keyword
MENU ▼
Read by QxMD icon Read
search

gamma secretase

keyword
https://www.readbyqxmd.com/read/28186678/gamma-secretase-inhibitor-ix-gsi-impairs-concomitant-activation-of-notch-and-wnt-beta-catenin-pathways-in-cd44-gastric-cancer-stem-cells
#1
Samarpita Barat, Xi Chen, Khac Cuong Bui, Przemyslaw Bozko, Julian Götze, Matthias Christgen, Till Krech, Nisar P Malek, Ruben R Plentz
Cancer stem cells (CSC) are associated with tumor resistance and are characterized in gastric cancer (GC). Studies have indicated that Notch and wnt-beta-catenin pathways are crucial for CSC development. Using CD44(+) CSCs, we investigated the role of these pathways in GC carcinogenesis. We performed cell proliferation, wound healing, invasion, tumorsphere, and apoptosis assays. Immunoblot analysis of downstream signaling targets of Notch and wnt-beta-catenin were tested after gamma-secretase inhibitor IX (GSI) treatment...
February 3, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28152299/development-of-a-reporter-system-for-in-vivo-monitoring-of-%C3%AE-secretase-activity-in-drosophila
#2
Young Gi Hong, Seyun Roh, Donggi Paik, Sangyun Jeong
The γ-secretase complex represents an evolutionarily conserved family of transmembrane aspartyl proteases that cleave numerous type-I membrane proteins, including the β-amyloid precursor protein (APP) and the receptor Notch. All known rare mutations in APP and the γ-secretase catalytic component, presenilin, which lead to increased amyloid βpeptide production, are responsible for early-onset familial Alzheimer's disease. β-amyloid protein precursor-like (APPL) is the Drosophila ortholog of human APP. Here, we created Notch- and APPL-based Drosophila reporter systems for in vivo monitoring of γ-secretase activity...
January 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28151717/synergistic-drug-combinations-with-a-cdk4-6-inhibitor-in-t-cell-acute-lymphoblastic-leukemia
#3
Yana Pikman, Gabriela Alexe, Giovanni Roti, Amy Saur Conway, Andrew Furman, Emily S Lee, Andrew E Place, Sunkyu Kim, Chitra Saran, Rebecca Modiste, David M Weinstock, Marian Harris, Andrew L Kung, Lewis B Silverman, Kimberly Stegmaier
PURPOSE: While significant progress has been made in the treatment of T-cell acute lymphoblastic leukemia (T-ALL), many patients will require additional therapy for relapsed/refractory disease. Cyclin D3 (CCND3) and CDK6 are highly expressed in T-ALL and have been effectively targeted in mutant NOTCH1-driven mouse models of this disease with a CDK4/6 small-molecule inhibitor. Combination therapy, however, will be needed for the successful treatment of human disease. EXPERIMENTAL DESIGN: We performed preclinical drug testing using a panel of T-ALL cell lines first with LEE011, a CDK4/6 inhibitor, and next with the combination of LEE011 with a panel of drugs relevant to T-ALL treatment...
November 9, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28115371/a-review-of-the-management-of-adults-with-t-cell-acute-lymphoblastic-leukemia
#4
David I Marks, Clare Rowntree
T-cell acute lymphoblastic leukemia (ALL) is a rare disease in adults with inferior survival outcomes compared to those seen in pediatric patients. Although potentially curable with about 50% survival at 5 years, adult patients with relapsed disease have dismal outcomes with less than 10% of patients surviving long term. This review will discuss the diagnosis and management of adult patients with newly diagnosed T-cell ALL with an emphasis on the immunophenotypic and genetic analyses required to assign prognosis, risk stratify and guide post remission therapy...
January 23, 2017: Blood
https://www.readbyqxmd.com/read/28030808/inhibition-of-gamma-secretase-in-notch1-signaling-pathway-as-a-novel-treatment-for-ovarian-cancer
#5
Zhaoyi Feng, Wandong Xu, Chenguang Zhang, Mengran Liu, Hongwu Wen
Epithelial ovarian cancer (EOC) is the leading cause of death for gynecological cancer. Most patients are not diagnosed until the cancer is at an advanced stage with poor prognosis. Notch1 signaling pathway plays an oncogenic role in EOC. There have been few studies on enzymatic activity of γ-secretase and the mechanism of how γ-secretase inhibitor works on cancer cell. Here, we show that Jagged1 and NICD were highly expressed in ovarian carcinoma. The expressions of Notch1, Jagged1 and NICD in Notch1 pathway did not correlate with outcome in ovarian cancer...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28026810/-development-of-blood-brain-barrier-under-the-modulation-of-hif-activity-in-astroglialand-neuronal-cells-in-vitro
#6
V A Ruzaeva, A V Morgun, E D Khilazheva, N V Kuvacheva, E A Pozhilenkova, E B Boitsova, G P Martynova, T E Taranushenko, A B Salmina
Barriergenesis is the process of maturation of the primary vascular network of the brain responsible for the establishment of the blood-brain barrier. It represents a combination of factors that, on the one hand, contribute to the process of migration and tubulogenesis of endothelial cells (angiogenesis), on the other hand, contribute to the formation of new connections between endothelial cells and other elements of the neurovascular unit. Astrocytes play a key role in barriergenesis, however, mechanisms of their action are still poorly examined...
November 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28005987/metabolic-characterization-of-intact-cells-reveals-intracellular-amyloid-beta-but-not-its-precursor-protein-to-reduce-mitochondrial-respiration
#7
Patrick M Schaefer, Bjoern von Einem, Paul Walther, Enrico Calzia, Christine A F von Arnim
One hallmark of Alzheimer´s disease are senile plaques consisting of amyloid beta (Aβ), which derives from the processing of the amyloid precursor protein (APP). Mitochondrial dysfunction has been linked to the pathogenesis of Alzheimer´s disease and both Aβ and APP have been reported to affect mitochondrial function in isolated systems. However, in intact cells, considering a physiological localization of APP and Aβ, it is pending what triggers the mitochondrial defect. Thus, the aim of this study was to dissect the impact of APP versus Aβ in inducing mitochondrial alterations with respect to their subcellular localization...
2016: PloS One
https://www.readbyqxmd.com/read/27999190/leptin-notch-signaling-axis-is-involved-in-pancreatic-cancer-progression
#8
Adriana Harbuzariu, Antonio Rampoldi, Danielle S Daley-Brown, Pierre Candelaria, Tia L Harmon, Crystal C Lipsey, Derrick J Beech, Alexander Quarshie, Gabriela Oprea Ilies, Ruben R Gonzalez-Perez
Pancreatic cancer (PC) shows a high death rate. PC incidence and prognosis are affected by obesity, a pandemic characterized by high levels of leptin. Notch is upregulated by leptin in breast cancer. Thus, leptin and Notch crosstalk could influence PC progression. Here we investigated in PC cell lines (BxPC-3, MiaPaCa-2, Panc-1, AsPC-1), derived tumorspheres and xenografts whether a functional leptin-Notch axis affects PC progression and expansion of pancreatic cancer stem cells (PCSC). PC cells and tumorspheres were treated with leptin and inhibitors of Notch (gamma-secretase inhibitor, DAPT) and leptin (iron oxide nanoparticle-leptin peptide receptor antagonist 2, IONP-LPrA2)...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27909050/notch-pathway-is-activated-via-genetic-and-epigenetic-alterations-and-is-a-therapeutic-target-in-clear-cell-renal-cancer
#9
Tushar D Bhagat, Yiyu Zou, Shizheng Huang, Jihwan Park, Matthew B Palmer, Caroline Hu, Weijuan Li, Niraj Shenoy, Orsolya Giricz, Gaurav Choudhary, Yiting Yu, Yi-An Ko, María C Izquierdo, Ae Seo Deok Park, Nishanth Vallumsetla, Remi Laurence, Robert Lopez, Masako Suzuki, James Pullman, Justin Kaner, Benjamin Gartrell, A Ari Hakimi, John M Greally, Bharvin Patel, Karim Benhadji, Kith Pradhan, Amit Verma, Katalin Susztak
Clear cell renal cell carcinoma (CCRCC) is an incurable malignancy in advanced stages and needs newer therapeutic targets. Transcriptomic analysis of CCRCCs and matched microdissected renal tubular controls revealed overexpression of NOTCH ligands and receptors in tumor tissues. Examination of the TCGA RNA-seq data set also revealed widespread activation of NOTCH pathway in a large cohort of CCRCC samples. Samples with NOTCH pathway activation were also clinically distinct and were associated with better overall survival...
January 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27908834/gamma-secretase-inhibitor-impairs-epithelial-to-mesenchymal-transition-induced-by-tgf-%C3%AE-in-ovarian-tumor-cell-lines
#10
M C Pazos, D Abramovich, A Bechis, P Accialini, F Parborell, M Tesone, G Irusta
Ovarian cancer is characterized by being highly metastatic, a feature that represents the main cause of failure of the treatment. This study investigated the effects of γ-secretase inhibition on the TGF-β-induced epithelial-mesenchymal transition (EMT) process in ovarian cancer cell lines. SKOV3 cells incubated in the presence of TGF-β showed morphological and biochemical changes related to EMT, which were blocked by co-stimulation with TGF-β and the γ-secretase inhibitor DAPT. In SKOV3 and IGROV1 cells, the co-stimulation blocked the cadherin switch and the increase in the transcription factors Snail, Slug, Twist and Zeb1 induced by TGF-β...
January 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27906684/phase-i-study-of-the-gamma-secretase-inhibitor-pf-03084014-in-combination-with-docetaxel-in-patients-with-advanced-triple-negative-breast-cancer
#11
Marzia A Locatelli, Philippe Aftimos, E Claire Dees, Patricia M LoRusso, Mark D Pegram, Ahmad Awada, Bo Huang, Rossano Cesari, Yuqiu Jiang, M Naveed Shaik, Kenneth A Kern, Giuseppe Curigliano
BACKGROUND: The NOTCH signaling pathway may be involved in the survival of stem cell-like tumor-initiating cells and contribute to tumor growth. In this phase Ib, open-label, multicenter study (NCT01876251), we evaluated PF-03084014, a selective gamma-secretase inhibitor in patients with advanced triple-negative breast cancer. METHODS: The dose-finding part was based on a 2×3 matrix design using the modified toxicity probability interval method. Oral PF-03084014 was administered twice daily continuously in combination with intravenous docetaxel given on day 1 of each 21-day cycle...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27852366/-effects-and-mechanisms-of-notch-signaling-pathway-on-immune-imbalance-in-chronic-obstructive-pulmonary-disease
#12
X N Yang, X J Liu, L T Zhao, X L Zeng, H R Bao
Objective: To explore the role of Notch signaling pathway on immune imbalance in chronic obstructive pulmonary disease (COPD). Methods: Thirty BALB/c mice were randomly assigned into the healthy control group, COPD group, and COPD Gamma secretase inhibitors (GSI) group. Cigarette smoke exposure was used to establish the COPD model. T cells were enriched by filtering through nylon wool columns. The proportion of spleen-derived T-lymphocyte subsets was detected by flow cytometry. Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot (WB) were used to detect the expression of splenic T cells' Notch1 and its downstream Hes1 mRNA and protein respectively...
November 12, 2016: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/27807401/alzheimer-disease-crosstalk-between-the-canonical-wnt-beta-catenin-pathway-and-ppars-alpha-and-gamma
#13
REVIEW
Alexandre Vallée, Yves Lecarpentier
The molecular mechanisms underlying the pathophysiology of Alzheimer's disease (AD) are still not fully understood. In AD, Wnt/beta-catenin signaling has been shown to be downregulated while the peroxisome proliferator-activated receptor (PPAR) gamma (mARN and protein) is upregulated. Certain neurodegenerative diseases share the same Wnt/beta-catenin/PPAR gamma profile, such as bipolar disorder and schizophrenia. Conversely, other NDs share an opposite profile, such as amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, multiple sclerosis, and Friedreich's ataxia...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27749937/plexind1-is-a-novel-transcriptional-target-and-effector-of-notch-signaling-in-cancer-cells
#14
Michael Rehman, Sreeharsha Gurrapu, Gabriella Cagnoni, Lorena Capparuccia, Luca Tamagnone
The secreted semaphorin Sema3E controls cell migration and invasiveness in cancer cells. Sema3E-receptor, PlexinD1, is frequently upregulated in melanoma, breast, colon, ovarian and prostate cancers; however, the mechanisms underlying PlexinD1 upregulation and the downstream events elicited in tumor cells are still unclear. Here we show that the canonical RBPjk-dependent Notch signaling cascade controls PlexinD1 expression in primary endothelial and cancer cells. Transcriptional activation was studied by quantitative PCR and promoter activity reporter assays...
2016: PloS One
https://www.readbyqxmd.com/read/27670423/high-selective-pressure-for-notch1-mutations-that-induce-myc-in-t-cell-acute-lymphoblastic-leukemia
#15
Mark Y Chiang, Qing Wang, Anna C Gormley, Sarah J Stein, Lanwei Xu, Olga Shestova, Jon C Aster, Warren S Pear
Activating NOTCH1 mutations are frequent in human T-cell acute lymphoblastic leukemia (T-ALL) and Notch inhibitors (γ-secretase inhibitors [GSIs]) have produced responses in patients with relapsed, refractory disease. However, sustained responses, although reported, are uncommon, suggesting that other pathways can substitute for Notch in T-ALL. To address this possibility, we first generated Kras(G12D) transgenic mice with T-cell-specific expression of the pan-Notch inhibitor, dominant-negative Mastermind (DNMAML)...
November 3, 2016: Blood
https://www.readbyqxmd.com/read/27590851/leptin-induced-transphosphorylation-of-vascular-endothelial-growth-factor-receptor-increases-notch-and-stimulates-endothelial-cell-angiogenic-transformation
#16
Viola Lanier, Corey Gillespie, Merle Leffers, Danielle Daley-Brown, Joy Milner, Crystal Lipsey, Nia Webb, Leonard M Anderson, Gale Newman, Johannes Waltenberger, Ruben Rene Gonzalez-Perez
Leptin increases vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), and Notch expression in cancer cells, and transphosphorylates VEGFR-2 in endothelial cells. However, the mechanisms involved in leptin's actions in endothelial cells are not completely known. Here we investigated whether a leptin-VEGFR-Notch axis is involved in these leptin's actions. To this end, human umbilical vein and porcine aortic endothelial cells (wild type and genetically modified to overexpress VEGFR-1 or -2) were cultured in the absence of VEGF and treated with leptin and inhibitors of Notch (gamma-secretase inhibitors: DAPT and S2188, and silencing RNA), VEGFR (kinase inhibitor: SU5416, and silencing RNA) and leptin receptor, OB-R (pegylated leptin peptide receptor antagonist 2: PEG-LPrA2)...
October 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27582570/the-relevance-of-pten-akt-in-relation-to-notch1-directed-treatment-strategies-in-t-cell-acute-lymphoblastic-leukemia
#17
REVIEW
Rui D Mendes, Kirsten Canté-Barrett, Rob Pieters, Jules P P Meijerink
The tumor suppressor phosphatase and tensin homolog (PTEN) negatively regulates phosphatidylinositol 3-kinase (PI3K)-AKT signaling and is often inactivated by mutations (including deletions) in a variety of cancer types, including T-cell acute lymphoblastic leukemia. Here we review mutation-associated mechanisms that inactivate PTEN together with other molecular mechanisms that activate AKT and contribute to T-cell leukemogenesis. In addition, we discuss how Pten mutations in mouse models affect the efficacy of gamma-secretase inhibitors to block NOTCH1 signaling through activation of AKT...
September 2016: Haematologica
https://www.readbyqxmd.com/read/27570480/gamma-secretase-inhibitor-prevents-proliferation-and-migration-of-ductus-arteriosus-smooth-muscle-cells-through-the-notch3-hes1-2-5-pathway
#18
Jiunn-Ren Wu, Jwu-Lai Yeh, Shu-Fen Liou, Zen-Kong Dai, Bin-Nan Wu, Jong-Hau Hsu
Patent ductus arteriosus (PDA) can cause morbidity and mortality in neonates. Vascular remodeling, characterized by proliferation and migration of smooth muscle cells (SMCs), is an essential process for postnatal DA closure. Notch signaling is an important mediator of vascular remodelling but its role in DA is unkonwn. We investigated the effects and underlying mechanisms of γ-secretase inhibitor DAPT, a Notch signaling inhibitor on angiotensin II (Ang II)-induced proliferation and migration of DASMCs. Proliferation and migration of DASMCs cultured from neonatal Wistar rats were induced by Ang II, with or without DAPT pre-treatment...
2016: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/27567808/changes-in-neuropsychiatric-inventory-associated-with-semagacestat-treatment-of%C3%A2-alzheimer-s-disease
#19
Paul B Rosenberg, Krista L Lanctôt, Nathan Herrmann, Jacobo E Mintzer, Anton P Porsteinsson, Xiaoying Sun, Rema Raman
BACKGROUND: In a recent report, 76 weeks' treatment with a gamma-secretase inhibitor (semagacestat) was associated with poorer cognitive outcomes in Alzheimer's disease (AD). OBJECTIVE: We sought to examine the effect of semagacestat treatment on neuropsychiatric symptoms (NPS). METHODS: 1,537 participants with mild to moderate AD were randomized to 76 weeks' treatment with placebo versus two doses of semagacestat. NPS were assessed with the Neuropsychiatric Inventory (NPI-Total and subdomains)...
August 10, 2016: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27553958/inhibition-of-notch-and-hif-enhances-the-antitumor-effect-of-radiation-in-notch-expressing-lung-cancer
#20
Yasuyuki Ikezawa, Jun Sakakibara-Konishi, Hidenori Mizugaki, Satoshi Oizumi, Masaharu Nishimura
BACKGROUND: The Notch receptor plays an important role in various cell fate decisions during development and in cancer. We have previously reported that Notch3 is upregulated by radiation in non-small cell lung cancer (NSCLC) cell lines and that the Notch pathway inhibitor γ secretase inhibitor GSI (gamma-secretase inhibitor), when combined with radiation therapy, significantly suppressed the growth of lung cancer cells. However, little is known about the mechanism of Notch upregulation induced by radiation...
February 2017: International Journal of Clinical Oncology
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"