharul Hoque Chowdhury
Cancer cells lose their control on cell cycle by numerous genetic and epigenetic alterations. In a tumor, these cells highly express growth factor receptors (GFRs), eliciting growth, and cell division. Among the GFRs, epidermal growth factor receptor-1 (EGFR1) (Her1/ERBB1) and epidermal growth factor receptor-2 (EGFR2) (Her2/ERBB2) from epidermal growth factor (EGF) family and insulin-like growth factor-1 receptor (IGF1R) are highly expressed on breast cancer cells, thus contributing to the aggressive growth and invasiveness, have been focused in this study...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29112114/role-of-scaffold-protein-proline-glutamic-acid-and-leucine-rich-protein-1-pelp1-in-the-modulation-of-adrenocortical-cancer-cell-growth
#11
Arianna De Luca, Paola Avena, Rosa Sirianni, Adele Chimento, Francesco Fallo, Catia Pilon, Ivan Casaburi, Vincenzo Pezzi
PELP1 acts as an estrogen receptor (ER) coactivator that exerts an essential role in the ER's functions. ER coregulators have a critical role in the progression and response to hormonal treatment of estrogen-dependent tumors. We previously demonstrated that, in adrenocortical carcinoma (ACC), ERα is upregulated and that estradiol activates the IGF-II/IGF1R signaling pathways defining the role of this functional cross-talk in H295R ACC cell proliferation. The aim of this study was to determine if PELP1 is expressed in ACC and may play a role in promoting the interaction between ERα and IGF1R allowing the activation of pathways important for ACC cell growth...
November 7, 2017: Cells
https://www.readbyqxmd.com/read/29100507/inhibition-of-pi3k-akt-mtor-overcomes-cisplatin-resistance-in-the-triple-negative-breast-cancer-cell-line-hcc38
#12
Katharina Gohr, Alexandra Hamacher, Laura H Engelke, Matthias U Kassack
BACKGROUND: Widely established targeted therapies directed at triple negative breast cancer (TNBC) are missing. Classical chemotherapy remains the systemic treatment option. Cisplatin has been tested in TNBC but bears the disadvantage of resistance development. The purpose of this study was to identify resistance mechanisms in cisplatin-resistant TNBC cell lines and select targeted therapies based on these findings. METHODS: The TNBC cell lines HCC38 and MDA-MB231 were subjected to intermittent cisplatin treatment resulting in the 3...
November 3, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29099871/the-role-of-h19-a-long-non-coding-rna-in-mouse-liver-postnatal-maturation
#13
Chad Pope, Stephanie C Piekos, Liming Chen, Shashank Mishra, Xiao-Bo Zhong
H19 RNA is highly expressed at early postnatal ages and precipitously decreases at a specific time corresponding with increases in expression of genes important for mature liver function, such as drug metabolizing enzymes. H19's role in the regulation of liver maturation is currently unknown. Using an H19 knockout mouse model to determine the role of H19 in liver development, we quantified gene expression for insulin growth factor signaling, Wnt signaling, key cytochrome P450 (P450) enzymes known to change as the liver develops, and fetal and adult plasma protein produced in liver...
2017: PloS One
https://www.readbyqxmd.com/read/29099264/co-targeting-pi3k-mtor-and-igf1r-with-small-molecule-inhibitors-for-treating-undifferentiated-pleomorphic-sarcoma
#14
Caitlin D May, Sharon M Landers, Svetlana Bolshakov, XiaoYan Ma, Davis R Ingram, Christine M Kivlin, Kelsey L Watson, Ghadah A Al Sannaa, Angela D Bhalla, Wei-Lien Wang, Alexander J Lazar, Keila E Torres
Undifferentiated pleomorphic sarcomas (UPSs) are aggressive mesenchymal malignancies with no definitive cell of origin or specific recurrent genetic hallmarks. These tumors are largely chemoresistant; thus, identification of potential therapeutic targets is necessary to improve patient outcome. Previous studies demonstrated that high expression of activated protein kinase B (AKT) in patients with UPS corresponds to poor disease-specific survival. Here, we demonstrate that inhibiting phosphatidylinositol-3-kinase/mammalian target of rapamycin (PI3K/mTOR) signaling using a small molecule inhibitor reduced UPS cell proliferation and motility and xenograft growth; however, increased phosphorylation of insulin-like growth factor 1 receptor (IGF1R) indicated the potential for adaptive resistance following treatment through compensatory receptor activation...
October 3, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29099049/receptors-for-insulin-like-growth-factor-2-and-androgens-as-therapeutic-targets-in-triple-negative-breast-cancer
#15
Nalo Hamilton, David Austin, Diana Márquez-Garbán, Rudy Sanchez, Brittney Chau, Kay Foos, Yanyuan Wu, Jaydutt Vadgama, Richard Pietras
Triple-negative breast cancer (TNBC) occurs in 10-15% of all breast cancer patients, yet it accounts for about half of all breast cancer deaths. There is an urgent need to identify new antitumor targets to provide additional treatment options for patients afflicted with this aggressive disease. Preclinical evidence suggests a critical role for insulin-like growth factor-2 (IGF2) and androgen receptor (AR) in regulating TNBC progression. To advance this work, a panel of TNBC cell lines was investigated with all cell lines showing significant expression of IGF2...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29090019/molecular-characterization-and-evaluation-of-complex-rearrangements-in-a-case-of-ring-chromosome-15
#16
Stuti Tewari, Naznin Lubna, Raju Shah, Ahmed B H Al-Rikabi, Krati Shah, Jayesh Sheth, Frenny Sheth
BACKGROUND: Ring chromosome 15 is a rare genetic entity. Only a few cases have been reported with characterization using molecular techniques. The clinical presentation is quite variable, as a result of differences in the breakpoints, haploinsufficiency of genes involved in deleted segment/s, level of mosaicism and ring instability resulting in a variability of rearrangement of genetic material. CASE PRESENTATION: The proband, a 2 months old boy, presented with small head size and facial dysmorphism...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29069833/differential-expression-of-microrna-let-7b-5p-regulates-burn-induced-hyperglycemia
#17
Yajie Zhang, Bin Yin, Bin Shu, Zhen Liu, Hong Ding, Chiyu Jia
One of the classical features observed in patients with burn injury is hyperglycemia. There have been previous reports that a cohort of microRNAs (miRNAs) is differentially expressed in the dermis of patients with burn injury. More specifically, it has been shown that the miR-194 can target the insulin-like growth factor receptor 1 (IGF1R) and silence its protein expression resulting in hyperglycemia. The objective of the current study was to discover if additional miRNA-mediated post-transcriptional mechanism exists that lead to suppression of IGF1R protein expression post-burn injury...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29069776/the-crucial-role-of-srpk1-in-igf-1-induced-emt-of-human-gastric-cancer
#18
Hong Wang, Chunlei Wang, Wenling Tian, Yanfen Yao
In recent years, the insulin-like growth factor (IGF-1) and serine-arginine protein kinase 1 (SRPK1) have been reported to be implicated in the pithelial-mesenchymal transition (EMT) in many kinds of malignancies. However, the potential roles of IGF-1-SRPK1 signaling in the EMT of gastric cancer (GC) have not been investigated. In the present study, the in-vitro assays were used to investigate the molecular role of SRPK1 in cell cycle, motility and invasiveness. We demonstrated that the expressions of SRPK1 or insulin-like growth factor receptor 1 (IGF1R) were significantly increased in GC tissues and cells than those in normal tissues and GES-1 cells, and closely associated with metastasis, stage and prognosis...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29067644/targeting-anaplastic-lymphoma-kinase-alk-in-rhabdomyosarcoma-rms-with-the-second-generation-alk-inhibitor-ceritinib
#19
Anke E M van Erp, Melissa H S Hillebrandt-Roeffen, Laurens van Houdt, Emmy D G Fleuren, Winette T A van der Graaf, Yvonne M H Versleijen-Jonkers
BACKGROUND: The receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (ALK) has been implicated in the tumorigenesis of rhabdomyosarcoma (RMS). However, the exact role of ALK in RMS is debatable and remains to be elucidated. OBJECTIVE: To determine the in vitro and in vivo effects and mechanism of action of the second-generation ALK inhibitor ceritinib on RMS cell growth. METHODS: Effects of ceritinib on cell proliferation, wound healing, cell cycle, and RTK signaling were determined in alveolar and embryonal rhabdomyosarcoma (ARMS, ERMS)...
October 24, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/29054976/regulation-of-insulin-like-growth-factor-receptors-by-ubiquilin1
#20
Zimple Kurlawala, Rain Dunaway, Parag P Shah, Julie A Gosney, Leah J Siskind, Brian P Ceresa, Levi J Beverly
Insulin-like growth factor-1 receptor (IGF1R) is a receptor tyrosine kinase that mediates growth, proliferation and survival. Dysregulation of IGF pathway contributes to initiation, progression and metastasis of cancer and is also involved in diseases of glucose metabolism, such as Diabetes. We have identified Ubiquilin1 (UBQLN1) as a novel interaction partner of IGF1R, IGF2R and Insulin Receptor. UBQLN family of proteins have been studied primarily in the context of protein quality control and in the field of neurodegenerative disorders...
October 20, 2017: Biochemical Journal
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