Read by QxMD icon Read

P53 -apoptosis

Jelena Krstic, Markus Galhuber, Tim J Schulz, Michael Schupp, Andreas Prokesch
Lifestyle-related disorders, such as the metabolic syndrome, have become a primary risk factor for the development of liver pathologies that can progress from hepatic steatosis, hepatic insulin resistance, steatohepatitis, fibrosis and cirrhosis, to the most severe condition of hepatocellular carcinoma (HCC). While the prevalence of liver pathologies is steadily increasing in modern societies, there are currently no approved drugs other than chemotherapeutic intervention in late stage HCC. Hence, there is a pressing need to identify and investigate causative molecular pathways that can yield new therapeutic avenues...
March 20, 2018: International Journal of Molecular Sciences
Yuhan Zhao, Lihua Wu, Xuetian Yue, Cen Zhang, Jianming Wang, Jun Li, Xiaohui Sun, Yiming Zhu, Zhaohui Feng, Wenwei Hu
Tumor suppressor p53 prevents early death due to cancer development. However, the role of p53 in aging process and longevity has not been well-established. In humans, single nucleotide polymorphism (SNP) with either arginine (R72) or proline (P72) at codon 72 influences p53 activity; the P72 allele has a weaker p53 activity and function in tumor suppression. Here, employing a mouse model with knock-in of human TP53 gene carrying codon 72 SNP, we found that despite increased cancer risk, P72 mice that escape tumor development display a longer lifespan than R72 mice...
March 20, 2018: ELife
Yi-Chao Hsu, Yu-Ting Wu, Chia-Ling Tsai, Yau-Huei Wei
In mammalian cells, there are seven members of the sirtuin protein family (SIRT1-7). SIRT1, SIRT6, and SIRT7 catalyze posttranslational modification of proteins in the nucleus, SIRT3, SIRT4, and SIRT5 are in the mitochondria and SIRT2 is in the cytosol. SIRT1 can deacetylate the transcription factor SOX2 and regulate induced pluripotent stem cells (iPSCs) reprogramming through the miR-34a-SIRT1-p53 axis. SIRT2 can regulate the function of pluripotent stem cells through GSK3β. SIRT3 can positively regulate PPAR gamma coactivator 1-alpha (PGC-1α) expression during the differentiation of stem cells...
March 2018: Experimental Biology and Medicine
Silvia Di Agostino, Fabio Valenti, Andrea Sacconi, Giulia Fontemaggi, Matteo Pallocca, Claudio Pulito, Federica Ganci, Paola Muti, Sabrina Strano, Giovanni Blandino
Over 70% of head & neck squamous cell carcinoma (HNSCC) patients carry TP53 oncogenic mutations. Here we studied the role of specific tumor-derived mutant p53 proteins in the aberrant transcription of long non-coding (lnc) MIR205HG gene in head and neck cancer cells. Methods: To understand the role of lncMIR205HG, that we showed to be transcriptionally regulated by mutant p53 in HNSCC, we have employed siRNA and shRNA in CAL27 and FaDu HNSCC cell lines to suppress p53 gene expression in ChIP assays and RT-qPCR...
2018: Theranostics
Rongqin Meng, Yang Wang, Liang He, Yuanqing He, Zedong Du
Numerous studies have assessed the diagnostic value of serum p53 (s-p53) antibody in patients with colorectal cancer (CRC); however, results remain controversial. The present study aimed to comprehensively and quantitatively summarize the potential diagnostic value of s-p53 antibody in CRC. The present study utilized databases, including PubMed and EmBase, systematically regarding s-p53 antibody diagnosis in CRC, accessed on and prior to 31 July 2016. The quality of all the included studies was assessed using quality assessment of studies of diagnostic accuracy (QUADAS)...
April 2018: Oncology Letters
Min Liu, Yen-Lin Chen, Yao-Haur Kuo, Mei-Kuang Lu, Chia-Ching Liao
Sapindus mukorossi is a deciduous plant and has recently been recognized to have anticancer property. In the present study, we discovered that S. mukorossi leaf and stem aqueous extract (SaM) contained two polysaccharides mainly made of myo-inositol, galactose, glucose, and fructose and the aim of this study was to investigate the antitumor property the aqueous extract SaM. In vitro treatment of SaM diminished proliferative potential of lung adenocarcinomic cells and induced intracellular oxidative stress, as well as necrotic cell death...
March 19, 2018: Scientific Reports
Zacharenia Nikitaki, Marcela Holá, Mattia Donà, Athanasia Pavlopoulou, Ioannis Michalopoulos, Karel J Angelis, Alexandros G Georgakilas, Anca Macovei, Alma Balestrazzi
Eukaryotic genome surveillance is dependent on the multiple, highly coordinated network functions of the DNA damage response (DDR). Highlighted conserved features of DDR in plants and animals represent a challenging opportunity to develop novel interdisciplinary investigations aimed at expanding the sets of DNA damage biomarkers currently available for radiation exposure monitoring (REM) in environmental and biomedical applications. In this review, common and divergent features of the most relevant DDR players in animals and plants are described, including the intriguing example of the plant and animal kingdom-specific master regulators SOG1 (suppressor of gamma response) and p53...
January 2018: Mutation Research
Beatrice Bergström, Hans Carlsten, Anna-Karin Hultgård Ekwall
BACKGROUND: A key feature of joints in rheumatoid arthritis (RA) is the formation of hyperplastic destructive pannus tissue, which is orchestrated by activated fibroblast-like synoviocytes (FLS). We have demonstrated that the RA risk gene and tumor suppressor Limb bud and heart development (LBH) regulates cell cycle progression in FLS. Methotrexate (MTX) is the first-line treatment for RA, but its mechanisms of action remain incompletely understood. Here, we studied the effects of MTX on mitogen-induced FLS proliferation and expression of cell cycle regulators in vitro...
March 20, 2018: Arthritis Research & Therapy
Mark E Hamilton, Niels C Bols, Bernard P Duncker
Rainbow trout cell cultures were exposed to three genotoxicants and examined for effects on γH2AX and p53 levels by western blotting and on cell viability using the indicator dyes Alamar Blue (AB) for energy metabolism and 5'-carboxyfluorescein diacetate acetoxymethyl ester (CFDA-AM) for plasma membrane integrity. Bleomycin induced γH2AX and p53 in a dose- and time-dependent manner and had little cytotoxic effect. However, induction was first seen at 0.3 μM for γH2AX but not until 16.5 μM for p53. Methyl methanesulfonate (MMS) increased H2AX phosphorylation but diminished p53 levels as the dose was increased from 908 μM up to 2724 μM...
March 5, 2018: Chemosphere
Henry H Nguyen, Abdel Aziz Shaheen, Natalia Baeza, Ellina Lytvyak, Stefan J Urbanski, Andrew L Mason, Gary L Norman, Marvin J Fritzler, Mark G Swain
BACKGROUND AND AIMS: Up to 20% of Primary Biliary Cholangitis (PBC) patients are estimated to have features that overlap with Autoimmune Hepatitis (AIH). Patients with PBC-AIH overlap syndrome (PBC-AIH OS) have been reported to exhibit suboptimal responses to ursodeoxycholic acid therapy, and are more likely to progress to cirrhosis. Anti-double stranded DNA (anti-dsDNA) and anti-p53 have been previously suggested to be potential autoantibodies for identifying patients with PBC-AIH OS...
2018: PloS One
Yijuan Xu, Wenzhe Wang, Minmin Wang, Xuejiao Liu, Mee-Hyun Lee, Mingfu Wang, Hao Zhang, Haitao Li, Wei Chen
Diet-related factors are thought to modify the risk of cancers, while the influence of high salt intake remains largely uncharacterized. Breast cancer is the most common cancer in women worldwide. In the present study, we examined the effect of salt intake on breast cancer by using a 4T1 mouse mammary tumor model. Unexpectedly, both the fitness and the survival rate of the tumor-bearing mice were improved by high salt intake. Similarly, high salt intake suppressed the primary tumor growth as well as metastasis to lung in mice...
March 19, 2018: Journal of Agricultural and Food Chemistry
Meng Wu, Zhihua Zhang, Fangxu Ma, Xiulong Zhang, Zhilin Zhang, Jianhua Tang, Ping Chen, Chunyan Zhou, Weiping Wang
TAp73 and p53 are involved in regulating tumor angiogenesis and vasohibin-1 (VASH1) is an anti-angiogenic factor. Whether TAp73 regulates angiogenesis positively or negatively is controversial. The status of P53 may determine the effect of TAp73 on angiogenesis. To the best of our knowledge it has not been previously reported whether TAp73, p53 and VASH1 are coexpressed in lung cancer. We profiled the association between TAp73 and p53 and VASH1 expression in lung adenocarcinoma (LAC) and investigated the function of TAp73 in regulating tumor angiogenesis...
April 2018: Oncology Letters
Maha S Al-Keilani, Dua H Alsmadi, Ruba S Darweesh, Karem H Alzoubi
Background: Approximately 90% of patients with metastatic colorectal cancer fail therapy mainly due to resistance. Taking advantage of currently approved agents for treatment of disease conditions other than cancer for the identification of new adjuvant anticancer therapies is highly encouraged. Pramlintide is a parenteral antidiabetic agent that is currently approved for treatment of types 1 and 2 diabetes mellitus. Objectives: To address the antineoplastic potential of pramlintide in colorectal cancer and to evaluate the ability of pramlintide to enhance the cytotoxicity of 5-fluorouracil, oxaliplatin, and irinotecan against colorectal cancer cell lines expressing wild-type and mutant p53...
2018: Clinical Pharmacology: Advances and Applications
Sebastian Overmans, Mikaela Nordborg, Rubén Díaz-Rúa, Diane L Brinkman, Andrew P Negri, Susana Agustí
Exposure to polycyclic aromatic carbons (PAHs) poses a growing risk to coral reefs due to increasing shipping and petroleum extraction in tropical waters. Damaging effects of specific PAHs can be further enhanced by the presence of ultraviolet radiation, known as phototoxicity. We tested phototoxic effects of the PAHs anthracene and phenanthrene on larvae of the scleractinian coral Acropora tenuis in the presence and absence of UVA (320-400 nm). Activity of superoxide dismutase (SOD) enzyme was reduced by anthracene while phenanthrene and UVA exposure did not have any effect...
March 9, 2018: Aquatic Toxicology
Ahmed H Ghobashi, Maher A Kamel
The maintenance of genome integrity is essential for organism survival. Therefore, eukaryotic cells possess many DNA repair mechanisms in response to DNA damage. Acetyltransferase, Tip60, plays a central role in ATM and p53 activation which are involved in DNA repair. Recent works uncovered the roles of Tip60 in ATM and p53 activation and how Tip60 is recruited to double-strand break sites. Moreover, recent works have demonstrated the role of Tip60 in cancer progression. Here, we review the current understanding of how Tip60 activates both ATM and p53 in response to DNA damage and his new roles in tumorigenesis...
March 16, 2018: Journal of Applied Genetics
Marcus J G W Ladds, Ingeborg M M van Leeuwen, Catherine J Drummond, Su Chu, Alan R Healy, Gergana Popova, Andrés Pastor Fernández, Tanzina Mollick, Suhas Darekar, Saikiran K Sedimbi, Marta Nekulova, Marijke C C Sachweh, Johanna Campbell, Maureen Higgins, Chloe Tuck, Mihaela Popa, Mireia Mayoral Safont, Pascal Gelebart, Zinayida Fandalyuk, Alastair M Thompson, Richard Svensson, Anna-Lena Gustavsson, Lars Johansson, Katarina Färnegårdh, Ulrika Yngve, Aljona Saleh, Martin Haraldsson, Agathe C A D'Hollander, Marcela Franco, Yan Zhao, Maria Håkansson, Björn Walse, Karin Larsson, Emma M Peat, Vicent Pelechano, John Lunec, Borivoj Vojtesek, Mar Carmena, William C Earnshaw, Anna R McCarthy, Nicholas J Westwood, Marie Arsenian-Henriksson, David P Lane, Ravi Bhatia, Emmet McCormack, Sonia Laín
The development of non-genotoxic therapies that activate wild-type p53 in tumors is of great interest since the discovery of p53 as a tumor suppressor. Here we report the identification of over 100 small-molecules activating p53 in cells. We elucidate the mechanism of action of a chiral tetrahydroindazole (HZ00), and through target deconvolution, we deduce that its active enantiomer (R)-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). The chiral specificity of HZ05, a more potent analog, is revealed by the crystal structure of the (R)-HZ05/DHODH complex...
March 16, 2018: Nature Communications
Chen Katz, Ana Maria Low-Calle, Joshua Choe, Oleg Laptenko, David Tong, Jazmine-Saskya N Joseph-Chowdhury, Francesca Garofalo, Yan Zhu, Assaf Friedler, Carol Prives
The p53 tumor suppressor protein is the most well studied as a regulator of transcription in the nucleus, where it exists primarily as a tetramer. However, there are other oligomeric states of p53 that are relevant to its regulation and activities. In unstressed cells, p53 is normally held in check by MDM2 that targets p53 for transcriptional repression, proteasomal degradation, and cytoplasmic localization. Here we discovered a hydrophobic region within the MDM2 N-terminal domain that binds exclusively to the dimeric form of the p53 C-terminal domain in vitro...
March 16, 2018: Genes & Development
Yukihiro Itoh, Miki Suzuki
Ubiquitin-activating enzyme (E1), which catalyzes the activation of ubiquitin in the initial step of the ubiquitination cascade, is a potential therapeutic target in multiple myeloma and breast cancer treatment. However, only a few E1 inhibitors have been reported to date. Moreover, there has been little medicinal chemistry research on the three-dimensional structure of E1. Therefore, in the present study, we attempted to identify novel E1 inhibitors using structure-based drug design. Following the rational design, synthesis, and in vitro biological evaluation of several such compounds, we identified a reversible E1 inhibitor (4b)...
March 3, 2018: Bioorganic & Medicinal Chemistry Letters
Panagiotis Galanos, George Pappas, Alexander Polyzos, Athanassios Kotsinas, Ioanna Svolaki, Nickolaos N Giakoumakis, Christina Glytsou, Ioannis S Pateras, Umakanta Swain, Vassilis L Souliotis, Alexandros G Georgakilas, Nicholas Geacintov, Luca Scorrano, Claudia Lukas, Jiri Lukas, Zvi Livneh, Zoi Lygerou, Dipanjan Chowdhury, Claus Storgaard Sørensen, Jiri Bartek, Vassilis G Gorgoulis
BACKGROUND: Genomic instability promotes evolution and heterogeneity of tumors. Unraveling its mechanistic basis is essential for the design of appropriate therapeutic strategies. In a previous study, we reported an unexpected oncogenic property of p21WAF1/Cip1 , showing that its chronic expression in a p53-deficient environment causes genomic instability by deregulation of the replication licensing machinery. RESULTS: We now demonstrate that p21WAF1/Cip1 can further fuel genomic instability by suppressing the repair capacity of low- and high-fidelity pathways that deal with nucleotide abnormalities...
March 16, 2018: Genome Biology
Po-Han Chen, Jen-Tsan Chi, Michael Boyce
In metazoans, thousands of intracellular proteins are modified with O-linked β-N-acetylglucosamine (O-GlcNAc) in response to a wide range of stimuli and stresses. In particular, a complex and evolutionarily conserved interplay between O-GlcNAcylation and oxidative stress has emerged in recent years. Here, we review the current literature on the connections between O-GlcNAc and oxidative stress, with a particular emphasis on major signaling pathways, such as KEAP1/NRF2, FOXO, NFκB, p53 and cell metabolism...
March 14, 2018: Glycobiology
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"