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https://www.readbyqxmd.com/read/28544786/mir-122-modification-enhances-the-therapeutic-efficacy-of-adipose-tissue-derived-mesenchymal-stem-cells-against-liver-fibrosis
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28528691/the-igf-axis-in-hpv-associated-cancers
#6
REVIEW
Adam Pickard, Julia Durzynska, Dennis J McCance, Elisabeth R Barton
Human papillomaviruses (HPV) infect and replicate in stratified epithelium at cutaneous and mucosal surfaces. The proliferation and maintenance of keratinocytes, the cells which make up this epithelium, are controlled by a number of growth factor receptors such as the keratinocyte growth factor receptor (KGFR, also called fibroblast growth factor receptor 2b (FGFR2b)), the epithelial growth factor receptor (EGFR) and the insulin-like growth factor receptors 1 and 2 (IGF1R and IGF2R). In this review, we will delineate the mutation, gene transcription, translation and processing of the IGF axis within HPV associated cancers...
April 2017: Mutation Research
https://www.readbyqxmd.com/read/28521298/insulin-like-growth-factor-2-axis-supports-the-serum-independent-growth-of-malignant-rhabdoid-tumor-and-is-activated-by-microenvironment-stress
#7
Ting Li, Jin Wang, Pengfei Liu, Jiadong Chi, Han Yan, Lei Lei, Zexing Li, Bing Yang, Xi Wang
Malignant rhabdoid tumors (MRTs) are rare, lethal, pediatric tumors predominantly found in the kidney, brain and soft tissues. MRTs are driven by loss of tumor suppressor SNF5/INI1/SMARCB1/BAF47. The prognosis of MRT is poor using currently available treatments, so new treatment targets need to be identified to expand treatment options for patients experiencing chemotherapy resistance. The growth hormone insulin-like growth factor 2 (IGF2) signaling pathway is a promising target to overcome drug resistance in many cancers...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515443/development-of-a-whole-organism-platform-for-phenotype-based-analysis-of-igf1r-pi3k-akt-tor-action
#8
Chengdong Liu, Wei Dai, Yan Bai, Changfeng Chi, Yi Xin, Gen He, Kangsen Mai, Cunming Duan
Aberrant regulation of the insulin-like growth factor (IGF)/insulin (IIS)-PI3K-AKT-TOR signaling pathway is linked to major human diseases, and key components of this pathway are targets for therapeutic intervention. Current assays are molecular target- or cell culture-based platforms. Due to the great in vivo complexities inherited in this pathway, there is an unmet need for whole organism based assays. Here we report the development of a zebrafish transgenic line, Tg(igfbp5a:GFP), which faithfully reports the mitotic action of IGF1R-PI3K-Akt-Tor signaling in epithelial cells in real-time...
May 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28515235/insulin-like-growth-factor-signaling-regulates-developmental-trajectory-associated-with-diapause-in-embryos-of-the-annual-killifish-austrofundulus-limnaeus
#9
S Cody Woll, Jason E Podrabsky
Annual killifishes exhibit a number of unique life history characters including the occurrence of embryonic diapause, unique cell movements associated with dispersion and subsequent reaggregation of the embryonic blastomeres, and a short post-embryonic life span. Insulin-like growth factor (IGF) signaling is known to play a role in the regulation of metabolic dormancy in a number of animals but has not been explored in annual killifishes. The abundance of IGF proteins during development, and the developmental effects of blocking IGF signaling by pharmacological inhibition of the insulin-like growth factor I receptor (IGF1R) were explored in embryos of the annual killifish Austrofundulus limnaeus Blocking of IGF signaling in embryos that would normally escape entrance into diapause resulted in a phenotype that was remarkably similar to embryos entering diapause...
May 17, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28507201/sensitivity-of-non-small-cell-lung-cancer-to-erlotinib-is-regulated-by-the-notch-mir-223-fbxw7-pathway
#10
Haiwei Zhang, Fanglin Chen, Yongpeng He, Lin Yi, Chuang Ge, Xiaolong Shi, Chao Tang, Donglin Wang, Yongzhong Wu, Weiqi Nian
Recent evidence supports a role for microRNA-223 (miR-223) in modulating tumor cell sensitivity to chemotherapeutic drugs; however, its role in cellular resistance to the effects of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) used in treatment of non-small cell lung cancer (NSCLC) remains to be elucidated. The levels of miR-223 in parental cell line (HCC827) and erlotinib resistant HCC827 cell line (HCC827/ER)  were detected by qRT-PCR. HCC827/ER cells were treated with MK-2206 to block the Akt signaling pathway or RO4929097 to block the Notch signaling pathway, and then transfected with a miR-223 inhibitor or interference expression plasmid of F-Box/WD repeat-containing protein 7 (FBXW7) or insulin-like growth factor 1 receptor (IGF1R)...
May 15, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28500773/the-energy-sensing-lkb1-ampk%C3%AE-1-pathway-regulates-igf1-secretion-and-consequent-activation-of-the-igf1r-pkb-pathway-in-primary-hepatocytes
#11
Liang Chen, Qiaoli Chen, Ping Rong, Hong Yu Wang, Shuai Chen
The insulin-like growth factor 1 (IGF1) pathway has been linked with various diseases including diabetes, cancer and aging. In contrast to the well-established regulatory mechanisms controlling IGF1 expression, molecular mechanisms regulating of its secretion is not fully understood. The AMP-activated protein kinase (AMPK) is a key energy sensor, and accumulative evidence shows that AMPK is an attractive therapeutic target for treatment of diabetes, cancer and aging. Here we found that deficiency of AMPK promoted IGF1 secretion in mouse primary hepatocytes...
May 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28498399/dual-inhibition-of-igf1r-and-er-enhances-response-to-trastuzumab-in-her2-positive-breast-cancer-cells
#12
Martina S J McDermott, Alexandra Canonici, Laura Ivers, Brigid C Browne, Stephen F Madden, Neil A O'Brien, John Crown, Norma O'Donovan
Although HER2 targeted therapies have improved prognosis for HER2 positive breast cancer, HER2 positive cancers which co-express ER have poorer response rates to standard HER2 targeted therapies, combined with chemotherapy, than HER2 positive/ER negative breast cancer. Administration of hormone therapy concurrently with chemotherapy and HER2 targeted therapy is generally not recommended. Using publically available gene expression datasets we found that high expression of IGF1R is associated with shorter disease-free survival in patients whose tumors are ER positive and HER2 positive...
April 26, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28495324/biology-of-the-somatotroph-axis-after-the-pituitary
#13
Ron G Rosenfeld, Vivian Hwa
Normal growth requires that pituitary-secreted growth hormone (GH) bind to its specific receptor and activate a complex signaling cascade, leaving to production of insulin-like growth factor-I (IGF-I), which, in turn, activates its own receptor (IGF1R). The GH receptor (GHR) is preformed as a dimer and is transported in a nonligand bound state to the cell surface. Binding of GH to the GHR dimer, results in a conformational change of the dimer, activation of the intracellular Janus Kinase 2 (JAK2) and phosphorylation of signal transducer and activator of transcription (STAT) 5B...
May 8, 2017: Annales D'endocrinologie
https://www.readbyqxmd.com/read/28479199/radiosynthesis-and-evaluation-of-igf1r-pet-ligand-11-c-gsk1838705a
#14
Kiran Kumar Solingapuram Sai, Jaya Prabhakaran, Anirudh Sattiraju, J John Mann, Akiva Mintz, J S Dileep Kumar
Radiosynthesis and evaluation of [(11)C]GSK1838705A in mice using microPET and determination of specificity in human GBM UG87MR cells are described herein. The radioligand was synthesized by reacting desmethyl-GSK1838705A with [(11)C]CH3I using GE FX2MeI module in ∼5% yield (EOS), >95% radiochemical purity and a specific activity of 2.5±0.5Ci/μmol. MicroPET imaging in mice indicated that [(11)C]GSK1838705A penetrated blood brain barrier (BBB) and showed retention of radiotracer in brain. The radioligand exhibited high uptake in U87MG cells with >70% specific binding to IGF1R...
April 27, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28473774/lncrna-six1-encodes-a-micropeptide-to-activate-six1-in-cis-and-is-involved-in-cell-proliferation-and-muscle-growth
#15
Bolin Cai, Zhenhui Li, Manting Ma, Zhijun Wang, Peigong Han, Bahareldin A Abdalla, Qinghua Nie, Xiquan Zhang
Long non-coding RNAs (lncRNAs) play important roles in epigenetic regulation of skeletal muscle development. In our previous RNA-seq study (accession number GSE58755), we found that lncRNA-Six1 is an lncRNA that is differentially expressed between White Recessive Rock (WRR) and Xinghua (XH) chicken. In this study, we have further demonstrated that lncRNA-Six1 is located 432 bp upstream of the gene encoding the protein Six homeobox 1 (Six1). A dual-luciferase reporter assay identified that lncRNA-Six1 overlaps the Six1 proximal promoter...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28472298/adiponectin-stimulates-lipid-metabolism-via-ampk-in-rabbit-blastocysts
#16
Maria Schindler, Mareike Pendzialek, Katarzyna Joanna Grybel, Tom Seeling, Jacqueline Gürke, Bernd Fischer, Anne Navarrete Santos
STUDY QUESTION: How does a maternal diabetic hyperadiponectineamia affect signal transduction and lipid metabolism in rabbit preimplantation blastocysts? SUMMARY ANSWER: In a diabetic pregnancy increased levels of adiponectin led to a switch in embryonic metabolism towards a fatty acid-dependent energy metabolism, mainly affecting genes that are responsible for fatty acid uptake and turnover. WHAT IS KNOWN ALREADY: Although studies in cell culture experiments have shown that adiponectin is able to regulate lipid metabolism via 5'-AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα), data on the effects of adiponectin on embryonic lipid metabolism are not available...
May 4, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28468775/targeting-insulin-receptor-in-breast-cancer-using-small-engineered-protein-scaffolds
#17
Jie Ying Chan, Benjamin J Hackel, Douglas Yee
Insulin receptor (InsR) and the type I insulin-like growth factor (IGF1R) are homologous receptors necessary for signal transduction by their cognate ligands insulin, insulin-like growth factor-I and -II (IGF-I and IGF-II). IGF1R monoclonal antibodies, intended to inhibit malignant phenotypic signaling, failed to show benefit in patients with endocrine-resistant tumors in phase III clinical trials. Our previous work showed that in tamoxifen-resistant cells IGF1R expression was lacking but InsR inhibition effectively blocked growth...
May 3, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28460125/how-protein-kinase-a-activates-canonical-tyrosine-kinase-signaling-pathways-to-promote-granulosa-cell-differentiation
#18
Nathan C Law, Elyse M Donaubauer, Anthony J Zeleznik, Mary Hunzicker-Dunn
Protein kinase A (PKA) has recently been shown to mimic the actions of follicle-stimulating hormone (FSH) by activating signaling pathways that promote granulosa cell (GC) differentiation, such as phosphatidylinositol 3-kinase (PI3K) and mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). We sought to elucidate the mechanism by which PKA, a Ser/Thr kinase, intersected the PI3K/AKT and MAPK/ERK pathways that are canonically activated by receptor tyrosine kinases (RTKs). Our results show that for both of these pathways, the RTK is active in the absence of FSH yet signaling down the pathways to commence transcriptional responses requires FSH-stimulated PKA activation...
April 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/28455310/exercise-induced-modification-of-the-skeletal-muscle-transcriptome-in-arabian-horses
#19
Katarzyna Ropka-Molik, Monika Stefaniuk-Szmukier, Kacper Żukowski, Katarzyna Piórkowska, Monika Bugno-Poniewierska
It has been found that Arabian and Thoroughbred horses differ in muscle fiber structure and thus in physiological changes occurring in muscles during exercise. The aim of the present study was to identify the global gene expression modifications that occur in skeletal muscle following a training regime to prepare for flat racing. Whole transcriptomes of muscle (gluteus medius) were compared between three time points of tissue collection: T0 (untrained horses), T1 (horses after intense gallop phase) and T2 (horses at the end of racing season), 23 samples in total...
April 28, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28454409/expression-of-imp3-as-a-marker-for-predicting-poor-outcome-in-gastroenteropancreatic-neuroendocrine-neoplasms
#20
Li-Mian Er, Yong Li, Ming-Li Wu, Qun Zhao, Bi-Bo Tan, Xiao-Ling Wang, Shi-Jie Wang
The aim of the present study was to investigate the expression and clinical significance of oncofetal protein insulin-like growth factor (IGF) II mRNA-binding protein 3 (IMP3) in the differentiation of gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). A total of 162 patients who were diagnosed with GEP-NEN, and who underwent surgical or endoscopic resection from January 2006 to March 2013, were enrolled in the study, including 85 cases of grade (G)1 neuroendocrine tumors, 40 cases of G2 neuroendocrine tumors, 28 cases of G3 neuroendocrine carcinomas and 9 cases of mixed stage adenoneuroendocrine carcinomas...
April 2017: Oncology Letters
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