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https://www.readbyqxmd.com/read/28454409/expression-of-imp3-as-a-marker-for-predicting-poor-outcome-in-gastroenteropancreatic-neuroendocrine-neoplasms
#1
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
https://www.readbyqxmd.com/read/28447036/recent-translational-research-into-targeted-therapy-for-liposarcoma
#2
REVIEW
Rashi Bharat Patel, Ting Li, Zhichao Liao, Jivani Aakash Jaldeepbhai, H A Pavanika N V Perera, Sujani Kaushalya Muthukuda, Dholiya Hardeep Dhirubhai, Vaibhav Singh, Xiaoling Du, Jilong Yang
Liposarcomas (LPS) are among the most common soft tissue sarcomas, originating from adipocytes. Treatment for LPS typically involves surgical resection and radiation therapy, while the use of conventional cytotoxic chemotherapy for unresectable or metastatic LPS remains controversial. This review summarizes the results of recent translational research and trials of novel therapies targeting various genetic and molecular aberrations in different subtypes of LPS. Genetic aberrations such as the 12q13-15 amplicon, genetic amplification of MDM2, CDK4, TOP2A, PTK7, and CHEK1, point mutations in CTNNB1, CDH1, FBXW7, and EPHA1, as the fusion of FUS-DDIT3/EWSR1-DDIT3 are involved in the pathogenesis LPS and represent potential therapeutic candidates...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28446242/activity-of-distinct-growth-factor-receptor-network-components-in-breast-tumors-uncovers-two-biologically-relevant-subtypes
#3
Mumtahena Rahman, Shelley M MacNeil, David F Jenkins, Gajendra Shrestha, Sydney R Wyatt, Jasmine A McQuerry, Stephen R Piccolo, Laura M Heiser, Joe W Gray, W Evan Johnson, Andrea H Bild
BACKGROUND: The growth factor receptor network (GFRN) plays a significant role in driving key oncogenic processes. However, assessment of global GFRN activity is challenging due to complex crosstalk among GFRN components, or pathways, and the inability to study complex signaling networks in patient tumors. Here, pathway-specific genomic signatures were used to interrogate GFRN activity in breast tumors and the consequent phenotypic impact of GRFN activity patterns. METHODS: Novel pathway signatures were generated in human primary mammary epithelial cells by overexpressing key genes from GFRN pathways (HER2, IGF1R, AKT1, EGFR, KRAS (G12V), RAF1, BAD)...
April 26, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28439875/epigenetic-repression-of-mir-375-is-the-dominant-mechanism-for-constitutive-activation-of-the-pdpk1-rps6ka3-signalling-axis-in-multiple-myeloma
#4
Shotaro Tatekawa, Yoshiaki Chinen, Masaki Ri, Tomoko Narita, Yuji Shimura, Yayoi Matsumura-Kimoto, Taku Tsukamoto, Tsutomu Kobayashi, Eri Kawata, Nobuhiko Uoshima, Tomohiko Taki, Masafumi Taniwaki, Hiroshi Handa, Shinsuke Iida, Junya Kuroda
Cytogenetic/molecular heterogeneity is the hallmark of multiple myeloma (MM). However, we recently showed that the serine/threonine kinase PDPK1 and its substrate RPS6KA3 (also termed RSK2) are universally active in MM, and play pivotal roles in myeloma pathophysiology. In this study, we assessed involvement of aberrant miR-375 repression in PDPK1 overexpression in MM. An analysis of plasma cells from 30 pre-malignant monoclonal gammopathies of undetermined significance and 73 MM patients showed a significant decrease in miR-375 expression in patient-derived plasma cells regardless of the clinical stage, compared to normal plasma cells...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28439815/the-effects-of-voluntary-physical-exercise-activated-neurotrophic-signaling-in-rat-hippocampus-on-mrna-levels-of-downstream-signaling-molecules
#5
Christina A E Solvsten, Tina F Daugaard, Yonglun Luo, Frank de Paoli, Jane H Christensen, Anders L Nielsen
Physical exercise results in the increased expression of neurotrophic factors and the subsequent induction of signal transduction cascades with a positive impact on neuronal functions. In this study, we used a voluntary physical exercise rat model to determine correlations in hippocampus mRNA expression of the neurotropic factors Bdnf, VegfA, and Igf1; their receptors TrkB, Igf1R, VegfR1, and VegfrR2; and downstream signal transducers Creb, Syn1, and Vgf. In hippocampi of physically exercised rats, the mRNA expression levels of Bdnf transcript 4 (Bdnf-t4), VegfA, and Igf1, as well as VegfR1, TrkB, Creb, Vgf, and Syn1, were increased...
April 24, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28439706/cks1bp7-a-pseudogene-of-cks1b-is-co-amplified-with-igf1r-in-breast-cancers
#6
Yansong Liu, Wei Wang, Yan Li, Feifei Sun, Jiaxiang Lin, Li Li
Pseudogenes have been reported to exhibit functional roles. Amplification or overexpression of CDC28 protein kinase regulatory subunit 1B (CKS1B) was found in various human cancers. But it was known little about CKS1B pseudogene 7 (CKS1BP7), a pseudogene sharing considerable sequence identity with CKS1B. The aim of this study was to evaluate copy number alterations (CNAs) of CKS1BP7 and address its potential roles in breast cancer. We detected copy numbers of CKS1BP7 and insulin-like growth factor 1 receptor (IGF1R) using quantitative multi-gene fluorescence in situ hybridization (QM-FISH) technique, compared their status in both invasive carcinoma and ductal carcinoma in situ (DCIS) components within the same tumors, and investigated the associations of CNAs with tumor features and patients outcomes...
April 24, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28423001/pre-hatching-embryo-dependent-and-independent-programming-of-endometrial-function-in-cattle
#7
Mariana Sponchiado, Nathália Souza Gomes, Patrícia Kubo Fontes, Thiago Martins, Maite Del Collado, Athos de Assumpção Pastore, Guilherme Pugliesi, Marcelo Fábio Gouveia Nogueira, Mario Binelli
The bovine pre-implantation embryo secretes bioactive molecules from early development stages, but effects on endometrial function are reported to start only after elongation. Here, we interrogated spatially defined regions of the endometrium transcriptome for responses to a day 7 embryo in vivo. We hypothesize that exposure to an embryo changes the abundance of specific transcripts in the cranial region of the pregnant uterine horn. Endometrium was collected from the uterotubal junction (UTJ), anterior (IA), medial (IM) and posterior (IP) regions of the uterine horn ipsilateral to the CL 7 days after estrus from sham-inseminated (Con) or artificially inseminated, confirmed pregnant (Preg) cows...
2017: PloS One
https://www.readbyqxmd.com/read/28418902/igf1r-depletion-facilitates-met-amplification-as-mechanism-of-acquired-resistance-to-erlotinib-in-hcc827-nsclc-cells
#8
Dianna Hussmann, Anne Tranberg Madsen, Kristine Raaby Jakobsen, Yonglun Luo, Boe Sandahl Sorensen, Anders Lade Nielsen
EGFR-mutated non-small cell lung cancer patients experience relapse within 1-2 years of treatment with EGFR-inhibitors, such as erlotinib. Multiple resistance mechanisms have been identified including secondary EGFR-mutations, MET-amplification, and epithelial-mesenchymal transition (EMT). Previous studies have indicated a role of Insulin-like growth factor 1 receptor (IGF1R) in acquired resistance to EGFR-directed drugs as well as in EMT. In the present study, we have investigated the involvement of IGF1R in acquired high-dose erlotinib resistance in the EGFR-mutated lung adenocarcinoma cell line HCC827...
March 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417283/bis-anthracycline-wp760-abrogates-melanoma-cell-growth-by-transcription-inhibition-p53-activation-and-igf1r-downregulation
#9
Magdalena Olbryt, Aleksandra Rusin, Izabela Fokt, Anna Habryka, Patrycja Tudrej, Sebastian Student, Aleksander Sochanik, Rafał Zieliński, Waldemar Priebe
Anthracycline chemotherapeutics, e.g. doxorubicin and daunorubicin, are active against a broad spectrum of cancers. Their cytotoxicity is mainly attributed to DNA intercalation, interference with topoisomerase activity, and induction of double-stranded DNA breaks. Since modification of anthracyclines can profoundly affect their pharmacological properties we attempted to elucidate the mechanism of action, and identify possible molecular targets, of bis-anthracycline WP760 which previously demonstrated anti-melanoma activity at low nanomolar concentrations...
April 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28414111/screening-for-the-best-detergent-for-the-isolation-of-placental-membrane-proteins
#10
Dragana Robajac, Martina Zámorová, Jaroslav Katrlík, Željko Miković, Olgica Nedić
Although membrane proteins (MPs) play crucial roles in physiological processes, information on them are insufficient, mostly due to their peculiar nature and surrounding which demand specific procedures for their extraction (using detergents) and analysis. A pallet of ten detergents and β-cyclodextrin was employed to investigate their efficiency in extracting total placental MPs, glycoproteins and insulin-like growth factor receptors (IR/IGF1R/IGF2R). Regardless of detergent used, the identity of major extracted proteins was the same...
April 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28407051/igf1r-expression-in-ovarian-granulosa-cells-is-essential-for-steroidogenesis-follicle-survival-and-fertility-in-female-mice
#11
Sarah C Baumgarten, Marah Armouti, CheMyong Ko, Carlos Stocco
Folliculogenesis is a lengthy process that requires the proliferation and differentiation of granulosa cells (GCs) for preovulatory follicle formation. The most crucial endocrine factor involved in this process is follicle-stimulating hormone (FSH). Interestingly, previous in vitro studies indicated that FSH fails to stimulate GC proliferation in the absence of the insulin-like growth factor 1 receptor (IGF1R). To determine the role of the IGF1R in vivo, female mice with a conditional knockdown of the IGF1R in the GCs were produced and had undetectable levels of IGF1R mRNA and protein in the GCs...
April 12, 2017: Endocrinology
https://www.readbyqxmd.com/read/28404936/systematic-identification-and-comparison-of-expressed-profiles-of-lncrnas-and-circrnas-with-associated-co-expression-and-cerna-networks-in-mouse-germline-stem-cells
#12
Xiaoyong Li, Junping Ao, Ji Wu
Accumulating evidence indicates that long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) involve in germ cell development. However, little is known about the functions and mechanisms of lncRNAs and circRNAs in self-renewal and differentiation of germline stem cells. Therefore, we explored the expression profiles of mRNAs, lncRNAs, and circRNAs in male and female mouse germline stem cells by high-throughput sequencing. We identified 18573 novel lncRNAs and 18822 circRNAs in the germline stem cells and further confirmed the existence of these lncRNAs and circRNAs by RT-PCR...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404630/mir-424-322-503-is-a-breast-cancer-tumor-suppressor-whose-loss-promotes-resistance-to-chemotherapy
#13
Ruth Rodriguez-Barrueco, Erin A Nekritz, François Bertucci, Jiyang Yu, Felix Sanchez-Garcia, Tizita Z Zeleke, Andrej Gorbatenko, Daniel Birnbaum, Elena Ezhkova, Carlos Cordon-Cardo, Pascal Finetti, David Llobet-Navas, Jose M Silva
The female mammary gland is a very dynamic organ that undergoes continuous tissue remodeling during adulthood. Although it is well established that the number of menstrual cycles and pregnancy (in this case transiently) increase the risk of breast cancer, the reasons are unclear. Growing clinical and experimental evidence indicates that improper involution plays a role in the development of this malignancy. Recently, we described the miR-424(322)/503 cluster as an important regulator of mammary epithelial involution after pregnancy...
March 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28403518/formation-of-the-igf1r-cav1-src-tri-complex-antagonizes-trail-induced-apoptosis-in-gastric-cancer-cells
#14
Tianshu Guo, Ling Xu, Xiaofang Che, Simeng Zhang, Ce Li, Jin Wang, Jing Gong, Rui Ma, Yibo Fan, Kezuo Hou, Huiming Zhou, Xuejun Hu, Yunpeng Liu, Xiujuan Qu
Lipid rafts provide a biological platform for apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We previously reported that insulin-like growth factor 1 receptor (IGF1R) translocation into lipid rafts helped to explain TRAIL resistance. However, it was not clear whether TRAIL resistance was caused by the interaction of IGF1R with caveolin-1 (CAV1) and the non-receptor tyrosine kinase SRC in lipid rafts of gastric cancer cells. Here, we observed high IGF1R expression in TRAIL-resistant gastric cancer cells, and showed that IGF1R combined with both CAV1 and SRC in a native complex...
April 12, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28402847/igf1-shapes-macrophage-activation-in-response-to-immunometabolic-challenge
#15
Olga Spadaro, Christina D Camell, Lidia Bosurgi, Kim Y Nguyen, Yun-Hee Youm, Carla V Rothlin, Vishwa Deep Dixit
In concert with their phagocytic activity, macrophages are thought to regulate the host immunometabolic responses primarily via their ability to produce specific cytokines and metabolites. Here, we show that IL-4-differentiated, M2-like macrophages secrete IGF1, a hormone previously thought to be exclusively produced from liver. Ablation of IGF1 receptors from myeloid cells reduced phagocytosis, increased macrophages in adipose tissue, elevated adiposity, lowered energy expenditure, and led to insulin resistance in mice fed a high-fat diet...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28395282/expanding-genetic-and-functional-diagnoses-of-igf1r-haploinsufficiencies
#16
Paula Ocaranza, Marjorie C Golekoh, Shayne F Andrew, Michael H Guo, Paul Kaplowitz, Howard Saal, Ron G Rosenfeld, Andrew Dauber, Fernando Cassorla, Philippe F Backeljauw, Vivian Hwa
BACKGROUND: The growth-promoting effects of IGF-I is mediated through the IGF-I receptor (IGF1R), a widely expressed cell-surface tyrosine kinase receptor. IGF1R copy number variants (CNV) can cause pre- and postnatal growth restriction or overgrowth. METHODS: Whole exome sequence (WES), chromosomal microarray, and targeted IGF1R gene analyses were performed on 3 unrelated children who share features of small for gestational age, short stature, and elevated serum IGF-I, but otherwise had clinical heterogeneity...
April 10, 2017: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/28389567/large-scale-analysis-of-variation-in-the-insulin-like-growth-factor-family-in-humans-reveals-rare-disease-links-and-common-polymorphisms
#17
Peter Rotwein
The insulin-like growth factors IGF1 and IGF2 are closely related proteins that are essential for normal growth and development in humans and other species and play critical roles in many physiological and patho-physiological processes. IGF actions are mediated by trans-membrane receptors and modulated by IGF binding proteins. The importance of IGF actions in human physiology is strengthened by the rarity of inactivating mutations in their genes, and by the devastating impact caused by such mutations on normal development and somatic growth...
April 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28382840/strong-expression-and-amplification-of-igf1r-in-pleuropulmonary-blastomas
#18
Christian Vokuhl, Laura de Leon-Escapini, Ivo Leuschner
Pleuropulmonary blastoma (PPB) is a rare malignant intrathoracic tumor primarily affecting children under 5 years of age. PPBs are histologically divided into 3 subtypes: Type I PPBs are composed of multiple cysts, and type III is a solid lesion with a variable morphologic appearance. Type II has a mixed morphology consisting of cystic and solid areas. The genetics of PPB are poorly understood. We analyzed 16 cases of the Kiel Paediatric Tumor Registry with the diagnosis of PPB by comparative genomic hybridization and confirmed some genetic changes by fluorescence in situ hybridization...
January 1, 2017: Pediatric and Developmental Pathology
https://www.readbyqxmd.com/read/28380379/%C3%AE-cell-aging-markers-have-heterogeneous-distribution-and-are-induced-by-insulin-resistance
#19
Cristina Aguayo-Mazzucato, Mark van Haaren, Magdalena Mruk, Terence B Lee, Caitlin Crawford, Jennifer Hollister-Lock, Brooke A Sullivan, James W Johnson, Aref Ebrahimi, Jonathan M Dreyfuss, Jan Van Deursen, Gordon C Weir, Susan Bonner-Weir
We hypothesized that the known heterogeneity of pancreatic β cells was due to subpopulations of β cells at different stages of their life cycle with different functional capacities and that further changes occur with metabolic stress and aging. We identified new markers of aging in β cells, including IGF1R. In β cells IGF1R expression correlated with age, dysfunction, and expression of known age markers p16(ink4a), p53BP1, and senescence-associated β-galactosidase. The new markers showed striking heterogeneity both within and between islets in both mouse and human pancreas...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28378126/global-transcriptomic-analysis-of-induced-cardiomyocytes-predicts-novel-regulators-for-direct-cardiac-reprogramming
#20
Mahmood Talkhabi, Seyed Morteza Razavi, Ali Salari
Heart diseases are the most significant cause of morbidity and mortality in the world. De novo generated cardiomyocytes (CMs) are a great cellular source for cell-based therapy and other potential applications. Direct cardiac reprogramming is the newest method to produce CMs, known as induced cardiomyocytes (iCMs). During a direct cardiac reprogramming, also known as transdifferentiation, non-cardiac differentiated adult cells are reprogrammed to cardiac identity by forced expression of cardiac-specific transcription factors (TFs) or microRNAs...
April 4, 2017: Journal of Cell Communication and Signaling
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