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https://www.readbyqxmd.com/read/28649085/a-novel-heterozygous-igf-1-receptor-mutation-associated-with-hypoglycemia
#1
Ravid Solomon-Zemler, Lina Basel-Vanagaite, David Steier, Shoashana Yakar, Eran Mel, Moshe Phillip, Lily Bazak, Danni Bercovich, Haim Werner, Liat de Vries
Mutation in the insulin-like growth factor-1 receptor (IGF1R) gene is a rare cause for intrauterine and postnatal growth disorders. Patients identified with IGF1R mutations present with either normal or impaired glucose tolerance. None of the cases described so far showed hypoglycemia. We aimed to identify the genetic basis for small for gestational age, short stature and hypoglycemia over three generations in one family. The proband, a 9-year-old male presented in infancy with recurrent hypoglycemic episodes, symmetric intrauterine growth retardation and postnatal growth retardation...
June 25, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28646158/metabolic-recovery-of-lipodystrophy-liver-steatosis-and-pancreatic-%C3%AE-cell-proliferation-after-the-withdrawal-of-osi-906
#2
Kazuki Tajima, Jun Shirakawa, Yu Togashi, Shunsuke Yamazaki, Tomoko Okuyama, Mayu Kyohara, Hiromi Konishi, Yasuo Terauchi
Growth factor signaling via insulin receptor (IR) and IGF-1 receptor (IGF1R) plays several important roles in the pathogenesis of metabolic syndrome and diabetes. OSI-906 (linsitinib), an anti-tumor drug, is an orally bioavailable dual inhibitor of IR and IGF1R. To investigate the recovery from metabolic changes induced by the acute inhibition of IR and IGF1R in adult mice, mice were treated with OSI-906 or a vehicle for 7 days and the results were analyzed on the last day of injection (Day 7) or after 7 or 21 days of withdrawal (Day 14 or Day 28)...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28643781/recurrent-mutation-of-igf-signalling-genes-and-distinct-patterns-of-genomic-rearrangement-in-osteosarcoma
#3
Sam Behjati, Patrick S Tarpey, Kerstin Haase, Hongtao Ye, Matthew D Young, Ludmil B Alexandrov, Sarah J Farndon, Grace Collord, David C Wedge, Inigo Martincorena, Susanna L Cooke, Helen Davies, William Mifsud, Mathias Lidgren, Sancha Martin, Calli Latimer, Mark Maddison, Adam P Butler, Jon W Teague, Nischalan Pillay, Adam Shlien, Ultan McDermott, P Andrew Futreal, Daniel Baumhoer, Olga Zaikova, Bodil Bjerkehagen, Ola Myklebost, M Fernanda Amary, Roberto Tirabosco, Peter Van Loo, Michael R Stratton, Adrienne M Flanagan, Peter J Campbell
Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours...
June 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28624790/co-targeting-of-igf1r-mtor-pathway-by-mir-497-and-mir-99a-impairs-hepatocellular-carcinoma-development
#4
Henghui Cheng, Jin Xue, Shouhua Yang, Yaobin Chen, Yu Wang, Yuanli Zhu, Xiaoyan Wang, Dong Kuang, Qiurong Ruan, Yaqi Duan, Guoping Wang
Persistent activation of IGF1R/mTOR signaling pathway plays crucial role in the development of hepatocellular carcinoma (HCC). Therefore, our goal was to elucidate microRNAs (miRNAs) targeting IGF1R/mTOR and the therapeutic potential of single or dual miRNA on HCC development. In this study, we found that miR-497 and miR-99a that target the 3'-UTR of both IGF1R and mTOR were down-regulated in HCC human tissues and cell lines. Functional assay revealed that ectopic expression of miR-497 or miR-99a in HCC cells resulted in a significant inhibition on tumor growth and invasiveness in vitro and tumor development in vivo via repressing the expression of IGF1R and mTOR...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28613101/targeting-igf1r-pathway-in-cancer-with-micrornas-how-close-are-we
#5
Arathy S Kumar, Suresh K Rayala, Ganesh Venkatraman
Cancer of the head and neck are the most common cancers in India and account for 30% of all cancers. At molecular level, it could be attributed to the over-expression of growth factors like IGF1-R, EGFR, VEGF-R and deregulation of cell cycle regulators and tumor suppressors. IGF1-R is an emerging target in head and neck cancer treatment, because of its reported role in tumor development, progression and metastasis. IGF1R targeted agents are in advanced stages of clinical development. Nevertheless, these agents suffer from several disadvantages including acquired resistance and toxic side effects...
June 14, 2017: RNA Biology
https://www.readbyqxmd.com/read/28604966/-detection-of-a-patient-with-ring-chromosome-15-by-low-coverage-massively-parallel-copy-number-variation-sequencing
#6
Qiong Pan, Li Zhang, Fengting Zhang, Xin Jin, Yue Hu, Liyan Zhu, Longfei Cheng, Qigang Zhang, Ying Ning
OBJECTIVE: To explore the genetic cause for a child with developmental delay. METHODS: The karotypes of the child and her parents were analyzed with G-banding analysis. Their genome DNA was analyzed with low-coverage massively parallel copy number variation sequencing (CNV-seq) and verified by single nucleotide polymorphism array (SNP-array). RESULTS: The karyotype of the child was ascertained as 46,XX,r(15)(p13q26.3), while both parents showed a normal karyotype...
June 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/28599664/angiotensin-ii-type-2-receptor-promotes-apoptosis-and-inhibits-angiogenesis-in-bladder-cancer
#7
Nana Pei, Yingying Mao, Pengfei Wan, Xinglu Chen, Andrew Li, Huiying Chen, Jinlong Li, Renqiang Wan, Yanling Zhang, Hongyan Du, Baihong Chen, Guangyu Jiang, Minghan Xia, Colin Sumners, Guixue Hu, Dongsheng Gu, Hongwei Li
BACKGROUND: Bladder cancer (BCa) is the ninth most common form of cancer in the world. There is a continuing need not only for improving the accuracy of diagnostic markers but also for the development of new treatment strategies. Recent studies have shown that the renin-angiotensin system (RAS), which include the angiotensin type 1 (AT1R), type 2(AT2R), and Mas receptors, play an important role in tumorigenesis and may guide us in meeting those needs. RESULTS: In this study, we first observed that AT1R and Mas expression levels were significantly upregulated in BCa specimens while AT2R was significantly downregulated...
June 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28595357/the-alzheimer-s-disease-transcriptome-mimics-the-neuroprotective-signature-of-igf-1-receptor-deficient-neurons
#8
Caroline George, Géraldine Gontier, Philippe Lacube, Jean-Christophe François, Martin Holzenberger, Saba Aïd
Seminal studies using post-mortem brains of patients with Alzheimer's disease evidenced aberrant insulin-like growth factor 1 receptor (IGF1R) signalling. Addressing causality, work in animal models recently demonstrated that long-term suppression of IGF1R signalling alleviates Alzheimer's disease progression and promotes neuroprotection. However, the underlying mechanisms remain largely elusive. Here, we showed that genetically ablating IGF1R in neurons of the ageing brain efficiently protects from neuroinflammation, anxiety and memory impairments induced by intracerebroventricular injection of amyloid-β oligomers...
June 8, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28592245/in-silico-identification-of-potential-key-regulatory-factors-in-smoking-induced-lung-cancer
#9
Salem A El-Aarag, Amal Mahmoud, Medhat H Hashem, Hatem Abd Elkader, Alaa E Hemeida, Mahmoud ElHefnawi
BACKGROUND: Lung cancer is a leading cause of cancer-related death worldwide and is the most commonly diagnosed cancer. Like other cancers, it is a complex and highly heterogeneous disease involving multiple signaling pathways. Identifying potential therapeutic targets is critical for the development of effective treatment strategies. METHODS: We used a systems biology approach to identify potential key regulatory factors in smoking-induced lung cancer. We first identified genes that were differentially expressed between smokers with normal lungs and those with cancerous lungs, then integrated these differentially expressed genes (DEGs) with data from a protein-protein interaction database to build a network model with functional modules for pathway analysis...
June 7, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28590931/multiple-receptor-tyrosine-kinase-activation-related-to-alk-inhibitor-resistance-in-lung-cancer-cells-with-alk-rearrangement
#10
Se Hoon Choi, Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Woo Sung Kim, Chang-Min Choi, Jin Kyung Rho, Jae Cheol Lee
The activation of alternative receptor tyrosine kinases (RTKs) is known to mediate resistance to ALK inhibitors. However, the role of multiple RTK activation in resistance has yet to be determined. Two crizotinib-resistant (H3122/CR-1 and H3122/CR-2) and one TAE684-resistant (H2228/TR) cell lines were established. Multi-RTK arrays and Western blots were performed to detect the activation of bypass signals. There were no secondary mutations in the sequencing. EGFR and MET were activated in H3122/CR-1 cells whereas EGFR and IGF1R were activated in H3122/CR-2 cells...
May 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28586424/role-of-er%C3%AE-in-mediating-female-uterine-transcriptional-responses-to-igf1
#11
Sylvia C Hewitt, Wipawee Winuthayanon, Sydney L Lierz, Katherine J Hamilton, Lauren J Donoghue, J Tyler Ramsey, Sara A Grimm, Yukitomo Arao, Kenneth S Korach
Estrogen (E2) signaling through its nuclear receptor, estrogen receptor α (ERα) increases insulin-like growth factor 1 (IGF1) in the rodent uterus, which then initiates further signals via the IGF1 receptor (IGF1R). Directly administering IGF1 results in similar biological and transcriptional uterine responses. Our studies using global ERα-null mice demonstrated a loss of uterine biological responses of the uterus to E2 or IGF1 treatment, while maintaining transcriptional responses to IGF1. To address this discrepancy in the need for uterine ERα in mediating the IGF1 transcriptional vs...
June 6, 2017: Endocrinology
https://www.readbyqxmd.com/read/28585695/the-rhogap-myo9b-promotes-bone-growth-by-mediating-osteoblastic-responsiveness-to-igf-1
#12
Brooke K McMichael, Yong-Hoon Jeong, Justin A Auerbach, Cheol-Min Han, Ryan Sedlar, Vikram Shettigar, Martin Bähler, Sudha Agarwal, Do-Gyoon Kim, Beth S Lee
The RhoA subfamily of Rho GTPases regulates actin-based cellular functions in bone such as differentiation, migration, and mechanotransduction. Polymorphisms or genetic ablation of RHOA and some of its regulatory guanine exchange factors (GEFs) have been linked to poor bone health in humans and mice, but the effects of RhoA-specific GTPase-activating proteins (GAPs) on bone quality have not yet been identified. Therefore, we examined the consequences of RhoGAP Myo9b gene knockout on bone growth, phenotype and cellular activity...
June 6, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28574407/muscular-response-to-the-first-three-months-of-deflazacort-treatment-in-boys-with-duchenne-muscular-dystrophy
#13
L Jensen, S J Petersson, N O Illum, H C Laugaard-Jacobsen, T Thelle, L H Jørgensen, H D Schrøder
OBJECTIVE: Duchenne muscular dystrophy (DMD) patients are often treated with glucocorticoids; yet their precise molecular action remains unknown. METHODS: We investigated muscle biopsies from nine boys with DMD (aged: 7,6±2,8 yrs.) collected before and after three months of deflazacort treatment and compared them to eight healthy boys (aged: 5,3±2,4 yrs.). mRNA transcripts involved in activation of satellite cells, myogenesis, regeneration, adipogenesis, muscle growth and tissue inflammation were assessed...
June 1, 2017: Journal of Musculoskeletal & Neuronal Interactions
https://www.readbyqxmd.com/read/28572530/assessment-of-gsk1904529a-as-a-promising-anti-osteosarcoma-agent
#14
Hao-Dong Fei, Qi Yuan, Li Mao, Feng-Li Chen, Zhao-Hui Cui, Sha Tao, Feng Ji
The insulin growth factor-I receptor (IGF1R) signaling is a key mechanism for osteosarcoma (OS) cell proliferation. GSK1904529A is a novel small molecule IGF1R kinase inhibitor. Its activity against OS cells was tested. In both established OS cell lines (Saos-2 and MG-63) and primary human OS cells, treatment with GSK1904529A (at nM concentrations) significantly inhibited cell proliferation. At the molecular level, GSK1904529A almost completely blocked IGF1R activation in OS cells, and inhibited downstream AKT-ERK activation...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28571043/microrna-7-suppresses-the-homing-and-migration-potential-of-human-endothelial-cells-to-highly-metastatic-human-breast-cancer-cells
#15
Yu-Xin Cui, Robyn Bradbury, Valentina Flamini, Bo Wu, Nicola Jordan, Wen G Jiang
BACKGROUND: MicroRNA-7 (miR-7) has been observed as a potent tumour suppressor in multiple cancer types including breast cancer. The aim of this study was to investigate the response sensitivities of metastatic breast cancer cells to miR-7 and the roles of miR-7 in the interaction of endothelial cells and metastatic cancer cells. METHODS: Expression profile of miRNAs in a breast cancer specimen cohort and breast cancer cells were determined using real-time quantitative miRNA assays...
June 27, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28544786/mir-122-modification-enhances-the-therapeutic-efficacy-of-adipose-tissue-derived-mesenchymal-stem-cells-against-liver-fibrosis
#16
Guohua Lou, Ying Yang, Feifei Liu, Bingjue Ye, Zhi Chen, Min Zheng, Yanning Liu
Mesenchymal stem cell (MSC) transplantation alone may be insufficient for treatment of liver fibrosis because of complicated histopathological changes in the liver. Given that miR-122 plays an essential role in liver fibrosis by negatively regulating the proliferation and transactivation of hepatic stellate cells (HSCs), this study investigated whether miR-122 modification can improve the therapeutic efficacy of adipose tissue-derived MSCs in treating liver fibrosis. MiR-122-modified AMSCs (AMSC-122) were constructed through lentivirus-mediated transfer of pre-miR-122...
May 24, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28534942/gene-expression-analysis-of-growth-factor-receptors-in-human-chondrocytes-in-monolayer-and-3d-pellet-cultures
#17
Anika Witt, Achim Salamon, Diana Boy, Doris Hansmann, Andreas Büttner, Andreas Wree, Rainer Bader, Anika Jonitz-Heincke
The main goal of cartilage repair is to create functional tissue by enhancing the in vitro conditions to more physiological in vivo conditions. Chondrogenic growth factors play an important role in influencing cartilage homeostasis. Insulin‑like growth factor (IGF)‑1 and transforming growth factor (TGF)‑β1 affect the expression of collagen type II (Col2) and glycosaminoglycans (GAGs) and, therefore, the targeted use of growth factors could make chondrogenic redifferentiation more efficient. In the present study, human chondrocytes were postmortally isolated from healthy articular cartilage and cultivated as monolayer or 3D pellet cultures either under normoxia or hypoxia and stimulated with IGF‑1 and/or TGF‑β1 to compare the impact of the different growth factors...
May 18, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28534511/stromal-derived-igf2-promotes-colon-cancer-progression-via-paracrine-and-autocrine-mechanisms
#18
C Unger, N Kramer, D Unterleuthner, M Scherzer, A Burian, A Rudisch, M Stadler, M Schlederer, D Lenhardt, A Riedl, S Walter, A Wernitznig, L Kenner, M Hengstschläger, J Schüler, W Sommergruber, H Dolznig
The insulin-like growth factor (IGF)2/IGF1 receptor (IGF1R) signaling axis has an important role in intestinal carcinogenesis and overexpression of IGF2 is an accepted risk factor for colorectal cancer (CRC) development. Genetic amplifications and loss of imprinting contribute to the upregulation of IGF2, but insufficiently explain the extent of IGF2 expression in a subset of patients. Here, we show that IGF2 was specifically induced in the tumor stroma of CRC and identified cancer-associated fibroblasts (CAFs) as the major source...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28533226/igf1r-protein-expression-is-not-associated-with-differential-benefit-to-concurrent-trastuzumab-in-early-stage-her2-breast-cancer-from-the-north-central-cancer-treatment-group-alliance-adjuvant-trastuzumab-trial-n9831
#19
Monica M Reinholz, Beiyun Chen, Amylou C Dueck, Kathleen Tenner, Karla Ballman, Darren Riehle, Robert B Jenkins, Xochiquetzal J Geiger, Ann E McCullough, Edith A Perez
Background: Preclinical evidence indicates that increased insulin-like growth factor receptor-1 (IGF1R) signaling interferes with the action of trastuzumab suggesting a possible mechanism of trastuzumab resistance. Thus, we evaluated IGF1R prevalence, relationship with demographic data, and association with disease-free survival (DFS) of patients randomized to chemotherapy alone (Arm A) or chemotherapy with sequential (Arm B) or concurrent trastuzumab (Arm C) in the prospective phase III HER2(+) adjuvant N9831 trial...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28529015/targeted-next-generation-sequencing-approach-in-patients-referred-for-silver-russell-syndrome-testing-increases-the-mutation-detection-rate-and-provides-decisive-information-for-clinical-management
#20
Robert Meyer, Lukas Soellner, Matthias Begemann, Severin Dicks, György Fekete, Nils Rahner, Klaus Zerres, Miriam Elbracht, Thomas Eggermann
OBJECTIVE: To investigate the contribution of differential diagnoses to the mutation spectrum of patients referred for Silver-Russell syndrome (SRS) testing. STUDY DESIGN: Forty-seven patients referred for molecular testing for SRS were examined after exclusion of one of the SRS-associated alterations. After clinical classification, a targeted next generation sequencing approach comprising 25 genes associated with other diagnoses or postulated as SRS candidate genes was performed...
May 19, 2017: Journal of Pediatrics
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