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https://www.readbyqxmd.com/read/29146887/targeted-therapy-of-gastroenteropancreatic-neuroendocrine-tumours-preclinical-strategies-and-future-targets
#1
Elke Tatjana Aristizabal Prada, Christoph J Auernhammer
Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mTOR-inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression free survival due to tumor resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP-system are needed. This paper reviews preclinical research models and signaling pathways in NETs of the GEP-system...
November 16, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29110583/beta-mangostin-from-cratoxylum-arborescens-activates-the-intrinsic-apoptosis-pathway-through-reactive-oxygen-species-with-downregulation-of-the-hsp70-gene-in-the-hl60-cells-associated-with-a-g0-g1-cell-cycle-arrest
#2
Fatima Abdelmutaal Ahmed Omer, Najihah Binti Mohd Hashim, Mohamed Yousif Ibrahim, Firouzeh Dehghan, Maizatulakmal Yahayu, Hamed Karimian, Landa Zeenelabdin Ali Salim, Syam Mohan
Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of β-mangostin on the HL60 cell line...
November 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29106686/the-identification-of-pivotal-transcriptional-factors-mediating-cell-responses-to-drugs-with-drug-induced-liver-injury-liabilities
#3
Falgun Shah, Alex Medvedev, Anne Mai Wassermann, Marian Brodney, Liying Zhang, Sergei Makarov, Robert V Stanton
Drug-induced liver injury (DILI) is a leading cause of drug attrition during drug development and a common reason for drug withdrawal from the market. The poor predictability of conventional animal-based approaches (Olson et al. 2000) necessitates the development of alternative testing approaches. Body of evidence associates DILI with the induction of stress-response genes in the liver cells (Yuan and Kaplowitz 2013). Here, we set out to identify signal transduction pathways predominantly involved in the regulation of gene transcription by DILI drugs...
November 2, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29063982/role-of-beta-adrenergic-receptors-and-sirtuin-signaling-in-the-heart-during-aging-heart-failure-and-adaptation-to-stress
#4
REVIEW
Regina Celia Spadari, Claudia Cavadas, Ana Elisa T Saturi de Carvalho, Daniela Ortolani, Andre Luiz de Moura, Paula Frizera Vassalo
In the heart, catecholamine effects occur by activation of beta-adrenergic receptors (β-ARs), mainly the beta 1 (β1-AR) and beta 2 (β2-AR) subtypes, both of which couple to the Gs protein that activates the adenylyl cyclase signaling pathway. The β2-ARs can also couple to the Gi protein that counterbalances the effect of the Gs protein on cyclic adenosine monophosphate production and activates the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway. In several cardiovascular disorders, including heart failure, as well as in aging and in animal models of environmental stress, a reduction in the β1/β2-AR ratio and activation of the β2-AR-Gi-PI3K-Akt signaling pathway have been observed...
October 24, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29044182/long-term-intake-of-pasta-containing-barley-1-3-beta-d-glucan-increases-neovascularization-mediated-cardioprotection-through-endothelial-upregulation-of-vascular-endothelial-growth-factor-and-parkin
#5
Valentina Casieri, Marco Matteucci, Claudia Cavallini, Milena Torti, Michele Torelli, Vincenzo Lionetti
Barley (1-3)β-D-Glucan (BBG) enhances angiogenesis. Since pasta is very effective in providing a BBG-enriched diet, we hypothesized that the intake of pasta containing 3% BBG (P-BBG) induces neovascularization-mediated cardioprotection. Healthy adult male C57BL/6 mice fed P-BBG (n = 15) or wheat pasta (Control, n = 15) for five-weeks showed normal glucose tolerance and cardiac function. With a food intake similar to the Control, P-BBG mice showed a 109% survival rate (P < 0.01 vs. Control) after cardiac ischemia (30 min)/reperfusion (60 min) injury...
October 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28962864/blocking-sirt1-inhibits-cell-proliferation-and-promotes-aging-through-the-pi3k-akt-pathway
#6
Hongyan Li, Rong Wang
AIMS: Alzheimer's disease (AD) is the most prevalent age-related disease and the most common cause of dementia in the elderly. Its hallmark neuropathological features are the presence of amyloid-beta oligomers and neurofibrillary tangles that are composed of hyperphosphorylated tau protein. SIRT1 has been shown to have a neuroprotective effect; however, its working mechanisms are not well understood. This study aimed to address this issue. MAIN METHODS: We used an in vitro neuronal SH-SY5Y cell culture model to investigate the effect of SIRT1 knockdown on cell survival, proliferation, functionality, and cytotoxicity...
December 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28929344/glucosidase-ii-beta-subunit-gluii%C3%AE-plays-a-role-in-autophagy-and-apoptosis-regulation-in-lung-carcinoma-cells-in-a-p53-dependent-manner
#7
Worapong Khaodee, Nichanan Inboot, Suruk Udomsom, Warunee Kumsaiyai, Ratchada Cressey
PURPOSE: Glucosidase II plays a major role in regulating the post-translational modification of N-linked glycoproteins. Previously, we found that the beta subunit of glucosidase II (GluIIβ) levels are significantly increased in lung carcinoma tissues, indicating a potential role in lung tumorigenesis. Here, we investigated the role of GluIIβ in the regulation of autophagy and apoptosis in lung carcinoma- and immortalized human bronchial epithelial-derived cells. METHODS: A selective glucosidase II inhibitor, bromoconduritol, was used to inhibit GluII enzyme activity and a siRNA-based technology was used to suppress the expression of the GluIIβ encoding gene PRKCSH in lung carcinoma cells differing in p53 status...
September 19, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28913356/expression-profiling-of-cellular-microrna-in-asymptomatic-hbsag-carriers-and-chronic-hepatitis-b-patients
#8
Xianliang Hou, Yan Liang, Jianing Chen, Yingfeng Wei, Ping Zeng, Lin Wang, Chong Lu, Hongyan Diao
BACKGROUND: MicroRNAs (miRNAs) may serve as potential molecular markers to predict liver injury resulting from chronic hepatitis B (CHB). In the present study, we want to study the expression profile and clinical significance of miRNAs at different stages of CHB virus infection. METHODS: Using miRNA microarray, we investigated the global expression profiles of cellular miRNA in asymptomatic hepatitis B antigen carriers (ASCs) and CHB patients, compared with healthy controls (HCs)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28889351/multidimensional-phenotyping-of-breast-cancer-cell-lines-to-guide-preclinical-research
#9
Jodi M Saunus, Chanel E Smart, Jamie R Kutasovic, Rebecca L Johnston, Priyakshi Kalita-de Croft, Mariska Miranda, Esdy N Rozali, Ana Cristina Vargas, Lynne E Reid, Eva Lorsy, Sibylle Cocciardi, Tatjana Seidens, Amy E McCart Reed, Andrew J Dalley, Leesa F Wockner, Julie Johnson, Debina Sarkar, Marjan E Askarian-Amiri, Peter T Simpson, Kum Kum Khanna, Georgia Chenevix-Trench, Fares Al-Ejeh, Sunil R Lakhani
PURPOSE: Cell lines are extremely useful tools in breast cancer research. Their key benefits include a high degree of control over experimental variables and reproducibility. However, the advantages must be balanced against the limitations of modelling such a complex disease in vitro. Informed selection of cell line(s) for a given experiment now requires essential knowledge about molecular and phenotypic context in the culture dish. METHODS: We performed multidimensional profiling of 36 widely used breast cancer cell lines that were cultured under standardised conditions...
September 9, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28878400/thiamine-antagonists-trigger-p53-dependent-apoptosis-in-differentiated-sh-sy5y-cells
#10
Sergiy Chornyy, Yulia Parkhomenko, Nataliya Chorna
Accumulating evidences suggest that p53 is a key coordinator of cellular events triggered by oxidative stress often associated with the impairment in thiamine metabolism and its functions. However, there are limited data regarding the pursuant feedback between p53 transactivation and thiamine homeostasis. Impairment in thiamine metabolism can be induced experimentally via interference with the thiamine uptake and/or inhibition of the thiamin pyrophosphate-dependent enzymes using thiamine antagonists - amprolium (AM), oxythiamine (OT) or pyrithiamine (PT)...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28877067/diagnostic-and-prognostic-biomarkers-of-adrenal-cortical-carcinoma
#11
Ozgur Mete, Hasan Gucer, Mehmet Kefeli, Sylvia L Asa
The diagnosis of low-grade adrenal cortical carcinoma (ACC) confined to the adrenal gland can be challenging. Although there are diagnostic and prognostic molecular tests for ACC, they remain largely unutilized. We examined the diagnostic and prognostic value of altered reticulin framework and the immunoprofile of biomarkers including IGF-2, proteins involved in cell proliferation and mitotic spindle regulation (Ki67, p53, BUB1B, HURP, NEK2), DNA damage repair (PBK, γ-H2AX), telomere regulation (DAX, ATRX), wnt-signaling pathway (beta-catenin) and PI3K signaling pathway (PTEN, phospho-mTOR) in a tissue microarray of 50 adenomas and 43 carcinomas that were characterized for angioinvasion as defined by strict criteria, Weiss score, and mitotic rate-based tumor grade...
September 4, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28806777/a-synthetic-sickness-screen-for-senescence-re-engagement-targets-in-mutant-cancer-backgrounds
#12
Claire J Cairney, Lauren S Godwin, Alan E Bilsland, Sharon Burns, Katrina H Stevenson, Lynn McGarry, John Revie, Jon D Moore, Ceri M Wiggins, Rebecca S Collinson, Clare Mudd, Elpida Tsonou, Mahito Sadaie, Dorothy C Bennett, Masashi Narita, Christopher J Torrance, W Nicol Keith
Senescence is a universal barrier to immortalisation and tumorigenesis. As such, interest in the use of senescence-induction in a therapeutic context has been gaining momentum in the past few years; however, senescence and immortalisation remain underserved areas for drug discovery owing to a lack of robust senescence inducing agents and an incomplete understanding of the signalling events underlying this complex process. In order to address this issue we undertook a large-scale morphological siRNA screen for inducers of senescence phenotypes in the human melanoma cell line A375P...
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28771191/somatic-host-cell-alterations-in-hpv-carcinogenesis
#13
REVIEW
Tamara R Litwin, Megan A Clarke, Michael Dean, Nicolas Wentzensen
High-risk human papilloma virus (HPV) infections cause cancers in different organ sites, most commonly cervical and head and neck cancers. While carcinogenesis is initiated by two viral oncoproteins, E6 and E7, increasing evidence shows the importance of specific somatic events in host cells for malignant transformation. HPV-driven cancers share characteristic somatic changes, including apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC)-driven mutations and genomic instability leading to copy number variations and large chromosomal rearrangements...
August 3, 2017: Viruses
https://www.readbyqxmd.com/read/28764929/inhibition-of-aurora-kinase-a-induces-necroptosis-in%C3%A2-pancreatic%C3%A2-carcinoma
#14
Yangchun Xie, Shan Zhu, Meizuo Zhong, Manhua Yang, Xiaofan Sun, Jinbao Liu, Guido Kroemer, Michael Lotze, Herbert J Zeh, Rui Kang, Daolin Tang
BACKGROUND & AIMS: Induction of nonapoptotic cell death could be an approach to eliminate apoptosis-resistant tumors. We investigated necroptosis-based therapies in mouse models of pancreatic ductal adenocarcinoma cancer (PDAC). METHODS: We screened 273 commercially available kinase inhibitors for cytotoxicity against a human PDAC cell line (PANC1). We evaluated the ability of the aurora kinase inhibitor CCT137690 to stimulate necroptosis in PDAC cell lines (PANC1, PANC2...
November 2017: Gastroenterology
https://www.readbyqxmd.com/read/28734833/transforming-growth-factor-%C3%AE-promotes-liver-tumorigenesis-in%C3%A2-mice-via-up-regulation-of-snail
#15
Hyuk Moon, Hye-Lim Ju, Sook In Chung, Kyung Joo Cho, Jung Woo Eun, Suk Woo Nam, Kwang-Hyub Han, Diego F Calvisi, Simon Weonsang Ro
BACKGROUND & AIMS: Transforming growth factor beta (TGF-β) suppresses early stages of tumorigenesis, but also contributes to migration and metastasis of cancer cells. A large number of human tumors contain mutations that inactivate its receptors, or downstream proteins such as Smad transcription factors, indicating that the TGF-β signaling pathway prevents tumor growth. We investigated the effects of TGF-β inhibition on liver tumorigenesis in mice. METHODS: C57BL/6 mice received hydrodynamic tail-vein injections of transposons encoding HRAS(G12V) and a short hairpin RNA (shRNA) to down-regulate p53, or those encoding HRAS(G12V) and MYC, or those encoding HRAS(G12V) and TAZ(S89A), to induce liver tumor formation; mice were also given injections of transposons encoding SMAD7 or shRNA against SMAD2, SMAD3, SMAD4, or SNAI1 (Snail), with or without ectopic expression of Snail...
November 2017: Gastroenterology
https://www.readbyqxmd.com/read/28706153/inhibitor-of-growth-protein-4-interacts-with-beclin-1-and-represses-autophagy
#16
Valentina Sica, José Manuel Bravo-San Pedro, Guo Chen, Guillermo Mariño, Sylvie Lachkar, Valentina Izzo, Maria Chiara Maiuri, Mireia Niso-Santano, Guido Kroemer
Beclin 1 (BECN1) is a multifunctional protein that activates the pro-autophagic class III phosphatidylinositol 3-kinase (PIK3C3, best known as VPS34), yet also interacts with multiple negative regulators. Here we report that BECN1 interacts with inhibitor of growth family member 4 (ING4), a tumor suppressor protein that is best known for its capacity to interact with the tumor suppressor protein p53 (TP53) and the acetyltransferase E1A binding protein p300 (EP300). Removal of TP53 or EP300 did not affect the BECN1/ING4 interaction, which however was lost upon culture of cells in autophagy-inducing, nutrient free conditions...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28677541/generation-of-induced-pluripotent-stem-cell-ipsc-line-from-a-36-year-old-charcot-marie-tooth-disease-patient-with-gjb1-mutation-cmtx
#17
Daryeon Son, Phil Jun Kang, Wonjin Yun, Seungkwon You
Charcot-Marie-Tooth disease (CMTX) is inherited neurological disorder caused by gap junction beta 1 gene (GJB1) mutation. We generated induced pluripotent stem cell (iPSC) line from 36-year-old CMTX disease patient by electroporation of skin fibroblasts with episomal vectors encoding OCT4, SOX2, KLF4, L-MYC, LIN28 and shRNA-p53. Established iPSCs expressed various pluripotency markers, had differentiation potential of three germ layers in vitro, had normal karyotype and retained GJB1 mutation. This CMT patient-derived iPSC line could be useful in vitro tool for CMTX research as disease modeling and drug development...
May 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28677373/commitment-of-protein-p53-and-amyloid-beta-peptide-a%C3%AE-in-aging-of-human-cerebellum
#18
Danuta Maślińska, Milena Laure-Kamionowska, Dariusz Szukiewicz, Sławomir Maśliński, Krystyna Księżopolska-Orłowska
Protein p53 is known to induce the cell cycle arrest and apoptosis in response to a variety of cellular distress signals and DNA damage. A recent study has demonstrated that in blood cells of aging subjects, p53 may induce early pathological changes that precede the amyloidogenic cascade. However, it is not clear whether p53 participates in the local deposition of amyloid-beta peptide (Aβ) in the nerve tissue of normal aging subjects. Therefore, in the present study, we analyse the distribution of both (Aβ and p53) proteins in the cerebellum of individuals without any history of dementia or other neurological illness who died suddenly in traffic accidents...
2017: Folia Neuropathologica
https://www.readbyqxmd.com/read/28673316/somatic-loss-of-estrogen-receptor-beta-and-p53-synergize-to-induce-breast-tumorigenesis
#19
Igor Bado, Fotis Nikolos, Gayani Rajapaksa, Wanfu Wu, Jessica Castaneda, Savitri Krishnamurthy, Paul Webb, Jan-Åke Gustafsson, Christoforos Thomas
BACKGROUND: Upregulation of estrogen receptor beta (ERβ) in breast cancer cells is associated with epithelial maintenance, decreased proliferation and invasion, and a reduction in the expression of the receptor has been observed in invasive breast tumors. However, proof of an association between loss of ERβ and breast carcinogenesis is still missing. METHODS: To study the role of ERβ in breast oncogenesis, we generated mouse conditional mutants with specific inactivation of ERβ and p53 in the mammary gland epithelium...
July 3, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28656629/p53-induced-mir-30e-5p-inhibits-colorectal-cancer-invasion-and-metastasis-by-targeting-itga6-and-itgb1
#20
Sara Laudato, Nitin Patil, Mohammed L Abba, Joerg H Leupold, Axel Benner, Timo Gaiser, Alexander Marx, Heike Allgayer
The tumor suppressor P53 is a critical regulator of normal cellular homeostasis whose function is either distorted or lost in several cancer types including colorectal cancer (CRC). A small group of microRNAs have come to be recognized as essential mediators of P53 function. In a genome-wide systematic approach, we explored miRNAs that are substantially altered by P53 loss and found miR-30e to be the most significantly deregulated miRNA in P53-knockout human CRC cells. We identified miR-30e-5p to be a novel direct transcriptional target of P53 with gain and loss of function experiments revealing miR-30e-5p to be a significant regulator of tumor cell migration, invasion and in vivo metastasis mediated in part by integrins alpha-6 and beta-1 as novel targets...
November 1, 2017: International Journal of Cancer. Journal International du Cancer
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