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https://www.readbyqxmd.com/read/29777904/axed-muc4-muc4-x-aggravates-pancreatic-malignant-phenotype-by-activating-integrin-%C3%AE-1-fak-erk-pathway
#1
Rahat Jahan, Muzafar A Macha, Satyanarayana Rachaghani, Srustidhar Das, Lynette M Smith, Sukhwinder Kaur, Surinder K Batra
Alternative splicing is evolving as an eminent player of oncogenic signaling for tumor development and progression. Mucin 4 (MUC4), a type I membrane-bound mucin, is differentially expressed in pancreatic cancer (PC) and plays a critical role in its progression and metastasis. However, the molecular implications of MUC4 splice variants during disease pathogenesis remain obscure. The present study delineates the pathological and molecular significance of a unique splice variant of MUC4, MUC4/X, which lacks the largest and polymorphic exon 2, along with exon 3...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777544/gingipains-disrupt-f-actin-and-cause-osteoblast-apoptosis-via-integrin-%C3%AE-1
#2
Q Qiu, F Zhang, J Wu, N Xu, M Liang
BACKGROUND AND OBJECTIVE: The aim of this study was to explore the cellular mechanisms underlying gingipain-caused changes in cell morphology and apoptosis of osteoblasts. MATERIAL AND METHODS: Human calvarial osteoblasts and mouse osteoblasts MC3T3-E1 were treated with gingipain extracts from Porphyromonas gingivalis stain W83. Apoptosis was detected with annexin V and propidium iodide flow cytometry analysis or terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling staining...
May 18, 2018: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29777221/chemokines-and-integrins-independently-tune-actin-flow-and-substrate-friction-during-intranodal-migration-of-t-cells
#3
Miroslav Hons, Aglaja Kopf, Robert Hauschild, Alexander Leithner, Florian Gaertner, Jun Abe, Jörg Renkawitz, Jens V Stein, Michael Sixt
Although much is known about the physiological framework of T cell motility, and numerous rate-limiting molecules have been identified through loss-of-function approaches, an integrated functional concept of T cell motility is lacking. Here, we used in vivo precision morphometry together with analysis of cytoskeletal dynamics in vitro to deconstruct the basic mechanisms of T cell migration within lymphatic organs. We show that the contributions of the integrin LFA-1 and the chemokine receptor CCR7 are complementary rather than positioned in a linear pathway, as they are during leukocyte extravasation from the blood vasculature...
May 18, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29776956/integrin-%C3%AE-3-inhibition-enhances-the-antitumor-activity-of-alk-inhibitor-in-alk-rearranged-nsclc
#4
Ka-Won Noh, Insuk Sohn, Ji-Young Song, Hyun-Tae Shin, Yu Jin Kim, Kyungsoo Jung, Minjung Sung, Mingi Kim, Sungbin An, Joungho Han, Se-Hoon Lee, Mi-Sook Lee, Yoon-La Choi
BACKGROUND: Anaplastic lymphoma kinase (ALK)-positive cancers are sensitive to small molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication. PATIENTS AND METHODS: We screened ALK-rearranged non-small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence in situ hybridization, and then conducted multiplex gene expression analysis...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29775303/simultaneous-targeting-of-rgd-integrins-and-dual-murine-double-minute-proteins-in-glioblastoma-multiforme
#5
Francesco Merlino, Simona Daniele, Valeria La Pietra, Salvatore Di Maro, Francesco Saverio Di Leva, Diego Brancaccio, Stefano Tomassi, Stefano Giuntini, Linda Cerofolini, Marco Fragai, Claudio Luchinat, Florian Reichart, Chiara Cavallini, Barbara Costa, Rebecca Piccarducci, Sabrina Taliani, Federico Da Settimo, Claudia Martini, Horst Kessler, Ettore Novellino, Luciana Marinelli
In the fight against Glioblastoma Multiforme, recent literature data have highlighted that integrin α5β1 and p53 are part of convergent pathways in the control of glioma apoptosis. This observation prompted us to seek a molecule able to simultaneously modulate both target families. Analyzing the results of a previous virtual screening against murine double minute 2 protein (MDM2), we envisaged that Arg-Gly-Asp (RGD)-mimetic molecules could be inhibitors of MDM2/4. Herein we present the discovery of compound 7, which inhibits both MDM2/4 and α5β1/αvβ3 integrins...
May 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29775225/cytokines-and-chemokines-differentially-regulate-innate-immune-cell-trafficking-during-post-kala-azar-dermal-leishmaniasis
#6
Ashish K Singh, Vidya N R Das, Ajay Amit, Manas R Dikhit, Vijaya Mahantesh, Shubhankar K Singh, Shyam Naryan, Krishna Pandey, Pradeep Das, Neena Verma, Sanjiva Bimal
Post kala-azar dermal leishmaniasis (PKDL) is often considered to be the anthroponotic reservoir of visceral leishmaniasis (VL) in India. A better understanding of the host immune-response in dermal lesions of PKDL patients is therefore of utmost significance to minimize such patients and to restrict VL transmission. Although the innate immune response is known to play an important role in parasite clearance from dermal lesions, the actual contribution of innate cells to the pathogenicity of PKDL is poorly understood...
May 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29774910/design-of-rgd-atwlppr-peptide-conjugates-for-the-dual-targeting-of-%C3%AE-v-%C3%AE-3-integrin-and-neuropilin-1
#7
Fabien Thoreau, Laetitia Vanwonterghem, Maxime Henry, Jean-Luc Coll, Didier Boturyn
Targeting the tumour microenvironment is a promising strategy to detect and/or treat cancer. The design of selective compounds that co-target several receptors frequently overexpressed in solid tumours may allow a reliable and selective detection of tumours. Here we report the modular synthesis of compounds encompassing ligands of αVβ3 integrin and neuropilin-1 that are overexpressed in the tumour microenvironment. These compounds were then evaluated through cellular experiments and imaging of tumours in mice...
May 18, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29774773/mir-711-induced-down-regulation-of-angiopoietin-1-mediates-neuronal-cell-death
#8
Boris Sabirzhanov, Alan Faden, Taryn Aubrecht, Rebecca Henry, Ethan Glaser, Bogdan A Stoica
Angiopoietin-1 (Ang-1) is a well-known endothelial growth factor but its effects on neurons have yet to be elucidated. We show that Ang-1 is rapidly down-regulated in the injured brain after controlled cortical impact (CCI), a mouse experimental TBI model and in etoposide-induced neuronal apoptosis in vitro. Ang-1 treatment inhibits etoposide-induced up-regulation of pro-apoptotic Bcl-2 family members Noxa, Puma, Bim, and Bax; reduces markers of caspase-dependent (cytochrome c release/caspase activation) and caspase-independent (apoptosis-inducing factor release) pathways; and limits neuronal cell death...
May 18, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29774654/a-photoactivatable-%C3%AE-5%C3%AE-1-specific-integrin-ligand
#9
Aranzazu Del Campo, Roshna V Nair, Aleeza Farrukh
The integrin α5β1 is overexpressed in colon, breast, ovarian, lung and brain tumors and has been identified as key component in mechanosensing. In order to study how dynamic changes of α5β1 engagement affect cellular behaviour, photoactivatable derivatives of α5β1 specific ligands are presented in this article. A photoremovable protecting group (PRPG) was introduced into the ligand structure at a relevant position for integrin recognition. The presence of the chromophore temporally inhibited ligand bioactivity...
May 18, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29774158/efficacy-of-vedolizumab-for-induction-of-clinical-response-and-remission-in-patients-with-moderate-to-severe-inflammatory-bowel-disease-who-failed-at-least-two-tnf-antagonists
#10
Martine De Vos, Barbara Dhooghe, Severine Vermeire, Edouard Louis, Fazia Mana, Ann Elewaut, Peter Bossuyt, Filip Baert, Catherine Reenaers, Marc Van Gossum, Elisabeth Macken, Marc Ferrante, Pieter Hindryckx, Olivier Dewit, Tom Holvoet, Denis Franchimont
Background: Vedolizumab is a recently available monoclonal antibody targeting α4β7 integrin for the treatment of ulcerative colitis (UC) and Crohn's disease (CD). Objective: The objective of this article is to evaluate the efficacy of vedolizumab induction therapy in anti-TNF-refractory/intolerant UC and CD patients in real life. Methods: A cohort of 149 moderately to severely active UC and CD patients who failed or showed intolerance to at least two TNF antagonists participated in a medical need program and received vedolizumab in 37 Belgian centers (April-September 2015)...
April 2018: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/29774124/long-term-exposure-to-carcinoma-associated-fibroblasts-makes-breast-cancer-cells-addictive-to-integrin-%C3%AE-1
#11
Angela Dittmer, Jürgen Dittmer
We studied the long-term effect of stromal factors on the development of fulvestrant-resistance (FR) and fulvestrant-induced dormancy (D). Sublines established from stroma-treated FR-cells (C-FR cells) and D-cells (C-D cells) show permanently high expression of integrin β1 as well as Bcl-3 and P-STAT3 (C-FR) or IGF1R (C-D). Yet, cells fail to withstand fulvestrant better and do not migrate or grow faster than control cells. Instead, C-D cells rely on stromal factors to perform as well as control cells. In addition, C-FR cells adapted to integrin β1 for growth in 3D cultures...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774068/platelet-camouflaged-nanococktail-simultaneous-inhibition-of-drug-resistant-tumor-growth-and-metastasis-via-a-cancer-cells-and-tumor-vasculature-dual-targeting-strategy
#12
Lijia Jing, Haijing Qu, Dongqi Wu, Chaojian Zhu, Yongbo Yang, Xing Jin, Jian Zheng, Xiangsheng Shi, Xiufeng Yan, Yang Wang
Multidrug resistance (MDR) poses a great challenge to cancer therapy. It is difficult to inhibit the growth of MDR cancer due to its chemoresistance. Furthermore, MDR cancers are more likely to metastasize, causing a high mortality among cancer patients. In this study, a nanomedicine RGD-NPVs@MNPs/DOX was developed by encapsulating melanin nanoparticles (MNPs) and doxorubicin (DOX) inside RGD peptide (c(RGDyC))-modified nanoscale platelet vesicles (RGD-NPVs) to efficiently inhibit the growth and metastasis of drug-resistant tumors via a cancer cells and tumor vasculature dual-targeting strategy...
2018: Theranostics
https://www.readbyqxmd.com/read/29774029/lfa-1-in-t-cell-migration-and-differentiation
#13
REVIEW
Brandon L Walling, Minsoo Kim
Maintenance of homeostatic immune surveillance and development of effective adaptive immune responses require precise regulation of spatial and temporal lymphocyte trafficking throughout the body to ensure pathogen clearance and memory generation. Dysregulation of lymphocyte activation and migration can lead to impaired adaptive immunity, recurrent infections, and an array of autoimmune diseases and chronic inflammation. Central to the recruitment of T cells, integrins are cell surface receptors that regulate adhesion, signal transduction, and migration...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29773794/calreticulin-and-integrin-alpha-dissociation-induces-anti-inflammatory-programming-in-animal-models-of-inflammatory-bowel-disease
#14
Masayoshi Ohkuro, Jun-Dal Kim, Yoshikazu Kuboi, Yuki Hayashi, Hayase Mizukami, Hiroko Kobayashi-Kuramochi, Kenzo Muramoto, Manabu Shirato, Fumiko Michikawa-Tanaka, Jun Moriya, Teruya Kozaki, Kazuma Takase, Kenichi Chiba, Kishan Lal Agarwala, Takayuki Kimura, Makoto Kotake, Tetsuya Kawahara, Naoki Yoneda, Shinsuke Hirota, Hiroshi Azuma, Nobuko Ozasa-Komura, Yoshiaki Ohashi, Masafumi Muratani, Keiji Kimura, Ieharu Hishinuma, Akiyoshi Fukamizu
Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic intestinal inflammatory condition initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Calreticulin (CRT), a calcium-binding chaperone, is known as a partner in the activation of integrin α subunits (ITGAs). The relationship between their interaction and the pathogenesis of IBD is largely unknown. Here we show that a small molecule, orally active ER-464195-01, inhibits the CRT binding to ITGAs, which suppresses the adhesiveness of both T cells and neutrophils...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29772958/arf6-and-rab11-as-intrinsic-regulators-of-axon-regeneration
#15
Bart Nieuwenhuis, Richard Eva
Adult central nervous system (CNS) axons do not regenerate after injury because of extrinsic inhibitory factors, and a low intrinsic capacity for axon growth. Developing CNS neurons have a better regenerative ability, but lose this with maturity. This mini-review summarises recent findings which suggest one reason for regenerative failure is the selective distribution of growth machinery away from axons as CNS neurons mature. These studies demonstrate roles for the small GTPases ARF6 and Rab11 as intrinsic regulators of polarised transport and axon regeneration...
May 17, 2018: Small GTPases
https://www.readbyqxmd.com/read/29772738/angiogenesis-pet-tracer-uptake-68-ga-nodaga-e-crgdyk-%C3%A2-in-induced-myocardial-infarction-and-stromal-cell-treatment-in-minipigs
#16
Thomas Rasmussen, Bjarke Follin, Jens Kastrup, Malene Brandt-Larsen, Jacob Madsen, Thomas Emil Christensen, Morten Juhl, Smadar Cohen, Karsten Pharao Hammelev, Christian Holdflod Møller, Jens Peter Goetze, Philip Hasbak, Andreas Kjær
Angiogenesis is considered integral to the reparative process after ischemic injury. The αv β₃ integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. 68 Ga-NODAGA-E[(cRGDyK)]₂ (RGD) is a positron-emission-tomography (PET) ligand targeted towards αv β₃ integrin. The aim was to present data for the uptake of RGD and correlate it with histology and to further illustrate the differences in angiogenesis due to porcine adipose-derived mesenchymal stromal cell (pASC) or saline treatment in minipigs after induction of myocardial infarction (MI)...
May 16, 2018: Diagnostics
https://www.readbyqxmd.com/read/29772438/itgbl1-promotes-migration-invasion-and-predicts-a-poor-prognosis-in-colorectal-cancer
#17
Xiao Qiu, Jue-Rong Feng, Jun Qiu, Lan Liu, Yang Xie, Yu-Peng Zhang, Jing Liu, Qiu Zhao
Colorectal cancer (CRC) is one of the most common malignancies worldwide; its progression and prognosis are associated with oncogenes. The present study aimed to identify differentially expressed genes (DEGs) and explore the role and potential mechanism of integrin subunit β like 1 (ITGBL1) in CRC. The microarray dataset GSE41258 was used to screen DEGs involved in CRC. Survival analysis was performed to predict the prognosis of CRC patients. To validate ITGBL1 expression, immunohistochemistry, quantitative real-time PCR and western blotting were performed in CRC tissues and cells...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29771991/progenitor-renin-lineage-cells-are-not-involved-in-the-regeneration-of-glomerular-endothelial-cells-during-experimental-renal-thrombotic-microangiopathy
#18
Leo Ruhnke, Jan Sradnick, Moath Al-Mekhlafi, Michael Gerlach, Florian Gembardt, Bernd Hohenstein, Vladimir T Todorov, Christian Hugo
Endothelial cells (EC) frequently undergo primary or secondary injury during kidney disease such as thrombotic microangiopathy or glomerulonephritis. Renin Lineage Cells (RLCs) serve as a progenitor cell niche after glomerular damage in the adult kidney. However, it is not clear whether RLCs also contribute to endothelial replenishment in the glomerulus following endothelial injury. Therefore, we investigated the role of RLCs as a potential progenitor niche for glomerular endothelial regeneration. We used an inducible tet-on triple-transgenic reporter strain mRen-rtTAm2/LC1/LacZ to pulse-label the renin-producing RLCs in adult mice...
2018: PloS One
https://www.readbyqxmd.com/read/29771500/rational-design-of-cancer-targeted-selenadiazole-derivative-as-efficient-radiosensitizer-for-precise-cancer-therapy
#19
Delong Zeng, Shulin Deng, Chengcheng Sang, Jianfu Zhao Zhao, Tianfeng Chen
Chemical drug design based on the biochemical characteristics of cancer cells has become an important strategy for discovery of targeted therapies for personalized cancer medicine. Herein, cancer targeting RGD peptide has been covalently conjugated to selenadiazole derivative (RGD-SeD) to improve its cancer selectivity. The RGD decoration significantly enhances the anticancer efficacy of RGD-SeD in αVβ3 integrin-overexpressing HepG2 liver cancer cells, but not in normal liver cells. Cellular uptake assay and fluorescent imaging confirmed the selectivity of RGD-SeD to integrin overexpressing cancer cells...
May 17, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29769839/a-novel-association-of-polymorphism-in-the-itga4-gene-encoding-the-vla-4-%C3%AE-4-subunit-with-increased-risk-of-alzheimer-s-disease
#20
Vladimira Durmanova, Zuzana Parnicka, Juraj Javor, Gabriel Minarik, Lubomir Vrazda, Barbora Vaseckova, Karin Gmitterova, Maria Kralova, Jan Pecenak, Peter Filipcik, Ivana Shawkatova
Alzheimer's disease (AD) is the most prevalent cause of dementia in elderly people worldwide. Many studies support the hypothesis that the inflammation of the CNS contributes to the neurodegeneration and disease progression. The integrin molecule α 4 β 1, also known as very late antigen 4 (VLA-4), belongs to adhesion molecules that activate the inflammatory process through the migration of immune cells into the CNS. Therefore, the objective of our study was to analyze the association between two polymorphisms located in the ITGA4 gene encoding the α 4 subunit of VLA-4 and the risk of AD...
2018: Mediators of Inflammation
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