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p53 mdm2

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https://www.readbyqxmd.com/read/28325293/a-pirna-like-small-rna-induces-chemoresistance-to-cisplatin-based-therapy-by-inhibiting-apoptosis-in-lung-squamous-cell-carcinoma
#1
Yuyan Wang, Tyler Gable, Mark Z Ma, David Clark, Jun Zhao, Yi Zhang, Wei Liu, Li Mao, Yuping Mei
Lung cancer is the leading cause of cancer-related death worldwide. Although advanced drugs have benefitted patients, therapeutic success has largely been hampered because of rapid development of resistance. Here we report that PIWI-interacting RNA likes (piR-Ls), a novel type of functional sncRNAs, play key roles in chemoresistance to cisplatin (CDDP)-based chemotherapy in lung squamous cell carcinoma (LSCC). piR-L-138 was upregulated upon CDDP-based chemotherapy both in LSCC cells and in patient-derived xenograft (PDX) LSCC models...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28322991/thyroid-hormone-induce-a-p53-dependent-dna-damage-through-pi3k-akt-activation-in-sperm
#2
Hong Xian, Fang Wang, Wending Teng, Dong Yang, Ming Zhang
Accumulating evidences showed that thyroid hormone was participated in the functioning of the reproductive system, and an elevated level of thyroid hormones had a negative impact on reproductive system. However, the molecular basis for this observation still remains to be fully understood. Here, we show that l-Thyroxine significantly impaired human sperm motility. The molecular basis showed that thyroxine receptor stimulation triggers Phosphatidyl Inositol 3-kinase (PI3K)/Akt signaling activation leading to the E3 ligase MDM2 phosphorylation at serine 166, which directly interacted with p53 for degradation...
March 16, 2017: Gene
https://www.readbyqxmd.com/read/28315337/p53-signaling-pathway-polymorphisms-associated-with-emphysematous-changes-in-copd-patients
#3
Shiro Mizuno, Takeshi Ishizaki, Maiko Kadowaki, Masaya Akai, Kohei Shiozaki, Masaharu Iguchi, Taku Oikawa, Ken Nakagawa, Kazuhiro Osanai, Hirohisa Toga, Jose Gomez-Arroyo, Donatas Kraskauskas, Carlyne D Cool, Herman J Bogaard, Norbert F Voelkel
BACKGROUND: The p53 signaling pathway may be important for the pathogenesis of emphysematous changes in the lungs of smokers. Polymorphism of p53 at codon 72 is known to affect apoptotic effector proteins, and the polymorphism of mouse double minute 2 homolog (MDM2) SNP309 is known to increase MDM2 expression. The aim of this study was to assess polymorphisms of the p53 and MDM2 genes in smokers and confirm the role of SNPs in these genes in the pathogenesis of pulmonary emphysema. METHODS: 365 patients with a smoking history were included in this study, and the polymorphisms of p53 and MDM2 genes were identified...
March 14, 2017: Chest
https://www.readbyqxmd.com/read/28296148/dimp53-1-a-novel-small-molecule-dual-inhibitor-of-p53-mdm2-x-interactions-with-multifunctional-p53-dependent-anticancer-properties
#4
Joana Soares, Margarida Espadinha, Liliana Raimundo, Helena Ramos, Ana Sara Gomes, Sara Gomes, Joana B Loureiro, Alberto Inga, Flávio Reis, Célia Gomes, Maria M M Santos, Lucília Saraiva
The transcription factor p53 plays a crucial role in cancer development and dissemination, and thus p53-targeted therapies are amongst the most encouraging anticancer strategies. In human cancers with wild-type (wt) p53, its inactivation by interaction with murine double minute (MDM)2 and MDMX is a common event. Simultaneous inhibition of the p53 interaction with both MDMs is crucial to restore the tumor suppressor activity of p53. Here we describe the synthesis of the new tryptophanol-derived oxazoloisoindolinone DIMP53-1 and identify its activity as a dual inhibitor of the p53-MDM2/X interactions using a yeast-based assay...
March 10, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28287985/policy-iteration-algorithm-for-optimal-control-of-stochastic-logical-dynamical-systems
#5
Yuhu Wu, Tielong Shen
This brief investigates the infinite horizon optimal control problem for stochastic multivalued logical dynamical systems with discounted cost. Applying the equivalent descriptions of stochastic logical dynamics in term of Markov decision process, the discounted infinite horizon optimal control problem is presented in an algebraic form. Then, employing the method of semitensor product of matrices and the increasing-dimension technique, a succinct algebraic form of the policy iteration algorithm is derived to solve the optimal control problem...
March 6, 2017: IEEE Transactions on Neural Networks and Learning Systems
https://www.readbyqxmd.com/read/28284458/p53-dysregulation-in-b-cell-malignancies-more-than-a-single-gene-in-the-pathway-to-hell
#6
REVIEW
B Tessoulin, M Eveillard, A Lok, D Chiron, P Moreau, M Amiot, A Moreau-Aubry, S Le Gouill, C Pellat-Deceunynck
TP53 deletion or mutation is frequent in B-cell malignancies and is associated with a low response rate. We describe here the p53 landscape in B-cell malignancies, from B-Acute Lymphoblastic Leukemia to Plasma Cell Leukemia, by analyzing incidence of gain or loss of function of actors both upstream and within the p53 pathway, namely MYC, RAS, ARF, MDM2, ATM and TP53. Abnormalities are not equally distributed and their incidence is highly variable among malignancies. Deletion and mutation, usually associated, of ATM or TP53 are frequent in Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma...
March 4, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28283504/mk-8242-is-active-in-patients-with-p53-wild-type-advanced-solid-tumors
#7
(no author information available yet)
The MDM2 inhibitor MK-8242 is tolerable in patients with liposarcoma and other advanced solid tumors.
March 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28281901/tp53-and-its-potential-therapeutic-role-as-a-target-in-bladder-cancer
#8
Chiara Ciccarese, Francesco Massari, Ana Blanca, Giampaolo Tortora, Rodolfo Montironi, Liang Cheng, Marina Scarpelli, Maria R Raspollini, Nuno Vau, Jorge Fonseca, Antonio Lopez-Beltran
Despite more than 30 years of research on p53 resulting in >50,000 publications, we are now beginning to figure out the complexity of the p53 pathway, gene ontology and conformational structure of the molecule. Recent years brought great advances in p53 related drugs and the potencial ways in which p53 is inactivated in cancer. Areas covered: We searched for related publications on Pubmed and ClinicalTrial.gov using the following keywords 'p53, Tp53, p53 and bladder cancer, p53 and therapeutic target'. Relevant articles improved the understanding on p53 pathways and their potential as candidate to targeted therapy in bladder cancer...
April 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/28276427/trib2-confers-resistance-to-anti-cancer-therapy-by-activating-the-serine-threonine-protein-kinase-akt
#9
Richard Hill, Patricia A Madureira, Bibiana Ferreira, Inês Baptista, Susana Machado, Laura Colaço, Marta Dos Santos, Ningshu Liu, Ana Dopazo, Selma Ugurel, Angyal Adrienn, Endre Kiss-Toth, Murat Isbilen, Ali O Gure, Wolfgang Link
Intrinsic and acquired resistance to chemotherapy is the fundamental reason for treatment failure for many cancer patients. The identification of molecular mechanisms involved in drug resistance or sensitization is imperative. Here we report that tribbles homologue 2 (TRIB2) ablates forkhead box O activation and disrupts the p53/MDM2 regulatory axis, conferring resistance to various chemotherapeutics. TRIB2 suppression is exerted via direct interaction with AKT a key signalling protein in cell proliferation, survival and metabolism pathways...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28274247/gossypol-has-anti-cancer-effects-by-dual-targeting-mdm2-and-vegf-in-human-breast-cancer
#10
Jing Xiong, Jiansha Li, Qin Yang, Jun Wang, Tiefen Su, Sheng Zhou
BACKGROUND: Mouse double minute 2 (MDM2) and vascular endothelial growth factor (VEGF) are important molecules involved in tumor progression. We researched potential inhibitors that simultaneously target MDM2 and VEGF. In our recent study involving the performance of high-throughput screening with a fluorescence polarization assay, gossypol was identified as one of the top hits that inhibit protein-RNA binding activity. Because MDM2 is an RNA-binding protein and its targets include VEGF mRNA, we investigated whether gossypol has an inhibitory effect on MDM2-VEGF...
March 9, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28270530/targeting-the-mdm2-p53-protein-protein-interaction-for-new-cancer-therapy-progress-and-challenges
#11
Shaomeng Wang, Yujun Zhao, Angelo Aguilar, Denzil Bernard, Chao-Yie Yang
MDM2 is a primary cellular inhibitor of p53. It inhibits p53 function by multiple mechanisms, each of which, however, is mediated by their direct interaction. It has been proposed that small-molecule inhibitors designed to block the MDM2-p53 interaction may be effective in the treatment of human cancer retaining wild-type p53 by reactivating the p53 tumor suppressor function. Through nearly two decades of intense efforts, a number of structurally distinct, highly potent, nonpeptide, small-molecule inhibitors of the MDM2-p53 interaction (MDM2 inhibitors) have been successfully designed and developed, and at least seven such compounds have now been advanced into human clinical trials as new anticancer drugs...
March 7, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28265066/resistance-mechanisms-to-tp53-mdm2-inhibition-identified-by-in-vivo-piggybac-transposon-mutagenesis-screen-in-an-arf-mouse-model
#12
Emilie A Chapeau, Agnieszka Gembarska, Eric Y Durand, Emeline Mandon, Claire Estadieu, Vincent Romanet, Marion Wiesmann, Ralph Tiedt, Joseph Lehar, Antoine de Weck, Roland Rad, Louise Barys, Sebastien Jeay, Stephane Ferretti, Audrey Kauffmann, Esther Sutter, Armelle Grevot, Pierre Moulin, Masato Murakami, William R Sellers, Francesco Hofmann, Michael Rugaard Jensen
Inhibitors of double minute 2 protein (MDM2)-tumor protein 53 (TP53) interaction are predicted to be effective in tumors in which the TP53 gene is wild type, by preventing TP53 protein degradation. One such setting is represented by the frequent CDKN2A deletion in human cancer that, through inactivation of p14ARF, activates MDM2 protein, which in turn degrades TP53 tumor suppressor. Here we used piggyBac (PB) transposon insertional mutagenesis to anticipate resistance mechanisms occurring during treatment with the MDM2-TP53 inhibitor HDM201...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28240680/inhibition-of-wnt-signaling-reduces-differentiation-and-induces-sensitivity-to-doxorubicin-in-human-malignant-neuroblastoma-sh-sy5y-cells
#13
Junjira Suebsoonthron, Thiranut Jaroonwitchawan, Montarop Yamabhai, Parinya Noisa
Neuroblastoma is one of the most common cancers in infancy, arising from the neuroblasts during embryonic development. This cancer is difficult to treat and resistance to chemotherapy is often found; therefore, clinical trials of novel therapeutic approaches, such as targeted-cancer signaling, could be an alternative for a better treatment. WNT signaling plays significant roles in the survival, proliferation, and differentiation of human neuroblastoma. In this report, WNT signaling of a malignant human neuroblastoma cell line, SH-SY5Y cells, was inhibited by XAV939, a specific inhibitor of the Tankyrase enzyme...
February 24, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28240161/dihydromyricetin-reduces-tgf-%C3%AE-via-p53-activation-dependent-mechanism-in-hepatocellular-carcinoma-hepg2-cells
#14
Xiaojie Huang, Tianming Lian, Xiaoqian Guan, Bin Liu, Zeqing Song, Jingjing Zhang, Shiting Bao, Runzhi Zhu
Natural antineoplastic drug development is crucial to treatment of clinical oncology. Dihydromyricetin, a bioactive flavonoid compound was extracted from the stems and leaves of Ampelopsis grossedentata. It exhibited anticancer activity and induced apoptosis in human hepatocellular carcinoma cells according to our previous studies. In this study, we demonstrated that DHM could significantly inhibit proliferation and induce apoptosis in HepG2 cells with MTT and Flow Cytometry methods. It is very interesting that we found DHM could regulate TGF-β signal pathway and which has a crosstalk with P53, Smad3 and P-Smad2/3 proteins...
February 23, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28223335/cooperation-of-musashi-2-numb-mdm2-and-p53-in-drug-resistance-and-malignant-biology-of-pancreatic-cancer
#15
Weiwei Sheng, Ming Dong, Chuanping Chen, Zixin Wang, Yunwei Li, Kewei Wang, Yuji Li, Jianping Zhou
Our earlier work showed that Musashi (MSI)-2 promoted the development of pancreatic cancer (PC) by down-regulating Numb, which prevented murine double-minute (MDM)-2-mediated p53 ubiquitin degradation. Thus, we investigate the relationship among MSI2, Numb, MDM2, and p53 in PC in vitro and invivo, an association that has not been reported to our knowledge. MSI2 had no relationship with mutant p53 (mtp53) and wild-type p53 (wtp53) in normal PC cells. However, in response to gemcitabine or cisplatin treatment, MSI2 silencing simultaneously down-regulated MDM2 and up-regulated Numb and wtp53 protein levels...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28219709/cordycepin-diminishes-thymic-stromal-lymphopoietin-induced-interleukin-13-production
#16
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 20, 2017: European Journal of Pharmacology
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
#17
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/28216291/ovarian-tumor-domain-containing-protein-1-deubiquitinates-and-stabilizes-p53
#18
Shudong Piao, Han Zhong Pei, Bin Huang, Suk-Hwan Baek
Ubiquitination and deubiquitination pathways play important roles in the regulation of p53 stability and activity. p53 is ubiquitinated and destabilized by E3 ubiquitin ligases and is deubiquitinated and stabilized by deubiquitinases (DUBs). We screened ovarian tumor (OTU) subfamily proteins to identify novel DUBs that stabilized p53. OTU domain-containing protein 1 (OTUD1) is a DUB belonging to the OTU family; however, its substrates and its role in cells are unknown. Here, we used an overexpression and knockdown system to show that OTUD1 is a novel regulator of p53 stability...
February 13, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28216017/usp7-inhibitor-p5091-inhibits-wnt-signaling-and-colorectal-tumor-growth
#19
Tao An, Yaxiao Gong, Xue Li, Lingmei Kong, Pengcheng Ma, Liang Gong, Huifang Zhu, Chunlei Yu, Jianmei Liu, Hongyu Zhou, Bingyu Mao, Yan Li
Aberrant activation of Wnt/β-catenin signaling is closely associated with the development of various human cancers, especially colorectal cancers (CRC). The ubiquitin proteasome system (UPS) is essential in the regulation of Wnt signaling and inhibitors targeting the UPS could have great potential in CRC therapy. Ubiquitin-specific protease 7 (USP7), a deubiquitinating enzyme, plays a significant role in neoplastic diseases due to its well-known function of regulating the MDM2-p53 complex. Inspired by our recent study identifying the positive role of USP7 in the Wnt signaling, we report here that USP7 is overexpressed in colorectal carcinoma cell lines and tissues, which is closely related with the poor prognosis...
February 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28203268/steady-state-preserving-simulation-of-genetic-regulatory-systems
#20
Ruqiang Zhang, Julius Osato Ehigie, Xilin Hou, Xiong You, Chunlu Yuan
A novel family of exponential Runge-Kutta (expRK) methods are designed incorporating the stable steady-state structure of genetic regulatory systems. A natural and convenient approach to constructing new expRK methods on the base of traditional RK methods is provided. In the numerical integration of the one-gene, two-gene, and p53-mdm2 regulatory systems, the new expRK methods are shown to be more accurate than their prototype RK methods. Moreover, for nonstiff genetic regulatory systems, the expRK methods are more efficient than some traditional exponential RK integrators in the scientific literature...
2017: Computational and Mathematical Methods in Medicine
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