keyword
MENU ▼
Read by QxMD icon Read
search

gamma secretase

keyword
https://www.readbyqxmd.com/read/29138057/hidradenitis-suppurativa-like-lesions-associated-with-pharmacologic-inhibition-of-gamma-secretase
#1
Geraldine O'Sullivan Coyne, Therese S Woodring, Chyi-Chia R Lee, Alice P Chen, Heidi H Kong
No abstract text is available yet for this article.
November 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29104587/notch-and-its-oncogenic-activity-in-human-malignancies
#2
REVIEW
Marlena Brzozowa-Zasada, Adam Piecuch, Marek Michalski, Oliwia Segiet, Józef Kurek, Marzena Harabin-Słowińska, Romuald Wojnicz
Background: Increasing evidence has demonstrated that Notch signaling is deregulated in human hematological malignancies and solid tumors. This signaling has a protumorigenic effect but may also act as a tumor suppressor. How induction of a single pathway gives rise to the opposite effects in different cell types is still unknown. Methods: This review article includes available data from peer-reviewed publications associated with the role of Notch signaling during cancer pathogenesis...
2017: European Surgery: ACA: Acta Chirurgica Austriaca
https://www.readbyqxmd.com/read/29045054/variants-regulating-zbtb4-are-associated-with-age-at-onset-of-alzheimer-s-disease
#3
Elizabeth E Blue, Chang-En Yu, Timothy A Thornton, Nicola H Chapman, Eric Kernfeld, Nan Jiang, Kathryn M Shively, Kati J Buckingham, Colby T Marvin, Michael J Bamshad, Thomas D Bird, Ellen M Wijsman
The identification of novel genetic modifiers of age-at-onset of Alzheimer's disease could advance our understanding of AD and provide novel therapeutic targets. A previous genome scan for modifiers of age-at-onset among families affected by early-onset Alzheimer's disease caused by the PSEN2 N141I variant identified two loci with significant evidence for linkage: 1q23.3 and 17p13.2. Here, we describe the fine-mapping of these two linkage regions, and test for replication in six independent data sets. By fine-mapping these linkage signals in a single large family, we reduced the linkage regions to 11% their original size and nominated 54 candidate variants...
October 16, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/29027990/il6-blockade-potentiates-the-anti-tumor-effects-of-%C3%AE-secretase-inhibitors-in-notch3-expressing-breast-cancer
#4
Dong Wang, Jiahui Xu, Bingjie Liu, Xueyan He, Lei Zhou, Xin Hu, Feng Qiao, Anli Zhang, Xiaojun Xu, Huafeng Zhang, Max S Wicha, Lixing Zhang, Zhi-Ming Shao, Suling Liu
Notch pathways have important roles in carcinogenesis including pathways involving the Notch1 and Notch2 oncogenes. Pan-Notch inhibitors, such as gamma secretase inhibitors (GSIs), have been used in the clinical trials, but the outcomes of these trials have been insufficient and have yielded unclear. In the present study, we demonstrated that GSIs, such as MK-0752 and RO4929097, inhibit breast tumor growth, but increase the breast cancer stem cell (BCSC) population in Notch3-expressing breast cancer cells, in a process that is coupled with IL6 induction and is blocked by the IL6R antagonist Tocilizumab (TCZ)...
October 13, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28978720/gamma-secretase-inhibition-by-bms-906024-enhances-efficacy-of-paclitaxel-in-lung-adenocarcinoma
#5
Katherine M Morgan, Bruce S Fischer, Francis Y Lee, Jamie J Shah, Joseph R Bertino, Jeffrey Rosenfeld, Amartya Singh, Hossein Khiabanian, Sharon R Pine
Notch signaling is aberrantly activated in approximately one third of non-small cell lung cancers (NSCLC). We characterized the interaction between BMS-906024, a clinically relevant Notch gamma secretase inhibitor (GSI), and front-line chemotherapy in preclinical models of NSCLC. Chemosensitivity assays were performed on 14 human NSCLC cell lines. There was significantly greater synergy between BMS-906024 and paclitaxel than BMS-906024 and cisplatin (mean CI value = 0.54 and 0.85, respectively, P = 0.01). On an extended panel of 31 NSCLC cell lines, 25 of which were adenocarcinoma, the synergy between BMS-906024 and paclitaxel was significantly greater in KRAS- and BRAF-wildtype than KRAS- or BRAF-mutant cells (mean CI = 0...
October 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28971991/targeted-gamma-secretase-inhibition-of-notch-signaling-activation-in-acute-renal-injury
#6
Jean-Christophe Wyss, Rajesh Kumar, Josip Mikulic, Manfred Schneider, Johannes D Aebi, Lucienne Juillerat-Jeanneret, Dela Golshayan
The Notch pathway has been reported to control tissue damage in acute kidney diseases. To investigate potential beneficial nephroprotective effects of targeting Notch, we developed chemically functionalized γ-secretase inhibitors (GSIs) targeting γ-glutamyltranspeptidase (γ-GT) and/or γ-glutamylcyclotransfase (γ-GCT), two enzymes overexpressed in the injured kidney, and evaluated them in in vivo murine models of acute tubular and glomerular damage. Exposure of the animals to disease-inducing drugs together with the functionalized GSIs improved proteinuria and, to some extent, kidney dysfunction...
September 27, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28955143/new-drug-research-and-development-for-alzheimer-s-pathology-present-and-prospect
#7
Tao Wang
Cholinesterase inhibitors and N-methyl-D-aspartic receptor antagonists are currently the main treatments for Alzheimer's disease (AD), targeting the clinical symptoms of AD. β-amyloid (Aβ) deposition and the highly-phosphorylated Tau protein-induced neurofibrillary tangles are some of the common pathological features of AD. In the past 20 years, many new drugs that focus on the pathogenesis of Alzheimer's disease have been assessed in clinical trials. Drugs such as β-amyloid monoclonal antibody and gamma-secretase inhibitor target the Aβ pathological pathway...
August 25, 2017: Shanghai Archives of Psychiatry
https://www.readbyqxmd.com/read/28947978/notch1-activates-the-wnt-%C3%AE-catenin-signaling-pathway-in-colon-cancer
#8
Hideyuki Ishiguro, Tomotaka Okubo, Yoshiyuki Kuwabara, Masahiro Kimura, Akira Mitsui, Nobuyoshi Sugito, Ryo Ogawa, Takeyasu Katada, Tatsuya Tanaka, Midori Shiozaki, Koji Mizoguchi, Yosuke Samoto, Yoichi Matsuo, Hiroki Takahashi, Shuji Takiguchi
PURPOSE AND METHODS: The translocation of β-catenin/CTNNB1 to the nucleus activates Wnt signaling and cell proliferation; however, the precise mechanism underlying this phenomenon remains unknown. Previous reports have provided evidence that NOTCH1 is involved in the Wnt signaling pathway. Therefore, we sought to determine the mechanism by which NOTCH1 influences the Wnt/β-catenin pathway. We constructed a vector expressing the NOTCH1 intracellular domain (NICD1) and transfected the vector into HCT116 which has low expression of NICD1...
September 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28930532/neuroprotective-role-of-asiatic-acid-in-aluminium-chloride-induced-rat-model-of-alzheimer-s-disease
#9
Mashoque Ahmad Rather, Arokiasamy Justin Thenmozhi, Thamilarasan Manivasagam, Mathiyazahan Dhivya Bharathi, Musthafa Mohamed Essa, Gilles J Guillemin
Alzheimer's disease (AD) is the most common form of dementia, characterized by memory loss, cognitive impairment and personality disorders accompanied by diffuse structural abnormalities in the brain of elderly people. The current investigation explored the neuroprotective potential of asiatic acid (AA), a natural triterpene of Centella asiatica on aluminium chloride (AlCl3) induced rat model of AD. Oral administration of AlCl3 (100 mg/kg b.w.) for 42 days significantly elevated the levels of Al, activity of acetyl cholinesterase and expressions of amyloid precursor protein, amyloid beta1-42, beta and gamma secretases, glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, interleukins -1β, 6, 4, 2, tumor necrosis factor alpha, inducible nitric oxide synthase, nuclear factor- k beta and cyclooxygenase-2 in the hippocampus and cortex  compared to the control group...
January 1, 2018: Frontiers in Bioscience (Scholar Edition)
https://www.readbyqxmd.com/read/28922471/a-phenotype-combining-hidradenitis-suppurativa-with-dowling-degos-disease-caused-by-a-founder-mutation-in-psenen
#10
M Pavlovsky, O Sarig, M Eskin-Schwartz, N Malchin, R Bochner, J Mohamad, A Gat, A Peled, A Hafner, E Sprecher
Dowling-Degos disease, featuring reticulate pigmentation, and familial hidradenitis suppurativa share many clinical features including autosomal dominant inheritance, flexural location and follicular defects. The co-existence of the two disorders was recently found to result from mutations in PSENEN, encoding protein presenilin enhancer gamma-secretase subunit. Here we report 4 additional families of Jewish Ashkenazi origin who presented with clinical features characteristic of both disorders. All patients were found to carry the same, heterozygous mutation in PSENEN (c...
September 18, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28920078/notch1-activation-depletes-the-pool-of-side-population-stem-cells-in-atl
#11
Xue Tao Bai, Chien-Hung Yeh, Christophe Nicot
BACKGROUND: HTLV-I infection is associated with the development of adult T-cell leukemia (ATL), a malignancy characterized by a high rate of disease relapse and poor survival. Previous studies reported the existence of side population (SP) cells in HTLV-I Tax transgenic mouse models. These studies showed that these ATL-like derived SP cells have both self-renewal and leukemia renewal capacity and represent Cancer Stem Cells (CSC)/Leukemia-Initiating Cells (LIC). Since CSC/LIC are resistant to conventional therapies, a better characterization is needed...
June 2017: Journal of Cancer Sciences
https://www.readbyqxmd.com/read/28919280/soluble-gamma-secretase-modulators-attenuate-alzheimer-s-%C3%AE-amyloid-pathology-and-induce-conformational-changes-in-presenilin-1
#12
Frank Raven, Joseph F Ward, Katarzyna M Zoltowska, Yu Wan, Enjana Bylykbashi, Sean J Miller, Xunuo Shen, Se Hoon Choi, Kevin D Rynearson, Oksana Berezovska, Steven L Wagner, Rudolph E Tanzi, Can Zhang
A central pathogenic event of Alzheimer's disease (AD) is the accumulation of the Aβ42 peptide, which is generated from amyloid-β precursor protein (APP) via cleavages by β- and γ-secretase. We have developed a class of soluble 2-aminothiazole γ-secretase modulators (SGSMs) that preferentially decreases Aβ42 levels. However, the effects of SGSMs in AD animals and cells expressing familial AD mutations, as well as the mechanism of γ-secretase modulation remain largely unknown. Here, a representative of this SGSM scaffold, SGSM-36, was investigated using animals and cells expressing FAD mutations...
October 2017: EBioMedicine
https://www.readbyqxmd.com/read/28904208/genome-wide-screen-of-gamma-secretase-mediated-intramembrane-cleavage-of-receptor-tyrosine-kinases
#13
Johannes A M Merilahti, Veera K Ojala, Anna M Knittle, Arto T Pulliainen, Klaus Elenius
Receptor tyrosine kinases (RTKs) have been demonstrated to signal via regulated intramembrane proteolysis, in which ectodomain shedding and subsequent intramembrane cleavage by gamma-secretase leads to release of a soluble intracellular receptor fragment with functional activity. For most RTKs, however, it is unknown whether they can exploit this new signaling mechanism. Here we used a system-wide screen to address the frequency of susceptibility to gamma-secretase cleavage among human RTKs. The screen covering 45 of the 55 human RTKs identified 12 new as well as all nine previously published gamma-secretase substrates...
November 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28887726/long-term-follow-up-of-desmoid-fibromatosis-treated-with-pf-03084014-an-oral-gamma-secretase-inhibitor
#14
Victor Manuel Villalobos, Francis Hall, Antonio Jimeno, Lia Gore, Kenneth Kern, Rossano Cesari, Bo Huang, Jeffrey T Schowinsky, Patrick Judson Blatchford, Brianna Hoffner, Anthony Elias, Wells Messersmith
BACKGROUND: Desmoid fibromatosis is a fibroblastic neoplasm driven by aberrations within the WNT pathway, exhibiting mutations in β-catenin or APC. We review the long-term follow-up of patients in a phase I study treated with an oral gamma secretase inhibitor, PF-03084014. METHODS: PF-03084014 was administered orally at doses ranging from 20 to 330 mg twice daily. Tumor assessments were performed using computed tomography/magnetic resonance imaging (CT/MRI) within 4 weeks of study entry, and every other cycle through cycle 9...
September 8, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28842505/the-glycosyltransferase-gnt-iii-activates-notch-signaling-and-drives-stem-cell-expansion-to-promote-the-growth-and-invasion-of-ovarian-cancer
#15
Heba Allam, Blake P Johnson, Mao Zhang, Zhongpeng Lu, Martin J Cannon, Karen L Abbott
Glycosylation changes associated with cellular transformation can facilitate the growth and progression of tumors. Previously we discovered that the gene Mgat3 encoding the glycosyltransferase GnT-III is elevated in epithelial ovarian carcinomas (EOCs) and leads to the production of abnormal truncated N-linked glycan structures instead of the typical bisected forms. In this study, we are interested in discovering how these abnormal glycans impact the growth and progression of ovarian cancer. We have discovered using stable shRNA gene suppression that GnT-III expression controls the expansion of side-population cells, also known as cancer stem cells...
September 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28829038/dual-control-of-pcdh8l-pcns-expression-and-function-in-xenopus-laevis-neural-crest-cells-by-adam13-33-via-the-transcription-factors-tfap2%C3%AE-and-arid3a
#16
Vikram Khedgikar, Genevieve Abbruzzese, Ketan Mathavan, Hannah Szydlo, Helene Cousin, Dominique Alfandari
Adam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pcdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migration. In addition, the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates multiple genes. Here, we show that adam13 interacts with the arid3a/dril1/Bright transcription factor...
August 22, 2017: ELife
https://www.readbyqxmd.com/read/28790170/dimerization-of-the-transmembrane-domain-of-amyloid-precursor-protein-is-determined-by-residues-around-the-%C3%AE-secretase-cleavage-sites
#17
Yan Yan, Ting-Hai Xu, Kaleeckal G Harikumar, Laurence J Miller, Karsten Melcher, H Eric Xu
One of the hallmarks of Alzheimer's disease is the formation of extracellular amyloid plaques that consist mainly of abnormally aggregated forms of amyloid β (Aβ) peptides. These peptides are generated by γ-secretase-catalyzed cleavage of a dimeric membrane-bound C-terminal fragment (C99) of the amyloid precursor protein. Although C99 homodimerization has been linked to Aβ production and changes in the aggregation-determining Aβ42/Aβ40 ratio, the motif through which C99 dimerizes has remained controversial...
September 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28769027/synergistic-effect-of-notch-3-specific-inhibition-and-paclitaxel-in-non-small-cell-lung-cancer-nsclc-cells-via-activation-of-the-intrinsic-apoptosis-pathway
#18
Fenglian He, Ting Du, Qian Jiang, Yanbei Zhang
BACKGROUND Lung cancers are resistant to conventional chemotherapeutic interventions such as paclitaxel. Notch signaling is crucial in the chemoresistance of lung cancer cells. The Notch inhibitor gamma-secretase inhibitor (GSI) inhibits the Notch signaling pathway. MATERIAL AND METHODS Here, we evaluated how Notch-3 inhibition by GSI can enhance the sensitivity of lung cancer cells to paclitaxel. To study how Notch-3-specific inhibition affects non-small cell lung cancer (NSCLC), we compared the cell viability, apoptosis, and colony formation of A549 and H1299 cells treated with Notch-3 siRNA and GSI...
August 3, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
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
#19
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/28736522/gliotoxin-targets-nuclear-notch2-in-human-solid-tumor-derived-cell-lines-in-vitro-and-inhibits-melanoma-growth-in-xenograft-mouse-model
#20
Rainer Hubmann, Wolfgang Sieghart, Susanne Schnabl, Mohammad Araghi, Martin Hilgarth, Marlies Reiter, Dita Demirtas, Peter Valent, Christoph Zielinski, Ulrich Jäger, Medhat Shehata
Deregulation of NOTCH2 signaling is implicated in a wide variety of human neoplasias. The current concept of targeting NOTCH is based on using gamma secretase inhibitors (GSI) to regulate the release of the active NOTCH intracellular domain. However, the clinical outcome of GSI remains unsatisfactory. Therefore we analyzed human solid tumor derived cell lines for their nuclear NOTCH activity and evaluated the therapeutic potential of the NOTCH2 transactivation inhibitor gliotoxin in comparison to the representative GSI DAPT...
2017: Frontiers in Pharmacology
keyword
keyword
32510
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"