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https://www.readbyqxmd.com/read/28819788/insulin-like-growth-factor-1-activates-different-catalytic-subunits-p110-of-pi3k-in-a-cell-type-dependent-manner-to-induce-lipogenesis-dependent-epithelial-mesenchymal-transition-through-the-regulation-of-adam10-and-adam17
#1
Ga Bin Park, Daejin Kim
The activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) is critical for the induction of epithelial-mesenchymal transition (EMT) by growth factors, including insulin-like growth factor 1 (IGF-1). The activation of intracellular lipogenesis provides proliferative and survival signals for cancer cells. In this study, we investigated the connection between lipogenesis-related EMT processes and IGF-1-mediated PI3K p110 isoform activation in primary (SW480 cells) and metastatic (SW620) colon carcinoma cells...
August 17, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28815577/emerging-roles-of-rhomboid-like-pseudoproteases-in-inflammatory-and-innate-immune-responses
#2
REVIEW
Wei-Wei Luo, Hong-Bing Shu
Rhomboid-like pseudoproteases are a conserved superfamily of proteins related to rhomboid intramembrane serine proteases that lack key catalytic residues. iRhom2, a member of the rhomboid-like pseudoprotease superfamily, has been reported to regulate the maturation and trafficking of ADAM17, and be associated with inflammatory arthritis. Recent studies demonstrate that iRhom2 is also involved in innate immunity by regulating the trafficking and stability of MITA (also called STING), which is a central adaptor in innate antiviral signalling pathways...
August 17, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28815047/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#3
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28807052/whole-blood-rna-transcript-based-models-can-predict-clinical-response-in-two-large-independent-clinical-studies-of-patients-with-advanced-melanoma-treated-with-the-checkpoint-inhibitor-tremelimumab
#4
Philip Friedlander, Karl Wassmann, Alan M Christenfeld, David Fisher, Chrisann Kyi, John M Kirkwood, Nina Bhardwaj, William K Oh
BACKGROUND: Tremelimumab is an antibody that blocks CTLA-4 and demonstrates clinical efficacy in a subset of advanced melanoma patients. An unmet clinical need exists for blood-based response-predictive gene signatures to facilitate clinically effective and cost-efficient use of such immunotherapeutic interventions. METHODS: Peripheral blood samples were collected in PAXgene® tubes from 210 treatment-naïve melanoma patients receiving tremelimumab in a worldwide, multicenter phase III study (discovery dataset)...
August 15, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28806983/profiling-of-metalloprotease-activities-in-cerebrospinal-fluids-of-patients-with-neoplastic-meningitis
#5
Catharina Conrad, Kristina Dorzweiler, Miles A Miller, Douglas A Lauffenburger, Herwig Strik, Jörg W Bartsch
BACKGROUND: Neoplastic invasion into leptomeninges and subarachnoid space, resulting in neoplastic meningitis (NM) is a fatal complication of advanced solid and hematological neoplasms. Identification of malignant involvement of the cerebrospinal fluid (CSF) early in the disease course has crucial prognostic and therapeutic implications, but remains challenging. As indicators of extracellular matrix (ECM) degradation and breakdown of the blood-brain-barrier, Matrix Metalloproteases (MMPs) and A Disintegrin and Metalloproteases (ADAMs) are potential analytes for cerebral pathophysiology and metastatic dissemination of tumor cells into the CSF...
August 14, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28762604/tmeff2-shedding-is-regulated-by-oxidative-stress-and-mediated-by-adams-and-transmembrane-serine-proteases-implicated-in-prostate-cancer
#6
Katarzyna Gaweł-Bęben, Nazim Ali, Vincent Ellis, Gloria Velasco, Zaruhi Poghosyan, Ann Ager, Vera Knäuper
TMEFF2 is a type I transmembrane protein with two follistatin (FS) and one EGF-like domain over-expressed in prostate cancer, however its biological role in prostate cancer development and progression remains unclear, which may, at least in part, be explained by its proteolytic processing. The extracellular part of TMEFF2 (TMEFF2-ECD) is cleaved by ADAM17 and the membrane-retained fragment is further processed by the gamma-secretase complex. TMEFF2 shedding is increased with cell crowding, a condition associated with the tumour microenvironment, which was mediated by oxidative stress signalling, requiring jun-kinase (JNK) activation...
August 1, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28754469/long-non-coding-rna-ccat1-promotes-metastasis-and-poor-prognosis-in-epithelial-ovarian-cancer
#7
Yuan Cao, Huirong Shi, Fang Ren, Yanyan Jia, Ruitao Zhang
In this study, we reported that long non-coding RNA (lncRNA) CCAT1 was upregulated in epithelial ovarian cancer (EOC) tissues, and was associated with FIGO stage, histological grade, lymph node metastasis and poor survival of EOC patients. Multivariate Cox regression analysis showed that CCAT1 was an independent prognostic indicator. While CCAT1 downregulation inhibited EOC cell epithelial-mesenchymal transition (EMT), migration and invasion, CCAT1 upregulation promoted EOC cell EMT, migration and invasion...
July 25, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28751722/hepatocyte-specific-timp3-expression-prevents-diet-dependent-fatty-liver-disease-and-hepatocellular-carcinoma
#8
Viviana Casagrande, Alessandro Mauriello, Simone Bischetti, Maria Mavilio, Massimo Federici, Rossella Menghini
Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions, ranging from non-progressive bland steatosis to hepatocarcinoma. Tissue inhibitor of metalloproteinase 3 (Timp3) has a role in the pathogenesis of fatty liver disease associated with obesity and is silenced during metabolic disorders and liver cancer. We generated an hepatocyte-specific TIMP3 'gain-of-function' mouse model under the control of the Albumin promoter (AlbT3) and investigated its effects during high-fat diet (HFD)...
July 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28740508/hydrogen-sulfide-inhibits-high-glucose-induced-sflt-1-production-via-decreasing-adam17-expression-in-3t3-l1-adipocytes
#9
Tian-Xiao Hu, Gang Wang, Wei Wu, Lu Gao, Qing-Ying Tan, Jing Wang
Hydrogen sulfide (H2S) has recently been identified as an endogenous gaseous signaling molecule. The aim of the present study was to investigate the effect of H2S on high glucose- (HG-) induced ADAM17 expression and sFlt-1 production in 3T3-L1 adipocytes. Firstly, we found that HG DMEM upregulated the expression of ADAM17 and production of sFlt-1 in 3T3-L1 adipocytes. Knocking down ADAM17 attenuated the effect of high glucose on sFlt-1 production in adipocytes. HG decreased the expression of CSE and 3-MST, as well as the endogenous H2S production...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28733814/neuroprotective-effect-of-ipriflavone-against-scopolamine-induced-memory-impairment-in-rats
#10
Hani S Hafez, Doaa A Ghareeb, Samar R Saleh, Mariam M Abady, Maha A El Demellawy, Hend Hussien, Nihad Abdel-Monem
BACKGROUND: Alzheimer's disease is an age-related neurodegenerative disorder characterized clinically by a progressive loss of memory and cognitive functions resulting in severe dementia. Ipriflavone (IPRI) is a non-hormonal, semi-synthetic isoflavone, clinically used in some countries for the treatment and prevention of postmenopausal osteoporosis. Moreover, ipriflavone is a non-peptidomimetic small molecule AChE inhibitor with an improved bioavailability after systemic administration, due to its efficient blood-brain barrier permeability in comparison with peptidomimetic inhibitors...
July 22, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28705384/the-shedding-protease-adam17-physiology-and-pathophysiology
#11
REVIEW
Friederike Zunke, Stefan Rose-John
The disintegrin metalloprotease ADAM17 has been a matter of intense studies aiming to unravel structure, function and regulation of protease expression, maturation and activity. In this review, we summarize data on the physiological role of ADAM17 in health and disease. Here we provide an overview of ADAM17 substrates, mouse models of ADAM17-deficiencies and discuss recent findings of ADAM17 function in the immune system and central nervous system as well as in cancer. Whereas ADAM17 function in EGF-R-, in Interleukin-6 (IL-6)- and in TNFα-biology has been shown to play a decisive role in regulation of the immune system as well as cancer development, the role of ADAM17 in the central nervous system and neurodegeneration still remains elusive...
July 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28703301/the-xenoestrogens-biphenol-a-and-nonylphenol-differentially-regulate-metalloprotease-mediated-shedding-of-egfr-ligands
#12
Paulina Urriola-Muñoz, Xue Li, Thorsten Maretzky, David R McIlwain, Tak W Mak, Juan G Reyes, Carl P Blobel, Ricardo D Moreno
The xenoestrogens Bisphenol-A (BPA) and Nonylphenol (NP) are endocrine disruptors used in the plastic polymer industry to manufacture different products for human use. Previous studies have suggested a role of these compounds in the shedding of signaling molecules, such as tumor necrosis factor α (TNF- α). The aim of this work was to evaluate the effect of BPA and NP on the sheddase ADAM17 and its newly discovered regulators iRhom1 and iRhom2 in the release of EGFR-ligands. We report that BPA and NP can stimulate the release of the ADAM17-substrates HB-EGF and TGF- α...
July 13, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28675418/the-soluble-interleukin-6-receptor-advanced-therapeutic-options-in-inflammation
#13
Stefan Rose-John
Interleukin (IL)-6 binds to IL-6R and the complex of IL-6 and IL-6R associates with the receptor subunit gp130, which initiates signaling. gp130 is expressed on all cells. IL-6R is cleaved by the ADAM17, generating a soluble IL-6R (sIL-6R). The sIL-6R binds IL-6 and the complex of IL-6 and sIL-6R binds to gp130 even on cells that do not express IL-6R. This process, which has been called IL-6 trans-signaling, increases the spectrum of target cells for IL-6. We generated a protein, sgp130Fc, which inhibits IL-6 trans-signaling without affecting IL-6 classic signaling...
July 4, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28671983/isoflurane-promotes-phagocytosis-of-apoptotic-neutrophils-through-ampk-mediated-adam17-mer-signaling
#14
Xueke Du, Chunling Jiang, Yang Lv, Randal O Dull, You-Yang Zhao, David E Schwartz, Guochang Hu
A patient's recovery from lung inflammatory injury or development of multi-system organ failure is determined by the host's ability to resolve inflammation and repair tissue damage, both of which require the clearance of apoptotic neutrophils by macrophages (efferocytosis). Here, we investigated the effects of isoflurane on macrophage efferocytosis and resolution of lung inflammatory injury. Treatment of murine bone marrow-derived macrophages (BMDMs) or alveolar macrophages with isoflurane dramatically enhanced phagocytosis of apoptotic neutrophils...
2017: PloS One
https://www.readbyqxmd.com/read/28637950/adam17-regulates-tnf-%C3%AE-expression-upon-lipopolysaccharide-stimulation-in-oral-keratinocytes
#15
Aya Hirayama, Shuji Awano, Yuji Seta, Toshihiro Ansai
A disintegrin and metalloprotease 17 (ADAM17) is a tumor necrosis factor (TNF)-converting enzyme and was first identified as the enzyme that cleaves the prodomain of TNF-α, a proinflammatory cytokine that plays a central role in immune regulation and a variety of inflammatory responses in destructive periodontal disease. The aim of the present study was to verify the presence of ADAM17 in the gingival epithelium and elucidate its involvement in the release of TNF-αin oral keratinocytes. Immunohistochemical analyses of ADAM17 were performed in gingival tissues obtained from patients and in human oral keratinocytes (HOKs)...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28631723/pharmacogenetic-biomarkers-of-response-in-crohn-s-disease
#16
REVIEW
T M Linares-Pineda, M Cañadas-Garre, A Sánchez-Pozo, M Á Calleja-Hernández
Crohn's disease (CD) is a chronic condition, which affects the immune system. It can also affect any part of the digestive tract and be associated with external manifestations. The causes of the disease remain unknown, although it seems to be the result of a combination of factors, such as genetic predisposition, environment, lifestyle and the composition of the microbiota, among others. The treatment protocol begins with a change in eating and smoking habits, and is continued with different lines of treatment, including corticosteroids, immunomodulators and biologic therapy (infliximab and adalimumab), which have shown differences in response among patients, especially with biologic treatment...
June 20, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28624437/the-plasma-membrane-penultimate-regulator-of-adam-sheddase-function
#17
REVIEW
Karina Reiss, Sucharit Bhakdi
BACKGROUND: ADAM10 and ADAM17 are the best characterized members of the ADAM (A Disintegrin and Metalloproteinase) - family of transmembrane proteases. Both are involved diverse physiological and pathophysiological processes. ADAMs are known to be regulated by posttranslational mechanisms. However, emerging evidence indicates that the plasma membrane with its unique dynamic properties may additionally play an important role in controlling sheddase function. SCOPE OF REVIEW: Membrane events that could contribute to regulation of ADAM-function are summarized...
June 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28571693/molecular-insights-into-the-multilayered-regulation-of-adam17-the-role-of-the-extracellular-region
#18
REVIEW
Joachim Grötzinger, Inken Lorenzen, Stefan Düsterhöft
In contrast to many other signalling mechanisms shedding of membrane-anchored proteins is an irreversible process. A Disintegrin And Metalloproteinase (ADAM) 17 is one of the major sheddases involved in a variety of physiological and pathophysiological processes including regeneration, differentiation, and cancer progression. Due to its central role in signalling the shedding activity of ADAM17 is tightly regulated, especially on the cell surface, where shedding events take place. The activity of ADAM17 can be subdivided into a catalytic activity and the actual shedding activity...
May 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28570994/targeting-adam17-inhibits-human-colorectal-adenocarcinoma-progression-and-tumor-initiating-cell-frequency
#19
Joseph Dosch, Elizabeth Ziemke, Shanshan Wan, Kathryn Luker, Theodore Welling, Karin Hardiman, Eric Fearon, Suneetha Thomas, Matthew Flynn, Jonathan Rios-Doria, Robert Hollingsworth, Ronald Herbst, Elaine Hurt, Judith Sebolt-Leopold
ADAM17 (a disintegrin and metalloproteinase 17)/TACE (TNFα converting enzyme) has emerged as a potential therapeutic target in colorectal cancer (CRC) and other cancers, due in part to its role in regulating various tumor cell surface proteins and growth factors and cytokines in the tumor microenvironment. The emergence of MEDI3622, a highly potent and specific antibody-based ADAM17 inhibitor, has allowed testing of the concept that targeting ADAM17 may be an important new therapeutic approach for CRC patients...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28554668/anti-tumor-effects-of-a-human-mouse-cross-reactive-anti-adam17-antibody-in-a-pancreatic-cancer-model-in-vivo
#20
Jie Ye, Shun Ming Yuen, Gillian Murphy, Ruiyu Xie, Hang Fai Kwok
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of tumor amongst all human cancers due to late diagnosis and resistant to treatment with chemotherapy and radiation. Preclinical and clinical studies have revealed that ErbB family for example epidermal growth factor receptor (EGFR) is a validated molecular target for pancreatic cancer prevention and therapy. The ErbB signaling cascade is regulated by a member of the ADAM (a disintegrin and metalloprotease) family, namely ADAM17, by enzymatic cleavage of precursor ligands into soluble cytokines and growth factors...
May 26, 2017: European Journal of Pharmaceutical Sciences
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