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https://www.readbyqxmd.com/read/28101891/different-expression-of-leptin-and-igf1-in-the-adult-and-prepubertal-testis-in-dogs
#1
L Müller, M P Kowalewski, I M Reichler, E Kollár, O Balogh
Leptin (Lep) and insulin-like growth factor 1 (IGF1) are implicated in the regulation of testicular function, but in dogs, our knowledge is limited to the possible role of the IGF1 system in testicular tumours. In this study, we aimed to describe and compare gene expression and protein localization of Lep, IGF1 and their receptors (LepR and IGF1R, respectively) in the testis of healthy adult and prepubertal dogs. Testes were collected from sexually healthy mature (n = 7) and from 8-week-old dogs (n = 7)...
January 18, 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28099935/frequent-amplification-of-receptor-tyrosine-kinase-genes-in-welldifferentiated-dedifferentiated-liposarcoma
#2
Naofumi Asano, Akihiko Yoshida, Sachiyo Mitani, Eisuke Kobayashi, Bunsyo Shiotani, Motokiyo Komiyama, Hiroyuki Fujimoto, Hirokazu Chuman, Hideo Morioka, Morio Matsumoto, Masaya Nakamura, Takashi Kubo, Mamoru Kato, Takashi Kohno, Akira Kawai, Tadashi Kondo, Hitoshi Ichikawa
Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are closely related tumors commonly characterized by MDM2/CDK4 gene amplification, and lack clinically effective treatment options when inoperable. To identify novel therapeutic targets, we performed targeted genomic sequencing analysis of 19 WDLPS and 37 DDLPS tumor samples using a panel of 104 cancer-related genes (NCC oncopanel v3) developed specifically for genomic testing to select suitable molecular targeted therapies. The results of this analysis indicated that these sarcomas had very few gene mutations and a high frequency of amplifications of not only MDM2 and CDK4 but also other genes...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28096258/regulation-of-glucose-uptake-and-enteroendocrine-function-by-the-intestinal-epithelial-insulin-receptor
#3
Siegfried Ussar, Max-Felix Haering, Shiho Fujisaka, Dominik Lutter, Kevin Y Lee, Ning Li, Georg K Gerber, Lynn Bry, C Ronald Kahn
Insulin and IGF-1 receptors (IR and IGF1R) are major regulators of metabolism and cell growth throughout the body, however, their roles in the intestine remain controversial. Here we show that genetic ablation of the IR or IGF1R in intestinal epithelial cells of mice does not impair intestinal growth or development or the composition of the gut microbiome. However, loss of IR alters intestinal epithelial gene expression, especially in pathways related to glucose uptake and metabolism. More importantly, loss of IR reduces intestinal glucose uptake...
January 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28096202/hasf-c3orf58-is-a-novel-ligand-of-the-insulin-like-growth-factor-1-receptor
#4
Akshay Bareja, Conrad Hodgkinson, Alan Payne, Richard Pratt, Victor Dzau
We have recently shown that Hypoxia and Akt induced Stem cell Factor (HASF) protects the heart from ischemia-induced damage and promotes cardiomyocyte proliferation. While we have identified certain signaling pathways responsible for these protective effects, the receptor mediating these effects was unknown. Here, we undertook studies to identify the HASF receptor. A yeast two-hybrid screen identified a partial fragment of Insulin-like Growth Factor 1 Receptor (IGF1R) as a binding partner of HASF. Subsequent co-immunoprecipitation experiments showed that HASF bound to full-length IGF1R...
January 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28094870/igf1r-signaling-acts-on-the-anagen-to-catagen-transition-in-the-hair-cycle
#5
Mathieu Castela, Fabien Linay, Edwige Roy, Philippe Moguelet, Jie Xu, Martin Holzenberger, Kiarash Khosrotehrani, Selim Aractingi
Insulin like growth factor 1 (IGF1) is important for skin development and homeostasis. However, overexpression and inactivation studies have produced variable findings regarding its role in hair follicle (HF) biology. Here, we studied a conditional and inducible knockout of the IGF1 receptor (IGF1R) in keratin 15-expressing bulge cells. Deletion of IGF1R after the development of the skin appendages in K15-IGF1R(KO) mice showed no abnormalities in epidermal homeostasis. Numbers of bulge cells were lower in K15-IGF1R(KO) mice than in controls, without consequences on wound healing, at least in young mice...
January 17, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28094184/in-vivo-evaluation-of-igf1r-ir-pet-ligand-18-f-bms-754807-in-rodents
#6
Jaya Prabhakaran, Stephen L Dewey, Richard McClure, Norman R Simpson, Mohammed N Tantawy, J John Mann, Wellington Pham, J S Dileep Kumar
In vivo evaluation of [(18)F]BMS-754807 binding in mice and rats using microPET and biodistribution methods is described herein. The radioligand shows consistent binding characteristics, in vivo, in both species. Early time frames of the microPET images and time activity curves of brain indicate poor penetration of the tracer across the blood brain barrier (BBB) in both species. However, microPET experiments in mice and rats show high binding of the radioligand outside the brain to heart, pancreas and muscle, the organs known for higher expression of IGF1R/1R...
January 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28089377/phase-ii-trial-of-albumin-bound-paclitaxel-and-granulocyte-macrophage-colony-stimulating-factor-as-an-immune-modulator-in-recurrent-platinum-resistant-ovarian-cancer
#7
John B Liao, Ron E Swensen, Kelsie J Ovenell, Katie M Hitchcock-Bernhardt, Jessica L Reichow, Minjun C Apodaca, Leonard D'Amico, Jennifer S Childs, Doreen M Higgins, Barbara J Buening, Barbara A Goff, Mary L Disis
BACKGROUND: Granulocyte macrophage colony-stimulating factor (GM-CSF) stimulates immunity via recruitment of antigen presenting cells and tumor specific T-cell stimulation. Albumin-bound paclitaxel (nab-paclitaxel) followed by GM-CSF may enhance antitumor responses and prolong remissions in ovarian cancer. Immune phenotypes present before treatment may identify responders to chemo-immunotherapy. METHODS: Recurrent platinum-resistant ovarian, peritoneal, or fallopian tube cancer patients received nab-paclitaxel, 100mg/m(2) days 1, 8, 15 followed by GM-CSF 250μg days 16-26 every 28days for 6 planned cycles...
January 12, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28075701/expression-analysis-of-genes-associated-with-prolificacy-in-fecb-carrier-and-noncarrier-indian-sheep
#8
S Goyal, J Aggarwal, P K Dubey, B P Mishra, P Ghalsasi, C Nimbkar, B K Joshi, R S Kataria
The effect of FecB mutation on the gene expression in FecB carrier and noncarrier estrous synchronized ewes, has been analyzed. For this study the whole ovarian tissues and Graafian follicles were collected from estrus synchronized FecB carrier Garole, and non-carrier Deccani Indian sheep, showing remarkable differences in the numbers of preovulatory follicles among two groups. Eleven potential candidate genes (BMP15, GDF9, BMP4, BMP7, BMPR1B, BMPR1A, SMAD9, LHCGR, FSHR, IGF1R, and STAT5) were selected for their expression analysis by SybrGreen based real-time PCR, across ovaries and Graafian follicles of different fecundity groups, for having better insights into the effect of FecB genotypes on follicular development...
January 11, 2017: Animal Biotechnology
https://www.readbyqxmd.com/read/28075048/the-sti-and-uba-domains-of-ubqln1-are-critical-determinants-of-substrate-interaction-and-proteostasis
#9
Zimple Kurlawala, Parag P Shah, Charmi Shah, Levi J Beverly
There are 5 Ubiquilin proteins (UBQLN1-4, UBQLN-L), which are evolutionarily conserved and structurally similar. UBQLN proteins have 3 functional domains: N-terminal ubiquitin-like domain (UBL), C-terminal ubiquitin-associated domain (UBA) and STI chaperone-like regions in the middle. Alterations in UBQLN1 gene have been detected in a variety of disorders ranging from Alzheimer's disease to cancer. UBQLN1 has been largely studied in neurodegenerative disorders in the context of protein quality control. Several studies have hypothesized that the UBA domain of UBQLN1 binds to poly-ubiquitin chains of substrate and shuttles it to the proteasome via its UBL domain for degradation...
January 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28067383/the-functional-consequences-and-prognostic-value-of-dosage-sensitivity-in-ovarian-cancer
#10
Zichuang Yan, Yongjing Liu, Yunzhen Wei, Ning Zhao, Qiang Zhang, Cheng Wu, Zhiqiang Chang, Yan Xu
Copy number alteration (CNA) represents an important class of genetic variations that may contribute to tumorigenesis, tumor growth and metastatic spread. CNA can directly affect the expression of genes within the CNA regions; however, genes within the CNA regions exhibit heterogeneity in gene dosage sensitivity. In this study, a computational framework was built to identify 1170 dosage-sensitive genes (DSGs) and 1215 dosage-resistant genes (DRGs) that were related to ovarian serous cystadenocarcinoma (OV) through the association between CNA and gene expression...
January 9, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28065828/adipocyte-dynamics-and-reversible-metabolic-syndrome-in-mice-with-an-inducible-adipocyte-specific-deletion-of-the-insulin-receptor
#11
Masaji Sakaguchi, Shiho Fujisaka, Weikang Cai, Jonathon N Winnay, Masahiro Konishi, Brian T O'Neill, Mengyao Li, Rubén García-Martín, Hirokazu Takahashi, Jiang Hu, Rohit N Kulkarni, C Ronald Kahn
Insulin and IGF1 signaling are important for adipose tissue development and function; however, their role in mature adipocytes is unclear. Mice with a tamoxifen-inducible knockout of insulin and/or IGF1 receptors (IR/IGF1R) demonstrate a rapid loss of white and brown fat due to increased lipolysis and adipocyte apoptosis. This results in insulin resistance, glucose intolerance, hepatosteatosis, islet hyperplasia with hyperinsulinemia, and cold intolerance. This phenotype, however, resolves over 10-30 days due to a proliferation of preadipocytes and rapid regeneration of both brown and white adipocytes as identified by mTmG lineage tracing...
January 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28064447/up-regulation-of-mir-497-confers-resistance-to-temozolomide-in-human-glioma-cells-by-targeting-mtor-bcl-2
#12
Danhua Zhu, Ming Tu, Bo Zeng, Lin Cai, Weiming Zheng, Zhipeng Su, Zhengquan Yu
The occurrence of an inherent or acquired resistance to temozolomide (TMZ) is a major burden for patients suffering from glioma. Recently, studies have demonstrated that microRNAs play an important role in the regulation of tumor properties in cancers. However, whether miR-497 contributes to glioma resistance to chemotherapy is not fully understood. In this study, we showed that the expression of miR-497 was markedly up-regulated in TMZ-resistant glioma cells; high miR-497 expression level was associated with TMZ-resistant phenotype of glioma cells...
January 8, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28062706/combinatorial-drug-screening-identifies-ewing-sarcoma-specific-sensitivities
#13
Branka Radic-Sarikas, Kalliopi P Tsafou, Kristina B Emdal, Theodore Papamarkou, Kilian V M Huber, Cornelia Mutz, Jeffrey A Toretsky, Keiryn L Bennett, Jesper V Olsen, Søren Brunak, Heinrich Kovar, Giulio Superti-Furga
Improvements in survival for Ewing sarcoma pediatric and adolescent patients have been modest over the past 20 years. Combinations of anticancer agents endure as an option to overcome resistance to single treatments caused by compensatory pathways. Moreover, combinations are thought to lessen any associated adverse side effects through reduced dosing, which is particularly important in childhood tumors. Using a parallel phenotypic combinatorial screening approach of cells derived from three pediatric tumor types, we identified Ewing sarcoma-specific interactions of a diverse set of targeted agents including approved drugs...
January 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28055425/igf1-regulates-runx1-expression-via-irs1-2-implications-for-antler-chondrocyte-differentiation
#14
Zhan-Qing Yang, Hong-Liang Zhang, Cui-Cui Duan, Shuang Geng, Kai Wang, Hai-Fan Yu, Zhan-Peng Yue, Bin Guo
Although IGF1 is important for the proliferation and differentiation of chondrocytes, its underlying molecular mechanism is still unknown. Here we addressed the physiological function of IGF1 in antler cartilage and explored the interplay of IGF1, IRS1/2 and RUNX1 in chondrocyte differentiation. The results showed that IGF1 was highly expressed in antler chondrocytes. Exogenous rIGF1 could increase the proliferation of chondrocytes and cell proportion in the S phase, whereas IGF1R inhibitor PQ401 abrogated the induction by rIGF1...
January 5, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28051262/bioinformatic-identification-of-igf1-as-a-hub-gene-in-hepatocellular-carcinoma-hcc-and-in-vitro-analysis-of-the-chemosensitizing-effect-of-mir-379-via-suppressing-the-igf1-igf1r-signaling-pathway
#15
D-J Huang, J-Z Huang, J Yang, Y-H Li, Y-C Luo, H-Y He, H-J Huang
OBJECTIVE: We investigated the interactions among the dysregulated genes in hepatocellular carcinoma (HCC) and identified the hub genes in the protein-protein interaction (PPI) network. Also, we also investigated the regulative effect of miR-379 on the IGF1/IGF1R signaling pathway and chemoresistance in HCC. MATERIALS AND METHODS: Raw data of a microarray that compared transcriptional gene profile between 3-paired HCC tissue samples and adjacent normal tissues were downloaded from Expression Atlas (E-GEOD-33006)...
December 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28050756/endothelial-cell-mediated-promotion-of-ciliated-cell-differentiation-of-human-airway-basal-cells-via-insulin-and-insulin-like-growth-factor-1-receptor-mediated-signaling
#16
Kazunori Gomi, Yongjiang Tang, Vanessa Arbelaez, Ronald G Crystal, Matthew S Walters
Human airway basal cells (BC) function as stem/progenitor cells of the human airway epithelium, capable of differentiating into ciliated and secretory cells during turnover and repair. The positioning of BC along the basement membrane allows for potential paracrine signaling from non-epithelial cells in the mesenchyme to regulate BC function. Based on the knowledge that interaction between the airway epithelium and mesenchyme is critical for proper maintenance of both tissues, and that endothelial cells (EC) can regulate multiple functions of BC, the present study was designed to help understand the role of BC and EC cross-talk in regulating BC stem/progenitor function...
January 3, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28050343/brain-insulin-resistance-deteriorates-cognition-by-altering-the-topological-features-of-brain-networks
#17
Fan Su, Hao Shu, Qing Ye, Zan Wang, Chunming Xie, Baoyu Yuan, Zhijun Zhang, Feng Bai
Insulin resistance represents one of the mechanisms underlying the link between type 2 diabetes (T2D) and Alzheimer's disease (AD), and we explored its in vivo neurobiology related to cognition based on a pathway-based genetic association analyses. Eighty-seven mild cognitive impairment (MCIs) subjects and 135 matched controls (HCs) were employed at baseline, and they underwent functional MRI scans, clinical evaluations and exon sequencings of 20 genes related to brain insulin resistance. A longitudinal study for an average of 35 months was performed to assess their cognitive decline over time...
2017: NeuroImage: Clinical
https://www.readbyqxmd.com/read/28043364/inhibition-of-peripubertal-sheep-mammary-gland-development-by-cysteamine-through-reducing-progesterone-and-growth-factor-production
#18
Yong Zhao, Yanni Feng, Hongfu Zhang, Xin Kou, Lan Li, Xinqi Liu, Pengfei Zhang, Liantao Cui, Meiqiang Chu, Wei Shen, Lingjiang Min
Cysteamine has been used for treating cystinosis for many years, and furthermore it has also been used as a therapeutic agent for different diseases including Huntington's disease, Parkinson's disease (PD), nonalcoholic fatty liver disease, malaria, cancer, and others. Although cysteamine has many potential applications, its use may also be problematic. The effects of low doses of cysteamine on the reproductive system, especially the mammary glands are currently unknown. In the current investigation, low dose (10 mg/kg BW/day) of cysteamine did not affect sheep body weight gain or organ index of the liver, spleen, or heart; it did, however, increase the levels of blood lymphocytes, monocytes, and platelets...
February 2017: Theriogenology
https://www.readbyqxmd.com/read/28032929/downregulation-of-mir-100-mir-125b-is-associated-with-lymph-node-metastasis-in-early-colorectal-cancer-with-submucosal-invasion
#19
Yasuteru Fujino, Shunsaku Takeishi, Kensei Nishida, Koichi Okamoto, Naoki Muguruma, Tetsuo Kimura, Shinji Kitamura, Hiroshi Miyamoto, Akiko Fujimoto, Jun Higashijima, Mitsuo Shimada, Kazuhito Rokutan, Tetsuji Takayama
A majority of early colorectal cancers (CRCs) with submucosal invasion undergo surgical operation despite very low incidence of lymph node metastasis. Our study aimed to identify microRNAs (miRNAs) specifically responsible for lymph node metastasis in submucosal CRCs. MicroRNA microarray analysis revealed that miR-100 and miR-125b expression levels were significantly lower in CRC tissues with lymph node metastases than in those without metastases. These results were validated by quantitative real-time PCR in a larger set of clinical samples...
December 29, 2016: Cancer Science
https://www.readbyqxmd.com/read/28030849/combined-and-individual-tumor-specific-expression-of-insulin-like-growth-factor-i-receptor-insulin-receptor-and-phospho-insulin-like-growth-factor-i-receptor-insulin-receptor-in-primary-breast-cancer-implications-for-prognosis-in-different-treatment-groups
#20
Sofie Björner, Ann H Rosendahl, Maria Simonsson, Andrea Markkula, Karin Jirström, Signe Borgquist, Carsten Rose, Christian Ingvar, Helena Jernström
Clinical trials examining insulin-like growth factor-I receptor (IGF1R)-targeting strategies have emphasized that better predictive biomarkers are required to improve patient selection.Immunohistochemical tumor-specific protein expression of IGF1R, insulin receptor (InsR), and phosphorylated IGF1R/InsR (pIGF1R/InsR) individually and combined in relation to breast cancer prognosis was evaluated in a population-based cohort of 1,026 primary invasive breast cancer patients without preoperative treatment diagnosed in Sweden...
December 21, 2016: Oncotarget
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