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αvβ3 integrin

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https://www.readbyqxmd.com/read/30333317/%C3%AE-v%C3%AE-3-integrin-drives-fibroblast-contraction-and-strain-stiffening-of-soft-provisional-matrix-during-progressive-fibrosis
#1
Vincent F Fiore, Simon S Wong, Coleen Tran, Chunting Tan, Wenwei Xu, Todd Sulchek, Eric S White, James S Hagood, Thomas H Barker
Fibrosis is characterized by persistent deposition of extracellular matrix (ECM) by fibroblasts. Fibroblast mechanosensing of a stiffened ECM is hypothesized to drive the fibrotic program; however, the spatial distribution of ECM mechanics and their derangements in progressive fibrosis are poorly characterized. Importantly, fibrosis presents with significant histopathological heterogeneity at the microscale. Here, we report that fibroblastic foci (FF), the regions of active fibrogenesis in idiopathic pulmonary fibrosis (IPF), are surprisingly of similar modulus as normal lung parenchyma and are nonlinearly elastic...
October 18, 2018: JCI Insight
https://www.readbyqxmd.com/read/30333171/%C3%AE-v%C3%AE-3-integrin-is-required-for-efficient-infection-of-epithelial-cells-with-human-adenovirus-type-26
#2
Davor Nestić, Taco G Uil, Jiangtao Ma, Soumitra Roy, Jort Vellinga, Andrew H Baker, Jerome Custers, Dragomira Majhen
Human adenoviruses (HAdVs) are being explored as vectors for gene transfer and vaccination. Human adenovirus type 26 (HAdV26), which belongs to the largest subgroup of adenoviruses, species D, has a short fiber and a so far unknown natural tropism. Due to its low seroprevalence, HAdV26 has been considered a promising vector for the development of vaccines. Despite the fact that the in vivo safety and immunogenicity of HAdV26 has been extensively studied, the basic biology of this virus, with regard to receptor use, cell attachment, internalization and intracellular trafficking is poorly understood...
October 17, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30323584/a-novel-rgdyc-peg-co-modified-pamam-dendrimer-loaded-arsenic-trioxide-of-glioma-targeting-delivery-system
#3
Yanping Lu, Shunping Han, Hongyue Zheng, Rui Ma, Yuting Ping, Jiafeng Zou, Hongxia Tang, Yongping Zhang, Xiuling Xu, Fanzhu Li
Background: The Traditional Chinese Medicine, arsenic trioxide (ATO, As2 O3 ) could inhibit growth and induce apoptosis in a variety of solid tumor cells, but it is severely limited in the treatment of glioma due to its poor BBB penetration and nonspecifcity distribution in vivo. Purpose: The objective of this study was encapsulating ATO in the modified PAMAM den-drimers to solve the problem that the poor antitumor effect of ATO to glioma, which provide a novel angle for the study of glioma treatment...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/30312846/an-efficient-bivalent-cyclic-rgd-pik3cb-sirna-conjugate-for-specific-targeted-therapy-against-glioblastoma-in-vitro-and-in-vivo
#4
Bohong Cen, Yuanyi Wei, Wen Huang, Muzhou Teng, Shuai He, Jianlong Li, Wei Wang, Guolin He, Xin Bai, Xiaoxia Liu, Yawei Yuan, Xinghua Pan, Aimin Ji
The PI3K-AKT-mTOR-signaling pathway is frequently activated in glioblastoma (GBM). Inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB)/p110β (a PI3K catalytic isoform) by RNAi substantially suppresses GBM growth with less toxicity to normal astrocytes. However, insufficient and non-specific small interfering RNA (siRNA) delivery may limit the efficacy of RNAi-based therapies against GBM. Here we prepared a novel methoxy-modified PIK3CB siRNA molecule (siPIK3CB) that was covalently conjugated to a [cyclo(Arg-Gly-Asp-D-Phe-Lys)-Ahx]2 -Glu-PEG-MAL (biRGD) peptide, which selectively binds to integrin αvβ3 receptors...
September 6, 2018: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/30307153/thyroid-hormones-stimulate-l-arginine-transport-in-human-endothelial-cells
#5
Marta Toral, Rosario Jimenez, Sebastián Montoro-Molina, Miguel Romero, Rosemary Wangensteen, Juan Duarte, Félix Vargas
Thyroid hormone activity is associated with L-arginine metabolism and nitric oxide (NO) production, which participate in the cardiovascular manifestations of thyroid disorders. L-arginine transporters play an important role in activating L-arginine uptake and NO production. However, the effects of thyroid hormones on L-arginine transporters in endothelial cells have not yet been evaluated. The following methods were used. We measured L-arginine uptake, mRNA expression of L-arginine transporters, endothelial nitric oxide synthase (eNOS) mRNA and NO generation after the administration of T3, T4 and the T3 analog, 3,3′,5-triiodothyroacetic acid TRIAC in human umbilical vein endothelial cells (HUVECs)...
October 1, 2018: Journal of Endocrinology
https://www.readbyqxmd.com/read/30281669/integrin-targeted-quantitative-optoacoustic-imaging-with-mri-correlation-for-monitoring-a-braf-mek-inhibitor-combination-therapy-in-a-murine-model-of-human-melanoma
#6
Philipp M Kazmierczak, Neal C Burton, Georg Keinrath, Heidrun Hirner-Eppeneder, Moritz J Schneider, Ralf S Eschbach, Maurice Heimer, Olga Solyanik, Andrei Todica, Maximilian F Reiser, Jens Ricke, Clemens C Cyran
PURPOSE: To investigate αvβ3-integrin-targeted optoacoustic imaging and MRI for monitoring a BRAF/MEK inhibitor combination therapy in a murine model of human melanoma. MATERIALS AND METHODS: Human BRAF V600E-positive melanoma xenograft (A375)-bearing Balb/c nude mice (n = 10) were imaged before (day 0) and after (day 7) a BRAF/MEK inhibitor combination therapy (encorafenib, 1.3 mg/kg/d; binimetinib, 0.6 mg/kg/d, n = 5) or placebo (n = 5), respectively. Optoacoustic imaging was performed on a preclinical system unenhanced and 5 h after i...
2018: PloS One
https://www.readbyqxmd.com/read/30280197/an-rgd-small-molecule-integrin-antagonist-induces-detachment-mediated-anoikis-in-glioma-cancer-stem-cells
#7
Mayra Paolillo, Marisa C Galiazzo, Antonio Daga, Emilio Ciusani, Massimo Serra, Lino Colombo, Sergio Schinelli
The malignancy of glioblastoma (GB) is primarily due to the ability of glioma cancer stem cells (GSC) to disseminate into surrounding brain tissues, despite surgery and chemotherapy, and to form new tumoral masses. Members of the RGD-binding integrin family, which recognize the arginine-glycine-aspartic acid (RGD) sequence present in components of the extracellular matrix, and which serve a crucial function in the dissemination of GCS, are overexpressed in GB. Small-molecule integrin antagonists (SMIAs) designed to recognize RGD-integrins may therefore be an effective tool for decreasing GB infiltration and recurrence...
October 3, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/30278131/-99m-tc-tc-n-pnp43-labeled-rgd-peptides-as-new-probes-for-a-selective-detection-of-%C3%AE-v%C3%AE-3-integrin-synthesis-structure-activity-and-pharmacokinetic-studies
#8
Cristina Bolzati, Nicola Salvarese, Debora Carpanese, Roberta Seraglia, Laura Meléndez-Alafort, Antonio Rosato, Domenica Capasso, Michele Saviano, Annarita Del Gatto, Daniela Comegna, Laura Zaccaro
New integrin-selective molecules suitable for therapeutic or imaging purposes are currently of interest in development of effective personalized medical platforms. RGDechi is a bifunctional peptide selective for integrin αv β3 . Herein, RGDechi and three truncated derivatives functionalized with a cysteine (1-4) were synthesized and labeled with the [99m Tc][Tc(N)PNP43]-synthon ([PNP43 = (CH3 )2 P(CH2 )2 N(C2 H4 OCH3 )(CH2 )2 P(CH3 )2 ]) (99m Tc1-4) as a basis for selective integrin recognition. The pharmacological parameters of all radiolabeled peptides were assessed along with the pharmacokinetic profiles of the most promising 99m Tc1 and 99m Tc2 compounds both on healthy and melanoma-bearing mice...
October 17, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30266752/%C3%AE-v%C3%AE-3-integrin-mediates-radioresistance-of-prostate-cancer-cells-through-regulation-of-survivin
#9
Tao Wang, Jiayi Huang, Mai Vue, Michael Rami Alavian, Hira Lal Goel, Dario C Altieri, Lucia R Languino, Thomas J Fitzgerald
The αvβ3 integrin is involved in various physiological and pathological processes such as wound healing, angiogenesis, tumor growth and metastasis. The impact of αvβ3 integrin on the radiosensitivity of prostate cancer (PrCa) cells and the molecular mechanism controlling cell survival in response to ionizing radiation (IR) was investigated. Both LNCaP cells stably transfected with αvβ3 integrin and PC3 cells that contain endogenous β3 integrin were used. This study demonstrated that αvβ3 integrin increases survival of αvβ3-LNCaP cells upon IR while shRNA-mediated knockdown of αvβ3 integrin in PC-3 cells sensitizes to radiation...
September 28, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/30262596/differential-effects-of-integrin-%C3%AE-v-knockdown-and-cilengitide-on-sensitisation-of-triple-negative-breast-cancer-and-melanoma-cells-to-microtubule-poisons
#10
Nikolina Stojanovic, Ana Dekanic, Mladen Paradzik, Dragomira Majhen, Kresimir Ferencak, Jelena Ruscic, Irena Bardak, Christine Supina, Maja T Tomicic, Markus Christmann, Maja Osmak, Andreja Ambriovic-Ristov
Low survival rates of patients with metastatic triple negative breast cancer (TNBC) and melanoma, in which current therapies are ineffective, emphasize the need for new therapeutic approaches. Integrin β1 appears to be a promising target when combined with chemotherapy, but recent data have shown that its inactivation increases metastatic potential due to the compensatory upregulation of other integrin subunits. Consequently, we decided to analyze the potential of integrin subunits αv, α3, or α4 as targets for improved therapy in seven TNBC and melanoma cell lines...
September 27, 2018: Molecular Pharmacology
https://www.readbyqxmd.com/read/30239013/biocompatibility-of-polysulfone-hemodialysis-membranes-and-its-mechanisms-involvement-of-fibrinogen-and-its-integrin-receptors-in-activation-of-platelets-and-neutrophils
#11
Yoko Koga, Hiroaki Fujieda, Hiroyuki Meguro, Yoshiyuki Ueno, Takao Aoki, Keishi Miwa, Mie Kainoh
Activation of blood cells during hemodialysis is considered to be a significant determinant of biocompatibility of the hemodialysis membrane because it may affect patient health adversely through microvascular inflammation and oxidative stress. This study found very different cell activation among various polysulfone (PSf) hemodialysis membranes. For example, CX-U, a conventional PSf membrane, induced marked adhesion of platelets to its surface and increased surface expression of activated CD11b and production of reactive oxygen species (ROS) by neutrophils; while NV-U, a hydrophilic polymer-immobilized PSf membrane, caused little platelet adhesion and slight CD11b expression and ROS production by neutrophils...
September 2018: Artificial Organs
https://www.readbyqxmd.com/read/30237860/autotaxin-%C3%AE-interaction-with-the-cell-surface-via-syndecan-4-impacts-on-cancer-cell-proliferation-and-metastasis
#12
Raphael Leblanc, Debashish Sahay, Audrey Houssin, Irma Machuca-Gayet, Olivier Peyruchaud
Autotaxin (ATX) promotes cancer cell metastasis through the production of lysophosphatidic acid (LPA). ATX binds to αvβ3 integrins controlling metastasis of breast cancer cells. We screened a series of cancer cell lines derived from diverse human and mouse solid tumors for the capacity of binding to ATX and found only a modest correlation with their level of αvβ3 integrin expression. These results strongly suggested the existence of another cell surface ATX-interacting factor. Indeed, ATXα has been shown to bind heparan-sulfate chains because of its unique polybasic insertion sequence, although the biological significance is unknown...
September 4, 2018: Oncotarget
https://www.readbyqxmd.com/read/30142160/a-dual-specific-macrophage-colony-stimulating-factor-antagonist-of-c-fms-and-%C3%AE-v%C3%AE-3-integrin-for-osteoporosis-therapy
#13
Yuval Zur, Lior Rosenfeld, Chen Anna Keshelman, Nofar Dalal, Gali Guterman-Ram, Ayelet Orenbuch, Yulia Einav, Noam Levaot, Niv Papo
There is currently a demand for new highly efficient and specific drugs to treat osteoporosis, a chronic bone disease affecting millions of people worldwide. We have developed a combinatorial strategy for engineering bispecific inhibitors that simultaneously target the unique combination of c-FMS and αvβ3 integrin, which act in concert to facilitate bone resorption by osteoclasts. Using functional fluorescence-activated cell sorting (FACS)-based screening assays of random mutagenesis macrophage colony-stimulating factor (M-CSF) libraries against c-FMS and αvβ3 integrin, we engineered dual-specific M-CSF mutants with high affinity to both receptors...
August 2018: PLoS Biology
https://www.readbyqxmd.com/read/30141897/gsh-activated-light-up-near-infrared-fluorescent-probe-with-high-affinity-to-%C3%AE-v-%C3%AE-3-integrin-for-precise-early-tumor-identification
#14
Zhenwei Yuan, Lijuan Gui, Jinrong Zheng, Yisha Chen, Sisi Qu, Yuanzhi Shen, Fei Wang, Murat Er, Yueqing Gu, Haiyan Chen
The development of tumor-associated, stimuli-driven, turn-on near-infrared (NIR) fluorophores requires urgent attention because of their potential in selective and precise tumor diagnosis. Herein, we describe a NIR fluorescent probe (CyA-cRGD) comprised of a fluorescence reporting unit (a cyanine dye) linked with a GSH-responsive unit (nitroazo aryl ether group) and a tumor-targeting unit (cRGD). The NIR fluorescence of CyA-cRGD with sensitive and selective response to GSH can act as a direct off-on signal reporter for GSH monitoring...
September 19, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/30140377/optical-in-vivo-imaging-detection-of-preclinical-models-of-gut-tumors-through-the-expression-of-integrin-%C3%AE-v%C3%AE-3
#15
Giulia Marelli, Roberta Avigni, Paola Allavena, Cecilia Garlanda, Alberto Mantovani, Andrea Doni, Marco Erreni
Optical imaging and Fluorescent Molecular Tomography (FMT) are becoming increasingly important for the study of different preclinical models of cancer, providing a non-invasive method for the evaluation of tumor progression in a relatively simple and fast way. Intestinal tumors, in particular colorectal cancer (CRC), represent a major cause of cancer-related death in Western countries: despite the presence of a number of preclinical models of intestinal carcinogenesis, there is a paucity of information about the possibility to detect intestinal tumors using fluorescent probes and optical in vivo imaging...
July 31, 2018: Oncotarget
https://www.readbyqxmd.com/read/30140193/intracellular-pathways-involved-in-bone-regeneration-triggered-by-recombinant-silk-silica-chimeras
#16
Zaira Martín-Moldes, Davoud Ebrahimi, Robyn Plowright, Nina Dinjaski, Carole C Perry, Markus J Buehler, David L Kaplan
Biomineralization at the organic-inorganic interface is critical to many biology material functions in vitro and in vivo . Recombinant silk-silica fusion peptides are organic-inorganic hybrid material systems that can be effectively used to study and control biologically-mediated mineralization due to the genetic basis of sequence control. However, to date, the mechanisms by which these functionalized silk-silica proteins trigger the differentiation of human mesenchymal stem cells (hMSCs) to osteoblasts remain unknown...
July 4, 2018: Advanced Functional Materials
https://www.readbyqxmd.com/read/30135398/contributions-of-thyroid-hormone-to-cancer-metastasis
#17
REVIEW
Shaker A Mousa, Gennadi V Glinsky, Hung-Yun Lin, Osnat Ashur-Fabian, Aleck Hercbergs, Kelly A Keating, Paul J Davis
Acting at a cell surface receptor on the extracellular domain of integrin αvβ3, thyroid hormone analogues regulate downstream the expression of a large panel of genes relevant to cancer cell proliferation, to cancer cell survival pathways, and to tumor-linked angiogenesis. Because αvβ3 is involved in the cancer cell metastatic process, we examine here the possibility that thyroid hormone as l-thyroxine (T4) and the thyroid hormone antagonist, tetraiodothyroacetic acid (tetrac), may respectively promote and inhibit metastasis...
August 22, 2018: Biomedicines
https://www.readbyqxmd.com/read/30130447/t-dm1-resistant-cells-gain-high-invasive-activity-via-egfr-and-integrin-cooperated-pathways
#18
Yukinori Endo, Yi Shen, Lamis Abou Youssef, Nishant Mohan, Wen Jin Wu
Ado-trastuzumab emtansine (Kadcyla®; T-DM1) is an antibody-drug conjugate developed to treat trastuzumab-resistant disease. Despite initial favorable outcomes, most patients eventually cease to respond due to developing acquired resistance to T-DM1. Currently, there is no targeted therapy to treat T-DM1-resistant disease. To explore novel therapeutic targets to improve therapeutic efficacy of T-DM1, we generated T-DM1-resistant cells using trastuzumab-resistant JIMT1 cells. We found that the loss of human epidermal growth factor receptor 2 confers T-DM1 resistance, which in turn activates a compensatory mechanism that increases epidermal growth factor receptor (EGFR) expression...
October 2018: MAbs
https://www.readbyqxmd.com/read/30128492/fenofibrate-exerts-protective-effects-in-diabetic-retinopathy-via-inhibition-of-the-angptl3-pathway
#19
Na Wang, Chen Zou, Shuzhi Zhao, Yunzhi Wang, Changjing Han, Zhi Zheng
Purpose: Fenofibrate has been demonstrated to exert a promising therapeutic effect against diabetic retinopathy. Angiopoietin-like 3 (ANGPTL3) has been shown to exert significant pathogenic effects on vascular endothelial cells, which are critically involved in the pathogenesis of diabetic retinopathy. The present study aimed to investigate the link between the therapeutic effects of fenofibrate and the pathogenic effects of ANGPTL3 in diabetic retinopathy. Methods: Diabetic and control rats were randomly assigned to the following treatments: intravitreal injection with ANGPTL3 small interfering RNA (siRNA), recombinant human (rh)ANGPTL3, fed with normal feeds, or fenofibrate-containing feeds for 8 weeks...
August 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/30127610/cyclic-rgd-conjugated-pluronic-%C3%A2-blending-system-for-active-targeted-drug-delivery
#20
Chaemin Lim, Junseong Moon, Taehoon Sim, Ngoc Ha Hoang, Woong Roeck Won, Eun Seong Lee, Yu Seok Youn, Han-Gon Choi, Kyungsoo Oh, Kyung Taek Oh
Background: Blending micellar systems of different types of polymers has been proposed as an efficient approach for tailor-made drug formulations. The lamellar structure of hydrophobic polymers may provide a high drug loading capacity, and hydrophilic polymers may provide good colloidal stability. Methods: In this study, the anticancer model drug docetaxel was loaded onto a nanosized blending micellar system with two pluronics (L121/F127). To achieve increased antitumor activity, the cyclic arginine-glycine-aspartic acid tripeptide (cRGD) as an active tumor targeting ligand was conjugated to the blending system...
2018: International Journal of Nanomedicine
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