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https://www.readbyqxmd.com/read/27914008/igf1r-dental-pulp-stem-cells-enhanced-neuroplasticity-in-hypoxia-ischemia-model
#1
Hsiao-Yu Chiu, Chen-Huan Lin, Chung Y Hsu, John Yu, Chia-Hung Hsieh, Woei-Cherng Shyu
Until now, the surface markers of multipotent mesenchymal stem cells (MSCs) had not been fully identified. Here, we found that the IGF1 receptor (IGF1R), regarded as a pluripotent marker of embryonic stem cells (ESCs), was also expressed in human dental pulp derived-mesenchymal stem cells (hDSCs), which displayed a potential for both self-renewal and multipotency. hDSC-secreted IGF1 interacted with IGF1R through an autocrine signaling pathway to maintain this self-renewal and proliferation potential. Stereotaxic implantation of immunosorted IGF1R(+) hDSCs in rats with neonatal hypoxia-ischemia (NHI) promoted neuroplasticity, improving the neurological outcome by increasing expression of the anti-apoptotic protein Bcl-2, which enhanced both neurogenesis and angiogenesis...
December 2, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27896672/mir-15b-inhibits-the-progression-of-glioblastoma-cells-through-targeting-insulin-like-growth-factor-receptor-1
#2
Jian Wang, Huaqiang Liu, Lin Tian, Fachen Wang, Liangbo Han, Wei Zhang, Yun-An Bai
The microRNAs (miRNAs) have been suggested as a tumor suppressor in recent years. miR-15b was reported to exert an anti-oncogenic role in the proliferation, migration, and invasion of diverse tumor cells. However, the mechanisms underlying miR-15b-mediated biology of glioblastoma are still unclear. In the present study, the expression of miR-15b was down-regulated in glioblastoma tumor tissues and U87 and U251 cells, but insulin-like growth factor receptor 1 (IGF1R) expression became up-regulated in these tumor tissues and cells (all p < 0...
November 28, 2016: Hormones & Cancer
https://www.readbyqxmd.com/read/27891760/muscle-ras-oncogene-homolog-mras-recurrent-mutation-in-borrmann-type-iv-gastric-cancer
#3
Makiko Yasumoto, Etsuko Sakamoto, Sachiko Ogasawara, Taro Isobe, Junya Kizaki, Akiko Sumi, Hironori Kusano, Jun Akiba, Takuji Torimura, Yoshito Akagi, Hiraku Itadani, Tsutomu Kobayashi, Shinichi Hasako, Masafumi Kumazaki, Shinji Mizuarai, Shinji Oie, Hirohisa Yano
The prognosis of patients with Borrmann type IV gastric cancer (Type IV) is extremely poor. Thus, there is an urgent need to elucidate the molecular mechanisms underlying the oncogenesis of Type IV and to identify new therapeutic targets. Although previous studies using whole-exome and whole-genome sequencing have elucidated genomic alterations in gastric cancer, none has focused on comprehensive genetic analysis of Type IV. To discover cancer-relevant genes in Type IV, we performed whole-exome sequencing and genome-wide copy number analysis on 13 patients with Type IV...
November 28, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27879396/integrating-network-reconstruction-with-mechanistic-modeling-to-predict-cancer-therapies
#4
Melinda Halasz, Boris N Kholodenko, Walter Kolch, Tapesh Santra
Signal transduction networks are often rewired in cancer cells. Identifying these alterations will enable more effective cancer treatment. We developed a computational framework that can identify, reconstruct, and mechanistically model these rewired networks from noisy and incomplete perturbation response data and then predict potential targets for intervention. As a proof of principle, we analyzed a perturbation data set targeting epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) pathways in a panel of colorectal cancer cells...
November 22, 2016: Science Signaling
https://www.readbyqxmd.com/read/27862334/tgf%C3%AE-signaling-confers-sorafenib-resistance-via-induction-of-multiple-rtks-in-hepatocellular-carcinoma-cells
#5
Nathan Ungerleider, Chang Han, Jinqiang Zhang, Lu Yao, Tong Wu
Transforming growth factor β (TGFβ) is a multifunctional cytokine which is importantly implicated in hepatocarcinogenesis. The current study provides novel evidence that TGFβ upregulates the expression of multiple receptor tyrosine kinases (RTKs), including IGF1R, EGFR, PDGFβR, and FGFR1 in human hepatocellular carcinoma (HCC) cells. This, in turn, sensitized HCC cells to individual cognate RTK ligands, leading to cell survival. Our data showed that the TGFβ-mediated increase in growth factor sensitivity led to evasion of apoptosis induced by the mutikinase inhibitor, sorafenib...
November 15, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27861515/involvement-of-igf1r-in-bronchiolar-epithelial-regeneration-role-during-repair-kinetics-after-selective-club-cell-ablation
#6
Icíar P López, Sergio Piñeiro-Hermida, Rosete S Pais, Raquel Torrens, Andreas Hoeflich, José G Pichel
Regeneration of lung epithelium is vital for maintaining airway function and integrity. An imbalance between epithelial damage and repair is at the basis of numerous chronic lung diseases such as asthma, COPD, pulmonary fibrosis and lung cancer. IGF (Insulin-like Growth Factors) signaling has been associated with most of these respiratory pathologies, although their mechanisms of action in this tissue remain poorly understood. Expression profiles analyses of IGF system genes performed in mouse lung support their functional implication in pulmonary ontogeny...
2016: PloS One
https://www.readbyqxmd.com/read/27858328/adverse-events-and-efficacy-of-cixutumumab-in-phase-ii-clinical-trials-a-systematic-review-and-meta-analysis
#7
REVIEW
Hongxin Cao, Lixuan Cui, Wei Ma, Linhai Zhu, Kai Wang, Yang Ni, Yibing Wang, Jiajun Du
BACKGROUND AND OBJECTIVES: Cixutumumab is a monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF1R). We sought to evaluate the efficacy of cixutumumab in the treatment of cancer, and to comprehensively assess the associated adverse events in phase II clinical trials. METHODS: Data were collected from PubMed, Embase, and Clinicaltrials.gov. The improvement on progression-free survival (PFS) was evaluated by hazard ratio (HR) and 95% confidence intervals (95% CIs)...
November 17, 2016: Clinical Drug Investigation
https://www.readbyqxmd.com/read/27856640/g-protein-coupled-receptors-gpcrs-that-signal-via-protein-kinase-a-pka-cross-talk-at-insulin-receptor-substrate-1-irs1-to-activate-the-pi3k-akt-pathway
#8
Nathan C Law, Morris F White, Mary E Hunzicker-Dunn
GPCRs (G protein-coupled receptors)2 activate PI3K/AKT (phosphatidylinositol-3 kinase/v-AKT thymoma viral oncoprotein) to regulate many cellular functions that promote cell survival, proliferation, and growth. However, the mechanism by which GPCRs activate PI3K/AKT remains poorly understood. We used ovarian preantral granulosa cells (GCs) to elucidate the mechanism by which the GPCR agonist FSH (follicle-stimulating hormone) via PKA (protein kinase A) activates the PI3K/AKT cascade. IGF1 (insulin-like growth factor 1) is secreted in an autocrine/paracrine manner by GCs and activates the IGF1R (IGF1 receptor), but in the absence of FSH fails to stimulate YXXM phosphorylation of IRS1 (insulin receptor substrate 1) required for PI3K/AKT activation...
November 17, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27842509/unravelling-the-genomic-architecture-of-bull-fertility-in-holstein-cattle
#9
Yi Han, Francisco Peñagaricano
BACKGROUND: Fertility is considered an important economic trait in dairy cattle. Most studies have investigated cow fertility while bull fertility has received much less consideration. The main objective of this study was to perform a comprehensive genomic analysis in order to unravel the genomic architecture underlying sire fertility in Holstein dairy cattle. The analysis included the application of alternative genome-wide association mapping approaches and the subsequent use of diverse gene set enrichment tools...
November 14, 2016: BMC Genetics
https://www.readbyqxmd.com/read/27836546/apbb1-reinforces-cancer-stem-cell-and-epithelial-to-mesenchymal-transition-by-regulating-the-igf1r-signaling-pathway-in-non-small-cell-lung-cancer-cells
#10
Jei Ha Lee, Jung Yul Kim, Seo Yeon Kim, Soo Im Choi, Kuk Chan Kim, Eun Wie Cho, In Gyu Kim
Amyloid β precursor protein binding family B member 1(APBB1) was first identified as a binding partner of amyloid precursor protein during brain development, but its function in the context of cancer remain unclear. Here we show for the first time that APBB1 is partly associated with intensifying cancer stem cell(CSC) and epithelial-to-mesenchymal transition (EMT) and enhancing radiation-resistant properties of lung cancer cells. We found that APBB1 was highly expressed in ALDH1(high) CSC-like cells sorted from A549 lung cancer cells...
November 9, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27832807/sex-specific-variation-in-signaling-pathways-and-gene-expression-patterns-in-human-leukocytes-in-response-to-endotoxin-and-exercise
#11
Asghar Abbasi, Rodolfo de Paula Vieira, Felix Bischof, Michael Walter, Masoud Movassaghi, Nicole C Berchtold, Andreas M Niess, Carl W Cotman, Hinnak Northoff
BACKGROUND: While exercise effects on the immune system have received increasing attention in recent years, it remains unclear to what extent gender and fluctuations in sex hormones during menstrual cycle influence immunological responses to exercise. METHODS: We investigated mRNA changes induced through exhaustive exercise (half-marathon; pre-exercise and post-exercise [30 min, 3 h, 24 h] on whole blood cultures ± lipopolysaccharide [LPS] [1 h]) with a specific focus on sex differences (men vs women in luteal phase) as an extension of our previous study...
November 10, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27830018/insulin-like-growth-factor-1-antagonizes-lumbar-disc-degeneration-through-enhanced-autophagy
#12
Zuo-Qing Liu, Shan Zhao, Wen-Qin Fu
Autophagy has been shown to antagonize the development of Lumbar disc degeneration (LDD), whereas the molecular regulation of autophagy is unknown. We recently reported a potential role of Insulin-like growth factor 1 receptor (IGF1R)/phosphatidylinositol-3 kinase (PI3k)/Akt signaling in the initiation and progression of LDD. Here, we studied the effects of IGF1R signaling on disc cell autophagy. We showed a correction of activation of IGF1R and disc cell autophagy in the resected discs in LDD patients. In vitro, activation of IGF1R signaling antagonized the decreases in cell viability of human disc cells, HNPSV, through suppression of apoptosis and enhancement of autophagy...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27826649/expanding-the-clinical-spectrum-of-chromosome-15q26-terminal-deletions-associated-with-igf-1-resistance
#13
Aisling M O'Riordan, Niamh McGrath, Farhana Sharif, Nuala P Murphy, Orla Franklin, Sally Ann Lynch, Michael J O'Grady
: Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene on chromosome 15q26.3 is associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. Terminal deletions of chromosome 15q26 arising more proximally may also be associated with congenital heart disease, epilepsy, diaphragmatic hernia and renal anomalies. We report three additional cases of 15q26 terminal deletions with novel features which may further expand the spectrum of this rarely reported contiguous gene syndrome...
November 8, 2016: European Journal of Pediatrics
https://www.readbyqxmd.com/read/27824314/a-serum-mirna-profile-of-human-longevity-findings-from-the-baltimore-longitudinal-study-of-aging-blsa
#14
Thalyana Smith-Vikos, Zuyun Liu, Christine Parsons, Myriam Gorospe, Luigi Ferrucci, Thomas M Gill, Frank J Slack
In C. elegans, miRNAs are genetic biomarkers of aging. Similarly, multiple miRNAs are differentially expressed between younger and older persons, suggesting that miRNA-regulated biological mechanisms affecting aging are evolutionarily conserved. Previous human studies have not considered participants' lifespans, a key factor in identifying biomarkers of aging. Using PCR arrays, we measured miRNA levels from serum samples obtained longitudinally at ages 50, 55, and 60 from 16 non-Hispanic males who had documented lifespans from 58 to 92...
November 7, 2016: Aging
https://www.readbyqxmd.com/read/27813576/divergence-and-polymorphism-analysis-of-igf1ra-and-igf1rb-from-orange-spotted-grouper-epinephelus-coioides-hamilton
#15
L Guo, S Yang, M M Li, Z N Meng, H R Lin
Orange-spotted grouper (Epinephelus coioides) is one of the most important marine fish and has a high market value. The insulin-like growth factor type 1 receptor (IGF1R) is a component of the insulin-like growth factor signaling system, and demonstrates important roles during growth. Based on information from livestock, we used IGF1R as a candidate gene to survey single nucleotide polymorphisms. In the present study, the sequences of IGF1Ra and IGF1Rb from orange-spotted grouper were obtained from the genome sequences and their clustering in clades a and b, respectively, was confirmed by phylogenetic analysis...
October 17, 2016: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/27813496/the-cea-lo-colorectal-cancer-cell-population-harbors-cancer-stem-cells-and-metastatic-cells
#16
Chang Yan, Yibing Hu, Bo Zhang, Lei Mu, Kaiyu Huang, Hui Zhao, Chensen Ma, Xiaolan Li, Deding Tao, Jianping Gong, Jichao Qin
Serum carcinoembryonic antigen (CEA) is the most commonly used tumor marker in a variety of cancers including colorectal cancer (CRC) for tumor diagnosis and monitoring. Recent studies have shown that colonic crypt cells expressing little or no CEA may enrich for stem cells. Numerous studies have clearly shown that there exist CRC patients with normal serum CEA levels during tumor progression or even tumor relapse, although CEA itself is considered to promote metastasis and block cell differentiation. These seemingly contradictory observations prompted us to investigate, herein, the biological properties as well as tumorigenic and metastatic capacity of CRC cells that express high (CEA+) versus low CEA (CEA-/lo) levels of CEA...
November 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27808166/lpa-receptor-activity-is-basal-specific-and-coincident-with-early-pregnancy-and-involution-during-mammary-gland-postnatal-development
#17
Deanna Acosta, Susmita Bagchi, Pilib Ó Broin, Daniel Hollern, Silvia E Racedo, Bernice Morrow, Rani S Sellers, John M Greally, Aaron Golden, Eran Andrechek, Teresa Wood, Cristina Montagna
During pregnancy, luminal and basal epithelial cells of the adult mammary gland proliferate and differentiate resulting in remodeling of the adult gland. While pathways that control this process have been characterized in the gland as a whole, the contribution of specific cell subtypes, in particular the basal compartment, remains largely unknown. Basal cells provide structural and contractile support, however they also orchestrate the communication between the stroma and the luminal compartment at all developmental stages...
November 3, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27803039/an-igf1r-dependent-pathway-drives-epicardial-adipose-tissue-formation-after-myocardial-injury
#18
Lior Zangi, Marcela S Oliveira, Lillian Y Ye, Qing Ma, Nishat Sultana, Yoav Hadas, Elena Chepurko, Daniela Später, Bin Zhou, Wei Leong Chew, Wataru Ebina, Maryline Abrial, Qing-Dong Wang, William T Pu, Kenneth R Chien
BACKGROUND: -Epicardial adipose tissue (EAT) volume and coronary artery disease are strongly associated, even after accounting for overall body mass. Despite its pathophysiological significance, the origin and paracrine signaling pathways that regulate EAT's formation and expansion are unclear. METHODS: -We used a novel modified mRNA (modRNA)-based screening approach to probe the effect of individual paracrine factors on epicardial progenitors in the adult heart...
November 1, 2016: Circulation
https://www.readbyqxmd.com/read/27779100/hmgb1-inhibits-klotho-expression-and-malignant-phenotype-in-melanoma-cells-by-activating-nf-%C3%AE%C2%BAb
#19
Biao Xie, Ke Cao, Jinjin Li, Jia Chen, Jintian Tang, Xiang Chen, Kun Xia, Xiao Zhou, Yan Cheng, Jianda Zhou, Huiqing Xie
The molecular and cellular mechanisms behind the involvement of inflammation in melanoma have not been fully elucidated. In this study, knockdown of Hmgb1 expression increased apoptosis, reduced invasion and p-NF-κB expression, but increased Klotho protein level in melanoma tumor cells. The effect of Hmgb1 knockdown was overcome by LPS. Introduction of exogenous Hmgb1 significantly decreased apoptosis, increased invasion, elevated p-NF-κB, but lowered Klotho protein level in melanoma cells. The effect of exogenous Hmgb1 was agonized by NF-κB inhibitor CAPE...
October 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27765041/lack-of-interaction-between-erbb2-and-insulin-receptor-substrate-signaling-in-breast-cancer
#20
Susan M Farabaugh, Bonita T Chan, Xiaojiang Cui, Robert K Dearth, Adrian V Lee
BACKGROUND: ErbB2 Receptor Tyrosine Kinase 2 (ErbB2, HER2/Neu) is amplified in breast cancer and associated with poor prognosis. Growing evidence suggests interplay between ErbB2 and insulin-like growth factor (IGF) signaling. For example, ErbB2 inhibitors can block IGF-induced signaling while, conversely, IGF1R inhibitors can inhibit ErbB2 action. ErbB receptors can bind and phosphorylate insulin receptor substrates (IRS) and this may be critical for ErbB-mediated anti-estrogen resistance in breast cancer...
October 21, 2016: Cell Communication and Signaling: CCS
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