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P53 -apoptosis

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https://www.readbyqxmd.com/read/28222492/discovery-of-mieap-regulated-mitochondrial-quality-control-as-a-new-function-of-tumor-suppressor-p53
#1
REVIEW
Yasuyuki Nakamura, Hirofumi Arakawa
The tumor suppressor p53 gene is frequently mutated in human cancers, and the p53 protein suppresses cancer. However, the mechanism behind the p53-mediated tumor suppression is still unclear. Recently, Mieap (the mitochondria-eating protein) was identified as a p53-inducible protein. Mieap induces the accumulation of lysosomal proteins within mitochondria (MALM: Mieap-induced accumulation of lysosome-like organelles within mitochondria) in response to mitochondrial damage, and eliminates the oxidized mitochondrial proteins to repair unhealthy mitochondria...
February 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/28220578/renal-damage-following-alloxan-induced-diabetes-is-associated-with-generation-of-reactive-oxygen-species-alterations-of-p53-tgf-%C3%AE-1-and-extracellular-matrix-metalloproteinases-in-rats
#2
Mohamed A Abdel Aziz, Dalia M Badary, Mahmoud Rezk Abdelwahed Hussein
: Renal damage is a common problem in diabetes. Alloxan , a potent hyperglycemic and diabetogenic molecule, can induce diabetes through oxidative stress-related mechanisms. Here, we hypothesize that "Alloxan-induced renal damage is associated with alterations of p53, TGF-β1 and extracellular matrix metalloproteinases". To test our hypothesis, we established an animal model (male abino rats) and induced diabetes by intraperitoneal injection of Alloxan monohydrate. Rats with fasting blood glucose level ≥ 200 mg/dl were considered diabetic and were sacrificed after 14, 28, and 42 day intervals...
February 21, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28220272/exposure-to-chronic-hyperglycemic-conditions-results-in-ras-related-c3-botulinum-toxin-substrate-1-rac1-mediated-activation-of-p53-and-atm-kinase-in-pancreatic-%C3%AE-cells
#3
Vaibhav Sidarala, Anjaneyulu Kowluru
Chronic hyperglycemia (HG) promotes pancreatic islet dysfunction which leads to the onset of T2DM. This study is aimed at defining regulatory roles of Rac1, a small G-protein, in the activation of p53 and ATM kinase in pancreatic β-cells, under the duress of HG conditions. We report significant stimulatory effects of HG (20 mM; 24 h) on p53 activation in INS-1 832/13 cells, normal rodent and human islets. Pharmacological inhibition of Rac1 (EHT1864 or NSC23766) significantly suppressed HG-induced p53 activation in INS-1 832/13 cells and rat islets, suggesting novel roles for this small G-protein in the activation of p53...
February 21, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28219709/cordycepin-diminishes-thymic-stromal-lymphopoietin-induced-interleukin-13-production
#4
Myoung-Schook Yoou, Kyoung Wan Yoon, Youngjin Choi, Hyung-Min Kim, Hyun-Ja Jeong
Atopic dermatitis (AD) is known to aggravate by thymic stromal lymphopoietin (TSLP) and TSLP is also known to up-regulate mast cell proliferation via production of interleukin (IL)-13. Thus, we investigated whether cordycepin could regulate mast cell proliferation induced by TSLP in human mast cell line, HMC-1 cell. Cordycepin significantly diminished the production and mRNA of IL-13 through the down-regulation of phosphorylated-signal transducer and activation of transcription 6 in the TSLP-stimulated HMC-1 cells...
February 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28219702/genetic-alterations-in-krebs-cycle-and-its-impact-on-cancer-pathogenesis
#5
REVIEW
Karishma Sajnani, Farhadul Islam, Robert Anthony Smith, Vinod Gopalan, Alfred King-Yin Lam
Cancer cells exhibit alterations in many cellular processes, including oxygen sensing and energy metabolism. Glycolysis in non-oxygen condition is the main energy production process in cancer rather than mitochondrial respiration as in benign cells. Genetic and epigenetic alterations of Krebs cycle enzymes favour the shift of cancer cells from oxidative phosphorylation to anaerobic glycolysis. Mutations in genes encoding aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase, and citrate synthase are noted in many cancers...
February 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28219046/synthesis-and-biological-evaluation-of-novel-pyrazolic-chalcone-derivatives-as-novel-hepatocellular-carcinoma-therapeutics
#6
Mohammed M A Hawash, Deniz Cansen Kahraman, Fikriye Eren, Rengul Cetin Atalay, Sultan Nacak Baytas
Despite having the second highest mortality associated with cancer, currently Sorafenib is the only FDA-approved chemotherapeutic agent available for liver cancer patients which can only improve survival for few months. In this study, various pyrazolic chalcone analogous compounds were synthesized and evaluated as potential chemotherapeutic agents for the treatment of hepatocellular carcinoma (HCC). Modifying the central pyrazole ring at the C(3)-position with different heteroaryl rings and substituting the C(4)-position of pyrazole with differently substituted chalcone moiety produced fouthy two variant compounds...
February 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28218667/essential-roles-of-e3-ubiquitin-ligases-in-p53-regulation
#7
REVIEW
Sanam Sane, Khosrow Rezvani
The ubiquitination pathway and proteasomal degradation machinery dominantly regulate p53 tumor suppressor protein stability, localization, and functions in both normal and cancerous cells. Selective E3 ubiquitin ligases dominantly regulate protein levels and activities of p53 in a large range of physiological conditions and in response to cellular changes induced by exogenous and endogenous stresses. The regulation of p53's functions by E3 ubiquitin ligases is a complex process that can lead to positive or negative regulation of p53 protein in a context- and cell type-dependent manner...
February 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28218344/familial-melanoma-associated-with-li-fraumeni-syndrome-and-atypical-mole-syndrome-total-body-digital-photography-dermoscopy-and-confocal-microscopy
#8
Priscila Giavedoni, Marnie Ririe, Cristina Carrera, Susana Puig, Josep Malvehy
Li-Fraumeni syndrome (LFS) is a rare autosomal dominant disorder caused by a mutation in the p53 gene. Melanoma is considered to be a rare, controversial component of LFS. The aim of this study is to describe the utility of systematic screening for melanoma in patients with LFS and atypical mole syndrome. Two 28-year-old identical twin sisters with LFS and atypical moles were monitored by physical examination, total-body digital photography and dermoscopy be-tween 2006 and 2014. A total of 117, predominantly dark-brown, reticular naevi were identified on case 1 and 105 on case 2...
February 20, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28218222/human-u-three-protein-14a-expression-is-increased-in-hepatocellular-carcinoma-and-associated-with-poor-prognosis
#9
Jing-Yi Zhang, Da Xu, Zhen-Zhen Liu, Yuan Li, Li-Jun Wang, Bao-Cai Xing
BACKGROUND: Human U three protein 14a (hUTP14a) promotes p53 degradation. Moreover, hUTP14a expression is upregulated in several types of tumors. However, the expression pattern of hUTP14a in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate hUTP14a expression and its prognostic value in HCC. METHODS: The hUTP14a expression was evaluated using immunohistochemistry (IHC) in HCC tissue specimens. The correlations between hUTP14a expression and clinicopathological variables were analyzed...
2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28218036/chemopreventive-effect-of-omega-3-polyunsaturated-fatty-acids-and-atorvastatin-in-rats-with-bladder-cancer
#10
Nahla E El-Ashmawy, Eman G Khedr, Hoda A El-Bahrawy, Samar M Al-Tantawy
Bladder cancer remains a huge concern for the medical community because of its incidence and prevalence rates, as well as high percentage of recurrence and progression. Omega-3 polyunsaturated fatty acids and atorvastatin proved anti-inflammatory effects through peroxisome proliferator-activated receptor gamma mechanism. However, their chemopreventive effect still remained to be examined and clarified. In this study, bladder cancer was induced in rats by the chemical carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28217890/cerebellar-hemangioblastoma-with-perivascular-pseudorosette-formation-and-glial-differentiation-a-case-report
#11
Jian Wang, Xu-Yong Lin, Xue-Shan Qiu, En-Hua Wang, Lian-He Yang, Juan-Han Yu
Hemangioblastoma is a well-circumscribed, highly vascular, lipid-rich and low-grade tumor of uncertain histogenesis. Its histopathological features have been well established. Herein, we present a case of cerebellar hemangioblastoma in a 43-year-old woman. Histologically, the tumor was predominantly composed of cellular areas showing eosinophilic or vacuolated stromal cells arranged in nests and sheets. Focally, conventional reticular areas could be seen. Additionally, in some areas, the stromal cells were arranged radially around blood vessels, exhibiting perivascular pseudorosette structures, which were similar mostly to those of ependymomas...
August 24, 2016: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28216878/nardostachys-jatamansi-root-extract-modulates-the-growth-of-imr-32-and-sk-n-mc-neuroblastoma-cell-lines-through-mycn-mediated-regulation-of-mdm2-and-p53
#12
Snehal Suryavanshi, Prerna Raina, Rashmi Deshpande, Ruchika Kaul-Ghanekar
AIM: The present study evaluated the effect of ethanolic extract of Nardostachys jatamansi roots (NJet) on MYCN mediated regulation of expression of MDM2 and p53 proteins in neuroblastoma cell lines, IMR-32 and SK-N-MC. MATERIALS AND METHODS: The effect of NJet on cell viability was determined by MTT; and on growth kinetics was evaluated by trypan blue dye exclusion method and soft agar assay. The expression of p53, MDM2 and MYCN proteins in response to NJet treatment was evaluated by immunoblotting...
January 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28216621/dual-anti-ischemic-effects-of-rosmarinic-acid-n-butyl-ester-via-alleviation-of-dapk-p53-mediated-neuronal-damage-and-microglial-inflammation
#13
Lei Wu, Hong-Min Wang, Jin-Long Li, Hong-Xuan Feng, Wei-Min Zhao, Hai-Yan Zhang
The discovery of efficacious anti-ischemic drugs remains a challenge. Recently we have found that rosmarinic acid n-butyl ester (RABE), a derivative of rosmarinic acid, significantly protects SH-SY5Y cells against oxygen glucose deprivation (OGD)-induced cell death. In the present study we simultaneously investigated the effects of RABE on the two key players in the pathophysiology of cerebral ischemia, ischemic neuronal damage and microglial inflammation. Pretreatment with RABE (1, 10 μmol/L) dose-dependently attenuated OGD- or H2O2-induced reduction of the viability of SH-SY5Y neuroblastoma cells...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28216618/1-2-5-6-dianhydrogalactitol-inhibits-human-glioma-cell-growth-in-vivo-and-in-vitro-by-arresting-the-cell-cycle-at-g2-m-phase
#14
Chun Peng, Xin-Ming Qi, Ling-Ling Miao, Jin Ren
1,2:5,6-dianhydrogalactitol (DAG) is a hexitol epoxide with marked antitumor activity against multiple types of cancer cells, but the molecular mechanisms by which DAG functions as an antitumor agent is largely unknown. In this study, we investigated the inhibitory effects of DAG on human glioma cell growth in vitro and in vivo and uncovered the underlying molecular mechanisms. Treatment with DAG (120 μmol/L) dose-dependently inhibited the proliferation and colony formation in human glioma cell lines LN229, U251, and U87MG in vitro...
February 20, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28216383/large-scale-analysis-of-crispr-cas9-cell-cycle-knockouts-reveals-the-diversity-of-p53-dependent-responses-to-cell-cycle-defects
#15
Kara L McKinley, Iain M Cheeseman
Defining the genes that are essential for cellular proliferation is critical for understanding organismal development and identifying high-value targets for disease therapies. However, the requirements for cell-cycle progression in human cells remain incompletely understood. To elucidate the consequences of acute and chronic elimination of cell-cycle proteins, we generated and characterized inducible CRISPR/Cas9 knockout human cell lines targeting 209 genes involved in diverse cell-cycle processes. We performed single-cell microscopic analyses to systematically establish the effects of the knockouts on subcellular architecture...
February 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28216063/the-nad-precursor-nicotinic-acid-improves-genomic-integrity-in-human-peripheral-blood-mononuclear-cells-after-x-irradiation
#16
Kathrin Weidele, Sascha Beneke, Alexander Bürkle
NAD(+) is an essential cofactor for enzymes catalyzing redox-reactions as well as an electron carrier in energy metabolism. Aside from this, NAD(+) consuming enzymes like poly(ADP-ribose) polymerases and sirtuins are important regulators involved in chromatin-restructuring processes during repair and epigenetics/transcriptional adaption. In order to replenish cellular NAD(+) levels after cleavage, synthesis starts from precursors such as nicotinamide, nicotinamide riboside or nicotinic acid to match the need for this essential molecule...
February 13, 2017: DNA Repair
https://www.readbyqxmd.com/read/28215675/basic-fibroblast-growth-factor-is-critical-to-reprogramming-buffalo-bubalus-bubalis-primordial-germ-cells-into-embryonic-germ-stem-cell-like-cells
#17
Caizhu Wang, Yanfei Deng, Feng Chen, Peng Zhu, Jingwei Wei, Chan Luo, Fenghua Lu, Sufang Yang, Deshun Shi
Primordial germ cells (PGCs) are destined to form gametes in vivo, and they can be reprogrammed into pluripotent embryonic germ (EG) cells in vitro. Buffalo PGC have been reported to be reprogrammed into EG-like cells, but the identities of the major signaling pathways and culture media involved in this derivation remain unclear. Here, the effects of basic fibroblast growth factor (bFGF) and downstream signaling pathways on the reprogramming of buffalo PGCs into EG-like cells were investigated. Results showed bFGF to be critical to buffalo PGCs to dedifferentiate into EG-like cells (20 ng/mL is optimal) with many characteristics of pluripotent stem cells, including alkaline phosphatase (AP) activity, expression of pluripotency marker genes such as OCT4, NANOG, SOX2, SSEA-1, CDH1, and TRA-1-81, and the capacity to differentiate into all three embryonic germ layers...
March 15, 2017: Theriogenology
https://www.readbyqxmd.com/read/28215174/the-inverse-relationship-between-cancer-and-alzheimer-s-disease-a-possible-mechanism
#18
Daniel W Nixon
Cancer and Alzheimer's disease are both associated with aging, but do not often occur together in the same patient, regardless of age. The underlying reason for this unexpected clinical observation is not known, but body weight might provide a clue. Obesity is a shared risk factor for both diseases, and the many properties of fat-produced adipokines, including leptin and adiponectin, are now becoming clear. Normally, these adipokines are involved in energy intake, glucose metabolism and other physiologic processes, but they also have activities that can promote disease...
February 16, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28214706/influence-of-oxygen-partial-pressure-on-the-characteristics-of-human-hepatocarcinoma-cells
#19
Jenifer Trepiana, Susana Meijide, Rosaura Navarro, M Luisa Hernández, José Ignacio Ruiz-Sanz, M Begoña Ruiz-Larrea
Most of the in vitro studies using liver cell lines have been performed under atmospheric oxygen partial pressure (21% O2). However, the oxygen concentrations in the liver and cancer cells are far from this value. In the present study, we have evaluated the influence of oxygen on 1) the tumor cell lines features (growth, steady-state ROS levels, GSH content, activities of antioxidant enzymes, p66 Shc and SOD expressions, metalloproteinases secretion, migration, invasion, and adhesion) of human hepatocellular carcinoma cell lines, and b) the response of the cells to an oxidant stimulus (aqueous leaf extract of the V...
February 13, 2017: Redox Biology
https://www.readbyqxmd.com/read/28214639/congenital-glioblastoma-with-distinct-clinical-and-molecular-characteristics-case-reports-and-a-literature-review
#20
Masahiro Kameda, Yoshihiro Otani, Tomotsugu Ichikawa, Akira Shimada, Koichi Ichimura, Isao Date
BACKGROUND: The molecular diagnosis of brain tumors is important in classifying tumors and determining appropriate treatment. Congenital glioblastoma multiforme (GBM) is a rare tumor that occurs in infants, and the prognosis is poor. Approximately 60 patients diagnosed as congenital GBM have been reported. However, few reports have conducted molecular analyses of congenital GBM. CASE DESCRIPTION: We describe two congenital GBM patients treated in our hospital, and report results of immunohistochemistry, fluorescent in situ hybridization (FISH), direct sequencing, and methylation analyses...
February 15, 2017: World Neurosurgery
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