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Heba A Metwaly, Amal M El-Gayar, Mamdouh M El-Shishtawy
AIM OF WORK: The study was conducted for evaluation of the antitumor activity of SSTN92-119 against HCC induced by thioacetamide in rats. METHODS: Sixty male Sprague-Dawley rats were randomized into four equal groups: Control, SSTN92-119 , HCC, and HCC + SSTN92-119 . Liver function tests were measured in serum. Liver homogenate was used for determination of: i) integrinαѴβ3 (ITGαѴβ3), insulin like growth factor-1 receptor (IGF-1R), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and alpha-fetoprotein (AFP) levels by ELISA, ii) syndecan-1 (CD-138), IGF-1R and VEGF genes expressions by qRT-PCR, iii) MDA, NO, GSH concentrations and SOD activity...
June 18, 2018: Archives of Biochemistry and Biophysics
Jose C Leyva-Corona, Javier R Reyna-Granados, Ricardo Zamorano-Algandar, Miguel A Sanchez-Castro, Milton G Thomas, R Mark Enns, Scott E Speidel, Juan F Medrano, Gonzalo Rincon, Pablo Luna-Nevarez
Prolactin (PRL), growth hormone (GH), and insulin-like growth factor-1 (IGF-1) are in hormone-response pathways involved in energy metabolism during thermoregulation processes in cattle. Objective herein was to study the association between single nucleotide polymorphisms (SNP) within genes of the PRL and GH/IGF-1 pathways with fertility traits such as services per conception (SPC) and days open (DO) in Holstein cattle lactating under a hot-humid climate. Ambient temperature and relative humidity were used to calculate the temperature-humidity index (THI) which revealed that the cows were exposed to heat stress conditions from June to November of 2012 in southern Sonora, Mexico...
June 20, 2018: Tropical Animal Health and Production
Clara I Juárez-Vázquez, Carmen M Gurrola-Díaz, Belinda Vargas-Guerrero, José A Domínguez-Rosales, Jessica F Rodriguez-Ortiz, Patricio Barros-Núñez, Silvia E Flores-Martínez, José Sánchez-Corona, Mónica A Rosales-Reynoso
Objectives: The mitogenic effect of the analogous insulin glargine is currently under debate since several clinical studies have raised the possibility that insulin glargine treatment has a carcinogenic potential in different tissues. This study aimed to evaluate the Igf-1r , Insr , and Igf-1 gene expression in colon and liver of streptozotocin-induced diabetic rats in response to insulin glargine, neutral protamine Hagedorn (NPH) insulin, and metformin treatments. Materials and Methods: Male Wistar rats were induced during one week with streptozotocin to develop Type 2 Diabetes (T2D) and then randomly distributed into four groups...
May 2018: Iranian Journal of Basic Medical Sciences
Kai Mao, Gabriela Farias Quipildor, Tahmineh Tabrizian, Ardijana Novaj, Fangxia Guan, Ryan O Walters, Fabien Delahaye, Gene B Hubbard, Yuji Ikeno, Keisuke Ejima, Peng Li, David B Allison, Hossein Salimi-Moosavi, Pedro J Beltran, Pinchas Cohen, Nir Barzilai, Derek M Huffman
Diminished growth factor signaling improves longevity in laboratory models, while a reduction in the somatotropic axis is favorably linked to human aging and longevity. Given the conserved role of this pathway on lifespan, therapeutic strategies, such as insulin-like growth factor-1 receptor (IGF-1R) monoclonal antibodies (mAb), represent a promising translational tool to target human aging. To this end, we performed a preclinical study in 18-mo-old male and female mice treated with vehicle or an IGF-1R mAb (L2-Cmu, Amgen Inc), and determined effects on aging outcomes...
June 19, 2018: Nature Communications
L-J Hou, J-J Han, Y Liu
OBJECTIVE: The present study is aimed to investigate the regulatory effect of microRNA (miRNA or miR)-503 on endothelial functions, as well as the mechanism by which high glucose leads to injury of endothelial cells. MATERIALS AND METHODS: When reaching 80% confluency, human umbilical vein endothelial cells (HUVECs) were subjected to non-serum synchronization for 12 h, and medium of cells in high-glucose (HG) group was replaced by normal medium supplemented with 25 mmol/L D-glucose...
June 2018: European Review for Medical and Pharmacological Sciences
Tao Ma, Jianping Li, Qian Jiang, Sufang Wu, Huaizhi Jiang, Qiaoling Zhang
In order to improve the production and quality of Chinese cashmere, the research of hair follicle development has aroused more and more attention; the regulation mechanism of miRNA in hair follicle development has become a hot spot. A survey of transcriptome profiling screened 10 hair follicle-related miRNAs that were differentially expressed, including miR-let7a. In this study, the expression of miR-let7a was lower in anagen of hair follicle of cashmere goats than that in catagen of hair follicle of cashmere goats (p < 0...
June 18, 2018: Functional & Integrative Genomics
Hui Zhu, Chengbin Xue, Min Yao, Hongkui Wang, Ping Zhang, Tianmei Qian, Songlin Zhou, Shiying Li, Bin Yu, Yongjun Wang, Xiaosong Gu
The microenvironment of peripheral nerve regeneration consists of multiple neurotrophic factors, adhesion molecules, and extracellular matrix molecules, secreted by unique glial cells in the peripheral nerve system (PNS)-Schwann cell (SCs). Following peripheral nerve injury (PNI), local IGF-1 production is upregulated in SCs and denervated muscle during axonal sprouting and regeneration. Regulation of IGF-1/IGF-1R signaling is considered as a potentially targeted therapy of PNI. We previously identified a group of novel miRNAs in proximal nerve following rat sciatic nerve transection...
June 18, 2018: Cell Death & Disease
Brittany A Simone, Ajay Palagani, Kimberly Strickland, Kevin Ko, Lianjin Jin, Meng Kieng Lim, Tu D Dan, Mak Sarich, Daniel A Monti, Massimo Cristofanilli, Nicole L Simone
Triple negative breast cancer (TNBC) is a heterogeneous disease that has no available targeted therapies. Previously, we have shown that caloric restriction (CR) can augment the effects of radiation therapy in a TNBC mouse model. To build upon this, we now present data regarding the combination of chemotherapy and CR in the same 4T1 model. Chemotherapy can induce inflammation that breeds resistance to therapy. We propose CR as a mechanism to decrease chemotherapy-induced inflammation and increase efficacy of therapy...
June 18, 2018: Cell Cycle
Zhizhen Chen, Jie Liu, Dafeng Chu, Yaming Shan, Guixing Ma, Hongmin Zhang, Xiaohua Douglas Zhang, Pu Wang, Qiang Chen, Chuxia Deng, Weizao Chen, Dimiter S Dimitrov, Qi Zhao
The insulin-like growth factors (IGFs), IGF-I and IGF-II, are essential for regulating cell growth, differentiation and metastasis of a broad range of malignancies. The IGF-I/II actions are mediated through the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR), which are overexpressed in multiple types of tumors. Here, we have firstly identified a human engineered antibody domain (eAd) from a phage-displayed VH library. The eAd suppressed the signal transduction of IGF-1R mediated by exogenous IGF-I or IGF-II in breast cancer cell lines through neutralizing both IGF-I and IGF-II...
2018: International Journal of Biological Sciences
Renata Ferrarotto, William N William, Jennifer E Tseng, Shanthi Marur, Dong M Shin, Barbara Murphy, Ezra E W Cohen, Christopher Y Thomas, Richard Willey, Jan Cosaert, Nusrat Harun, J Jack Lee, Ignacio W Wistuba, Robert I Haddad, Bonnie S Glisson
OBJECTIVES: Cixutumumab (CIX) and cetuximab (CET) monoclonal antibodies block ligand-binding to insulin-like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) respectively. The objective of this study was to assess the efficacy of CIX alone or combined with CET in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients. METHODS: In this open-label phase II trial, 91 R/M HNSCC patients who progressed within 90 days of platinum-based chemotherapy, were randomized to CIX 10 mg/kg alone or with CET 500 mg/m2 every 2 weeks...
July 2018: Oral Oncology
Yongquan Lin, Lihua Rong, Jingrong Zhao, Ronghui Lin, Shuhua Li
MicroRNAs (miRNAs) possess oncogenic and tumour‑suppressive roles in the carcinogenesis and progression of pancreatic ductal adenocarcinoma (PDAC) by regulating the expression of numerous cancer‑related genes. Thus, the investigation on the expression and roles of miRNAs in PDAC may facilitate the identification of novel and effective targets for the clinical diagnosis and treatment of patients with PDAC. miRNA‑539 (miR‑539) has been studied in multiple types of human cancer. However, its expression and potential biological function in PDAC remain unclear...
May 31, 2018: Molecular Medicine Reports
Hani Lee, Nayoung Kim, Young Ji Yoo, Hyejin Kim, Euna Jeong, SeokGyeong Choi, Sung Un Moon, Seung Hyun Oh, Gordon B Mills, Sukjoon Yoon, Woo-Young Kim
The availability of large-scale drug screening data on cell line panels provides a unique opportunity to identify predictive biomarkers for targeted drug efficacy. Analysis of diverse drug data on ~990 cancer cell lines revealed enhanced sensitivity of insulin-like growth factor 1 receptor/ Insulin Receptor (IGF-1R/IR) tyrosine kinase inhibitors (TKIs) in colon cancer cells. Interestingly, β-catenin/TCF(T cell factor)-responsive promoter activity exhibited a significant positive association with IGF-1R/IR TKI response, while the mutational status of direct upstream genes, such as CTNNB1 and APC, was not significantly associated with the response...
June 12, 2018: Oncogene
Olalekan M Ogundele, Joaquin Pardo, Joseph Francis, Rodolfo G Goya, Charles C Lee
Insulin-like growth factor 1 receptor (IGF-1R) signaling regulates the activity and phosphorylation of downstream kinases linked to inflammation, neurodevelopment, aging and synaptic function. In addition to the control of Ca2+ currents, IGF-1R signaling modulates the activity of calcium-calmodulin-dependent kinase 2 alpha (CaMKIIα) and mitogen activated protein kinase (MAPK/ErK) through multiple signaling pathways. These proteins (CaMKIIα and MAPK) regulate Ca2+ movement and long-term potentiation (LTP)...
2018: Frontiers in Neuroanatomy
Shaoting Fu, Lijun Yin, Xiaojing Lin, Jianqiang Lu, Xiaohui Wang
Myoblast proliferation is crucial to skeletal muscle hypertrophy and regeneration. Our previous study indicated that mechanical stretch altered the proliferation of C2C12 myoblasts, associated with insulin growth factor 1 (IGF-1)-mediated phosphoinositide 3-kinase (PI3K)/Akt (also known as protein kinase B) and mitogen-activated protein kinase (MAPK) pathways through IGF-1 receptor (IGF-1R). The purpose of this study was to explore the same stretches on the proliferation of L6 myoblasts and its association with IGF-1-regulated PI3K/Akt and MAPK activations...
June 2, 2018: International Journal of Molecular Sciences
Shuhua Chen, Narender Kumar, Zisu Mao, Regine Sitruk-Ware, Roberta Diaz Brinton
OBJECTIVE: Neurogenesis is the principal regenerative mechanism to sustain the plasticity potential in adult brains. Decreased neurogenesis parallels the cognition decline with aging, and has been suggested as a common hallmark in the progression of many neurodegeneration diseases. We previously reported that acute exposure to segesterone acetate (ST-1435; Nestorone), alone or in combination with 17β-estradiol (E2), increased human neural stem cells proliferation and survival both in vitro and in vivo...
May 29, 2018: Menopause: the Journal of the North American Menopause Society
Na Liu, Hua Yang, Hong Wang
Background: In recent years, the aberrant expression of miR-598 in tumorigenesis has been demonstrated, as well as the fact that the IGF-1R pathway is also involved in the development of human gastric cancer (GC). The present study aimed to investigate the molecular mechanisms underlying miR-598-regulated IGF-1R expression in human GC. Materials and methods: We analyzed the expression of miR-598 and IGF-1R in GC samples and cells, and evaluated the clinical significance of miR-598 and IGF-1R in GC patients...
2018: OncoTargets and Therapy
Reham Abdel-Wahab, Gauri R Varadhachary, Priya R Bhosale, Xuemei Wang, David R Fogelman, Rachna T Shroff, Michael J Overman, Robert A Wolff, Milind Javle
BACKGROUND: Binding of insulin-like growth factor-I (IGF-1) to its receptor (IGF-1R) initiates downstream signals that activate PI3K/Akt/mTOR and MEK/Erk pathways, which stimulate cancer cell proliferation and induce drug resistance. Cross talk between IGF-1R and epidermal growth factor receptor (EGFR) mediates resistance to anti-EGFR agents. We studied safety, tolerability, and outcomes of MK-0646, IGF-1 monoclonal antibody, in combination with gemcitabine (G) ± erlotinib (E) in metastatic pancreatic cancer...
May 30, 2018: Journal of Hematology & Oncology
Vicente Alonso, Pilar Escudero, Carlos Fernández-Martos, Antonia Salud, Miguel Méndez, Javier Gallego, Jose-R Rodriguez, Marta Martín-Richard, Julen Fernández-Plana, Hermini Manzano, José-Carlos Méndez, Monserrat Zanui, Esther Falcó, Mireia Gil-Raga, Federico Rojo, Miriam Cuatrecasas, Jaime Feliu, Xabier García-Albéniz, Joan Maurel
INTRODUCTION: The coexpression of pIGF-1R and MMP-7 (double-positive phenotype, DP) correlates with poor overall survival (OS) in KRAS wild-type (WT) (exon 2) metastatic colorectal cancer (mCRC) patients treated with irinotecan-cetuximab in second/third line. METHODS: We analyzed two prospective biomarker design trials of newly diagnosed RAS-WT mCRC patients treated with panitumumab-FOLFOX6 (PULSE trial; NCT01288339) or cetuximab plus either FOLFOX6/FOLFIRI (POSIBA trial; NCT01276379)...
May 25, 2018: Neoplasia: An International Journal for Oncology Research
Weiming Wang, Yang Wang, Jiani Wu, Likun Yang, Zhishun Liu
OBJECTIVE: To explore the effects of electroacupuncture (EA) at "Zhongliao" (BL 33) and "Tianshu" (ST 25) on ovarian function in rats with premature ovarian insufficiency (POI). METHODS: A total of 48 SD female rats with regular estrus were divided into a blank group ( n =8), a model group ( n =10), an EA group ( n =10), a binding group ( n =10) and a tamoxifen (TAM) group ( n =10). The rats in the model group, EA group, binding group and TAM group were all treated with intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD, 160 mg/kg) for 15 consecutive days to establish the model of POI; the rats in the blank group were treated with normal diet...
May 12, 2018: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
Hongyang Lu, Zhiming Jiang
The proportion of small-cell lung cancer (SCLC) among all lung cancers decreased from 17.26% in 1986 to 12.95% in 2002. Chemotherapy is the key mode of treatment. However, novel therapeutic strategies and drugs are imperative, as the prognosis remains poor. In recent years, antibody therapies have shown promising prospects against malignancy. This review focuses on the advances in antibody therapies in SCLC. Although the results of pembrolizumab, nivolumab, ipilimumab, and rovalpituzumab tesirine are inspiring, all of the clinical trials on these drugs are phase I/II and have been verified for further phase III clinical trials...
May 16, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
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