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https://www.readbyqxmd.com/read/27915270/chemoprevention-of-spontaneous-ovarian-cancer-in-the-domestic-hen
#1
E H Mocka, R A Stern, O J Fletcher, K E Anderson, J N Petitte, P E Mozdziak
The hen is an attractive animal model for in vivo testing of agents that thwart ovarian carcinogenesis because ovarian cancer in the domestic hen features clinical and molecular alterations that are similar to ovarian cancer in humans, including a high incidence of p53 mutations. The objective of the study was to test the potential ovarian cancer chemopreventive effect of the p53 stabilizing compound CP-31398 on hens that spontaneously present the ovarian cancer phenotype. Beginning at 79 wk of age, 576 egg-laying hens (Gallus domesticus) were randomized to diets containing different amounts of CP-31398 for 94 wk, 5 d, comprising a control group (C) (n = 144), which was fed a diet containing 0 ppm (mg/kg) of CP-31398; a low-dose treatment (LDT) group (n = 144), which was fed a diet containing 100 ppm of CP-31398; a moderate-dose treatment (MDT) group (n = 144) which was fed a diet containing 200 ppm of CP-31398; and a high-dose treatment (HDT) group (n = 144), which was fed a diet containing 300 ppm of CP-31398...
December 3, 2016: Poultry Science
https://www.readbyqxmd.com/read/27915231/predominant-role-of-dna-polymerase-eta-and-p53-dependent-translesion-synthesis-in-the-survival-of-ultraviolet-irradiated-human-cells
#2
Leticia K Lerner, Guilherme Francisco, Daniela T Soltys, Clarissa R R Rocha, Annabel Quinet, Alexandre T Vessoni, Ligia P Castro, Taynah I P David, Silvina O Bustos, Bryan E Strauss, Vanesa Gottifredi, Anne Stary, Alain Sarasin, Roger Chammas, Carlos F M Menck
Genome lesions trigger biological responses that help cells manage damaged DNA, improving cell survival. Pol eta is a translesion synthesis (TLS) polymerase that bypasses lesions that block replicative polymerases, avoiding continued stalling of replication forks, which could lead to cell death. p53 also plays an important role in preventing cell death after ultraviolet (UV) light exposure. Intriguingly, we show that p53 does so by favoring translesion DNA synthesis by pol eta. In fact, the p53-dependent induction of pol eta in normal and DNA repair-deficient XP-C human cells after UV exposure has a protective effect on cell survival after challenging UV exposures, which was absent in p53- and Pol H-silenced cells...
December 2, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27914813/normal-human-gingival-fibroblasts-undergo-cytostasis-and-apoptosis-after-long-term-exposure-to-butyric-acid
#3
Michihiro Shirasugi, Keisuke Nishioka, Toshiro Yamamoto, Takaaki Nakaya, Narisato Kanamura
The causes of periodontal disease are complex. Butyric acid, a metabolite of periodontopathic bacteria such as Porphyromonas gingivalis, acts as a histone deacetylase inhibitor that has a direct effect on mRNA expression. Butyric acid produced by Clostridium butyricum in the intestinal tract induces differentiation of regulatory T cells, thereby suppressing inflammation in the gut. Mice lacking Clostridium butyricum in the intestinal tract suffer from colitis. By contrast, butyric acid in the oral cavity worsens periodontal disease...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27914809/actein-enhances-trail-effects-on-suppressing-gastric-cancer-progression-by-activating-p53-caspase-3-signaling
#4
Zhi-Chao Yang, Ji Ma
Actein (ACT), isolated from the rthizomes of Cimicifuga foetida, is a triterpene glycoside, showing inhibitory role in breast cancer cells. However, the effects of ACT treatment on gastric cancer have little been known. Thus, the study is conducted to explore the in vitro and in vivo role of ACT in gastric cancer. And the interactions between ACT and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were investigated in gastric cancer cells. A synergistic effect of ACT and TRAIL combination on apoptosis induction in gastric cancer cells was observed...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27914807/phosphorylation-of-p53-by-lrrk2-induces-microglial-tumor-necrosis-factor-%C3%AE-mediated-neurotoxicity
#5
Dong Hwan Ho, Wongi Seol, Jin Hwan Eun, Il-Hong Son
Leucine-rich repeat kinase (LRRK2), a major causal gene of Parkinson's disease (PD), functions as a kinase. The most prevalent mutation of LRRK2 is G2019S. It exhibits increased kinase activity compared to the wildtype LRRK2. Previous studies have shown that LRRK2 can phosphorylate p53 at T304 and T377 of threonine-X-arginine (TXR) motif in neurons. Reduction of LRRK2 expression or inhibition of LRRK2 kinase activity has been shown to be able to alleviate LPS-induced neuroinflammation in microglia cells. In this study, we found that LRRK2 could also phosphorylate p53 in microglia model BV2 cells...
November 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27914769/clinicopathological-and-molecular-characteristics-of-ku-70-80-expression-in-nigerian-breast-cancer-and-its-potential-therapeutic-implications
#6
Ayodeji O J Agboola, Henry O Ebili, Victoria O Iyawe, Adekunbiola A F Banjo, Babatunde A Salami, Emad A Rakha, Chrstopher C Nolan, Ian O Ellis, Andrew R Green
Ku 70/80 is a regulator of the Non-Homologous End Joining (NHEJ) roles in clinicopathological features, and has prognostic significance in breast cancer (BC) in Caucasian populations. However, its significance in the Nigerian BC population, which is characterized by a higher rate of the triple-negative and basal phenotype, p53 mutation rate and BRCA1 deficiency, still needs to be investigated. We hypothesize that Ku70/80 expression shows adverse expression in Nigerian BC and, furthermore, that it is likely to have a therapeutic implication for Black BC management...
October 25, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27913931/prognostic-value-of-tumor-infiltrating-lymphocyte-subsets-in-breast-cancer-depends-on-hormone-receptor-status
#7
Yul Ri Chung, Hyun Jeong Kim, Min Hye Jang, So Yeon Park
PURPOSE: Interaction between immune-regulatory proteins and tumor infiltrating lymphocytes (TILs) is complex, and their associations may have significant clinical implications. This study was designed to evaluate the relationships between immunomodulatory proteins and TIL subsets and their impact on prognosis in breast cancer. METHODS: 377 invasive breast cancer cases were selected, and immunohistochemistry was performed for HLA-A, HLA-ABC, and indoleamine 2,3-dioxygenase (IDO); CD4+, CD8+, and FOXP3+ T cells were counted in intratumoral and stromal areas for both absolute numbers as well as their ratios...
December 2, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27913641/translation-repression-by-maternal-rna-binding-protein-zar1-is-essential-for-early-oogenesis-in-zebrafish
#8
Liyun Miao, Yue Yuan, Feng Cheng, Junshun Fang, Fang Zhou, Weirui Ma, Yan Jiang, Xiahe Huang, Yingchun Wang, Lingjuan Shan, Dahua Chen, Jian Zhang
Large numbers of maternal RNAs are deposited in oocytes and are reserved for later development. Control of maternal RNA translation during oocyte maturation has been extensively investigated and its regulatory mechanisms are well documented. However, translational regulation of maternal RNAs in early oogenesis is largely unexplored. In this study, we generated zebrafish zar1 mutants which result in early oocyte apoptosis and fully penetrant male development. Loss of p53 suppresses the apoptosis in zar1 mutants and restores oocyte development...
December 2, 2016: Development
https://www.readbyqxmd.com/read/27913611/silent-somatotroph-tumour-revisited-from-a-study-of-80-patients-with-and-without-acromegaly-and-a-review-of-the-literature
#9
Laura Chinezu, Alexandre Vasiljevic, Jacqueline Trouillas, Marion Lapoirie, Emmanuel Jouanneau, Gérald Raverot
BACKGROUND: Silent somatotroph tumours are growth hormone (GH) immunoreactive (IR) pituitary tumours without clinical and biological signs of acromegaly. Their better characterisation is required to improve the diagnosis. MATERIALS AND METHODS: Twenty-one silent somatotroph tumours were compared to 59 somatotroph tumours with acromegaly. Tumours in each group were classified into GH and plurihormonal (GH/prolactin (PRL)/±thyroid-stimulating hormone (TSH)) and into densely granulated (DG) and sparsely granulated (SG) types...
February 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27913434/a-study-of-tp53-rna-splicing-illustrates-pitfalls-of-rna-seq-methodology
#10
Sunali Mehta, Peter Tsai, Annette Lasham, Hamish Campbell, Roger Reddel, Antony Braithwaite, Cristin Print
TP53 undergoes multiple RNA-splicing events, resulting in at least nine mRNA transcripts encoding at least 12 functionally different protein isoforms. Antibodies specific to p53 protein isoforms have proven difficult to develop, thus researchers must rely on the transcript information to infer isoform abundance. In this study, we used deep RNA-seq, droplet digital PCR (ddPCR), and real-time quantitative reverse transcriptase PCR (RT-qPCR) from nine human cell lines and RNA-seq data available for tumors in The Cancer Genome Atlas to analyze TP53 splice variant expression...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27913286/cytotoxic-activity-of-soy-phytoestrogen-coumestrol-against-human-breast-cancer-mcf-7%C3%A2-cells-insights-into-the-molecular-mechanism
#11
Atif Zafar, Swarnendra Singh, Imrana Naseem
Coumestrol is a phytoestrogen present in soybean products and recognized as potential cancer therapeutic agent against breast cancer. However, the clear molecular mechanism of anticancer-activity of coumestrol in breast carcinoma has not been reported. It is well established that copper levels are elevated in different malignancies. Therefore, the objective of this study was to investigate the copper-dependent cytotoxic action of coumestrol in human breast cancer MCF-7 cells. Results showed that coumestrol inhibited proliferation and induced apoptosis in MCF-7 cells, which was prevented by copper chelator neocuproine and ROS scavengers...
November 29, 2016: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/27913065/hpv-status-cancer-stem-cell-marker-expression-hypoxia-gene-signatures-and-tumour-volume-identify-good-prognosis-subgroups-in-patients-with-hnscc-after-primary-radiochemotherapy-a-multicentre-retrospective-study-of-the-german-cancer-consortium-radiation-oncology
#12
Annett Linge, Fabian Lohaus, Steffen Löck, Alexander Nowak, Volker Gudziol, Chiara Valentini, Cläre von Neubeck, Martin Jütz, Inge Tinhofer, Volker Budach, Ali Sak, Martin Stuschke, Panagiotis Balermpas, Claus Rödel, Anca-Ligia Grosu, Amir Abdollahi, Jürgen Debus, Ute Ganswindt, Claus Belka, Steffi Pigorsch, Stephanie E Combs, David Mönnich, Daniel Zips, Frank Buchholz, Daniela E Aust, Gustavo B Baretton, Howard D Thames, Anna Dubrovska, Jan Alsner, Jens Overgaard, Mechthild Krause, Michael Baumann
OBJECTIVE: To investigate the impact of the tumour volume, HPV status, cancer stem cell (CSC) marker expression and hypoxia gene signatures, as potential markers of radiobiological mechanisms of radioresistance, in a contemporary cohort of patients with locally advanced head and neck squamous cell carcinoma (HNSCC), who received primary radiochemotherapy (RCTx). MATERIALS AND METHODS: For 158 patients with locally advanced HNSCC of the oral cavity, oropharynx or hypopharynx who were treated at six DKTK partner sites, the impact of tumour volume, HPV DNA, p16 overexpression, p53 expression, CSC marker expression and hypoxia-associated gene signatures on outcome of primary RCTx was retrospectively analyzed...
November 29, 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/27912880/combination-of-baicalein-and-10-hydroxy-camptothecin-exerts-remarkable-synergetic-anti-cancer-effects
#13
Qin Tang, Fangling Ji, Wenhui Sun, Jingyun Wang, Jianli Guo, Lianying Guo, Yachen Li, Yongming Bao
BACKGROUND: 10-Hydroxy camptothecin (HCPT), a naturally occurring alkaloid, is a clinical drug for cancer chemotherapy. Baicalein (BA) is a flavonoid extracted from the root of Scutellaria baicalensis. The synergistic anti-cancer effect of BA and HCPT has not been reported. PURPOSE: To explore whether and how BA enhances the anti-cancer effect of HCPT in BGC823 cells. METHODS: Cell viability was measured by MTT assay. Apoptosis and cell cycle were analyzed through flow cytometry and western blotting analysis...
December 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/27912097/lncpress1-is-a-p53-regulated-lncrna-that-safeguards-pluripotency-by-disrupting-sirt6-mediated-de-acetylation-of-histone-h3k56
#14
Abhinav K Jain, Yuanxin Xi, Ryan McCarthy, Kendra Allton, Kadir C Akdemir, Lalit R Patel, Bruce Aronow, Chunru Lin, Wei Li, Liuqing Yang, Michelle C Barton
Recent evidence suggests that lncRNAs play an integral regulatory role in numerous functions, including determination of cellular identity. We determined global expression (RNA-seq) and genome-wide profiles (ChIP-seq) of histone post-translational modifications and p53 binding in human embryonic stem cells (hESCs) undergoing differentiation to define a high-confidence set of 40 lncRNAs, which are p53 transcriptional targets. We focused on lncRNAs highly expressed in pluripotent hESCs and repressed by p53 during differentiation to identify lncPRESS1 as a p53-regulated transcript that maintains hESC pluripotency in concert with core pluripotency factors...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27912092/wrap53-a-natural-p53-antisense-transcript-required-for-p53-induction-upon-dna-damage
#15
Salah Mahmoudi, Sofia Henriksson, Martin Corcoran, Cristina Méndez-Vidal, Klas G Wiman, Marianne Farnebo
No abstract text is available yet for this article.
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27912078/mouse-double-minute-2-homolog-actively-suppresses-p53-activity-in-oocytes-during-mouse-folliculogenesis
#16
Chen-Xi Zhang, Qin Zhang, Yin-Yin Xie, Xue-Yan He, Cong Xiang, Xiao-Shuang Hou, Ying Zhou, Lai Chen, Guo-Xin Zhang, Geng Liu
The p53 signaling network is indispensible in cellular stress responses and tumor suppression. Negative regulations of p53 by mouse double minute 2 and 4 homologs (MDM2) and (MDM4) are an integrated component of the network and have been implicated in regulating the stress responses and the maintenance of normal development and homeostasis of multiple somatic cell lineages. However, the regulatory role of MDM2 on p53 and stress responses in female germ cells remains undetermined. Here, we used the Cre-loxP system to delete Mdm2 in oocytes at different stages of folliculogenesis in mice...
November 29, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27911860/id4-regulates-transcriptional-activity-of-wild-type-and-mutant-p53-via-k373-acetylation
#17
Derrick J Morton, Divya Patel, Jugal Joshi, Aisha Hunt, Ashley E Knowell, Jaideep Chaudhary
Given that mutated p53 (50% of all human cancers) is over-expressed in many cancers, restoration of mutant p53 to its wild type biological function has been sought after as cancer therapy. The conformational flexibility has allowed to restore the normal biological function of mutant p53 by short peptides and small molecule compounds. Recently, studies have focused on physiological mechanisms such as acetylation of lysine residues to rescue the wild type activity of mutant p53. Using p53 null prostate cancer cell line we show that ID4 dependent acetylation promotes mutant p53 DNA-binding capabilities to its wild type consensus sequence, thus regulating p53-dependent target genes leading to subsequent cell cycle arrest and apoptosis...
November 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/27911838/antagonists-of-growth-hormone-releasing-hormone-receptor-induce-apoptosis-specifically-in-retinoblastoma-cells
#18
Wai Kit Chu, Ka Sin Law, Sun On Chan, Jason Cheuk Sing Yam, Li Jia Chen, Hao Zhang, Herman S Cheung, Norman L Block, Andrew V Schally, Chi Pui Pang
Retinoblastoma (RB) is the most common intraocular cancer in children worldwide. Current treatments mainly involve combinations of chemotherapies, cryotherapies, and laser-based therapies. Severe or late-stage disease may require enucleation or lead to fatality. Recently, RB has been shown to arise from cone precursor cells, which have high MDM2 levels to suppress p53-mediated apoptosis. This finding leads to the hypothesis that restoring apoptosis mechanisms in RBs could specifically kill the cancer cells without affecting other retinal cells...
November 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911443/transient-mitochondrial-dna-double-strand-breaks-in-mice-cause-accelerated-aging-phenotypes-in-a-ros-dependent-but-p53-p21-independent-manner
#19
Milena Pinto, Alicia M Pickrell, Xiao Wang, Sandra R Bacman, Aixin Yu, Aline Hida, Lloye M Dillon, Paul D Morton, Thomas R Malek, Siôn L Williams, Carlos T Moraes
We observed that the transient induction of mtDNA double strand breaks (DSBs) in cultured cells led to activation of cell cycle arrest proteins (p21/p53 pathway) and decreased cell growth, mediated through reactive oxygen species (ROS). To investigate this process in vivo we developed a mouse model where we could transiently induce mtDNA DSBs ubiquitously. This transient mtDNA damage in mice caused an accelerated aging phenotype, preferentially affecting proliferating tissues. One of the earliest phenotypes was accelerated thymus shrinkage by apoptosis and differentiation into adipose tissue, mimicking age-related thymic involution...
December 2, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27910233/a-genetically-encoded-allysine-for-the-synthesis-of-proteins-with-site-specific-lysine-dimethylation
#20
Zhipeng A Wang, Yu Zeng, Yadagiri Kurra, Xin Wang, Jeffery M Tharp, Erol C Vatansever, Willie W Hsu, Susie Dai, Xinqiang Fang, Wenshe R Liu
Using the amber suppression approach, N(ϵ) -(4-azidobenzoxycarbonyl)-δ,ϵ-dehydrolysine, an allysine precursor is genetically encoded in E. coli. Its genetic incorporation followed by two sequential biocompatible reactions allows convenient synthesis of proteins with site-specific lysine dimethylation. Using this approach, dimethyl-histone H3 and p53 proteins have been synthesized and used to probe functions of epigenetic enzymes including histone demethylase LSD1 and histone acetyltransferase Tip60. We confirmed that LSD1 is catalytically active toward H3K4me2 and H3K9me2 but inert toward H3K36me2, and methylation at p53 K372 directly activates Tip60 for its catalyzed acetylation at p53 K120...
December 2, 2016: Angewandte Chemie
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